3 BACTERIAL

DISEASES
D. J. Taylor, Editor
 Actinobacillus pleuropneumoniae
26 D. J. Taylor
Actinobacillus pleuropneumoniae is the etiologic agent of
pleuropneumonia in pigs. The first observations of this
disease were made by Pattison et al. (1957), Matthews
and Pattison (1961), and Olander (1963). Shope (1964)
later described an acute outbreak of a similar infection
on a farm in Argentina. The name Haemophilus pleuro-
pneumoniae was given to the causal organism by Shope et
al. (1964) and White et al. (1964). The name was con-
firmed by Kilian et al. (1978). The designation H. para-
haemolyticus given to the California strains (Olander
1963; Biberstein et al. 1963) and the Swiss isolates (Nico-
let and König 1966; Nicolet 1968) is considered a syn-
onym.
H. pleuropneumoniae was later transferred to the
genus Actinobacillus and designated A. pleuropneumoniae
once DNA homology studies had demonstrated the close
relationship of H. pleuropneumoniae to A. lignieresii (Pohl
et al. 1983). The Pasteurella haemolytica–like organism
described by Bertschinger and Seifert (1978) as a
causative agent of necrotizing pleuropneumonia is con-
sidered to be a nicotinamide adenine dinucleotide
(NAD)-independent biovar of A. pleuropneumoniae (Pohl
et al. 1983) and is known as A. pleuropneumoniae biovar
2. Recent studies of isolates of V factor–dependent
strains from cases of disease (the “minor taxon”) have
shown that they belong to three separate species: A. mi-
nor, A. porcinus, and A. indolicus (Moeller et al. 1996).
Pleuropneumonia is one of the important bacterial
diseases of the respiratory tract of the pig and occurs in
most pig-keeping countries. Its importance derives from
the fact that it can cause pneumonia that results in death,
clinical disease that may become chronic, or subclinical
disease in successive batches of pigs and causes losses
from death, reduced production, and increased costs of
medication or vaccination. One of the problems of this
disease for the clinician is that animals may be treated
with antimicrobials effective against the organism, but
they may not respond because of the severity of the ini-
tial lesions and their nature. Both the organism and the
disease have been studied extensively and in consider-
able detail, and the knowledge has been used to design
new vaccines and diagnostic methods, but the best and
most economical methods for control of the disease are
still a matter for discussion.
ETIOLOGY
The etiologic agent A. pleuropneumoniae (formerly
Haemophilus pleuropneumoniae, H. parahaemolyticus),
neotype strains Shope 4074 and ATCC 27088, is a small,
gram-negative, encapsulated rod with typical coccobacil-
lary morphology. The organism does not grow on blood
agar unless it is supplemented with NAD and shows
satellitism around colonies of staphylococci. Staphylo-
coccal streaks are normally required for primary isola-
tion on this medium. The organism forms colonies 0.5–1
mm after 24 hours’ incubation on blood agar in the pres-
ence of staphylococcal colonies and is beta-hemolytic,
particularly when sheep red blood cells are used. Biovar
1 is NAD dependent, and biovar 2 is NAD independent
but requires the presence of specific pyridine nucleotides
or pyridine nucleotide precursors for its NAD biosynthe-
sis (Niven and Levesque 1988). A. pleuropneumoniae pro-
duces an increased zone of hemolysis within the zone of
partial lysis surrounding a beta-toxinogenic Staphylococ-
cus aureus (the CAMP phenomenon) (Nicolet 1970; Kil-
ian 1976) and this CAMP phenomenon has been shown
to be related to the possession of the three cytolysins
ApxI, ApxII, and ApxIII (Frey et al. 1994; Jansen et al.
1995). Additional detailed morphologic and biochemical
characteristics may be found in the original reports
(Shope 1964; Nicolet 1968; Kilian et al. 1978).
A number of related bacteria occur in pigs. A. pleu-
ropneumoniae can be distinguished from H. parasuis by
the presence of hemolysis around staphylococcal streaks
on blood agar; from the NAD-dependent former
Haemophilus sp. “minor group,” Haemophilus sp. “Taxon
C” (Rapp et al. 1985), now assigned to the actinobacilli as
A. minor, A. porcinus, and A. indolicus (Moeller et al.
1996) and Haemophilus sp. “Urease-negative” in the case
of biovar 1; and from actinobacilli commonly isolated
from pigs in the case of biovar 2 (Rapp et al. 1985). A. su-
is is described in Chapter 44.
A. pleuropneumoniae biovar 1 has been divided into 12
serovars. Serovars 1–5 were recognized by Kilian et al.
(1978); however, serovar 5 was subdivided into subtypes
5A and 5B (Nielsen 1986a). Subsequently, serovars 6, 7
(Rosendal and Boyd 1982), 8 (Nielsen and O’Connor
1984), 9 (Nielsen 1985b), 10 (Nielsen 1985c), 11 (Kamp
343
344 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
et al. 1987), and 12 (Nielsen 1986b) have been proposed.
Serovar 10 was erroneously proposed by Kamp et al.
(1987) and was later referred to as serovar 11 (Nielsen
1986b). The serologic specificity is given by the capsular
polysaccharides and cellular lipopolysaccharides (LPS).
However, some serovars show structural similarities or
have identical LPS O chains, thus explaining the cross-re-
actions observed between serovars 1–9 and 11; serovars
3, 6, and 8; and serovars 4 and 7 (Perry et al. 1990).
Serotyping has been extended into biovar 2, where three
serotypes have been identified.
A number of structures and proteins have been iden-
tified in A. pleuropneumoniae. Some are involved in path-
ogenicity and will be described in more detail below, and
many have been identified and their genes sequenced.
Because those of importance in pathogenesis, diagnosis,
and protection are mentioned elsewhere in the text, they
are only reviewed briefly here.
The cell wall is surrounded by a capsule as described
above. The capsular polysaccharides of most serotypes
have been studied in considerable detail and their com-
position is known (Perry et al. 1990). Nonencapsulated
forms have been produced (Inzana et al. 1993). The or-
ganism produces fimbriae 0.5–2 nm in diameter and
60–450 nm in length, which have been identified in elec-
tron microscopy (Utrera and Pijoan 1991). Outer-mem-
brane proteins of MW 43 kDa have been identified
(O’Reilly et al. 1991; Hartmann et al. 1995) and may vary
with NAD availability. Iron-binding proteins have been
identified (D’Silva et al. 1995) and characterized and the
genes sequenced (Gonzalez et al. 1995). Enzymes such as
superoxide dismutase have been identified and the gene
cloned (Langford et al. 1996), and secreted proteases
have been demonstrated (Negrete-Abascal et al. 1994).
The best-known extracellular products are the three cy-
totoxins belonging to the RTX family of toxins and
named by Frey et al. (1993). ApxI is a strong hemolysin of
105–110 kDa, is present in serotypes 1, 5, 9, 10, and 11,
and is encoded by the apx operon consisting of apxIC,
apxIIA, apxIB, and apxID for the activator, the structural
gene, and the two secretion genes, respectively. ApxII is a
hemolysin of 103–105 kDa found in all reference strains
except for serotype 10 and is governed by similar genes,
although secretion protein genes appear to be those of
ApxI. ApxIII is a nonhemolytic cytotoxic protein of 120
kDa found in serotypes 2, 3, 4, 6, and 8 and governed by
the apxIII operon. The genes and many of the operons
governing them have been cloned and sequenced (e.g.,
the apxIII operon; Jansen et al. 1994).
EPIDEMIOLOGY
Pleuropneumonia of the pig is widely distributed. It has
become more important as pig production has become
more intensive. Outbreaks have been reported from
practically all European countries and from different
parts of the United States and Canada, Mexico, South
America, Japan, Korea, Taiwan, and Australia. Although
some serovars are prevalent in certain countries (e.g.,
serovar 2 in Switzerland, Denmark, and Sweden and
serovars 1 and 5 in the United States and Canada), sever-
al serovars may occur in the same country. Some serovars
(e.g., serovar 3), considered to be of low virulence and of
no epidemiologic importance in certain countries, may
be epidemic in others (Desrosiers et al. 1984; Brandreth
and Smith 1985). Moeller et al. (1992) analyzed the mul-
tilocus enzyme electrophoresis (MEE) types of organ-
isms in one restricted area and found that the elec-
trophoretic type (ET) was unrelated to the severity of the
disease. The international relationship of the different
serovars is of special interest, for it points to a transmis-
sion through international exchange of animals. For fur-
ther information on the historic geographic distribution,
see the review of Sebunya and Saunders (1983). A series
of papers have provided further information on the dis-
tribution of serovars within countries (e.g., Austria,
where serovars 4–6 and 10 are most common; see Hofer
et al. 1996) or within regions of countries (e.g., Catalo-
nia, Spain, where 11 serovars, principally 1, 2, 4, 7, 9, and
11, have been identified; see Clota et al. 1996). McDowell
and Ball (1994) showed that serovars 1 and 4 were absent
from the British Isles, which may reflect the restrictions
on imports of live pigs to the U.K. from neighboring
countries of the European Union where these serovars
exist. Different serovars may also occur within farms.
The economic importance of the disease is principal-
ly due to the mortality and production and medical costs
in acute outbreaks. In chronically infected herds, Hunne-
man (1986) found that the rate of daily weight gain was
not affected, although a study by Hartley et al. (1988)
showed that pleurisy at slaughter was associated with an
increase of 1 day to slaughter, and clinical disease with
an increase of 8 days to slaughter. Rohrbach et al. (1993)
demonstrated that the presence of infection in a herd de-
layed slaughter at 113.6 kg by 5.64 days.
A. pleuropneumoniae is a parasite of the respiratory
tract with a high host specificity for pigs. In peracute and
acute infections, it can be found not only in pneumonic
lesions or in septicemia but also in large numbers in
nasal discharges. Survivors of acute infections become
carriers, and the infectious agent is located mainly in
necrotic lung lesions and/or in the tonsils, less frequent-
ly in the nasal cavity (Kume et al. 1984).
The incubation period can be quite variable. Experi-
mental infections show that an exposure to large num-
bers of organisms leads to death within a few hours to a
few days. Exposure to low levels of infection may result
in subclinical disease.
All age categories are susceptible, but the presence of
toxin-neutralizing antibody can affect susceptibility in
herds where the infection is endemic (Cruijsen et al.
1995). The demonstration of antibody in sow colostrum
in endemically infected herds and the persistence of
colostral antibody in piglets may account for the com-
 CHAPTER 26 ACTINOBACILLUS PLEUROPNEUMONIAE
mon development of the disease in pigs from 6 to 8
weeks of age. In the acute phase of the disease morbidi-
ty is generally high. Depending on the virulence of the
strain and on the particular environment, mortality may
vary but is generally high. Both morbidity and mortality
may be exacerbated by the presence of diseases such as
Aujeszky’s disease and porcine reproductive and respira-
tory syndrome (PRRS), although experimental studies
have confirmed that combined infection with A. pleuro-
pneumoniae and PRRS virus may not necessarily result in
more severe disease (Pol et al. 1997). Extensive reviews of
epidemiologic features are given by Nielsen (1982),
Nielsen and Mandrup (1977), and Rosendal and
Mitchell (1983).
The main route of spread is airborne and the disease
is transmitted mainly by direct contact from pig to pig or
by droplets within short distances. In acute outbreaks
the infection may not occur in every pen, suggesting the
possible role of aerosols and air movement in the trans-
mission of the disease over longer distances within
buildings or the indirect transmission of contaminated
exudate from acutely infected pigs by farm personnel.
Transmission by small rodents or birds is doubtful, and
humans are not common hosts of A. pleuropneumoniae.
Survival of the organism in the environment is consid-
ered to be of short duration. When protected with mu-
cus or other organic matter, it can, however, survive for a
few days and it can survive in clean water for periods of
up to 30 days at 4˚C.
Transmission between herds occurs through the in-
troduction of carrier animals to populations without
previous experience of the disease. Airborne transmis-
sion from farm to farm must be taken into consideration
but has not yet been demonstrated. Moving and mixing
pigs increase the risk of pleuropneumonia. Factors such
as crowding and adverse climatic conditions such as
rapid changes in temperature and high relative humidity
coupled with insufficient ventilation encourage the de-
velopment and spread of the disease and, consequently,
also affect morbidity and mortality. It is, therefore, not
surprising that the highest incidence of outbreaks is ob-
served in growing and finishing pigs, mainly in seasons
with adverse weather conditions. As a rule, large herds
which mix pigs frequently are more at risk than small
herds or herds with separate units.
Introduction of the disease by artificial insemination
or embryo transfer is improbable, since the genital tract
is not a common site of infection, and antimicrobials in
the diluent would prevent survival of the contaminating
organism.
PATHOGENESIS
The pathogenesis of pleuropneumonia has been studied
extensively, both in terms of the development of the le-
sions and in terms of the relationship of the organism to
the tissues at a more molecular level. Infection is usually
Taylor 345
by aerosol or by contact, and experimental studies have
shown that the organism can colonize the tonsil and ad-
here to the alveolar epithelium. The same ET type may be
present in both sites in natural infections (Moeller et al.
1992). Adhesion appears to be fimbrial in nature, al-
though it is not clear whether this also applies to the ad-
hesion between the A. pleuropneumoniae capsule and the
receptors found in respiratory tract secretions (Belanger
et al. 1994). A. pleuropneumoniae organisms in the lung
are rapidly phagocytosed by, or adhere to, alveolar
macrophages and produce the toxins ApxI, ApxII, and
ApxIII. All are potentially toxic for alveolar
macrophages, endothelial cells, alveolar epithelial cells,
and the endothelial cells of the capillaries of the alveolar
wall, although ApxIII is particularly active against alveo-
lar macrophages. The organisms appear to be protected
from digestion by phagocytes by their capsules and also
appear to be resistant to the action of complement
(Rycroft and Cullen 1990). Infection is accompanied by
the elaboration of cytokines such as interleukin-1β and
IL-8 in the alveolar fluid, and tumor necrosis factor
(TNF) is also present in the early tissue lesions (Baarsch
et al. 1995). The damage from toxins and cytokines
which accompanies infection is largely responsible for
the lesions which develop (Bertram 1990; Fenwick 1990;
Inzana 1990; Nicolet 1990). The peracute and acute
forms of the disease were considered by Kiorpes et al.
(1990) to produce a systemic effect similar to septic
shock in humans. Differences in the virulence between
the serovars or even within the same serovar have often
been observed (Desrosiers et al. 1984; Rosendal et al.
1985; Brandreth and Smith 1987). It is suggested that
such differences are due to capsular structure (Jacques et
al. 1988), LPS composition (Jensen and Bertram 1986),
or type of hemolysin (Frey and Nicolet 1990). In general,
strains of serovars 1, 5, 9, 10, and 11 are found to be more
virulent than those of other serovars. Concomitant in-
fections with other pathogens of the respiratory tract
which aid the development of pleuropneumonia have
been described by Caruso and Ross (1990).
Lung lesions resulting from the toxic changes may be
seen as early as 3 hours after experimental infection and
become progressively more obvious. The alveolar wall
becomes edematous and capillary congestion develops.
The lymphatics become dilated with edema fluid, fibrin,
and inflammatory cells. Platelet aggregation and neu-
trophil accumulation may also be seen in the damaged
alveolar wall, and both arteriolar thrombosis and wall
necrosis may develop to produce infarction. Micro-
colonies of the organism may be seen in infected alveoli,
and bacteremia may occur. The edges of the lesions be-
come filled with dead and damaged macrophages or de-
bris and can easily be demarcated from the surrounding
lung by 4 days postinfection. Purulent exudate contain-
ing organisms is present in the bronchi. As the lesions
age, their centers become necrotic and healing occurs by
fibrosis.
346 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
Experimental or natural infections stimulate an im-
mune response, and circulating antibodies can be detect-
ed approximately 10–14 days postinfection. These anti-
bodies reach a maximum level within 4–6 weeks
postinfection and may persist at low levels for many
months or even disappear after a bacteriologic cure
(Nicolet 1970; Nicolet et al. 1971; Bachmann 1972;
Nielsen 1982, 1988). Immune sows confer passive im-
munity on their offspring. Such colostral antibodies may
persist for about 5–9 weeks (Bachmann 1972), but the
protection may only last for as little as 3 weeks in some
cases (Nielsen 1975). The antibodies are directed against
a wide range of bacterial structures and products, in-
cluding capsule, LPS antigens, toxins (which can be neu-
tralized), outer-membrane proteins, superoxide dismu-
tase, and iron-binding proteins. Both local IgA
antibodies and serum IgG antibodies are produced.
CLINICAL SIGNS
Clinical signs vary with the age of the animals, their state
of immunity, the environmental conditions, and the de-
gree of exposure to the infectious agent. The clinical
course can be peracute, acute, or chronic (Nicolet et al.
1969; Nielsen 1982; Shope 1964).
In the peracute form, one or more weaned pigs in the
same or different pens suddenly become very ill with
fever to 106.7˚F (41.5˚C), apathy, and anorexia. There is
a short period of slight diarrhea and vomiting. The af-
fected animals lie on the floor without distinct respirato-
ry signs, the pulse rate increases very early, and cardiac
and circulatory failure develop. The skin on the nose,
ears, legs, and later the whole body becomes cyanotic. In
the terminal phase, there is a severe dyspnea with mouth
breathing, animals remain in a sitting posture, and rectal
temperatures decrease markedly. Shortly before death,
there is usually a copious, foamy, blood-tinged discharge
through the mouth and nostrils. Death occurs within
24–36 hours of the development of clinical signs. Occa-
sionally an animal may die suddenly without premonito-
ry clinical signs or be found dead in a pen; experimental
studies have shown that the course of the disease may be
as little as 3 hours from infection to death. In neonatal
pigs the disease occurs as a septicemia with fatal results.
In the acute form, many pigs in the same or different
pens are affected. Body temperature rises to 105–106˚F
(40.5–41˚C), the skin may be reddened, and the animals
are depressed, are reluctant to rise, refuse food, and are
reluctant to drink (Pijpers et al. 1990). Severe respiratory
symptoms with dyspnea, cough, and sometimes mouth
breathing are evident. Cardiac and circulatory failure are
usually present, with congestion of the extremities.
There is a marked loss of condition, which is apparent
within 24 hours of the onset of the disease. The course of
the disease differs from animal to animal, depending on
the extent of the lung lesions and the time of initiation of
therapy. All stages of disease, from intermediate to fatal,
subacute, or chronic, may develop within an affected
group.
The subacute and chronic forms develop after the dis-
appearance of acute signs. There is little or no fever, and
a spontaneous or intermittent cough of varying intensi-
ty develops. Appetite may be reduced, and this may con-
tribute to the decreased rate of gain in body weight. Af-
fected animals can be identified by their intolerance of
exercise. When moved, they lag behind the group and
struggle only feebly when restrained. In chronically in-
fected herds there are often many subclinically diseased
animals. The clinical signs may be exacerbated by other
respiratory infections (mycoplasmal, bacterial, or viral).
In primary outbreaks abortions may be observed (Wil-
son and Kierstead 1976), especially in specific-pathogen-
free (SPF) herds. Complications such as arthritis, endo-
carditis, and abscesses in different sites may occur in
individual animals and were considered by Nicolet
(1970) to be due principally to serovar 3 of A. pleuro-
pneumoniae, although other serovars have now been re-
ported from these sites. Middle-ear disease has recently
been associated with A. pleuropneumoniae infection (Duff
et al. 1996).
LESIONS
The gross pathological lesions are located mainly in the
respiratory tract. The pneumonia is mostly bilateral,
with involvement of the cardiac and apical lobes, as well
as at least part of the diaphragmatic lobes, where pneu-
monic lesions are often focal and well demarcated (Fig.
26.1). In rapidly fatal cases the trachea and bronchi are
filled with a foamy, blood-tinged, mucous exudate and
few gross changes may be obvious. In slightly later pera-
cute cases, the pneumonic areas appear dark and solid
with little or no fibinous pleurisy; and the cut surface is
friable. Fibrinous pleurisy is very obvious in animals
which die in the acute stage of the disease, at least 24
hours after infection, and the thoracic cavity contains a
blood-tinged fluid. As the lesions age, the fibrinous
pleurisy over the affected areas of lung becomes fibrous
and may adhere so strongly to the parietal pleura that
lung parenchyma may remain attached to the parietal
pleura when the lungs are removed at postmortem ex-
amination. The uniform dark red or black of the early
lung lesion becomes lighter in color and remains firm on-
ly in the worst-affected areas. The lesions shrink in size as
resolution progresses, until in more chronic cases nod-
ules of different sizes remain, mostly in the diaphrag-
matic lobes. These abscess-like nodules are delimited by
a thick capsule of connective tissue (Fig. 26.2) and may
be associated with areas of adhesive fibrous pleurisy. In
many cases the lung lesion resolves, and only a residual
 CHAPTER 26 ACTINOBACILLUS PLEUROPNEUMONIAE
26.1. Gross lesions of a peracute case of pleuropneumo-
nia showing a well-circumscribed pneumonic area in
different lobes with fibrinous pleurisy. (Courtesy
Professor H. König, Institute of Animal Pathology,
University of Berne.)
Taylor 347
focus of adhesive fibrous pleurisy remains. A high preva-
lence of chronic pleuritis at slaughter is very suggestive
of pleuropneumonia.
In the early stages of the disease, the histopathologic
changes are characterized by necrosis, hemorrhage, neu-
trophil infiltration, macrophage and platelet activation,
vascular thrombosis, widespread edema, and fibrinous
exudate (Bertram 1985, 1986, 1988; Liggett and Harri-
son 1987). Following the acute response, macrophage in-
filtration, marked fibrosis around areas of necrosis, and
fibrous pleuritis are characteristic (Häni et al. 1973). Fur-
ther descriptions are given in early papers by Pattison et
al. (1957), Olander (1963), and Shope (1964).
DIAGNOSIS
Pleuropneumonia may be suspected clinically in acute
outbreaks. In such cases the presence of characteristic
lung lesions with pleurisy at postmortem examination
enhances suspicion, which is enforced by the histological
appearance of the lesions. The presence of an acute ex-
udative pneumonia with areas of necrosis surrounded by
palisades and whorls of neutrophil debris provides fur-
ther evidence for pleuropneumonia. In chronic infec-
tions the necropsy findings of firm, well-demarcated ab-
scesses associated with pleurisy and pericarditis are very
suggestive. In view of the importance of this disease to
herd health control programs and the potential for eco-
nomic loss, bacteriologic confirmation of the diagnosis
should be carried out.
It is easy to demonstrate the etiologic agent in
bronchial or nasal exudate and pneumonic lesions from
freshly dead animals. Gram-stained smears of lung le-
sions contain numerous gram-negative coccobacilli.
Their identity can be confirmed as A. pleuropneumoniae
26.2. Chronic pleuropneumo-
nia. Cross section of a well-
capsulated nodule in the
diaphragmatic lobe. (Courtesy
Professor H. König, Institute of
Animal Pathology, University of
Berne.)
348 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
by using a fluorescent antibody test (Nicolet 1970), by
immunoperoxidase, by detection of serovar-specific anti-
gens in lung extracts with a coagglutination test (Mittal
et al. 1983), by using a latex agglutination test, or by
ELISA. Nucleic acid from bacteria may be detected by a
number of methods, including labeled DNA probes in
tissue and polymerase chain reaction (PCR). Direct con-
firmation by PCR of the presence of A. pleuropneumoniae
in tissue is not yet routine.
Primary isolation of A. pleuropneumoniae from tissues
and secretions may be carried out on 5% sheep blood
agar with a cross-streak of Staphylococcus epidermidis or
S. aureus. After aerobic incubation overnight, small
colonies appear in the neighborhood of the streak (NAD
requirement) surrounded by a clear zone of complete he-
molysis. This allows a rapid presumptive bacteriologic
diagnosis. Altered blood agars (“chocolate agar”) allow
the growth of the organism, but it is less distinctive on
these media. Biochemical identification can be carried
out by demonstrating the CAMP phenomenon, urease
activity, and the fermentation of mannitol. In the case of
mixed infections, particularly with P. multocida, or cont-
amination with other bacteria, the use of selective media
is recommended (Little and Harding 1971; Gilbride and
Rosendal 1983). Jacobsen and Nielsen (1995) described a
selective medium capable of isolating the organism from
tonsils, an important site of carriage. However, isolation
may fail in very old chronic lesions or where treatment
has been given. In peracute cases it is possible to isolate
the agent from other organs (septicemia).
Isolates may be confirmed as belonging to A. pleuro-
pneumoniae by PCR (Gram et al. 1996) or by serologic
tests using absorbed or monoclonal antibodies. They can
be identified to serovars using a PCR for the activator and
structural genes of the toxins (Frey et al. 1995) or, more
conventionally, using monoclonal antibodies to particu-
lar serovars (e.g., Lairini et al. 1995, for serovar 1; Ro-
driguez-Barbosa et al. 1995, for serovar 2). Serotyping
can be routinely achieved by slide agglutination from a
subculture on a medium enriched with serum (Nicolet
1971) or by the coagglutination test (Mittal et al. 1987).
In many cases the final identification can only be
achieved by agar gel diffusion and by indirect hemagglu-
tination. A critical evaluation of the earlier serotyping
methods is given by Nicolet (1988). It is possible to
serotype organisms in tissue and as isolates with latex
particle tests (Inzana 1995) using capsular polysaccha-
ride to sensitize the particles. The serotyping of isolates
is recommended for rapid confirmation of the bacterio-
logic diagnosis and is essential when vaccination policy is
being considered. It demonstrates the local distribution
of serovars and allows the epidemiologic situation to be
evaluated and the performance of specific serologic tests
to be monitored.
The detection of antibodies is of little diagnostic val-
ue in recent outbreaks but provides an important tool in
epidemiologic investigations (Nielsen 1988). Antibody
may be detected in a number of ways. Methods such as
the complement fixation (CF) test or a 2-mercap-
toethanol (2-ME) tube agglutination (Mittal et al. 1984)
are suitable for this purpose.
Simple methods include ELISAs (Nicolet et al. 1981;
Morrison et al. 1984), and antigens such as cell extracts
or long-chain LPSs have been evaluated (Gottschalk et al.
1994). Blocking ELISAs (Nielsen 1995) and testing with
serovar-specific antigens allow the identification of anti-
body to a specific serovar, while detection of antibody to
the toxins and, especially, neutralizing antibody to those
toxins can indicate a measure of protection (Cruijsen et
al. 1995). Serum antibody determination can be used to
determine antibody profiles of herds or to demonstrate
the presence of colostral antibody (Nielsen 1995). In all
serologic examinations, care should be taken to exclude
antibodies generated by infection with A. suis and other
members of the Pasteurellaceae.
Hog cholera, erysipelas, and streptococcal infections
must be considered in the possible differential diagnosis
of peracute and acute cases. In subacute and chronic in-
fections, the lung lesions should be distinguished from
those caused by pyogenic bacterial agents such as A. pyo-
genes, S. aureus, diphtheroid rods, and Fusobacterium
necrophorum. The lung lesions caused by other porcine
actinobacilli may be indistinguishable from those of
pleuropneumonia, and acute pasteurellosis may some-
times resemble pleuropneumonia.
TREATMENT
A. pleuropneumoniae is particularly susceptible in vitro to
penicillin, ampicillin, cephalosporin, chloramphenicol,
tetracyclines, colistin, sulfonamide, cotrimoxazole
(trimethoprim + sulfamethoxazole), and gentamicin, to
which it has low minimum inhibitory concentrations
(MIC). High MIC values are found for streptomycin,
kanamycin, spectinomycin, spiramycin, and lincomycin
(Nicolet and Schifferli 1982; Gilbride and Rosendal
1984; Nadeau et al. 1988; Inoue et al. 1984). Sensitivities
of A. pleuropneumoniae to antimicrobials have been re-
viewed by Prescott and Baggot (1993).
The emergence of resistance to ampicillin, strepto-
mycin, sulfonamides, tetracyclines, and chlorampheni-
col is of serious concern. It seems to be frequent in
serovars 1, 3, 5, and 7 (Gilbride and Rosendal 1984; Vail-
lancourt et al. 1988) but rare in other serovars, particu-
larly serovar 2 (Nicolet and Schifferli 1982; Inoue et al.
1984). The antibiotic resistance is plasmid mediated
(Hirsh et al. 1982; Huether et al. 1987; Wilson et al.
1989).
The antimicrobial of first choice should be the one
with the lowest MIC and with the most satisfactory phar-
macokinetic properties. Consequently, the betalactams
(principally penicillin and cephalosporin), chloram-
 CHAPTER 26 ACTINOBACILLUS PLEUROPNEUMONIAE
phenicol, cotrimoxazole, and, to some extent, tetracy-
clines are considered to be most active. Recently avail-
able substances such as the quinolone derivatives (en-
rofloxacin) (Kobisch et al. 1990) or the semisynthetic
cephalosporin ceftiofur sodium (Stephano et al. 1990)
have been shown to be particularly effective after experi-
mental challenge. Satisfactory results in the field have
been reported with tiamulin (Anderson and Williams
1990) and a combination of lincomycin and spectino-
mycin (Hsu 1990). Tilmicosin has been used in feed by
Moore et al. (1996). The determination of an antibi-
ogram is recommended where problems are being expe-
rienced with treatment.
Antibiotic therapy is effective in clinically affected an-
imals only in the initial phase of the disease, when it can
reduce mortality. The nature of the lesions means that
delay in treatment can result in a degree of infarction
and chronic damage which will leave the animal as a res-
piratory cripple even if it recovers. Antibiotics should be
given parenterally (subcutaneously or intramuscularly)
and in high dosage, as affected animals may not eat or
drink (Pijpers et al. 1990). To ensure effective and
durable blood concentrations, repeated injections may
be required, depending on the pharmacokinetic proper-
ties of the antibiotic used. The success of therapy de-
pends mainly on early detection of clinical signs and on
rapid therapeutic intervention. Water treatment may be
used to treat members of the affected group which are
still able to drink. Feed medicated with any of the above
antimicrobials may be used successfully if all pigs have a
normal food and water intake. Feed and water medica-
tion can be used for the strategic treatment of infected
groups on entry to an airspace. A combination of par-
enteral and peroral medication in a recent outbreak of-
ten yields the best results. In spite of apparent clinical
success, it must be remembered that antibiotic therapy
does not eliminate infection in a herd. Chronic infections
in lung abscesses or on the tonsils of carriers persist to
form an important source of infection for other animals.
Severely affected animals may not recover even after
treatment and nursing and should be killed.
PREVENTION
Prevention and control of pleuropneumonia may be ac-
complished in a number of different ways. Farms free
from the disease and infection should maintain a policy
of isolation coupled with the use of semen or embryos to
introduce new genes. Any animals introduced should be
hysterectomy derived or originate from herds known to
be free from the disease and from infection. It may be
appropriate to hold them in quarantine prior to intro-
duction to the herd; developments in detecting the or-
ganism and in serology make it increasingly worthwhile
to test them for either infection or antibody prior to in-
troduction to the main herd.
Taylor 349
Once the infection has been established on a farm, it
is difficult to eliminate the infectious agent, although the
herd may become clinically normal. Control programs
must take account of the epidemiologic features of pleu-
ropneumonia. The first priority must be to control eco-
nomic loss (mortality, clinical and subclinical disease)
and then to consider the control or elimination of infec-
tion. Mortality can be controlled by the treatment of cas-
es and of infected groups using the methods and antimi-
crobials outlined above. Disease may be treated at an
early stage by treating groups of animals into clean air-
spaces and then maintaining them as a group in isolation
until slaughter. Where this may not be possible, control
of environmental factors such as temperature and venti-
lation and use of solid partitions between pens may min-
imize the development and severity of disease. Continu-
ous medication or pulse dosing may be practiced, but
neither should be used for long, and the antimicrobial
sensitivity of the organism should be monitored contin-
uously. Strategic medication should be targeted at peri-
ods of risk, which can be identified by routine post-
mortem examinations, clinical examinations, and herd
antibody profiles. The generalized methods used to con-
trol respiratory disease, such as the all-in/all-out system
in fattening units, segregated early weaning, and large
airspaces with separation, will all considerably reduce
the risk of infection. Animals should be brought in only
from herds free from infection to avoid introducing new
serovars or new antimicrobial resistances. In chronically
infected herds, purchased seronegative animals should
be vaccinated before introduction to the herd.
A wide range of vaccines has been developed for this
disease. They fall into two main groups: the killed organ-
isms and the subunit vaccines. Vaccination with killed
organisms is serovar specific (Nielsen 1984), with possi-
ble cross-immunity with cross-reacting serovars (Nielsen
1985a). The protection afforded has been extended by
including all the serovars present in an area (e.g., 3, 6,
and 8 in the United Kingdom). The type of adjuvant used
may affect efficacy, and care may also be necessary before
using certain adjuvants in pigs intended for human con-
sumption, as some vaccines can produce undesirable
granulomatous lesions at the site of injection (Straw et
al. 1985). Vaccines in the second group are currently un-
der development or being marketed and consist of vary-
ing combinations of subunits such as toxins and outer-
membrane proteins. A wide range of antigens has been
found to be protective. They include the toxins (Haga et
al. 1997), combinations of Apx toxins and the outer-
membrane proteins (Valks et al. 1996), extracellular
products of A. pleuropneumoniae, and structural or func-
tioning antigens such as the iron-binding proteins. Vac-
cines of this type are generally protective against all
serovars.
All the vaccines currently used are administered par-
enterally, usually as a course of two injections, and are
350 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
intended to provide protection to the growing pig. Ex-
perimental vaccines consisting of attenuated organisms
(Inzana et al. 1993) and killed organisms or their sub-
units have been given by the aerosol and oral routes and
have provided some protection.
Vaccines are generally given as maternal antibody
wanes and provide high levels of protection against mor-
bidity in experiments, reduce mortality, reduce the num-
ber of treatments required, increase daily liveweight
gain, and may improve feed conversion efficiency. The
quality of the carcass is also improved, with fewer con-
demnations for pneumonia and lower slaughtering costs
through reductions in pleurisy and pericarditis. The old-
er generation of vaccines were not always effective in the
field (Hunneman 1986). Vaccines do not always prevent
the carrier state but have been used as an aid in eradica-
tion programs. The decision to vaccinate should be care-
fully evaluated; the costs of mortality alone should not
be the sole consideration, because the other effects on
productivity listed above contribute to the benefits of
vaccination.
Control of pleuropneumonia on a farm can be ac-
complished by combining treatment, vaccination, and
husbandry practices such as those outlined above. Disin-
fection should be included in any control program; the
organism is sensitive to a wide range of commonly used
disinfectants (Gutierrez et al. 1995).
Control of pleuropneumonia in a region or breeding
pyramid involves health schemes aimed at pleuropneu-
monia-free breeding and multiplying herds, serologic
monitoring, monitoring at slaughter and postmortem
examination of casualties, control of management, and
controlled pig traffic (serologic testing, quarantine). For
herds infected with A. pleuropneumoniae intending to join
such a scheme, an eradication program is the method of
choice but requires careful evaluation of the economic
consequences. Depopulation and restocking with pigs
originating from certified pleuropneumonia-free herds is
the method of choice. This method is expensive and may
lead to the loss of important bloodlines. These can be
saved by a program of hysterectomy and separate rear-
ing.
An extensive program of testing and evaluation is re-
quired before herds undergoing all other types of eradi-
cation program can be admitted to a pool of pleuro-
pneumonia-free herds. Methods which have succeeded
in the past include an eradication program in the existing
herd area but weaning at another farm, at the same time
supported by a program of vaccination, medication, and
culling and repopulation with disease-free gilts (Larsen
et al. 1990). Breeding herds with a relatively low percent-
age of seropositive animals (up to 30%) have used the
“test-and-removal” of seropositive animals under med-
ication (Nicolet 1970; Nielsen et al. 1976). The principle
is based on the serologic testing of sows shortly before
farrowing and by weaning the piglets at 2 weeks of age
under strict separation from the potentially infected
stock. These piglets, which are seronegative up to the age
of 12 weeks, serve to restock the herd. Seropositive sows
are systematically eliminated until the entire breeding
stock is seronegative. This program can take 6–12
months. During the elimination procedure, the whole
herd is protected from reinfection by medicated feed, for
example, cotrimoxazole (trimethoprim + sulfamethoxa-
zole 1:20, 250 mg/kg feed). Certain reports suggest that
only partial success (Lariviere et al. 1990) or even failure
(Hunnemann 1986) has resulted from the application of
such eradication programs, and the current require-
ments to avoid antimicrobial residues and to reduce an-
timicrobial resistance may make them impractical.
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 Progressive and Nonprogressive
27 Atrophic Rhinitis
M. F. de Jong
A disease condition in pigs referred to as “atrophic rhini-
tis” (or “infectious atrophic rhinitis”) and “chronic at-
rophic rhinitis” has been recognized for nearly two cen-
turies. A disease of the pig characterized by stunted
development or total disappearance of the nasal
turbinates (called “turbinate atrophy”) has been recog-
nized for over 160 years and was first described as
“Schnüffelkrankheit” in Germany (Franque 1830), where it
became prevalent in several areas.
These conditions are now classified as either nonpro-
gressive atrophic rhinitis (NPAR), caused by toxigenic
Bordetella bronchiseptica, or progressive atrophic rhinitis
(PAR), caused by toxigenic Pasteurella multocida, alone or
in combination with other agents (e.g., B. bronchiseptica).
The characteristic lesion caused by both agents is a hy-
poplasia of the nasal turbinate bones (conchal atrophy);
in moderate to severe outbreaks this is accompanied by
degrees of facial distortion (including brachygnathia su-
perior, lateral deviation of the snout, and septum devia-
tion) and nasal hemorrhage as a result of frequent sneez-
ing. Nasal hemorrhage is rare in NPAR but characteristic
in PAR.
In contrast to NPAR, PAR is of global economic sig-
nificance to swine production, since in PAR, these signs
are accompanied by poor growth of fattening pigs (Ped-
ersen and Barfod 1981). Toxigenic P. multocida is still
spreading in the pig population, especially where disease
control measurements are carried out ineffectively (Glat-
tleider et al. 1996; Frymus et al. 1996). The PAR toxigenic
P. multocida is also able to cause disease in other species,
such as rabbits, goats, sheep, cattle, poultry, and turkeys.
Even humans can become infected, and lesions some-
what comparable to those in swine can result. Poultry,
sheep, and cattle, along with rats, cats, and dogs, are de-
scribed as carriers (Avril et al. 1990; Donnio et al. 1991;
Nielsen and Frederiksen 1990). Toxigenic P. multocida
should therefore be considered a zoonosis and should be
of concern to governmental and human and veterinary
health organizations.
Toxigenic B. bronchiseptica is widespread in swine
production and considered to cause a minor or insignifi-
cant growth depression in diseased pigs and is therefore
called nonprogressive atrophic rhinitis.
The individual and combined importance of both
agents will be discussed in this chapter.
The precise etiology of the “condition” atrophic
rhinitis (AR) has been actively debated, with intermit-
tent attempts at definition, for well over a century. Since
the 1930s, observations by Ratke (1938), Thunberg and
Carlstrom (1940), and Philips (1946) have implied that
the disease was contagious. Shortly thereafter it was
demonstrated experimentally that turbinate atrophy was
transmissible between pigs; when young pigs were inoc-
ulated intranasally with crude material from atrophic
turbinates, they frequently developed turbinate atrophy
(Jones 1947; MacNabb 1948; Philips et al. 1948; Gwatkin
et al. 1949, 1951; Terpstra and Akkermans 1960). Much
research has since been directed toward defining the pre-
cise microbiological agent(s) responsible. While several
management and husbandry factors can influence the
severity and clinical expression of PAR, this disease is
now established primarily as an infectious disease de-
spite attempts at one time to redefine it as a disorder fun-
damentally of nutritional origin (Brown et al. 1966).
In 1956 Switzer suggested that turbinate atrophy may
be caused by several agents, including trichomonads
(Switzer 1951), filter-passing agents (Switzer 1953),
viruses (Switzer and L’Ecuyer 1960; Edington et al.
1976), and mycoplasmas (Switzer 1955; Edington et al.
1976; Gois et al. 1977). Only special AR-toxigenic strains
of B. bronchiseptica and AR-toxigenic strains of P. multo-
cida have consistently produced “turbinate atrophy”
when sufficient quantities of pure (broth) cultures have
been inoculated intranasally into young susceptible (e.g.,
colostrum-deprived specific-pathogen-free [SPF]) pigs.
Despite these observations, however, clinical (and patho-
logical) disease cannot be attributed solely to infection
with either one or both agents, since these infections can
occur in the field in the (temporary) absence of clinical
disease (the so-called subclinical stage of PAR). Interrup-
tions between periods of clinical disease that can vary in
duration from approximately 2 months to about 2 years
can occur in infected herds. Herd monitoring based on
clinical (and/or pathological) features, therefore, cannot
guarantee the absence of infectious PAR in a pig herd.
Complementary monitoring of a herd or connected
(breeding) herds for over 1 year, based on bacteriologic
and/or serologic detection of the PAR-toxigenic P. multo-
cida, may be necessary to obtain sufficient information
concerning the PAR-infected or PAR-free status of the
herd.
355
356 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
DEFINITION
At this point it is important to define carefully the condi-
tions described in this chapter. All diseases that cause
turbinate atrophy in swine are called infectious atrophic
rhinitis by farmers. The term “infectious progressive at-
rophic rhinitis” should be reserved for the disease pro-
duced by one etiologic agent, P. multocida. Pedersen and
Nielsen (1983) first recommended the use of this term as
a result of the deliberations of a European Economic
Community commission of specialists on PAR. To ob-
tain a consensus in a worldwide forum, the proposal was
repeated by Pedersen and coworkers in 1988. The first
agreement among specialists in swine diseases from Eu-
rope, North and South America, and Asia was achieved
in 1988 (de Jong and Nielsen 1990). It was agreed to de-
fine PAR as a disease caused by infection with toxigenic
P. multocida. In herds where suspicious manifestations
such as sneezing, nose bleeding, snout deformation,
growth retardation, turbinate atrophy, and septum devi-
ation are observed and where toxigenic P. multocida is de-
tected (bacteriologically or serologically), the diagnosis
of PAR can be confirmed. However, the disease may also
develop in or be transmitted by pigs from herds harbor-
ing toxigenic P. multocida even though only slight or sub-
clinical disease is present. The advantage of an etiologic
definition of PAR rests on the possibility of identifying,
independently of actual clinical status, those herds that
are able to transmit or develop the severe clinical disease
(Bollwahn 1988).
Estimates of the economic impact of PAR in swine
have varied, but in moderate to severe outbreaks it can
be of considerable economic importance (Pedersen and
Nielsen 1983; Glattleider et al. 1996). From the clinical
and pathological points of view, it is probably no longer
useful to employ the term “atrophic rhinitis” as denoting
a single disease complex. Rather, bordetellosis and toxi-
genic pasteurellosis should be distinguished as NPAR
and PAR. The infectious agents have completely different
economic impacts in swine production and require dif-
ferent methods and strategies for prevention and treat-
ment.
ETIOLOGY
Research suggests that toxigenic strains of both B. bron-
chiseptica and P. multocida are the primary infectious eti-
ologic factors in NPAR and PAR, respectively. The sever-
ity of the disease that develops in a pig is related to the
amount of one or of both toxins absorbed by the animal
(Van Diemen et al. 1994a). The susceptibility of pigs to a
certain amount of toxin that causes turbinate bone re-
duction has been shown to be age related. Toxigenic
strains of P. multocida have been shown to produce se-
vere PAR, including extreme growth retardation, even in
pigs older than 3 months of age; toxigenic strains of B.
bronchiseptica produce turbinate hypoplasia only in pigs
until about the age of 6 weeks.
The conditions for the growth and/or colonization of
P. multocida or B. bronchiseptica necessary to produce suf-
ficient amounts of toxin are influenced by bacteriologic
and/or virologic damage to the mucosa and by certain
environmental, management, and husbandry factors
that create the (multifactorial) disease complex. When
these factors are all present, very severe clinical PAR can
result. Since growth retardation and clinical PAR also oc-
cur after parenteral dosing with the toxin of P. multocida,
colonization of toxigenic P. multocida in the nose may
not be necessary for the development of the disease.
Tonsils and lungs also have to be considered as locations
for toxin production (Ackermann et al. 1994).
Infectious Agents
BORDETELLA BRONCHISEPTICA. B. bronchiseptica is
a small, motile, gram-negative rod or coccobacillus mea-
suring approximately 1.0 × 0.3 µm in size. The bacterium
is aerobic, does not ferment carbohydrates, utilizes cit-
rate, and splits urea.
B. bronchiseptica has been isolated widely from young
pigs with rhinitis and from pigs with pneumonia and al-
so from animals in herds showing no clinical signs of res-
piratory disease. It is also a pathogen or potential
pathogen of many other mammals, including dogs, cats,
and rats.
In the United States during the 1960s, B. bronchisepti-
ca was said to be the principal cause of atrophic rhinitis
(Switzer and Farrington 1975). After intranasal instilla-
tion of pure cultures of B. bronchiseptica in colostrum-
deprived pigs a few days old, Cross and Claflin (1962)
were able to produce typical experimental turbinate at-
rophy. This work was repeated by Ross et al. (1967), who
were able to reproduce turbinate atrophy with pure cul-
tures of AR-toxigenic B. bronchiseptica in 95% of pigs in-
oculated at 1–3 days of age but in only 66% of 4-week-old
pigs. Brassinne et al. (1976) reported that only high num-
bers of AR-toxigenic B. bronchiseptica caused turbinate
lesions. A toxigenic strain that caused 100% turbinate at-
rophy in 3-week-old colostrum-deprived SPF pigs did not
cause typical atrophy when intranasally instilled during
4 successive days in 6-week-old pigs (de Jong and Akker-
mans 1986). This indicated that between 3 and 6 weeks
of age, the sensitivity to a heavy infection with an AR-tox-
igenic B. bronchiseptica strain dropped drastically. Dun-
can et al. (1966a) had already stated that experimental
infections with B. bronchiseptica did not cause severe pro-
gressive lesions. Pearce and Roe (1966) were unsuccess-
ful in producing turbinate atrophy with cultures of B.
bronchiseptica in naturally farrowed pigs but were able to
produce the lesions when the culture was inoculated into
colostrum-deprived pigs. This indicated protection
against AR lesions by colostral immunity.
Bacteriologic data from nasal swabs taken from pigs
 CHAPTER 27 PROGRESSIVE AND NONPROGRESSIVE ATROPHIC RHINITIS
at different ages suggested that B. bronchiseptica infection
starts to build up in conventional herds with and without
clinical signs of PAR in the third week of age, when the
nasal sensitivity for toxigenic B. bronchiseptica has al-
ready started to decrease (Pedersen and Nielsen 1983;
de Jong 1985). This meant that, under natural (conven-
tional) conditions, the influence of B. bronchiseptica as a
primary cause of PAR has been overestimated. Turbinate
atrophy can occur in 2- to 3-month-old piglets in excep-
tional circumstances, such as after a primary B. bron-
chiseptica infection in SPF herds (Schöss 1982) and after
experimental infections in piglets free from antibodies.
Partial or total regeneration of such atrophy has been de-
scribed and such infections seem to result in only a limit-
ed and low percentage of transient clinical snout devia-
tions; animals with lesions caused by B. bronchiseptica
did not develop significant growth depression (Pedersen
and Barfod 1982).
Nearly all B. bronchiseptica strains from pigs pro-
duced the thermolabile AR toxin. B. bronchiseptica can al-
so affect the lower respiratory system, and toxin produc-
tion from such regions may have some influence on
clinical symptoms of NPAR.
Variations in virulence among porcine B. bronchisepti-
ca strains are known to exist. Collings and Rutter (1985)
determined that only those strains in phase 1 and isolat-
ed from pigs caused turbinate atrophy, and they estab-
lished that the ability to both colonize the nasal cavity in
large numbers and produce a cytotoxin were important
virulence determinants. The role of the cytotoxin was
clearly established by Magyar et al. (1988), who also ex-
amined the role of several other putative virulence deter-
minants, including a hemolysin, adenylate cyclase, and
an adhesin. By comparing the pathogenic effects of a
porcine cytotoxic phase 1 strain with a noncytotoxic
phase 1 strain also of porcine origin, they established
that it is the cytotoxin (which is probably the same as the
mouse lethal factor and dermonecrotic toxin) that is the
key virulence determinant in the production of turbinate
hypoplasia.
In a comparison of three biological assays for the de-
tection of toxigenic properties of B. bronchiseptica, dis-
crepancies were found between the guinea pig skin test,
the mouse spleen atrophy assay, and the suckling mice
mortality assay (Mendoza 1993), suggesting that differ-
ences exist between these toxigenic properties.
Discrepancies in the results of studies obtained in dif-
ferent countries could arise from variation in virulence or
the amount of toxin produced by the organism con-
cerned. This has been reported for isolates of B. bron-
chiseptica in the United States (Ross et al. 1967; Skelly et
al. 1980), Canada (Miniats and Johnson 1980), the Unit-
ed Kingdom (Collings 1983), and Hungary (Elias et al.
1982). However, even the most virulent of 10 U.K. iso-
lates did not cause progressive turbinate atrophy or sig-
nificant snout deformation in experimental infections
de Jong 357
(Rutter and Rojas 1982). More important, strains isolat-
ed from herds with or without progressive disease in the
United Kingdom all caused nonprogressive lesions of
similar severity (Rutter and Rojas 1982; Giles and Smith
1983). From observations in this laboratory, it appeared
that strains isolated in PAR-diseased herds and in herds
not suspected of PAR produced roughly the same
amount of toxin. Only a few strains differed from this
pattern (de Jong and Akkermans 1986). Thus, there is
strong evidence, contrary to the opinions of Kielstein
(1983) and Nakai et al. (1986), that although there are
differences in the virulence of isolates of B. bronchisepti-
ca, the severe lesions of clinical PAR cannot be attributed
only to this organism. Pigs infected with B. bronchiseptica
in the deeper respiratory system may be more sensitive
to other pulmonary infections. This means that B. bron-
chiseptica infections should not be neglected as a respira-
tory pathogen.
PASTEURELLA MULTOCIDA. P. multocida is a non-
motile, gram-negative rod or coccobacillus approximate-
ly 0.3 × 0.6 µm in size. The bacterium is aerobic, fer-
ments glucose without gas, and produces indole. In fresh
smears the organism shows distinct bipolar staining.
The colonies of P. multocida type A are larger and more
mucoid than those of type D. On blood agar plates a
characteristic odor is generally produced.
P. multocida and its subspecies have been isolated
widely from pigs with and without clinical symptoms of
rhinitis or pneumonia. Early studies (reviewed by
Gwatkin 1959) established that P. multocida could exper-
imentally produce turbinate atrophy in pigs and rabbits
and that it was frequently but not always isolated from
field outbreaks.
Several workers subsequently examined the ability of
this organism to produce turbinate atrophy under con-
trolled experimental conditions. Some strains studied
produced a mild rhinitis but were unable to induce
marked turbinate hypoplasia (Harris and Switzer 1968;
Smith 1971; Koshimizu et al. 1973; Nakagawa et al. 1974;
Edington et al. 1976), whereas in other studies, particu-
larly from Europe, cultures of P. multocida produced
nasal deformity and turbinate atrophy (Dirks et al. 1973)
and even severe PAR (Nielsen et al. 1976). In Germany
and in the Netherlands particularly, P. multocida was
considered to be an important primary pathogen in PAR
(Dirks et al. 1973). Medication and vaccination with bor-
detella vaccines in PAR herds reduced B. bronchiseptica
successfully but failed to affect PAR. In these herds P.
multocida was found to be the major pathogen. Reducing
P. multocida in these herds decreased PAR (de Jong 1976-
1979, 1980).
A major step in resolving these conflicting opinions
began in the Netherlands when de Jong (1976-1979) and
de Jong et al. (1980) began to test different P. multocida
strains isolated from herds with and without PAR in
358 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
colostrum-deprived SPF piglets, as described earlier by
Ross et al. (1967) for B. bronchiseptica.
P. multocida grows in a semifluid mucus on the mu-
cosal membrane of the nose rather than on the nasal ep-
ithelium itself, so studies were redirected from cultures
washed off solid medium and resuspended to broth cul-
tures. These broth cultures contained substances excret-
ed by the bacteria. After this change it was easy to repro-
duce AR lesions with the same strain in 3-week-old pigs
(or older) instead of in 3-day-old pigs.
Martineau et al. (1982) showed the importance of us-
ing broth cultures instead of cultures washed from solid
media, and explained that this could be a possible reason
for the different findings of investigators (Nakai et al.
1986). Pure cultures of both dermonecrotic and nonder-
monecrotic type D and type A isolates of P. multocida es-
tablish themselves poorly in the nasal cavity of healthy
conventional (Voets 1990), SPF (de Jong 1985), and gno-
tobiotic piglets (Rutter and Rojas 1982; Rutter 1983).
Nasal instillations of pure broth cultures of toxigenic P.
multocida needed to be repeated for approximately 4
days to produce a severe P. multocida nasal infection that
resulted in PAR. Uninoculated pigs kept in contact with
inoculated pigs became infected, but only mild lesions
were noticed 4 weeks later. Sneezing was sporadic in
these experiments with gnotobiotic and SPF pigs. In con-
trast, experimental infection with toxigenic P. multocida
in conventional pigs pretreated with chemical irritants
or with B. bronchiseptica resulted in sneezing, and PAR le-
sions also occurred in pigs in contact. The strains that
caused PAR lesions were called AR pathogenic. This
characteristic correlated with the ability to produce a
thermolabile toxin. PAR could be reproduced complete-
ly with bacteria-free filtrates of these unheated toxins.
Nasal infection by aerosol with 0.5 mL 5 and 13 µg
toxin/mL per nostril in 4-week-old piglets induced sub-
clinical ventral turbinate hypoplasia (atrophy). Amounts
of 40 µg/mL induced severe lesions. During the 5-week
period after challenge, depression of weight gain started
in week 3 after challenge. In the 5, 13, 20, and 40 µg/mL
groups, the growth depressions during this period were
32, 54, 52, and 96 grams/day/pig, respectively (Van
Diemen et al. 1994a). The severity of atrophy depended
on the amount of toxin administered into the nose of the
pig.
The first publication explaining the role of toxigenic
P. multocida in AR was by Ilina and Zasukhin (1975) in
Russia and it encouraged the development of tests for se-
lecting toxigenic P. multocida isolates. Instead of using a
rabbit test, the guinea pig skin test was chosen because it
also selected AR-pathogenic B. bronchiseptica strains
(de Jong 1980; Blobel and Schliesser 1981; de Jong and
Akkermans 1986). Differences between infections with
toxigenic B. bronchiseptica and toxigenic P. multocida
strains were revealed when pure broth cultures were in-
stilled intranasally in groups of colostrum-deprived SPF
pigs aged 3, 6, 9, 12, and 16 weeks. In pigs infected with
B. bronchiseptica, macroscopic turbinate lesions were no-
ticed only in 3- and 6-week-old pigs, not in pigs of 9
weeks and older. Toxigenic P. multocida still induced typ-
ical snout and turbinate alterations, including septal de-
viation, in pigs infected at 12 and at 16 weeks of age. The
severity of nose lesions decreased with increasing age
with the same dose of toxigenic P. multocida.
Other Factors
Despite the major role of infectious agents, other factors
contribute to the cause or at least the clinical expression
of AR, but they have proved difficult to evaluate and have
been inadequately defined quantitatively. Most experi-
enced clinicians have concluded that the severity of the
disease is markedly influenced by extrinsic factors (Pen-
ny 1977; Goodwin 1980). Smith (1983) provided a useful
review of these noninfectious determinants.
NUTRITION. Although the role of the dietary calci-
um:phosphorus imbalance is now discounted as a pri-
mary cause (Brown et al. 1966), nutritional deficiency of
any kind may enhance the severity of infectious disease.
Feed consumption may be influenced by AR, since
piglets with an acute rhinitis may accept feed less readily
and become stunted and weak. Growing pigs with con-
chal damage may also have reduced feed intake, thus
contributing to the reduced daily gain associated with
the condition.
GENETIC INFLUENCES. In the past it has been sug-
gested that heredity played a major role, but heritability
estimates have varied greatly, and attempts to control the
disease solely by genetic selection have failed. There is
probably a measure of genetically linked predisposition
to AR, since breeds and strains that vary in susceptibility
to the disease and are susceptible to genetic pressure do
occur. In the United Kingdom, for example, Large White
pigs are now generally considered more vulnerable than
Landrace pigs, although 30 years ago the reverse could
have been the case. The subject has been reviewed by
Smith (1983), Voets et al. (1986a), and Martineau et al.
(1988).
MANAGEMENT, HOUSING, AND ENVIRONMENT.
Severe growth-retarding AR is closely associated with in-
tensive methods of production; it is undoubtedly most
severe when successive batches of pigs are housed in
densely stocked, continuously occupied, poorly ventilat-
ed buildings (Smith and Giles 1980). Penny (1977) has
identified several management factors that tend to pre-
dispose to an increased severity of AR (Table 27.1).
Instances have been observed where the disease was
controlled, or at least reduced to economically accept-
able levels, solely by the manipulation of housing and
environment and improved management. It is also a
 CHAPTER 27 PROGRESSIVE AND NONPROGRESSIVE ATROPHIC RHINITIS de Jong 359

Table 27.1. Management factors influencing the may often be endemic because of infection passing later-
severity of atrophic rhinitis ally between different batches, particularly in systems
Increase Decrease where an all-in/all-out approach is not practiced.
B. bronchiseptica is primarily introduced by the intro-
Large herds, open herds Small herds, closed herds
Expanding herds Static herd size duction of carrier pigs (in SPF herds); recently purchased
High proportion of gilts Mainly old sows breeding stock are often held responsible.
Large farrowing unit Small or single farrowing unit Whether or not the sow is important in transmission,
(all-in/all-out) the recognized infectious agents pass readily between
Multiple suckling—piglets Single suckling
fostered between litters populations of young weaned pigs. Infection of pigs at
Large weaner pools More isolation, modular an early age may be vital, even when the clinical signs ap-
systems (all-in/all-out) pear late in the fattening period.
Large number in one airspace Small number in one airspace The chief mode of transmission of B. bronchiseptica
Frequent moving and mixing Little movement and mixing
from pig to pig is by aerosol droplet infection. The high
Intensive systems indoors Outdoor rearing
High stocking density Low stocking density prevalence of infection among growing pigs suggests
Poor ventilation and no Good ventilation and tempera- that transmission may occur at any age, but it is probably
temperature control ture control more common and more readily accomplished in sus-
Poor hygiene, little disinfection Good hygiene and disinfection ceptible young pigs, in which an active rhinitis with
Continual pig throughput Buildings rested
Dry-feeding, dusty atmosphere Wet-feeding, clean atmosphere sneezing develops. The infection can certainly spread
Mechanical food handling Hand delivery rapidly among populations of susceptible (nonimmune)
piglets (Smith et al. 1982).
Source: After Penny 1977.
B. bronchiseptica colonizes the ciliated mucosa of the
porcine respiratory tract very effectively; it is frequently
common belief that the disease may be more severe in a isolated from the tonsils, and large numbers (106/g) have
dusty atmosphere, particularly where dry and dusty feed been found in the intestinal contents of infected gnoto-
is delivered by automatic equipment. The influences of biotic pigs (Rutter 1985). Thus, direct-contact droplet in-
housing and feed, including the feed delivery system, on fection, and perhaps ingestion of fecal material, are like-
respiratory diseases of the pig have been reviewed by ly to be the main routes of transmission. The cycle of
Owen (1982) and Strang (1982), respectively. infection appears to be maintained by a small proportion
of breeding females. Litters within the farrowing house
EPIDEMIOLOGY become infected at an early age, but in the United King-
dom as well as in the Netherlands, the major spread
Bordetella bronchiseptica seems to occur after 2–3 weeks of age or after weaning,
B. bronchiseptica is widely prevalent in the pig population especially in large groups on flat decks, when 70–80% of
in countries with major swine-producing industries. The a group can become infected. The infection persists for
prevalence of B. bronchiseptica infection greatly exceeds several months, with a gradual reduction in the intensity
that of clinical AR or marked turbinate atrophy at and rate of infection. The age at which animals first be-
slaughter (Cameron et al. 1980), and although B. bron- come infected with B. bronchiseptica has an important ef-
chiseptica is frequently isolated from young pigs in out- fect on the development of lesions. The most severe le-
breaks of AR, the infection also occurs widely in herds sions occur in nonimmune animals infected during the
without the condition (Tornoe et al. 1976; Giles et al. first week of life (Duncan et al. 1966a). Animals infected
1980; Rutter 1981; Whittlestone 1982). at 4 weeks show less-severe lesions, while those infected
The dam has been considered a possible source of the at 9 weeks show virtually no lesions (de Jong and Akker-
important nasal infections for her suckling piglets, and mans 1986).
she has been reliably incriminated as a source of B. bron- The amount and type of immunity also influence the
chiseptica and P. multocida. Transmission also occurs be- epidemiology of bordetella infection. The presence of
tween sows and boars. Although traditionally viewed as passive antibody in the sera of piglets born to naturally
important, some observers have concluded that the infected dams (with toxigenic bordetellae) appeared to
sow’s role might be minor, since clinically NPAR-free provide protection against the development of turbinate
progeny resulted when sows from an affected herd were lesions (Rutter 1981) but not against infection (Kobisch
reared under improved conditions (Bercovich 1978). and Pennings 1989; Voets 1990). However, vaccination of
The degree of resistance to natural B. bronchiseptica sows appeared to delay infection in their piglets until
infection among sows does not appear to be marked, but 12–16 weeks of age compared to nonvaccinated herds, in
younger sows are more likely to be active shedders of the which litters became infected by 2 weeks of age (Rutter
organism. Although infection from the dam is probably et al. 1984).
the chief method of initiating the infection among pop- B. bronchiseptica shedding from vaccinated sows
ulations of suckling piglets, infection in weaner houses seems to be reduced in herds in which the sow popula-
360 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
tion has been vaccinated for some years.
B. bronchiseptica has been isolated from most domes-
tic and wild animal species (Goodnow 1980), and be-
cause it is a ubiquitous pathogen, there is always the risk
that infection could be introduced by nonporcine vec-
tors. Most isolates from other species appear to be of low
virulence in pigs, but it is possible that rodents might be-
come infected with pig strains and transmit them. Virtu-
ally every pig herd is infected with B. bronchiseptica, and
variable amounts of brachygnathia superior (BS), mod-
erately severe turbinate atrophy, and moderate signs of
septum deviation can be expected in all herds. For this to
occur, pigs from nonimmune dams must become infect-
ed within the first 4 weeks of life and develop lesions that
persist to slaughter, but in most, regeneration of
turbinates begins approximately 4 weeks after the start
of infection, when the scrolls are not totally damaged.
Lesions such as septal deviation, turbinate bone hyper-
plasia, and BS may be apparent at slaughter. The per-
centage of pigs with a twisted snout generally does not
reach 1%.
In the field, however, the picture is likely to be more
complicated. For example, there are reports that
Haemophilus parasuis in combined infections with type A
strains of P. multocida can produce mild turbinate lesions
(Gois et al. 1983a). Others could not repeat these results.
B. bronchiseptica is killed in 30 minutes at 56˚C. It sur-
vives outside the body in dried droplets for up to 5 days
on glass, 3 days on cloth, and a few hours on paper. The
survival time of B. bronchiseptica in soil is about 6 weeks.
Low humidity and raised temperatures rapidly reduce
numbers of live bacteria. In liquid media B. bronchisepti-
ca survived for more than 8 weeks at 21˚C. In lake water
and in phosphate buffered saline solution (PBS), B. bron-
chiseptica remained viable for at least 3 weeks (Porter et
al. 1991). In a rotating aerosol chamber, the mean half-
life at 21˚C and 76% relative humidity was 118.8 minutes
(Stehmann et al. 1992), and at 23˚C and 75% relative hu-
midity, it was 56.7 minutes (Müller et al. 1992). The or-
ganism is sensitive to common disinfectants (Stehmann
et al. 1990).
Pasteurella multocida
The introduction of a disease and its subsequent spread
within a population depend on numerous factors, in-
cluding the nature of the etiologic agent, the host, and
the structure of the population. In intensive pig rearing,
many animals are in close contact and there is often
widespread movement of breeding and replacement
stock between herds. The main risks of introducing in-
fection are associated with purchased pigs, and disease
may then spread rapidly within a seronegative herd. Ear-
ly reports that did not distinguish between PAR and
NPAR clearly recognized that (P)AR was introduced by
carrier pigs. The disease appeared in many Norwegian
herds that had imported pigs, several of which eventual-
ly developed severe clinical signs. This led Braend and
Flatla (1954) to conclude that “atrophic rhinitis was prac-
tically unknown in Norway prior to [World War II,] after
which it has been rather common, most certainly be-
cause of importation of pigs from Sweden where the dis-
ease is common.” It was, therefore, assumed that a new
infectious organism had been imported. The disease was
declared notifiable, and a slaughter policy was carried
out. This strategy was also followed in other European
countries, such as in the United Kingdom until 1959 and
in the Netherlands until 1980. Similarly, the introduc-
tion of AR into the United Kingdom was attributed to
the importation of Swedish stock (Anon. 1954). There
are at least two possible explanations for these observa-
tions: either B. bronchiseptica was introduced in uninfect-
ed animals and exacerbated existing infections with tox-
igenic P. multocida or, more likely, toxigenic P. multocida
was introduced with the imported stock.
Estimates of the prevalence of PAR, whether from an
individual farm or larger population, are usually con-
ducted by an examination of the heads of pigs after
slaughter. Such surveys have indicated that macroscopic
nasal turbinate atrophy is widespread in pig popula-
tions. It occurred in about 40% of Danish and British
herds (Nielsen 1983) in the late 1970s, although a later
estimate from England showed a decline to 25%
(Cameron et al. 1980). Such a high level of turbinate at-
rophy, however, does not reflect an equivalent level of
clinical disease, since mild lesions are common in com-
mercial fattening pigs, and mild or even moderate atro-
phy in individuals may occur in herds without obvious
clinical disease or adverse economic effects. Today it is
believed that these lesions are caused by B. bronchiseptica
(NPAR); growth retardation associated with more severe
outbreaks has proved difficult to quantify, and some ob-
servers (Straw et al. 1983) have found no correlation be-
tween the degree of turbinate atrophy and production
parameters and, in these herds, now consider atrophy to
result from infection with B. bronchiseptica (NPAR). Nev-
ertheless, where clinically apparent disease occurs, there
is frequently a reduction in average daily gain; this has
been conservatively estimated as 5–8% for pigs with se-
vere atrophy (Nielsen 1983). In combination with
pleurisy and pneumonia this reduction can double.
The epidemiology of P. multocida infection in pigs is
less well understood than that of B. bronchiseptica. The
organism colonizes the tonsils, but some factor or fac-
tors, the mechanisms of which are not understood, are
needed to assist colonization of the nasal mucosa. Non-
toxigenic and toxigenic type A strains can be isolated
from the lungs of pigs with pneumonia (Baekbo 1988),
but P. multocida is much less effective than B. bronchisep-
tica in colonizing the trachea. In contrast to type A
strains, toxigenic and nontoxigenic type D strains are iso-
lated less frequently in the lungs but more frequently in
the nose. P. multocida has also been isolated from most
 CHAPTER 27 PROGRESSIVE AND NONPROGRESSIVE ATROPHIC RHINITIS
animal species and is well recognized as an important
pathogen in cattle, rabbits, poultry, and turkeys (Carter
1967). In some studies its distribution in pig herds was
limited; only 9% were infected in one report (Harris and
Switzer 1969), but such results may be attributable to the
presence of the commensal flora in the nasal cavity
(Chanter and Rutter 1989). Today in most laboratories,
selective media and the technique of mouse passage can
be used for primary isolation of the organism. Material
from herds examined in this way (Rutter 1985) has yield-
ed toxigenic and nontoxigenic isolates of type A or D,
and mixed infections with these two types in the same
pig can occur.
In contrast, the distribution of toxigenic isolates of P.
multocida appears to be limited to those herds with PAR
or a history of the disease (Rutter 1985). In Germany, the
Netherlands, and Denmark (Pedersen 1983), the picture
is similar, indicating that the majority of herds infected
with toxigenic P. multocida exhibit clinical signs of pro-
gressive disease. In the Netherlands, however, toxigenic
P. multocida has been isolated from 15% of breeding
herds with no history or clinical signs of progressive dis-
ease at the moment of the first detection of the toxigenic
P. multocida. Most of these breeding herds were moni-
tored and became clinically diseased within 2 years after
this detection. Only 5% of pigs 4–12 weeks of age were
infected in these herds. A few herds remain clinically un-
affected for some years (de Jong 1983a; Goodwin et al.
1990), which indicates that toxigenic strains may be pres-
ent in some clinically unaffected herds, and these could
transmit progressive disease if infected stock were pur-
chased from them.
The main source of P. multocida infection for young
pigs appears to be pharyngeal transport of the organism
among breeding stock; 10–15% of sows in farrowing
houses were infected with toxigenic isolates (de Jong
1983b), and some piglets were already infected with
these strains within a week after birth. Toxigenic P. mul-
tocida was also isolated from the vaginas of a few sows.
The age at which piglets first become infected with P.
multocida affects the severity of the lesions produced, but
unlike B. bronchiseptica infection, older pigs may still de-
velop lesions. Significant turbinate atrophy occurred in
pigs infected with toxigenic P. multocida up to 16 weeks of
age; Rutter et al. (1984) found that pigs that became nat-
urally infected between 12 and 16 weeks of age had
turbinate lesions. It has been shown that apparently
healthy 3-month-old pigs can develop PAR when intro-
duced into a commercial production unit where severe
disease is occurring (Nielsen et al. 1976). Injection of P.
multocida toxin (125 µg/kg) produced significant atro-
phy in conventional pigs of 10 weeks of age (Rutter
1985). With 13 µg/mL instilled nasally, a subclinical PAR
could be achieved in 4-week-old piglets necropsied 5
weeks later. With 40 µg/mL, severe lesions were ob-
tained in the trials (Van Diemen et al. 1994a).
de Jong 361
The prevalence of toxigenic P. multocida may be relat-
ed to the extent of clinical disease. The organism was iso-
lated from 50% to 60% of young pigs sampled in a herd in
which almost 30% of fattening pigs had twisted snouts.
In less severely affected herds, larger numbers of young
pigs had to be sampled before toxigenic strains were iso-
lated (Rutter 1985; de Jong et al. 1988).
The distribution of toxigenic P. multocida in other
species has still to be determined. Pedersen (1983),
de Jong (1985), Rutter (1985), Baalsrud (1987), Ohkubo
et al. (1987), Kamp et al. (1990), and Frymus et al. (1996)
reported that dermonecrotic strains occurred in cattle,
rabbits, dogs, cats, rats, poultry, goats, and sheep. A tox-
igenic strain from pasteurellosis in turkeys produced se-
vere turbinate atrophy in gnotobiotic pigs, but a toxi-
genic strain thought to have been isolated from ovine
pneumonia colonized the nasal cavity of pigs poorly and
did not produce significant lesions in combined infec-
tion with B. bronchiseptica (Rutter 1983, 1985). Toxigenic
strains were isolated from humans suffering from tonsili-
tis, rhinitis, sinusitis, pleuritis, appendicitis, and sep-
ticemia and were pathogenic for pigs (Nielsen and Fred-
eriksen 1990; Donnio et al. 1991). This implies special
risks for all persons who have contact with herds or ani-
mals infected with toxigenic P. multocida: farmers and
their families, farmhands, drivers, merchants, vets, con-
sultants, butchers, and employees of slaughterhouses.
Wearing face masks will reduce the risk of becoming in-
fected and spreading the infection.
The infectious agents are usually introduced into a
previously unaffected herd by carrier pigs. Recently pur-
chased breeding stock, gilts or boars, are commonly held
responsible, although the evidence for their involvement
is often circumstantial. The introduction of toxigenic
strains of P. multocida is the principal event preceding an
outbreak. Poorly colonizing strains with a low toxin pro-
duction may represent an exception (Kavanagh 1994).
Infection from other sources is rare but seems to become
more important if the spread of toxigenic P. multocida in
pigs is not stopped.
P. multocida is easily destroyed by 60˚C in 10 minutes,
by 0.5% phenol in 15 minutes, and by a 3.5% solution of
cresol in a few minutes. In manure P. multocida remains
infective for a month and in decomposing or frozen car-
casses for 3 months. In a rotating aerosol chamber, the
mean half-life was 20.85 minutes at 23˚C and 75% rela-
tive humidity.
The organism is susceptible to commonly used disin-
fectants, including those of the following general cate-
gories: quaternary ammonium compounds, phenolics,
sodium hypochlorite, iodophores, glutaraldehyde, and
chlorhexidine.
Formalin at a concentration of 0.2% or greater and
phenol at 0.5% will kill in less than 18 hours at 37˚C. On
stock culture agar P. multocida often survives for months
or even years if kept at room temperature, but if stored
362 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor

in the refrigerator, the bacteria may die in several days.
Their viability can be maintained for many years in
blood or tissues in the frozen state at −20˚C or lower
(Blobel and Schliesser 1981).
PATHOGENESIS
Bordetella bronchiseptica
It is believed that B. bronchiseptica colonizes the nasal
cavity by adhering to the nasal mucosa, where it proba-
bly preferentially attaches to the ciliated epithelial cells
(Yokomizo and Shimizu 1979). This is followed by mul-
tiplication at the mucosal surface and toxin production,
leading to inflammatory, proliferative, and degenerative
changes in the nasal epithelium, including the loss of cil-
ia (Duncan et al. 1966a; Edington et al. 1976). The or-
ganism is not believed to invade the deeper tissues.
It is assumed that the organism at the mucosal sur-
face elaborates a toxin that diffuses into the osseous core
of the nasal turbinate and is responsible for the osteopa-
thy. The nature of this toxic factor has received much at-
tention. Cell-free sonicated extracts from phase 1 B. bron-
chiseptica were originally shown to contain a heat-labile
and dermonecrotic toxin, and it was assumed that this
was probably an important factor in the pathogenesis.
Since then, such bacteria-free extracts containing high
levels of this toxin have been repeatedly inoculated in-
tranasally into piglets, where they produce nasal lesions
similar to those seen in naturally occurring AR (Hanada
et al. 1979; Nakase et al. 1980; Magyar et al. 1988).
The degree of severity of the hypoplastic lesions seen
in young pigs varies, and only rarely does severe hy-
poplasia result (Figs. 27.1–27.3). The ventral scroll of the
ventral turbinate is the area most commonly and consis-
tently affected; grossly it varies in appearance from a
slightly shrunken and distorted scroll to virtually com-
plete absence. In the more severe cases the dorsal scrolls
of the ventral turbinate and the dorsal turbinate are also

27.1. Cross section of the snouts

of three uninfected 6-week-old pigs
showing normal anatomy of the
turbinate scrolls (conchae Kontr.
1-2-3). (Courtesy P. Schöss.)

27.2. Turbinate hypoplasia

in three pigs experimentally
infected at 5 and 10 days old
with B. bronchiseptica and
necropsied 40 days post-
infection (Va 6-7-8). (Courtesy
P. Schöss.)

27.3. Cross section of the snouts

of four pigs infected at 5 and 10
days old with B. bronchiseptica
and slaughtered at 6 months of
age. Presumed turbinate regenera-
tion and deformations of the
ventral turbinates and nasal bones
(os vomer) (Va 9-10-11-12).
(Courtesy P. Schöss.)
 CHAPTER 27 PROGRESSIVE AND NONPROGRESSIVE ATROPHIC RHINITIS
usually affected. The important factors that affect the
severity of the hypoplasia are the degree of resistance of
the pig to the infection (Smith et al. 1982) and the age
when it was first acquired, since susceptibility to the
damage the infection can produce declines as the pig gets
older.
The histologic changes in bordetella-induced hy-
poplastic rhinitis have been reported by Duncan et al.
(1966a) and are detailed in Switzer and Farrington
(1975). Briefly, there is a hyperplasia of the epithelium
and, in places, a metaplasia, the epithelium becoming
more stratified in structure with polyhedral cells devoid
of cilia. There is a degree of cellular infiltration (princi-
pally with neutrophils and mononuclear cells), a fibro-
blastic proliferation in the lamina propria, and a reduc-
tion in size and replacement fibrosis of the osseous core.
In more chronic stages there are increased numbers of
osteoblasts around the trabeculae, but osteoclasts are
rarely found.
There is some variation in the toxigenicity of differ-
ent strains of B. bronchiseptica; porcine phase 1 strains
are more toxigenic than phase 3 or nonporcine isolates
(Collings and Rutter 1985).
TURBINATE REGENERATION. There is considerable
field and experimental evidence that the hypoplasia of
the turbinates produced by the uncomplicated infection
of young pigs (up to about 8 weeks old) is capable of re-
generation, which may sometimes be almost complete
(Duncan et al. 1966a; Tornoe and Nielsen 1976; Rutter
1981; Smith et al. 1982).
A degree of turbinate hypoplasia in young pigs (Fig.
27.2), with a variable amount of subsequent regenera-
tion as the pig grows to slaughter weight (Fig. 27.3), may
thus occur in most herds infected with B. bronchiseptica.
This probably accounts for the high prevalence of mild
lesions of turbinate atrophy seen at slaughter in the
many bordetella-infected herds free from obvious clini-
cal AR, especially in cases where the nasal cavity remains
infected with other species, particularly with nontoxi-
genic P. multocida or Haemophilus sp.
A reaction in the regeneration of the scrolls is the ir-
regular increased (“hyperplastic”) bone structures in the
turbinate bones and other nose bones as well. Once in-
duced, the BS does not seem to regenerate and is difficult
to separate from breed-associated BS. Only after elimina-
tion of B. bronchiseptica in such pig populations can the
breed-associated BS be studied properly.
Pasteurella multocida
The mechanisms of colonization by P. multocida and the
subsequent processes affecting the turbinate bone cells
and leading to progressive atrophy and clinical PAR have
been partially clarified. Furthermore, the mechanisms by
which these chronic nasal changes and their associated
malfunctions cause growth retardation have been clari-
de Jong 363
fied to a large extent (Becker et al. 1986; Williams et al.
1986; Doster et al. 1990; Dugal and Jacques 1990).
P. multocida apparently colonizes the nasal cavity
poorly unless there is preexisting mucosal damage
(Elling and Pedersen 1983). Chemical irritants (e.g.,
acetic acid and B. bronchiseptica) induce different modifi-
cations of the nasal epithelium, but both actions cause
the production of nasal mucus, which results in a nasal
environment favorable to colonization by P. multocida
(Gagne and Martineau-Doize 1993). The different types
of mucins produced by the piglets’ nasal mucosa at dif-
ferent ages may contribute to an understanding of P.
multocida and B. bronchiseptica colonization (Martineau-
Doize et al. 1991a, b).
Given this preconditioning, the organism will set up
a nasal infection and, if toxigenic, the toxin will be elab-
orated. The nasal cavity, however, is not necessarily the
only possible site of toxin production. The toxin appears
to be of crucial significance in the pathogenesis of PAR,
since only toxigenic strains of P. multocida produce PAR
lesions; furthermore, the toxin will produce progressive
snout shortening and turbinate atrophy when given to
pigs intranasally (Ilina and Zasukhin 1975) and by a va-
riety of parenteral routes (Rutter and Mackenzie 1984).
The precise mechanism of action of the P. multocida
toxin has not been clearly defined; but it will produce a
variety of changes in the ventral turbinates, consisting of
epithelial hyperplasia, atrophy of mucosal glands, in-
creasing volume of blood vessels, osteolysis, and a pro-
liferation of mesenchymal cells. These eventually will re-
place the bone trabeculae and osteogenic and
osteoclastic tissues (Rutter and Mackenzie 1984). PAR
therefore seems to result from a combination of early os-
teoblastic damage followed by a series of toxin-induced
chronic changes that result in osteolysis and subsequent
replacement fibrosis. The toxins of B. bronchiseptica and
P. multocida are different. Also, the ways in which the
turbinates are destroyed differ. The combination of both
toxins has detrimental effects on the turbinates and skull
bones (Martineau-Doize et al. 1990).
CLINICAL SIGNS
Bordetella bronchiseptica
RHINITIS. The principal signs seen in bordetellosis
are sneezing and snuffling in young pigs. This can occur
in piglets as young as 1 week but is frequently seen at 3–4
weeks of age or about the time of weaning, which may be
related to both maternal colostral protection and the
mixing of pigs at this stage.
Affected piglets sneeze, snuffle, and snort with a vari-
able degree of catarrhal rhinitis producing a variable
amount of serous or frequently mucopurulent nasal dis-
charge, which may be observed by swabbing the nasal
cavity. Generally, the younger the piglet when initially af-
fected, the more severe the clinical signs. The appetite is
364 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
usually only moderately to slightly impaired. The clinical
signs increase in severity for a time, then tend to abate af-
ter a few weeks, except in herds with clinical PAR, where
continued progressive turbinate damage causes frequent
sneezing to continue. Uncomplicated B. bronchiseptica in-
fections in older pigs produce only mild signs or remain
clinically inapparent.
Not all sneezing in young pigs is attributable solely to
B. bronchiseptica, since infection with porcine cy-
tomegalovirus or other agents may also produce or exac-
erbate these signs.
BRONCHOPNEUMONIA. A more severe manifesta-
tion of infection is bronchopneumonia, which is usually
seen as a primary condition in very young piglets (3–4
days). Although this type of disease is relatively uncom-
mon compared with the wide prevalence of nasal infec-
tion, B. bronchiseptica is an important pathogen in those
cases of pneumonia with bronchitis that occur in young
pigs. The condition only affects young pigs and is most
common in winter (Whittlestone 1982). The major clin-
ical sign is coughing, perhaps with whooping and dysp-
nea. Pyrexia is not usually marked (Switzer and Farring-
ton 1975). Morbidity is high within litters, and mortality
may be so in untreated cases.
B. bronchiseptica is not infrequently isolated from
pneumonic lesions in older fattening pigs, but it is con-
sidered to be a secondary opportunist pathogen, and the
clinical significance of its presence remains largely un-
known.
Pasteurella multocida
Clinical signs of PAR are not usually seen in pigs until
about 4–12 weeks of age or later, depending on the sever-
ity of the outbreak, but sneezing and snuffling in baby
pigs are commonly recorded as the first signs. They are
not, however, specific to or diagnostic of the condition,
since they frequently occur in the absence of subsequent
clinical PAR. Sneezing and snuffling in baby pigs is mere-
ly a reflection of an acute catarrhal rhinitis, which may
be due to bordetellosis and/or infection with porcine cy-
tomegalovirus; other agents may possibly be involved,
for example, Mycoplasma sp., Actinobacillus sp., and Au-
jeszky’s disease, influenza, and porcine reproductive and
respiratory syndrome (PRRS) viruses. In herds where
subsequent infectious and other factors combine to
cause progression to clinical AR, affected pigs will con-
tinue to sneeze, snuffle, and snort throughout the grow-
ing period; this is accompanied by a variable amount of
serous to mucopurulent nasal discharge. In severely af-
fected animals, sneezing may be pronounced and occa-
sionally nasal bleeding may occur. Hemorrhage is usual-
ly unilateral and varies in severity. Blood may be seen on
the walls of the pen or on the backs of the pigs; muco-
purulent material and even pieces of turbinate debris
may be expelled from the nose following episodes of
forceful, violent sneezing. In gilts and sows the hemor-
rhage in late gestation and farrowing can be life threat-
ening to the dam and her piglets.
The most characteristic clinical signs of PAR are due
to disturbances of normal bone development of the
nose; conspicuous deformities of the face may occur. The
most common is BS, in which the upper jaw is shortened
in relation to the lower, as a result of growth depression
of the ossa nasales and maxillares, giving the face a
“pushed-up” appearance. The skin and subcutis over the
dorsum of the shortened snout are thrown into folds;
when the disturbance of bone growth affects one side of
the face more than the other, lateral deviation of the
snout occurs (Figs. 27.4 and 27.5). This may vary in
severity from a barely perceptible misalignment to severe
twisting (possibly by as much as 50˚). These facial defor-
mities reflect an underlying turbinate atrophy; in the
case of lateral deviation the atrophy is more pronounced
on the side of the deviation. The prevalence of facial dis-
tortion varies among outbreaks, and not all pigs with sig-
nificant turbinate atrophy develop marked facial distor-
tion.
Dirty streaks on the face radiating from the medial
canthus of the eye, caused by tear staining and the en-
trapment of dust following occlusion of the nasolachry-
mal duct, are common in PAR outbreaks (Fig. 27.4).
However, they are not diagnostic and may occur in the
absence of PAR.
In moderate to severe herd outbreaks of PAR, the
clinical signs are frequently accompanied by growth re-
tardation and reduction in the efficiency of feed utiliza-
tion. Feed utilization is particularly reduced in severely
diseased pigs. The amount of P. multocida toxin may in-
fluence growth performance (Doster et al. 1990; Van
Diemen et al. 1994a).
Some clinical parameters have been used in an at-
tempt to monitor and quantify disease levels. The preva-
lence of gross distortion among growing pigs is a crude
measure of disease level but is not a sensitive index of
turbinate atrophy. The prevalence and degree of BS in
weaned pigs can provide useful information (Bercovich
and de Jong 1976) but is not always diagnostic (Schöss
1983), and confusion can arise with breeds that are natu-
rally brachygnathic (e.g., Large White) (Van Groenland
1984). Sneeze counts have been used successfully in an
attempt to assess the effects of treatment (Douglas and
Ripley 1984; Kobisch and Pennings 1989).
LESIONS OF NPAR AND PAR
Gross Lesions
The gross lesions of PAR are restricted to the nasal cavi-
ty and adjacent structures of the skull, although in severe
cases the pig may also be stunted. At necropsy both BS
and facial distortion are observed in the intact head. The
dominant lesion is an atrophy of the ventral and dorsal
 CHAPTER 27 PROGRESSIVE AND NONPROGRESSIVE ATROPHIC RHINITIS
27.4. A 17-week-old pig with clinical PAR showing
marked brachygnathia superior, wrinkling of the skin on
the dorsum of the nose, and tear staining.
27.5. The head of a 15-week-old pig with clinical PAR
showing severe lateral deviation of the snout. The anato-
my of the skull is distinctly abnormal due to a failure of
normal bone development.
turbinates, and this can vary greatly in severity. The at-
rophy is assessed by a cross section of the snout at the
level of the first/second upper premolar, at which point
the conchae, dorsal and ventral, are symmetrically and
maximally developed in the normal pig (Fig. 27.6). In
de Jong 365
mild to moderate cases the ventral scrolls of the
turbinates are by far the most consistently and severely
affected area; they vary from slightly shrunken to com-
plete atrophy (Figs. 27.7 and 27.8).
In more severe cases, atrophy of the dorsal scrolls of
the ventral turbinate and the dorsal and ethmoidal
turbinates may occur (Figs. 27.9 and 27.10); in the most
severe form there is a complete absence of all turbinate
structures (Fig. 27.11). In between these mild and severe
forms, a whole spectrum of atrophic changes may be ob-
served; occasionally the turbinates are bizarrely shaped
(Fig. 27.10), which may represent some degree of re-
growth of the conchae (Done 1985). Another gross
change that may be observed is bowing or buckling of
the nasal septum (Fig. 27.11); this is not uncommon and
is often associated with BS, facial distortion, and/or
asymmetrical atrophy. Irregular formation of the ossa
nasales and maxillares also occurs in PAR (de Jong 1985)
and should not be neglected (Figs. 27.10 and 27.11).
Exudate may be found in the nasal cavity but is not a
constant finding. The amount and character depend on
the age of the lesion and the type of infection. The exu-
date consists of variable amounts of mucopurulent to
purulent material, possibly flecked with blood. The mu-
cosa lining the frontal sinus is sometimes inflamed, and
the sinus itself may contain mucopurulent material. The
bones surrounding the nasal cavity may have undergone
thinning or may be irregularly shaped to some extent.
Hyperplasia/hyperostosis can be observed in older pigs
(de Jong 1985).
ASSESSMENT OF TURBINATE ATROPHY. The vary-
ing severity of the atrophic changes has led to the devel-
opment of methods of quantitative assessment, but un-
fortunately, no one system has gained universal
acceptance. Subjective scoring of snouts (e.g., on a 0–5
scale as in the British system; Anon. 1978) has proved
very useful in evaluating treatment and monitoring
schemes. As well as wide variation between systems,
there is also considerable interobserver variation within
a system (D’Allaire et al. 1988). At least one reason for
this is probably the clinicians’ unwillingness to score a
herd as having PAR, despite a degree of mild atrophy,
when there has never been any clinical evidence of dis-
ease. Today, bacteriologic or serologic tests are necessary
to confirm downgrading of the health status of a herd
(e.g., when toxigenic P. multocida is present). The cutoff
point between normality and being affected is imprecise,
and the condition should not be regarded as a simple all-
or-nothing phenomenon (Done 1985). The situation in
many herds with only mild atrophy probably represents
only the effects of a normally transient and often-resolv-
ing hypoplastic rhinitis without the progression charac-
teristic of clinical PAR (see Definition above).
Objective measures of assessing atrophy on a contin-
uous scale have also been developed, including a mor-
366 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor

27.6. Cross section of the snout of an 18-week-old pig showing normal anatomy of the
turbinates.

27.7. Cross section of the snout of an 18-week-old pig. Slight distortion of the ventral scrolls of
the turbinates is present, a common finding.
 CHAPTER 27 PROGRESSIVE AND NONPROGRESSIVE ATROPHIC RHINITIS de Jong 367

27.8. Cross section of the snout of an 18-week-old pig showing modest but definite turbinate
atrophy.

27.9. Cross section of the snout of an 18-week-old pig showing severe bilateral turbinate
atrophy.
368 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor

27.10. Cross section of the snout of an 18-week-old pig; the atrophic turbinates have developed
into bizarre shapes.

27.11. Cross section of the snout of a 22-week-old pig showing total atrophy of all turbinate
structures, with severe bending of the nasal septum.
 CHAPTER 27 PROGRESSIVE AND NONPROGRESSIVE ATROPHIC RHINITIS
phometric index (area of free space as a percentage of to-
tal cross-sectional area of snout section) (Done et al.
1984). Such systems provide parametric data suitable for
analysis, but as diagnostic tools they offer few advan-
tages over subjective snout scoring (Collins et al. 1988,
1989).
Histologic Changes
Depending on the type of process active at the time of
necropsy, acute, subacute, or chronic histologic changes
may be observed.
The pathognomonic lesion of PAR by toxigenic P.
multocida is a fibrous replacement of the bony plates of
the ventral conchae (Done 1983a; Elling and Pedersen
1983; Martineau-Doize et al. 1990). Additionally, there
may be a variable metaplasia of the respiratory epitheli-
um and inflammation of the mucosal lamina propria;
subacute cases of rhinitis in conventional pigs will show
various mixtures of degenerative, inflammatory, dys-
trophic, and reparative processes. In SPF pigs infection
with toxigenic P. multocida does not induce a typical in-
flammatory reaction but does induce toxic alterations.
The histologic changes in pigs with PAR that show re-
tarded growth have been described by Yoshikawa and
Hanada (1981).
Lesions in parenchymatous organs may also be pres-
ent in cases of severe infection with toxigenic P. multoci-
da (de Jong 1983a; Rutter 1983). Parenteral injections
with P. multocida toxin induced liver cirrhosis, renal fail-
ure, marked decrease of peripheral blood lymphocytes
without lysis, and growth retardation (Becker et al. 1986;
Williams et al. 1986; Cheville et al. 1988).
BRONCHOPNEUMONIA. Pneumonic lesions occur
principally in young pigs and have a characteristic scat-
tered monolobular or bilobular distribution, mainly in
the apical and cardiac lobes. Affected areas are initially
dark red, become brown, then yellowish brown after a
time and develop a contracted appearance. The lesions
are associated with the B. bronchiseptica element of the
complex.
Histologically, the pneumonic lesions in bordetellosis
are characteristic. Detailed descriptions of the
histopathology of experimental B. bronchiseptica bron-
chopneumonia are given by Duncan et al. (1966b) and
Meyer and Beamer (1973) in conventional and germfree
swine, respectively. The lesions from these experimental
cases are similar to those of field cases. Briefly, the most
severe cases affect the pneumonic vasculature, and there
are areas of extensive alveolar hemorrhage with necrosis
and interlobular edema. In areas where hemorrhagic
changes are less extensive, there is an acute inflammato-
ry reaction with cellular infiltration, principally with
neutrophils. There is an accompanying bronchiolitis
with neutrophilic exudate. As the lesions age, vascular
changes become less prominent and epithelialization of
the alveoli, fibroblastic activity, and deposition of colla-
de Jong 369
gen occur. Large alveolar macrophages are present in
some alveoli.
DIAGNOSIS
Bordetella bronchiseptica
Although the clinical signs are suggestive of infection, a
definitive diagnosis of bordetellosis in pigs is only possi-
ble by the bacteriologic examination of lung washings,
lungs at postmortem, or nasal secretions. Nasal secre-
tions are best collected on cotton-tipped swabs with ei-
ther metal or elastic plastic stems. Wooden-stemmed
swabs and swabs with quick-breaking plastic stems
should be avoided, since sudden movement of the pig
may break the shaft. The live pig should be adequately re-
strained and the external nares cleaned. Swabs are care-
fully inserted in a naris with a gentle rotating motion and
pushed carefully along the ventral meatus so as to avoid
trauma to the delicate turbinates. The swabs are then
submitted for laboratory examination, preferably in a
bacteriologic transport medium or a phosphate buffered
saline solution (PBS) under cool conditions (±4oC).
The organism grows well on blood agar or Mac-
Conkey agar plus 1% glucose, but its isolation from field
specimens is often complicated by the overgrowth of
other organisms (Smith and Baskerville 1979); hence,
culture on more selective media is recommended. Proce-
dures for isolating and identifying the organism from
field specimens from pigs are given by Farrington and
Switzer (1977), Smith and Baskerville (1979), and Rutter
(1981). Selective media to isolate both B. bronchiseptica
and P. multocida on the same plate are discussed below
under the detection of P. multocida.
The serologic diagnosis of bordetella infection by the
detection of agglutinating antibodies in the serum has
been described. The various methods of antigen prepa-
ration, details of some of the tests employed, and their
interpretation have been reviewed by Giles and Smith
(1983). Agglutinating antibodies to B. bronchiseptica are
widespread in the pig population, but although their de-
tection by serologic tests can be useful in making a herd
diagnosis of bordetellosis, these are not commonly em-
ployed for routine diagnostic purposes, since, practically,
serologic tests offer few advantages over the culture of
nasal swabs.
Pasteurella multocida
CLINICAL DIAGNOSIS. When the full range of clin-
ical signs is present, a preliminary diagnosis of PAR on
clinical signs alone is possible, but none of the snout de-
formations by themselves are pathognomonic for PAR.
Animals showing lateral deviation of the snout and/or
marked BS, especially at an age of 10–12 weeks, almost
always have pronounced turbinate atrophy (Bercovich
and de Jong 1976; de Jong 1985; Kobisch and Pennings
1989). However, when these signs are not apparent or are
of decreasing prevalence (e.g., following treatment), it is
370 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
not possible for even experienced observers to assess the
extent of turbinate atrophy in the live animal. The pres-
ence of a few twisted snouts or sneezing alone is not suf-
ficient evidence to justify a diagnosis of PAR (see Defini-
tion).
RADIOGRAPHIC DIAGNOSIS. Radiographic exami-
nation of the snout has been developed to facilitate im-
proved diagnosis of turbinate atrophy in the live animal;
a suitable procedure is described by Done (1976). In
some countries this method has enjoyed widespread
popularity, but it is beset with technical difficulties and
problems in interpretation of the radiographs. The
method may not detect mild lesions reliably, and its val-
ue has been questioned (Eikelenboom et al. 1978; Web-
bon et al. 1978); furthermore, pigs must be sedated,
anesthetized, or physically immobilized, and the proce-
dure is costly and time-consuming. With experience,
however, some observers consider radiographic exami-
nation a useful aid (Schöss 1983). The same disadvan-
tages apply to rhinoscopy (Plonait et al. 1980). Modern
methods such as computerized tomography, used as a di-
agnostic tool for PAR, facilitate the macroscopic grading
of the nasal structures in live pigs of any age (Jolie et al.
1990).
POSTMORTEM DIAGNOSIS. The prevalence and
severity of turbinate atrophy are best estimated by ex-
amination of snouts after slaughter. Snouts should be
transversely sectioned at the level of the first/second up-
per premolar; sectioning cranial to this should be avoid-
ed, since this will reveal a different pattern of turbinate
development. Pigs of 4 weeks old or older that died dur-
ing weaning or prefattening can present turbinate atro-
phy at an early stage, and cross-sectioning can be carried
out with a simple iron saw by qualified local veterinari-
ans during regular herd inspections. Material from ton-
sils, lungs, and the nose can be sent to laboratories to en-
sure a proper diagnosis. To make a preliminary herd
diagnosis, pigs have to be examined at slaughter at regu-
lar intervals. As many pigs as practical should be exam-
ined; between 20 and 30 per time is suggested by Good-
win (1988). Atrophy is scored on subjective grading
systems (Bendixen 1971; Anon. 1978; Done 1983a, b;
de Jong 1985). With low levels it is not possible to define
a single cutoff point as representing freedom from PAR.
An acceptable level for an individual (toxigenic P. multo-
cida–infected) herd is a matter of reasoned clinical judg-
ment but must be one in which the economic effects of
the disease are minimal (Goodwin 1988). A monitoring
scheme that could serve as a useful model with a dia-
grammatic representation of snout grading is described
by Goodwin (1980). Computerized versions have been
developed by Collins et al. (1988), Barfod et al. (1990),
and Jolie and Thacker (1990).
CULTURAL AND SEROLOGIC DIAGNOSIS. Today,
a definite diagnosis of PAR cannot be based solely on
clinical and pathomorphologic observations but requires
laboratory tests (Pedersen 1983). Detection of the two
most significant bacterial pathogens is possible by the
culture of nasal and tonsillar swabs or tonsillar biopsies.
The live pig should be adequately restrained and the ex-
ternal nares cleaned; slender cotton-tipped swabs with
plastic or metal shafts should be inserted with slight ro-
tation deep into both sides of the nasal cavity. Swabbing
the tonsillar surface or tonsillar biopsies can aid the iso-
lation and differentiation of P. multocida and toxigenic P.
multocida (Van Leengoed et al. 1986; de Jong et al. 1988;
Ackermann et al. 1994). Swabs should be transported to
the laboratory within 24 hours, preferably in a transport
medium under cooled conditions (4–8˚C). Nutrient
transport media that support the growth of fast-growing
contaminants are best avoided, but sterile phosphate-
buffered saline is suitable (Pedersen 1983).
Detection of P. multocida (and B. bronchiseptica).
Special selective media are described on which both B.
bronchiseptica and P. multocida can grow (de Jong and
Borst 1985; de Jong 1994; Moore 1994).
The cultural isolation of P. multocida from nasal
swabs and the testing of their toxigenicity are detailed by
Pedersen (1983). When the nasal cavity is heavily infect-
ed with P. multocida, the organism can be recovered on
simple blood agars (Smith and Baskerville 1983). How-
ever, field specimens frequently contain low numbers of
organisms, and the other nasal flora may mask the pres-
ence of P. multocida on nonselective media. Mouse inoc-
ulation greatly improves the recovery rate from field
specimens, but a good in vitro method would be prefer-
able. Some selective media are described by Smith and
Baskerville (1983), Rutter and Luther (1984), de Jong
and Borst (1985), Leblanc et al. (1986a, b), Chanter and
Rutter (1989), Avril et al. (1990), and de Jong (1994).
Evidence suggests that the tonsil is the preferred habitat
for P. multocida in the pig, and improved detection rates
may be achieved by the collection of tonsillar swabs or
biopsies in combination with nasal swabs (de Jong et al.
1988). Tonsils and lungs can also be collected in the
slaughterhouse and examined in the laboratory. Swabs
from noses of pigs sampled after immersion in the hot-
water tank are unsatisfactory for the detection of toxi-
genic P. multocida (Chanter and Rutter 1989).
When clinical severe PAR is first detected in pigs, in-
fection by toxigenic P. multocida actually occurred weeks
or months earlier. The detection of the toxigenic P. mul-
tocida from these pigs can be difficult. Therefore, it is rec-
ommended to also examine clinically less severely affect-
ed pigs in such groups or pens.
Detection of P. multocida Toxin. The central etio-
logic importance of toxigenic strains of P. multocida is
 CHAPTER 27 PROGRESSIVE AND NONPROGRESSIVE ATROPHIC RHINITIS
that classification of field isolates into PAR toxin-positive
or toxin-negative strains is necessary in understanding
the epidemiology of the disease. The toxin is thermola-
bile, dermonecrotic in the guinea pig and lethal for the
mouse when administered intraperitoneally. All three
tests give broadly comparable results; the methods are
described by de Jong (1980, 1985), Pedersen (1983), and
Rutter (1983), respectively. An in vitro system of detec-
tion by assessing the cytopathogenic effect in monolay-
ers of Vero cells or embryonic bovine lung cells has been
developed (Pennings and Storm 1984; Rutter and Luther
1984). Today, enzyme-linked immunosorbent assays
(ELISAs) are replacing the earlier tests (Foged et al.
1988). DNA probes have been developed to detect the
gene responsible for toxin production in toxigenic P. mul-
tocida (Andresen et al. 1990; Kamps et al. 1990; Lax and
Chanter 1990). The use of polymerase chain reaction
(PCR) tests is becoming of interest in diagnosis and in
proposals for eradication of toxigenic P. multocida in
PAR-diseased herds (Nagai et al. 1994; de Jong 1994;
de Jong et al. 1996).
P. multocida Serotypes. Determination of the cap-
sular serotype of P. multocida is also often useful for epi-
demiological purposes; most toxin-positive strains are
type D, although toxin-positive type A strains also occur.
In some regions the toxigenic type D is prevalent, in oth-
ers it seems to be type A (Cowart and Backstrom 1984;
Iwamatsu and Sawada 1988; Pijoan et al. 1988). The usu-
al method of capsular serotyping is the indirect hemag-
glutination test with rabbit antisera (Carter 1955). The
hyaluronidase test (Carter and Rundell 1975) and acri-
flavine test (Carter and Subronto 1973) are simpler
methods for the detection of type A and D strains, re-
spectively, but not all porcine isolates are typeable by
these methods (Pedersen 1983). Piliation, hemagglutina-
tion, and capsular serotypes did not show a correlation
with toxin production (Trigo and Pijoan 1988). An atyp-
ical P. multocida strain producing a toxin similar to the
dermonecrotic toxin of P. multocida subsp. multocida has
been described in cattle (Kamp et al. 1990). Not only the
capsule and somatic structure are of epidemiological in-
terest; the phage types and plasmid types are also inter-
esting tools with which to follow the distribution pattern
of the different toxigenic strains (Lugtenberg et al. 1984;
Nielsen and Rosdahl 1988, 1990; Hoje et al. 1990, Rubies
et al. 1996).
Serologic Tests. Although agglutinating antibodies
to B. bronchiseptica can be detected in pig serum (Giles
and Smith 1983), this is of little diagnostic value. Sero-
logic tests to detect antibodies against toxigenic P. multo-
cida resulting from vaccination or infection have been
described (de Jong and Akkermans 1986; Bechmann
and Schöss 1990; Foged et al. 1990; Schimmelpfennig
1990). The toxin in natural infection is a weak immuno-
de Jong 371
gen, and antibodies to it take 3 months or longer to de-
tect and only then in some pigs (Bording et al. 1990; Van
Diemen et al. 1994b). This means that serology may on-
ly be of importance in detecting antibodies in the sow
population. A skin test has been described to detect anti-
bodies in sow herds that have been infected (Schim-
melpfennig and Jahn 1988; Breuer and Schimmelpfennig
1990).
In the skin test the purified concentrated toxin is ap-
plied intradermally in one or different concentrations.
Neutralization of the toxin indicates the presence of an-
tibodies as a response to the infection or vaccination
with toxigenic P. multocida. Difficulties in application
and in the identification of the correct amount of toxin
per dose have limited the use of the skin test in practice.
DIFFERENTIAL DIAGNOSIS. Sneezing in young pigs
occurs in herds with active PAR, but it is not diagnostic
itself, since it regularly occurs due to uncomplicated bor-
detellosis or porcine cytomegalovirus infection (Rond-
huis et al. 1980). Both agents are widely spread in the pig
industry and can cause severe mucous membrane dam-
age, which is necessary for colonization by toxigenic P.
multocida. The frequency of severe sneezing can be used
in clinical monitoring of PAR (Kobisch and Pennings
1989). Influenza, PRRS, and pseudorabies are other
viruses causing damage to the nasal mucosa.
A variety of other conditions (reviewed by Done
1977) may cause facial deformity in pigs; these are likely
to cause confusion in clinical and postmortem diagnosis,
since malformations of the turbinates can be observed.
A localized bacterial infection entering via wounds may
produce a paranasal abscess (bull nose) in young pigs.
PROBLEMS WITH DIAGNOSIS. Should pigs from a
herd with no clinically apparent disease that have no ob-
vious growth retardation but show mild turbinate atro-
phy at slaughter be considered to be suffering from PAR
or NPAR? It is suggested that when BS, lateral deviation,
and poor growth are obvious within the herd and atro-
phy at slaughter is marked, the herd should be suspected
of having clinical PAR. Conversely, where no turbinate
atrophy is seen in slaughtered pigs, the herd must be re-
garded as clinically free from PAR. However, defining the
status of herds where mild atrophy occurs in the absence
of clinical disease presents problems, since there is no
satisfactory single cutoff point between affected and un-
affected herds (Goodwin 1988). These low levels of atro-
phy have been regarded as representing degrees of sub-
clinical PAR but are probably better viewed as indicating
risk of developing clinical PAR. The level of atrophy
deemed satisfactory or acceptable for a given enterprise
is often a matter of reasoned clinical judgment. With the
help of bacteriologic and serologic investigations this
problem can be avoided (see Definition).
BS can occur as a breed-associated characteristic in
372 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
certain lines of the Large White/Yorkshire breed. Breed-
associated BS increases with age and cannot be influ-
enced by a medication program intended to combat the
influence of a bordetella and/or a pasteurella infection
in these pigs. The breed-associated level of BS can easily
be assessed by such a medication method. All BS grading
higher than this lower genetic level may be a result of
PAR or NPAR. A warning limit can be chosen (e.g., at an
age of 8–12 weeks) to allow early selection of clinically
diseased animals and to limit further damage in grower
or fattening pigs as well as in the younger pigs that will
follow such groups.
Breed-associated BS is easily distinguished from PAR
by the absence of turbinate atrophy, except where regen-
eration of the turbinates has occurred.
Sows and gilts kept in stalls often bite, chew, or play
with bars or drinkers, and this can give rise to asymmet-
ric bone development causing protrusion of the lower
jaw or mandibular misalignment. These conditions can
be confused with the facial deformity of AR, especially in
the older pig, but careful inspection should reveal that
the lower jaw is abnormally placed rather than that the
snout is shortened or laterally deviated. A useful tech-
nique is to draw an imaginary line between the center of
the ears and eyes and project it forward onto the snout.
Some sows keep their snouts more to one side. This can
cause misinterpretation. By pressing the molar teeth on
top of each other and comparing the diastema between
the incisor teeth in the upper and lower jaw, distortion
can be noticed clinically at an early stage. This method
can be carried out in combination with the BS-grading
method. With thin nasal swabs an increase in internasal
space can be observed clinically, but some experience is
necessary for the interpretation.
TREATMENT
The effective treatment of an outbreak of NPAR or PAR
requires a selected combination of management, envi-
ronmental, chemotherapeutic, and vaccination proce-
dures. No one combination is equally applicable to all af-
fected herds. The overall aims of treatment are (1) to
reduce the prevalence and load of the important specific
bacterial infections (bordetellosis and pasteurellosis) in
young pigs by sow vaccination, medication of feed, and
antibiotic treatment of piglets; (2) to treat growing pigs
with an acute rhinitis to reduce the weight of bacterial
infection and severity of the hypoplastic changes and
maintain efficient growth and feed utilization; and (3) to
manipulate housing, ventilation, and management to
improve the overall environment for the pigs (de Jong
and Bartelse 1980; Smith 1983).
Management and therapeutic measures to control
bordetellosis in commercial pig herds are required or
usually deemed necessary by experienced clinicians only
in herds where this infection is associated with clinically
significant disease, whether rhinitis, bronchopneumo-
nia, or infectious PAR. The mere presence of the infec-
tion within an ordinary commercial herd is not, on its
own, sufficient ground for initiating therapeutic mea-
sures against it.
The sulfonamides were the first drugs to be used
successfully in this respect (Switzer 1963) and are still
widely employed, either alone or in combination with
antibiotics, or potentiated with trimethoprim. Bron-
chopneumonia in piglets should be treated with par-
enteral injections of sulfadoxine or sulfadiazine at 12.5
mg/kg with trimethoprim at 2.5 mg/kg daily for 3–5
days.
Alternatives to the sulfonamide drugs have been ex-
amined. Most porcine isolates of B. bronchiseptica appear
to be sensitive to the tetracyclines (Sisak et al. 1978;
Smith et al. 1980; Pijpers et al. 1989), and these drugs,
particularly a long-acting formulation of oxytetracycline
given by parenteral injection to young pigs, appear to be
suitable for the control of bordetellosis.
The new fluoroquinolones are also active against
porcine B. bronchiseptica (Hannan et al. 1989).
Antibiotic Resistance
The in vitro activity of 12 sulfonamide drugs against B.
bronchiseptica was compared by Mengelers et al. (1989),
who showed that the minimum inhibitory concentration
(MIC)50 ranged from 0.5 to 8 µg/mL. Against a selection
of the pathogenic respiratory bacteria of swine, sul-
famethoxazole had the highest antimicrobial activity,
and sulfamezathine had an overall low activity. Isolates
of B. bronchiseptica from pigs have been shown to have
transmissible R factors that carry antibiotic resistance
(Terakado et al. 1974).
Medication
SOWS AND PIGLETS. To reduce the prevalence and
severity of nasal infection acquired from dams, the feed
of the sow can be medicated during the final month of
gestation. Sulfadimidine (sulfamethazine) (400–2000
g/ton) and oxytetracycline (400–1000 g/ton) are the
products most widely used.
Suckling piglets are best medicated by strategic injec-
tions of antibacterial agents in therapeutic dosages four
to eight times during the first 3–4 weeks of life. The most
useful are potentiated sulfonamides, oxytetracycline,
and penicillin/streptomycin.
If bordetellosis is the major infection in suckling
piglets, potentiated sulfonamides are the drugs of choice
(12.5 mg/kg sulfadiazine or sulfadoxine + 2.5 mg/kg
trimethoprim). Injections of oxytetracycline (20–80
mg/kg) once or twice a week are also clinically effective
for PAR (de Jong and Oosterwoud 1977; Mefford et al.
1983). The long-acting formulation (20–80 mg/kg) may
be the preferred product and is best given once or twice
a week during each of the first 3 or 4 weeks of life. If the
 CHAPTER 27 PROGRESSIVE AND NONPROGRESSIVE ATROPHIC RHINITIS
organism is not resistant, the drug is effective against
pasteurellosis, since, experimentally, long-acting oxytet-
racycline has reduced the prevalence of nasal infection
and the severity of turbinate atrophy induced by P. mul-
tocida (Gois et al. 1983b); although other researchers
prefer doxycycline (Pijpers et al. 1988). In the Nether-
lands, intranasal spraying of oxytetracycline in a 5% so-
lution is used in piglets twice a week, when starting the
treatment. If effective after 2–3 months, a reduction
from twice to once a week can be recommended (de Jong
1983b). This withdrawal of medication also depends on
the average antibody titer against the toxin of P. multoci-
da in the dams resulting from the vaccination program.
Other antibiotics to which P. multocida may be sensi-
tive and that are frequently used in therapeutic concen-
trations against pneumonia caused by pasteurellosis in-
clude penicillin/streptomycin (20,000 IU/10–25
mg/kg), tylosin (10–25 mg/kg), lincomycin/spectino-
mycin (50/100 mg/kg), ampicillin (10–20 mg/kg),
amoxycillin (10–20 mg/kg), spiramycin (25 mg/kg),
quinolone derivatives (0.5–5 mg/kg), cephalosporins
(1–5 mg/kg), and tiamulin (10–20 mg/kg) (Plonait and
Bickhardt 1988). The benefits of the treatments have not
been critically evaluated as far as nasal and pulmonary
protection and/or elimination of the toxigenic P. multo-
cida are concerned.
WEANERS AND GROWERS. The PAR in weaned pigs
that leads eventually to marked turbinate atrophy at
slaughter can be controlled to some extent by medica-
tion of weaner and/or grower rations or by the addition
of antibiotics to the drinking water. Such medication al-
so assists in the maintenance of growth and efficiency of
feed utilization in the face of active PAR, but as might be
expected, medication is always much more effective
when the pigs’ environment is improved. Various an-
tibacterial agents alone or in combination are effective.
The sulfonamides are frequently included in rations be-
cause of their known efficacy against bordetellosis. Their
use and the problems of the development of drug resis-
tance are of great concern.
Well-established drugs or combinations suitable for
the control of PAR are (1) sulfadimidine (sulfameth-
azine) (400–2000 g/ton) in feed or sulfathiazole
(0.08–0.13 g/L) in the drinking water; (2) chlortetracy-
cline (165 g/ton), sulfadimidine (sulfamethazine) (165
g/ton), and penicillin G (83 g/ton) in feed; (3) tylosin
(100 g/ton) and sulfadimidine (sulfamethazine) (100
g/ton) in feed; (4) carbadox (50 g/ton) and sulfadimi-
dine (sulfamethazine) (100 g/ton) in feed; (5) oxytetracy-
cline in feed (400 g/ton) or in drinking water (0.18 g/L)
(Giles 1986). Various other antibacterial agents, alone or
in combination, also have broadly similar beneficial ef-
fects on PAR lesions and help to maintain growth. For ex-
ample, the following have been demonstrated as clinical-
ly effective in feed: lincomycin (220 g/ton); lincomycin
de Jong 373
(220 g/ton) and sulfamethazine (550 g/ton); lincomycin,
spectinomycin, and amoxicillin trihydrate (10–20
g/ton).
When a number of drugs are used in feed, a decrease
of bioavailability can occur, which may result from the
amount of calcium, the feed processing, and the water
ration given to the treated pigs (Counotte et al. 1984;
Froe 1990; Sutter and Wanner 1990). The availability of
some of these drugs and the regulations regarding their
use in food-producing animals vary between countries.
Selection of an appropriate antibiotic or combina-
tion depends partly on cost, legislation, and clinical ex-
perience but should also be related to the antibiotic sen-
sitivity patterns of B. bronchiseptica and P. multocida
isolates and the established MICs (Pijpers et al. 1988;
Fales et al. 1990; Awad-Masalmeh et al. 1994). Differ-
ences in MIC between P. multocida type D and type A
strains may occur in the same herd (Schimmelpfennig
1990). In a severe outbreak, treatment should be direct-
ed at pigs of all age groups other than those immediate-
ly destined for slaughter; as the severity declines, reduc-
ing antibiotic use for the older fatteners should be the
first priority. The appropriate withdrawal times before
slaughter must always be adhered to. It is usually neces-
sary for pigs at risk to receive medicated feed for a mini-
mum of 4–5 weeks and frequently for longer periods, de-
pending on the results of the vaccination program and
the improvement in housing, ventilation, and manage-
ment.
Vaccination
SOWS. Vaccination of the sow induces a significant
degree of passive colostral protection against B. bron-
chiseptica in the serum of her suckling piglets
(Koshimizu et al. 1973; Smith et al. 1982); in the field,
this protection will often persist until about the time of
weaning. The colostral protection afforded by sow vacci-
nation is thus an effective aid in controlling B. bron-
chiseptica infections among populations of young suck-
ling piglets; in herds where early piglet infection occurs
and rhinitis and/or bronchopneumonia develop in
young pigs, sow vaccination should be recommended.
Initially two doses should be given 6 and 2 weeks before
farrowing, followed by revaccination at 2 weeks before
each subsequent farrowing. Bordetella vaccines which in-
duce toxin-neutralizing antibodies and pilus antibodies
are of interest.
In a prolonged vaccination scheme for gilts and the
sow and boar population, the number of B. bronchisepti-
ca carriers is reduced. This in combination with the in-
creased colostrum protection and all-in/all-out proce-
dures in the farrowing and weaner sections may be
helpful in producing B. bronchiseptica–free offspring or in
reducing the B. bronchiseptica colonization in such popu-
lations. These procedures also reduced bordetella pneu-
monia. In NPAR herds the use of combined bordetella
374 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
and pasteurella vaccines is not recommended, because
the antibodies against the pasteurella toxin lead to suspi-
cion of PAR in such herds. Downgrading the health sta-
tus could be the result.
Vaccination of the sow with a potent B. bronchiseptica
vaccine is an effective way to reduce the prevalence and
severity of nasal bordetellosis in suckling and weaned
piglets (de Jong 1985) but exerts only a limited effect on
clinical PAR (Giles and Smith 1983). Pathogenic deter-
minants important in vaccines include the toxigenic
characters, the pilus-producing factor, and outer-mem-
brane proteins. Lack of antibody to some of these prop-
erties seems to influence the reduction of B. bronchisepti-
ca in sows and piglets.
B. bronchiseptica/P. multocida vaccines have been eval-
uated experimentally and in the field. In some countries
combined vaccines are available commercially. Such vac-
cines have reduced the prevalence of clinical PAR
(Schuller et al. 1980; Baars et al. 1982; de Jong et al.
1984) but do not eliminate the condition. As might be
expected, the thermolabile toxin for P. multocida appears
to be an important determinant in eliciting protection,
because experimental vaccination of sows with crude
toxin significantly protected their offspring against PAR
(Baars et al. 1982, 1986; Pedersen and Barfod 1982). The
specific importance of the toxoid fraction has been eluci-
dated (Nagy et al. 1986; Foged et al. 1989; Frymus et al.
1989; Chanter and Rutter 1990).
The antigens and mechanisms of protection against
toxigenic P. multocida infection and associated disease
have yet to be fully defined; reports show that toxoid
preparations of P. multocida produce an antitoxin re-
sponse, with an effect on colonization (Chanter and Rut-
ter 1990). Claims made for B. bronchiseptica vaccines in
the control of AR were not fully substantiated in field use
(Giles and Smith 1983); thus, a rush to develop further
combined vaccines without full appraisal of the required
antigens is undesirable.
Some of the currently available combined B. bron-
chiseptica/P. multocida vaccines may be of benefit in con-
trolling bordetellosis and toxigenic pasteurellosis and in
reducing the prevalence and severity of PAR when com-
bined with housing and management changes (de Jong
et al. 1984). The marked reduction in toxigenic P. multo-
cida in the nose following vaccination with a potent tox-
oid vaccine requires further evaluation to determine
whether the expression of high antibody levels can erad-
icate toxigenic P. multocida. Vaccination of sows with
combined vaccines can be as effective as piglet medica-
tion. However, neither procedure constitutes a means of
protection against the condition nor necessarily obviates
the need for medication. Such a vaccination program,
once started in an infected herd, has to be maintained, at
least for many years.
PIGLETS. Vaccination of older pigs undoubtedly pro-
duces an active humoral response but its value is debat-
able, since the main effects of the infection occur in
younger animals. Specific measures against B. bron-
chiseptica infection should be directed toward preventing
the infection from arising in suckling pigs (by manage-
ment, sow vaccination, or chemotherapy) or mitigating
its effects in young pigs (by management and/or
chemotherapy).
B. bronchiseptica vaccine has been widely employed.
Although some observers have concluded that it has lit-
tle benefit against clinical PAR and is generally less effec-
tive than sow vaccination (Giles and Smith 1982, 1983),
in some countries (notably the United States) the proce-
dure nevertheless still enjoys fairly widespread use. B.
bronchiseptica/P. multocida bacterin vaccines are also
widely employed, but the composition of many of them
means that they may be of little benefit in the field. In a
study in which both sows and piglets were inoculated
with a combined vaccine, Mefford et al. (1983) demon-
strated that vaccination alone did not influence turbinate
atrophy and only marginally improved profitability.
Only vaccination of the piglets born of inadequately
vaccinated or unvaccinated dams is of value in the case of
P. multocida toxoid vaccines. When sows are properly
vaccinated and produce good levels of antitoxic antibod-
ies, piglets may not respond to vaccination. If the dams
show good titers, the colostral protection in pigs can last
for 3–4 months. Vaccinations of the young breeding
stock can be started after this age. A high antitoxin titer
seems to reduce colonization by toxigenic P. multocida.
The additional use of therapeutics (e.g., long-acting
oxytetracycline) in piglets significantly reduced turbinate
atrophy at slaughter and markedly improved profitabili-
ty (Pejsak et al. 1990). Furthermore, some commercially
available vaccines contain neither toxigenic strains nor P.
multocida toxoid, the manufacturers only claiming effica-
cy against pneumonic pasteurellosis.
Housing and Husbandry
Medication and vaccination procedures should never be
introduced without concurrent attempts to improve
swine management and husbandry. Although the nonin-
fectious factors that contribute to the severity of PAR are
inadequately defined quantitatively, steps should always
be taken to reduce their influence. All-in/all-out systems
are favored for farrowing, weaner, and preferably fatten-
er management; the age of the sow herd can be allowed
to rise and the introduction of large numbers of infected
new gilts can be avoided; stocking density can be re-
duced; strict hygiene measures should be implemented;
and correct ventilation rates should be maintained to re-
duce the airborne concentration of bacterial pathogens,
noxious gases, and dust. Steps should also be taken to re-
duce factors that stress young pigs, including large tem-
perature variations, chilling, and drafts. Replacement
breeding stock should not only be free from clinical signs
of disease but also be raised in herds free from infections
with toxigenic P. multocida; introduced weaners should
 CHAPTER 27 PROGRESSIVE AND NONPROGRESSIVE ATROPHIC RHINITIS
be free from active rhinitis and the associated sneezing
and typical BS. Newly purchased stock should originate
from herds free from toxigenic P. multocida, be isolated
(quarantined), be tested bacteriologically or serological-
ly for freedom from toxigenic P. multocida, and be inte-
grated slowly. Severely affected pigs with obvious and se-
vere growth retardation should be culled. Vaccination
programs should be started if breeding stock free from
toxigenic P. multocida infection is brought into infected
herds. Vaccination can reduce colonization by toxigenic
P. multocida when infection cannot be avoided. Such an
AR vaccination program needs to be carried out continu-
ously in the whole sow population of the infected herd.
Effective vaccination with potent vaccines in sows alone
can also limit the economic damage in weaners. The risk
to breeders, multipliers, and fatteners of becoming in-
fected by toxigenic P. multocida can be limited by asking
for or giving guarantees that the pigs bought or sold orig-
inate directly from herds certified free from the organ-
ism. This certification can be carried out under govern-
mental legislation. Only by means of such a system of
enforced restrictions can the spread of toxigenic P. mul-
tocida via sales or auctions be prevented.
Depopulation
Depopulation and restocking with swine from a source
known to be free from toxigenic P. multocida are often the
only viable solution. Buildings should be thoroughly
cleaned and disinfected, then fumigated and left empty
for 2 weeks to 2 months, depending on the efficacy and
quality of the hygiene program. Eradication of rats,
mice, and birds must be carried out properly and contin-
ually. Replacement pigs should be bought from sources
known to be free from PAR and toxigenic P. multocida in-
fection, based on clinical, abattoir, bacteriologic, and/or
serologic monitoring.
PREVENTION
Since B. bronchiseptica is widely prevalent in the pig pop-
ulation, its total exclusion from a herd is only possible by
the development of an SPF system or by medicated and
segregated early-weaning methods and the strict mainte-
nance of an effective barrier. B. bronchiseptica is often one
of the first agents to infect an SPF herd.
Vaccination
B. bronchiseptica vaccines have been developed and used
in several countries in an attempt to control both the in-
fection and the clinical condition AR by immunologic
methods. Killed whole-culture vaccines with aluminum
salt adjuvants were the first to be available commercially
and have been licensed for use in several countries since
the 1970s. Other types of vaccine have also been investi-
gated, including live avirulent strains (Krüger and
Horsch 1992) and subunit vaccines, but generally have
not been used widely in practice. Killed whole-culture
de Jong 375
adjuvanted vaccines were at one time widely employed in
pig herds because several reports, mainly from the Unit-
ed States and Japan (e.g., Nakase et al. 1976; Goodnow
1977; Goodnow et al. 1979), indicated that such prod-
ucts were highly effective in the control of field out-
breaks of clinical PAR. In Europe, however, these bene-
fits were much less obvious (Bercovich and Oosterwoud
1977; Pedersen and Barfod 1977; Giles and Smith 1982).
Later, further studies from the United States also con-
cluded that such bordetella vaccines are of limited effica-
cy in the overall control of PAR. A critical review of bor-
detella vaccines (Giles and Smith 1983) concluded that,
as single antigens, their beneficial effects in the control of
PAR are indeed limited and the previous claims for their
usefulness overstated. In the light of new knowledge,
combined vaccines have been developed consisting of B.
bronchiseptica/P. multocida bacterins or B. bronchiseptica
bacterin combined with P. multocida toxoid. Such vac-
cines are of use in the field, provided their limitations are
fully realized by the clinician.
Single bordetella vaccines should be used to limit the
influence of bordetellosis or NPAR but not in PAR-dis-
eased herds.
PAR can be prevented effectively only by rearing
swine free from the specific infections required for dis-
ease to develop. The adoption of an SPF system of pro-
duction and the maintenance of an effective microbio-
logic barrier are the only sure ways of achieving this.
Medicated early weaning (Alexander et al. 1980) may
well be a viable alternative to the established methods of
producing SPF stock free from toxigenic P. multocida
(James 1989; Blaha et al. 1990; Larsen et al. 1990). Tradi-
tional vaccination or medication regimes applied to in-
fected herds are not likely to create herds free from the
infections; thus, the infected herds pose a serious threat
to free herds in their neighborhood and also pose risks to
other branches of animal production, such as poultry,
rabbits, goats, sheep, and cattle (Nielsen et al. 1986; Fry-
mus et al. 1996). In a preventive disease control pro-
gram, eradication schemes have to be carried out in all
types of herds and in all kinds of animals infected with
toxigenic P. multocida. B. bronchiseptica appears to be
very widespread in the pig population, but the preva-
lence of infection with toxigenic strains of P. multocida is
less well defined. A positive correlation exists between
the prevalence of toxigenic strains of P. multocida in a
herd and the known occurrence of PAR (de Jong 1983b;
Nielsen 1983; Pedersen 1983; Cowart and Backstrom
1984; Leblanc et al. 1986b; Bechmann and Schöss 1988;
Cowart et al. 1989), although the mere presence of this
infection does not always mean clinical disease. The po-
tential risk of clinical PAR developing in a herd could be
eliminated simply by ensuring that pigs are free from
toxigenic P. multocida infection. Therefore, it is desirable
to monitor breeding herds for this pathogen and to take
steps to reduce its dissemination and introduction into
unaffected herds. It is definitely beneficial to maintain
376 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
herds with no history of PAR and low scores of atrophy
at slaughter behind effective barriers or to bring in pigs
only from sources known to be free from the condition.
Breeding companies that sell and export pigs from in-
fected herds, inadequately monitored for infectious dis-
eases like PAR, are involved more and more in financial
claims by new clients who will not accept the cost of
medication and vaccination and the degradation of the
health status of their own breeding herds. Because aero-
genic spread has been described (Baekbo and Nielsen
1988; Stehmann et al. 1989) and spread of infection may
be possible from surrounding herds, special attention to
air filtration and decontamination systems (Rutter et al.
1986; Voets et al. 1986b) could be necessary if distances
become too small (probably within 200–2000 m, de-
pending on the size of the surrounding herds). PAR has
also been found in outdoor systems. Prevention of toxi-
genic P. multocida infection in outdoor systems can be
difficult. Prevention by artificial insemination seems
possible, but some risks exist when the antibiotics used
in the semen diluter do not eliminate the toxigenic pas-
teurellae (Overby 1990).
Monitoring
Commercial producers should be aware of the current
disease status of their herds. This applies to herds that
have past or present evidence for the clinical condition,
as well as to producers who need to monitor the effects of
control measures or whose herds have remained free
from the condition and who appreciate early warning of
any change in herd status. Hence, ideally, herds need
monitoring systems that can quantify not only the pres-
ence but also the effects of PAR (Done 1983b), especially
in the case of an infected herd. Since this disease is not a
simple all-or-nothing condition, merely relying on the
presence of clinical disease disguises moderate to low
levels of infection and recognizes it too late for the intro-
duction of prophylactic measures.
Parameters that can be usefully measured are indirect
production or economic data, such as liveweight gain or
efficiency of feed utilization, and clinical/pathological
data related to PAR, including the amount of sneezing,
the incidence of facial distortion, and the two most use-
ful criteria, the prevalence and extent of BS in weaned
pigs and the prevalence and severity of turbinate atro-
phy at slaughter. The latter is the most popular in some
countries. In large, modern slaughterhouses the gather-
ing of snouts and cross sections is difficult; in such situa-
tions a scoring system on longitudinally opened snouts
can be useful (Visser et al. 1988). Sophisticated methods
of monitoring have been developed, one of which is the
plotting of cumulative-sum charts with decision bound-
aries, since it gives early signals of deterioration or im-
provement. Done (1983b) has reviewed the methods of
monitoring PAR. Use of computer technology in slaugh-
terhouses and on pig farms means that important dis-
ease-monitoring systems may be effectively employed
without laborious clerical work (Collins et al. 1988). Be-
cause the antibody titer against the toxin of P. multocida
correlates with increased protection against turbinate at-
rophy (Sorensen et al. 1990), serologic monitoring be-
comes of interest in determining a possible increase in
PAR risk when a decrease in the titers occurs in herds
with a sow vaccination program. A program in which on-
ly sows are vaccinated can also protect the pigs during
the fattening period. Recent investigations have shown a
relationship between antitoxin titers and some protec-
tion against colonization by toxigenic pasteurellae
(Chanter and Rutter 1990). Modern methods for the de-
tection of toxigenic P. multocida by DNA probes from
samples of noses, tonsils, or lungs may soon become use-
ful in monitoring systems (Kamps et al. 1990). Positive
results have already been achieved by bacteriologic
(Schöss 1982; Schöss and Thiel 1984; de Jong et al. 1988)
or serologic monitoring (de Jong et al. 1988; Bechmann
and Schöss 1990; Foged et al. 1990; Schimmelpfennig
1990).
Toxigenic P. multocida can be eliminated from infect-
ed breeding farms after intensive vaccination for a period
of more than 5 years. These regularly vaccinated sows
produce high anti–P. multocida toxin titers. During this
period the replacement gilts and boars must be bought
from herds free from toxigenic P. multocida. The replace-
ments should be introduced into the infected sow popu-
lation only after being vaccinated several times with an
atrophic rhinitis toxoid (ART) vaccine. The herd vaccina-
tion program needs to be continued until the last sow
from the infected population has left the farm, which
generally takes about 5 years. Methods to shorten such
periods by selecting and slaughtering the toxigenic P.
multocida carriers are being developed with the help of
the new PCR techniques. First attempts have been par-
tially successful (de Jong 1994; de Jong et al. 1994, 1996;
de Jong and Braamskamp 1994).
Selecting carrier sows in nonvaccinating herds by
bacteriological procedures and by the (DAKO) ELISA
test or the PCR test and removing them have been de-
scribed as successful in creating infection-free sow herds
(Alt et al. 1996).
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 Brucellosis
28 A. P. MacMillan
Brucellosis of pigs is an infectious disease that has been
recognized as a specific entity since 1914, when Traum
(1914) isolated the organism from aborted porcine fetus-
es in Indiana, but for many years it was thought to be
caused by an exceptionally pathogenic form of Brucella
abortus until Huddleston (1929) named the infectious
agent, B. suis, as a separate species. Brucellosis occurs in
most countries throughout the world where pigs exist in
the wild or domesticated state.
In the United States porcine brucellosis was recog-
nized as a major disease, causing considerable economic
loss during the 1920s-1950s. Since that time, changes in
management combined with regulatory programs to
eradicate the disease have gradually eliminated brucel-
losis as a major disease problem from large areas of the
country. Since 1989 all states have become participants
in the federal eradication program, and regions where
the majority of pigs are raised appear to be virtually free
of brucellosis. Pigs in the southeastern United States
seem to have the highest incidence of brucellosis, al-
though the herd infection rate there is less than 1.5%. Ac-
cording to USDA statistical information (Frye et al.
1993), 0.5% of 1.6 million pigs tested on farms, at live-
stock markets, and at slaughter establishments during
fiscal year 1993 were serologic reactors. This information
indicates a higher incidence than actually exists, since
single serologic reactors in noninfected herds are a fre-
quent occurrence. The actual number of herds classified
as infected in 1993 was 83, and these were for the most
part small herds in endemic areas.
The disease appears to be widespread in South Amer-
ica, where it is predominantly caused by biovar 1. In Eu-
rope (apart from Britain and Scandinavia, which are bru-
cellosis free), there is a general low prevalence of porcine
brucellosis. In Africa, the disease is reported by some
countries, but the number of pigs on the continent is not
large, and the true position is not entirely clear. Asia, par-
ticularly Southeast Asia, seems to have a generally high
prevalence of the disease, predominantly caused by bio-
var 3 in South China and Singapore and by biovar 1 else-
where. In Australia the disease is confined to feral pigs in
Queensland (Alton 1990).
Porcine brucellosis also has noteworthy public health
implications. Until recently the source of the majority of
human brucellosis has been Brucella suis–infected pigs
(Fox and Kaufmann 1977). The public health hazard
caused by porcine brucellosis is of proportionately
greater significance than the risk from bovine brucellosis
primarily because B. suis (biovars 1 and 3) appears to
have a much higher degree of pathogenicity for humans
than B. abortus. There also tend to be higher numbers of
B. suis organisms in the tissues, providing a greater expo-
sure to persons who come in contact with infected pigs.
As pigs do not produce dairy products, the incidence of
B. suis in humans is almost entirely occupational: in
farmers, veterinarians, and abattoir workers. Interest-
ingly, although the infection of cattle with B. suis is rare,
Cook and Noble (1984), working in Australia, reported
several cases, probably contracted following contact with
feral pigs. Persistent excretion in the milk may give rise
to human epidemics (Borts et al. 1943). B. suis infection
of a ram has been reported by Paolicchi et al. (1993),
who suggest that this may represent a public health haz-
ard.
ETIOLOGY
The genus Brucella comprises six nomen species: B. abor-
tus, B. melitensis, B. suis, B. neotomae, B. ovis, and B. canis
(Brinley-Morgan and McCullough 1974; Alton et al.
1975). The genus appears to be genetically very homoge-
neous (Verger et al. 1985) but does not appear to be
closely related to any other animal pathogens (de Ley et
al. 1987). The first three nomen species are further di-
vided into 8, 3, and 5 biovars, respectively. The principal
hosts for B. melitensis are goats and sheep; for B. abortus,
cattle; for B. neotomae, desert wood rats; for B. ovis, sheep;
and for B. canis, dogs. The most common host for B. suis
biovars 1 and 3 is the pig, and these biovars are world-
wide in distribution. B. suis biovar 2 occurs in Europe,
where the hosts are pigs and the European hare (Lepus
capinensis), which can form a reservoir for occasional
outbreaks in both wild and domestic pigs. The disease in
pigs caused by biovar 2 differs slightly from that caused
by biovars 1 and 3 in that miliary brucellosis of the
uterus is a feature, and unlike them, it does not appear to
be pathogenic for humans. B. suis biovar 4 is enzootic in
reindeer and caribou (Rangifer spp.) in Siberia, Alaska,
and Canada and is apparently not pathogenic for pigs al-
though it causes many cases of human brucellosis. B. su-
is biovar 5 causes murine brucellosis.
385
386 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
B. suis is the only recognized Brucella species that
causes systemic or generalized infection leading to re-
productive failure in pigs. Pigs can be infected naturally
or experimentally with other Brucella species, but a char-
acteristic of the infection is almost invariably a symp-
tomless, self-limiting localized infection of lymph nodes
regional to the point of entry. It should be noted, howev-
er, that the differentiation of biovars of Brucella must be
accomplished using methods only available in large ref-
erence centers, and this probably accounts for the fre-
quent reports before the early 1960s of the isolation of B.
melitensis from pigs (Alton 1990).
Bacteriological examination is often of great assis-
tance in aiding a diagnosis, but it must be remembered
that handling B. suis in the laboratory is extremely haz-
ardous unless appropriate precautions are taken. The
genus Brucella belongs to Hazard Group III and should
be handled in a Class I/III safety cabinet within Contain-
ment Level III accommodation by staff with adequate
training and experience.
Primary isolations of B. suis, like the other species in
the genus, appear as small, convex, translucent colonies
on the surface of agar media after incubation at 37˚C for
2–7 days. All Brucella species and biovars, except B. ovis
and B. canis, occur naturally with smooth colonial mor-
phology. B. ovis and B. canis always occur as rough forms,
even on primary isolation. All smooth forms of brucellae
may dissociate into intermediate, rough, or mucoid
forms under certain artificially induced environmental
conditions. This dissociation frequently occurs if cul-
tures are left for a long period without being subcul-
tured, and it renders them incapable of being assigned to
species or biovar. Microscopically, Brucella organisms are
small, gram-negative bacilli or coccobacilli and are non-
motile and arranged singly. B. suis organisms from dif-
ferent sources may vary considerably in size but are gen-
erally 0.4–0.8 × 0.6–3.0 µm.
Several commercially available agar media are suit-
able for isolation and propagation of B. suis; those more
commonly used include tryptose, trypticase-soy, Albimi,
serum dextrose, Farrell’s, and potato infusion. The addi-
tion of serum to the media to a final concentration of 5%
Table 28.1. Characteristics used for the differentiation of Brucella suis
H2S Growth on
Production Thionin
Biovar 1 + +
Biovar 2 − +
Biovar 3 − +
Biovar 4 − +
Biovar 5 − +
a
Agglutination with A and M monospecific serum.
b
No lysis.
c
Lysis.
d
Some strains may grow.
frequently enhances the growth of brucellae, particular-
ly on primary isolation. Increased carbon dioxide ten-
sion does not enhance the growth of B. suis. A more com-
plete discussion of biotyping procedures, biovars, and
formulation of growth media, as well as descriptive char-
acteristics of the entire genus, can be obtained from Al-
ton et al. 1988.
In general, all biovars of B. suis have a noticeably
greater urease and catalase activity than other species of
Brucella. Classification of B. suis into biovars is based on
the combined findings of a variety of conventional and
specialized tests. Briefly, B. suis biovar 1 produces large
amounts of hydrogen sulfide, whereas biovars 2, 3, 4,
and 5 produce little or none; growth of biovars 1, 2, and
5 is inhibited to a greater degree by basic fuchsin than
growth of biovars 3 and 4; B. suis is not lysed by routine
test dilutions (RTD) of Tbilisi Brucella phage but may be
partially lysed by 10,000 × RTD; using monospecific an-
tisera for the dominant A and M antigens, B. suis biovars
1, 2, and 3 are A dominant, while biovar 4 is AM (the on-
ly distinguishing feature separating biovars 3 and 4), and
biovar 5 is M dominant (Table 28.1).
As the oxidative metabolic characteristics of all B. su-
is biovars are very similar, there are insufficient differ-
ences for differentiation.
Among the B. suis, only biovars 1 and 3 are known to
occur in pig-raising areas of the United States. Until 1946
the only recognized cause of pig brucellosis in the Unit-
ed States was the organism now known as B. suis biovar
1. At that time, B. suis biovar 3 (originally classified as
American B. melitensis) was first isolated from tissues of
infected pigs by S. H. MacNutt (Borts et al. 1946). Since
the 1950s, reported isolations of B. suis biovar 1 have be-
come comparatively less frequent, while isolations of B.
suis biovar 3 have become more frequent. There is little
doubt that biovar 3 is now the predominant biovar in
porcine brucellosis in the United States.
EPIDEMIOLOGY
Most evidence indicates that most B. suis infection is
transmitted to susceptible animals through direct associ-
Lysis by Lysis by
Growth on Dominant Tb Phage Tb Phage
Fuchsin Antigen at RTD at 104 RTD
−a A NLb Lc
−a A NLb Lc
+a A NLb Lc
−d AM NLb Lc
−d M NLb Lc
 CHAPTER 28 BRUCELLOSIS MacMillan
ation with infected pigs. In this species, the most impor-
tant routes of infection are through the alimentary and
genital tracts. The habits of pigs and usual character of
the disease strongly suggest that the alimentary tract is
the most common portal of entry. Pigs of all ages may
eat food or drink fluid contaminated with discharges
from infected pigs. Piglets are frequently infected by
nursing infected dams, and when breeding pigs are con-
fined together, aborted fetuses and fetal membranes are
readily consumed. Brucellosis is a venereal disease in
pigs, and sows are readily infected when mated with in-
fected boars or when artificially inseminated with semen
containing B. suis. Experimentally, pigs are readily infect-
ed by conjunctival or intranasal exposure with suspen-
sions of B. suis. It is possible that organisms could also
enter through scarified or, possibly, intact skin.
The survival of brucellae under environmental con-
ditions is a relatively important factor in transmission of
the disease. The survival rate of brucellae is similar to
that of other nonsporing gram-negative bacteria and as
such is extremely variable depending on prevailing con-
ditions. Experimental evidence indicates that B. suis is
readily killed by pasteurization, 2–4 hours of direct sun-
light, and the most commonly used disinfectants. Bru-
cellae can survive in organic matter at freezing or near-
freezing temperatures in excess of 2 years. Consequently,
efforts to eliminate brucellosis from pig-raising premises
must include an effective sanitation program
(Luchsinger et al. 1965). The most suitable methods for
preserving Brucella organisms for long periods are
lyophilization and/or storage at subfreezing tempera-
tures.
There are few known reservoirs of B. suis infection
other than infected domestic pigs. Only the European
hare and feral pigs have been established as significant
potential reservoirs. The European hare was incriminat-
ed as a natural host for B. suis biovar 2 as early as 1954
(Bendtsen et al. 1954) and is apparently responsible for
periodic outbreaks of brucellosis of pigs in Europe. Feral
pigs in the southeastern United States, and to a much
lesser extent elsewhere (Drew et al. 1992), have been dis-
covered to have a high rate of serologic reactors, with iso-
lation of B. suis biovar 1 from some animals (Wood et al.
1976; Becker et al. 1978). Extensive studies conducted in
Florida showed that although only some populations are
infected, the incidence within these groups is usually
high (Leek et al. 1993). The epidemiological importance
of feral pigs in the maintenance of porcine brucellosis
depends largely on the degree of contact between wild
and domestic pigs (Nettles 1991). If pig management
systems in regions where feral pigs exist prevent contact,
B. suis infection in feral pigs may be of greater public
health importance than a threat to the pig industry. The
vaccination of feral populations using dosed baits has
been shown to be a feasible option to be considered in
certain situations in the future (Fletcher et al. 1990), pos-
387
sibly using strain RB51, a rough mutant strain recently
introduced for routine use in cattle in the United States
(Enright 1995). There have been numerous instances of
B. suis infection or seropositivity in rodents or carnivo-
rous species trapped near areas where brucellosis in do-
mesticated pigs has occurred. However, general indica-
tions are that these species acquired infection from the
pigs and are terminal hosts of the infection. With few or
no exceptions, epidemiological investigation of newly in-
fected pig herds has revealed the source as another herd
of domesticated pigs.
Experimental studies have shown that pigs can be in-
fected with B. suis biovar 4, B. abortus, B. melitensis, B. ca-
nis, and B. neotomae. However, there has been no evi-
dence that these organisms invade the genital tract, are
transmissible between pigs, or localize in any tissues oth-
er than lymph nodes draining the site of infection. All
available evidence indicates that these biovars or species
are not highly pathogenic for pigs, pigs are not likely to
show clinical evidence of disease, and the infection is
self-limiting and usually persists less than 60 days. Nev-
ertheless, these infections do have importance for public
health. In particular, pigs are associated with B. abortus
infection in packinghouse workers.
Pigs infected with B. suis biovars 1, 2, or 3 can serve as
a source of infection for other domesticated animal
species. B. suis infection can occur naturally in horses,
cattle, and dogs. Although the most common brucella in-
fection in horses is B. abortus, fistulous withers and other
syndromes have been recorded as caused by B. suis when
horses were associated with infected pigs. Cattle are
rarely infected with B. suis; when infection does occur,
the characteristic infection is mastitis, with B. suis organ-
isms excreted in the milk representing a public health
risk. It can cause an acute infection in dogs, with preg-
nant bitches frequently aborting. There is a some evi-
dence that B. canis, a significant pathogen in dogs,
evolved from B. suis biovar 3.
PATHOGENESIS
Available literature and comparative studies indicate
that the pathogenesis of B. suis biovars 1, 2, and 3 is very
similar (Thomsen 1934; Hutchings 1950; Hoerlein et al.
1954; Deyoe 1967). Differences are generally related to
factors such as method of exposure, infecting dose, age
and breed of pigs, and possibly minor differences be-
tween strains of the same biovar. However, the charac-
teristics of the disease produced are usually indistin-
guishable.
Regardless of the route of infection, the organism
must be able to attach to and penetrate the mucosal ep-
ithelium, although the mechanisms for this have not yet
been fully elucidated. Following the initial penetration,
submucosal aggregations of lymphocytes and plasma
cells form in response. Invading organisms are carried to
388 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
local lymph nodes, although it is not known whether
they travel as free organisms or within phagocytes, and
infected nodes become enlarged due to lymphoid and
reticuloendothelial hyperplasia and infiltration. Brucella
organisms surviving regional node colonization enter a
phase of bacteremia, now protected from humoral im-
mune mechanisms by their intracellular location within
neutrophils and macrophages.
In B. suis infection of pigs, bacteremia is an invariable
finding in acute stages of the disease if frequent blood
samples are collected and examined bacteriologically. In
general, the onset of bacteremia ranges from 1 to 7
weeks after exposure, with a mean of about 2 weeks post-
exposure. Bacteremia persists an average of about 5
weeks and is generally continuous during that time. In-
termittent bacteremia in individual pigs has been ob-
served to be as brief as 1 week to as long as 34 months. It
is this bacteremia that is probably responsible for the
wide range of tissues secondarily infected during the
course of the disease.
Within a short time after the bacteremia stage, B. su-
is can be isolated from a large number of sites in the
body (Deyoe and Manthei 1967). The entire lymphatic
system is often affected for a period of time. With in-
creasing time after exposure, the sites of localization of
the organism tend to be reduced in number. Among
lymph nodes, the most frequent sources of B. suis are
mandibular, gastrohepatic, internal iliac, and suprapha-
ryngeal, in that order, depending essentially on the route
of infection. Organs of the genital system containing
high levels of erythritol, a sugar promoting the growth of
brucellae, become involved in many pigs and may re-
main persistently infected. The placenta is a privileged
site, and brucellae localize in the rough endoplasmic
reticulum of the chorionic trophoblasts. Despite severe
placental infection, only mild inflammation of the en-
dometrium is observed. The spleen, liver, kidney, blad-
der, mammary gland, and brain may be involved (Jubb
et al. 1985), although not as regularly as lymph nodes.
Other significant sources of B. suis, particularly in chron-
ically infected pigs, are joint fluids and bone marrow.
The response to invasion of B. suis becomes evident
with the appearance of humoral antibody, activation of
the cell-mediated immune system, and development of
microscopic lesions. These manifestations may occur si-
multaneously but usually are subsequent to the appear-
ance of detectable bacteremia; bacteremia may precede
detectable antibody levels possibly by as much as 6–8
weeks. As pigs recover from B. suis infection (i.e., when
viable organisms are no longer present in their tissues),
other manifestations, such as antibody levels, cellular hy-
persensitivity, and microscopic lesions, recede and dis-
appear also. Unfortunately, many pigs remain perma-
nently infected.
In a series of experiments, infection was established
in 248 sexually mature pigs (Deyoe 1972a). They were
killed at various intervals after exposure to B. suis and
their tissues subjected to thorough bacteriological exam-
ination. Three-fourths of the pigs in each group of fe-
males had recovered from infection by 4–6 months or
longer after exposure, whereas the recovery rate in males
never exceeded 50%. In contrast, Goode et al. (1952) and
Manthei et al. (1952) isolated B. suis from only 12 of 474
adult pigs exposed as suckling pigs. This information
demonstrates beyond doubt that the majority of pigs in-
fected with B. suis will eventually recover spontaneously.
Nevertheless, sufficient numbers of permanently infect-
ed animals will remain to serve as a continual source of
infection.
CLINICAL SIGNS
Clinical evidence of B. suis infection varies considerably
in different herds. The majority of affected herds may
have no signs of brucellosis recognizable by the herd
owner. The classic manifestations of pig brucellosis are
abortion, infertility, orchitis, posterior paralysis, and
lameness. Infected pigs fail to show any persisting or un-
dulating pyrexia. Clinical signs may be transient and
death is a rare occurrence.
Abortions may occur at any time during gestation
and are influenced more by the time of exposure than by
the time of gestation. The rate of abortion is highest in
sows or gilts exposed via the genital tract at the time of
breeding (Deyoe and Manthei 1969). Abortions have
been observed as early as 17 days following natural in-
semination by boars disseminating B. suis in the semen.
Early abortions are usually overlooked under field condi-
tions, and the first indication is a large percentage of
sows or gilts showing signs of estrus 30–45 days after the
service that resulted in conception. Little or no vaginal
discharge is observed with early abortions. Abortions
that occur during the middle or late stages of gestation
are usually associated with females that acquire infection
after pregnancy has advanced past 35 or 40 days. The
persistence of genital infection in females varies consid-
erably.
A small percentage of sows have been shown to shed
B. suis in vaginal discharges for as long as 30 months.
However, the majority ceased shedding organisms with-
in 30 days. A clinically apparent abnormal vaginal exu-
date is seldom observed in sows that have uterine infec-
tion except just prior to and for a short time after
abortion. The majority of female pigs eventually recover
from genital infection.
When genital infection in sows persists only a short
time after abortion, parturition, or breeding to an infect-
ed boar and the sows are permitted two or three estrous
cycles of sexual rest, subsequent conception rates and re-
productive capacity are usually very good.
Genital infection tends to be more persistent in boars
than in sows. Some infected boars do not develop a lo-
 CHAPTER 28 BRUCELLOSIS MacMillan
calized genital infection. However, boars that do develop
genital infection seldom recover from it. Pathologic
changes in the male accessory glands or testes are gener-
ally more extensive and irreversible than in the uterus.
Infertility and lack of sexual drive may occur in infected
boars and are frequently associated with testicular in-
volvement. More commonly, however, boars have infec-
tion in accessory genital glands and as a result dissemi-
nate large numbers of B. suis in their semen. These boars
do not necessarily have reduced fertility (Vandeplassche
et al. 1967). In most circumstances, clinically apparent
lesions of B. suis biovar 1, 2, or 3 infection in boars are
seldom encountered.
Clinical brucellosis in suckling and weaning pigs usu-
ally appears as spondylitis associated with posterior
paralysis. These clinical signs are occasionally observed
in any age of pigs.
LESIONS
Macroscopic pathologic changes produced by B. suis in
pigs are quite variable. Enough abscess formation may
occur in affected organs to result in necrosis and desqua-
mation of a significant proportion of the mucous mem-
brane. Generally, the histopathological changes consist
of uterine glands filled with leukocytes, cellular infiltra-
tion of the endometrial stroma, and hyperplasia of
periglandular connective tissue. Diffuse suppurative in-
flammation is usually present in affected placentas.
There also may be considerable necrosis of epithelium
and diffuse hyperplasia of fibrous connective tissue.
Focal microscopic granulomatous lesions frequently
can be observed in livers of pigs with brucellosis, partic-
ularly during bacteremic phases of the disease. These fo-
ci frequently are necrotic areas infiltrated with lympho-
cytes, macrophages, neutrophils, and giant cells, with
sheets of histocytic and epithelioid cells with a central
zone of caseous or coagulative necrosis. The lesions are
usually partially or completely enclosed by a fibrous cap-
sule. The necrotic portions of the granulomas are heavi-
ly infiltrated with neutrophils, and liquefaction and min-
eralization may occur (Enright 1990).
These lesions are not specific for brucellosis, since
similar hepatic lesions are associated with other bacteri-
al infections.
Microscopic lesions of bones are sometimes caused
by B. suis infection. These occur both in vertebrae and in
long bones. The lesions are most frequently located adja-
cent to the epiphyseal cartilage and usually consist of
caseous centers surrounded by a zone of macrophages
and leukocytes and often by an outer zone of fibrous
connective tissue.
Focal areas of chronic lymphocytic and macrocytic
inflammation or focal abscesses are found infrequently
in kidneys, spleen, brain, ovaries, adrenal glands, lungs,
and other tissues of infected pigs (Deyoe 1968).
389
DIAGNOSIS
The most accurate and possibly the most sensitive
method of diagnosis of porcine brucellosis is isolation of
Brucella organisms by direct culture methods. It has been
shown that routine culture of a small sample of lymph
nodes from carcasses will reveal as many positives as
serologic diagnosis (Alton 1990; Rogers et al. 1989). This
is a very practical survey strategy, as virtually all the pro-
duce of the industry passes through abattoirs and the
material can be removed without damage to the carcass.
Culture of other material that becomes available is often
fruitful, such as vaginal swabs or products of abortion,
semen samples or castrated testicles, the contents of
swollen joints, and blood samples. However, culture is
often not feasible because of inadequate or unavailable
laboratory facilities and trained personnel (Deyoe 1969).
B. suis can readily be grown on all the normal Brucella
media in the absence of added CO2, the techniques being
fully described by Alton et al. (1988).
Detection of B. suis antigen in tissues of infected pigs
has been investigated, primarily using fluorescent anti-
body (FA) techniques. The general conclusion has been
that brucellae are seldom detectable in lymph node im-
pression smears with FA procedures because of the rela-
tively low numbers of organisms typically present (Dey-
oe 1972b). Nevertheless, FA tests could probably be
useful for examining aborted materials, since large num-
bers of B. suis are typical in such specimens. More re-
cently, potentially sensitive methods for the detection of
the presence of brucellae, such as the polymerase chain
reaction (PCR), are gradually being introduced into rou-
tine use and may, in the future, prove a valuable method
of diagnosis in certain situations (Lealklevezas et al.
1995).
Serologic procedures to detect antibodies against
brucellae in infected pigs are generally the most practical
and most common means of diagnosis, but the results
obtained are far from perfect. Market pig surveys have
shown that as many as 18% of normal pigs may react at
the 1:25 level when plate agglutination tests are used
(Deyoe 1969). On the other hand, some pigs produce lit-
tle or no antibody against brucellae. Because of variation
in the stage of disease, an infected herd of pigs will near-
ly always contain some infected animals that have no de-
tectable brucella antibody. Some strains of B. suis appar-
ently do not stimulate antibody production as well as
others (Deyoe 1967). Pigs exposed to a minimal infective
dose of B. suis generally have a prolonged incubation pe-
riod before significant quantities of antibody are pro-
duced.
Because of the foregoing factors, current serologic
tests are much less effective for the diagnosis of individ-
ual pigs than they are in cattle. However, most serologic
tests are entirely adequate as herd tests. Characteristical-
ly, infected herds include a majority or large numbers of
390 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
infected individuals. Because of close contact between
animals and the tendency of brucellosis to spread rapid-
ly through a herd, 50–80% is a common morbidity range
(Spencer and Mattison 1975). When large herds have on-
ly a single serologic reactor disclosed during a herd test,
it can generally be concluded that B. suis infection is not
present.
Numerous serologic tests are available or have been
investigated for use in diagnosis of porcine brucellosis
(Alton et al. 1988). Many of these were developed for di-
agnosis of bovine brucellosis and have been adapted for
testing pig sera. Most tests utilize B. abortus whole-cell
antigens. Since the commonly used antigen strains B.
abortus 1119-3 and S99 have the same or very similar sur-
face lipopolysaccharide complexes as smooth B. suis, the
standardized antigens produced and distributed by the
Animal and Plant Health Inspection Service (APHIS) of
the USDA and by the Central Veterinary Laboratory,
Weybridge, United Kingdom, are equally useful for diag-
nosis of both bovine and porcine brucellosis. This has
been confirmed by extensive laboratory testing of pig
sera with both B. abortus and B. suis antigens.
The original test methods for the diagnosis of
porcine brucellosis were tube and plate agglutination
procedures. Interpretation of results was based on the
finding that most infected pig herds contained one or
more animals with more than 100 international units
(IU) of agglutination. It is now known that serum agglu-
tination tests (SAT), although sensitive, are not suffi-
ciently specific to be reliable diagnostic tools when used
alone. Some of the inaccuracies can be overcome in situ-
ations where frequent and repeated testing is practicable
and the trend of antibody titers can be determined.
Reducing the pH of antigen-serum mixtures to 3–4
was also found to reduce nonspecific agglutination while
not affecting agglutination caused by serum from infect-
ed animals. This led to the development of methods clas-
sified as buffered brucella antigen tests, in which stained
brucella antigen is buffered at pH 3.65. The buffered bru-
cella antigen became the basis of the brucellosis card test
and similar procedures such as buffered plate antigen
and Rose-Bengal tests (RBT). These tests are the most
practical method of diagnosis for porcine brucellosis at
present, are possibly still the preferred method for large-
scale surveillance testing, and are “prescribed tests for in-
ternational trade” (Office International des Epizooties
1997). They have a distinct advantage over standard ag-
glutination tests because they are relatively unaffected by
nonspecific agglutinins and are generally as sensitive as
any other serologic test for diagnosis of porcine brucel-
losis.
Other tests, such as the Rivanol precipitation–serum
agglutination, 2-mercaptoethanol, and complement fixa-
tion tests (CFT), are frequently used for the diagnosis of
brucellosis in pigs and are very useful in confirming re-
sults of card tests. The above tests very seldom or never
detect IgM brucella antibodies in pig serum; therefore,
they are highly specific. However, the relative sensitivity
of these methods is usually low in early stages of brucel-
losis. By the time the antibody response peaks and there-
after in chronic stages, the Rivanol, mercaptoethanol,
and CFT methods are generally as sensitive as the card
test. An evaluation of a range of serologic tests on cul-
ture-positive pigs was reported by Rogers et al. (1989).
The sensitivity of the RBT was 79%; of the CFT, 49%; and
of the SAT, 51%. The specificity of the RBT was reported
to be 98% based on the results of testing over 30,000
serum samples. Other studies generally confirm the low
levels of diagnostic sensitivity achievable (Ferris et al.
1995; Payeur et al. 1990).
Regardless of the serologic test used for diagnosis, de-
tection of 80–90% of infected pigs must be regarded as
the best that can be achieved at present.
Limited investigation of the enzyme-linked im-
munosorbent assay (ELISA) has been conducted, and it
appears that this method may be equal or slightly supe-
rior to other serologic procedures for diagnosis of
porcine brucellosis in the future (Office International des
Epizooties 1997). Further investigation of this test for
use in eradication campaigns is warranted.
Experimental studies reviewed by Corbel (1985) have
shown that infection with organisms of several other
genera can produce antibodies reactive in brucellosis di-
agnostic tests. These organisms include Escherichia coli
serogroup O:157, Salmonella serobiovars of Kaufman-
White group N, and most importantly Yersinia enteroco-
litica serogroup O:9. Infection of pigs with this latter or-
ganism has often been confirmed, and the cross-reaction
that results (the dominant O polysaccharide antigen is
chemically identical to the A antigen present on the sur-
face of all smooth brucellae) is highly significant. In
some situations, yersiniosis poses a greater threat to the
agricultural industry than does brucellosis itself, due to
the confusion with brucellosis in diagnosis and the con-
sequent effect on the export trade. Great Britain has al-
ways been free from B. suis infection and enjoys a thriv-
ing export trade as a result of the generally high health
status of its stock. During the 7 years prior to 1988, the
number of pigs tested for export certification giving a
CFT reaction of greater than 20 international comple-
ment-fixation test units (icftu) never exceeded 0.004%,
whereas the figures for 1988, 1989, and 1990 were 0.42%,
0.70%, and 1.5%, respectively. Since 1988, at least 4% of
exporting herds have had more than 5% CFT positive re-
actions, with some herds reaching levels of more than
50% of animals tested failing at this level. Y. enterocolitica
O:9 has been isolated from many herds involved, and de-
spite extensive investigation, B. suis has not been recov-
ered (Wrathall et al. 1991).
Lymphocyte transformation tests have been used to
measure cell-mediated immune responses in infected
pigs on a limited scale (Kaneene et al. 1978). There was
 CHAPTER 28 BRUCELLOSIS MacMillan
high correlation between recovery of B. suis from tissues
and detectable lymphocyte stimulation responses. How-
ever, the complexity of the method probably eliminates
it from consideration as a diagnostic tool except in spe-
cial cases.
Tests for delayed hypersensitivity, using intradermal
injection of brucella allergens, have been studied, but re-
sults have not stimulated much enthusiasm in the United
States. However, they are of similar accuracy to serologic
tests and would be more appropriate for farm testing in
some circumstances, although they are more difficult to
apply and read and would not be applicable in testing
programs for market pigs. In the face of cross-reactions
caused by Y. enterocolitica O:9, the use of such tests is per-
haps the most specific method of diagnosis. Skin tests
are used frequently for diagnosis of porcine brucellosis
in many countries, particularly in Eastern Europe.
One of the most important aids to diagnosis is an ad-
equate herd history. Good records of clinical manifesta-
tions, movement of animals, additions to the herd,
breeding records, and illnesses in persons working with
the pigs provide invaluable information necessary to ar-
rive at a diagnosis of brucellosis. Accurate epidemiologi-
cal information is an essential supplement to laboratory
tests.
TREATMENT
No treatments, such as antibiotic therapy, dietary sup-
plements, or other chemotherapy, have been proven ef-
fective and economically feasible in curing pigs of bru-
cellosis. Large doses of tetracyclines, streptomycin, or
sulfonamides given over relatively long periods have
been investigated. In some trials these antibiotics alone
or in combination appeared promising. In general, how-
ever, antibiotic therapy was effective in limiting the bac-
teremic stage of the disease, but after therapy was dis-
continued, viable B. suis was still present in tissues.
Although treatments have not been effective in eliminat-
ing all organisms from the host, chemotherapy in care-
fully selected circumstances could probably suppress
multiplication of B. suis in vivo sufficiently to alleviate
clinical manifestations and shedding of organisms. Even
though such an approach may have limited practicabili-
ty, it could have beneficial effects in an infected herd and
should not be dismissed as useless.
PREVENTION
Immunity
Safe and reliable vaccines that produce serviceable im-
munity against brucellosis in pigs have not been devel-
oped. Significant resistance can be stimulated, but per-
sistence of immunity has been a limiting factor (Deyoe
1972a). Interest in vaccination of pigs in the United
States has declined along with the decline in incidence of
391
the disease. With the present incidence of porcine bru-
cellosis in the United States, the cost of developing and
applying vaccination cannot be justified.
There have been no basic studies specifically directed
toward the mechanism of immunity against B. suis infec-
tion in pigs. Nevertheless, one must assume from the
overwhelming evidence accumulated in research on bru-
cellosis in other species that the fundamental mecha-
nism is a cell-mediated immunity, with humoral immu-
nity having only a minor or nonexistent role.
Investigations into antibrucella immunity in pigs can
be summarized as follows:
1. Some pigs are naturally resistant to brucella infec-
tion, and this resistance could be enhanced markedly by
selective breeding programs (Cameron et al. 1941) if all
other genetic factors could be ignored.
2. The majority of pigs infected with virulent B. suis
will recover from the disease, but subsequent resistance
induced by the virulent infection may be transient, as
most will be susceptible to reexposure probably within
6–12 months after the initial infection.
3. Trials with attenuated B. suis or B. abortus strain 19
have been unsuccessful in producing a persistent immu-
nity with products considered to be safe for use.
4. Bacterins or extracts of killed B. suis have general-
ly been ineffective in stimulating immunity or else there
has been no conclusive evidence that the persistence of
immunity is adequate.
Control Measures
Experiences in control of porcine brucellosis indicate
that eradication of the disease from pigs in the United
States is desirable and feasible. Marked reduction in the
incidence of the disease has occurred since 1950. One
significant factor in this reduction has been the tendency
for pig production to become more specialized and less a
part of diversified farming operations. Consequently,
the occurrence of reproductive disease in pigs has be-
come proportionately more important, confinement sys-
tems and closed herds have eliminated many opportuni-
ties for interfarm spread of disease, and larger units have
eliminated the “community boar” in most instances. An-
other important instrument in control of porcine bru-
cellosis has been the establishment and maintenance of
validated brucellosis-free herds, particularly purebred
herds or those selling breeding stock. Implementation of
effective surveillance programs such as identification
and testing of market pigs (sows and boars) has been in-
strumental in locating and eliminating large numbers of
infected herds. Finally, it has been found that whenever
recommended procedures to eradicate brucellosis from
an individual herd or an enzootic area are conscientious-
ly followed, there is very seldom any recurrence of the
disease in that locality (e.g., Spencer and Mattison 1975).
The current brucellosis eradication program in the
392 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
United States is a joint state-federal and livestock indus-
try program. The program is administered, supervised,
and funded by cooperative efforts between state and fed-
eral animal health regulatory agencies. The livestock in-
dustries have input into procedures to be used through
representation on advisory committees that ultimately
determine the Uniform Methods and Rules for Brucel-
losis Eradication, the principal guideline for conducting
the program. These rules and guidelines are revised fre-
quently; therefore, current information regarding the
program as it applies in each state is always available
from each state veterinarian.
There are three acceptable alternative plans recom-
mended for use when pigs herds are found to be, or sus-
pected of being, infected with B. suis. Plan 1 consists of
depopulation of the entire herd, which is by far the most
successful and the most economical in the long run. Plan
2 is a procedure designed to salvage irreplaceable blood-
lines and basically consists of marketing the adult pigs
for slaughter and retaining weanling pigs for breeding
stock, a plan that is not always successful and necessi-
tates considerable isolation and retesting requirements.
Plan 3 consists of removing only serologic reactors and
retesting the herd as many times as necessary. This last
procedure is rarely successful if the herd is actually in-
fected but is the plan of choice if the herd contains only
a single reactor or if a very low proportion of animals are
reactors and there is reasonable doubt that brucellosis
exists.
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Alton, G. G.; Jones, L. M.; Angus, R. D.; and Verger, J. M.
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Becker, H. N.; Belden, R. C.; Breault, T.; Burridge, M. J.;
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 Clostridial Infections
29 D. J. Taylor
A number of species of clostridia are involved in disease
in swine. Clostridium perfringens (welchii) types A and C,
C. tetani, C. novyi, C. botulinum, and, to a lesser extent, C.
chauvoei and C. septicum are the causes of recognizable
clinical syndromes. The recognizable syndromes include
C. perfringens type C enteritis, C. perfringens type A en-
teritis, tetanus, botulism, sudden death in sows associat-
ed with C. novyi, and blackleg (C. chauvoei and C. sep-
ticum). Some species are also involved as contaminants
of wounds and lesions and may affect the clinical signs
and the pathological and bacteriological findings in oth-
er diseases. Species which may invade existing lesions in-
clude C. perfringens types A and C, C. novyi, C. septicum,
and C. chauvoei. Other species may be recorded in swine
from time to time, and carcasses that are not chilled im-
mediately after death are frequently invaded by
clostridia from the gut. This invasion can be so rapid that
it may be difficult to identify the actual cause of death.
The presence of clostridia in specific or nonspecific dis-
ease in swine affects the prognosis of the disease and re-
quires specific treatment and supportive and preventive
measures appropriate to the control of the organism(s)
present.
Clostridia are all large, gram-positive, spore-forming
bacilli. All are anaerobic and can be grown in culture un-
der appropriate conditions. Species can be identified by
the size and shape of the bacterial cell, by the presence or
absence of spores and their shape and position, by their
CLOSTRIDIUM PERFRINGENS TYPE C ENTERITIS
Fatal necrotic enteritis in nonimmune pigs is caused by
C. perfringens type C and is most common in piglets less
than 1 week of age. Affected animals may be found dead
or develop hemorrhagic diarrhea, which is rapidly fol-
lowed by death in acute cases. Subacute cases occur in
which mortality is less common. All are associated with a
necrotic enteritis caused by multiplication of the organ-
ism in the small intestine. The disease was first identified
in 1955 in the United Kingdom (Field and Gibson 1955)
and Hungary (Szent-Iványi and Szabo 1955) but was sub-
sequently identified in the United States (Barnes and
Moon 1964), Denmark (Høgh 1965), Germany
colonial morphology, by their biochemical characters, by
the presence of specific antigens, and by the production
of toxins. These toxins can also be used to distinguish be-
tween different varieties or types of a species. In some
cases the organisms can be identified in fixed smears by
their morphology or antigenicity; or toxins can be identi-
fied in pathological material, allowing confirmation of
diagnosis without isolation. Some clostridial species and
types can now be identified by DNA probes, polymerase
chain reaction (PCR), and sequencing technology in clin-
ical specimens.
All of the clostridial species mentioned above cause
disease by the elaboration of specific toxins or enzymes.
This fact is of vital importance when considering treat-
ment and prevention. Clostridia are sensitive to a wide
range of antimicrobials, but these can only be effective in
treatment and prevention of disease when tissue de-
struction is not very far advanced. Once toxins have been
produced and are fixed to tissues, antimicrobials can on-
ly eliminate the bacteria and cannot reverse the damage.
They may be of value in treatment, particularly in the
early stages of disease, but are of most use in short-term
prevention. Antitoxin may affect the course of the dis-
ease in some cases and protect in the short term, but
most recognizable clostridial diseases can be prevented
reliably by vaccinating the animal at risk or the sow to
provide colostral protection.
(Matthias et al. 1968), the Netherlands (Plaisier 1971),
Canada (Morin et al. 1983), and Japan (Azuma et al.
1983). It has now been identified in most swine-rearing
areas of the world.
Etiology
C. perfringens is an encapsulated, gram-positive bacillus
measuring 1–1.5 µm by 4.8 µm. Spores are rarely visible
but are ovoid to eccentric. The colonies are clearly visible
on horse or bovine blood agar after 24 hours’ incubation
in anaerobic conditions and are 3–5 mm in diameter,
grayish, circular, and surrounded by a variable zone of
395
396 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
beta hemolysis. Type C organisms produce alpha and be-
ta toxins most consistently, as well as smaller amounts of
other toxins. C. perfringens type B has been recovered
from a syndrome resembling that described below
(Bakhtin 1956) and also produces beta toxin, but type D,
which does not do so, has also been isolated (Harbola
and Khera 1990). Most isolates from the disease are iden-
tified as belonging to type C. Type C organisms are not
only primary causes of disease but can colonize the le-
sions caused by diseases of piglets such as transmissible
gastroenteritis (TGE).
Epidemiology
Outbreaks of C. perfringens type C enteritis have been
recorded in large numbers of herds in an area over a
short period of time, as in the epizootic reported from
Minnesota and Iowa (Bergeland et al. 1966) when 41
herds were affected. Once the disease has been identified
in a country or area, it becomes restricted to individual
herds as outbreaks which may last for up to 2 months. In
a few units, the acute disease may occur over longer peri-
ods, and in these cases nonimmune gilts or sows may
have been introduced to an infected area or unit or
piglets may not have received adequate levels of specific
antibody in the colostrum. The age incidence of the dis-
ease is marked, as it normally occurs in pigs aged from 12
hours to 7 days, usually at around 3 days, although the
disease has been recorded in pigs aged 2–4 weeks (Berge-
land et al. 1966; Høgh 1974) and in weaned pigs
(Meszaros and Pesti 1965; Matthias et al. 1968). Clinical-
ly affected pigs usually die, and mortality within affected
litters may reach 100% in the progeny of nonimmune
sows. When protective immunity develops in the sow as
a consequence of disease in her litter, subsequent litters
are usually unaffected. Morbidity varies from herd to
herd according to the immune status of the sows in the
herd and the time period over which morbidity is mea-
sured. In 20 herds from Minnesota and Iowa, the inci-
dence of affected litters ranged from 9% to 100%, and the
total herd mortality ranged from 5% to 59%, with a mean
herd mortality of 26% (Bergeland et al. 1966). An aver-
age mortality of 54% was observed in 24 herds in Den-
mark (Høgh 1967b).
The organism can be transmitted as a vegetative or-
ganism from piglet to piglet in an infected farrowing
house or can be acquired from maternal feces. It can per-
sist in the environment as a vegetative organism or in the
spore form, and the disease can affect litters over long pe-
riods of time if vaccination is not practiced. Spores are
resistant to boiling for up to an hour and can persist for
periods of at least a year in contaminated buildings. The
purchase of carrier sows is the most likely source of the
disease for farms, but it can also be introduced in fecal
contamination on boots and clothing.
Pathogenesis
Infection is oral and newborn piglets become infected
within minutes or hours of birth. The organisms multi-
ply in the gut to reach 108 –109 per gram of contents (Oh-
nuna et al. 1992) and become attached to the jejunal ep-
ithelial cells at the apexes of the villi (Arbuckle 1972;
Walker et al. 1980). Desquamation of these epithelial
cells is accompanied by proliferation of the organisms
along the basement membrane and complete necrosis of
the lamina propria of the villi (Fig. 29.1). In peracute cas-
es hemorrhage accompanies the necrosis. The necrotic
zone later advances to involve the crypts, the muscularis
mucosae and submucosa, and occasionally the muscular
layers. Some organisms penetrate the intestinal wall to
cause emphysema in the muscle layers and occasionally
beneath the peritoneum and in the draining mesenteric
lymph nodes. Thrombosis may develop in emphysema-
tous areas. Most bacteria remain adherent to the necrot-
ic villi or are shed into the intestinal lumen along with
cell debris and blood and may sporulate there (Kubo and
Watase 1985).
The lethal, necrotizing beta toxin is the most impor-
tant factor in the pathogenesis of the disease. Strains iso-
lated from piglets consistently produce alpha toxin
(lecithinase), beta toxin (Warrack 1963; Høgh 1967a),
and a variety of the minor toxins, including the delta tox-
in. Evidence for the importance of the toxin comes from
the widespread use of the toxoid alone in the prevention
of the disease. Experimental evidence is more equivocal.
The disease was reproduced by the oral administration
of the toxin to pigs subsequently found to be carrying
the organism (Field and Goodwin 1959; Bergeland 1965)
and by the inoculation of gut loops with whole-broth cul-
tures (Bergeland 1972), but no necrosis was produced by
29.1. Villus of the jejunum early in the course of
C. perfringens type C infection in a 12-hour-old piglet.
Numerous bacilli are present beneath the desquamated
epithelium in the area of the epithelial basement mem-
brane (H&E).
 CHAPTER 29 CLOSTRIDIAL INFECTIONS
the inoculation of beta toxin alone. The sensitivity of the
toxin to trypsin may account for these results and for the
occurrence of the disease in pigs of less than 4 days of
age, in which trypsin secretion is absent.
Death results primarily from the effects of the intesti-
nal damage and to a lesser extent from the extraintestinal
effects of the toxin. The toxin can cause sudden death fol-
lowing intravenous infusion in high doses and at lower
doses causes polioencephalomalacia, adrenal cortical
necrosis, nephrosis, and pulmonary edema (Bergeland
1965). It has been demonstrated both in the intestinal
contents of affected pigs and in the peritoneal fluid. Hy-
poglycemia occurs in field cases (Field and Goodwin
1959; Høgh 1967b) and may be a factor in mortality
along with secondary bacteremia due to C. perfringens or
E. coli.
Clinical Signs
Clinical signs vary according to the immune status and
the age of the piglets affected within a herd and from
herd to herd. Peracute, acute, subacute, and chronic dis-
ease can be distinguished. The onset of clinical signs nor-
mally occurs within the first 2–3 days of life in all forms
of the disease.
PERACUTE FORM. Piglets may be found dead within
12–36 hours of birth. Affected piglets remain normal for
the first 10 hours of life. They develop hemorrhagic diar-
rhea in most cases and this may stain the perineum but
can be overlooked. Piglets become weak, move with re-
luctance, rapidly become moribund, and may be crushed
by the sow. The rectal temperature falls to 35˚C and the
abdominal skin may blacken before death. Death may
occur in some animals without diarrhea being seen.
ACUTE FORM. Acute cases survive 2 days after the
onset of clinical signs and commonly die when 3 days
old. Throughout the course of the disease they have red-
dish-brown liquid feces that contain shreds of gray
necrotic debris. They lose condition and become gaunt
and weak, making only feeble attempts to suck on the
last day of life.
SUBACUTE FORM. These pigs have a persistent non-
hemorrhagic diarrhea and usually die when about 5–7
days of age. They remain active and alert and have a fair
appetite but become progressively more emaciated and
may be extremely thin and dehydrated at the time of
death. The feces tend to be yellow at first and then
change to a clear liquid containing flecks of necrotic de-
bris.
CHRONIC FORM. Chronic cases may have an inter-
mittent or persistent diarrhea for 1 or more weeks. The
Taylor 397
feces are yellow-gray and mucoid, and the tail may be
coated with dried feces. Affected pigs may remain alert
and vigorous for 10 days or more, but their rate of
growth is depressed. These pigs may eventually die after
several weeks or be killed because of their failure to gain
weight.
Lesions
Piglets that die from the peracute form are often in good
condition and do not appear dehydrated. There may be
blackish discoloration of the abdominal skin even in an-
imals killed in extremis. The umbilical cord is usually
still present. Reddish feces may be present on the per-
ineum. The abdominal wall is often edematous when cut.
The most immediate and striking findings are the pres-
ence of intensely hemorrhagic small intestines (Fig. 29.2)
and the presence of bloodstained fluid in the abdominal
cavity. The lesions vary in extent, occurring in the je-
junum but extending into the ileum. They may extend
from 14 cm posterior to the pylorus to the cecum or af-
fect only 2–3 cm of bowel. Lesions are reddish or black in
color and there may be gas bubbles in the intestinal wall.
The mesenteric lymph nodes may be reddened. The con-
tents of the affected area are hemorrhagic, and hemor-
rhagic contents may be found in the intestine distal to
the lesion, often as far as the rectum. The mucosa is in-
tensely hemorrhagic and no villi can be distinguished.
Microscopically, the villi in the affected portion of the je-
junum are necrotic and covered by large gram-positive
bacilli. The epithelium of the crypts may or may not be
29.2. Necrohemorrhagic jejunitis in a 1-day-old piglet
with peracute C. perfringens type C enteritis.
398 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor

necrotic, and there is profuse hemorrhage throughout

the mucosa and submucosa (Figs. 29.3 and 29.4). Large
numbers of gram-positive bacilli are present in smears of
the lesions.
Acute cases may be dehydrated or show loss of bodi-
ly condition, and there may be scalding of the perineum
and adherent reddish feces. The intestines are less fre-
quently reddened, and any reddish lesions may be local-
ized. Emphysema of a sharply demarcated portion of up
to 40 cm of the jejunum may be present from 30 cm pos-
terior to the pylorus, and this portion of the intestine
may be loosely adherent to adjacent segments by acute
fibrinous peritonitis (Fig. 29.5). The wall of the intestine
is usually thickened, and the contents are sometimes
bloodstained and often contain some necrotic debris.
The mucosa is yellow or grayish in color and covered
with loosely adherent necrotic debris. Microscopic le-
sions include the absence of most villi; those that survive
29.5. Acute C. perfringens type C enteritis in a 3-day-
are necrotic and covered with bacteria. The luminal sur- old piglet. An emphysematous segment of upper jejunum
face is covered with a necrotic membrane made of bacte- (left) is held together by acute peritonitis. Mucosal necro-
sis of the lower jejunum (right) is seen from the serosal
surface.

ria, shed epithelial cells, fibrin, and degenerating inflam-

matory cells lying directly over the submucosa. The sub-
mucosal vessels are necrotic and many contain thrombi.
Emphysema may be evident in the submucosa, tunica
muscularis, and under the serosa (Fig. 29.6). Large gram-
positive bacteria may be present in deeper layers of the
intestinal wall.
Subacute cases are usually in poor condition, and
there may be adhesions between affected areas of the
small intestine. The intestinal wall is thickened and fri-
able, and the mucosal surface is covered by a tightly ad-
herent necrotic membrane which may be seen from the
29.3. Jejunum of a piglet with peracute C. perfringens
serosal surface as longitudinal grayish-yellow bands (Fig.
type C enteritis. There is acute necrosis of the mucosa
and massive hemorrhage in the submucosa (H&E).
29.7).

29.6. Jejunum of a piglet with acute C. perfringens

29.4. The necrotic jejunal villi from a piglet with pera- type C enteritis. The mucosa is completely necrotic, and
cute C. perfringens type C infection are covered by nu- there is emphysema of the submucosa and tunica muscu-
merous gram-positive bacilli (Gram). laris (H&E).
 CHAPTER 29 CLOSTRIDIAL INFECTIONS
29.7. Subacute form of C. perfringens type C enteritis
in a 6-day-old piglet. The entire jejunum is lined with a
necrotic membrane.
Chronically affected pigs may have lesions resem-
bling those described above, but they may not be obvi-
ous from the serosal surface of the intestine. There may
be local thickening of the intestinal wall and local, well-
defined areas to which necrotic membrane is adherent.
These areas may only be 1–2 cm in length and consist of
areas in which the mucosa has been replaced by a necrot-
ic membrane with a variety of bacteria along the deep
edge. Deeper layers of the intestinal wall show evidence
of chronic inflammation (Fig. 29.8).
Diagnosis
The clinical signs and gross postmortem findings are suf-
ficient for a presumptive diagnosis of C. perfringens type
29.8. Ileum of a piglet with chronic C. perfringens
type C enteritis. The mucosa is replaced by a necrotic
membrane containing a variety of bacterial species. The
submucosa, tunica muscularis, and serosa are infiltrated
by chronic inflammatory cells (H&E).
Taylor 399
C enteritis to be made. Hemorrhagic diarrhea in young
piglets, the pattern of mortality, and the presence of the
hemorrhagic, necrotic lesions in the small intestine are
the most important features on which to base this diag-
nosis. The presence of emphysematous sections of the
small intestine in freshly dead piglets is also significant.
Diagnosis of the chronic disease is more difficult and
may depend upon a history of previous infection in the
herd, the elimination of other causes of necrotic enteri-
tis, and laboratory confirmation of the presence of the
agent in the lesions. Coccidiosis (Isospora suis) and other
causes of villous atrophy such as rotavirus, TGE, and
porcine epidemic diarrhea may all cause lesions which
are colonized by bacteria, including C. perfringens type C
(Bergeland 1977). C. perfringens type A (see below) may
also cause clinical signs and lesions resembling those of
the subacute and chronic forms and may be distin-
guished from them only by laboratory means.
The diagnosis can be supported in the laboratory by
the examination of smears of the intestinal contents and
mucosal lesions and histological sections of the intesti-
nal wall for the presence of large, gram-positive rods.
The microscopic appearance of the hemorrhagic lesions
is characteristic and is almost pathognomonic. Diagno-
sis can be confirmed beyond doubt by the demonstration
of the beta toxin of C. perfringens type C in supernates of
the hemorrhagic intestinal contents and sometimes in
peritoneal fluid. Mouse inoculation and protection tests
using type-specific antisera have been used to detect the
toxin, but ELISA tests using the beta toxin as antigen are
now more frequently used (Havard et al. 1992). PCR
methods that use primers to detect alpha, beta, epsilon,
and enterotoxins have also been described (Buogo et al.
1995) and reveal that, although many animals with clin-
ical signs and postmortem findings of C. perfringens type
C contain organisms producing the beta toxin (types B
and C), some contain only the alpha toxin, which may be
caused by type A.
In more chronic cases and in some acute ones the tox-
in cannot be identified, and less satisfactory confirma-
tion can be obtained by isolating C. perfringens type C
from scrapings of the intestinal mucosa by direct inocu-
lation of blood agar plates and identification and toxin
typing of the colonies isolated. This method of confir-
mation is less satisfactory because the organism has been
found as a secondary agent colonizing the lesions of
piglets with TGE and other virus diseases. When the dis-
ease is chronic, the organism may be impossible to iso-
late, and in those situations, earlier cases of the disease
must be sought in the herd to confirm a diagnosis.
Treatment and Prevention
There is little to be done once clinical signs are present,
because the intestinal damage is already extensive
(Szabo and Szent-Iványi 1957; Høgh 1967b). Even when
the organism is eliminated, the animal still dies or re-
400 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
mains stunted. Prophylaxis is of more value than thera-
py.
The disease can be prevented by passive immuniza-
tion with antitoxin to C. perfringens type C in litters of
nonimmune sows in an outbreak. Parenteral injection of
antitoxin should be carried out as soon after birth as pos-
sible because the disease may already be occurring in
piglets only a few hours old. Oral antimicrobials such as
ampicillin may also be given as soon after birth as possi-
ble and should prevent the development of the disease.
Treatment should be repeated daily for the first 3 days of
life. Recent studies suggest that resistance to antimicro-
bials commonly used on a farm may develop in C. per-
fringens, and tetracycline resistance plasmids have been
CLOSTRIDIUM PERFRINGENS TYPE A ENTERITIS
C. perfringens type A has been isolated from the intestines
of pigs for many years and has been considered to form
part of the normal flora (Mansson and Smith 1962). Ev-
idence has gradually accumulated that it is involved in
enteric disease, both in neonatal piglets and in older pigs
in the postweaning period (Jestin et al. 1985). The or-
ganism is present in every pig and is distributed world-
wide. Reports of its involvement in clinical disease or the
reproduction of disease have come from Germany
(Amtsberg et al. 1976), France (Ramisse et al. 1979), the
United Kingdom (Olubunmi 1982), the Netherlands
(Nabuurs et al. 1983), and Romania (Secasiu 1984) in re-
cent years, and the syndrome is increasingly being recog-
nized worldwide.
Etiology
C. perfringens type A resembles C. perfringens type C, but
colonies are often surrounded by a double zone of he-
molysis, the outer of which is caused by the alpha toxin
and the inner by theta toxin. The organism does not pro-
duce beta toxin or the other major toxins used in typing,
but some strains produce a powerful enterotoxin on
sporulation. An ability to sporulate is generally consid-
ered a prerequisite for enterotoxin production. Spores
may require heat shocking to germinate. Enterotoxin-
producing strains rarely produce large amounts of alpha
toxin, and there appear to be two separate syndromes as-
sociated with the two types of C. perfringens type A. Both
sporulating and enterotoxin-producing strains of C. per-
fringens type A have been demonstrated in pigs (Estrada
Correa and Taylor 1989). Damme-Jongsten et al. (1990)
failed to demonstrate the gene in isolates of the organ-
ism, but it was demonstrated at low levels in normal fe-
ces (fewer than 10 cells per gram) by Miwa et al. (1997)
using a most-probable-number method combined with
the nested PCR.
identified in this species (Rood et al. 1985).
Prevention of the disease on a more permanent basis
relies on the vaccination of the sow with C. perfringens
type C toxoid on two occasions, the first at service or
midgestation and the second 2–3 weeks before farrow-
ing. Provided the piglets suck colostrum, they will be
protected (Ripley and Gush 1983). The level of passive
antibody in the piglet is related to that in the sow at far-
rowing. Levels can vary markedly from 4.5 IU/mL to 123
IU/mL (Matishek and McGrinley 1986). Booster injec-
tions should be given about 3 weeks before subsequent
farrowings. Toxoid may also be of value in protecting
weaned pigs (Meszaros and Pesti 1965).
Epidemiology
The organism is ubiquitous in gut contents and in soil.
Spores can survive freezing and boiling for up to 10 min-
utes, but the vegetative cells are fully susceptible to heat.
The epidemiology of C. perfringens type A is not com-
pletely known. The organism can be isolated on all
farms, and antibody is widespread in finishing pigs and
in sows (Estrada Correa and Taylor 1989). Outbreaks of
disease in litters and on farms appear to be associated
with organisms with similar cultural characteristics, but
no detailed studies have yet been carried out to deter-
mine whether these are individual strains. It must be as-
sumed that the major source of the organism for pigs
housed intensively is pig feces, but the organism can be
demonstrated in some diets and in the environment.
Enterotoxigenic strains are capable of causing hu-
man food poisoning, usually following growth in slowly
cooling joints of meat following cooking. It is not known
whether food poisoning strains found in cooked pork are
the same as those causing disease in the live animal, al-
though it is considered that the enterotoxin gene is chro-
mosomal in human strains and plasmid borne in animal
strains.
Pathogenesis
Infection with C. perfringens type A occurs in most piglets
within a few hours of birth, and the organism can be
demonstrated in the first feces following the clearance of
meconium. In nonimmune piglets infected with patho-
genic strains, numbers build up in the ileum and je-
junum to levels of 108–109 per gram of contents. Similar
levels may be found in large-intestinal contents and fe-
ces. Vegetative forms produce alpha toxin and possibly
other toxins which cause necrosis of the intestinal ep-
ithelium in experimental infections in vivo. Consistent
changes were not produced by the inoculation of gut
 CHAPTER 29 CLOSTRIDIAL INFECTIONS
loops with purified alpha toxin (Estrada Correa 1986),
but Johannsen et al. (1993b) detected slight edema of the
villi when 6-hour-old piglets were given 80–800 mouse
lethal doses. Johannsen et al. (1993c) confirmed previous
observations (Estrada Correa 1986) that invasion and at-
tachment did not appear in experimental cases of the
disease. Sporulating forms produce enterotoxin, which
causes dramatic villous necrosis and outpourings of flu-
id into the intestinal lumen. The toxin fixes to the cells of
the colonic epithelium and may be responsible for failure
to resorb water. Antibody to both toxins is present in
colostrum, and disease associated with enterotoxin is
commonly seen in weaned pigs aged 5–7 weeks after ma-
ternal antibody disappears (Estrada Correa 1986).
C. perfringens type A also colonizes existing lesions.
Clinical Signs
Piglets develop a creamy or pasty diarrhea within 48
hours of birth and lose condition in infections with veg-
etative forms of C. perfringens type A. Affected piglets ap-
pear hairy and have fecal staining of the perineum.
There is no fever and animals rarely die. If they do, there
is often discoloration of the abdominal skin similar to
that seen in C. perfringens type C infections. Diarrhea
lasts for up to 5 days, and feces on the pen floor appear
mucoid and may be pink in color. Recovered piglets re-
main in poor condition for some time. These clinical
signs have been reproduced experimentally by Olubun-
mi (1982), Estrada Correa (1986), and Johannsen et al.
(1993a), who also recorded submandibular edema. In-
fections caused by the sporulating form cause a transient
watery diarrhea which may last for only 24–48
hours.
Weaned pigs 5–7 weeks of age develop diarrhea or
soft feces lasting 4–7 days. This diarrhea does not result
in death, but affected animals lose condition and become
covered with feces. The rate of daily liveweight gain is
depressed. Onset of the diarrhea can be delayed by the
use of antimicrobial feed additives that affect clostridia.
The clinical signs may form part of the “colitis” complex
(see Chapters 40 and 42).
Lesions
Piglets are usually dehydrated, with fecal staining of the
perineum. The small intestine is flaccid and thick-walled,
with pasty contents and no blood. Its mucosa is mildly
inflamed and necrotic material may be adherent to it.
The absence of villi is obvious using a hand lens. The
large intestine is distended with whitish, pasty contents.
The mucosa is often normal or may be coated in necrot-
ic debris. In weaned pigs there are few if any gross le-
sions in the mucosa, but there may be frothy, mucoid
contents in both the ileum and the cecum.
Microscopic lesions in piglets include villous atrophy
Taylor 401
with superficial necrosis and accumulations of fibrin. Al-
though there is capillary dilatation, the hemorrhage seen
in C. perfringens type C infections is absent. There may al-
so be an inflammatory colitis. Gram-positive rods may
be seen adjacent to the mucosa in Gram-stained sections
but they do not appear to be attached to the mucosa (Jo-
hannsen et al. 1993c). In the weaned pig, there may be
some villous atrophy in the ileum and superficial colitis,
but in some cases the mucosa appears normal.
Clostridia are obvious in smears of feces or gut con-
tents, and large numbers of spores are present when en-
terotoxin-producing strains are involved. C. perfringens
type A can be isolated from the small intestine in profuse
culture in affected piglets and from the large-intestinal
contents in weaned pigs. Sporulating bacteria can be iso-
lated by heating samples to 80˚C for 10 minutes before
culture.
Diagnosis
The clinical signs of disease in piglets resemble those of
mild C. perfringens type C infection. There is little or no
blood in the feces and there is little or no mortality. The
condition can be confirmed by isolation of the organism
in profuse culture, by the demonstration of toxin in gut
contents by ELISA, by the demonstration of the alpha
toxin gene by PCR (Buogo et al. 1995), and by failure to
demonstrate the presence of other agents. In weaned
pigs the organism rarely occurs alone, and a diagnosis of
uncomplicated C. perfringens type A infection requires
the failure to demonstrate other enteropathogens cou-
pled with the presence of high numbers of sporulating
organisms and the demonstration of preformed entero-
toxin in fecal filtrates by reverse passive agglutination
tests or counter-immunoelectrophoresis (CIE). Toxin lev-
els of 1:32 were considered significant by Jestin and
Popoff (1987) and Popoff and Jestin (1985), and maxi-
mum levels of 1:160 were recorded.
Treatment
The disease in piglets can be treated by using antimicro-
bials in the same way as with C. perfringens type C infec-
tion, but with more likelihood of success. Vaccination is
not possible, as current commercial clostridial vaccines
rarely include alpha toxin or enterotoxin. Experimental
vaccination of the sow has shown that vaccination is pos-
sible, but the ubiquitous nature of the organism means
that it is usually sufficient to ensure that piglets ingest
sufficient colostrum. In weaned pigs it is usually suffi-
cient to include a growth promoter such as avoparcin
(Taylor and Estrada Correa 1988) or salinomycin (Kyri-
akis et al. 1995) in the ration at a level capable of inhibit-
ing the organism. Madsen (1995) has described the use
of bacitracin methylene salicylate in the treatment of C.
perfringens type A enteritis in piglets.
402 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
CELLULITIS AND GAS GANGRENE
Infected wounds in swine often contain bacteria of sev-
eral species. When the histotoxic clostridia become es-
tablished in a wound, however, they rapidly become the
most predominant and significant pathogen. These
clostridial wound infections are highly fatal and are
characterized by intense acute inflammation with abun-
dant edema and varying amounts of gas and local tissue
necrosis. The inflammation spreads rapidly from the pri-
mary invasion site, and there terminal generalized sepsis
usually occurs.
C. septicum, C. perfringens type A, C. novyi, and C.
chauvoei are the common causes of clostridial cellulitis
and gas gangrene in swine.
CLOSTRIDIUM SEPTICUM INFECTION
(MALIGNANT EDEMA)
Etiology
C. septicum appears to be the most common etiologic
agent of clostridial cellulitis and gas gangrene of swine.
The organism is an anaerobic gram-positive rod, ap-
proximately 0.6–0.8 µm wide and 3–8 µm long, which
forms oval subterminal spores. It is known to produce
four toxins, of which the alpha toxin is hemolytic, necro-
tizing, and lethal. In addition, hyaluronidase, deoxyri-
bonuclease, and an oxygen-labile hemolysin are pro-
duced (Moussa 1958).
Epidemiology
C. septicum is a common potential wound contaminant
because it is a widespread inhabitant of the soil
(MacLennan 1962). The incidence of malignant edema
is particularly high on certain premises that have had
large populations of livestock for many years, suggesting
that there is a buildup of spore numbers in the environ-
ment of these farms.
Pathogenesis
Since C. septicum infection nearly always involves the
skin and subcutis, it appears that most cases result from
perforated wounds, even though evidence of a wound
may sometimes not be found. Tissue damage at the site
of inoculation favors the initial establishment of the in-
fection. It is probable that the local lesion is largely the
result of the necrotizing effect of the alpha toxin. It has
been proposed that the hyaluronidase produced by C.
septicum causes disappearance of the endomysium
(Aikat and Dible 1960), which may aid the spread of the
infection through muscle.
Toxemia undoubtedly is a major factor in causing
death of the animal. Experimental intravenous infusion
of C. septicum toxins in the cat causes a specific constric-
tion in the coronary and pulmonary circulations with the
development of pulmonary edema (Kellaway et al.
1941). On the basis of this evidence, it could be speculat-
ed that the pulmonary edema and the serofibrinous exu-
dates found in the pericardial and pleural cavities of
some cases of malignant edema in swine are the result of
bacterial toxemia.
Clinical Signs
C. septicum infection has an acute course and is often fa-
tal in less than 24 hours. Gross swelling may be located
in any area of the body. Common sites include the in-
guinal and ventral abdominal region, the head and ven-
tral cervical area, and the shoulder. The swelling spreads
rapidly from the primary site, but it usually remains con-
fined to one general region of the body. If the limbs are
involved, there is reluctance to bear weight on the affect-
ed leg. The skin overlying the swollen area has a blotchy
reddish-purple discoloration. Palpation of the swollen
area reveals pitting edema, and crepitation may also be
evident late in the course of the disease. In the terminal
stage, affected swine lie in lateral recumbency and com-
monly make a groaning noise during forced expiration.
Lesions
There is conspicuous swelling in the general region of
the primary infection site (Fig. 29.9). Incision of the ery-
thematous skin overlying the infection reveals subcuta-
neous edema that may be colorless with focal hemor-
rhages or may be uniformly sanguinous. Gas is present in
varying quantities. The adjacent skeletal muscle may be
edematous, with essentially normal color, or may have
the features of typical gas gangrene, in which there are
black, dry, and crepitant areas (Fig. 29.10). Affected mus-
cle may have a butyric odor indistinguishable from the
characteristic odor of C. chauvoei infection in the rumi-
nant. The regional lymph nodes are enlarged and hem-
orrhagic and may be emphysematous. There is common-
ly an acute fibrohemorrhagic peritonitis. The spleen is
only slightly enlarged. There is moderate pulmonary
edema and congestion. Varying amounts of amber fluid
and fibrin may be found in the pleural cavity and peri-
cardial sac.
Postmortem decomposition occurs rapidly, and sub-
cutaneous gas accumulates progressively until the sub-
cutis of the entire carcass is emphysematous. Focal post-
mortem lysis of the liver is commonly seen, with
resulting grayish-tan foci being evident within several
hours after death. As postmortem decomposition pro-
gresses, the foci become confluent, giving the liver a uni-
form tan color with numerous gas bubbles.
Microscopically, there is edema of the subcutis that
contains large numbers of degenerating acute inflamma-
tory cells and bacteria. Septic thrombi in subcutaneous
 CHAPTER 29 CLOSTRIDIAL INFECTIONS
29.9. C. septicum infection. The grossly swollen area
involves the entire left rear leg and extends cranially to
the umbilicus. The overlying skin has a blotchy reddish-
purple discoloration.
29.10. Rear leg of a pig with C. septicum infection.
There is prominent subcutaneous edema. The infection
extends into the ham, which has foci of black, dry
necrotic muscle.
veins and lymphatics are commonly found (Fig. 29.11).
Affected skeletal muscle fibers undergo coagulation
necrosis with fragmentation and lysis, and bacteria are
readily found between the degenerating muscle fibers
(Fig. 29.12).
Diagnosis
A presumptive diagnosis is made by observation of typi-
cal gross lesions in the freshly dead animal. Laboratory
confirmation is based on pathologic findings, together
with exclusion of other diseases, and identification of
the organism. Many bacteria are seen on direct smears of
Taylor 403
29.11. Acute septic thrombophlebitis involving the sub-
cutaneous vein of a pig with C. septicum infection. The
thrombus contains many long slender rods and degener-
ating leukocytes (H&E).
29.12. C. septicum infection of the rear leg of a pig.
Skeletal muscle fibers are undergoing fragmentation and
lysis. The adjacent connective tissues are edematous and
emphysematous and contain bacteria and degenerating
inflammatory cells (H&E).
the affected subcutis or muscle. Fluorescent-labeled anti-
body staining (Batty and Walker 1963) of direct impres-
sion smears of the local lesion is a rapid and accurate
method of positively identifying C. septicum. An alterna-
tive method is isolation of the organism by anaerobic
culture and identification by biochemical tests; however,
this is more time-consuming and less reliable than the
use of immunofluorescence (Martig 1966). The swarm-
ing nature of C. septicum on commonly used media
means that small numbers of the organism may appear
following postmortem contamination and result in a
false-positive diagnosis.
Treatment and Prevention
Treatment with antibiotics may be successful if given
early in the course of the disease. There is little specific
information available of the therapy of malignant edema
404 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
in swine. Zeller (1956) mentions the recovery of two pigs
after treatment with oxytetracycline. Experimentally, the
prophylactic use of tetracyclines, penicillin, or chloram-
phenicol prevented the disease in mice; however, their ef-
fectiveness was greater when administered locally at the
inoculation site than when given systemically (Taylor
and Novak 1952).
Prevention of the disease involves good sanitation
and the prevention of injuries. Sharp objects that may
cause perforating wounds should be removed from the
environment. In many instances C. septicum infection is a
sequel of hypodermic injections in swine; therefore, ade-
quate sanitary procedures should be followed when mak-
ing injections or performing surgery. On premises where
there are recurrences of the disease, immunization with
C. septicum bacterin could be considered; however, this is
seldom done in swine.
CLOSTRIDIUM PERFRINGENS TYPE A
INFECTION (GAS GANGRENE)
C. perfringens is occasionally involved in wound infec-
tions in swine. The infection is acute and highly fatal and
usually of only sporadic incidence.
A high herd incidence of C. perfringens gas gangrene
is occasionally seen in young piglets as a complication of
injection of iron-containing preparations used for the
prevention of nutritional anemia. Circumstantial evi-
dence suggests that injection of iron preparations creates
a microenvironment in tissue that favors the growth of
C. perfringens. Jaartsveld et al. (1962) reported the occur-
rence of C. perfringens infection in two herds following
intramuscular injection of an iron preparation. Twelve of
25 piglets in one herd died the morning following injec-
tion. It was assumed that contaminated hypodermic nee-
dles were the source of the infection. A similar problem
was seen by Bergeland (Taylor and Bergeland 1992) in
several herds in which C. perfringens occurred as a pure
infection in some cases and as a mixed infection with E.
coli and staphylococci in others. When the problem oc-
curs, the herd incidence is usually high, with mortality
approaching 50%.
The affected piglets have marked swelling of the en-
tire rear limb that was injected, and the swelling extends
cranially to the umbilical area. The skin overlying the
swollen area has a dark reddish-brown discoloration. In-
cision of the affected area reveals extensive edema, and
there may be a copious quantity of gas in the muscle and
subcutis. The inflammatory exudate is brownish red, due
largely to staining by the injected iron preparation. The
lesion usually has a putrid odor. Postmortem decompo-
sition occurs rapidly, and the livers of pigs dead more
than a few hours may have conspicuous gray foci of lysis
that surround minute gas bubbles. Microscopically,
acute thrombophlebitis may be evident, and affected
muscle fibers undergo fragmentation and liquefaction
necrosis. Gangrene of the uterus and decomposition of
its contents may follow dystocia and attendant interfer-
ences in the sow. A foul-smelling, reddish, watery vulval
discharge may be seen in life, and the animal dies within
12–24 hours. The uterus and its contents are usually
dark green or black and contain gas bubbles which give
off a foul odor. There may be foul-smelling reddish fluid
in the peritoneal cavity. Decomposition of the remainder
of the carcass is rapid, and lesions in other sites are rarely
identified.
The alpha toxin (lecithinase) of C. perfringens has
been shown to be almost solely responsible for the pro-
duction of the local lesion (Aikat and Dible 1956). It is
proposed that the lecithinase causes necrosis by action
on lipoprotein complexes of cell membranes. In addi-
tion, there is evidence that the mu toxin (hyaluronidase)
causes separation of the muscle sarcolemma from the en-
domysium.
The diagnosis is based on clinical and pathologic
findings, together with the isolation and identification of
C. perfringens. In mixed infections, direct Gram-stained
smears of the lesion are helpful in estimating the relative
numbers of different bacteria present. C. perfringens is
evident as a robust gram-positive bacillus that seldom
contains spores. Isolation of the organism is easily ac-
complished by anaerobic incubation for 18–24 hours of
blood agar and egg yolk agar plates streaked directly
from the lesion.
Treatment of C. perfringens infections with antibiotics
may be successful if instituted early in the course of the
disease. Experimentally, penicillin injections given at the
same time as inoculation of C. perfringens in mice gave al-
most complete protection; however, a delay in penicillin
injection of over 3 hours appreciably lowered the sur-
vival rate (Hac and Habert 1943). Jaartsveld et al. (1962)
mention the recovery of some clinically sick pigs follow-
ing penicillin injection.
Prevention of C. perfringens gas gangrene in swine in-
volves preventing the occurrence of deep, contaminated
wounds and prompt treatment of any such wounds with
systemic penicillins or antimicrobials other than amino-
glycosides.
CLOSTRIDIUM CHAUVOEI INFECTION
(BLACKLEG)
The pig is generally considered to be quite resistant to C.
chauvoei infection, and historically there have been very
few substantiated reports of this disease in swine. Sterne
and Edwards (1955) reported the occurrence of blackleg
in swine kept under very poor hygienic conditions in a
lot where there previously had been high losses of cattle
from blackleg. Four pigs were examined, 2 of which were
found to be infected with C. chauvoei and 2 with C. sep-
ticum. Gualandi (1955) reported an outbreak of C. chau-
voei infection in which 15 of 34 pigs died in 2 days. Ede-
 CHAPTER 29 CLOSTRIDIAL INFECTIONS
ma of the pharynx was a constant finding. Eggleston
(1950) described the losses of 3 pigs weighing 100–140
pounds (45–63 kg) that had been fed a blackleg calf car-
cass. There was swelling of the face and throat region, in-
cluding the ears, and the odor of the lesions resembled
rancid butter. Two large outbreaks were described from
Zimbabwe by Mavenyengwa and Matope (1995) where
34 pigs on one farm and 36 on another developed
swollen and edematous limbs with reddish discoloration
of the overlying skin, fever of 40–41˚C, and edema and
dark, hemorrhagic muscles in the affected legs.
C. chauvoei is a pleomorphic, anaerobic, gram-posi-
tive rod, measuring 0.5–1 µm by 3–8 µm, that readily
forms central to subterminal spores. It produces several
exotoxins, of which the alpha toxin is lethal, necrotizing,
and possibly hemolytic. In addition, deoxyribonuclease,
hyaluronidase, and an oxygen-labile hemolysin are pro-
duced (Moussa 1958).
The pathogenesis of C. chauvoei infection in pigs is
not completely understood. It is assumed that the organ-
ism usually has an oral portal rather than being a wound
infection. It is postulated that the bacteria sometimes
may lie dormant in various tissues until there is a favor-
able microenvironment for their growth. Tissue damage
such as bruising may then be the factor that triggers the
disease. Once bacterial growth occurs, the disease ap-
pears to be a manifestation of the effects of bacterial tox-
ins and pathologically may closely resemble C. septicum
infection.
Because of the pathologic similarity between C. sep-
ticum and C. chauvoei infections and the apparent higher
incidence of C. septicum infection in swine, a diagnosis of
blackleg can be made only by bacterial identification.
The fluorescent antibody test (Batty and Walker 1963)
applied to direct impression smears of infected tissue is
a rapid and practical method of identification. Isolation
by anaerobic culture may be difficult in decomposing
specimens since C. chauvoei is relatively fastidious and
easily overgrown by other bacteria such as C. septicum.
The prevention of C. chauvoei infection involves min-
imizing exposure to the organism. Even though C. chau-
voei has not been demonstrated to be a common soil or-
ganism, circumstantial evidence from the few reports of
the disease in pigs suggests that keeping swine on known
contaminated premises or allowing them to eat carcasses
of ruminants dead of blackleg are factors in its inci-
dence.
CLOSTRIDIUM NOVYI INFECTION
(SUDDEN DEATH)
C. novyi may cause sudden death in swine. Batty et al.
(1964) reported the sudden death of 12 pigs over a 3-
week period. Postmortem decomposition progressed un-
usually rapidly. The lungs were congested, the trachea
contained bloodstained froth, and there was some hem-
Taylor 405
orrhage on the surface of the kidney. They reported the
loss 4 days after farrowing of an adult sow that showed
marked decomposition and the presence of massive
numbers of C. novyi in the internal organs. A further case
report by Bourne and Kerry (1965) involved 4 cases of
sudden death in sows on grass. Necropsy findings in-
cluded rapid postmortem tympany; submandibular
swellings; bloodstained fluid in the pleural, pericardial,
and peritoneal cavities; serosal hemorrhages; splenic en-
largement; and marked degeneration and emphysema of
the liver. C. novyi was demonstrated in various tissues, in-
cluding heart blood. An obvious feature of pigs that had
died from this disease was the bronze color of the liver
and the presence of large numbers of small gas bubbles
in the substance of the organ when cut. These are partic-
ularly significant when the remainder of the carcass is
fresh. A detailed study of 17 cases of C. novyi infection in
sows (Duran and Walton 1997) confirms many of these
features.
C. novyi is an anaerobic, spore-forming, gram-positive
rod that varies in size but generally is the largest of the
clostridia encountered in swine. The organism produces
highly potent exotoxins. The lethal, necrotizing alpha
toxin is considered to be the principal toxin of type A
and B strains. The type involved in swine infections was
identified as type B by Itoh et al. (1987), although Duran
and Walton (1997) report the isolation of type A alone in
3 cases, type B in 4 cases, and a mixed culture in another.
The disease affects large finishing pigs and breeding
stock, principally sows, and was recorded more fre-
quently in spring and in older sows of parity greater than
4 in moderate to good condition by Duran and Walton
(1997) and was characterized by sudden death.
A positive diagnosis of C. novyi infection in swine is
difficult, since suspect cases are usually found dead, and
some interval of time elapses between death and necrop-
sy. The organism is a common and early postmortem in-
vader, especially of adult swine in warm weather. There-
fore, a detailed examination to exclude other possible
causes of death must always be made. The disease
should be suspected when there is a history of sudden
death, together with typical necropsy findings. Animals
that have died from C. novyi infection are generally in
good condition, with surface changes of congestion,
swelling, and tympany associated with the rapid decom-
position of the carcass. A serous or frothy exudate may
be present at the nostrils. There is subcutaneous edema,
particularly in the cervical and inguinal regions. Pul-
monary edema and tracheal froth, serofibrinous or
serosanguinous exudates in pericardial and pleural cavi-
ties, and unusually rapid decomposition with accumula-
tion of gas in the liver are all commonly found. The pres-
ence of gas bubbles in the liver in an otherwise fresh
carcass is particularly significant. The stomach is often
full and there may be congestion of the spleen (Duran
and Walton 1997).
406 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
The organism is rapidly identified by fluorescent an-
tibody staining of direct smears of infected tissue. Isola-
tion and typing of the organism are difficult since it has
the most fastidious growth requirements of the
clostridia commonly encountered in swine, but isolation
has been described by Itoh et al. (1987) and Duran and
Walton (1997). Isolation may be improved by the use of
alcohol and heat treatment of specimens followed by cul-
ture on prereduced fastidious anaerobe agar. The organ-
ism may be recovered from the livers of some apparent-
ly healthy animals on infected farms.
Information on pathogenesis and epidemiology in
TETANUS
Tetanus is a disease characterized by uncontrollable
spasms of voluntary muscles caused by the toxin of C.
tetani elaborated at the site of a deep infection. Swine of
all ages may be affected; however, the majority of cases
involve young pigs, usually as a complication of either
castration wound infection or umbilical infection.
C. tetani is a slender, anaerobic, gram-positive rod
measuring 0.3–0.6 µm by 2–8 µm that characteristically
forms terminal spores. Its major lethal toxin, tetanospas-
min, is a highly potent neurotoxic protein. An oxygen-la-
bile hemolysin, tetanolysin, is also produced.
Epidemiology
C. tetani is a common inhabitant of the soil. Sergeeva and
Matveev (1966) conducted a survey of 5338 soil samples
collected from various regions of the former USSR and
found that the highest level of soil contamination was in
the southern regions having fertile black soil, long peri-
ods of growth for plants and soil organisms, and highly
developed agriculture and cattle breeding. In some re-
gions the rate of isolation was as high as 40–62% of the
samples examined. In areas where the soil was not fertile,
regions with concentrated cattle raising and fields fertil-
ized with animal manure had a significantly higher inci-
dence of soil contamination than regions without live-
stock. Tetanus morbidity in various areas of the former
USSR correlated directly with the prevalence of the or-
ganism in the soil. Sakurai (1966) also reported a high in-
cidence of tetanus in areas of Japan where stock farms
and pastures had been located since early times.
Pathogenesis
The development of tetanus is dependent upon the pres-
ence of C. tetani in tissue in an environment that will per-
mit its growth and toxin production, and the toxin
formed must subsequently reach the central nervous sys-
tem (CNS) in sufficient quantity to produce overt dis-
ease. The organism gains entrance to the tissue via a de-
swine awaits further study of the disease. The disease can
be controlled by reducing the incidence of pneumonias,
metritis, and enteritis in affected groups of pigs, coupled
with vaccination of finishing pigs and sows against the
disease using alum-adjuvanted vaccines such as those
readily available for sheep. Marco (1995) reported using
zinc bacitracin at 200 ppm and twice daily feeding to re-
duce mortality in an affected sow population. The
prompt disposal of carcasses by incineration or deep
burial may reduce the contamination of the environ-
ment by spores.
fect in the normal barriers to infection, usually via a deep
skin wound. Since spores are commonly present in soil,
any contaminated wound should be regarded as a possi-
ble site of C. tetani infection. Tetanus bacilli have little or
no invasive ability and tend to remain localized at the
primary site of infection.
C. tetani is a strict anaerobe; thus, its growth requires
a microenvironment with lowered oxidation-reduction
potential. Deep foci of devitalized tissue provide a suit-
able environment for growth of the organism. Such foci
may be formed by traumatic tissue injury, the presence of
foreign bodies, or infection by histotoxic bacteria intro-
duced during or subsequent to wounding. In swine the
most commonly reported location of tetanus infection is
castration wounds. Sakurai (1966) reported that 202 of
220 cases in Japan in which the infection site was known
were postcastration infections. Kaplan (1943) reported
the loss of 60 of 250 young pigs from tetanus; 40 cases
were postcastration and 20 probably were umbilical in-
fections. Wounds inflicted by unclipped canine teeth as
well as infected dental alveoli during eruption of teeth
have also been suggested as possible sources of infection
(Morrill 1964).
The incubation period (interval between establish-
ment of the infection focus and onset of clinical signs)
ranges from several days to several weeks. In general, cas-
es with a short incubation period run a more acute and
fulminating course with a higher fatality rate than cases
with a long incubation period.
Toxin-containing vesicles pass by retrograde axonal
transport along the motor nerve fibers from neuromus-
cular junctions at the site of the injury to act on the in-
hibitory neurons in the ventral horn of the spinal cord to
inhibit their activity. Reflex arcs are potentiated and
tetany occurs. The toxin consists of a large molecule of
140–170 kDa that is split by protease to give a light chain
that is enzymatic (a zinc-dependent endopeptidase) and
a heavy chain that binds to receptors. The L chain acts by
 CHAPTER 29 CLOSTRIDIAL INFECTIONS
cleaving proteins involved in the exocytosis of neuro-
transmitters by neurons. Tetanus toxin cleaves synapto-
brevin at the neuromuscular junction as well as having
an effect in the CNS, but this peripheral action is not clin-
ically apparent in affected pigs.
Many factors may contribute to the cause of death.
The consequences of prolonged recumbency and depri-
vation of nutrients may be factors in animals with a rela-
tively long survival time. In acute cases, respiratory fail-
ure resulting from severe skeletal muscle spasms is likely
to be the single most important factor. Whether or not
the toxin produces a specific metabolic lesion that is di-
rectly involved in causing death in the pig is not known.
Clinical Signs and Lesions
The clinical features of tetanus relate to spasms of skele-
tal muscle which occur in the generalized form in swine.
The earliest sign is a stiffened gait. The disease progress-
es rapidly and usually is fully developed in 1–2 days. As
the disease progresses, the pig has difficulty walking, the
ears are erect, the tail tends to be extended straight out
posteriorly, the head is slightly elevated, and there may
be some protrusion of the nictitating membrane. Fur-
ther progression of the disease renders the pig incapable
of walking, and the skeletal muscles are very firm on pal-
pation. Ultimately the pig lies in lateral recumbency in
opisthotonus, with both thoracic and pelvic limbs ex-
tended and directed posteriorly (Fig. 29.13). The tetanic
spasms are noticeably heightened by sudden sensory
stimuli such as noise, touch, or motion of a visible ob-
ject. Terminally, there are tachycardia and increased res-
piration rate, and white froth may be present around the
mouth and external nares.
No lesions specific for tetanus are found at necropsy.
Conspicuous abrasions of the skin over pressure points
may be seen, and there may be pulmonary congestion
and edema.
Diagnosis
The diagnosis of tetanus in swine is based on observa-
tion of typical clinical signs. An obvious area of infection
29.13. Generalized tetanus in a 10-day-old pig that
apparently resulted from umbilical infection. The ears
are erect and the limbs are rigidly extended.
Taylor 407
such as a castration wound or umbilical abscess is appar-
ent in many cases. Direct Gram-stained smears of exu-
date from the lesion may reveal bacteria with typical C.
tetani morphology, that is, slender gram-positive bacilli
with terminal spherical spores (“drumstick” forms)
among the bacterial flora. The organism may be isolated
by anaerobic culture or can be identified by immunoflu-
orescence (Batty and Walker 1964); however, this is usu-
ally not necessary if there is adequate antemortem clini-
cal observation of the affected animals.
Treatment and Prevention
The prognosis in affected swine is poor, and there is little
evidence that treatment by currently practical methods
is of real benefit. Mihaljevic (1966) reported that all 6
tetanus cases submitted to the clinic at Zagreb during
1948–1965 succumbed to the disease. Kaplan (1943) de-
scribed 4 recoveries of 60 affected pigs; however, the re-
covered cases may have been mild and were not neces-
sarily associated with therapy. Only 11 of 240 cases
described in a report from Japan survived the disease
(Sakurai 1966). Various suggested treatments include re-
opening castration wounds and flushing them with hy-
drogen peroxide, administration of antitoxin in an at-
tempt to neutralize toxin not already fixed by nervous
tissue, administration of antibiotics, and the use of tran-
quillizers or barbiturates as muscle relaxants.
Since there is no practical way to eliminate the spores
of C. tetani from the soil, control is directed toward the
prevention of wound contamination by soil or feces.
Good sanitation in the farrowing house, treatment of the
umbilical cord with antiseptics soon after birth, and
prompt clipping of the canine incisors are recommend-
ed preventive measures against neonatal tetanus. Sharp
objects that may cause skin wounds should be removed
from the environment. Because most tetanus in swine
follows castration, particular emphasis should be placed
on proper surgical technique, with the provision of clean
quarters for the pigs after castration to prevent undue
contamination of the castration wound by soil or
feces.
If reasonable preventive measures cannot be fol-
lowed or if valuable animals are wounded, passive im-
munization with tetanus antitoxin, the prophylactic use
of antibiotics, and/or active immunization with tetanus
toxoid may be indicated. Veronesi (1966) concluded that
the prophylactic use of large doses of long-acting peni-
cillin or tetracyclines (or repeated injections of short-act-
ing preparations of these drugs for 5 days) may be supe-
rior to antitoxin in preventing experimental tetanus in
mice if treatment is instituted within a few hours after in-
fection. An appreciable amount of active immunity may
be obtained from a single injection of alum-precipitated
tetanus toxoid, and excellent protection for a year or
more can be expected if three doses are given several
weeks apart (Morrill 1964).
408 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
BOTULISM
Botulism is a toxicosis characterized by rapidly progres-
sive flaccid paralysis caused by the toxins of C. botulinum.
The toxin is produced by the organism as it grows in de-
composing organic matter of animal or vegetable origin,
and poisoning follows oral consumption of toxin-con-
taining material by a susceptible animal.
Swine are considered to be quite highly resistant to
botulism, and there are few authentic reports of natural-
ly occurring botulism in this species.
Etiology
The organism is an anaerobic, gram-positive bacillus,
usually having a size range of 0.6–1.2 µm by 4–6 µm;
however, much longer forms may be found in some cul-
tures (Smith and Holdeman 1968). It forms oval, usually
subterminal, spores. Growth requires rather strictly
anaerobic conditions and occurs within a wide range of
temperatures up to body temperature but is perhaps op-
timal at about 30˚C.
The lethal toxin, a protein, is an extremely potent poi-
son. There is variation among different strains of the or-
ganism with respect to neurotoxin production. These dif-
ferences involve the antigenic properties of the toxin as
well as the spectrum of animal species susceptible to the
toxin. C. botulinum is currently divided into six types
(A–F) on the basis of major toxin antigenic structure.
Type C strains are further subdivided into types Ca and
Cb, whose toxins are antigenically related but not identi-
cal. Regardless of the type of toxin involved or the
species of animal affected, however, all animals with bot-
ulism exhibit similar clinical signs.
Epidemiology
C. botulinum is commonly present in soil throughout the
world. There are geographic variations in the incidence
of the different types. The prevalence appears to be asso-
ciated with the quantity of organic matter in the soil, and
factors such as fertilization with manure may increase
bacterial numbers.
The occurrence of botulism is dependent upon the
consumption of a sufficient quantity of toxin by a sus-
ceptible pig to produce disease, which implies that a po-
tential foodstuff must provide an environment suitable
for growth and toxin elaboration by C. botulinum. The tis-
sues of dead animals, including crustaceans, fish, birds,
and mammals, that decompose during warm or hot
weather are the most common source of toxin for ani-
mals. Since botulism rarely occurs in swine, there are few
recorded sources of toxin for this species. The death of
five adult swine after eating dead fish from the edge of a
partially dried-up lagoon was reported by Beiers and
Simmons (1967). The loss of pigs being fed swill and de-
composing brewers waste has also been reported
(Doiurtre 1967). Type C strains were incriminated in
these cases.
The eating habits of nonconfined pigs should make
them likely candidates for botulism. The very low inci-
dence of the disease in swine is explained on the basis of
innate resistance. In 1919 Thom et al. reported that tox-
in produced by a strain isolated from spoiled canned as-
paragus failed to affect a pig when administered orally.
The pig succumbed, however, when the toxin was inject-
ed subcutaneously. Dack and Gibbard (1926a) reported
similar findings. Two pigs fed 10 million and 7.5 million
mouse lethal doses (LD) of type A toxin failed to develop
signs. One of these pigs was later injected intraperi-
toneally with a large dose of toxin and died 4 days later.
Dack and Gibbard indicated (1926b) that hog intestine
has a low permeability for the toxin. More recently,
Scheibner (1955) found young swine resistant to 1 mil-
lion mouse LD of types B, C, D, and E toxins given oral-
ly. A similar dose of type A toxin produced typical signs
and death; however, 60,000 mouse LD of type A toxin
had no effect.
Smith et al. (1971) found weanling pigs to be moder-
ately susceptible to type B toxin when it was infused in-
travenously, but they were highly resistant to the toxin
when given orally (oral:intravenous ratio = 16,700:1).
The intravenous LD of type B toxin was approximately
180 mouse LD/kg body weight. This group of experi-
mental pigs was moderately resistant to intravenous in-
fusion of types A, Cb, E, and F toxins (LD = 4000–20,000
mouse LD/kg), at least moderately resistant to Ca toxin
(LD = 18,000 mouse LD/kg), and highly resistant to type
D toxin (LD = 67,000 mouse LD/kg). They were highly
resistant to all types given orally.
Pathogenesis
Botulism is generally considered to be strictly a food poi-
soning; that is, any significant quantity of the toxin is
elaborated in the foodstuff before it is eaten, and poi-
soning results from absorption of preformed toxin. The
bacteria are, of course, consumed along with the toxin,
and it has been proposed that there may be further toxin
production in the intestine.
Absorption of type A toxin was found to occur much
more readily in the upper small intestine than in the
ileum of rats, rabbits, and mice, and absorption from the
stomach was poor in these species (May and Whaler
1958). These workers also found that the toxin was ab-
sorbed by the lymphatics, with passage into the general
circulation by way of thoracic lymph rather than portal
blood.
The toxin consists of a large molecule of 140–170
kDa that is split by protease to give a light chain that is
enzymatic (a zinc-dependent endopeptidase) and a
 CHAPTER 29 CLOSTRIDIAL INFECTIONS
heavy chain that binds to receptors. The L chain acts by
cleaving proteins involved in the exocytosis of neuro-
transmitters by neurons. Toxin types B, D, and F cleave
synaptobrevin, types A and E act on SNAP-25, and type
C toxin acts on syntaxin, at the myoneural junction, pre-
venting muscular contraction. Death is generally as-
cribed to asphyxia resulting from paralysis of the mus-
cles of respiration.
Clinical Signs
The latent period between consumption of toxic materi-
al and onset of signs ranges from 8 hours to 3 days or
more. The clinical features are a manifestation of pro-
gressive flaccid paralysis of voluntary muscles. The ini-
tial signs are weakness, incoordination, and staggering.
Morrill and Bajwa (1964) stated that weakness often ap-
pears in the forelegs of swine first, followed by involve-
ment of the hindlegs. The paralysis may then progress to
lateral recumbency with complete flaccidity. Smith et al.
(1971) observed an initial weakness of the pelvic limbs
and lumbar region, followed by general motor paralysis
and dilation of the pupils of the eyes. Other clinical signs
include anorexia; lordosis; reduced vision or complete
blindness; aphonia; excessive salivation; involuntary uri-
nation and defecation; and deep labored breathing
(Smintzis and Durin 1950; Beiers and Simmons 1967).
The time interval between onset of signs and death or
recovery is variable and probably is largely determined
by the amount of toxin consumed. Five adult swine that
consumed decomposing fish died between 19 and 52
hours after eating the fish, and 2 that staggered recov-
ered later (Beiers and Simmons 1967). Smintzis and
Durin (1950) reported mortality on the sixth day of the
disease.
No lesions specific for botulism are found at necrop-
sy. Significant findings might include the presence in the
stomach of the material suspected as the toxin source
and the occurrence of aspiration pneumonia consequent
to paralysis of the muscles of deglutition (Beiers and
Simmons 1967).
Diagnosis
Because the pig apparently is quite highly resistant to
botulism, a diagnosis should be made only after thor-
ough investigation and exclusion of other possible diag-
noses. A presumptive diagnosis is based on observation
of typical clinical signs, that is, a progressive flaccid
paralysis. Disclosure of a possible source such as spoiled
canned goods or a decomposing animal carcass is also
helpful.
Methods of laboratory confirmation of the disease in
swine are not clearly defined. Valuable confirmatory evi-
dence can be obtained by demonstrating the presence of
the toxin in the suspected source material or in the poi-
soned animal’s gastrointestinal content or serum. Toxin
is readily detected in the serum of some species by
Taylor 409
mouse protection tests and employing type-specific diag-
nostic antitoxins, but this does not appear to be the case
in swine. On the 4 days following intravenous inocula-
tion of a pig with 21,400 mouse LD of type A toxin/kg
body weight, Smith et al. (1971) demonstrated 100, 100,
30, and 10 mouse LD of toxin/mL serum. No toxin was
found in the serum of pigs 1 day after giving large doses
of types B, Cb, or D toxin, and no toxin was demonstrat-
ed in urine from pigs inoculated with any of the types.
Identification of type C toxin in filtrates of small-intes-
tine content from a poisoned sow has been reported
(Beiers and Simmons 1967).
The isolation and identification of C. botulinum may
also be of some value in establishing the diagnosis.
Narayan (1967) reported recovery of C. botulinum from
swine that were silent carriers of the organism. Müller
(1967) stated that type Cb organisms were isolated from
only 3–4% of the livers of healthy slaughtered cattle and
swine in Denmark, whereas this type was isolated from
90% of cattle and horses that had died from botulism.
Yamakawa et al. (1992) found the organism to be wide-
spread in the livers, feces, and the environment of
healthy pigs on infected farms. PCR using toxin gene se-
quences has been used in other species but has not been
reported in swine.
Treatment and Prevention
If botulism is suspected, an effort should be made to find
the toxin source and prevent further consumption of any
remaining suspect material by the herd.
The only specific treatment for botulism is the use of
antitoxin. Antitoxins have been effective in reducing
mortality in humans when given after consumption of
food suspected of containing toxin. It has been suggest-
ed that antitoxin may be beneficial not only when given
parenterally but when given orally as well in an attempt
to neutralize toxin in the alimentary tract (Lamanna and
Carr 1967). As pointed out by Burgen et al. (1949), the
toxin appears to produce an irreversible neuromuscular
block; therefore, the principal benefit of antitoxin prob-
ably is to prevent additional fixation of toxin at my-
oneural junctions, thereby impeding the progressive
severity of the disease. If antitoxins are to be of value,
they must contain antibodies to the specific type of tox-
in involved. Therapy therefore indicates the use of poly-
valent antitoxins that incorporate the types most com-
monly present in a geographic area.
Therapy aimed at reducing continued absorption of
toxin from the intestine was suggested by Beiers and
Simmons (1967). They fed affected sows 1 gallon (4.5 L)
of skim milk containing 4 ounces (120 g) of magnesium
sulfate, repeating this treatment three times at 12-hour
intervals. Only 2 of 4 sows that were weak and staggering
consumed the preparation, and both subsequently re-
covered, whereas the other 2 died. The use of sedatives
also has been recommended.
410 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
Prevention of botulism involves preventing the con-
sumption of potentially toxic material such as spoiled
garbage and decomposing animal tissue. Prophylactic
immunization with toxoids is not practical in swine be-
cause of the infrequent occurrence of the disease.
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 Eperythrozoonosis
30 K. Heinritzi
Eperythrozoonosis in swine is caused by the rickettsial
organism Eperythrozoon suis (Ristic and Kreier 1984).
HISTORY
The disease was first reported by Doyle in Indiana in
1932 as “a rickettsia-like or anaplasmosis-like disease in
swine” (Doyle 1932). He described obvious icteroane-
mia, dyspnea, weakness, and fever up to 40.5˚C in 2- to
8-month-old pigs, noted that the blood of the affected
pigs was thin, that the red blood cells tend to agglutinate
spontaneously, and that the serum was tinted an icterous
color. More recently, eperythrozoonosis has been ob-
served in pigs of a wide age range, from piglets to preg-
nant sows, all over the world. Splitter and Williamson
(1950) described the organism responsible for icteroane-
mia in pigs as Eperythrozoon suis because of its similarity
to known species of eperythrozoa: E. wenyoni of cattle
and E. ovis of sheep.
Eperythrozoon species have also been identified in oth-
er animals (Gothe and Kreier 1977). Pathogenicity, how-
ever, has only been demonstrated for E. suis, E. ovis
(sheep), E. wenyoni (cattle), and E. coccoides (mice).
ETIOLOGY AND PATHOGENESIS
E. suis are round to oval organisms with an average di-
ameter of 0.2–2 µm that adhere either individually or in
chains to the outer erythrocyte membrane (Zachary and
Basgall 1985; Liebich and Heinritzi 1992); they can also
encompass the entire erythrocyte. For a long time the
eperythrozoon organisms from pigs were divided into
two forms—E. suis and E. parvum—on the basis of their
size, form, pathogenicity, incubation period, therapeutic
resistance, filterability, and structure (Splitter 1950).
More recent studies indicate these differences are not a
question of two pathogenetically different organisms,
but rather that the E. suis organism changes its size and
form as it matures (Zachary and Basgall 1985; Liebich
and Heinritzi 1992). Scanning electron microscope stud-
ies show that an infection with E. suis changes the
erythrocyte surface, causing a deformation (Zachary and
Basgall 1985; Liebich and Heinritzi 1992). During acute
eperythrozoon attacks, immature and adult forms of the
organism are found next to each other on the erythro-
cyte, representing the various sizes and forms of their de-
velopmental stage (Zachary and Basgall 1985; Liebich
and Heinritzi 1992). These studies demonstrated that
the organism changes its size and shape during its devel-
opment. They provide evidence that the former E.
parvum, considered to be nonpathogenic, is an immature
or intermediate form of E. suis. Free organisms are also
seen in the plasma. Those erythrocytes that have been
deformed by the organism are removed and then he-
molyzed by the spleen. In the acute stage, a generalized
hemolytic icterus can occur. It is assumed that these
changes in the erythrocyte’s shape influence its fluidity
and its osmotic resistance (Heinritzi and Plank 1992;
Zachary and Basgall 1985).
Eperythrozoonosis causes an autoimmune hemolytic
anemia mediated by or associated with a cold agglutinin.
The mechanisms that cause the hemolysis during the
acute stage are not fully understood. Zachary and Smith
(1985) assumed that during the interaction of E. suis and
the erythrocyte membrane, the membrane structure
changes, thereby resulting in the freeing of masked anti-
gens or the modification of existing antigens that are
then seen as foreign by the body’s own immune system.
After the organism adheres to the erythrocyte cell mem-
brane, autoantibodies are produced as part of the de-
fense mechanism and attack the erythrocytes of the in-
fected animal. These antibodies are cold agglutinins of
the M isotype that, depending on the temperature, are
deposited on the erythrocyte membrane to cause the ag-
glutination of individual erythrocytes. At higher temper-
atures the cold agglutinin can be removed from the
erythrocyte membrane. At 0˚C it is tightly fixed to the
membrane (Zachary 1984; Jüngling et al. 1994).
In the acute phase an increased bleeding potential is
observed, caused by activated intravascular coagulation
with a consecutive consumptive coagulopathy. The
thromboplastin time is increased and the number of
thrombocytes decreased. The thromboelastogram shows
an increase in the reaction and coagulation time, as well
as a decrease in the maximum amplitude. The larger the
number of erythrocytes that are affected by E. suis, the
more striking are the changes. Latent infection with E.
suis has no influence on blood coagulation (Plank and
Heinritzi 1990). Acute E. suis infection produces a seri-
ous blood acidosis and hypoglycemia. In vivo and in vit-
ro experiments demonstrate that during an acute attack
of eprythrozoonosis, the amount of glucose used in-
413
414 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
creases strongly. This results from the metabolic activi-
ties of E. suis (Heinritzi et al. 1990; Smith et al. 1990).
The acidosis results from an increase in the lactic acid
concentration (metabolic component), as well as from a
disturbance in the pulmonary gas exchange (respiratory
component). The erythrocyte sedimentation rate is
markedly increased during an acute attack.
It has not yet been possible to cultivate E. suis on a
cell-free medium.
EPIDEMIOLOGY
Eperythrozoa are species specific (Ristic and Kreier
1984). Eperythrozoonosis caused by E. suis organisms
has only been observed in domestic pigs. Serologic tests
from wild pigs have been uniformly negative for E. suis in
the indirect hemagglutination (IHA) test.
Transmission can occur directly via the oral uptake of
blood and blood components: licking tail-docking
wounds, cannibalism, or the uptake of blood-contami-
nated urine. Indirect transmission is by means of live
vectors, such as ectoparasites (lice), and nonliving vec-
tors, such as contaminated syringes or surgical instru-
ments used for docking tails, tattooing, or castration.
Transmission is also possible via the use of a contami-
nated upper-jaw sling. Transmission during copulation is
only possible if the boar leaves blood-contaminated se-
men in the vaginal area. Intrauterine transmission of E.
suis is considered unlikely (Heinritzi 1992).
In experimentally infected and splenectomized pigs,
the incubation period lasts an average of 7 days (3–20).
Eperythrozoonosis is a so-called multifactorial dis-
ease. The reason for this view is that under experimental
conditions, it is not possible to produce an acute case in
a healthy pig that is kept under clean and correct condi-
tions solely by infecting it with the pathogen. If the host
has a functioning defense system, a balance develops be-
tween itself and the pathogen; the number of eperythro-
zoon organisms in the blood are kept at a constant low
level. Clinically obvious signs of anemia, fever, and occa-
sional icterus will occur only in especially stressed indi-
vidual animals within a herd. Stress in the form of over-
stocking, bad climatic conditions, a change in housing or
food, or chronic general disease predisposes the pigs to
clinical illness.
The spread of the pathogen is strongly dependent on
the potential for infection within an individual herd or
between herds. Precise epidemiological studies are possi-
ble only to a limited extent since serologic tests are at the
moment not dependable enough for the detection of la-
tent infected animals. Serologically negative animals
could still carry E. suis and transmit it to others. For this
reason it is difficult to determine precisely the impor-
tance and spread of the pathogen within a definite pop-
ulation.
CLINICAL SIGNS
Within an infected herd, eperythrozoon attacks occur in
individual animals that are already suffering from re-
duced resistance resulting from conditions likely to cause
stress: after zootechnical procedures or dominance fights
or during parturition. The disease can also break out in a
herd where the animals are already suffering from an-
other chronic infectious disease.
Pigs of any age can be affected by E. suis infection.
Weaned piglets are particularly predisposed to infection,
as are piglets a few weeks after being castrated. The clin-
ical signs of an acute attack are pallor, fever up to 42˚C,
occasional icterus, as well as cyanotic changes on the ex-
tremities, especially on the margins of the ear cartilage.
The classic form of icteroanemia as described by Robb
(1943) is now seldom seen. Anorexia, apathy, and dysp-
nea may occur depending on the severity of the anemia.
Growth rate is depressed in those pigs that survive the
acute phase of the disease .
Marbling (mottling) or red discoloration of the ear
cartilage can occur due to the impairment of the blood
supply in the capillary vessels of the extremities. The
cold agglutinins that are present during an acute attack
are most likely responsible for the microagglutination
and thrombosis that occur in the capillaries of the ex-
tremities, the temperature in these areas being lower
than that of the core. Fine, light to dark red discol-
orations of the ear margins are characteristic. In some
cases marked cyanotic discolorations of the complete ear
cartilage, the tail, and the distal parts of the extremities
can be observed. Healing can be expected within a few
days after therapy. Necrosis of the ear margins or large
parts of the ear cartilage can occur if the eperythrozoon
attack extends for a longer period of time, or if consecu-
tive attacks occur. Since affected pigs do not develop a
strong immunity, reinfection is possible at any time.
The chronic form of eperythrozoonosis causes un-
thriftiness, pallor, and sometimes allergic skin reactions
in the form of urticaria or Morbus maculosus. It is impor-
tant to differentiate the clinical signs of Morbus maculo-
sus, with its numerous petechiae and ecchymoses, from
those of hog cholera.
Sows with eperythrozoonosis usually show clinical
signs 3–4 days after introduction to the farrowing ac-
commodation or after farrowing. Acutely sick sows suffer
from anorexia and fever to 42˚C, and mammary or vulval
edema may be visible for 1–3 days. These sows have a
depressed milk flow, and their maternal behavior is sub-
normal or absent. Since the clinical signs of the E. suis in-
fection can last until the puerperal period, differentiation
between eperythrozoonosis and puerperal disease can be
very difficult (Bugnowski and Horsch 1988). Secondary
bacterial or viral infections and stressful factors, such as
mange, poor housing conditions, and lack of food, en-
courage the development of eperythrozoonosis. Finally,
 CHAPTER 30 EPERYTHROZOONOSIS Heinritzi
the disease can lead to the so-called thin-sow syndrome
in affected pigs.
Reproductive problems have been described in sows
infected with E. suis. Poor conception rates, anestrus,
abortion, and the birth of weak piglets have all been re-
ported. Brownback (1981) described a case where 65% of
the sows in an infected herd showed no signs of estrus
within the first 7 days after weaning. Sisk et al. (1980) al-
so identified reproductive problems, irregular cycles,
abortions, small litters, premature births, and stillbirths,
as well as weak piglets, in serologically positive herds.
Schweighardt et al. (1986) described fertility problems in
the form of anestrus, a return to estrus, and an increased
weaning to estrus interval for up to 60% of the sows ex-
amined.
No noticeable influence on herd reproduction was
found in another study, however, where the effect of an
E. suis infection on productivity and on newborn piglets
was investigated. The authors did not observe delayed es-
trus, embryonic death, or abortions (Zinn and Jesse
1982; Zinn et al. 1983). Rosenkrans et al. (1984) found
no difference in the number of mummies, neonatal mor-
tality, average birth weight, growth rate, and fertility be-
tween sows chronically infected and uninfected with E.
suis. The authors postulated that in the course of time an
adaptation takes place and that the organism loses some
of its virulence. Laboratory control studies have not
proven that the reproductive problems reported are due
to eperythrozoonosis.
Piglets of anemic sows are born anemic, without be-
ing infected themselves. The piglets are often pale and
sometimes underweight and tend to develop disease eas-
ily.
The acute clinical signs in feeder pigs usually develop
following cannibalism, overcrowding, poor housing, and
inadequate nutrition. Frequent injections for treatments
and vaccinations also play a major role in the spread of
the organism and in subsequent reinfections. Cannibal-
ism is particularly important as a source of infection for
feeder pigs compared to other groups. Oral treatment
with tetracycline used in the control of respiratory dis-
eases can mask the clinical signs of eperythrozoonosis
during treatment. The affected pigs later show skin pal-
lor, poor weight gain, and an increased sensitivity to oth-
er secondary diseases.
Morbidity due to the progress of subclinical infection
in an infected herd is difficult to measure. Mortality due
to eperythrozoonosis is less than 1%.
HEMATOLOGY AND METABOLISM
Blood collected during the febrile stage is watery, has a
lacquered appearance, and does not stick to the test tube
wall. When blood that was collected into a tube contain-
ing an anticoagulant is poured after being cooled to
room temperature, fine-grained microagglutination can
415
be seen on the test tube wall and is specific for epe-
rythrozoonosis. The phenomenon is enhanced by cool-
ing the blood and almost vanishes when the blood is
warmed to 37˚C.
Eperythrozoonosis causes hemolytic anemia with the
character of a normochromic and normocytic anemia.
The red cell status of sick animals shows an almost par-
allel decrease in the number of erythrocytes, the hemo-
globin concentration, and its hematocrit value. Capillary
tubes containing blood from affected pigs are very strik-
ing when centrifuged because of the small percentage of
red blood cells, the broad leukocyte band, and the slight-
ly icteric color of the plasma.
At the beginning of an attack, a few days before the
fever reaches its highest point, single eperythrozoon or-
ganisms can be demonstrated in blood smears. The high-
er the number of eperythrozoon organisms in the blood,
the lower the hematocrit and hemoglobin value, and the
lower the number of erythrocytes.
Iron that is released during hemolysis is deposited at
the site of phagocytosis. The amount of serum iron de-
creases slightly with increased number of organisms. If
the body has adequate stores of iron, the concentration
of serum iron rises sharply after therapy, supporting the
massive erythropoesis that develops. This rapid stimula-
tion of erythropoesis is associated with the sudden in-
crease in the red blood cell numbers, increased numbers
of immature cells, and a large increase in reticulocytes.
In the acute form of hemolytic anemia, an increase in
the amount of noncoupled (indirect) bilirubin can occur
in the blood, as conjugation to glucuronic acid in the liv-
er is depressed. After treatment, there is a rapid decrease
in the levels of serum bilirubin. This signals the end of
erythrocyte destruction and indicates that a rapid
change from hemolysis to hematopoesis has occurred. A
definite leukocytosis is evident 1–2 days before or short-
ly after an attack of fever. The leukocyte response is seen
in terms of a neutrophilic leukocytosis.
DIAGNOSIS AND
DIFFERENTIAL DIAGNOSIS
The diagnosis of eperythrozoonosis can be based upon
five criteria: clinical signs, hematological changes, direct
demonstration of the organism, indirect tests, and infec-
tion in splenectomized pigs.
Clinical Signs
The most important clinical signs for diagnosis are the
occurrence of anemia with apathy and fever of 40˚C or
more. Additional clinical signs suggestive of eperythro-
zoonosis are discolorations of the ear margin and the
presence of allergic skin reactions. Weaned piglets short-
ly after zootechnical procedures (castration) and feeder
pigs are most likely to be affected. Sows usually only suf-
fer from the subclinical form.
416 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
Hematological Changes
Blood taken during the febrile stage produces visible mi-
croagglutination on blood films, and the normochromic,
normocytic character of a hemolytic anemia is proof of
the disease. The mean corpuscular hemoglobin concen-
tration (MCHC), derived from the quotient of the hemo-
globin concentration and the hematocrit, indicates the
quantitative changes in the amount of hemoglobin in the
erythrocytes and confirms the presence of a
hypochromic anemia. Hypochromic conditions (MCHC
under 300 g/L) occur when the production of new he-
moglobin cannot match the rate of red cell production.
Other plasma biochemical effects include a fall in the
blood glucose level and a transient increase in the level of
bilirubin.
Direct (Microscopic) Demonstration
of the Organism
Microscopic demonstration of the organism is best per-
formed during the acute febrile stage. Meticulous sam-
pling technique and preparation of a good-quality smear
are essential for visualizing eperythrozoa by light mi-
croscopy. Before preparing a blood smear, the blood
must be warmed to 38˚C; otherwise the erythrocytes ag-
glomerate due to the cold agglutinin, making the detec-
tion of eperythrozoa difficult. The size of the organism
varies and decreases with increasing duration of the
chronic disease. The organisms are visible on the sur-
faces of the erythrocytes as oval to round individual rings
or as chains completely encompassing the erythrocyte.
Wright-Giemsa is the most common stain for demon-
strating eperythrozoa in fixed blood smears. Both this
stain and conventional quick stains may produce arti-
facts (Giemsa precipitations) that adhere to the erythro-
cyte membrane and that could be mistaken for epe-
rythrozoa.
It is also possible to see individual eperythrozoa in
their various forms under a fluorescent microscope with
acridine orange staining (Kreier and Gothe 1976). The
complexity of this technique makes it suitable only for
diagnostic laboratories or clinics. One milliliter of blood
in EDTA, heparin, or acid citrate dextrose is required and
should be sent to the appropriate diagnostic laboratory
(Heinritzi 1990). The advantage of this staining method
is that the bright orange organisms can easily be differ-
entiated from the dark green background, even if their
numbers are small. During the acute stage, eperythrozoa
appear as light to dark orange dots; in chronically infect-
ed pigs, however, the organisms are less distinctive, ap-
pearing as small light yellow to light green dots that can
be distinguished on the edge of the erythrocyte or are ly-
ing free in the plasma (filter set 09-450-490/FT 510, LP
520).
False positives are possible with this stain. Nuclei and
nuclear fragments can also fluoresce with the acridine or-
ange stain. This means that immature erythrocytes and
Howell-Jolly bodies are also stained. Live mycoplasmas
present in the sample fluoresce with this acridine deriva-
tive and appear as light yellow to light green fluorescent
dots or disks, depending on the concentration of dye
used and the degree of absorption (Stübner 1976). The
erythrocytes differ from the mycoplasms in their size and
position. Eperythrozoa stain more strongly, are almost
twice the size, and are usually found on the erythrocyte
or on its edge. Degenerating eperythrozoa appear small-
er and are usually seen as green dots on the edge of the
erythrocyte. The blood smear should, therefore, always
be done on the day of sampling.
Indirect Serologic or PCR Tests
Serologic methods include the demonstration of anti-
bodies by the IHA test, complement fixation test (CFT),
or ELISA. The cold agglutinins that occur during epe-
rythrozoonosis are not specifically directed against the
organism but are directed against erythrocyte mem-
branes that have been specifically damaged by E. suis
(Smith and Rahn 1975; Jüngling et al. 1994). The pro-
duction of antibodies is related temporally to the in-
creasing number of organisms but not to the time of the
infection. This means that antibody production occurs in
a wavelike phase. Every new attack produces a new anti-
body response. In splenectomized pigs this undulating
phase of the antibody titer can easily be followed. Even
after several acute attacks, the antibody titer persists on-
ly for 2–3 months, often falling below the threshold val-
ue. This means that false-negative titers are common.
The booster effect, known from other infectious diseases,
has not been demonstrated in E. suis infection in the pig.
In spite of this, the time interval between intermittent at-
tacks becomes longer, and the intensity of the fever phas-
es weakens. Serologically negative pigs can be E. suis car-
riers and infect other animals via blood contact. All
serologic procedures are suitable only for herd diagnos-
tics (Baljer et al. 1989; Schuller et al. 1990). Gwaltney et
al. (1993) describe a polymerase chain reaction (PCR)
that for the moment seems to be the diagnostic aid of
choice. The results demonstrate the potential of PCR as
a valuable tool for diagnosing and studying E. suis infec-
tion in pigs.
Animal Infection in Splenectomized Pigs
Ultimate confirmation of the presence of infection can
be accomplished by splenectomizing a pig considered to
be infected or by transfusing blood from a suspected pig
to a splenectomized pig. Splitter (1950) used splenec-
tomized pigs for his experiment with E. suis, and diag-
nostic splenectomy is still considered the surest way of
diagnosing an E. suis infection. Between 3 and a maxi-
mum of 20 days after removing the spleen, the E. suis–in-
fected pig develops an acute attack, which can then be
easily diagnosed by demonstrating the organism in the
blood smear.
 CHAPTER 30 EPERYTHROZOONOSIS Heinritzi
TREATMENT
The treatment of choice is the parenteral application of
oxytetracycline in a dose of 20–30 mg/kg body mass
(BM). Pigs developing acute eperythrozoonosis with
fever must be treated parenterally, since they are unable
to eat sufficient medicated feed for therapy to be effec-
tive. Parenteral oxytetracycline can also be given to pigs
on infected farms at times of extreme stress, such as dur-
ing rehousing or after zootechnical procedures. Howev-
er, neither with parenteral nor with constant oral treat-
ment can the organism be eliminated. Oral
chlortetracycline treatment can reduce the occurrence of
anemia. Continuous treatment with chlortetracycline
may not be worthwhile, however, since splenectomized
pigs have developed acute eperythrozoonosis during oral
therapy with chlortetracycline at 20 mg/kg BM in an ex-
perimental study. Piglets and chronically ill pigs should
also be given iron (200 mg iron dextran/piglet).
PREVENTION
Treatment should be supplemented by supportive and
prophylactic measures (Claxton and Kunesh 1975). It is
important to stop the spread of infection and to prevent
reinfection within a herd. There should be an ecto- and
endoparasite management program, and hygienic pre-
cautions should be taken during any procedure where
blood could be transmitted from one animal to the next.
Transmission by needles and by surgical instruments
contaminated with blood can be limited by changing
needles between injections and bleeding of sows. Sepa-
rate sterile instruments should be used for each litter in
zootechnical procedures such as tooth resection, castra-
tion, tattooing, tail docking, or even injections. This
means that every unit must have at least two sets of sur-
gical instruments. The contaminated set can then be
placed in a properly diluted disinfectant and used for al-
ternate litters.
Attacks may increase in frequency in infected herds,
but a certain equilibrium is eventually reached between
the host and the organism. This also holds true for
splenectomized animals. If this balance is disturbed, an
acute eperythrozoon attack can occur at any time, and
thus it is important to maintain good husbandry. Infec-
tion with E. suis can become manifest only if other stress-
ful factors are also affecting the pig. On the other hand, a
latent infection with E. suis is also a factor that can cause
the outbreak of an otherwise latent infection. The im-
portance of an E. suis infection does not lie in its prima-
ry disorder but rather in the poor performances that it
can cause.
There are no vaccines. If a herd is free from infection,
new additions should be from eperythrozoon-free herds.
Freedom from infection can be assumed if serologic or
PCR tests of serum of 10 pigs in the farrowing house are
417
negative or if the transfusion of 10 blood samples to a
splenectomized growing pig has no effect. The use of un-
infected pigs minimizes the introduction of eperythro-
zoonosis.
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 Erysipelas
31 R. L. Wood
Swine erysipelas (SE) or its equivalent in other lan-
guages—Schweinerotlauf, vlekziekte, rouget du porc, mal
rossino, entrace eresipelatoso, rozyca, and erisipela del
cerdo—is a disease caused by the bacterium Erysipelothrix
rhusiopathiae (Sneath et al. 1986) and manifested by
acute or subacute septicemia and chronic proliferative le-
sions. The disease is worldwide in distribution and is of
economic importance throughout Europe, Asia, and the
Australian and American continents.
The identification of SE as a disease entity began in
1878 when Koch isolated from an experimental mouse
an organism that he called “the bacillus of mouse sep-
ticemia.” In 1882–83 Pasteur and Thuillier briefly de-
scribed the organism isolated from pigs with rouget. In
1886 Löffler published the first accurate description of
the causative agent of Schweinerotlauf and described the
infection in swine.
In the United States the recorded history of SE began
when Smith (1885) isolated the causative organism from
a pig. The disease was not considered important, howev-
er, until serious outbreaks were reported in South Dako-
ta in 1928; by 1959 acute SE had been reported in 44
states. Since that time the prevalence of SE apparently
has decreased overall (Wood 1984). However, the disease
is still considered to be of economic importance, espe-
cially in the chronic form, and outbreaks of acute SE con-
tinue to occur sporadically in endemic areas.
E. rhusiopathiae occurs in most parts of the world,
and SE occurs in most areas where domestic swine are
produced. The organism also causes polyarthritis of
sheep and lambs and serious death losses in turkeys. It
has been isolated from body organs of many species of
wild and domestic mammals and birds as well as rep-
tiles, amphibians, and the surface slime of fish.
In humans E. rhusiopathiae causes erysipeloid, a local
skin lesion that occurs chiefly as an occupational disease
of persons engaged in handling and processing meat,
poultry, and fish as well as of rendering-plant workers,
veterinarians, game handlers, leather workers, laborato-
ry workers, and the like. The organism occasionally is
isolated from cases of endocarditis in humans and rarely
causes acute septicemic disease.
ETIOLOGY
E. rhusiopathiae, the causative agent of SE, is a gram-pos-
itive bacillus with a marked tendency to form elongated
filaments.
Physicochemical Characteristics
MORPHOLOGY AND STAINING. The morphology
of E. rhusiopathiae is variable. In smears or cultures made
directly from tissues in cases of acute infection, the or-
ganism appears as slender, straight or slightly curved
rods, 0.2–0.4 by 0.8–2.5 µm, occurring singly or in short
chains (Fig. 31.1). An occasional coccoid or clubbed form
may be seen. Palisades and angular formations (“snap-
ping division”) are common. The organism is nonmotile,
non-spore-forming, and non-acid-fast. It stains readily
with ordinary dyes and is gram-positive but is easily de-
colorized. After several subcultures on an artificial medi-
um, filamentous forms of the organism begin to appear.
These forms may predominate in old cultures or in
chronic lesions. Filamentous forms are somewhat thick-
ened, are greatly elongated (4–60 µm), and may form a
mass resembling mycelia, especially in a liquid medium
(Fig. 31.1). The filamentous forms sometimes have a
beaded appearance when Gram’s stain is used.
GROWTH CHARACTERISTICS. Growth of E. rhu-
siopathiae at 37˚C in a nutrient broth appears at 24 hours
as a faint turbidity with no odor or pellicle. Shaking typ-
ically reveals a momentary appearance of rolling clouds.
Slight sedimentation will be seen after 36–48 hours of in-
cubation. Growth is much heavier in broth enriched with
serum. In gelatin stabs incubated at 22˚C for 4–8 days,
growth of the organism radiates out from the stab in all
directions, resembling a test-tube brush.
Colonies of E. rhusiopathiae on agar media at 48
hours are tiny (less than 1 mm), are transparent, and
vary from smooth to rough, depending on cellular mor-
phology (Fig. 31.1). Colonies of most strains have entire
edges, but some strains form colonies that are slightly
larger and have somewhat undulate edges. Granulelike
structures usually appear under a colony just below the
surface of the agar. Dissociation from smooth to rough
form may occur during the development of a colony,
producing a sector (Fig. 31.1); the morphology of cells
from these intermediate forms will include a variety of
shapes from short, curved rods to short filaments.
Most strains of E. rhusiopathiae produce a narrow
419
420 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor

SMOOTH INTERMEDIATE ROUGH

31.1. Cellular and colonial morphology of Erysipelothrix rhusiopathiae. Upper row: ×1200,
crystal violet; lower row: ×32. (Courtesy National Animal Disease Center, Ames, Iowa.)

zone of partial hemolysis on blood agar, usually with a
greenish color. Rough colonies do not induce hemolysis.
BIOCHEMICAL PROPERTIES. E. rhusiopathiae is rel-
atively inactive in commonly used tests of biochemical
activity (Cottral 1978). The organism produces acid but
no gas from certain fermentable carbon compounds and
produces hydrogen sulfide in triple-sugar iron agar
(Vickers and Bierer 1958; White and Shuman 1961).
ANTIGENIC STRUCTURE. Most, if not all, strains of
E. rhusiopathiae have one or more common heat-labile
antigens, which are proteins or protein-saccharide-lipid
complexes. The organism does not possess flagellar anti-
gens, since no flagella are present.
Heat-stable antigens consisting of peptidoglycan
fragments from the cell wall form the basis for identifica-
tion of various serovars (formerly referred to as
serotypes) within the species. The serovars are identified
by precipitin reactions with specific hyperimmune rab-
bit sera, usually in a gel double-diffusion system. Most
isolates of the organism (75–80%) from swine fall into
two major serovars designated 1 and 2 (Wood and Har-
rington 1978; Takahashi et al. 1996). About 20% of iso-
lates make up a group of less-common serovars. Under a
numerical system introduced by Kucsera (1973), a total
of 26 serovars have been described so far (Kucsera 1973;
Wood et al. 1978; Nørrung 1979; Xu et al. 1984, 1986;
Nørrung et al. 1987; Nørrung and Molin 1991). Strains
that do not possess the specific antigen are referred to as
serovar N.
Immunizing antigen is discussed in the section on
prevention.
Biological Characteristics
GROWTH REQUIREMENTS. E. rhusiopathiae is fac-
ultatively anaerobic; some strains grow better in an at-
mosphere of reduced oxygen containing 5–10% carbon
dioxide. The organism will grow at temperatures of
5–42˚C. Optimum growth occurs at 30–37˚C and at a pH
range of 7.4–7.8. Growth is enhanced by serum, glucose,
protein hydrolysates, or surfactants such as Tween-80.
The organism is fastidious; that is, a complex medium is
required, but specific nutrient requirements are not
known.
RESISTANCE. E. rhusiopathiae is relatively resistant to
adverse conditions for a non-spore-forming organism
(see also the section on epidemiology). The organism is
somewhat resistant to drying and can remain viable for
several months in animal tissues under a variety of con-
ditions. It can persist in frozen or chilled meat, decaying
carcasses, dried blood, or fish meal. It is remarkably re-
sistant to salting, pickling, and smoking and can survive
several months in cured and smoked hams. The organ-
ism can survive in swine feces or fish slime for 1–6
 CHAPTER 31 ERYSIPELAS Wood
months if temperatures remain below 12˚C. It is sensi-
tive to penicillin and usually to the tetracyclines; it is
quite resistant to polymyxin B, neomycin, and
kanamycin and is relatively resistant to streptomycin
and the sulfonamides (see the section on treatment). It is
killed readily by common disinfectants, heat (15 minutes
at 60˚C), and gamma irradiation.
Other Species within the Genus
Another species within the genus Erysipelothrix has been
proposed (Takahashi et al. 1987a). This species, desig-
nated E. tonsillarum, is distinguished from E. rhusiopathi-
ae by DNA homology values. Phenotypic characteristics
of the two species are indistinguishable by the usual di-
agnostic bacteriologic methods. E. tonsillarum has been
isolated from a variety of sources, including the tonsils of
healthy swine. Reported isolates of E. tonsillarum have
little or no virulence for swine; therefore, the species is
not considered significant in the etiology of SE.
Classification of Erysipelothrix has challenged taxono-
mists throughout the recorded history of this ubiquitous
genus. It is likely that the use of current techniques in
bacterial genetic analysis will continue to generate pro-
posals of additional species among isolates from various
animal hosts and other sources.
EPIDEMIOLOGY
Sources of Infection
The most important reservoir of E. rhusiopathiae is prob-
ably the domestic pig. It is estimated that 30–50% of ap-
parently healthy or convalescent swine harbor the or-
ganism in their tonsils and other lymphoid tissues. These
carriers can discharge the organism in their feces or
oronasal secretions, creating an important source of in-
fection. Swine affected with acute erysipelas shed E. rhu-
siopathiae profusely in feces, urine, saliva, and nasal se-
cretions.
Although secondary to swine in importance as
sources of infection, the large variety of wild mammals
and birds known to harbor E. rhusiopathiae provides an
extensive reservoir (Wood and Shuman 1981; Shuman
1971). Various species of domestic animals from which
the organism has been isolated provide an additional po-
tential reservoir on swine-producing farms; however,
with the possible exception of turkeys and sheep, their
importance is doubtful.
The belief that E. rhusiopathiae can lead a saprophyt-
ic existence in the soil, living on dead and decaying or-
ganic material, has persisted for many years. However,
available research data have consistently indicated that
the organism, like most other non-spore-forming patho-
genic bacteria, finds an unfavorable environment in the
soil and dies out in a relatively short time, most likely be-
cause of the action of protozoa. E. rhusiopathiae can be
found in the soil of swine pens and in feces of apparent-
421
ly healthy swine inhabiting the pens. However, Wood
(1973) found no evidence of growth or maintenance of
the organism in test soils under various conditions of
temperature, pH, moisture content, and organic matter
content or in samples of swine-pen soils from which E.
rhusiopathiae had been isolated previously. Rapid death
curves were consistently demonstrated. This failure to
establish a stable population of the organism in soil is
similar to results reported by other investigators since
1955. Present information indicates that soil that is more
or less continually inoculated by infected animals pro-
vides only a temporary medium for transmission of E.
rhusiopathiae.
Factors of Susceptibility
AGE AND GENETICS. Swine less than 3 months or
more than 3 years of age are generally least predisposed
to SE. The relationship of age to susceptibility may be ex-
plained by naturally acquired passive immunity in the
young and active immunity following subclinical infec-
tion in older animals. Suckling pigs of immune sows are
immune to infection for several weeks after birth. The
degree and duration of passive immunity are related to
the immune status of the sow.
There is no experimental evidence that susceptibility
to SE is related to genetics of the animal. Anecdotal ac-
counts of apparent resistance (or susceptibility) of cer-
tain breeds or families of swine can most likely be ex-
plained by the presence of varying degrees of naturally
acquired passive or active immunity.
NATURAL ACTIVE IMMUNITY. For many decades
after SE research was begun in the 1880s, a major prob-
lem was the inability to consistently induce acute SE in
swine by experimental infection with E. rhusiopathiae.
The problem eventually was eliminated by use of specif-
ic-pathogen-free (SPF) pigs delivered aseptically by
surgery, deprived of colostrum, and raised in isolation.
This development revealed the importance of naturally
acquired immunity as a factor in susceptibility to
erysipelas.
Naturally acquired active immunity is induced by
previous infection with E. rhusiopathiae. It is well known
that immunity to acute SE follows clinical disease. Less
well recognized is the immunity that can be induced by
organisms of low virulence, which are capable of causing
mild unnoticed subacute disease or subclinical infection.
PREDISPOSING FACTORS. SE can occur with other
swine diseases, but the significance of preexisting infec-
tious disease as a predisposing factor is uncertain. Para-
sitic infestations have been reported to increase the
severity of clinical SE. In addition, Cysewski et al. (1978)
showed that the susceptibility of swine to acute SE can
be enhanced by subclinical toxicity from aflatoxin in the
422 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
feed. This treatment also interfered with the induction of
immunity to SE by vaccination.
Environmental and stress factors such as nutrition,
ambient temperature, and fatigue, particularly sudden
changes in these conditions, have long been linked to the
appearance of SE. For example, acute disease has oc-
curred following sudden changes in diet such as acciden-
tal access to tankage or to a field of corn, feeding new
corn, or placing pigs on new pasture. Experimentally,
sudden exposure to either excessive heat or cold or expo-
sure to a sustained high temperature (30˚C) has been re-
ported to enhance susceptibility. Under natural condi-
tions, sudden changes in weather involving extreme
temperature changes may have the same effect. Varia-
tions in prevalence of SE believed to be related to yearly
cycles or to season of the year have been reported, but
consistent patterns of prevalence corresponding to these
factors have not emerged. Except for a possible relation-
ship to temperature changes, the apparent variations re-
main unexplained.
When attempting to evaluate factors that may be re-
lated to the occurrence of SE on the farm, it should be
kept in mind that a variety of stimuli in the animal’s to-
tal environment can affect the level of susceptibility ex-
isting at any given time. Sudden outbreaks of acute SE
may be the result of a combination of susceptibility of
the animals and virulence of the causative organism,
both of which are variable.
PATHOGENESIS
Investigations using germfree pigs have demonstrated
that E. rhusiopathiae is the sole causative agent of SE and
does not require the presence of any other infectious
agent for its disease-producing ability.
Mode of Entry
E. rhusiopathiae can gain entry to the body by a variety of
routes. Infection through ingestion of contaminated feed
and water is considered a common mode. There is no in-
formation on specific areas within the digestive system
where entry may occur, nor is it known whether the or-
ganism can invade normal mucosa. Early investigators
postulated it gained entrance through lesions produced
by intestinal parasites; however, their presence is unnec-
essary. The organism can readily gain access to the body
through the palatine tonsils or other lymphoid tissue in
the wall of the digestive tract, but entrance is probably
not limited to these areas.
Natural infection no doubt can result from infected
skin wounds, which may be concealed or too small to be
readily noticeable. Experimental infection can be accom-
plished easily by inoculation of scarified skin (Shuman
1951); therefore, it is likely that infection in this manner
from a contaminated environment is not uncommon.
Acute SE
Acute systemic SE begins with bacteremia, which quick-
ly results in clinical signs of generalized infection (sep-
ticemia). A nonsystemic infection consisting only of a lo-
cal skin lesion may occur upon cutaneous exposure to a
strain of low virulence or when the pig is partly immune.
In such cases the organism is eliminated without induc-
ing septicemia and the lesion disappears. In the more
typical systemic infection caused by virulent organisms,
bacteremia usually develops within 24 hours after expo-
sure. The organism usually can no longer be cultured
from blood or most body organs after a few days but may
persist, often for months, in the joints and in lymphoid
tissue such as tonsils, Peyer’s patches, and spleen.
According to Schulz et al. (1975b, 1977), pathogene-
sis of the early septicemic phase consists of changes in-
volving capillaries and venules of most body organs, in-
cluding synovial tissues. As early as 36 hours after
subcutaneous exposure of swine to virulent E. rhu-
siopathiae, they observed swelling of endothelium, with
adherence of monocytes to vascular walls and evidence
of widespread hyaline thrombosis. This process was re-
ferred to as a shocklike generalized coagulopathy leading
within 4 days to fibrinous thrombosis, diapedesis, inva-
sion of vascular endothelium by bacteria, and deposition
of fibrin in perivascular tissues. They stated that this
process leads eventually to connective-tissue activation
in predisposed sites such as joints, heart valves, and
blood vessels.
In severe acute SE, hemolysis is commonly observed.
Ischemic necrosis of perivascular tissues may occur,
caused by interference with microcirculation. Drommer
et al. (1970) observed a high incidence of encephaloma-
lacia in acute experimental SE and theorized that certain
strains of the organism are endotheliotropic and damage
the endothelial cell barrier in the central nervous system
(CNS).
Mild, delayed hypersensitivity responses to E. rhu-
siopathiae can be elicited and transferred by lymphoid
cells. It is doubtful, however, that delayed hypersensitivi-
ty has a significant part in the pathogenesis of acute SE.
Chronic SE
Information on the pathogenesis of chronic SE is derived
primarily from studies on development of the arthritic
lesion, which has stimulated interest because of its ap-
parent similarity to the lesion of rheumatoid arthritis of
humans.
According to observations by Schulz et al. (1975a,
1977), the joint lesion in chronic SE begins with acute
synovitis that may occur as early as 4–10 days after expo-
sure to E. rhusiopathiae. Within 3 months, fibrinous exu-
dation, proliferation, and pannus formation occur, de-
veloping further into severe fibrosis and destruction of
articular cartilage in 5–8 months. During this time, the
 CHAPTER 31 ERYSIPELAS Wood
organism can be found sequestered within chondrocytes
in addition to its presence in synovial tissue and fluid
(Franz et al. 1995). The earliest changes in the synovial
tissue are described as consisting of coagulopathy and
fibrinous exudate into perivascular tissues. Fibrin de-
posited during the vascular phase, not bacterial colo-
nization, is believed to act as mediator of the subsequent
connective-tissue proliferation.
Affected joints appear to become culture-negative af-
ter 3–6 months, yet the arthritic lesions usually undergo
a progressive development that can continue at least 2
years. The development of such lesions in the apparent
absence of the infectious agent has stimulated investiga-
tion of the role of immunopathologic processes in
chronic arthritis. Hypersensitivity may be a significant
factor in the chronic proliferative and destructive
changes but probably not in initiation of the lesion.
There is evidence that the bacteria do not entirely dis-
appear from chronically affected joints, and the long-
term progressive lesion may occur in response to the con-
tinued presence of either whole bacterial cells or their
antigens. Schulz et al. (1977) reported that living E. rhu-
siopathiae was occasionally isolated from such joints for
up to 2 years. Furthermore, they stated that E. rhu-
siopathiae antigen could be detected by immunofluores-
cence and whole or fragmented bacteria could be seen
with the electron microscope in culturally negative
joints. Denecke and Trautwein (1986) reported detection
of E. rhusiopathiae in arthritic joints microbiologically
and immunohistologically for up to 3 years. Specific an-
tibodies to the organism have been detected in synovial
fluid of chronically arthritic joints and apparently are
produced locally by plasma cells in the synovial tissue,
which can assume a lymphoid function. It is not known
whether the chronicity of the joint lesion is maintained
entirely by specific immune reactions against E. rhu-
siopathiae antigen or whether superimposed autoim-
mune reactions are involved.
A preponderance of evidence exists to indicate that
erysipelatous arthritis is initiated by active infection of
the joint. Mild synovitis and arthritis have been induced
in rabbits and rats by massive intravenous or intraarticu-
lar injections with nonliving whole cells or fractions of
the organism (White et al. 1975; Hermanns et al. 1982),
but the lesions were not as severe as those typically
caused by infection. White et al. (1975) suggested that
the mild response induced by such antigens may predis-
pose the joint to infection during a subsequent transient
septicemia.
Studies on the pathogenesis of endocarditis indicate
that the valvular lesions begin with vascular inflamma-
tion and myocardial infarcts, possibly resulting from
bacterial emboli. These processes, together with exuda-
tion of fibrin, lead to destruction of valvular endocardi-
um.
423
Mechanism of Pathogenicity
The mechanism by which E. rhusiopathiae incites disease
processes is not clearly understood. The organism is not
known to produce toxins. Considerable evidence has ac-
cumulated indicating that neuraminidase, an enzyme
produced by a number of species of pathogenic bacteria,
is a factor in pathogenicity of E. rhusiopathiae. This en-
zyme specifically cleaves alpha-glycosidic linkages in
neuraminic acid (sialic acid), a reactive mucopolysaccha-
ride on surfaces of body cells. The enzyme is produced
by E. rhusiopathiae during logarithmic growth, and the
amount of activity is reported to be less in avirulent
strains or strains of low virulence than in fully virulent
strains (Müller 1981). Specific antibody activity against
E. rhusiopathiae neuraminidase has been demonstrated
in sera of swine with chronic SE, in commercial equine
antierysipelas serum, and in serum of rabbits hyperim-
munized with a preparation of neuraminidase from the
organism. This latter preparation also induced a low lev-
el of protection in mice to E. rhusiopathiae infection.
Neuraminidase is not a toxin; it must be produced in
large amounts to be pathogenically active. It can act on
substrates in cell membranes throughout the body, and
no doubt its activity reaches high levels in an acute sep-
ticemia. Therefore, its activity could be a major factor
mediating the widespread vascular damage, thrombosis,
and hemolysis described (see the section on pathogene-
sis of acute SE). The ability to adhere to cell surfaces may
also play a role in the pathogenicity of E. rhusiopathiae,
and there is evidence that the process involves neu-
raminidase. Takahashi et al. (1987b) reported that viru-
lent strains of the organism adhered better to porcine
kidney cells in vitro than did avirulent strains. Nakato et
al. (1987) reported that neuraminidase was essential for
adherence of E. rhusiopathiae bacteria to vascular en-
dothelial cells.
Although neuraminidase activity may be largely re-
sponsible for the pathogenicity of E. rhusiopathiae, it
does not explain virulence, which is the ability of an in-
fectious agent to overcome the host’s defenses and initi-
ate the pathologic process. There is evidence that the vir-
ulence of E. rhusiopathiae, which is known to be variable,
is related to the organism’s ability to resist the action of
phagocytes (see also Mechanism of Immunity in the sec-
tion on prevention), and resistance to phagocytosis is
correlated with the presence of a protective capsulelike
structure on the surface of virulent bacteria but not on
avirulent mutants (Shimoji et al. 1994).
Serovar and Clinical Form
In the United States, reports of field cases frequently
have described serovar 1 (usually subserovar 1a) as the
predominant isolate from acute septicemic disease and
serovar 2 as the most common isolate from subacute and
chronic cases of SE. However, experimentally, all clinical
424 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
forms of SE can be induced readily in susceptible swine
by strains of serovar 1 or 2. The less-common serovars (3
through 26; N) tend to have low virulence for swine, and
their clinical significance is doubtful.
CLINICAL SIGNS
The clinical signs of SE can be divided into three general
classifications: acute, subacute, and chronic. In addition,
subclinical infection can occur in which no visible signs
of acute disease are evident but which can lead to chron-
ic SE.
Acute SE
Acute SE is characterized by sudden onset, sometimes
with sudden death of one or more animals. Other ani-
mals in the herd may be noticeably sick, and some of
these may subsequently die. Those visibly sick will have
temperatures of 104–108˚F (40–42˚C) and over, and
those with the higher temperatures may show signs of
chilling. Some pigs may appear normal and yet have tem-
peratures of around 106˚F (41˚C). In surviving pigs, tem-
peratures usually return to normal within 5–7 days.
Affected animals withdraw from the herd and will be
found lying down. When approached, they resent being
disturbed but usually will get up and move away. This
usually is accompanied by squealing; when walking, they
show a stiff, stilted gait. Upon stopping, they may be seen
to shift their weight in an apparent effort to ease the pain
in their legs. If left alone, they will soon lie down careful-
ly. Pigs showing severe depression are nevertheless usu-
ally aware of activities around them. They may show
some resentment at being disturbed but will make little
or no effort to rise. Upon being forced to get up, they may
stand for only a few moments before lying down again.
While standing, the feet are carried well under them and
the head is hung dejectedly, giving the back line a
marked arched appearance. Others will not be able to
stand even when assisted.
Most affected animals will show partial or complete
inappetence. Bowel movements are usually retarded and
the feces firm and dry in pigs of market age and older, al-
though as the disease progresses, a diarrhea may appear
in younger animals. Abortion may occur in sows that
contract acute or subacute SE during pregnancy.
Cutaneous lesions (urticarial, or “diamond-skin” le-
sions) appear as early as the second and usually by the
third day after exposure to E. rhusiopathiae (Fig. 31.2).
On the light-skinned pig they can be seen as small, light
pink to dark purple areas that usually become raised, are
firm to the touch, and in most instances are easily pal-
pated. In animals with dark-pigmented skin, one must
rely mainly on palpation, although the weltlike lesions
may be detected by observing raised areas in the hair
coat. The lesions may be few in number and easily over-
looked or so numerous it would be difficult to count
them all. An animal also may die before recognizable ur-
ticarial lesions are evident. Individual lesions, by exten-
sion of the borders, assume a characteristic square or
rhomboid shape. In acute nonfatal erysipelas, these le-
sions may spread considerably but will gradually disap-
pear within 4–7 days after their first appearance, with no
subsequent effect other than a superficial desquamation
to mark the site. The intensity of skin lesions has a direct
relationship to the outcome of the disease. Light pink to
light purplish-red lesions are characteristic of acute non-
fatal SE, whereas angry dark purplish-red lesions usually
precede death of the animal. In acute fatal disease, ex-
tensive dark purplish discoloration often occurs over the
belly, ears, tail, posterior aspect of the thighs, and jowls.
Infrequently, severely affected pigs do not die, and skin
necrosis may follow the severe cutaneous lesions. The ar-
eas of necrotic skin are dark, dry, and firm and eventual-
ly become separated from the healing underlying tissue.
Affected areas, particularly the ears and tail, will eventu-
ally slough. Healing may require many weeks as a result
of secondary infection.
Subacute SE
Subacute SE includes signs that are less severe in their
manifestations than the acute form. The animals do not
appear as sick; temperatures may not be as high or may
not persist as long; appetite may be unaffected; a few
skin lesions may appear that may be easily overlooked;
and, if visibly sick, the animals will not remain so for as
long as those acutely ill. Some cases of subacute SE are so
mild as to remain unnoticed.
Chronic SE
Chronic SE may follow acute or subacute disease or sub-
clinical infection and is characterized most commonly by
signs of arthritis. Signs of cardiac insufficiency may be
31.2. Typical rhomboid urticarial lesions (“diamond-
skin” lesions) of SE. (Courtesy National Animal Disease
Center, Ames, Iowa.)
 CHAPTER 31 ERYSIPELAS Wood
seen occasionally and will be most noticeable following
exertion, sometimes causing sudden death. Chronic
arthritis results in joints that show various degrees of
stiffness and enlargement, sometimes as early as 3 weeks
after infection. Interference with locomotion ranges
from a slight limp to complete refusal to put weight on
the limb, depending upon the extent of damage. Arthri-
tis is the most important clinical manifestation of SE
from an economic standpoint. The condition not only af-
fects growth rate but is responsible for significant losses
of prime cuts at the packing plant.
LESIONS
Rhomboid urticarial lesions (“diamond-skin” lesions)
are characteristic of acute SE, and when generalized (Fig.
31.2), they are a reliable indicator of septicemia. This ob-
servation is important in meat inspection as well as in
field diagnosis (see also the section on clinical diagnosis).
Acute SE
Most lesions of acute SE are similar to those of sep-
ticemia caused by a variety of organisms.
MACROSCOPIC LESIONS. In swine dead from acute
SE, evidence of diffuse cutaneous hemostasis is often
prominent, particularly in the skin of the snout, ears,
jowls, throat, abdomen, and thighs. The lungs may be
congested and edematous. Petechial and ecchymotic he-
morrhages may be seen on the epicardium and in the
musculature of the atria, particularly the left atrium. Ca-
tarrhal to hemorrhagic gastritis is common, and hemor-
rhage of the serosa of the stomach may be present. The
liver usually is congested. The appearance of the spleen
is of particular note, for it may be congested and
markedly enlarged, particularly in animals affected for
several days. Petechial hemorrhages may be present in
the cortex of the kidneys. The appearance of the lymph
nodes will depend upon the degree of involvement in the
area they drain. There is some degree of enlargement
with moderate to marked congestion; subcapsular hem-
orrhage of peripheral nodes may be seen after several
days of illness. The mucosa of the urinary bladder usual-
ly appears normal but may present areas of congestion.
MICROSCOPIC LESIONS. A histologic examination
of skin lesions reveals damage to the capillaries and
venules, with perivascular infiltration by lymphoid cells
and fibroblasts. The pathologic changes occur in the
papillae and upper layers of the derma. Blood vessels of
the papillae are congested and may contain microthrom-
bi and bacteria. The papillae may also present focal
necrotic areas as a result of circulatory stasis. Vascular le-
sions can be seen in the heart, kidney, lung, liver, nervous
system, skeletal muscle, and synovial membranes. Cellu-
425
lar response to infection by E. rhusiopathiae consists
predominantly of mononuclear leukocytes and
macrophages. Neutrophils may appear but do not pre-
dominate. Purulent lesions are not characteristic of E.
rhusiopathiae infection.
Affected lymph nodes usually show acute hyperplas-
tic lymphadenitis, with hyperemia and hemorrhage. In
some nodes there may be evidence of thrombosis and
necrosis of small blood vessels and capillaries. Hemor-
rhagic nephritis with inflammatory changes in glomeruli
may be seen occasionally. In addition, necrosis of renal
tubules with hyaline and granular casts has been report-
ed. Focal accumulations of mononuclear cells may be
seen in subcapsular sinuses of the adrenal cortex. Le-
sions of skeletal muscle may occur, associated with vas-
cular lesions. These consist of a segmented hyaline and
granular necrosis of muscle fibers, which may be fol-
lowed by fibrosis, calcification, and regeneration. Le-
sions of the CNS have been described, consisting of an-
giopathies with disturbances in permeability,
degeneration of neurons, swelling of endothelial cells,
and malacic foci in the cerebrum, brain stem, and spinal
cord.
CLINICAL PATHOLOGY. Leukocytosis may occur in
field cases of SE that last for several days or possibly from
mixed bacterial infection, but in uncomplicated acute SE
a leukopenia accompanied by a relative lymphocytosis is
characteristic during the first 3–5 days. There may be a
relative increase in the number of eosinophils.
Hemoglobin and hematocrit values decrease during
acute disease, followed later by the appearance of nucle-
ated erythrocytes. The sedimentation rate increases.
Changes in plasma components during acute SE include
a decrease in glucose and increases in glutamic ox-
aloacetic transaminase activity, blood creatinine, and
blood urea nitrogen.
Chronic SE
The predominant lesion of chronic SE in swine is a pro-
liferative, nonsuppurative arthritis, occurring most com-
monly in hock, stifle, elbow, and carpal joints. Spondyli-
tis is occasionally seen. Vegetative proliferation on the
heart valves is less common.
MACROSCOPIC LESIONS. Animals affected with
chronic arthritis have an enlargement of one or more
joints, most readily visible in hock and carpal joints. The
joint capsule is thickened with fibrous connective tissue.
The joint cavity contains an excessive amount of serosan-
guinous synovial fluid, which may be slightly cloudy, in-
dicating a small amount of purulent material. The pres-
ence of frank pus, however, is not characteristic of the
lesion. The synovial membrane presents varying degrees
of hyperemia and proliferation (Fig. 31.3), which gives
426 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
the tissue a swollen, somewhat granular appearance, and
often takes irregular forms, producing fringes (“tags”)
that project into the joint cavity. These fringes may be
caught between the articulating surfaces and produce se-
vere pain. The proliferating tissue also may extend across
the surface of articular cartilage, forming a pannus that
leads to destruction of the articular surface and eventu-
ally to fibrosis and ankylosis of the joint. Lymph nodes
associated with arthritic joints are usually enlarged and
edematous.
Vegetative endocarditis consists of proliferative gran-
ular growths on the heart valves and may be accompa-
nied by lesions resulting from cardiac insufficiency. Oth-
er internal organs may show chronic inflammatory
changes such as infarcts of kidneys and spleen. Enlarge-
ment of the adrenal gland has been reported.
MICROSCOPIC LESIONS. Lesions of the synovial
tissue may vary in severity, from slight perivascular accu-
mulation of mononuclear cells to an extensive prolifera-
tive process. The typical synovial lesion in chronic SE is
characterized by pronounced hyperplasia of the synovial
intima and subintimal connective tissue, with vascular-
ization and accumulation of lymphoid cells and
macrophages, forming a villous pad of inflammatory tis-
sue. Deposition and organization of fibrin may be seen.
As the lesion progresses, proliferation of fibrous connec-
tive tissue becomes more prominent, and long fronds of
hyperplastic synovium may be seen. The surface lining
may become necrotic, with deposition of a fibrinous to
fibrinopurulent exudate. Some tendency to follicle for-
mation may be evident in the heavy accumulations of
lymphoid cells. There may be erosion of the articular car-
tilages along with periostitis and osteitis. In old lesions
ankylosis of the involved joint by fibrous adhesion may
be accompanied by calcification.
Vegetative growths on the heart valves are composed
of granulation tissue and superimposed masses of fib-
rin. Connective-tissue proliferation occurs with addition-
al fibrin formation, which can be the source of emboli.
31.3. Synovitis and arthritis
of chronic SE in a hock joint 8
weeks after exposure to E.
rhusiopathiae. Note hyperemia
and proliferation of synovial
tissue. (Courtesy National Animal
Disease Center, Ames, Iowa).
DIAGNOSIS
Clinical and bacteriologic examinations are the most re-
liable means of diagnosis of acute SE.
Clinical Diagnosis
Acute SE often cannot readily be differentiated clinically
from other septicemic diseases, such as Actinobacillus su-
is septicemia (Miniats et al. 1989). Nevertheless, certain
clinical features of an outbreak in a herd are more
characteristic of SE than of other diseases if viewed in
combination. For example, the following are presump-
tive of SE: a history of a few sudden deaths with no pri-
or evidence of illness; several others sick with high tem-
peratures and apparent stiffness in legs; reluctance of
sick pigs to move but unexpected vitality when aroused;
and clear, alert eyes. Other characteristic signs include a
fair appetite in some visibly sick animals; normal to dry
feces; death or recovery of sick animals within a few
days; and, when present, the characteristic rhomboid
skin lesions. Marked improvement within 24 hours after
treatment with penicillin supports the diagnosis. At
necropsy the presence of an enlarged spleen is sugges-
tive.
Bacteriologic Diagnosis
Isolation of E. rhusiopathiae from the acutely affected an-
imal provides a definite laboratory diagnosis of SE. He-
moculture is a useful diagnostic aid in living animals, but
specimens should be taken from several affected animals
in the herd, as the presence of the organism in the blood
of an individual may be inconstant. At necropsy of a pig
that has died in the acute phase, the organism is easily
cultured from a variety of body organs (heart, lungs, liv-
er, spleen, kidneys, joints). If the illness has persisted for
several days, however, the organism often can no longer
be cultured from internal organs but may still be found
in the joints. Under these conditions it is important to
take several specimens of fluid and synovial tissue from
as many synovial sacs of a joint as possible, because the
 CHAPTER 31 ERYSIPELAS Wood
organisms may be present in small numbers and limited
to certain areas.
Culture of E. rhusiopathiae from tissue specimens is
relatively simple and requires only basic laboratory
equipment and culture media such as tryptose or meat
infusion media with or without blood or serum added.
Care should be taken to avoid accidental skin infection,
as the organism is pathogenic for humans. Selective cul-
ture methods for isolation of the organism from conta-
minated specimens are described elsewhere (Cottral
1978).
The use of immunofluorescence for rapid identi-
fication of E. rhusiopathiae has been reported; how-
ever, the method may not be sufficiently specific and sen-
sitive for routine diagnostic purposes (Harrington et al.
1974).
Serologic Diagnosis
A variety of serologic tests have been used in attempts to
diagnose SE. These include plate, tube, and microtitra-
tion agglutination; passive hemagglutination; hemagglu-
tination inhibition; complement fixation; enzyme-linked
immunosorbent assay (ELISA); and indirect immunoflu-
orescence. An agglutination test involving the use of
growing culture as antigen was developed by Wellmann
(1955). In this test, called the Wachstumsprobe or growth-
agglutination test, a culture of E. rhusiopathiae growing
in liquid medium in the presence of sterile test serum ag-
glutinates if sufficient specific antibody is present.
No serologic test has proved useful for routine diag-
nosis of acute infection or for differentiation between
immune and susceptible pigs. Serologic diagnosis may
have some value in detection of chronic infection, pri-
marily on a herd basis. Microtitration agglutination,
growth agglutination, and ELISA are probably the most
reliable for this purpose but may be difficult to interpret.
It can be concluded that serologic testing has limited
practical application in clinical diagnosis of SE in the
field. The chief value of serologic procedures resides in
research.
TREATMENT
The treatment of SE with hyperimmune serum, usually
obtained from horses, was introduced in 1899, several
years after it had been developed for use in conjunction
with live-culture vaccination. Until the introduction of
antibiotics nearly 50 years later, the administration of
antiserum was the only worthwhile available form of
treatment. Although now considered obsolete by some
veterinarians, antiserum can still be useful. For maxi-
mum effectiveness the serum must be given early in the
course of the disease. The recommended therapeutic
dose, given subcutaneously, varies from 5 to 10 mL for
pigs weighing less than 50 pounds (23 kg) to 20–40 mL
for pigs weighing more than 100 pounds (45 kg).
It is generally accepted that the treatment of choice
427
for acute erysipelas is administration of penicillin. E.
rhusiopathiae is highly sensitive to this antibiotic, and
treatment early in an acute outbreak usually results in
dramatic response within 24–36 hours. Specific treat-
ment regimens generally involve giving penicillin alone
or in combination with other antibiotics or antiserum
(occasionally both) to provide a longer action. For exam-
ple, long-acting penicillin (available under various pro-
prietary names), consisting of a combination of 150,000
units procaine penicillin G and 150,000 units benzathine
penicillin G/cm3, may be given intramuscularly at a sin-
gle dose of 5000–10,000 units/pound (454 g) to visibly
sick pigs (the entire herd may be treated with tetracycline
in the drinking water: 500 mg/gallon, 132 mg/L) until 5
days after no sick pigs are observed. The entire herd may
also be given antiserum if the outbreak is very severe. As
an alternative, long-acting penicillin may be given in se-
vere outbreaks, and procaine penicillin G in less severe
cases. The use of antiserum for treatment of suckling
pigs is a fairly common practice. Initiation of a vaccina-
tion program in previously unvaccinated herds where
outbreaks occur is strongly recommended.
Although penicillin has been consistently found to be
the most effective antibiotic for treatment of acute SE,
satisfactory results have been reported also with tetracy-
clines (including chlortetracycline and oxytetracycline),
lincomycin, and tylosin. The organism is sensitive in
vitro to erythromycin, but this antibiotic has been re-
ported to be relatively ineffective in vivo. Streptomycin,
dihydrostreptomycin, chloramphenicol, bacitracin,
polymyxin B, neomycin, and sulfonamides are not effec-
tive against SE. There have been no published reports of
development of resistance by E. rhusiopathiae to peni-
cillin in the field since use of the antibiotic for treatment
of SE was first reported in 1949. However, some isolates
of the organism from swine have been found to be resis-
tant to tetracyclines.
There is no practical treatment for chronic SE. Exper-
imentally, the administration of antiinflammatory
agents has provided some alleviation of the effects of
chronic arthritis, and they may be used in treatment of
especially valuable individual animals.
PREVENTION
Prevention of SE is best accomplished by sound prac-
tices of herd health management, including a program of
immunization.
General Management Practices
Swine should be raised according to sound husbandry
practice relative to nutrition, housing, and condition of
lots and pastures, and they should be observed regularly
for deviations from their usual attitude. Replacements
should be obtained from clean sources. The recent intro-
duction of a new boar is a relatively common historical
finding preceding acute outbreaks of SE in a herd. New-
428 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
ly purchased animals should be isolated for at least 30
days.
It is advisable to eliminate chronically affected swine
from the herd, as they can remain carriers of the organ-
ism indefinitely.
Good sanitation is important in general herd man-
agement and is essential following the cessation of an
outbreak. Walls and floors should be cleaned and disin-
fected. Phenolic, alkali, hypochlorite, or quaternary am-
monium disinfectants are effective against the organism
but must be applied to clean surfaces.
Immunization
A variety of biological products have been produced for
the purpose of conferring immunity to SE in swine. The
simultaneous or serum-culture method of immunization
was introduced in 1893 and consists of concomitant in-
jections of virulent culture and antiserum. This method
was first used in the United States in 1938, and its use
continued for about 20 years until safer products became
available. The method is no longer used. Active immu-
nization against SE is now carried out by the use of either
attenuated (so-called avirulent) vaccines or nonliving
products (bacterins).
ATTENUATED VACCINES. Vaccines made from E.
rhusiopathiae of reduced virulence were first licensed in
the United States in 1955. Attenuation of virulence has
been accomplished by passage through rabbits or chick-
en embryos, by air-drying, or by growth in media con-
taining acridine dyes. Although these vaccines are com-
monly referred to as avirulent, they are in fact strains of
extremely low virulence for swine, often retaining some
virulence for mice. They stimulate immunity in swine by
limited multiplication in the body; therefore, the re-
sponse to vaccination is subject to such variables as sta-
tus of passive or active immunity already existing in the
animal. In addition, there is some evidence that anti-
serum given concomitantly may interfere with develop-
ment of immunity in response to attenuated vaccines.
Manufacturers generally do not recommend use of
serum with their attenuated products except when im-
mediate protection is necessary, as in the case of suckling
pigs being given both vaccine and serum during a herd
outbreak. In this case, repeated vaccination at weaning is
recommended.
Attenuated vaccines should not be given to swine be-
ing treated with antibiotics to which E. rhusiopathiae is
sensitive. Antibiotic treatment should be discontinued at
least 8–10 days before vaccination.
Attenuated vaccines are usually given by injection or
administered orally in drinking water. Some manufac-
turers provide a product that can be given either way. In
some parts of Europe and the former Soviet Union, vac-
cination by aerosol has been practiced. Elaborate equip-
ment for generating and distributing the aerosol is nec-
essary.
Use of living vaccines leaves open the possibility,
however remote, of vaccinated animals becoming carri-
ers and disseminators of the organism, which conceiv-
ably could undergo increased virulence through serial
passage. There is no experimental evidence, however,
that attenuated SE vaccines can regain their virulence
and pose a hazard to susceptible swine.
BACTERINS. Use of a bacterin consisting of a forma-
lin-killed whole culture adsorbed on aluminum hydrox-
ide gel was first reported in 1947. This type of product
has been used in the United States since 1953. It is typi-
cally made from selected strains of serovar 2 that pro-
duce a soluble immunogenic product when grown in a
complex liquid medium containing serum. This sub-
stance, most of which is released into the medium, has
been described as a glyco-lipoprotein (White and Verwey
1970). It is considered by most investigators to be a nec-
essary ingredient for stimulation of immunity by the
bacterin. The most active component of the immuno-
genic substance has been identified as a protein fraction
with a molecular weight of 64–66 kDa (Timoney and
Groschup 1993; Sato et al. 1995; Goodman 1996;
Zarkasie et al. 1996). The combination of the soluble im-
munogenic product and whole killed bacteria, concen-
trated and adsorbed on aluminum hydroxide gel or oth-
er suitable adjuvant, constitutes the basic features of an
E. rhusiopathiae bacterin.
Lysate bacterin, first reported in 1953, has been used
in the United States since 1955. It is similar to whole-cul-
ture bacterin except that the bacterial cells have been
lysed.
Bacterins are given by subcutaneous or intramuscu-
lar injection; a second (booster) injection in 3–5 weeks is
generally recommended. Breeding animals should be
given an additional booster injection annually.
PASSIVE IMMUNITY. Temporary passive immunity
can be induced by administration of commercially avail-
able antiserum. Pigs given antiserum subcutaneously re-
ceive immediate passive protection, which persists for
about 2 weeks. The preventive dose is half the therapeu-
tic dose (see the section on treatment). Antiserum may
be useful during a herd outbreak for temporary protec-
tion of suckling pigs until they are old enough to be vac-
cinated.
MECHANISM OF IMMUNITY. The mechanism of
immunity to E. rhusiopathiae infection is not clearly de-
fined, but there is little doubt that opsonization is a ma-
jor factor. Studies have shown that virulent E. rhu-
siopathiae bacteria opsonized with immune serum were
readily eliminated by polymorphonuclear leukocytes
 CHAPTER 31 ERYSIPELAS Wood
(Sawada et al. 1988) and by macrophages (Shimoji et al.
1996). Nonopsonized virulent organisms were resistant
to phagocytosis.
EFFICACY OF BIOLOGICS. No presently available
immunizing product adequately fills the need for effec-
tive long-term protection against SE. Some veterinarians
consider living vaccines to be superior to bacterins, but
Shuman (1959) found no significant difference in their
efficacies under experimental conditions. According to
most reports, vaccination generally can be expected to
induce immunity lasting 3–5 months. A second (boost-
er) injection may increase this duration to 6 months and
is recommended, especially for bacterins. Development
of immunity in vaccinated swine may be adversely af-
fected by such environmental factors as overheating or
poor nutrition.
A serious deficiency of SE vaccination is its inability
to prevent the chronic form. Most investigators agree
that vaccination has little effect on the incidence of
arthritis caused by E. rhusiopathiae, although this obser-
vation is difficult to evaluate in the field, since SE vacci-
nation is not universally practiced in the United States. It
is possible that vaccination reduces the overall preva-
lence of arthritis by reducing the prevalence of acute
erysipelas. On the other hand, some believe vaccination
actually causes an increase in arthritic lesions by initiat-
ing a state of hypersensitivity to subsequent contact with
the organism. An alternative explanation for the failure
of vaccination to prevent arthritis may exist, however.
The organism may be carried to synovial tissues by
loaded macrophages soon after exposure, thereby escap-
ing the opsonic effects of humoral immunity (Drommer
et al. 1970). Sequestration of the bacteria in chondro-
cytes (Franz et al. 1995) might provide similar protection
from immune mechanisms.
It is possible that certain uncommon serovars of E.
rhusiopathiae may be refractory to the immunity induced
in mice and swine by standard SE vaccines. However,
such serovars are usually isolated from healthy carrier
pigs or nonporcine sources, and none have been directly
associated with cases of acute SE in the field.
Although vaccination against SE is not entirely effec-
tive in preventing the disease, it provides a worthwhile
means of control when used with other good manage-
ment practices. A regular vaccination program for both
breeding and market animals is recommended. Because
of the ubiquity of E. rhusiopathiae, together with its
poorly understood ability to exist in nature, the possibil-
ity of eradication of the organism seems remote.
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 Escherichia coli Infections
32 H. U. Bertschinger and J. M. Fairbrother
INTRODUCTION
H. U. Bertschinger
The genus Escherichia is named after the German pedia-
trician Theodor Escherich (1857–1911). It is classified
with the family Enterobacteriaceae, which belongs to the
gram-negative facultatively anaerobic rods. The species
Escherichia (E.) coli includes normal inhabitants of the
gastrointestinal tract and organisms causing a broad va-
riety of intestinal and extraintestinal diseases in the
porcine species.
BACTERIOLOGY
E. coli are gram-negative, peritrichous flagellated rods of
variable length and with a diameter of about 1 µm.
Colonies on solid media reach their full size within 1 day
of incubation. The appearance may vary from smooth to
rough or mucoid. There is a broad range of selective me-
dia available. Some strains produce hemolysins. Species
identification relies mainly on biochemical characters. It
should be borne in mind that there are exceptions with
every single biochemical character. Commercially avail-
able identification kits therefore make use of up to 50
characters to achieve a high level of accuracy. The inter-
pretation may be facilitated by computer-assisted pro-
cessing of the data. The determination of DNA related-
ness, the scientific base of discrimination between
species, is restricted to research laboratories.
SEROTYPING
There are several ways to subdivide the species into
types. So far, serotypes have shown the best association
with certain virulence traits. Complete serotyping in-
cludes determination of O (somatic), K (capsular or mi-
crocapsular), H (flagellar), and F (fimbrial) antigens. Un-
like salmonellae, only a small percentage of E. coli
isolates are typeable with available antisera, since sero-
typing has been limited to isolates of proven or sus-
pected pathogenicity. Presently, at least 173 O, 80 K, 56
H, and a fast-growing number of F antigens are officially
recognized.
In diagnostic laboratories serotyping is often reduced
to one or two classes of antigens and to a limited spec-
trum of antisera. This may be quite suitable, since in a
given region, animal species, and organ, pathogenic
serotypes maintain their characteristic antigenic make-
up. Thus one may deduce the complete serotype from a
simple slide agglutination with a living culture. Serotyp-
ing is diagnostically helpful in communicable types of
disease caused by a limited number of serotypes, such as
postweaning E. coli diarrhea and edema disease.
VIRULENCE FACTORS
Bacterial traits involved in pathogenesis are called
virulence factors. Much has been learned in this fast-
progressing field (Gyles 1994), but we are far from
understanding every step in the development of the
different kinds of disease caused by E. coli. Potent
exotoxins trigger the secretion of fluid into the gut
lumen in enterotoxigenic E. coli (ETEC) infections and
are responsible for systemic pathology caused by entero-
toxemic E. coli (ETEEC) strains. Endotoxin is present in
the outer membrane of most E. coli strains. Its signifi-
cance is well documented only in extraintestinal infec-
tions, such as septicemia, mastitis, and urinary tract in-
fections.
Many E. coli infections require the colonization of
mucous membranes. With ETEC and ETEEC, adhesion
to the small intestine is mediated by extracellular pro-
teinaceous appendages, which are called fimbriae or pili
and are highly host-specific. In some strains capsular
polysaccharide has been shown to enhance the ability to
colonize. Enteropathogenic E. coli (EPEC) colonizing the
lower gastrointestinal tract adhere by an attaching and
effacing mechanism. In the pig, colonization of the uri-
nary tract has received little attention so far.
Some E. coli utilize high-affinity iron-uptake systems
to compete with the host for available iron. In extrain-
testinal sites E. coli have to resist the natural bactericidal
activity of serum, a characteristic called serum resis-
tance. A given pathogenic strain may exhibit a whole set
of virulence factors, that is, more than one toxin and
even more than three adhesion factors. Detection of
more virulence factors can be expected.
431
432 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
GENETICS OF VIRULENCE
Very specific sets of virulence factors are needed to cause
a particular disease. Thus, strains causing enteric dis-
eases are not associated with extraintestinal infections
and vice versa. E. coli strains may be classed into patho-
types based on the production of particular virulence de-
terminants. Many virulence factors examined so far are
plasmid determined. This applies in particular to he-
molysins, toxins, and adhesins of ETEC. In strains from
most extraintestinal infections, however, the genes en-
coding for fimbriae, cytotoxins, and hemolysin are chro-
mosomally located. In the laboratory, plasmids can easi-
ly be transmitted from donor to recipient strains.
However, such exchanges of genetic material do not ap-
pear to play a major role in the field. The genetic makeup
of pathogenic E. coli strains is remarkably stable. This
may be because a whole set of virulence factors is in-
volved in the virulence of a particular strain, and certain
recipient strains may not express transmitted plasmid-
determined functions. The clinically important develop-
ment of antimicrobial resistance is an exception to this
observation.
The time-consuming and sometimes cumbersome as-
says for virulence factors are increasingly being replaced
by hybridization and polymerase chain reaction (PCR)
techniques. However, these techniques are not yet used
in all diagnostic laboratories.
ECOLOGY
The particular ecology of pathogenic E. coli strains has
been somewhat neglected. Intestinal infections caused
by ETEC and ETEEC are often contagious. The same
strain is usually found in many sick pigs and often in con-
secutive batches of pigs. When edema disease spread
through Denmark, 63% of the outbreaks were connected
by trade of pigs to one single infected breeding herd (Jor-
sal et al. 1996). On the other hand, clinical edema disease
occurred in no more than 5% of the herds with trading
contacts. These strains may sometimes appear in healthy
pigs without overt disease. They are usually shed in high
numbers for a period of a few days only. The ensuing
dramatic decrease seems to be due to the development of
local immunity.
Extraintestinal infections, however, do not behave
like communicable diseases. Individual pigs in a given
herd are affected most often by different strains. Mixed
infections by more than one strain are frequent. In hu-
mans, the fecal flora is obviously the reservoir of such
pathogenic strains. In 18 out of 67 sows with mastitis, E.
coli of the same O types present in samples of mammary
secretion were isolated from the feces (Awad-Masalmeh
et al. 1990). This underlines the endogenous character of
most extraintestinal infections in the pig as well.
The primary habitat of porcine E. coli is the gastroin-
testinal tract. The E. coli flora of individual pigs is ex-
tremely complex. When strains were distinguished by
the combined application of O serogrouping, biotyping,
and resistogram typing, up to 25 strains were identified
in the gastrointestinal tract of one individual (Hinton et
al. 1985). Numerically dominant strains change at inter-
vals from 1 day to several weeks, leading to successive
waves of dominant strains (Katouli et al. 1995). Prolifer-
ation of E. coli takes place mainly in the course of the
passage through the small intestine. Increase from the
ileum to the rectum is minimal or absent (McAllister et
al. 1979). Numbers in the large intestine fluctuate
around 107 colony-forming units/g. However, E. coli con-
tribute less than 1% to the total bacterial count. When
found elsewhere (feed, water, soil, etc.), E. coli are derived
from this habitat, usually by fecal contamination. Long
survival times in the environment are promoted by low
temperature and sufficient available water, among other
factors. In an experiment with five slurry samples, a
porcine E. coli O139:K82(B) retained viability for be-
tween 5 and over 11 weeks (Burrows and Rankin
1970).
REFERENCES
Awad-Masalmeh, M.; Baumgartner, W.; Passernig, A.; Sil-
ber, R.; and Hinterdorfer, F. 1990. Bakteriologische Un-
tersuchungen bei an puerperaler Mastitis (MMA-Syn-
drom) erkrankten Sauen verschiedener Tierbestände
Österreichs. Tierärztl Umschau 45:526–535.
Burrows, M. R., and Rankin, J. D. 1970. A further examina-
tion of the survival of pathogenic bacteria in cattle slur-
ry. Br Vet J 126:32–34.
Gyles, C. L. 1994. Escherichia coli in Domestic Animals and
Humans. Wallingford, U.K.: CAB International.
Hinton, M.; Hampson, D. J.; Hampson E.; and Linton, A. H.
1985. A comparison of the ecology of Escherichia coli in
the intestine of healthy unweaned pigs and pigs after
weaning. J Appl Bact 58:471–478.
Jorsal, S. E.; Aarestrup, F. M.; Ahrens, P.; Johansen, M.; and
Baekbo, P. 1996. Oedema disease in Danish pig herds:
Transmission by trade of breeding animals. Proc Int
Congr Pig Vet Soc 14:265.
Katouli, M.; Lund, A.; Wallgren, P.; Kühn, I., Söderlind, O.;
and Möllby, R. 1995. Phenotypic characterization of in-
testinal Escherichia coli of pigs during suckling, post-
weaning and fattening periods. Appl Environ Microbiol
61:778–783.
McAllister, J. S.; Kurtz, H. J.; and Short, E. C., Jr. 1979.
Changes in the intestinal flora of young pigs with post-
weaning diarrhea or edema disease. J Anim Sci
49:868–879.
 CHAPTER 32 ESCHERICHIA COLI INFECTIONS
NEONATAL ESCHERICHIA COLI DIARRHEA
J. M. Fairbrother
Diarrhea has become an economically important disease
in pigs as a result of increasing intensification of farrow-
ing management. It may be classified into three main en-
tities: neonatal diarrhea (within the first few days of
birth), young piglet diarrhea (from the first week of birth
to weaning), and postweaning diarrhea. Escherichia coli
is the most important etiologic agent of neonatal and
postweaning diarrhea. Etiologic agents of diarrhea in
young piglets are more numerous and include transmis-
sible gastroenteritis virus, rotavirus, coccidia, and E. coli
(Biehl and Hoefling 1986). E. coli are normal inhabitants
of the intestinal tract of animals but may also cause dis-
ease. Pathogenic enteric E. coli belong to a restricted
number of serogroups and produce one or more viru-
lence factors, which are not usually found in nonpatho-
genic E. coli. Over the last several years, our knowledge of
enteric E. coli virulence factors and their role in the
pathogenesis of enteric disease has rapidly expanded.
The terminology used to describe pathogenic E. coli has
greatly changed. Thus, E. coli may now be categorized by
pathotype, based on production of virulence factors.
Specific E. coli pathotypes are associated with each of the
main disease entities. A less frequently encountered
manifestation of enteric E. coli infection is an acute shock
syndrome which provokes gross lesions of hemorrhagic
gastroenteritis. Neonatal diarrhea in pigs has been re-
viewed by Alexander (1994).
ETIOLOGY
Neonatal diarrhea associated with E. coli is observed
most commonly in pigs aged from 0 to 4 days. Causative
strains produce one or more enterotoxins and have been
designated enterotoxigenic E. coli (ETEC). ETEC adhere
to the small intestinal mucosa in neonatal pigs by means
of one or more of the fimbrial adhesins F4 (K88), F5
(K99), F6 (987P), or F41 (Table 32.1). They colonize the
small intestine and produce one or more of the entero-
Table 32.1. Predominant E. coli pathotypes associ-
ated with neonatal diarrhea in piglets
Toxin(s) Fimbrial Adhesins O Serogroups
STa F5, F5 + F41, F6, F6 + F41 O8, O9, O20, O64, O101
F41, F5 + 6, F5 + F6 + F41 O141
Sta + STb F4, F4 + 5, F5 + F6, F6, O20, O64, O141
not known
LT + STb F4, F4 + F6 O8, O147, O149, O157
LT + Sta +
STb F4, F4 + F6 O8, O147, O149, O157
STb F4, F6, not known O149
Bertschinger, Fairbrother 433
toxins STa (STI), STb (STII), or LT. Until recently, the
most commonly observed ETEC in cases of neonatal di-
arrhea belonged to the classic serogroups O149, O8,
O147, and O157, were F4-positive, and produced the en-
terotoxins LT and STb (Harel et al. 1991; Soderlind et al.
1988; Wilson and Francis 1986). An increasing number
of ETEC of serogroups such as O8, O9, O64, and O101
which are F5-, F6-, and/or F41-positive and mainly pro-
duce the enterotoxin STa, or less often STb, are now be-
ing isolated. These ETEC cause diarrhea mainly in pigs
aged from 0 to 6 days, and to a lesser extent in older pigs,
whereas F4-positive ETEC are often isolated in diarrheic
pigs from birth to weaning. Fewer F4-positive ETEC
within the classic serogroups, especially O157, are now
being isolated.
Enteric colibacillosis complicated with shock also oc-
curs in young pigs before and after weaning. E. coli asso-
ciated with this disease either (1) are ETEC and com-
monly belong to serogroups O149, O157, and O8, which
are F4-positive, produce STb and LT, but only occasion-
ally produce Shiga-like toxin (SLT-IIe) (Faubert and Dro-
let 1992), or (2) produce SLT-IIe and are associated with
edema disease. The latter will be discussed in a later sec-
tion.
EPIDEMIOLOGY
The occurrence of E. coli diarrhea depends on an interac-
tion between the causative bacteria, environmental con-
ditions, and certain host factors. Only E. coli that carry
virulence factors as described in the previous section and
are ingested in large numbers are able to cause diarrhea.
The newborn pig, on leaving the uterus and before reach-
ing the teats of the sow, encounters the heavily contami-
nated environment of the farrowing crate and the skin of
the dam, resulting in ingestion of microbes from the in-
testinal flora of the sow. Thus, in conditions of poor hy-
giene or in a continuous-farrowing system, a buildup of
pathogenic E. coli in the environment could lead to an
outbreak of neonatal E. coli diarrhea. The colostrum con-
tains nonspecific bactericidal factors and specific anti-
body (IgA) that inhibit the adherence of pathogenic E.
coli in the intestine. If the dam has not been exposed to
the pathogenic E. coli present in the environment of the
piglets, specific antibodies are not present in the
colostrum, and the piglets are susceptible to infection.
Similarly, when individual piglets do not have access to
colostrum, due to injury or inability to compete or due to
agalactia or insufficient teats of the sow, they are more
susceptible to infection. Ambient temperature in the far-
rowing house is also very important. In pigs kept at tem-
434 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
peratures of less than 25˚C, intestinal peristaltic activity
is greatly reduced, and passage of bacteria and protective
antibodies through the intestine is delayed (Sarmiento
1983). Increased numbers of pathogenic E. coli in the in-
testinal tract of these pigs result in a more severe diar-
rhea than in pigs kept at 30˚C.
PATHOGENESIS
In the presence of the appropriate predisposing environ-
mental conditions and host factors, pathogenic E. coli
proliferate in the intestine and cause diarrhea by means
of specific virulence factors. Pathogenesis will be dis-
cussed with respect to the E. coli categories defined by the
production of these factors.
Enterotoxigenic E. coli
Most pathogenic E. coli produce one or more fimbrial ad-
hesins that mediate their attachment to specific recep-
tors on mucosal epithelial cells and in the adjacent
mucous layer. These fimbriae (or pili) are hairlike ap-
pendages extending from the bacterial cell and consist of
structural protein subunits that, in many cases, act as a
support for a separate adhesive protein found at the tips
of the fimbriae. Fimbriae are classified by serologic reac-
tivity or by receptor specificity, the latter being manifest-
ed by agglutination of red blood cells from different ani-
mal species. The nomenclature for fimbriae has been
very diverse. For example, the first fimbrial adhesins
demonstrated on porcine ETEC were thought to be cap-
sular antigens and were named K88 and K99. A more
standardized nomenclature based on serologic activity in
crossed immunoelectrophoresis and using an F designa-
tion has been proposed (Orskov and Orskov 1983). The
latter nomenclature will be used in this chapter.
Although an increasing number of fimbrial adhesins
have been described (more than 30), most fimbrial ad-
hesins, with the exception of F1 (type 1) common fim-
briae, are associated with E. coli of particular serogroups
isolated from specific animal species. F1 fimbriae are
found on most E. coli isolates and cause an agglutination
of guinea pig red cells which is inhibited by D-mannose.
Their role in attachment of porcine ETEC to the intesti-
nal mucosa is still unclear (Jayappa et al. 1985; To et al.
1984).
We have found only F1 and no other known fimbrial
adhesins on certain diarrheagenic ETEC strains (Broes et
al. 1988). The four important fimbrial adhesins of
neonatal porcine ETEC are F4 (K88), F5 (K99), F6
(987P), and F41. F4 (K88) fimbriae have been divided in-
to three variants, F4ab, F4ac, and F4ad, based on sero-
logic cross-reactions (Guinée and Jansen 1979). Many
ETEC isolates produce more than one fimbrial adhesin,
and common combinations are F5 and F6, F5 and F41,
and F4 and F6. Production of fimbriae is controlled by
genes on the bacterial chromosome (F1, F41) or on plas-
mids (F4, F5, F6). Many fimbriae, such as F1 and F6, un-
dergo phase variation and may be very poorly expressed
after several passages in culture conditions. Other fim-
briae (F5 and F41) undergo quantitative variation and
are only well expressed in culture media low in glucose or
alanine such as Minca medium (Guinée et al. 1977).
Fimbriae adhere to specific receptors on the cell
membrane of intestinal epithelial cells and to specific re-
ceptors or nonspecifically in the mucus coating the ep-
ithelium. ETEC producing fimbriae F5, F6, and F41
mostly colonize the posterior jejunum and ileum, where-
as F4-positive ETEC tend to colonize the length of the je-
junum and the ileum. Certain pigs do not have receptors
for the F4 adhesin on intestinal epithelial cells and are
thus resistant to infection by F4-positive ETEC (Sellwood
et al. 1975). This genetic resistance to infection is inher-
ited in a simple Mendelian way, and the allele for the re-
ceptor is dominant. Subsequent studies have demon-
strated at least five pig phenotypes, based on
susceptibility of brush borders of different pigs to ad-
herence of isolates producing the different variants F4ab,
F4ac, and F4ad (Bijlsma et al. 1982; Hu et al. 1993). The
loci encoding porcine intestinal receptors for F4ab and
F4ac are closely linked on chromosome 13 (Edfors-Lilja
et al. 1995). A similar genetic resistance has not been ob-
served for the other fimbriae of neonatal porcine ETEC.
On the other hand, there appears to be an age resistance
to infection by F5-positive isolates, which is not observed
for F4-positive isolates. Piglets are most susceptible to in-
fection with F5-positive ETEC during the first several
days of life and subsequently become more resistant.
This susceptibility could be related to a reduction of the
number of receptors present on intestinal epithelial cells
with age (Runnels et al. 1980).
ETEC adhering to the intestinal mucosa produce en-
terotoxins which change the water and electrolyte flux of
the small intestine and may lead to diarrhea if the excess
fluid from the small intestine is not absorbed in the large
intestine. Two major classes of enterotoxin are produced
by porcine ETEC: heat-stable toxin (ST), which is resis-
tant to heat treatment at 100˚C for 15 minutes, and heat-
labile toxin (LT), which is inactivated at 60˚C for 15 min-
utes (Guerrant et al. 1985). ST has been further divided
into STa and STb based on solubility in methanol and bi-
ological activity (Burgess et al. 1978). The E. coli entero-
toxins have been reviewed in detail (Gyles 1994).
LT is a high-molecular-weight toxin complex that
consists of five B subunits able to bind to ganglioside re-
ceptors on the intestinal epithelial cell surface and a bio-
logically active A subunit (Gill et al. 1981). After binding,
the latter activates adenylate cyclase, which stimulates
the production of cyclic AMP. High levels of cyclic AMP
in the cell result in increased secretion of Cl, Na, HCO3,
and water into the intestinal lumen. Excessive secretion
will lead to dehydration, metabolic acidosis, and eventu-
ally death. Two subgroups of LT, LTI and LTII, have been
 CHAPTER 32 ESCHERICHIA COLI INFECTIONS
described (Holmes et al. 1986). Only LTI is neutralized
by anticholera toxin. LT produced by porcine isolates be-
longs to the LTI subgroup. The LT produced by human
and porcine ETEC has been designated LTh and LTp
based on slight differences in the genes coding for the
toxin.
STa (STI, ST1, and ST mouse) is a small, nonim-
munogenic protein with a molecular weight (MW) of
2000 (Lallier et al. 1982). STa binds to a guanylyl cyclase
intestinal epithelial receptor (De-Sauvage et al. 1991)
and activates guanylate cyclase, which stimulates pro-
duction of cyclic GMP. High levels of cyclic GMP in the
cell inhibit the Na/Cl cotransport system and reduce the
absorption of electrolytes and water from the intestine
(Dreyfus et al. 1984). STa is active in infant mice and
young piglets of less than 2 weeks of age but is less active
in older pigs. This could be due to differences in the con-
centration of intestinal receptors with age (Cohen et al.
1988). As with LT, STa produced by human and porcine
ETEC has been designated STah and STap, based on dif-
ferences in the genes coding for the toxin.
STb (STII, ST2, ST pig) is a small, 5000 MW protein
that is antigenically and genetically unrelated to STa and
is poorly immunogenic (Dubreuil 1997). STb stimulates
cyclic-nucleotide-independent fluid secretion in the gut
(Kennedy et al. 1984), which is independent of the cyclic
nucleotides but appears to be mediated by prostaglandin
E2 and possibly other secretagogues (Harville and Drey-
fus 1995; Peterson and Whipp 1995). STb is inactivated
by trypsin and, in the presence of trypsin-inactivator, is
active in intestines of mice, rats, and calves (Whipp
1990). STb is found in 74% of all porcine ETEC isolates;
33% of ETEC from older pigs with enteric colibacillosis is
only positive for STb (Moon et al. 1986). The role of STb
in the development of diarrhea is not yet known, al-
though ETEC producing only STb can induce diarrhea in
experimentally infected newborn pigs (Fairbrother et al.
1989), and STb induces some villous atrophy in pig in-
testinal gut loops (Rose et al. 1987).
Attaching and Effacing E. coli
Porcine attaching and effacing E. coli (AEEC) attach to
the intestinal mucosa and cause lesions similar to those
observed for enteropathogenic E. coli (EPEC) isolated
from human infantile diarrhea (Hélie et al. 1990). They
attach intimately to the intestinal epithelial cell mem-
brane by means of a bacterial outer-membrane protein
termed “intimin” or “EPEC attaching and effacing factor”
(Eae), efface the microvilli, and invade the epithelial cells
(Zhu et al. 1994).
CLINICAL SIGNS
Enteric E. coli infection is usually manifested by diarrhea,
the severity of which depends on the virulence factors of
the E. coli and the age and immune status of the piglets.
Bertschinger, Fairbrother 435
In severe cases, clinical signs of dehydration, metabolic
acidosis, and death are observed. In certain cases, partic-
ularly in young animals, the infection may be so rapid
that death occurs before the development of diarrhea.
Neonatal diarrhea may first be observed 2–3 hours
after birth and may affect single pigs or whole litters. Gilt
litters are more often affected than sow litters. A large
number of piglets in a farrowing house may be affected
and mortality may be very high in the first few days of
life. Diarrhea may be very mild with no evidence of de-
hydration or may be clear and watery. The feces vary in
color from clear to whitish or various shades of brown.
The fecal material may just dribble from the anus down
the perineum and only be detected by close examination
of the perineal area. In very severe outbreaks, a small
proportion of affected animals may vomit. In severe cas-
es, 30–40% of total body weight may be lost as fluid into
the intestinal lumen and result in signs of dehydration.
The abdominal musculature is flaccid and atonic, the
pigs are depressed and sluggish, the eyes may be sunken,
and the skin may be bluish-gray in color and resemble
parchment in texture. The loss of fluid and weight re-
sults in the exaggerated appearance of the bony promi-
nences. These animals usually die. In more chronic or
less severely affected cases, the anus and perineum may
be inflamed from contact with the alkaline fecal materi-
al. Pigs with less severe dehydration may continue to
drink and, if treated appropriately, may recover with on-
ly minimal long-term effects.
Diarrhea in pigs from the neonatal to the postwean-
ing period is similar to that observed in neonatal piglets
but tends to be less severe. Morbidity may be the same as
in the neonatal period but mortality is invariably lower.
The feces vary from grayish to whitish in unweaned
piglets to brownish in recently weaned piglets. Enteric
colibacillosis complicated by shock, when associated
with ETEC strains, occurs both in unweaned pigs from a
few days of age and in recently weaned pigs (Faubert and
Drolet 1992), in contrast to earlier reports. Apparently
healthy pigs die suddenly or decline rapidly with
cyanosis of the extremities. A yellowish to brownish di-
arrhea is sometimes observed.
LESIONS
Few specific pathological changes may be attributed to
enteric E. coli infection. Gross lesions that may be ob-
served include dehydration, dilation of the stomach
(which may contain undigested milk curd or feed in the
case of postweaning diarrhea), venous infarcts on the
greater curvature of the stomach, and dilation of the
small intestine with some congestion of the small-in-
testinal wall. In cases of ETEC infection complicated by
shock, characteristic lesions include marked congestion
of the small-intestinal and stomach walls and blood-
tinged intestinal contents.
436 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
Histologic lesions depend on the category of E. coli
involved. In ETEC infections, layers of E. coli are ob-
served adhering to the mucosal epithelial cells of most of
the jejunum and ileum in the case of F4-positive ETEC
isolates, and of the posterior jejunum and/or the ileum
in the case of other ETEC isolates. Adhering bacteria may
be found only in the crypts of Lieberkühn, or more often
covering the crypts and the tips of the villi. On transmis-
sion electronmicroscopy, bacteria are usually located ap-
proximately half a bacterial width away from the mi-
crovilli, and fimbriae may sometimes be visualized
between the bacteria and the microvilli (Fig. 32.1). His-
tological lesions, if observed, may include vascular con-
gestion in the lamina propria with some hemorrhages in-
to the intestinal lumen, increased numbers of
neutrophils and macrophages in the lamina propria and
migrating into the lumen, and some villous atrophy. In
cases of ETEC enteric infection complicated by shock, E.
coli are found adhering to the mucosal epithelial cells of
the small intestine. Congestion, some hemorrhages, and
in severe cases villous necrosis and microvascular fibri-
nous thrombi are observed in the lamina propria of the
stomach, small intestine, and colon.
In pigs infected with AEEC isolates, a multifocal colo-
nization of the brush border of mature enterocytes by E.
32.1. Electron micrograph of attachment of E. coli
987P positive strain in the intestine.
coli arranged in palisades with enterocyte degeneration
and light to moderate inflammation of the lamina pro-
pria is observed, mostly in the ileum (Hélie et al. 1990).
Colonization is most intense in the duodenum and ce-
cum, bacteria are sometimes observed in intracytoplas-
mic vacuoles in enterocytes, and there is a light to mod-
erate villous atrophy in the small intestine. On
transmission electronmicroscopy, bacteria are intimate-
ly attached to the cytoplasmic membrane of mature en-
terocytes and arranged in regular palisades, parallel to
the microvilli, with effacement of adjacent villi (Fig.
32.2). The bacterial cell wall and the apical cell mem-
brane of the enterocyte are separated by a narrow, regu-
lar gap of 10 nm at the cupping pedestal, and apical
dense regions are seen at attachment sites.
DIAGNOSIS
Enteric E. coli infection in young, unweaned pigs must be
differentiated from other common infectious causes of
diarrhea in pigs of this age group. These include Clostrid-
ium perfringens, transmissible gastroenteritis virus, ro-
tavirus, and coccidia. More than one etiologic agent may
be associated with a particular animal or outbreak. A
presumptive diagnosis may be made by determination of
32.2. Electron micrograph of AEEC lesions.
 CHAPTER 32 ESCHERICHIA COLI INFECTIONS
the fecal pH. Secretory diarrheic fluid as a result of en-
teric ETEC infection has an alkaline pH, whereas that
from diarrheas associated with malabsorption as a result
of transmissible gastroenteritis virus or rotavirus infec-
tion are acid.
Diagnosis of enteric E. coli infection is based on clin-
ical signs, histopathological lesions, and the presence of
gram-negative organisms usually closely adhering to the
small-intestinal mucosa (Wilson and Francis 1986). This
diagnosis is strengthened by the isolation of E. coli of the
appropriate serogroup or, more important, possessing
one or more of the above-mentioned virulence factors.
Detection of production of enterotoxins and cytotoxins
has been arduous. Until recently, it has been based on de-
tection of toxin biological activity. STa activity is deter-
mined in the infant mouse test, STb activity in pig and,
more recently, in rat ligated gut loops, and LT and VT in
cell culture assays. Fimbrial adhesins are detected by
serologic assays such as agglutination, immunofluores-
cence, and ELISA, using rabbit polyclonal antisera. How-
ever, F5 and F41 are only produced when E. coli are
grown on special minimal media, and F6 is often poorly
produced in in vitro conditions. Alternatively, E. coli ad-
hering to the intestinal mucosa may be demonstrated di-
rectly in infected pigs by examination of frozen sections
using indirect immunofluorescence or by examination of
formalin-fixed, paraffin-embedded tissues using the im-
munoperoxidase technique.
Recent technological advances have greatly improved
the detection of E. coli virulence factors (Woodward et al.
1990, 1992; Wray and Woodward 1994). Use of mono-
clonal antibodies has led to more specific, sensitive, and
reproducible assays for the detection of STa, F4, F5, F6,
and F41. Such antibodies could be used in diagnostic kits
for the rapid detection and identification of pathogenic
E. coli directly in the feces or intestinal contents of af-
fected piglets. Probes and the polymerase chain reaction
(PCR) have now been developed for the detection of the
genes coding for the fimbrial adhesins and enterotoxins
of swine ETEC (Nagy et al. 1990; Woodward et al. 1990,
1992; Wray and Woodward 1994). There is a high corre-
lation between the results of the standard serologic and
biological assays and those of gene probes for the detec-
tion of fimbrial adhesins and enterotoxins of swine
ETEC (Harel et al. 1991). Probes are currently used in
many diagnostic laboratories for the identification of
ETEC isolates and for the detection of ETEC directly in
the feces of pigs with diarrhea (Harel et al. 1991; Monck-
ton and Hasse 1988; Ojeniyi et al. 1994; Woodward et al.
1990). Gene probe techniques often involve the use of ra-
dioactivity and thus must be performed in controlled
laboratory conditions. Nonradioactive gene probes are
being developed and could feasibly be used in kits for the
detection of pathogenic E. coli directly in the fecal or in-
testinal contents of diarrheic pigs by the veterinary prac-
titioner. Use of the PCR technique will greatly enhance
Bertschinger, Fairbrother 437
the sensitivity of current gene probe techniques.
However, the traditional approach for identification
of pathogenic E. coli by serotyping will still be necessary,
at least in reference laboratories, in order to monitor
changing trends and to identify new, emerging E. coli vir-
ulence determinants which could gain importance due to
the pressure of vaccination of sows against the currently
predominant determinants.
TREATMENT
Treatment of enteric E. coli infection should be aimed at
removal of the pathogenic E. coli, correction of their
harmful effects, and provision of optimal environmental
conditions. Therapy should be rapidly instituted to be as
effective as possible. It is important to confirm the diag-
nosis of E. coli infection by culture and to perform an-
tibiotic sensitivity tests, because antibiotic sensitivity
varies greatly among E. coli isolates (Table 32.2). A
broad-spectrum antibiotic treatment could be used ini-
tially until the results of antibiotic sensitivity are known.
In vitro resistance of E. coli isolates to a wide range of an-
timicrobial agents has greatly increased over the last sev-
eral years. An alternative approach to the treatment of
enteric E. coli infection is the use of bacteriophages, an
approach that has been successful experimentally but
has not been extensively applied in the field.
Fluid therapy, consisting of electrolyte replacement
solutions containing glucose given orally, is useful for the
treatment of dehydration and acidosis. Drugs which in-
hibit the secretory effects of enterotoxin, such as chlor-
promazine and berberine sulfate, may be useful for the
treatment of diarrhea, although many of these drugs
have undesirable side effects. The use of such antisecre-
tory drugs as bencetimide and loperamide, alone or in
combination with antibacterial agents, has also been
suggested (Solis et al. 1993).
It is important to ensure that younger piglets are
maintained at a constant temperature of 30–34˚C and
Table 32.2. Sensitivity to antimicrobial agents of E.
coli isolates from pigs aged from 0 to 7 days with
diarrhea in Quebec, 1994–96
Antimicrobial Agent % Sensitive Isolates (n = 38)
Amikacin 100
Ampicillin 46
Apramycin 79
Ceftiofur 92
Cephalothin 70
Enrofloxacin 100
Gentamycin 63
Neomycin 56
Spectinomycin 41
Tetracycline 7
Tiamulin 5
Trimethoprim-sulfamethoxazole 71
438 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
that recently weaned pigs are held in a draft-free envi-
ronment at a constant temperature of about 29.5˚C.
PREVENTION
A program for prevention of enteric E. coli infection
should be aimed at reduction of numbers of pathogenic
E. coli in the environment by good hygiene, maintenance
of suitable environmental conditions, and provision of a
high level of immunity. Because most pathogenic E. coli
belong to a limited number of serogroups, enteric E. coli
infection could be eliminated from some herds.
Husbandry
One of the most important factors in prevention of en-
teric E. coli infection is the maintenance of piglets at an
adequate environmental temperature (30–34˚C for un-
weaned pigs), free of drafts, and on a low-heat-conduct-
ing floor. This is particularly true for piglets of below-av-
erage weight, who lose heat more rapidly because they
have a greater skin surface area per unit body weight.
Good hygiene in the farrowing area leads to a reduc-
tion in the numbers of E. coli being presented to the
piglet to a level that it is able to control through its own
defense mechanisms.
Farrowing-crate design is important because it affects
the position at which feces are deposited by the sow. In
crates that are too long, the feces are deposited over a
large area of the available floor space, thereby increasing
the heavily contaminated area. Ideally, the crate should
be adjustable, allowing for a shorter crate for gilts than
for sows. Crates on raised, perforated floors allow fecal
material to drop through and away from the piglets, and
litters farrowed onto such floors have a noticeably lower
incidence of diarrhea than those on solid concrete floors.
A dry, warm environment reduces the moisture avail-
able to enhance the survival of E. coli. This is largely af-
fected by ventilation rates, although if room temperature
is too high, sows tend to try and spread water over their
lying area to cool themselves, thereby defeating other hy-
gienic procedures. The sow should be at a temperature of
approximately 22˚C, necessitating a warmer creep area
for the piglets.
Quarantine should be used to control the introduc-
tion of different E. coli pathotypes or other infectious
agents into the herd. Animals in the herd will have little
immunity to E. coli fimbrial antigens with which they
have not had contact. Farrowing crates should be thor-
oughly cleaned and disinfected between litters. An all-
in/all-out farrowing system with thorough disinfection
of the farrowing room between batches will reduce the E.
coli population in the environment.
Diet may be modified in order to reduce colonization
of the intestine by E. coli (Thomlinson and Lawrence
1981). Feeding of cultures of Streptococcus faecium to
young pigs may reduce the incidence of diarrhea
(Morkoc et al. 1984).
Immunity
Immunity to enteric E. coli infections is humoral and is
initially provided through the maternal colostrum, lacto-
genic antibodies in the milk of the sow, and subsequent-
ly by a local intestinal immune response. Specific anti-
bodies inhibit bacterial adherence to receptors on the
intestinal epithelial cells and neutralize the activity of
the enterotoxins or cytotoxins produced by E. coli.
Colostrum from the sow contains high levels of im-
munoglobulin G (IgG), which rapidly decrease during
lactation and IgA becomes the main immunoglobulin
class (Bourne 1976). The latter protects the gut against E.
coli infection. It appears that most IgA, IgM, and IgG in
the milk of the sow is produced within the mammary
gland. During pregnancy, a proportion of the lympho-
cytes stimulated by antigens in the intestine migrate to
the mammary gland and produce specific antibody
against enteric pathogens. These antibodies are actively
transported to the colostrum and then the milk during
lactation.
The newborn piglet begins to synthesize specific im-
munoglobulin and develop intestinal immunity during
the first week of life (Butler 1973). At first, IgM predom-
inates, but after 2–3 weeks, it is replaced by IgA as the
most important immunoglobulin class in the intestine.
Thus, during the first weeks of life, colostrum is the main
source of immunologic protection for the piglet.
Breakdown in the protection provided by colostrum
may occur for several reasons. If the dam has not been
exposed to ETEC present in the environment of the
piglets, her colostrum will not contain the specific anti-
bodies necessary for protection against adherence and
proliferation of ETEC. Also, any disease process causing
agalactia in the sow will diminish transfer of colostrum.
Generalized systemic infection may cause a total reduc-
tion in colostrum production, whereas mastitis or in-
jured teats may affect production in one or several
glands. Piglets failing to receive colostrum due to defor-
mities, infection, small size, or damage at birth will also
be more susceptible to ETEC infection.
Maternal vaccination has been one of the most effec-
tive ways of controlling neonatal ETEC diarrhea in
piglets. Identification of virulence factors important in
the pathogenesis of ETEC diarrhea and application of re-
combinant DNA technology have resulted in the produc-
tion of more efficient vaccines over the last several years.
One of the earliest vaccination techniques consisted of
taking the small-intestinal contents from a piglet with
diarrhea, culturing it in milk, and feeding the culture to
pregnant sows, usually about a month before parturition
(Kohler 1974). This technique is effective, conferring an
immunity lasting throughout the suckling period, and is
still used, particularly in the United States.
Commonly used commercially available vaccines are
given parenterally and may be killed whole-cell bacterins
or purified fimbrial vaccines. Both of the latter types of
vaccines appear to work equally well (Fahy 1987). Bac-
 CHAPTER 32 ESCHERICHIA COLI INFECTIONS
terins usually contain strains representing the most im-
portant serogroups and producing the fimbrial antigens
F4, F5, F6, and F41 (Nagy 1986). They are usually given
parenterally at about 6 weeks and 2 weeks prior to par-
turition. Addition of the common fimbrial antigen F1 to
a fimbrial bacterin appeared to have been protective in
one study (Jayappa et al. 1985) but was not protective in
another study (To et al. 1984). Recombinant DNA tech-
nology has enabled the production of large quantities of
purified fimbrial antigens for use in parenteral vaccines
for immunization of the dam (Clarke et al. 1985).
In cases where vaccination is ineffective, it is impor-
tant to identify the serotypes involved for possible inclu-
sion into an autogenous bacterin. Further characteriza-
tion of these isolates may identify new or variant
fimbrial adhesins important in the pathogenesis of
ETEC diarrhea. An alternative approach to the problem
of emerging ETEC negative for the known fimbriae has
been the use of vaccines containing the nontoxic form of
the enterotoxin LT-B conjugated to the nonimmunogenic
STa (Klipstein 1986). Following conjugation, STa be-
comes immunogenic, and this vaccine has given protec-
tion in experimental animals. Addition of these compo-
nents to fimbrial vaccines will provide protection against
emerging ETEC with new fimbrial antigens in neonates
and against ETEC negative for the known fimbrial anti-
gens and commonly found in older pigs. Isaacson (1994)
has recently reviewed the use of vaccines for the preven-
tion of E. coli diseases.
Finally, a novel approach to the prevention of ETEC
diarrhea in piglets could be the oral administration of ex-
ogenous proteases such as bromelain (Mynott et al.
1996). Such proteases can inhibit attachment of F4-pos-
itive ETEC to the intestinal mucosa due to modification
of the receptor attachment sites.
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 CHAPTER 32 ESCHERICHIA COLI INFECTIONS
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POSTWEANING ESCHERICHIA COLI DIARRHEA AND
EDEMA DISEASE
H. U. Bertschinger
Postweaning Escherichia coli diarrhea and edema disease
are treated in one section because they often both occur
in the same batch of pigs, and the causative bacteria
share certain virulence factors. Treatment and preven-
tion are mainly the same for both diseases.
Postweaning E. coli diarrhea (PWECD) is a communi-
cable diarrhea mediated by enterotoxins and observed
mainly after weaning. It is also called postweaning en-
teric colibacillosis.
Edema disease (ED) is a communicable enterotox-
emia caused by certain E. coli colonizing the small intes-
tine and producing an exotoxin that gets to the blood
and damages vessel walls. The names “edema disease,”
“bowel edema,” and “gut edema” were coined because
edema of the submucosa of the stomach and the meso-
colon is often a prominent feature of the disease.
A clear-cut distinction between PWECD and ED is
not possible, because certain strains of E. coli are in-
volved in both conditions. The early history of the two
diseases has been extensively reviewed by Sojka (1965).
E. coli is an important cause of death in weaned pigs.
In Switzerland, PWECD or ED was diagnosed in 57% of
3301 4- to 12-week-old pigs submitted for postmortem
examination. PWECD had a prevalence of 35% and ED of
22% (Häni et al. 1976). Wegmann (1990) reported an es-
sentially unchanged situation. A peak of postweaning
deaths caused by E. coli was seen in 5- to 10-week-old
pigs. In the former East Germany, with 750,000 produc-
tive sows, Jahn and Uecker (1987) reported a mortality in
weaned pigs of 1.8% due to E. coli. Direct and indirect an-
nual losses were estimated at about 50 million East Ger-
man marks. Svensmark et al. (1989) reported an overall
mortality of 2.4% in the period between weaning at 2–4
weeks and transfer to the fattening unit at a weight of
Bertschinger, Fairbrother 441
Woodward, M. J.; Carroll, P. J.; and Wray, C. 1992. Detec-
tion of entero- and verocytotoxin genes in Escherichia
coli from diarrhoeal disease in animals using the poly-
merase chain reaction. Vet Microbiol 31:251–261.
Wray, C., and Woodward, M. J. 1994. Laboratory diagnosis
of Escherichia coli infections. In Escherichia coli in Do-
mestic Animals and Humans. Ed. C. L. Gyles. Walling-
ford, U.K.: CAB International, pp. 595–628.
Zhu, C.; Harel, J.; Jacques, M.; Desautels, C.; Donnenberg,
M. S.; Beaudry, M.; and Fairbrother, J. M. 1994. Viru-
lence properties and attaching-effacing activity of Es-
cherichia coli O45 from swine postweaning diarrhea. In-
fect Immun 62:4153–4159.
about 20 kg. About 75% of the losses were associated
with PWECD. The study included nearly 49,000 litters.
In affected herds, losses in some batches of weaners may
be as high as 50%. However, mortality due to ED is not as
great in North America.
ED bears substantial similarities to the human dis-
eases caused by enterohemorrhagic strains of E. coli
(EHEC), which produce closely related, but not identical,
Shiga-like toxins. However, the human EHEC strains col-
onize the porcine digestive tract by a mechanism distinct
from enterotoxemic E. coli (ETEEC) (Tzipori et al. 1986).
Serotypes associated with ED are different from those of
EHEC.
ETIOLOGY
PWECD and ED are caused by strains of E. coli that pos-
sess certain adhesion factors enabling the bacteria to col-
onize the small intestine and that produce one or several
exotoxins. Nearly all of these E. coli are alpha-hemolytic.
Most of them belong to a very limited number of
serotypes. In a given area, the serotypes are closely asso-
ciated with a rather constant set of adhesion factors and
toxins. Thus, the serogroup O139 has been found world-
wide to bear the fimbrial variant F18ab. Strains of this
serogroup from Australia always cause PWECD, whereas
those from Europe typically induce ED.
The most comprehensive study on the prevalence of
virulence factors with E. coli isolates from weaner pigs
with diarrhea was performed in Denmark (Ojeniyi et al.
1994). The fimbrial types F18 (earlier called F107, 2134P,
8813, and Av24) (Rippinger et al. 1995) and F4 (K88)
were detected with 44% and 36%, respectively, of the tox-
igenic isolates (Table 32.3). In about 24% of the latter,
442 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor

Table 32.3. Fimbrial types and toxins detected in 184 E. coli isolates from 28- to 49-day-old pigs with diarrhea
Toxin(s)
SLT
LT SLT SLT SLT STa
Fimbrial Number LT STa STa SLT SLT STb STa STa STb Toxin
Group of Strains STb LT STb STb STb SLT STb LT LT LT STb LT Negative
F18 75 11 2 16 15 3 2 1 1 6 8 1 9
F18 + F6 4 4
F18 + F41 1 1
F18 + F4 5 5
F4 52 1 6 39 1 1 1 2 1
F4 + F6 1 1
F6 2 1 1
None 44 10 4 6 1 20 1 2
Total 184 22 12 62 18 9 23 2 1 13 1 10 2 9
Source: Modified from Ojeniyi et al. 1994.

genes coding for known fimbrial types were not detected.
More than one fimbrial type was found in about 6%. F6
(987P) was most often present in association with either
F4 or F18. In Canada, 11% of the toxigenic isolates were
positive for F18, 9% for F4, 5% for F5, and none for F6
(Fairbrother et al. 1994). The antigenic variants of F18
fimbriae were serologically determined using 380 iso-
lates obtained from fatal cases of PWECD and ED in Ger-
many (Wittig et al. 1995). Variants F18ab and F18ac
were found in 40% and 35%, and F4 in 14%, of the iso-
lates. The remaining isolates were negative for F18 and
F4.
PWECD and ED are mediated by toxins. E. coli iso-
lates from fatal cases are nearly always toxigenic (Im-
berechts et al. 1994; Wittig et al. 1995), whereas fecal
samples from weaners with diarrhea less often give rise
to growth of toxigenic E. coli (Fairbrother et al. 1994;
Ojeniyi et al. 1994). This points to the multiple etiology
of postweaning diarrhea (see Chapter 57). It is notewor-
thy that strains producing SLT-IIe occur in pig popula-
tions in the absence of typical ED. This was, for example,
the case in Denmark (Table 32.3) before the recent inva-
sion of strains of serogroup O139 (Aarestrup et al.
1997).
A more detailed description of the enterotoxins is
given in the preceding subchapter. The term “Shiga-like
toxin” (SLT-IIe) is a synonym of verotoxin, edema dis-
ease principle, neurotoxin, and vasotoxin. MacLeod and
Gyles (1990) developed a purification scheme resulting
in a homogeneous preparation of SLT-IIe free of endo-
toxin. As little as 3 ng of pure SLT-IIe per kilogram of
body weight administered intravenously to young pigs
induces disease. Clinical signs and gross and microscop-
ic lesions are characteristic of ED, thus confirming that
SLT-IIe and EDP (edema disease principle) are identical.
Incubation time and severity of disease are directly relat-
ed to the toxin dose.
In a given pig population, strains with a certain anti-
genic makeup are often equipped with certain patterns
of virulence factors (Table 32.4). Identical serotypes
were detected in all continents, but their frequencies can
vary in different geographic regions.
Enteropathogenic E. coli
An enteric syndrome distinct from classic PWECD was
described by several investigators. It is characterized by
attaching and effacing lesions caused by E. coli (AEEC).
The spontaneous disease is nonfatal. The AEEC do not
possess any virulence factors of classic PWECD or ED
strains (Zhu et al. 1994). Their virulence attributes are
dealt with in the subchapter on neonatal E. coli diarrhea.
Experimental infection of gnotobiotic pigs allows repro-
duction of the lesions (Fig. 32.2). A weaner diet contain-
ing soya and field peas enhances bacterial colonization
and development of attaching and effacing lesions but
causes no diarrhea (Neef et al. 1994). AEEC will not be
further dealt with in this chapter.
A comprehensive overview of E. coli and its role in
human and animal disease appeared in 1994 (Gyles
1994).
EPIDEMIOLOGY
The epidemiologies of PWECD and ED have many fea-
tures in common. The age group primarily affected by
Table 32.4. Examples of prevailing pathotypes of
E. coli in fatal cases of PWECD and ED in Switzerland
Serotype Colonization Factor Toxin(s)
O139:K12:H1 F18ab SLT-IIe
O141ab:H4 F18ac SLT-IIe, LT, STII
O149:K91:H10 F4ac LT, STII
Source: Modified from Imberechts et al. 1994.
 CHAPTER 32 ESCHERICHIA COLI INFECTIONS
PWECD and/or ED depends on the weaning age. There
are some differences between E. coli with F4 and with
F18. The former can cause neonatal, preweaning, and
postweaning diarrhea, most often in the very first days
after weaning. The latter, however, more often cause dis-
ease between 5 and 14 days after weaning (Svendsen et
al. 1974) or after introduction to fattening herds. Un-
weaned piglets can also be affected by PWECD and ED.
In suckling pigs, the severity of the disease depends on
antibody titers in the milk of the sow (Sarmiento et al.
1988b). In adult pigs, ED is the more frequent cause of
central nervous system signs and a significant cause of
mortality (Sydler et al. 1996).
The morbidity in an affected herd is extremely vari-
able. Within a particular litter it may be up to 80% or
more, but the average is 30–40%. With ED, the case fatal-
ity rate ranges from 50% to over 90%. The course of the
disease in the herd varies from 4 to 14 days, the average
being slightly under a week. The disease disappears as
abruptly as it appears. Recurrence on premises is com-
mon (Kurtz et al. 1969). With PWECD the case fatality
rate and the mortality tend to be lower. In untreated
herds, the latter may attain 26% (Svendsen et al. 1974).
The environment of the weaner unit appears to be
the most likely source of pathogenic E. coli strains. Un-
weaned pigs may acquire infection in the farrowing
house, presumably from the same source, and carry it in-
to the weaning unit. Routine cleaning and disinfection
are usually insufficient to break the cycle of infection
(Hampson et al. 1987). Under experimental conditions,
however, transmission can be prevented by strict hygien-
ic measures (Smith and Halls 1968; Kausche et al. 1992).
The minimal infectious dose is not known. In transmis-
sion experiments with a K88-positive ETEC strain, air-
borne transmission between pigs in wire cages 1.5 m
apart was repeatedly observed (Wathes et al. 1989). Out-
breaks tend to involve only one strain of E. coli at any one
time. Occasionally, two potential pathogens are isolated,
but one usually predominates. Multiple infections of
herds involving more than one serogroup were detected
in 47% of 84 herds (Awad-Masalmeh et al. 1988).
The spread of pathogenic E. coli is presumed to occur
via aerosols, feed, other vehicles, pigs, and possibly oth-
er animals. Introduction of new pathogenic strains of E.
coli into closed primary specific-pathogen-free (SPF)
herds with a high isolation standard was observed at in-
tervals of 1–2 years. Once a site is contaminated with a
particular strain, it can remain so for an extended period.
The serotypes associated with postweaning diseases tend
to be similar in broad geographic areas. When ED en-
tered Denmark in 1994, it spread from one SPF breeding
herd by trade of pigs to at least 37 other herds. The close
clonal relationship of the causal strains was confirmed
(Aarestrup et al. 1997; Jorsal et al. 1996). Another 22
herds became infected without known trading contact.
Bertschinger, Fairbrother 443
PATHOGENESIS
For the sake of clarity, intestinal colonization and tox-
emia will be presented separately. However, there may be
mutual interactions.
Colonization of the Small Intestine
An E. coli strain of O group 141 causing PWECD and ED
(Smith and Halls 1968) and two strains of O group 139
devoid of enterotoxins (Bertschinger and Pohlenz 1983;
Bertschinger et al. 1990) reached high population densi-
ties throughout the intestinal tract, including the upper
small intestine. Such colonization requires both mucosal
adhesion and proliferation. The degree of colonization
determines whether or not disease will result from infec-
tion. Adhering microcolonies or layers of bacteria were
observed on the small-intestinal mucosae of pigs experi-
mentally infected with two strains of O group 139 (Fig.
32.3) (Bertschinger and Pohlenz 1983; Methiyapun et al.
1984; Bertschinger et al. 1990). ETEEC adhere to the
brush border similarly to enterotoxigenic E. coli (ETEC),
whereas other producers of SLTs show the “attaching
and effacing” phenomenon. Since colonization depends
on a multiplicity of factors, it is not reliably repro-
ducible. Some of the known factors are discussed here.
Brush border receptors for pathogenic E. coli are not
present in every pig. Genetic resistance resulting from
lack of receptors for F4 was first described by Sellwood
et al. (1975) (see section on neonatal colibacillosis). The
receptor for F18 fimbriae is also controlled in a single lo-
cus, and the presence of a receptor is dominant over ab-
sence (Bertschinger et al. 1993). The receptor for F18 is
distinct from the receptor for F4. The genes for F4 were
determined on chromosome 13 (Guérin et al. 1993),
whereas the genes for the F18 receptor were located on
chromosome 6 close to the locus for stress susceptibility.
In a high proportion of the Swiss pig population, resis-
tance against stress is linked to susceptibility to adhesion
of E. coli with F18 fimbriae (Vögeli et al. 1996). In view of
the low prevalence of stress-susceptible pigs, the fre-
quency of pigs with the F18 receptor must be high.
Fimbrial receptors are thought to be glycoconjugates.
The latter are subject to modulation by feed lectins such
as constituents of leguminous plants (Kelly et al. 1994).
It may be speculated that feed-induced changes of the re-
ceptor are involved in the reduced susceptibility to colo-
nization by F18-positive E. coli in the very first days after
weaning (Bertschinger et al. 1993). Endogenous as well
as orally administered proteases may reduce the receptor
activity for F4 fimbriae (Mynott et al. 1996). Receptors
for F4 are fully expressed from birth to adult age, where-
as the F18 receptor is not yet fully expressed by piglets
under about 20 days of age (Nagy et al. 1992). This ex-
plains why E. coli with F18 fimbriae do not cause disease
in neonatal pigs. Constant expression of receptors may
444 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
32.3. Bacteria adhering patch-
wise to microvilli of small-intestinal
epithelium of a weaner 6 days after
oral inoculation with a culture of
E. coli O139:K12:H1.
underlie the earlier appearance after weaning of E. coli
strains with F4 in herds where F4- and F18-positive
strains are endemic.
Sarmiento et al. (1988b) detected specific antibodies
in milk and suggested that milk antibody protects the
piglets against colonization as long as they are nursing.
A variety of viruses infect the porcine intestine and
may thereby change the bacterial environment. In an ex-
perimental postweaning diarrhea model, an F4-positive
ETEC strain colonizes weaned pigs in the absence of ro-
taviral infection (Sarmiento et al. 1988a). Dual infection
of pigs with rotavirus and with an ETEC strain without
F4 results in a more severe diarrhea than inoculation
with either agent alone (Lecce et al. 1982). The investiga-
tors concluded that viral damage of the epithelium fa-
vors colonization by E. coli.
An acid environment has an inhibitory effect on E.
coli. The pH of the stomach contents falls after weaning
(Risley et al. 1992). Several investigators found that the
pH of the jejunum cannot be reduced by acidification of
the feed. The pH close to the jejunal brush border is
slightly acid and highly regulated. It is not influenced by
the pH of the chyme (McEwan et al. 1990).
Veterinary practitioners and farmers were convinced
years ago that nutritious feed would play an important
role. Thus ED was named “protein intoxication.” Smith
and Halls (1968) inoculated pigs on various feed regi-
mens with an ETEEC strain of serogroup O141:K85a,c.
They found that severe feed restriction resulted in much
lower fecal numbers of the bacteria and absence of dis-
ease. A similar effect was achieved by feeding pigs ad li-
bitum on a diet extremely rich in fiber and low in nutri-
ents. The authors concluded that the physiological state
of the intestinal epithelium might influence bacterial
adhesion. These experiments were extended by
Bertschinger et al. (1978) using an ETEEC strain of
serogroup O139:K12 for inoculation. The findings of
Smith and Halls (1968) were confirmed. However, the
poor diets inhibited growth of the pigs. When these diets
were replaced by a conventional type of feed, coloniza-
tion and clinical disease developed. The inhibitory effect
of the poor diet was abolished by supplementation with
fish meal but not with starch or fat. The precise mecha-
nism behind these phenomena remains to be elucidated.
Low room temperature in the weaner rooms was pro-
posed as responsible for a more severe course of post-
weaning diarrhea (Wathes et al. 1989). Under experi-
mental conditions, ED was not aggravated by cold stress
(Kausche et al. 1992).
Diarrhea
The mechanisms by which enterotoxins induce diarrhea
are described in the preceding section (neonatal E. coli
diarrhea). Almost all E. coli involved in fatal cases of
PWECD produce LT (Imberechts et al. 1994). Pigs colo-
nized about 12 days after weaning with ETEC producing
one or both heat-stable enterotoxins develop diarrhea
only exceptionally (Sarrazin and Bertschinger 1997).
This difference between neonates and weaned pigs may
be explained at least in part by the marked increase of
antisecretory factor beginning a few days after weaning
(Lange et al. 1993).
Enterotoxemia
Highly purified SLT-IIe induces a disease indistinguish-
able from ED when administered intravenously to pigs
(MacLeod and Gyles 1990). Transportation of the toxin
into the circulation is still somewhat of a mystery. SLT-
IIe binds preferentially to globotetraosyl ceramide and
therefore to the red blood cells. Thus, vessels are subject-
 CHAPTER 32 ESCHERICHIA COLI INFECTIONS
ed to prolonged toxin exposure (Boyd et al. 1993). By im-
munological methods the toxin can be detected in en-
dothelial cells of small blood vessels of the intestine and
in microvillous membranes of enterocytes at the base of
the villi (Waddell et al. 1996).
The most consistent injury observed in natural cases,
after injection of partially purified toxin (Clugston et al.
1974b; Gannon et al. 1989), and in pigs inoculated oral-
ly with live cultures (Methiyapun et al. 1984; Kausche et
al. 1992) is a degenerative angiopathy of small arteries
and arterioles. The edema fluid found in various tissues
is low in protein and could be the result of a mild in-
crease in vascular permeability. Information on patho-
physiology of ED is scarce. Clugston et al. (1974a) ob-
served an increase of blood pressure after intravenous
administration of EDP. Hypertension developed later
than clinical edema and was therefore thought to be the
result of vascular injury rather than its cause. Hyperten-
sion might exacerbate the lesions in the already damaged
vessels. The development of injuries in the nervous sys-
tem may be due to hypoxia resulting from impaired
blood flow (Clugston et al. 1974b).
A distinct type of ED is characterized by terminal
bloody diarrhea and hemorrhagic lesions in the cardiac
region of the stomach, the ileum, and the large intestine
(Fig. 32.4) (Bertschinger and Pohlenz 1983). According
to Gannon et al. (1989) and MacLeod and Gyles (1990),
acute hemorrhagic gastroenteritis occurs in some of the
pigs to which a high dose of SLT-IIv is administered. Ep-
32.4. Extended hemorrhages and minor mesenteric
edema in the colon of a pig that developed bloody
diarrhea 5 days after inoculation with a culture of
E. coli O139:K12:H1.
Bertschinger, Fairbrother 445
ithelial necrosis secondary to necrosis of small arteries
and arterioles may be responsible for luminal hemor-
rhage.
CLINICAL SIGNS
Postweaning E. coli Diarrhea
In the spontaneous outbreaks caused by an E. coli strain
of O149 without F4 investigated by Svendsen et al.
(1974), the first manifestation of PWECD was sudden
death of one or several pigs as early as 2 days after wean-
ing. At the same time, feed consumption of the affected
batch of pigs dropped markedly, and a watery diarrhea
developed. At the onset, some pigs exhibited a character-
istic quivering of the tail. The rectal temperature was
normal. Affected pigs became dehydrated and de-
pressed. They ate irregularly, but even in the terminal
stage of the disease, they tried to drink. Many pigs
showed cyanotic discoloration of the tip of the nose, the
ears, and the abdomen. Even severely affected pigs tried
to move around with staggering, uncoordinated move-
ments. The peak of mortality occurred 6–10 days after
weaning. Surviving pigs recovered well. Some pigs were
completely spared from the disease.
In pigs experimentally infected with a strain with vir-
ulence factors F4, LT, and STII, diarrhea started 1–2 days
after inoculation and was fulminating and fatal in some
of the pigs, whereas others survived after diarrhea of 3–4
days’ duration (Sarmiento et al. 1988a). The pigs lost
some weight in the first 2 days after inoculation. From
the fifth day on, the growth curve of susceptible pigs re-
sumed a course parallel to that of genetically resistant
pigs. The latter were not colonized and remained free
from any symptoms.
Postweaning E. coli Diarrhea Combined
with Edema Disease
Smith and Halls (1968) described the disease experimen-
tally induced with a strain of serogroup O141:K85a,c,
obviously a producer of SLT-IIe and of enterotoxin(s).
The first sign was anorexia, which started at the onset of
shedding bacterial numbers above 109 colony-forming
units (CFU)/g of feces 3 (2–5) days postinoculation (PI)
and was observed in 20 out of 21 experimental pigs.
Anorexia lasted for several days in the 2 pigs that recov-
ered and until euthanasia in the 19 pigs killed when
death was imminent. Diarrhea appeared on day 4 (1–8)
PI. Usually it was severe but of short duration. It was fa-
tal in only 1 out of 17 diarrheic pigs. In most pigs diar-
rhea was no longer present when signs of nervous in-
volvement became apparent, that is, on day 6 (5–13) PI.
Swollen eyelids were seen at about the same time. Ataxia
was accompanied with varying degrees of mental confu-
sion and was usually progressive. Affected pigs soon be-
came completely recumbent. Severe dyspnea was usually
present at this final stage. Nine out of 13 pigs with atax-
446 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
ia had to be killed on the day the nervous signs appeared.
Three others survived for 2–4 days. Pigs were moribund
7 (5–13) days PI. The rectal temperature always re-
mained within the normal range.
Edema Disease
A very similar disease was seen in pigs inoculated with a
nonenterotoxigenic ED strain of serotype O139:K12:H1
(Bertschinger et al. 1978). Discrepancies were that diar-
rhea was not associated with colonization and that more
pronounced edema developed in some cases. In such cas-
es ears, subcutaneous tissue over the frontal bones, nose,
and lips were swollen (Fig. 32.5). In mild cases, subcuta-
neous edema was accompanied by pruritus, which dis-
appeared after recovery. In some pigs with or without
dyspnea, respiration was accompanied by a snoring
sound.
Watery diarrhea with clots of fresh blood became ap-
parent in a few pigs at the terminal stage (Bertschinger
and Pohlenz 1983). Hemorrhagic colitis developed also
in pigs to which high doses of toxin SLT-IIe were admin-
istered (MacLeod et al. 1991).
Chronic ED occurred in a variable, but mostly low,
proportion of pigs recovering from acute attacks of ED
or PWECD (Bertschinger and Pohlenz 1974; Nakamura
et al. 1982). The condition was called cerebrospinal an-
giopathy before its association with ED became appar-
ent. For periods varying from days to several weeks after
intestinal infection, growth stops, and sick pigs often
show unilateral nervous disturbances such as circling
movements, twisting of the head, or atrophy of limb
muscles with progressive weakness. Subcutaneous ede-
32.5. Edematous swelling of eyelids, forehead, and
lips, breathing through open mouth, and inability to rise
in a weaner 4 days after oral inoculation with a culture of
E. coli O139:K12:H1.
ma is rare. Affected pigs should be destroyed. Subclinical
ED was observed in 28 of 29 pigs surviving for 2 weeks
after inoculation with a strain of E. coli O139 positive for
SLT-IIe and STII. The pigs were clinically normal but de-
veloped vascular lesions. No pigs were allowed to survive
beyond the two weeks (Kausche et al. 1992).
LESIONS
Postweaning E. coli Diarrhea
GROSS LESIONS. Pigs dead from PWECD are gener-
ally in good condition but severely dehydrated with
sunken eyes and some cyanosis. Lungs look pale and dry,
like from well-bled pigs (Svendsen et al. 1974). The stom-
ach is often extended by dry feed. Variable hyperemia of
the gastric mucosa is often noted in the fundic region.
The small intestine is dilated, slightly edematous, and
hyperemic. The contents vary from watery to mucoid,
with a characteristic smell. The mesentery is heavily con-
gested. Contents of the large intestine most often look
light greenish or yellowish and are mucoid to watery.
Pigs dying late in an outbreak look emaciated and exhib-
it a strong smell of ammonia. There are irregularly
shaped superficial ulcerations in the fundic region of the
stomach and similar lesions of smaller size in the large
intestine. The feces look yellow and pasty. The fluid from
the anterior chamber of the eye gives a positive reaction
for urea (P. Wegmann, Zurich, pers. comm.).
Some authors use the terms “hemorrhagic gastroen-
teritis” or “colibacillary shock” to describe a form of E.
coli diarrhea characterized by severe congestion of the
gastric fundus and the small intestine with or without
blood-tinged contents of the small intestine and some-
times the upper large intestine, but only exceptionally
with bloody feces (Faubert and Drolet 1992). This type of
lesion was always caused by E. coli with F4 fimbriae.
MICROSCOPIC LESIONS. Bacteria adhering to the
ileal and less consistently to the jejunal surface are always
seen. The bacterial layers are restricted to villi and look
patchy (Sarmiento et al. 1988a; Casey et al. 1992; Faubert
and Drolet 1992). The mucosa and the epithelium ap-
pear intact. Some investigators have reported increased
numbers of neutrophils in the superficial lamina pro-
pria. In pigs with so-called hemorrhagic gastroenteritis,
severe congestion of the gastric and small-intestinal mu-
cosae is commonly associated with microvascular fibri-
nous thrombi. Necrosis of villi with marked infiltration
of neutrophils occurs in severe cases. There is only occa-
sional hemorrhage in the lamina propria of the jejunum
and the ileum (Svendsen et al. 1974; Faubert and Drolet
1992).
Edema Disease
GROSS LESIONS. Pigs dead of ED are mostly in good
condition, somewhat pale, and the bodies retain a fresh
 CHAPTER 32 ESCHERICHIA COLI INFECTIONS
appearance. Edema at specific sites is variable and may
be absent in some animals. Subcutaneous edema may oc-
cur. Edema in the submucosa of the stomach is charac-
teristic when present and is located in the region of the
glandular cardia (Fig. 32.6). It may vary from being bare-
ly detectable to 2 cm or more in thickness. The edema
fluid is usually serogelatinous in nature and occasionally
may be bloodstained adjacent to the mucosa. If severe,
the edema may extend into the fundic submucosa. In-
flammatory edema associated with acute ulceration of
the esophageal cardia must not be confused with that of
ED.
Edema of the gallbladder is sometimes seen. The
mesocolon is a common site for edema. Careful inspec-
tion of the pericardial, pleural, and peritoneal cavities
may reveal occasional whitish fibrin strands and a slight
increase in serous fluid. The mesenteric and colic nodes
vary in appearance from normal to being swollen, ede-
matous, and congested. Typically, the stomach is full of
dry, fresh-looking feed, and the small intestine is rela-
tively empty. Colonic contents may be diminished in
amount. It may be inferred that this is a manifestation of
delayed gastric emptying, since some animals have a pe-
riod of anorexia before death. Also, it has been shown ex-
perimentally that pigs with ED may eat very little for 48
hours before death and at necropsy have full stomachs
(Smith and Halls 1968). The suggestion that some pigs
with ED are affected by constipation is also in accord
with these observations.
The lungs may display varying degrees of edema and
a characteristic, patchy, sublobular congestion. In some
cases this may be the only observable lesion. Cases with
laryngeal edema have also been observed. A few epicar-
dial and endocardial petechiae may occur. This lesion
must not be confused with mulberry heart disease.
In some pigs with spontaneous or experimental ED, a
Bertschinger, Fairbrother 447
form of hemorrhagic gastroenteritis occurs which is
quite different from that described with PWECD. In ad-
dition to marked edema, the edematous submucosa of
the cardiac region of the stomach and the mucosa of the
lower small and upper large intestine show extensive he-
morrhage. Watery diarrhea with clots of coagulated
blood occurs shortly before death in some of these pigs
(Bertschinger and Pohlenz 1983). Endothelial swelling,
vacuolation and proliferation, microthrombus forma-
tion, subendothelial fibrin, medial necrosis, and perivas-
cular edema were detected in such cases (Methiyapun et
al. 1984). The similarity to human hemorrhagic colitis is
striking.
If the causative strain of E. coli is also capable of pro-
ducing enterotoxin, lesions of postweaning diarrhea
may be added, and edema may be mild or absent.
MICROSCOPIC LESIONS. Patchy layers of adhering
bacteria are present throughout the small intestine early
in the course of ED (Bertschinger and Pohlenz 1983; Me-
thiyapun et al. 1984; Bertschinger et al. 1990). Contrast-
ing with PWECD, the colonization has often disappeared
when pigs with ED become moribund (Smith and Halls
1968).
The most important microscopic lesions are those of
a degenerative angiopathy affecting small arteries and ar-
terioles (Clugston et al. 1974b; Kausche et al. 1992). The
lesions may occur in many organs and tissues. The dense
arterial network in the mesocolon adjacent to the colic
lymph nodes is frequently affected. The early acute lesion
is one of necrosis of smooth muscle cells in the tunica
media characterized by pyknosis and karyorrhexis of nu-
clei and hyaline change in cytoplasmic elements. In the
walls of some affected vessels, fibrinoid material is de-
posited (Fig. 32.7). Swelling of endothelial cells has also
been observed. In acute experimental cases, edema of
32.6. Edematous swelling of
glandular mucosa of the cardiac
region and gelatinous submucosal
edema of the cut stomach wall from
a field case from which E. coli
O139:K12:H1 was isolated.
448 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
32.7. Arterioles in submucosa
of the urinary bladder: (left)
normal; (right) fibrinoid or
hyaline change, acute experi-
mental ED. (Clugston et al.
1974b.)
the leptomeninges and perivascular spaces has been
demonstrated. In older lesions, there may be prolifera-
tion of adventitial and medial cells (Fig. 32.8). Vascular
lesions may be difficult to detect in acute cases, but in
surviving pigs or those affected subclinically, they are
more readily apparent (Kausche et al. 1992). Thrombosis
is not usually a feature of uncomplicated naturally oc-
curring ED.
In pigs that have recovered from natural outbreaks or
survived for several days following acute signs, there are
lesions of focal encephalomalacia in the brain stem to-
gether with lesions in the small arteries and arterioles
(Kurtz et al. 1969; Kausche et al. 1992). These are
thought to be the result of vascular injury leading to ede-
ma and ischemia. A cerebrospinal angiopathy of pigs has
been recognized as a clinicopathologic entity for some
years. Its microscopic features are those described above
32.8. Submucosa of cardial gland region of the stom-
ach 17 days after inoculation with EDP (edema disease
principle containing SLT-IIe); arteriole with proliferative
arteriopathy. (Clugston et al. 1974b.)
plus the occurrence of eosinophilic, Periodic Acid Schiff
(PAS)–positive droplets around affected vessels. This an-
giopathy is considered to most likely be a manifestation
of edema disease (Bertschinger and Pohlenz 1974).
DIAGNOSIS
Postweaning E. coli Diarrhea
Postweaning diarrhea is a very complex disease with
multiple etiologies (see Chapter 57). Occurrence of diar-
rhea early after weaning, marked dehydration, and at
least some mortality are characteristics in the field allow-
ing a preliminary diagnosis of ETEC. The gross lesions,
including the characteristic smell, are also helpful. The fi-
nal diagnosis requires detection of ETEC, which are shed
in high numbers. Hemolysis is not a valid criterion for
identification of ETEC. Laboratories not equipped for
the determination of virulence factors should at least use
serotyping of living cultures with OK-antisera against
serotypes most prevalent in a given region.
Edema Disease
The diagnosis of acute ED is based on sudden appear-
ance and on clinical signs of neurologic disease in thriv-
ing pigs 1–2 weeks after weaning. In the live pig the most
important and constant diagnostic sign is partial ataxia
or a staggering gait. Subcutaneous edema in the palpe-
brae and over the frontal bones is also a cardinal sign
when present. At necropsy the characteristic lesions of
edema, when present, are helpful in confirming the diag-
nosis but may be absent in a significant number of cases,
especially when severe diarrhea has preceded ED. Diag-
nosis of ED in adult pigs may require additional efforts,
such as histopathology and postmortem examination of
more than one pig.
Bacteriologic examination of the small intestine and
colon should yield nearly pure cultures of hemolytic E.
 CHAPTER 32 ESCHERICHIA COLI INFECTIONS Bertschinger, Fairbrother 449

coli. However, bacterial numbers may already be drop- Table 32.5. Prevalences of sensitive isolates of
ping in more protracted cases (Bertschinger and Pohlenz typable E. coli from pigs over 2 weeks of age with
PWECD or ED from Switzerland
1983). After death the small numbers of organisms may
be overgrown by other enterobacteria. In contrast to Sensitive Isolates (%) in Serogroup
ETEC infections, a negative bacteriologic result therefore Antimicrobial O139 O141 O149
does not exclude the diagnosis of ED. Serologic identifi- Substance (n = 52) (n = 9) (n = 59)
cation of the common serotypes associated with ED is
Ampicillin 81 67 73
additional evidence. Serotyping is essential, because he- Amoxicillin/ 100 100 100
molytic E. coli not associated with other virulence factors clavulanic acid
are frequently encountered in the intestinal flora and Cefoxitin 100 100 100
may be present in high numbers. Streptomycin 35 44 37
Subacute or chronic ED is diagnosed by the demon- Spectinomycin 15 0 19
stration of arteriopathy and eventually lesions of focal Neomycin 90 100 81
encephalomalacia. Apramycin 92 89 93
Gentamicin 96 89 91
In cases of sudden death, differential diagnosis will
have to include microangiopathia dietetica and circulato- Tetracycline 36 44 47
ry failure, as seen after severe fighting. When pigs show Chloramphenicol 69 78 81
Enrofloxacin 100 100 100
nervous signs, viral encephalitis (enteroviral polioen- Colistina 87 89 100
cephalomyelitis, pseudorabies) and bacterial menin-
goencephalitis (Streptococcus suis, Haemophilus parasuis) Sulfonamide 31 11 15
Trimethoprim 77 44 73
as well as water deprivation should be considered. Furazolidone 88 44 100
a
TREATMENT Modified agar dilution technique (Bertschinger et al. 1996).

Much less is known about the treatment of these dis-
eases than about pathogenesis and about treatment of
neonatal colibacillosis.
Antimicrobial Therapy
Chemotherapeutic control of bacterial proliferation is
therapeutically much more effective in PWECD than in
ED, because in the latter, toxin production in the gut is
nearly completed when clinical signs become visible. The
development of bacterial resistance against every active
principle hitherto used (Table 32.5) renders this ap-
proach uncertain. It is not possible to give universal data
on resistance, because the situation varies in different pig
populations depending on the substances preferentially
used.
Sick pigs must be treated parenterally. They eat
and drink very little, even if they stand close to the
creep and to the drinking nipple. Substances must be
selected which reach the intestinal lumen, such as
amoxicillin/clavulanic acid, fluoroquinolones, cephalo-
sporins, or trimethoprim. Testing bacterial resistance is
indispensable if there is a herd problem.
Supportive Therapy for PWECD
The supportive therapy has to counteract dehydration
and acidosis. Attractive rehydration fluid should be of-
fered for spontaneous intake or injected intraperitoneal-
ly if the pig is anorectic. Such fluids may contain glucose,
glycine, citric acid, and potassium dihydrogen phos-
phate in an isotonic solution (Bywater and Woode 1980).
Uptake should be equal to the loss (i.e., up to 25% of the
body weight).
Edema Disease
There is not much chance to save the lives of pigs with
advanced signs such as severe subcutaneous edema, res-
piratory distress, or inability to rise. Evaluation of thera-
py is difficult because the severity of the illness cannot be
quantified. Numerous remedies have been recommend-
ed in the past and have then been abandoned.
PREVENTION
No universally effective prophylaxis is so far available. In
view of the unpredictable, erratic occurrence of PWECD
and ED in sequential batches of weaners and even in
contemporaneously weaned litters, efficacy of prophy-
lactic measures is hard to assess.
Breeding of Resistant Pigs
This is the approach to prevention that will be most
effective and economical in the long term. The selection
of breeding stock is not yet feasible, because the tools for
the identification of the genotype in living pigs are not
yet available. Work in this direction is in progress. It will
be important to avoid coselection of unwanted traits
closely linked with loci coding for the F4 and the F18
receptors. It cannot be predicted if additional types
of adhesive fimbriae or new variants of known types
will emerge which could bind to yet unidentified recep-
tors.
Prevention of Infection
The transmissible character of PWECD and ED is evi-
dent. In Denmark most of the recent spread of ED fol-
450 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
lowed the routes of pig trade (Jorsal et al. 1996). It was
logical to start an eradication program involving depop-
ulation of affected farms and disinfection of the build-
ings (Johansen et al. 1996b). With one exception, the 15
participating farms remained free of clinical disease for a
minimum of 4–7 months. They are under continuing
surveillance. Some problems render the procedure risky.
The tools to prove the absence of pathogenic types of E.
coli from a given herd are not available. E. coli has a high
tenacity in the environment. In our experience the isola-
tion measures applied in the Swiss SPF nucleus herds
were not suitable to keep out pathogenic E. coli.
Immunoprophylaxis
Acquired immunity results in perfect protection against
intestinal colonization and/or against effects of the tox-
ins. Weaned pigs can be protected passively or actively.
PASSIVE IMMUNITY. A daily dose of 525 mL, but
not of 270 mL, milk obtained from sows in late lactation
fed to weaned pigs completely inhibited colonization,
whereas pigs fed the same amount of cow’s milk shed
high numbers of the ETEEC bacteria (Deprez et al.
1986). Spray-dried porcine blood plasma fed at a dose of
90 g per pig/day had a similar inhibitory effect that last-
ed only as long as the plasma was fed, and the inhibitory
effect could be improved by vaccination of the donor
pigs (Deprez et al. 1990, 1996). Immune protection
against colonization with F4- and F18-positive E. coli was
achieved by feeding eggs produced by vaccinated hens
(Deprez et al. 1992; Erhard et al. 1996). Such protection
was achieved against challenge strains which had only
the F18 fimbriae in common with the vaccine strains
(Zúñiga et al. 1998). It remains to be shown if the anti-
body-containing egg powder can be produced at an ac-
ceptable price.
ACTIVE IMMUNITY. Pigs that have been colonized
by an F18 ETEC producing STI and STII are protected
against recolonization by a heterologous ETEC sharing
no other antigens with the immunizing strain except F18
fimbriae. There is complete cross-protection between
strains with fimbrial variants F18ab and F18ac (Sarrazin
and Bertschinger 1997). In this experimental model, 6
days after the onset of colonization, pigs are protected
against recolonization (unpublished). Intestinal colo-
nization leads to an increase of serum antibodies against
the fimbriae, especially of the IgA class. Partial protec-
tion against PWECD was reported by Fahy et al. (1992)
in pigs orally vaccinated before weaning with an attenu-
ated strain of E. coli.
Sera from neonatal and from weaned pigs from herds
with and without clinical ED do not contain neutralizing
antibody against SLT-IIe (Gannon et al. 1988). However,
in pigs that had survived an outbreak of ED, Wieler et al.
(1995) found antibodies reacting in an ELISA to the B
subunit of SLT-IIe.
Active immunity against intravenous challenge with
SLT-IIe was induced in young pigs by a toxoid vaccine
prepared from SLT-IIe by treatment with glutaraldehyde
(Dobrescu 1982). A similar toxoid was used for vaccina-
tion of pigs 1 week before weaning (Awad-Masalmeh et
al. 1989). The vaccine conferred highly significant pro-
tection against ED after the pigs were orally challenged
with ETEEC serogroup O139:K12. Vaccinated principals
shed lower numbers of the inoculated bacteria and had
better weight gains than placebo-vaccinated littermates.
A toxoid prepared by treatment of SLT-IIe with
formaldehyde was not completely free of toxic activity.
Therefore, the toxin was modified by site-directed muta-
genesis. The genetically modified toxin was found to
have no deleterious effect on the growth of vaccinated
pigs, and it prevented overt and subclinical ED when vac-
cinated pigs were challenged with an E. coli O139:F18
positive for SLT-IIe and STII (Bosworth et al. 1996). A
different approach was chosen by MacLeod and Gyles
(1991), who detoxified purified SLT-IIe with glutaralde-
hyde. An adjuvanted experimental vaccine was evaluated
in two herds infected by a strain of E. coli O139:F18, SLT-
IIe. Mortality due to ED was significantly reduced, and
daily gain in the nursery was significantly improved.
Deaths caused by ETEC in one of the herds were not pre-
vented (Johansen et al. 1996a; M. Johansen, Kjellerup,
Denmark, pers. comm.). These toxoid vaccines are not
yet commercially available.
Chemoprophylaxis
At present, preventive feed medication is practiced in a
majority of the affected herds in most countries despite
serious drawbacks such as nonacceptance by the con-
sumer, impaired buildup of immunity, and selection of
resistant bacteria. Resistance is often induced within
days or a few weeks. Isolates from PWECD and ED show
the highest rate of resistance within porcine E. coli. Be-
sides the classes of substances mentioned above for par-
enteral therapy, the aminoglycosides and colistin are
widely used. The latter has the advantages of high stabil-
ity, low toxicity, absence of infectious resistance, and
slow development of resistance. With colistin, resistance
cannot reliably be detected by the agar diffusion tech-
nique (Bertschinger et al. 1996). Investigators have re-
ported that oxytetracycline reduces the adhesion of E.
coli at concentrations below the minimum inhibitory
concentration. Sarmiento and Moon (1988) reported
that PWECD induced by a tetracycline-resistant strain
takes an identical course in pigs eating feed with and
without tetracycline.
Zinc oxide offers an alternative to antimicrobials.
Feeds with contents between 2400 and 3000 ppm of zinc
reduce diarrhea and mortality and improve growth. The
activity is explained by an antibacterial effect (Holm and
Poulsen 1996). However, environmental considerations
should be included in discussions of zinc oxide at such
high levels.
 CHAPTER 32 ESCHERICHIA COLI INFECTIONS
Dietary Measures
Restriction of feed intake, high-fiber diets, or ad libitum
feeding of fiber have been reported as effective deter-
rents to the development of ED and postweaning diar-
rhea (Smith and Halls 1968; Bertschinger et al. 1978;
Rantzer et al. 1996). The nutritive value of the feed may
be reduced by increasing fiber content to 15–20% and re-
ducing crude protein and digestible energy to one-half of
the normal values (Bertschinger et al. 1978). The addi-
tion of fiber to normal diets may be beneficial. Dunne
(1975) advocated feeding high-quality alfalfa coupled
with restriction of daily feed intake. To be effective, nu-
trient intake has to be low enough to maintain daily gain
below 1% of body weight in the 2 weeks after weaning.
Such diets prevent colonization and impair the develop-
ment of immunity in the same way as antimicrobials.
Later outbreaks are frequently seen.
A lower mortality due to E. coli enterotoxemia and
improved weight gains were reported after introduction
of rations with a reduced acid-binding capacity. A simi-
lar effect is ascribed to organic acids. Others were unable
to reduce the mortality due to ED by the inclusion of a
mixture of organic and inorganic acids in the feed (Jo-
hansen et al. 1996b). This result is not surprising in view
of the highly regulated pH close to the mucosal surface
(McEwan et al. 1990).
Exogenous as well as endogenous proteases lower the
activity of intestinal F4 receptors. Bromelain, a protease
from pineapple stems, applied orally to pigs reduced the
binding of F4-positive ETEC to brush borders in a dose-
dependent manner (Mynott et al. 1996). The efficacy in a
clinical situation remains to be demonstrated.
Scandinavian workers have shown that antisecretory
factor reverses secretory diarrhea induced by heat-labile
enterotoxin. The levels of antisecretory factor in the
blood plasma can be increased by addition of glucose
and of some amino acids to the feed. Treated weaner pigs
were reported to have a lower incidence of diarrhea and
a greater weight gain (Göransson et al. 1993). Antisecre-
tory factor probably exerts its effects on the enteric ner-
vous system (Hansen and Skadhauge 1995).
Bacterial Probiotics
In recent investigations Enterococcus faecium, Lactobacil-
lus sp., and Bacillus cereus strain “toyoi” were fed to ex-
perimentally (De Cupere et al. 1992) and to naturally in-
fected (Johansen et al. 1996b) pigs. No preventive effect
was recorded. Schulze (1977) confirmed earlier compar-
ative quantitative studies of the gastrointestinal flora in
weaned and in unweaned pigs, where no evidence was
found for an interdependence between E. coli and the
other components of the flora.
General Management
Management of the weanling pig should minimize envi-
ronmental and other forms of stress such as unnecessary
mixing of litters, chilling, transportation, assignment to
Bertschinger, Fairbrother 451
new pens, etc. Wathes et al. (1989) observed a higher in-
cidence of scours and greater mortality due to PWECD
in experimentally infected pigs kept at 15˚C than in con-
trols at higher temperatures. The experiment was not
perfectly conclusive because genetic resistance was ne-
glected.
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SYSTEMIC INFECTION
J. M. Fairbrother
E. coli may induce systemic infections such as septicemia
or localized extraintestinal infections such as meningitis
or arthritis, resulting from bacteremia (Fairbrother and
Ngeleka 1994; Fairbrother et al. 1989; Morris and Sojka
1985). Septicemia due to E. coli may be primary, occur-
ring predominantly in newborn to 4-day-old pigs, or sec-
ondary, when associated with diarrhea or other compro-
mising diseases in young pigs.
ETIOLOGY
Only a relatively small number of E. coli serogroups have
been reported in natural cases of septicemia. Serogroups
O6, O8, O9, O11, O15, O17, O18, O20, O45, O60, O78,
O83, O93, O101, O112, O115, and O116 have most com-
monly been identified in isolates associated with sep-
ticemia (Morris and Sojka 1985; Gyles 1986; Nielsen et
al. 1975a; Fairbrother et al. 1989). Other gram-negative
bacteria such as Klebsiella spp. and Pseudomonas spp.
have been reported to be associated with systemic infec-
tions in pigs (Nielsen et al. 1975b). In a 4-year study in
our laboratory from 1989 to 1992, the most commonly
observed serogroups in isolates from cases of primary
septicemia were O9 (10%) and O20 (18%) (Fairbrother
and Ngeleka 1994). Serogroups O1, O18, O60, O78,
O101, O141, and O147 were isolated in relatively
Wieler, L. H.; Franke, S.; Menge, C.; Rose, M.; Bauerfeind,
R.; Karch, H.; and Baljer, G. 1995. Investigations on the
immunoresponse during edema disease of piglets after
weaning by using a recombinant B subunit of Shiga-like
toxin IIe. Dtsch Tierärztl Wochenschr 102:40–43.
Wittig, W.; Klie, H.; Gallien, P.; Lehmann, S.; Timm, M.;
and Tschäpe, H. 1995. Prevalence of the fimbrial anti-
gens F18 and K88 and of enterotoxins and verotoxins
among Escherichia coli isolated from weaned pigs. Zbl
Bakt 283:95–104.
Zhu, C.; Harel, J.; Jacques, M.; Desautels, C.; Donnenberg,
M. S.; Beaudry, M.; and Fairbrother, J. M. 1994. Viru-
lence properties and attaching-effacing activity of Es-
cherichia coli O45 from swine postweaning diarrhea. In-
fect Immun 62:4153–4159.
Zúñiga, A.; Yokoyama, H.; Albicker-Rippinger, P.; Eggen-
berger, E.; and Bertschinger H. U. 1998. Reduced intesti-
nal colonization with F18-positive enterotoxigenic Es-
cherichia coli in weaned pigs fed chicken egg antibody
against the fimbriae. FEMS Immunol Med Microbiol (in
press).
lower numbers (2–4% each), but 49% of isolates were
nontypeable. Not all E. coli isolates are able to cause sep-
ticemia in colostrum-deprived piglets (Meyer et al. 1971;
Murata et al. 1979).
The characteristics of E. coli involved in porcine sep-
ticemia have not been greatly studied. However, sep-
ticemia-inducing strains may express virulence determi-
nants which include fimbriae, polysaccharide capsule
and O-antigen capsule, lipopolysaccharide (LPS), the
aerobactin system, hemolysin, and other cytotoxins.
Fimbrial adhesins associated with E. coli isolates from
piglets with septicemia include the F1651, F1652 (Contre-
pois et al. 1989; Fairbrother et al. 1986), and other fim-
briae of the P, S, and F1C fimbrial families (Dozois et al.
1997).
Enterotoxigenic E. coli may be associated with sec-
ondary septicemia, particularly in older piglets. These
isolates most frequently belong to the pathotypes LT +
STb, Sta + STb, or STb and may produce the F4 fimbriae
(see Table 32.1).
The virulence determinants most frequently associat-
ed with isolates from primary septicemia in pigs or iso-
lates inducing septicemia in newborn colostrum-de-
prived pigs are F1651, F1652, or other fimbriae of the P, S,
and F1C fimbrial families, production of colicin V, pro-
duction of the siderophore aerobactin, and resistance to
 CHAPTER 32 ESCHERICHIA COLI INFECTIONS
the bactericidal effects of serum (Fairbrother and Ngele-
ka 1994). Isolates from cases of primary septicemia may
occasionally produce cytotoxic necrotizing factor
(CNF1).
EPIDEMIOLOGY
Primary septicemia is most often seen as sporadic cases
and rarely in the form of a small outbreak (Nielsen et al.
1975a). The disease may occur throughout the suckling
period, with exceptional cases in pigs up to 80 days old.
Epidemiology of the secondary systemic infection is de-
termined by the underlying disease.
PATHOGENESIS
Primary neonatal septicemia occurs in piglets lacking
immunity, due either to an absence of ingested
colostrum or to ingestion of colostrum lacking specific
antibody. The disease may develop after bacterial inva-
sion of the respiratory or the gastrointestinal tract in the
nonimmune host. Contamination of the umbilicus after
birth may also lead to colisepticemia. However, the intes-
tine is considered as a major route of E. coli invasion
since the disease can be experimentally induced by oral
or intragastric administration of the organisms (Ngeleka
et al. 1993).
Secondary septicemia may develop after invasion of
the host by enterotoxigenic E. coli (ETEC), but in most
cases development of primary neonatal septicemia is as-
sociated with intestinal permeability to macromolecules,
to some defect of the immune system (e.g., low levels of
maternal colostrum), to low birth weight, and to sub-
lethal malformations (Gyles 1986; Murata et al. 1979).
Bacteria may pass through the mucosa of the alimen-
tary tract, probably by endocytic uptake into intestinal
epithelial cells or through the intercellular spaces formed
by lateral plasma membranes of adjacent epithelial cells,
to locate in the mesenteric lymph nodes before entering
the bloodstream. This bacterial invasion may result in a
generalized infection (septicemia, polyserositis) with
bacteria disseminated in different extraintestinal organs
such as lung, liver, spleen, kidney, brain, and heart
blood, or in a localized infection (meningitis or arthritis)
(Morris and Sojka 1985). In the sow, a puerperal sepsis
may be induced by an enteric E. coli soon after farrowing
(Sojka 1965).
Septicemia may be produced experimentally in
colostrum-deprived piglets by intragastric inoculation
with isolates of porcine origin (Fairbrother and Ngeleka
1994; Ngeleka et al. 1993). However, the disease can also
be reproduced in piglets with isolates from other sources,
such as calves, cats, and poultry (Fairbrother et al. 1993;
Murata et al. 1979; Meyer et al. 1971). Animals may de-
velop fever, anorexia, diarrhea, dyspnea, or nervous
Bertschinger, Fairbrother 455
signs, due in part to the effect of bacterial endotoxin or
cytotoxins or to the effects of inflammatory cytokines in-
duced by these bacterial products (Nakajima et al. 1991;
Jesmok et al. 1992).
The role of some of the virulence determinants asso-
ciated with E. coli–inducing septicemia is only partially
understood. LPS, K capsule and O-antigen capsule, and
production of siderophores such as aerobactin are
thought to allow the bacteria to invade the host and es-
cape its defense mechanisms. These determinants in-
crease bacterial resistance to the bactericidal effect of
complement and to phagocytosis and allow bacterial
growth in body fluids with low concentrations of free
iron (Crosa 1989; Ngeleka et al. 1992, 1993).
Fimbriae appear to be important for the survival and
spread of bacteria within the host and subsequent bacte-
rial pathogenicity, in part by promoting bacterial resis-
tance to the bactericidal effects of phagocytosis (Ngeleka
et al. 1992, 1993, 1994).
CLINICAL SIGNS
Clinical signs of infection include depression, lameness,
reluctance to move, anorexia, rough hair coat, and la-
bored respiration (Nielsen et al. 1975a). The affected
piglets may show sternal recumbency and the abdomen
may be somewhat distended. Sometimes piglets become
unconscious, with convulsions and paddling move-
ments; they may be in good bodily condition but
cyanosis of the extremities may be observed. Some
piglets are found dead while others are comatose without
any sign of diarrhea. These clinical signs may develop
within 12 hours after birth and piglets can die within 48
hours (Taylor 1989). In older piglets, the clinical signs
may include periodic scouring or other ailments which
precede the onset of acute septicemia with clinical signs
resembling those in the newborn pigs.
LESIONS
In acute primary septicemia, there may be no gross le-
sions other than congestion of the intestine, the mesen-
teric lymph nodes, and the extraintestinal organs. In sub-
acute cases, subserous or submucosal hemorrhages and
fibrinous polyserositis with gross signs of pneumonia
are usually observed, often accompanied by fibrinopuru-
lent arthritis and meningitis (Morris and Sojka 1985;
Waxler and Britt 1972). Histological examination of the
lung reveals interalveolar interstitial pneumonia with
edema and neutrophilic infiltration, but alveoli are free
of exudates. In secondary septicemia resulting from en-
teric colibacillosis, icterus, petechial hemorrhages in the
serosal membranes, and splenomegaly accompanied by
severe diarrhea and dehydration can be observed in
some cases (Svendsen et al. 1975). In many cases of sec-
456 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
ondary systemic E. coli infection, presumably occurring
at a very late stage in the underlying disease, the changes
are slight or no lesions at all are recorded.
DIAGNOSIS
Systemic colibacillosis is generally suspected with the ap-
pearance of the clinical signs described above. However,
in the case of polyserositis, a differential diagnosis be-
tween Mycoplasma hyorhinis and Hemophilus parasuis has
to be made. In the former infection, gross lesions can be
detected more than 6 days after infection. Mortality is
lower than in E. coli infection. In polyserositis due to E.
coli, the exudates encountered in piglets are serofibri-
nous or fibrinopurulent, whereas in Hemophilus parasuis
they tend to be serofibrinous. In the central nervous sys-
tem and joints, these exudates are fibrinopurulent to pu-
rulent (Waxler and Britt 1972). Infection due to H. para-
suis is rarely seen in the early suckling period but is more
common in piglets of 2–3 months of age. However, dif-
ferential diagnosis can be established after a careful mi-
crobiological examination. In most of the cases, post-
mortem examination and bacteriology are useful for
identifying the infection. Diagnosis of primary systemic
colibacillosis is strengthened by the isolation in pure cul-
ture or by the predominance of E. coli in extraintestinal
tissues, particularly E. coli of one of the above-men-
tioned serogroups or, more important, possessing one or
more of the virulence factors, such as adhesins of the P,
S, or F1C families, serum resistance, or production of
aerobactin. Diagnosis of secondary systemic colibacillo-
sis is strengthened by the isolation in pure culture or by
the predominance in extraintestinal tissues of E. coli pos-
sessing one or more of the enterotoxins LT, STa, or STb
and possibly one of the fimbrial adhesins associated with
ETEC, particularly F4.
PREVENTION AND TREATMENT
Inadequate hygiene and poor environmental tempera-
ture control increase the likelihood of infection. Thus,
prevention of infection should concentrate on reduction
or elimination of significant pathogenic E. coli popula-
tions in the environment of the piglets and in providing
a plentiful supply of colostrum at birth. Hygiene, espe-
cially washing and disinfection of the farrowing pens,
will efficiently contribute to reduction of the infection.
Young piglets should be maintained at an even tempera-
ture of 35˚C for the first week of life. They must be kept
dry and warm in clean surroundings. Affected piglets
should be treated if necessary, and other litters of sus-
ceptible age watched. However, in the case of small out-
breaks, careful monitoring of the causative serogroup(s)
and autovaccination of the pregnant sows might be ben-
eficial.
Treatment may be attempted after diagnostic confir-
mation of E. coli infection and antibiotic sensitivity test-
ing. Meanwhile, parenteral or oral administration of
broad-spectrum antibiotics to affected piglets is recom-
mended while waiting for results of diagnostic lab tests.
This treatment may be useful in subacute cases of infec-
tion but is mostly ineffective after the appearance of clin-
ical signs. However, the remaining piglets in the litter
and affected piglets and littermates in adjacent litters
should be treated.
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1989. Pathogenicity of Escherichia coli O115:K“V165”
strains isolated from pigs with diarrhea. Am J Vet Res
50:1029–1036.
Fairbrother, J. M.; Harel, J.; Forget, C.; Desautels, C.; and
Moore, J. 1993. Receptor binding specificity and patho-
genicity of Escherichia coli F165-positive strains isolated
from piglets and calves and possessing pap related se-
quences. Can J Vet Res 57:53–55.
Gyles, C. L. 1986. Escherichia coli. In Pathogenesis of Bacter-
ial Infections in Animals. Ed. C. L. Gyles and C. O.
Thoen. Ames: Iowa State Univ Press, pp. 114–131.
Jesmok, G.; Lindsey, C.; Duerr, M.; Fournel, M.; and Emer-
son, T. Jr. 1992. Efficacy of monoclonal antibody against
human recombinant tumor necrosis factor in E.
coli–challenged swine. Am J Pathol 141:1197–1207.
Meyer, R. C.; Saxena, S. P.; and Rhoades, H. E. 1971. Poly-
serositis induced by Escherichia coli in gnotobiotic swine.
Infect Immun 3:41–44.
Morris, J. A., and Sojka, W. J. 1985. Escherichia coli as a
pathogen in animals. In The Virulence of Escherichia
coli: Reviews and Methods. Ed. M. Sussman. London:
Academic Press, pp. 47–77.
 CHAPTER 32 ESCHERICHIA COLI INFECTIONS
Murata, H.; Yaguchi, H.; and Namioka, S. 1979. Relation-
ship between the intestinal permeability to macromole-
cules and invasion of septicemia-inducing Escherichia
coli in neonatal piglets. Infect Immun 26:339–347.
Nakajima, Y.; Ishikawa, Y.; Momotani, E.;, Takahashi, K.;
Madarame, H.; Ito, A.; Ueda, H.; Wada, M.; and Taka-
hashi, H. 1991. A comparison of central nervous lesions
directly induced by Escherichia coli lipopolysaccharide in
piglets, calves, rabbits and mice. J Comp Pathol
104:57–64.
Ngeleka, M.; Harel, J.; Jacques, M.; and Fairbrother, J. M.
1992. Characterization of a nonacidic polysaccharide
capsular antigen of septicemic Escherichia coli O115:K
“V165”:F165 and evaluation of its role in pathogenicity.
Infect Immun 60:5048–5056.
Ngeleka, M.; Jacques, M.; Martineau-Doizé, B.; Harel, J.;
and Fairbrother, J. M. 1993. Pathogenicity of an Es-
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fimbriae in septicemia of gnotobiotic pigs. Infect Im-
mun 61:836–843.
Ngeleka, M.; Martineau-Doizé, B.; and Fairbrother,
J. M. 1994. Septicemia-inducing Escherichia coli
COLIFORM MASTITIS
H. U. Bertschinger
The term “coliform mastitis” (CM) has been introduced
to denominate puerperal mastitis in the pig. The term
should end the confusing terminology in this field. In ad-
dition, this expression points out the parallels to CM in
the cow. Other terms used to denominate CM and relat-
ed conditions are discussed in Chapter 58 of this book. A
cumulative tabulation of necropsies performed on
agalactic sows revealed that 59 of 72 sows (82%) had
gross lesions of mastitis (Ross et al. 1981).
CM has a worldwide distribution. Hermansson et al.
(1978) disclosed an average incidence of agalactia post-
partum of 12.8%, with a variation among individual
herds from 0.5% to 50%. In a Danish study covering more
than 72,000 farrowings on farms with a high manage-
ment level, the incidence amounted to 9.5% of the far-
rowings (Jorsal 1986). In these studies, the true inci-
dence of CM was not determined. Wegmann et al.
(1986) examined samples of colostrum from 59 sows in
15 herds with a so-called mastitis-metritis-agalactia
(MMA) problem. No fewer than 83% of the sows were af-
fected with mastitis in at least one mammary complex. E.
coli or Klebsiella pneumoniae were isolated from 79% of
the 131 complexes with mastitis.
Economic loss results from a number of factors and
therefore is difficult to estimate. The death rate of affect-
ed sows is low. The cost of extra care and of treatment is
Bertschinger, Fairbrother 457
O115:K“V165” resist killing by porcine polymorphonu-
clear leukocytes in vitro: Role of F1651 fimbriae and
K “V165” O-antigen capsule. Infect Immun 62:398–
404.
Nielsen, N. C.; Bille, N.; Riising, H. J.; and Dam, A. 1975a.
Polyserositis in pigs due to generalized Escherichia coli
infection. Can J Comp Med 39:421–426.
Nielsen, N. C.; Riising, H. J.; Larsen, J. L.; Bille, N.; and
Svendsen, J. 1975b. Preweaning mortality in pigs: Acute
septicaemias. Nordisk Vet Med 27:129–139.
Sojka, W. J. 1965. Escherichia coli in Domestic Animals and
Poultry. Farnham Royal, Bucks, England: Commonw
Agric Bur.
Svendsen, J.; Bille, N,; Nielsen, N. C.; Larsen, J. L.; and Riis-
ing, H.-J. 1975. Preweaning mortality in pigs. 4. Diseases
of the gastrointestinal tract in pigs. Nord Vet Med
27:85–101.
Taylor, D. J. 1989. Pig Diseases, 5th ed. Lennoxtown, Glas-
gow, pp. 171–172.
Waxler, G. L., and Britt, A. L. 1972. Polyserositis and arthri-
tis due to Escherichia coli in gnotobiotic pigs. Can J Comp
Med 36: 226–233.
hard to assess. The piglets suffer more than the affected
dam. Bäckström et al. (1984) reported that the mortality
of piglets nursing multiparous sows with MMA was
55.8%, whereas that of piglets nursing healthy sows was
17.2%. The corresponding figures determined by Madec
et al. (1992) from 286 parturitions were 21% and 17%, re-
spectively. Mortality of piglets may result from length-
ened farrowing time, crushing by the sow, starvation,
and impaired immunity to infectious agents because of
insufficient uptake of colostral immunoglobulins. The
average milk yield of three sows affected with CM on the
first 2 days after farrowing was about half the yield of
healthy sows, and the piglets of the sick sows lost some
weight (Ross et al. 1975). Piglets sucking glands with
mastitis of sows with subclinical CM had smaller weight
gains only for days 1–4 postpartum (Bertschinger et al.
1990).
ETIOLOGY
The term “coliform,” when used in the context of masti-
tis, covers the bacterial genera Escherichia, Klebsiella, En-
terobacter, and Citrobacter. However, the methods used
for identification in several studies were not adequate to
determine the genera and even less the species of the
bacterial isolates. E. coli was the organism most often
458 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
identified in either milk samples or affected mammary
tissue (Ringarp 1960; Armstrong et al. 1968;
Bertschinger et al. 1977a; Ross et al. 1981; Wegmann et
al. 1986). Klebsiella, mostly K. pneumoniae, was prevalent
in the cases investigated by Ross et al. (1975) and Jones
(1976). Staphylococcus epidermidis and a variety of strep-
tococci were also found in the mammary glands of sows
with signs of mastitis, either mixed with coliforms or as
pure cultures. The noncoliform organisms were only ex-
ceptionally associated with microscopic lesions of masti-
tis (Bertschinger et al. 1977a; Ross et al. 1981).
EPIDEMIOLOGY
CM of the sow appears to be noncontagious. Serologic
typing of isolates from mastitis revealed an extreme mul-
tiplicity of serologic types not only within a herd but al-
so within distinct glands of one sow. A significant pro-
portion of subcomplexes harbor more than one type
(Bertschinger et al. 1977a; Awad-Masalmeh et al. 1990).
The great variety of coliform bacteria associated with
CM indicates an abundant reservoir of potentially path-
ogenic bacteria. The coliforms causing mastitis may orig-
inate from the flora of the sow as well as from the envi-
ronment. In about one-third of the sows with mastitis,
identical isolates were found in mastitic glands, the uter-
ine contents, and the urinary bladder (Bertschinger et al.
1977a). The intestinal flora of the sow, the oral flora of
the neonatal piglet, and environmental bacteria may sig-
nificantly contribute to contamination of the nipples.
Awad-Masalmeh et al. (1990) found identical O
serogroups of E. coli in mammary secretion and in feces
of about one-fourth of 67 sows with CM. Muirhead
(1976) considered the bedding of the sow of paramount
importance. Dung and urine contaminate the udder.
Klebsiella spp. may also originate from wood shavings
used for bedding. Bertschinger et al. (1990) compared 12
farrowings each in conventional farrowing crates and in
an experimental pen where the sows could lie down in a
clean resting area. Sows in the experimental pen had
much lower counts of coliform bacteria on their teat
ends and an incidence of intramammary E. coli infec-
tions 10 times lower than that of the sows in the crates.
PATHOGENESIS
Invasion of the Mammary Gland
Mastitis was reproduced in the sow by intramammary
instillation of not more than 120 organisms of a strain of
K. pneumoniae. Following massive external contamina-
tion of the nipples with the same strain, the bacteria
were recovered from 60 out of 142 subcomplexes exam-
ined. External contamination of the nipples was as suc-
cessful on gestation day 111 as 2 hours after completion
of farrowing (Bertschinger et al. 1977b). It is largely un-
known at what time spontaneous invasion of the cistern
takes place. McDonald and McDonald (1975) found sig-
nificant numbers of coliform bacteria in about one-
fourth of mammary glands cultured just before parturi-
tion. In a sequential examination of the mammary
secretions, E. coli was isolated from 30 glands. In 17 of
these glands, the bacteria were detected before the first
piglet was born (Bertschinger et al. 1990). New infec-
tions appeared not later than day 2 postpartum.
The bacteria are located in the ductular and alveolar
lumina, either free or within phagocytic cells. Adhesion
to surfaces is not prominent. At postmortem examina-
tion the causative bacteria are frequently isolated from
regional lymph nodes, whereas isolations from liver,
spleen, or kidney are rare (Armstrong et al. 1968;
Bertschinger et al. 1977a, b; Ross et al. 1981).
Multiplication of bacteria in the mammary secretion
is controlled by antimicrobial mechanisms, which so far
have been studied in the pig with respect to piglet enteri-
tis only. The antimicrobial activity of cow’s milk is due to
a variety of inhibitors acting in concert and conferring
on the dry udder a nearly total resistance to coliform pro-
liferation (Bramley 1976). Growth in vitro of a given
strain of E. coli in secretions of individual sows varies
enormously. The secretion of atrophic glands exerts a
bactericidal effect (Wegmann 1985). CM is a self-curing
disease. The bacteria generally disappear between 1 and
6 days after parturition (Wegmann and Bertschinger
1984; Bertschinger et al. 1990). In severe cases, however,
they persist in necrotic foci throughout lactation (Löpfe
1993).
Mammary Inflammation
CM in the sow is associated with massive accumulation
of neutrophils in the lumina of affected glands. Simulta-
neous induction of CM in several mammary subcom-
plexes of sows from which the piglets had been removed
resulted in severe leukopenia within 24 hours
(Bertschinger et al. 1977b). Intracisternal instillation of
identical bacterial inocula following a highly standard-
ized protocol led to a spectrum of reactions ranging from
very severe local and general signs to subclinical mastitis
(Löpfe 1993; Mossi 1995). Severe reaction is the conse-
quence of massive and persistent multiplication of inoc-
ulated bacteria. In the experiments of Löfstedt et al.
(1983) susceptibility to experimental infection was asso-
ciated with impaired function of circulating neutrophils.
The cause of the impaired neutrophil function is still a
mystery. Cytological findings in the secretion must be in-
terpreted with caution. Mammary glands not chosen by
a piglet undergo involution soon after parturition. Invo-
lution is accompanied by an increase in the total somatic
cell count as well as in the proportion of polymorphonu-
clear (PMN) cells (Wegmann and Bertschinger 1984). In
some sows many glands show increases of total somatic
and of PMN cells in the absence of cultivable bacteria
(Bertschinger et al. 1990).
 CHAPTER 32 ESCHERICHIA COLI INFECTIONS
Systemic Reaction
The systemic signs of CM are brought about by the bac-
terial endotoxin. An outline of the systemic changes is
given in Chapter 58. CM in the absence of systemic reac-
tion is often revealed by methodical examination of
mammary secretion (Wegmann 1985; Bertschinger et al.
1990; Persson et al. 1996b).
Immunity
CM apparently does not result in protection against ho-
mologous reinfection (Bertschinger and Bühlmann
1990). Ringarp (1960) reported a higher incidence in
sows than in gilts, as well as repeated occurrence in indi-
vidual sows of up to 10 times. Vaccination is not a
promising method for control of mastitis. Even when an
autogenous vaccine was used, protection was unsatisfac-
tory (R. Ross, Ames, Iowa, unpublished data—1983).
In the cow, there is considerable evidence that vacci-
nation with an R-mutant of E. coli results in a dramati-
cally reduced incidence of CM (Tyler et al. 1993). Vacci-
nation has little impact on the frequency of new
infections but decreases the incidence of overt disease.
No reports have appeared so far on the efficacy of such
vaccines in the sow.
CLINICAL SIGNS
Ross et al. (1975) described the clinical findings in sows
with proven CM and demonstrated changes quite similar
to those described earlier in sows with lactational failure.
Interpretation of clinical parameters is rendered difficult
by the presence of subclinical CM in apparently healthy
sows (Nachreiner and Ginther 1972; Middleton-
Williams et al. 1977; Persson et al. 1996b).
The initial signs are most often detected on the first
or second day and more rarely on the third day after far-
rowing. However, they may be observed as early as dur-
ing parturition (Martin et al. 1967). The first symptoms
are temperature response, listlessness, weakness, and
loss of interest in piglets. Affected sows prefer sternal re-
cumbency. In severe cases they become stiff and dizzy,
do not stand up, and may even become comatose. Con-
sumption of feed and water is either reduced or absent.
Body temperature is moderately elevated and only rarely
exceeds 42˚C. Afebrile cases have been reported; howev-
er, the temperature was not taken continuously. On the
other hand, many normal sows will have rectal tempera-
tures that exceed the 39.7˚C limit on the day of parturi-
tion and for 2 days thereafter (King et al. 1972). In af-
fected sows respiratory and heart rates are increased. In
general the symptoms described do not last for more
than 2–3 days.
The behavior of the piglets is very helpful in the early
detection of lactational failure. Undernourished piglets
look gaunt. They frequently try to suck, move from nip-
ple to nipple, nibble at litter, and lick urine from the
Bertschinger, Fairbrother 459
floor. If access to the nipples is given by the sow, the pe-
riods of suckling are shortened. After suckling, the
piglets stray about instead of resting in close contact
with their littermates.
Precise localization of mammary lesions is often not
possible because reddening and heat of the skin extend
over several subcomplexes. The reliable clinical assess-
ment of the state of the actual mammary tissue is ren-
dered difficult by subcutaneous fat and considerable sub-
cutaneous edema. If palpable, the mastitic tissue is
firmer and palpation may cause pain. The red color of
the skin is blanched by finger pressure, which causes a
depression of the tissue lasting for some time. Mere clin-
ical examination will at best detect some of the affected
subcomplexes (Persson et al. 1996b). The inguinal
lymph nodes may be swollen.
The fluid expressed from a nipple originates from
more than one subcomplex, because two or, rarely, three
teat canals end in each nipple. Therefore, in samples tak-
en from a nipple, secretion from the unaffected, produc-
tive subcomplex dominates. The exudate from inflamed
subcomplexes looks serous to creamy, like pus. It may
contain clots of fibrin or blood. The pH is of limited di-
agnostic value (Ross et al. 1981; Persson et al. 1996b), but
cytological examination allows differentiation between
healthy and mastitic complexes at least during the first
48 hours after parturition (Wegmann and Bertschinger
1984). Because mastitis is a local process, samples must
be taken from individual complexes and not pooled. The
threshold value of the total cell count varies depending
on the investigator. Bertschinger et al. (1990) suggested
5 × 106 cells per mL and fewer than 70% PMN. In a recent
study, Persson et al. (1996a) proposed 10 × 106 cells per
mL. However, these authors did not distinguish between
sucked and unsucked glands. Involution of some glands
starts as early as 1 day after parturition (Wegmann and
Bertschinger 1984). It leads to a significant increase of
the total cell count accompanied by a transient increase
of up to 60% of the proportion of PMN cells. As a con-
sequence, cytological distinction between involution and
mastitis may be difficult or impossible between 2 and 7
days postpartum (Wegmann 1985). Bacteriological ex-
amination of the secretion may be necessary in unclear
cases. Infection persisting for several days is limited to
severely affected complexes (Löpfe 1993).
LESIONS
Despite the high incidence of CM, there are not many re-
ports of necropsy findings (Martin et al. 1967; Jones
1976; Middleton-Williams et al. 1977; Ross et al. 1981).
In general, lesions are confined to the mammary glands
and regional lymph nodes. The subcutaneous tissue may
be edematous over affected parts of the udder. For reli-
able demonstration of mastitis, Middleton-Williams et
al. (1977) recommended a longitudinal section at the lev-
460 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
el of the nipples through each row of glands. Using this
technique, irregularly scattered foci of mastitis were de-
tected in 1–23 subcomplexes (Fig. 32.9). The appearance
of affected mammary tissue varied from slightly in-
creased firmness and grayish discoloration to sharply de-
marcated, red-mottled, hard, and dry areas (Fig. 32.10).
The secretion was sparse and sometimes mixed with
clots.
32.9. Distribution and intensity of histologic lesions in
nine field cases of CM. (Modified from Middleton-
Williams et al. 1977.)
32.10. Acute CM of one subcom-
plex adjacent to unaltered glandular
tissue in longitudinal cut surface: (a)
subcutaneous edema, (b) demarcation
from adjacent subcomplex, (c) mot-
tled appearance of affected tissue.
By histological examination additional lesions were
detected that had not been recognized at gross examina-
tion. In every case there was an acute purulent exudative
mastitis with congestion. An extreme variability in sever-
ity ranging from a small number of neutrophils in the
alveolar lumina to severe purulent infiltration with
necrosis was obvious (Fig. 32.11). The severity of the le-
sions varied not only between but also within subcom-
plexes, where unaffected tissue was found adjacent to se-
verely inflamed areas. Acute purulent lymphadenitis was
present in the inguinal and iliac lymph nodes (Middle-
ton-Williams et al. 1977). A sequential study of the mi-
croscopic lesions consequent to experimental intracister-
nal inoculation revealed in severe cases the persistence
throughout lactation of abscesslike large necrotic foci
surrounded by granulomatous connective tissue (Löpfe
1993). A predilection of microscopic lesions for certain
areas within a given complex was not evident. The mu-
cosa lining the cisternae was not affected.
DIAGNOSIS
Any hypogalactia at the beginning of lactation arouses
suspicion of CM. The diagnosis may be supported by
fever, anorexia, reluctance to stand up, lying on the
gland, and disinterest in the piglets. In severe cases some
affected glands may be reddened, swollen, and firm, and
the secretion may look abnormal. A reliable rapid test for
use on the farm is not available. Due to the higher cell
content of sow milk, tests developed for use with the cow
cannot be recommended. Bacteriological and cytological
examinations of the secretion make sense only if all
glands are sampled or if affected glands are known.
The differential diagnosis of CM is reviewed in Chapter
58.
 CHAPTER 32 ESCHERICHIA COLI INFECTIONS Bertschinger, Fairbrother 461

32.11. Histopathology of a mammary gland 24 hours after experimental inoculation with a

culture of Klebsiella pneumoniae. (A) Low-power magnification within a single subcomplex
showing different types of mastitis next to secreting alveoli. (B) Dark area filled with densely
packed polymorphonuclear leukocytes and local destruction of epithelium. (C) Nearly empty-
looking alveoli containing low numbers of polymorphonuclear leukocytes. (D) Alveoli with
normal-looking secretion. (Institute of Veterinary Pathology, University of Zurich.)

TREATMENT er than the MIC (Oliel and Bertschinger 1990). Awad-

Therapeutic measures are usually not taken before the
sow shows signs of dysgalactia. Thus, treatment may at
best shorten the period of underfeeding of the piglets.
Chemotherapy is complicated by the heterogeneous
pattern of antimicrobial susceptibility of individual iso-
lates not only within a herd but also within a sow. There-
fore, sensitivity testing is of little value in individual cases.
The pharmacokinetics of antimicrobials has received
only limited attention. One injection of 20 mg/kg body
weight of a slow-release formulation of oxytetracycline
results in milk levels not surpassing 2 µg/mL, that is, just
above the minimum inhibitory concentration (MIC) of
susceptible E. coli (Schoneweis et al. 1982). Enrofloxacin,
a quinolone antibiotic, given at 2.5 mg/kg body weight
orally every half day, is concentrated in colostrum and
milk to mean levels of 1.2 µg/mL, which is 20 times high-
Masalmeh et al. (1990) tested 107 strains of E. coli isolat-
ed from sows with CM from 43 herds and found no re-
sistance to enrofloxacin (Table 32.6). Therapeutic trials
are generally difficult to evaluate because the curing ef-
fect is not quantified and often hardly distinguishable
from spontaneous improvement. Options for supportive
therapy are discussed in Chapter 58.
Much attention should be given to the piglets. They
may either be fostered by other sows or remain with their
mother and receive a milk substitute. Sweetened con-
densed milk diluted with water 1:1 can be used instead of
commercial products. Sterile 5% glucose solution in a
dose of approximately 15 mL can be repeatedly injected
intraperitoneally several hours apart, or a more concen-
trated solution may be applied intragastrically. When
the pig obtains insufficient amounts of milk, protection
against chilling is particularly important.
462 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
Table 32.6. Sensitivity to antimicrobials of coliform isolates from mammary glands in Switzerland and Austria
Bertschinger et al. 1977a
Substance (n = 80)
Ampicillin 90
Tetracycline 19
Chloramphenicol 95
Streptomycin 21
Neomycin 96
Gentamicin 100
Trimethoprim plus 100
sulfamethoxazole
Enrofloxacin not tested
PREVENTION
Hygiene Measures
Muirhead (1976) and Jones (1979) suggested that pro-
tection of the teats from bacterial contamination might
be an effective prophylaxis of CM. Bertschinger et al.
(1990) performed a prospective study of farrowing in
two types of pens. They concluded that the density of
the coliform flora on the teat apex reflects the degree of
contamination of the lying area. Optimal prophylaxis is
achieved by designing farrowing accommodation in such
a manner that the sow is prevented from lying down in
her own excreta. On the other hand, washing and disin-
fection of the pen and of the newly housed sow con-
tribute much less to efficient prophylaxis. If cases of CM
accumulate, the bedding materials should be checked.
Nutrition of the Sow
Drastic reduction of the sow’s ration shortly before par-
turition is a widespread practice. In a carefully designed
long-term study using pairs of full sibs, the reduction of
the daily feed allowance from 3.2 to 1.0 kg of a commer-
cial-type feed lowered the incidence of agalactia from
26.6% to 14.4% (Persson et al. 1989). Udder changes were
registered in a high percentage of the agalactic sows, and
significant numbers of bacteria were found in more than
80% of the agalactic sows. The two feed regimens did not
influence the total cell count, the rate of PMN, or the pH
of the secretion (Persson et al. 1996b). Plonait et al.
(1986) reported a corresponding observation. Experi-
mentally induced CM takes a similar course with sows on
high and low rations (H. U. Bertschinger and A.
Bühlmann, unpublished data). This finding led to the
suggestion that feed reduction might act through re-
duced exposure of the teats due to the much smaller
amounts of feces and urine contaminating the lying area.
Immunoprophylaxis
Induction of specific immunity is hampered by the wide
range of antigenic types of coliforms isolated from sows
with CM. Use of an E. coli bacterin induced poor protec-
Sensitive Isolates (%)
Wegmann et al. 1986 Awad-Masalmeh et al. 1990
(n = 107) (n = 107)
86 74
42 16
81 64
21 21
92 86
100 100
84 51
not tested 100
tion in sows against intramammary challenge with the
same strain used to prepare the bacterin (R. Ross, Ames,
Iowa, unpublished data—1982).
Hormones
Some investigators found an extended period of gesta-
tion in sows developing lactational failure. The length of
gestation can be controlled by use of prostaglandins.
However, the prophylactic application led to conflicting
results. Studies focusing on CM are not known.
Chemoprophylaxis
For the time being, chemoprophylaxis appears to be the
most promising method of control where accommoda-
tion cannot be improved. The prevalence of drug resis-
tance (Table 32.6) and the wide variety of bacteria asso-
ciated with the disease in a given herd must be
considered when the drug is selected. Feed medication
should be replaced by individual application of the drug
in a small amount of feed because the feed consumption
of the sow in the periparturient period is quite variable.
Keeping the period of treatment as short as possible
helps to postpone the emergence of drug resistance. In
field trials, the morbidity from MMA was reduced from
30% to 12% by giving 0.4 g trimethoprim, 1 g sulfadimi-
dine, and 1 g sulfathiazole/150 kg body weight twice a
day. The treatment began on gestation day 112 and last-
ed for 4 days regardless of the day of farrowing (Boll-
wahn 1978). Six intramuscular injections of apramycin
(6.25 mg/kg) at 12-hour intervals reduced the severity of
experimentally induced mastitis (Ross and Zimmer-
mann 1982).
Oliel and Bertschinger (1990) tested oral chemopro-
phylaxis with enrofloxacin on experimentally induced
CM. Three glands of each sow were inoculated with E.
coli and three glands with K. pneumoniae. Eight sows were
not treated (treatment I), eight sows received 2.5 mg
(treatment II), and eight sows received 5.0 mg/kg body
weight twice a day (treatment III). The inoculated bacte-
ria were reisolated in treatment I from 100%, in treat-
ment II from 10%, and in treatment III from 2% of the in-
 CHAPTER 32 ESCHERICHIA COLI INFECTIONS
oculated glands. A beneficial effect on milk productivity
would be expected but could not be demonstrated be-
cause the control sows did not develop systemic signs.
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M. 1977b. Untersuchungen über das Mastitis-Metritis-
Agalaktie-Syndrom (Milchfieber) der Sau. III. Galakto-
gene Erzeugung von Klebsiellen-Mastitis. Schweiz Arch
Tierheilkd 119:265–275.
Bertschinger, H. U.; Bürgi, E.; Eng, V.; and Wegmann, P.
1990. Senkung der Inzidenz von puerperaler Mastitis
bei der Sau durch Schutz des Gesäuges vor Ver-
schmutzung. Schweiz Arch Tierheilkd 132:557–566.
Bollwahn, W. 1978. Effect of strategic TMP/S treatment on
puerperium and conception in sows. Proc Int Congr Pig
Vet Soc 5:KA16.
Bramley, A. J. 1976. Variations in the susceptibility of lac-
tating and non-lactating bovine udders to infection
when infused with Escherichia coli. J Dairy Res
43:205–211.
Hermansson, I.; Einarsson, S.; Larsson, K.; and Bäckström,
L. 1978. On the agalactia postpartum in the sow: A clin-
ical study. Nord Vet Med 30:465–473.
Jones, J. E. T. 1976. Bacterial mastitis and endometritis in
sows. Proc Int Congr Pig Vet Soc 4:E6.
———. 1979. Acute coliform mastitis in the sow. Vet Annu
19:97–101.
Jorsal, S. E. 1986. Epidemiology of the MMA-syndrome, a
field survey in Danish sow herds. Proc Int Congr Pig Vet
Soc 9:93.
King, G. J.; Willoughby, R. A.; and Hacker, R. R. 1972. Fluc-
tuations in rectal temperature of swine at parturition.
Can Vet J 13:72–74.
Bertschinger, Fairbrother 463
Löpfe, P. J. 1993. Experimentelle Mastitis bei der Sau: Kor-
relation der pathologisch-anatomischen und histologis-
chen Befunde mit den klinischen Befunden 4–30 Tage
nach der Ansteckung mit E. coli und Klebsiella pneumoni-
ae. DVM thesis, Zurich.
Löfstedt, J.; Roth, J. A.,; Ross, R. F.; and Wagner, W. C. 1983.
Depression of polymorphonuclear leukocyte function
associated with experimentally induced Escherichia coli
mastitis in sows. Am J Vet Res 44:1224–1228.
Madec, F.; Miquet, J. M.; and Léon, E. 1992. La pathologie
de la parturition chez la truie: Étude épidémiologique
dans cinq élevages. Rec Méd Vét 168:341–349.
Martin, C. E.; Hooper, B. E.; Armstrong, C. H.; and Amstutz,
H. E. 1967. A clinical and pathologic study of the masti-
tis-metritis-agalactia syndrome of sows. J Am Vet Med
Assoc 151:1629–1634.
McDonald, T. J., and McDonald, J. S. 1975. Intramammary
infections in the sow during the peripartum period. Cor-
nell Vet 65:73–83.
Middleton-Williams, D. M; Pohlenz, J.; Lott-Stolz, G.; and
Bertschinger, H. U. 1977. Untersuchungen über das
Mastitis-Metritis-Agalaktie-Syndrom (Milchfieber) der
Sau. I. Pathologische Befunde bei Spontanfaellen.
Schweiz Arch Tierheilkd 119:213–222.
Mossi, R. 1995. Experimentelle Kolimastitis bei der Sau:
Korrelation der pathologisch-anatomischen und histol-
ogischen mit den klinischen Befunden 6–72 Stunden
nach der Inokulation. DVM thesis, Zurich.
Muirhead, M. R. 1976. Veterinary problems of intensive pig
husbandry. Vet Rec 99:288–292.
Nachreiner, R. F., and Ginther, O. J. 1972. Porcine agalactia:
Hematologic, serum chemical and clinical changes dur-
ing the preceding gestation. Am J Vet Res 33:799–809.
Oliel, N., and Bertschinger, H. U. 1990. Prophylaxis of ex-
perimentally induced coliform mastitis in the sow with
enrofloxacin (BAYTRIL®). Proc Int Congr Pig Vet Soc
11:186.
Persson, A.; Pedersen, A. E.; Göransson, L.; and Kuhl, W.
1989. A long term study on the health status and perfor-
mance of sows on different feed allowances during late
pregnancy. I. Clinical observations, with special refer-
ence to agalactia post partum. Acta Vet Scand 30:9–17.
Persson, A.; Pedersen Mörner, A.; and Kuhl, W. 1996a. A
long term study on the health status and performance of
sows on different feed allowances during late pregnancy.
II. The total cell content and its percentage of polymor-
phonuclear leucocytes in pathogen-free colostrum and
milk collected from clinically healthy sows. Acta Vet
Scand 37:279–291.
———. 1996b. A long term study on the health status and
performance of sows on different feed allowances dur-
ing late pregnancy. III. Escherichia coli and other bacte-
ria, total cell content, polymorphonuclear leucocytes
and pH in colostrum and milk during the first 3 weeks of
lactation. Acta Vet Scand 37:293–313.
Plonait, H.; Kump, A. W.-S.; and Schöning, G. 1986. Pro-
464 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
phylaxis of the MMA-syndrome by antibacterial med-
ication and restricted feeding. Proc Int Congr Pig Vet Soc
9:96.
Ringarp, N. 1960. Clinical and experimental investigation
into a post-parturient syndrome with agalactia in sows.
Acta Agric Scand Suppl 7.
Ross, R. F., and Zimmermann, B. J. 1982. Control of Es-
cherichia coli–induced mastitis in sows with apramycin.
Proc Int Congr Pig Vet Soc 7:14.
Ross, R. F.; Zimmermann, B. J.; Wagner, W. C.; and Cox, D.
1975. A field study of coliform mastitis in sows. J Am Vet
Med Assoc 167:231–235.
Ross, R. F.; Orning, A. P.; Woods, R. D.; Zimmermann, B. J.;
Cox, D. F.; and Harris, D. L. 1981. Bacteriologic study of
sow agalactia. Am J Vet Res 42:949–955.
Schoneweis, D. A.; Hummels, S.; and Schulteis, L. 1982.
URINARY TRACT INFECTION
H. U. Bertschinger
Urinary tract infection (UTI) is present whenever any of
the typically sterile sections of the urinary tract are colo-
nized by microbes. UTI may or may not be accompanied
by clinically manifest or subclinical disease. In the
pig, specific UTI caused by Actinobaculum (formerly
Actinomyces) suis (Chapter 63) is distinguished from non-
specific UTI caused by a variety of microbes and dealt
with in this chapter. According to Liebhold et al. (1995),
a nonspecific UTI often paves the way for A. suis.
Severe acute UTI is important to the veterinarian car-
ing for breeding stock (Stirnimann 1984), and UTI is the
predominant cause of death in pigs over 1 year of age
(Häni et al. 1976). In a survey of culled sows, significant
bladder colonization was detected in 17% of the sows,
and 80% of the colonized bladders exhibited histological
lesions of cystitis (Colman et al. 1988).
Many authors have suggested a relationship between
bacteriuria and reproductive disorders, including masti-
tis-metritis-agalactia (MMA). Sows developing MMA
have a much higher prevalence of UTI in the preceding
gestation period than sows with a normal puerperium
(Miquet et al. 1990). According to Petersen (1983), ex-
amination of urine in late pregnancy allows recognition
of sows at risk to develop MMA at subsequent farrow-
ing. However, this view is not without controversy. Simi-
lar prevalences of UTI in herds with and without MMA
were reported by Becker et al. (1985). Potential patho-
genetic relations between UTI and MMA were discussed
in detail by Berner (1988).
Levels of oxytetracycline in plasma and milk in pig. Proc
Int Congr Pig Vet Soc 7:291.
Tyler, J. W.,; Cullor, J. S.; and Ruffin, D. C. 1993. Immuniza-
tion and immunotherapy for mastitis. Vet Clinics N Am:
Food Anim Pract 9:537–549.
Wegmann, P. 1985. Zur Pathogenese der Colimastitis beim
Mutterschwein. DVM thesis, Zurich.
Wegmann, P., and Bertschinger, H. U. 1984. Sequential cy-
tological and bacteriological examination of the secre-
tions from sucked and unsucked mammary glands with
and without mastitis. Proc Int Congr Pig Vet Soc 8:287.
Wegmann, P.; Bertschinger, H. U.; and Jecklin, H. 1986. A
field study on the prevalence of coliform mastitis
(MMA) in Switzerland and the antimicrobial suscepti-
bility of the coliform bacteria isolated from the milk.
Proc Int Congr Pig Vet Soc 9:92.
ETIOLOGY
Stirnimann and Tschudi (1985) gave a description of
postmortem bacteriological findings in 12 sows with
acute urinary tract disease. A. suis was diagnosed in 9
sows, 3 of them monoinfected, by means of an immuno-
fluorescence technique. Two or three bacterial species
were isolated from the 9 sows not monoinfected: E. coli (7
sows), Streptococcus sp. (5 sows), Staphylococcus epider-
midis (2 sows), Klebsiella sp. (1 sow), Pseudomonas sp. (1
sow), Aeromonas sp. and Bacteroides sp. (1 sow). Carr and
Walton (1993) reported that A. suis was detected in 21
out of 23 cases of pyelonephritis. It was only exception-
ally present as a monoinfection.
Urine was obtained by catheter from 90 sows with se-
vere acute urinary tract disease (Stirnimann 1984). A. su-
is was again looked for by immunofluorescence but was
detected in only 10 sows. Thirty-seven sows were
monoinfected. The bacterial spectrum was comparable
to that described above. In a German study, 13 out of 25
sows with a significant bacteriuria but no pyelonephritis
were infected with enterobacteria and streptococci but
were free from A. suis (Liebhold et al. 1995).
In aspirates taken at a slaughterhouse from 114 sow
bladders with significant colonization, Colman et al.
(1988) identified E. coli (81 sows), diverse gram-negative
rods (4 sows), S. aureus (11 sows), S. hyicus (3 sows),
E. faecalis (6 sows), E. faecium (3 sows), S. dysgalactiae
(5 sows), and diverse gram-positive bacteria (7 sows).
 CHAPTER 32 ESCHERICHIA COLI INFECTIONS
A. suis was not detected by anaerobic culture. These fig-
ures suggest a high prevalence of A. suis only in sows
with severe urinary tract disease. Furthermore, nonspe-
cific UTI cannot be regarded as a disease exclusively
caused by E. coli.
The urinary tract is a dynamic microbiological
ecosystem. Dominant bacterial species change sponta-
neously in a significant proportion of sows surveyed over
prolonged periods (Berner 1990). These changes become
more frequent when sows are treated with antimicro-
bials.
EPIDEMIOLOGY
Nonspecific UTI behaves like a noncontagious infectious
disease of endogenous origin. In the canine species, E.
coli isolates from urine and from rectal samples of the
same dog show identity in extended phenotypic and
genotypic tests (Low et al. 1988). Corresponding studies
with the pig are lacking. The fecal flora may achieve ac-
cess to the urinary tract more efficiently in females than
in males. Under intensive confinement conditions, sows’
vulvas are often placed in direct contact with feces
(Smith 1983). The dog-sitting position helps to force fe-
cal material into the vagina. Sows resting for long peri-
ods void urine at longer intervals. However, housing con-
ditions have not yet been studied with respect to UTI.
The age distribution of UTI favors the concept of
continuous exposure to fecal contamination. The preva-
lence of UTI increases from 18% in young sows with 1–3
litters to 38% in old sows with 7 and more litters (Becker
et al. 1985).
PATHOGENESIS
In humans and in dogs colonization of the lower genital
tract and of the urinary tract by E. coli is greatly facilitat-
ed by adhesive fimbriae. In the pig, however, only com-
mon pili were detected on some of the E. coli isolates ex-
amined (Carr and Walton 1992). It is assumed that most
agents ascend through the urethra (Smith 1983). Inva-
sion is favored by the short, wide urethra of the female
pig, the relaxation of the sphincter muscle in late preg-
nancy and puerperium, trauma to the urethra and blad-
der at coitus and parturition, abnormal bacterial colo-
nization of the sinus urogenitalis and the genital organs,
incomplete closure of the vulva, and catheterization of
the bladder (Berner 1988). Repeated examination of in-
dividual sows led to the conclusion that asymptomatic
bacteriuria may temporarily deteriorate to cystitis with
spontaneous remission (Berner 1988). Liebhold et al.
(1995) assumed that nonspecific infection promotes col-
onization of the bladder by A. suis. Carr et al. (1990) pos-
tulate that bacterial colonization leads to shortening and
deformation of the ureteric valve and thereby promotes
Bertschinger, Fairbrother 465
vesicoureteric reflux. The latter could be easily demon-
strated postmortem in cases of acute pyelonephritis.
Serum antibody against the infecting E. coli strain can
regularly be detected in sows with pyelonephritis, less of-
ten in sows with cystitis, and rather rarely in sows with
asymptomatic bacteriuria (Wagner 1990). E. coli strains
may persist in the urinary tract despite high antibody
concentrations in the urine.
UTI predisposes to MMA in one or several ways
(Berner 1988). Ascending invasion of the uterus at par-
turition and of the mammary glands from contamina-
tion of the lying area appears most likely. However, oth-
er routes cannot be ruled out. Identical OK serotypes of
E. coli were found in the urinary bladders and in the uteri
of 3 sows and in the bladder and mammary gland of 1
out of 9 sows with MMA killed for postmortem exami-
nation (Bertschinger et al. 1977).
CLINICAL SIGNS
In the vast majority of nonspecific UTI cases there are no
clinical signs (Berner 1988). Akkermans and Pomper
(1980) concluded from an extended field study that sows
with a significant bacteriuria tend to wean small litters,
have increased intervals between litters, show a lower
fertility rate, and exhibit an inferior body condition. In
many sows with cystitis, careful observation reveals ab-
normal urination (Becker et al. 1988). The sows stand in
one place before they void urine in small quantities with
straining. They are more often seen in a dog-sitting posi-
tion. Proteinuria, macrohemoturia, and pH increases are
more prevalent in sows infected with A. suis than with E.
coli (Liebhold et al. 1995).
Vulval discharge may appear as dried deposits
around the vulva, on the underside of the tail, or more
often as a pool on the floor underneath the sows (Dial
and MacLachlan 1988a). The discharge may be mucoid,
mucohemorrhagic, or purulent and is observed most of-
ten during the final phase of urination. However, dis-
charge may result from inflammation of any part of the
urogenital tract. Significant discharge is more often the
consequence of endometritis than of UTI.
Severe pyelonephritis becomes clinically manifest
during the first 2 weeks postpartum in 40% of the cases
(Stirnimann 1984). Typical cases exhibit a rectal temper-
ature below 38.0˚C, a heart rate over 120, polypnoea,
cyanosis, ataxia, and more rarely generalized tremor
(Stirnimann and Tschudi 1985). The blood concentra-
tions of urea and creatinine are higher than normal.
LESIONS
Berner (1981) examined 118 culled sows for bacteria and
lesions. Twenty-six out of 29 sows with a UTI presented
a cystitis and 12 sows an additional pyelonephritis.
466 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor

The gross lesions of cystitis begin as focal or diffuse
mucosal hyperemia (Dial and MacLachlan 1988b). Sub-
sequently, there may be mucosal ulceration with fib-
rinopurulent exudate over affected areas. The bladder
wall becomes thickened. Similar lesions occur in the
ureters and the renal pelvis if infection ascends the uri-
nary tract. In pyelonephritis the inflammatory process
extends into the renal parenchyma. Wedge-shaped foci
extend from the distorted pelvis to the cortex. Fibrosis of
the kidneys may occur with time.
Microscopic bladder lesions can be found even in
sows with nonspecific UTI and no proteinuria. They con-
sist of a prominent goblet cell proliferation and of in-
traepithelial cysts containing a few granulocytes. The ep-
ithelial layer is infiltrated with neutrophils, whereas
mononuclear cells dominate in the lamina propria (Lieb-
hold et al. 1995).
DIAGNOSIS
Mere clinical examination of the animal is of little value
in the diagnosis of UTI (Stirnimann 1984); urine must be
examined in most cases. Bacteriology of the urinary tract
is complicated by the normal flora colonizing the vagina
and the distal part of the urethra. Therefore, distinction
between contamination and infection is based on the
number of bacteria in the urine. A viable count of 105
CFU/mL is interpreted as indicative of infection and 104
CFU/mL as suspicious. Dip slides (i.e., commercially
available slides covered by bacterial culture media) give
satisfactory quantitative results (Akkermans and Pom-
per 1980). Dip slides have the shortcoming that anaer-
obes such as A. suis and slow growers will be missed.
Catheterization of the sow is possible (Stirnimann
1984) but does not circumvent contamination and in-
volves the risk of setting up a new UTI. Voiding can be in-
duced by rousing the sows in the morning before feeding
time (Becker et al. 1985). When collecting midstream
urine, the attendant should avoid contact with the urine,
which may contain zoonotic agents such as leptospires.
Diagnostic test strips are applicable to the urine of
pigs except for nitrite. The sensitivity of the latter test is
too low due to the low nitrite concentration in porcine
urine (Becker et al. 1985). The most useful parameters
are protein, hemoglobin, and pH. In cases due to A. suis,
the pH is strongly alkaline (greater than 8.5) (Carr et al.
1995). Cytological examination may allow discrimina-
tion between bacteriuria, cystitis, and pyelonephritis.
The presence and concentrations of antibodies in the
urine are not well correlated with the severity of the con-
dition (Wagner 1990). Test strips permit the rapid deter-
mination of blood urea (Liebhold et al. 1995). Concen-
trations greater than 10 mmol/L indicate uremia.
TREATMENT
Nearly all the treatments recommended in the literature
are aimed at elimination of the bacteria by antimicro-
bials. The variable susceptibilities of the diverse bacteria
involved and the frequent acquisition of R factors pose
considerable problems (Table 32.7). With regard to the
observed changes of infecting bacterial species or types

Table 32.7. Antimicrobial sensitivity of significant isolates from porcine UTI in Belgium and Switzerland
Rate of Sensitive Isolates (%)
Colman et al. 1988 Stirnimann 1988
Gram-negative Gram-positive E. coli
Substance (n = 62) (n = 18) (n = 21)
Penicillin G NT 44 NT
Penicillinase-stable penicillins NT 72 NT
Ampicillin 68 44 71
Amoxycillin and clavulanic acid 100 72 NT

Streptomycin 40 44 NT
Neomycin 98 61 86
Spectinomycin 85 72 NT
Gentamicin 100 61 100

Tetracycline 47 61 33
Chloramphenicol 82 83 67
Nitrofurane 95 94 14
Sulfonamide 37 50 52
Trimethoprim 76 61 NT
Trimethoprim and sulfonamide NT NT 76
Macrolide NT 61 NT
Lincomycin NT 72 NT
Note: NT = not tested.
 CHAPTER 32 ESCHERICHIA COLI INFECTIONS
in the course of antimicrobial treatments, Berner (1990)
recommended the use of either broad-spectrum or com-
bined antimicrobials and suggested intensifying the
search for alternative strategies.
Becker et al. (1988) treated 9 sows twice daily for 2
weeks via feed with sulfadimidine 1.0 g; sulfathiazole 1.0
g; and trimethoprim 0.4 g/sow. Significant bacteriuria
was present in 2 sows 1 week after the treatment and in 3
sows 7 weeks later. The same substances applied over 4
days gave much inferior results. Gentamicin, 2.5 mg/kg
body weight, was injected intramuscularly to 15 sows on
the first day, followed by 2.0 mg on the next 3 days. One
week after this treatment, 10 sows were free of significant
bacteriuria. The authors concluded that prolonged treat-
ment should be preferred. Antimicrobial resistance was
not checked.
Treatment of severely affected sows was reported by
Stirnimann (1988). With 34 sows each, injection of
ampicillin 3 g/sow daily for 4 days was compared with
the same antibiotic combined with novaminsulfon 10
g/sow. The combined treatment led to a smaller number
of emergency slaughters. Subclinical UTI persisted in
about half of the successfully treated sows.
Dial and MacLachlan (1988b) concluded that treat-
ment of urogenital infections of swine generally is frus-
trating.
PREVENTION
Results of long-term prospective studies are not avail-
able. Berner (1988) recommended that all pregnant sows
be checked repeatedly for UTI and that positive sows be
treated with antimicrobials shortly before parturition.
Smith (1983) suggested medicating all dry sows on prob-
lem farms for 7–10 days at 6-week intervals. The interval
between treatments can be increased gradually as experi-
ence dictates. Antibiotics such as tetracyclines or a suit-
able form of penicillin have been successfully used in the
diet. In view of the disappointing results reported by
Berner (1990), these recommendations should be viewed
with caution.
According to Wagner (1990), immunoprophylaxis
holds little promise. Thus, Smith (1983) and Carr et al.
(1995) recommended the reduction of environmental
exposure by improving fecal drainage and housing con-
ditions. These factors as well as the role of water intake
should be further investigated. Frequency of urination
was increased by giving access to an exercise yard and by
increasing water intake, which was achieved by a salt
content of 1% in the diet (Smith 1983).
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cance of a bacteriuria with reference to disturbances in
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Becker, H.-A.; Kurtz, R.; and Von Mickwitz, G. 1985.
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———. 1993. Bacterial flora of the urinary tract of pigs as-
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———. 1995. Cystitis and ascending pyelonephritis in the
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 Exudative Epidermitis
33 H. C. Wegener and E. W. Skov-Jensen
Exudative epidermitis (EE) has been known by its clinical
signs for over 150 years (Spinola 1842). The classic dis-
ease occurs as an acute or peracute infection in suckling
and newly weaned piglets in which a generalized epider-
mitis may lead to dehydration and death. Early occur-
rence and distribution have been comprehensively re-
viewed by Jones (1956), who provided a good description
of the disease and its effects on production. It has been
recorded in most pig-rearing countries in both piglets
and weaners. Major studies have been carried out by
Sompolinsky (1953), Jones (1956), Underdahl et al.
(1963, 1965), L’Ecuyer (1966), L’Ecuyer and Jericho
(1966), Hunter et al. (1970), and Wegener and Skov-
Jensen 1992. The condition is of sporadic occurrence in
all countries but may be of great importance in individ-
ual herds, especially in newly established or repopulated
herds (Pepper and Taylor 1977).
ETIOLOGY
Staphylococcus hyicus is the causal agent of the general-
ized form of the disease seen in piglets. Although it is
present in profuse culture in lesions in adult pigs, the
disease has not been reproduced in that age group.
Strains of S. hyicus can be divided into virulent and avir-
ulent types with regard to the ability to reproduce EE ex-
perimentally in piglets (Wegener et al. 1993). Both types
can be present simultaneously on the skin of diseased, as
well as healthy, piglets (Park and Kang 1986; Wegener et
al. 1993). The production of an exfoliative toxin appears
to be the single most important virulence determinant of
S. hyicus (Amtsberg 1979; Sato et al. 1991; Wegener et al.
1993; Andresen et al. 1993; Andresen et al. 1997). How-
ever, a range of other factors may also be necessary, but
not sufficient, to render S. hyicus capable of causing EE in
piglets.
S. hyicus was first described by Sompolinsky (1953) as
Micrococcus hyicus; it was then defined as a staphylococ-
cus by Baird-Parker (1965). S. hyicus was separated into
S. hyicus subsp. hyicus and S. hyicus subsp. chromogenes, a
nonpathogen, by Devriese et al. (1978). S. hyicus subsp.
chromogenes was subsequently elevated to species S. chro-
mogenes by Hajek et al. (1986), making S. hyicus the taxo-
nomically correct designation for the causal agent of EE.
The organism is a gram-positive coccus that forms 3–4
mm porcelain-white nonhemolytic colonies on sheep
blood agar after 24 hours’ incubation. It is coagulase neg-
ative using the slide test and is heat-stable DNase, lipase,
and hyaluronidase positive, and mannitol and acetoin
negative. These biochemical characteristics are of value
in distinguishing the organism by conventional means
from other staphylococci found in pigs (Devriese 1977).
A selective indicator medium described by Devriese
(1977) which utilizes the lipase activity as the indicative
principle can be very useful for isolation of S. hyicus from
pathological samples.
S. hyicus may be isolated from a range of other ani-
mals, including ruminants and fowl (Devriese et al.
1978). Phenotypic and genotypic differences from
porcine isolates suggest that S. hyicus from other animals
may belong to separate ecovars (Devriese et al. 1978;
Schleifer 1986; Takeuchi et al. 1988). Their virulence
with regard to EE is not known.
EPIDEMIOLOGY
EE has been described from all major pig-producing
countries, and the incidence has been reported to be in-
creasing in some regions (Anon. 1991; Wegener 1992).
This increase may reflect changes in pig production to-
ward larger units, earlier weaning, and higher animal
densities. The disease may occur sporadically and with
low morbidity among litters in some pig herds, whereas
in others it reaches epidemic proportions affecting all lit-
ters. This suggests that immunity plays an important
part in the cause of the disease in the individual animal
as well as in the herd. The significance of immunity in re-
lation to EE has, however, not been thoroughly investi-
gated.
The disease occurs most commonly following the in-
troduction of carrier animals to a nonimmune herd and
affects successive litters of piglets, usually those born to
nonimmune sows. All litters in an affected herd may be
affected, and up to 70% of affected piglets may die. Out-
breaks are usually self-limiting and last for 2–3 months
but may persist or recur if nonimmune sows are brought
into infected buildings or exposed to infected animals.
Outbreaks may start among the weaned piglets, possibly
as a result of mixing nonimmune litters and litters of im-
mune carriers, and then spread to the farrowing section
of the herd.
S. hyicus can frequently be recovered from the nasal
469
470 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
mucosa of healthy pigs, from the conjunctiva, the skin of
the snout or ear, and from the vagina in gilts and sows
(Hajsig et al. 1985; Wegener and Skov-Jensen 1992). S.
hyicus strains indistinguishable from those present in the
vaginas of sows have been recovered from the skin of
their offspring, suggesting that colonization takes place
during passage through the birth canal (Wegener and
Skov-Jensen 1992).
S. hyicus is very resistant to adverse conditions (as
most staphylococci are) and can persist in the environ-
ment for long periods. The organism can persist for
weeks on fittings and surfaces, and it has been recovered
from the air of infected units at levels up to 2.5 × 104/m3,
suggesting that airborne transmission is possible (We-
gener 1992). Other species such as horses, dogs, cattle,
goats, and chickens may be of little importance as
sources of infection for pigs.
PATHOGENESIS
Application of pure cultures of virulent S. hyicus to the
scarified skin of a nonimmune pig is sufficient to repro-
duce the disease (Underdahl et al. 1965; L’Ecuyer and
Jericho 1966), but it can also be produced by subcuta-
neous injection in specific-pathogen-free (SPF) piglets
(Underdahl et al. 1965; Wegener et al. 1993). Conven-
tional animals may be resistant to such applications, sug-
gesting that immunity may be an important protective
factor. Studies indicate that other elements of the skin
flora, especially other staphylococci, may contribute to
this resistance to colonization (Allaker et al. 1988). Trau-
ma from fighting, unclipped teeth, rough bedding, or
pen walls leading to exposure of dermis may allow the
organism to establish infection, although S. hyicus may
also be able to penetrate the epidermis directly.
The earliest changes are seen as skin reddening ac-
companying the multiplication of the organism on the
skin surface and its growth between the corneocytes of
the epidermis, where microcolonies develop. Inflamma-
tion, marked hyperplasia of the stratum corneum, and
invasion by neutrophils occur, with an increase in thick-
ness of the epidermis, followed by its erosion. The stra-
tum germinativum becomes disorganized and pene-
trates deeply into the dermis. Clinical signs develop in
gnotobiotic piglets when the number of organisms on
the skin exceeds 105/cm2 (Allaker et al. 1988). S. hyicus
may adhere to fibronectin in the dermis by fibronectin-
binding proteins on the bacterial surface (Lämmler et al.
1985).
The phagocyte-opsonin system is the pig’s first active
line of defense against the infection. Many S. hyicus
strains harbor determinants that may protect them from
phagocytosis: protein A, present in the cell wall of most
porcine S. hyicus strains, reduces opsonization by bind-
ing immunoglobulins at the Fc terminal (Takeuchi et al.
1990), and a capsule present in all virulent but not all
avirulent strains of S. hyicus inhibits phagocytosis by
neutrophils and macrophages (Wegener 1990). All
porcine S. hyicus strains coagulate pig plasma, suggesting
a potential for forming aggregates which may increase
protection of the bacterium against phagocytosis. In ad-
dition, the production of catalase may protect the bac-
terium from being killed by the phagocytic cells. All of
these properties may contribute to overcoming the initial
immune response of the piglet.
The most important factor in the pathogenesis is
probably the production of an exfoliative toxin of ap-
proximately 30 kDa. Crude or purified exfoliative toxin,
which is demonstrable in culture supernates of the or-
ganism, can reproduce the skin alterations seen in clini-
cal EE when injected subcutaneously in piglet skin local-
ly (Wegener et al. 1993; Andresen et al. 1993; Sato et al.
1991). There are different antigenic variants of the toxin;
however, they all seem to exert the same activity in pig
skin (Andresen et al. 1997). The effect of the purified tox-
in is separation of the cells in the epidermis, notably sep-
aration of cells in the upper stratum spinosum, allowing
for rapid intraepidermal spread of the bacteria (An-
dresen et al. 1993). Exfoliation of the skin is accompa-
nied by excess sebaceous secretion and serous exudate. S.
hyicus is present in large numbers in the skin and may be
isolated from the draining lymph nodes and blood. The
mortality associated with this disease results from dehy-
dration and possibly also septicemia.
Exudative epidermitis shares many similarities with
the human infection called the staphylococcal scalded
skin syndrome, which is a Staphylococcus aureus infection
of the skin of neonates. The infection leads to a local or
a generalized exfoliation of the epidermis and excessive
sebaceous secretion and is caused by strains of S. aureus
capable of producing exfoliative toxins. Two variants of
the toxin are known: ET-A, which is encoded by a gene lo-
cated on the chromosome, and ET-B, which is plasmid
encoded. The exfoliative toxins of S. aureus and S. hyicus
have different species specificity. ET-A and ET-B affect
the skin of humans and mice but not pigs, whereas the
exfoliative toxin of S. hyicus affects pigs and chickens but
not mice.
CLINICAL SIGNS
Piglets usually develop the disease between 4–6 days and
5–6 weeks of age. Clinical signs begin with dejection and
a reddish or coppery skin color. Thin, pale brown scales
of exudate develop in the axillae and groin and within
3–5 days spread to all parts of the body and rapidly be-
come dark in color and greasy in texture (Fig. 33.1). The
skin of affected piglets often feels hot, the hair coat is
matted, and exudate may extend to the eyelashes. Ulcers
may occur in the mouth, and separation of horn may oc-
 CHAPTER 33 EXUDATIVE EPIDERMITIS Wegener, Skov-Jensen
cur at the bulbs of the heels. Anorexia and dehydration
are features of this disease. Severely affected piglets lose
weight rapidly and may die within 24 hours; death usu-
ally occurs within 3–10 days. There is no pruritis, and
fever is not common.
Not all piglets in a litter are affected to the same ex-
tent, and some individuals will suffer from chronic dis-
ease in which smaller areas of the body are involved (Fig.
33.2). Mildly affected piglets may have a yellowish skin,
appear hairy, and have only a few flakes of exudate in the
axillae or groin or near facial scratches or damage on the
knees or adjacent to badly clipped teeth. Growth depres-
33.2. A single piglet with generalized exudative
epidermitis among only mildly affected or unaffected
littermates.
471
33.1. Generalized exudative
epidermitis in a 3-week-old piglet.
sion is marked in survivors, and productivity of the herd
may be depressed by up to 35% during an outbreak and
up to 9% in the year following infection (Pepper and Tay-
lor 1977). Disease in adults varies in severity but occurs
as localized lesions on the back or flanks. Mild forms
may appear as brownish areas of EE, but in some cases,
there may be ulceration (Smith et al. 1990).
LESIONS
Gross Lesions
Early lesions of the infection include reddening of skin
and the presence of a clear exudate. The abdominal skin
can be peeled off by slight rubbing. Early lesions are usu-
ally present around the mouth, eyes, and ears as well as
on the abdomen. Later cases are covered by a thick
brownish, greasy, and odorous layer due to dirt and feces
sticking to the affected skin. During the recovery phase,
the skin is dry and crusted for a period of several days to
weeks. The carcasses of pigs that have died from EE are
dehydrated and emaciated. The superficial lymph nodes
are usually edematous and swollen. Most animals have
empty stomachs, and urate crystals may be seen in the
medulla of the kidney on section. There is often an accu-
mulation of mucoid or crystalline material in the pelvis
of the kidney, and pyelonephritis may be present.
Microscopic Lesions
Early changes of the epidermis are exfoliation, exocyto-
sis, crust formation, and formation of vesicles and pus-
tules classified as an “intraepidermal vesicular and pus-
tular dermatitis.” In the later stages, acanthosis
(hyperplasia of the epidermis) is observed (Fig. 33.3). In
the dermis, perivascular inflammation occurs (Andresen
et al. 1993). In histological sections of the skin, bacterial
microcolonies may occur in the keratinized layer of the
epidermis.
472 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
33.3. Histological section of
skin of pig with generalized
exudative epidermitis (magnifica-
tion ×1200). Changes present in
the epidermis are exfoliation,
exocytosis, crust formation,
formation of vesicles and pustules
classified as an “intraepidermal
vesicular and pustular dermati-
tis,” and acanthosis (hyperplasia
of the epidermis). In the dermis,
perivascular inflammation can be
seen.
Bacteriology
S. hyicus can usually be isolated from the lesions, from
the superficial lymph nodes, and frequently also from
the liver and spleen of untreated cases but may be diffi-
cult to demonstrate on nonselective culture media if
treatment has been given or if secondary infection by
Proteus sp. and Pseudomonas aeruginosa has occurred.
The use of a selective indicative agar facilitates isolation
of S. hyicus from pathological samples (Devriese 1977).
Both virulent and avirulent strains of S. hyicus can be iso-
lated as mixed cultures from the skin, lymph nodes, and
organs of diseased piglets (Wegener 1992). Whether the
avirulent strains take any active part in the establish-
ment or course of the infection remains unknown.
DIAGNOSIS
The clinical signs are generally sufficient to reach a diag-
nosis in young piglets. The lack of fever or of pruritis and
the generalized nature of the lesions, their appearance,
and the variation in severity within an affected litter are
all features suggestive of the disease. Confirmation may
be obtained by histological and bacteriological means. It
may be necessary to confirm the identity of the staphy-
lococci isolated as S. hyicus by conventional bacteriologi-
cal means (Devriese 1977) or by use of strip tests such as
the Staph-Zym test (Lämmler 1989). These have the ad-
vantage of revealing the identity of non–S. hyicus staphy-
lococci.
S. hyicus from pigs are very heterogeneous with re-
gard to phago-, sero-, and DNA fingerprinting types
(Wegener 1993a; Park and Kang 1987). Diagnosis is
complicated by the simultaneous presence of up to 8 dif-
ferent types of S. hyicus on diseased piglets. Wegener
(1993b) found that each diseased piglet on average har-
bored 1.9 different phage types and 2.3 different antibi-
otic resistance patterns among 10 randomly selected iso-
lates of S. hyicus recovered from the skin. Only a slightly
lower diversity was observed for strains recovered from
the liver or the spleen of the animals. In the absence of
simple methods to differentiate virulent from avirulent
strains in the diagnostic laboratory, all types of S. hyicus
should be regarded as potentially virulent. Thus, antimi-
crobials for therapy which affect all types present should
be chosen. Similarly, autogenous vaccines should be pre-
pared from all types present on the diseased animals.
Diagnosis is less easy when the lesions are mild, lo-
calized around predisposing lesions such as fight
wounds, or have been treated. The demonstration of S.
hyicus and response to antimicrobials may help confirm
 CHAPTER 33 EXUDATIVE EPIDERMITIS
uncomplicated disease of this type, but the organism
may be present in lesions caused by a number of initiat-
ing agents.
Other skin conditions that may be confused with EE
include swine pox (localized lesions, rarely fatal), mange
(pruritis, demonstration of mites), ringworm (expand-
ing superficial lesions, isolation of fungus), pityriasis
rosea (expanding circles, nonfatal, lesions not greasy),
zinc deficiency (weaners, symmetrical dry lesions), der-
matosis vegetans (inherited in Landrace, fatal pneu-
monitis), and local wounds such as facial fight wounds
and abraded knees in piglets and crate injuries in adults.
The organism may be isolated from other pathologic
conditions such as arthritis in piglets (Noda and Fukui
1986) and cystitis in sows as well as from the skin of
healthy pigs.
TREATMENT AND PREVENTION
Treatment is most successful if carried out early in the
disease; severely affected animals may not respond. The
effect of systemic treatment is reduction in the severity
of the skin lesions, development of only superficial le-
sions, and promotion of the healing process. S. hyicus is
frequently resistant to antibiotics. This resistance has
been shown to be predominantly mediated by plasmids
(Wegener and Schwarz 1993). Combinations of
trimethoprim and sulfonamides or lincomycin and
spectinomycin have been shown to have good in vitro ac-
tivity against S. hyicus (Wegener et al. 1994). Antimicro-
bial treatment should be accompanied by the provision
of a fluid replacer or at least clean water for affected
piglets and by local treatment with antibiotics or skin
disinfectants such as cetrimide, hexocil, or Virkon X in
order to speed recovery and prevent spread of the infec-
tion. Treatment may have to be continued for at least 5
days, and clinically affected piglets may make a slow re-
covery or remain stunted.
Vaccination of sows with autogenous bacterins made
from strains isolated on the affected farm may be of val-
ue in protecting the litters of newly purchased sows
when given before farrowing. Antibodies can effectively
neutralize the effect of the exfoliative toxin in the skin. It
is possible that the toxin may be able to serve as a single
protective antigen; however, this has not yet been shown
under field conditions. Therefore, autogenous vaccines
should be prepared from both the bacterial cells and the
culture supernatant, which contains the exfoliative toxin.
The incidence of the disease may be reduced by clip-
ping the teeth of litters at risk, by ensuring that pen sur-
faces are not abrasive, and by providing soft and dry bed-
ding, such as softwood sawdusts or chaffed straw. Sows
entering farrowing accommodation should be washed
and disinfected and placed in clean, disinfected, or fumi-
gated pens. Prompt treatment of local lesions on both
sows and piglets may also help.
Wegener, Skov-Jensen 473
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 Haemophilus parasuis
34 V. J. Rapp-Gabrielson

Once considered a sporadic disease of young pigs com- further investigation (Kobisch and Desmettre 1980; Mo-
promised by stress, porcine polyserositis and arthritis rozumi and Nicolet 1986a; Kielstein 1991). Nicoti-
(Glasser’s disease), caused by Haemophilus parasuis, has namide adenine dinucleotide (NAD, or V factor) is re-
emerged as one of the significant bacterial diseases af- quired for growth and can be supplied by heated blood
fecting swine throughout the world. Adoption of new (chocolate agar) or by satellitic growth in the vicinity of a
production technologies for high-health-status herds streak of a staphylococcus strain. After 24–48 hours’
and the emergence of new respiratory syndromes have growth, colonies are small, translucent, and non-
contributed to an increase in prevalence and severity of hemolytic on blood agar.
the disease. Disease management with antibiotics, vacci- The existence of serovars was first reported by Bakos
nation, and other strategies is not always successful in et al. (1952). In subsequent years, expansion of this
countering production losses due to H. parasuis infec- serotyping scheme by other investigators led to several
tion. It has long been known that the immune status of a proposals for new serovars (Schimmel et al. 1985; Mo-
herd is a determinant of pathogenic outcome of infec- rozumi and Nicolet 1986b; Nicolet et al. 1986; Kielstein
tion (Nielsen and Danielsen 1975). However, the hetero- 1991; Rapp-Gabrielson and Gabrielson 1992). Presently,
geneity among H. parasuis strains is striking, and a better 15 serovars based on immunodiffusion are recognized
understanding of the association of these phenotypic (Kielstein and Rapp-Gabrielson 1992). The type-specific
and genotypic differences with virulence potential and antigen is heat-stable polysaccharide (Morozumi and
protective immunity is beginning to emerge. Nicolet 1986b) presumed to be capsule or lipopolysac-
charide (LPS). Serotyping of isolates from Japan, Ger-
ETIOLOGY many, the United States, Canada, and Australia shows
serovars 5, 4, and 13 to be most prevalent (Table 34.1).
Glässer (1910) first reported the association of a small A large percentage of isolates are nontypeable, in-
gram-negative rod with fibrinous serositis and pol- dicating some isolates may not express sufficient type-
yarthritis of swine. Initially, the causative agent was specific antigen or the probable existence of additional
identified as Haemophilus suis by Hjärre and Wramby serovars.
(1943) and as Haemophilus influenza suis by Lecce (1960).
The name was changed to H. parasuis based on demon-
Table 34.1. Prevalence of H. parasuis serovars
stration that the organism did not require X factor
(haemin or other porphyrins) for growth (Biberstein and Frequency (%)
White 1969; Kilian 1976). The taxonomic position of H. H. parasuis Canada and the
parasuis within the Pasteurellaceae is still uncertain, due Serovar Japana United States Germany Australia
to a lack of nucleic acid homology with other
1 2.5 2.2 4.1 2.4
Haemophilus species (De Ley et al. 1990; Dewhirst et al. 2 5.8 7.9 5.5 7.3
1992). Considerable genotypic heterogeneity has also 4 9.2 16.2 17.2 12.2
been demonstrated among H. parasuis strains (Smart et 5 14.2 23.3 23.8 31.7
al. 1988; Rapp-Gabrielson et al. 1992a; Blackall et al. 7 or 10b — 4.8 4.5 9.8
12 — 7.0 2.8 2.4
1997). It has been proposed that more than one bacteri- 13 — 11.0 4.5 17.1
al species may be represented by strains identified as 14 — 9.2 1.7 0
H. parasuis (Morozumi et al. 1986; Dewhirst et al. 3,6,8,9,11, or 15 — 4.3 10.3 1.0
1992). Nontypeable 68.3 14.1 26.2 12.2
Microscopically, H. parasuis cells are pleomorphic, Sources: Morikoshi et al. 1990; Rapp-Gabrielson and
varying from single coccobacilli to long, thin, filamen- Gabrielson 1992; Kielstein and Rapp-Gabrielson 1992; Blackall et
tous chains. A capsule can usually be demonstrated, but al. 1996.
a
expression is influenced by in vitro culture (Rapp- Only tested for H. parasuis serovars 1–5.
b
Some strains react to both serovars 7 and 10 and cannot be
Gabrielson et al. 1992b). Thus, the significance of re- distinguished by immunodiffusion (Rapp-Gabrielson, unpub-
ports associating lack of capsule with virulence needs lished data—1995; Blackall et al. 1996).

475
476 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
EPIDEMIOLOGY
Haemophilus parasuis infects only swine. It is commonly
isolated from nasal secretions of healthy swine
(Bertschinger and Nicod 1970; Harris et al. 1969; Smart
et al. 1989) and from the lungs of pigs with pneumonia,
but not generally from normal lungs (Little 1970; Møller
et al. 1993). In conventional herds, the organism is one of
the earliest and most prevalent bacterial isolates from
nasal swabs of pigs at 1 week of age (Kott 1983).
Historically, Glasser’s disease has been considered a
sporadic disease of young swine compromised by stress.
However, the epizootiologic picture in specific-pathogen-
free (SPF) or high-health-status herds that represent an
immunologically naive population is much different
(Nielsen and Danielsen 1975; Baehler et al. 1974;
Menard and Moore 1990). Introduction of H. parasuis
may result in systemic disease of high morbidity and
mortality, affecting swine at any stage of production.
Presently, H. parasuis is one of the most serious prob-
lems associated with mixing swine from different herds
or introduction of new breeding stock into a herd (Smart
et al. 1989; Menard and Moore 1990).
The role of H. parasuis in swine respiratory disease is
more problematic. Demonstration of purulent rhinitis
associated with H. parasuis colonization supports a pos-
sible role as a predisposing factor for other viral and bac-
terial pathogens (Gois et al. 1983; Vahle et al. 1995,
1997). In pneumonia, H. parasuis has been assumed to
be an opportunistic secondary invader, causing disease
only in association with other viral or bacterial agents.
Such a relationship was evident after accidental infection
of pigs experimentally inoculated with pseudorabies
virus with H. parasuis serovar 4 (Narita et al. 1994). How-
ever, several recent reports indicate H. parasuis may be a
primary agent in fibrinosuppurative bronchopneumonia
(Pöhle et al. 1992; Barigazzi et al. 1994; Solano et al.
1998). Isolation of H. parasuis from pneumonia has in-
creased substantially in recent years and is believed to be
associated with the increased prevalence of mycoplasma
pneumonia as well as viral respiratory pathogens such as
porcine reproductive and respiratory syndrome (PRRS)
virus, swine influenza virus, and porcine respiratory
coronavirus. H. parasuis, in combination with Mycoplas-
ma hyorhinis, was isolated from 51.2% of lungs from
PRRS-infected swine (Kobayashi et al. 1996). However,
clinical impressions that PRRS is exacerbated by H. para-
suis infection have not been substantiated in experimen-
tal models (Solano et al. 1997; Cooper et al. 1995).
The pathogenic potential of H. parasuis strain(s) oc-
curring in a herd is also a factor in the severity and pro-
gression of systemic disease. Serovars commonly isolat-
ed from upper respiratory sites in swine include serovars
infrequently isolated from systemic sites (Bloch 1985;
Rapp-Gabrielson 1993). There may be a subpopulation
of H. parasuis strains occurring in the respiratory tract
that is capable of invading systemically and causing dis-
ease (Rapp et al. 1986; Rapp-Gabrielson 1993).
An association between serovar and isolation from
polyserositis was apparent in several studies (Bakos et al.
1952; Morozumi and Nicolet 1986b; Kielstein 1991). Re-
cently, differences in virulence among serovars was
demonstrated by inoculation of SPF or cesarean-derived,
colostrum-deprived (CDCD) swine with strains repre-
senting the 15 serovars (Kielstein and Rapp-Gabrielson
1992; Nielsen 1993; Amano et al. 1994; Rapp-Gabrielson
et al. 1995). In these studies, strains representing some
serovars were highly virulent and strains representing
other serovars were avirulent. Virulence of field isolates
was consistent with that of the reference strain, indicat-
ing a causal relationship between serovar and virulence
(Table 34.2). However, the demonstration that two
serovar 14 strains differed in virulence for CDCD pigs in-
dicates that factors other than serovar contribute to the
virulence potential of a strain (Rapp-Gabrielson et al.
1995).
Sodium dodecyl sulfate-polyacrylamide gel elec-
trophoresis (SDS-PAGE) of whole-cell and outer-mem-
brane (OM) proteins also demonstrates phenotypic het-
erogeneity among strains (Morozumi and Nicolet 1986a;
Rapp et al. 1986; Morikoshi et al. 1990; Rosner et al.
1991; Rapp-Gabrielson et al. 1992a). These reports indi-
cate a possible association of virulence potential with
specific protein patterns, but the precise relationship be-
tween protein pattern, serovar, and virulence potential
remains to be defined. Heterogeneity of H. parasuis LPS
has been demonstrated by SDS-PAGE patterns and im-
munoblotting with monoclonal antibodies, but LPS pat-
terns have not been associated with virulence (Zucker et
al. 1994; Zucker et al. 1996). Filamentous structures pre-
sumed to be fimbriae have been demonstrated on some
H. parasuis strains, but their role in adhesion or
pathogenicity remains to be defined (Münch et al.
1992).
Table 34.2. Virulence of strains representing
H. parasuis serovars for SPF swine
No. of
H. parasuis Strains
Serovar Evaluated Virulencea
1, 5, 10, 12, 13, 14 10 Death within 96 hours
2, 4, 15 10 Severe polyserositis and arthritis
at necropsy
8 1 Mild clinical signs and gross
lesions
3, 6, 7, 9, 11 8 No clinical signs or gross lesions
Source: Kielstein and Rapp-Gabrielson 1992.
a
Swine inoculated intraperitoneally with 5 × 108 colony-
forming units.
 CHAPTER 34 HAEMOPHILUS PARASUIS Rapp-Gabrielson
PATHOGENESIS
Experimental challenge models have been developed to
investigate the pathogenesis of H. parasuis infection.
Vahle et al. (1995) examined sequential events in infec-
tion by inoculating CDCD pigs intranasally with a viru-
lent strain of H. parasuis. Within 12 hours postinocula-
tion, H. parasuis was isolated from the nasal cavity and
trachea; within 36 hours, from blood cultures; and at
36–108 hours, from systemic tissues. Early colonization
of the middle and caudal nasal cavity and trachea was al-
so demonstrated by immunohistochemistry and trans-
mission electron microscopy (Vahle et al. 1997). Colo-
nization was associated with purulent rhinitis, focal loss
of cilia, and acute cell swelling within the nasal and tra-
cheal mucosa. In vitro infection of nasal turbinate ex-
plants also resulted in marked reduction in ciliary activi-
ty and damage to ciliated epithelial cells (Vahle 1996).
Bacterial cells were not closely associated with cilia or ep-
ithelium, and the mechanism of colonization or cellular
destruction was not defined. The observation by these
investigators that H. parasuis preferentially colonizes the
nasal cavity and trachea, and not the tonsil, is in concor-
dance with the ability to isolate H. parasuis from the
nasal cavity, but not tonsil or lung specimens, from
slaughterhouse pigs (Møller et al. 1993). In contrast, it
has been reported that H. parasuis antigen was detected
in tonsillar tissue but not in the nasal cavity by im-
munoperoxidase stain and electron microscopic exami-
nation (Amano et al. 1994).
Mucosal injury may enhance invasion. Microbial and
host factors involved with systemic infection are not
known; however, the virulence of some strains is re-
markable. Intratracheal inoculation of less than 100
colony-forming units of strains representing several
serovars caused systemic disease and death in CDCD
pigs within a few days (Rapp-Gabrielson et al. 1995).
Bacteremia is apparent in pigs in the early stages of in-
fection (Vahle et al. 1995). Septicemic lesions consist of
petechiae or ecchymoses in the liver, kidney, and
meninges; high levels of endotoxin are detected in plas-
ma, and fibrinous thrombi are present in many organs
(Amano et al. 1994). Subsequent replication at multiple
serosal surfaces produces the typical fibrinosuppurative
polyserositis, polyarthritis, and meningitis observed in
field cases (Amano et al. 1994; Vahle et al. 1995). Pneu-
monia was not prominent in one challenge model, even
though H. parasuis was isolated from the lung (Vahle et
al. 1997). Pneumonia was also not evident following in-
oculation of the reference strains of serovars 1, 4, or 5
(Amano et al. 1994). Differing observations on the abili-
ty of H. parasuis to produce pneumonia may be due to
differences per se in the challenge models, the doses ad-
ministered, or pathogenic potential of the strains exam-
ined.
477
CLINICAL SIGNS AND LESIONS
Clinical presentation is dependent on the location of in-
flammatory lesions. In naive herds or pigs, onset is rapid,
occurring a few days after exposure. Clinical signs in-
clude pyrexia and apathy followed by inappetence and
anorexia. Dyspnea, pain (evidenced by squealing),
swollen joints, lameness, tremor, incoordination,
cyanosis, recumbency, and death may follow. Abortion
in gilts and chronic lameness in boars may be sequelae to
acute infection. Even if infection of gilts is controlled by
antibiotic treatment, pigs in subsequent farrowings may
experience severe disease (Menard and Moore 1990). In
conventional herds, chronic infections in nursery pigs
may result in poorly performing pigs. Cough, dyspnea,
weight loss, lameness, and rough hair coat are the pri-
mary clinical signs.
Primary macroscopic lesions are a serofibrinous to
fibrinopurulent exudate at single or multiple serosal sur-
faces, including the peritoneum, pericardium, and pleu-
ra; articular surfaces, particularly the carpal and tarsal
joints, and the meninges may also be involved (Hjärre
1958; Amano et al. 1994). Microscopically, the exudate
consists of fibrin, neutrophils, and lesser numbers of
macrophages (Vahle et al. 1995). Less commonly, H.
parasuis infection may result in acute septicemic disease
in which cyanosis, subcutaneous and pulmonary edema,
and death can occur without the typical serosal inflam-
mation (Riley et al. 1977; Peet et al. 1983; Desrosiers et
al. 1986). Fasciitis and myositis (Hoefling 1991) and pu-
rulent rhinitis (Gois et al. 1983; Vahle et al. 1995) have al-
so been reported.
DIAGNOSIS
Diagnosis is usually based on herd history, clinical signs,
and necropsy. Bacterial isolation, necessary for confir-
mation, is not always successful. This is due in part to the
fragility and fastidious growth requirements of H. para-
suis relative to other bacteria that may also be present in
the specimen. Retrospective analysis of submissions to
diagnostic laboratories in Ontario indicate that the true
incidence of disease may be 10-fold higher than report-
ed, due in part to the inability to confirm the presence of
H. parasuis from submitted specimens (Miniats et al.
1986). Necropsies should be performed not only on pigs
with severe clinical signs and lesions but also on pigs in
the acute phase of disease, prior to administration of an-
tibiotics. The best chance for isolation is by culturing sev-
eral serosal surfaces or exudates, cerebrospinal fluid, and
heart blood, even if lesions are mild or not apparent. H.
parasuis can be recovered from these fluids when inocu-
lated into a transport medium prior to shipment to the
diagnostic laboratory (Mendez-Trigo and Trigo 1996).
Although somewhat laborious for routine diagnosis, spe-
478 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor

cial dilution techniques followed by plating on selective
media containing antibiotics have been used successfully
for culturing H. parasuis in high numbers from respira-
tory specimens (Møller and Kilian 1990; Møller et al.
1993). Incubation in 5% CO2 or a candle jar does not en-
hance growth of H. parasuis. However, the use of defibri-
nated horse blood and tryptose blood agar base, rather
than bovine or sheep blood and trypticase soy agar, does
appear to enhance growth.
Biochemical tests are required to distinguish H. para-
suis from other NAD or V factor–dependent organisms
belonging to the family Pasteurellaceae that have been
isolated from swine (Table 34.3; Møller et al. 1996).
Occasionally misidentified as H. parasuis, these other
NAD-dependent organisms are present in high numbers
in the nasal cavity, tonsils, or lungs and are believed to be
of low pathogenic potential (Møller and Kilian 1990;
Møller et al. 1993).
It is not uncommon for several strains or serovars to
be present in a herd, or even in different specimens from
a single pig (Smart et al. 1989; Rapp-Gabrielson and
Gabrielson 1992; Rapp-Gabrielson 1993). Thus, recov-
ery from systemic sites or gross lesions is the only assur-
ance that the isolate obtained is involved in the disease
process. Serotyping, critical to an understanding of the
epizootiology of the disease outbreak and immune re-
sponse to infection or vaccination, is available only at a
few diagnostic laboratories.
Differential diagnosis should include septicemic bac-
terial infections caused by Streptococcus suis,
Erysipelothrix rhusiopathiae, Actinobacillus suis, Salmonel-
la choleraesuis var. kunzendorf, and Escherichia coli. My-
coplasma hyorhinis polyserositis and arthritis in 3- to 10-
week-old pigs produces lesions similar to H. parasuis.
The significance of H. parasuis in bronchopneumonia
can be ascertained only after identification of other viral
and bacterial pathogens that may be involved in the mul-
tifactoral disease process.
TREATMENT
Prophylactic use of antibiotics or therapeutic oral med-
ication may be of little value in severe H. parasuis out-
breaks (Madsen 1984; Wiseman et al. 1989; Menard and
Moore 1990). High antibiotic doses should be adminis-
tered parenterally as soon as clinical signs have manifest-
ed, and all pigs in the affected group, not just those show-
ing signs, should be treated (Desrosiers et al. 1986).
Penicillin has been considered the drug of choice, but an
increasing resistance to penicillin has been reported
(Kielstein and Leirer 1990). Most H. parasuis strains are
also sensitive in vitro to ampicillin, fluoroquinolone,
cephalosporins, gentamicin, spectinomycin, and poten-
tiated sulfas; higher numbers of strains are resistant to
tetracycline, erythromycin, other aminoglycosides, and
lincosamide (Kielstein 1985; Trigo et al. 1996).
PREVENTION AND IMMUNITY
Because nasal mucosa of baby pigs may be colonized be-
fore 1 week of age, elimination of H. parasuis by early
weaning alone is unlikely to be successful. Clark et al.
(1994) evaluated several medicated early-weaning strate-
gies and found that H. parasuis could be eliminated only
when parenteral and oral administration of high doses of
antibiotics to baby pigs was a part of the treatment.
Elimination of H. parasuis from a herd may not be desir-
able, inasmuch as subsequent mixing of naive pigs with
pigs harboring H. parasuis during later stages in produc-
tion may result in a disease course with devastating eco-

Table 34.3. Differential biochemical reactions of swine NAD-dependent Pasteurellaceae

Other NAD-dependent Pasteurellaceae
Biochemical H. Actinobacillus Actinobacillus Haemophilus Actinobacillus Actinobacillus
Characteristic parasuis pleuropneumoniae minor Taxon C porcinus indolicus
Urease − + + − − −
Hemolysis − + − − − −
Indole − − − − − +
Fermentation of
Glucose + + + + +/− +
Lactose − − + − +/− +/−
Sucrose + + + + +/− +
Mannitol − + − − +/− +/−
Xylose − + +/− − +/− +/−
L-Arabinose − − − + +/− −
Raffinose − − + + +/− +
Sources: Møller and Kilian 1990; Rapp-Gabrielson and Gabrielson 1992; and Møller et al. 1996.
Note: A. minor was formerly known as Haemophilus taxon “Minor Group”; A. porcinus was formerly known as Haemophilus sp. taxons
D and E; A. indolicus was formerly known as Haemophilus sp. taxon F.
Key: + indicates greater than 90% of isolates are positive; −, less than 10% of isolates positive; +/−, variable reactions among isolates.
 CHAPTER 34 HAEMOPHILUS PARASUIS Rapp-Gabrielson
nomic losses. Introduction of new breeding stock from a
herd with a different health background should include
isolation and acclimation periods long enough to allow
for development of protective immunity from either vac-
cination or natural exposure.
Maternal and natural immunity are critical factors
for controlling the disease process (Nielsen and
Danielsen 1975). Swine previously exposed to nonpatho-
genic H. parasuis strains develop resistance to subse-
quent challenge with virulent strains (Nielsen 1993).
Vaccination of gilts resulted in protective maternal im-
munity for up to 4 weeks when piglets were challenged
with the same serovar contained in the bacterin (Solano
et al. 1998). Because of the septicemic nature of the dis-
ease, antibodies are probably the major protective im-
mune mechanism.
There are numerous reports of successful disease
control by vaccination with commercial or herd-specific
bacterins (Nielsen and Danielsen 1975; Riising 1981;
Wiseman et al. 1989; Menard and Moore 1990; Schim-
mel et al. 1992). There are also instances where bacterins
are not efficacious, and these may be due to lack of cross-
protection for the strain or serovar involved in the dis-
ease process. Cross-protection against other virulent
strains is not always evident in experimental challenge
models (Miniats et al. 1991; Kielstein and Raßbach 1991;
Rapp-Gabrielson et al. 1997). Although cross-protection
is primarily a concern for commercial bacterins, herd-
specific bacterins may also lack efficacy because of the
presence of more than one strain or serovar or the sub-
sequent introduction of a new strain into the herd.
Demonstration that virulent strains may not protect
against challenge with different strains of the same
serovar, or even against challenge with the homologous
strain, indicates that the protective antigens may not be
identical to the virulence factors or the type-specific anti-
gens (Kielstein and Raßbach 1991; Rapp-Gabrielson et
al. 1997).
Efficacy against challenge with different strains of the
same serovar, as well as cross-protection against some
heterologous serovars, has been demonstrated with a
bacterin containing H. parasuis serovars 4 and 5 (Rapp-
Gabrielson et al. 1996, 1997). However, in these same re-
ports, evaluation of this bacterin, as well as other com-
mercial bacterins, demonstrated that none protected
fully against the six most prevalent serovars associated
with disease in North America. Strains representing nine
serovars, as well as nontypeable strains, have been
demonstrated to be virulent. Because of the heterogene-
ity of strains with pathogenic potential and the current
lack of understanding of protective antigens and viru-
lence factors, it is unlikely that any bacterin will provide
cross-immunity against all strains of etiologic signifi-
cance in the swine population. Control programs may in-
clude vaccination and antibiotic treatments but also
should address management practices to reduce or elim-
479
inate other respiratory pathogens, tighten weaning age
and pig flow, and eliminate mixing of pigs at all stages of
production.
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 Leptospirosis
35 W. A. Ellis
Leptospirosis is a cause of reproductive loss in breeding
herds and has been reported in swine from all parts of
the world; however, knowledge of the incidence and eco-
nomic impact of the disease is largely confined to the in-
tensive pig industries of the Northern Hemisphere, Aus-
tralia, New Zealand, Argentina, and Brazil.
Endemic infection in a herd of swine may produce lit-
tle evidence of clinical disease, but when it is first intro-
duced into a susceptible breeding herd, or during peri-
ods of waning herd immunity, it can cause very
appreciable losses through abortion, the full-term birth
of dead pigs or of weak pigs of reduced viability, or in-
fertility.
Leptospires persist in the kidneys and genital tracts
of carrier swine and are excreted in urine and genital flu-
ids. Survival outside the host is favored by warm, moist
conditions. Transmission is by direct or indirect contact
with a carrier animal.
Interruption of transmission from an infected pig or
other host to the pig is the critical factor in control.
Leptospirosis is an occupational zoonosis of those
who work with pigs.
ETIOLOGY
Leptospirosis of swine is a disease caused by a variety of
morphologically similar, but antigenically and genetical-
ly distinct, small, motile, aerobic spirochetes belonging
to the genus Leptospira. They are thin, helical, motile,
gram-negative organisms that are often hooked at one or
both ends. They spin constantly on their long axis. They
range in length from about 6 to 20 µm, with an ampli-
tude of approximately 0.1–0.15 µm and a wavelength of
about 0.5 µm. Under adverse nutritional conditions, lep-
tospires may be greatly elongated, whereas under condi-
tions such as high salt concentrations or in aging culture
or tissues, leptospires may form coccoid forms of about
1.5–2 µm in diameter (Faine 1994). They divide by bina-
ry fission. They stain poorly with aniline dyes. Unstained
cells are visible only by dark-field microscopy. In a suit-
able liquid environment, motility is accomplished by ro-
tating along the long axis, but this changes to an undu-
lating action in semisolid media. They require special
media containing mammalian serum or albumin for cul-
tivation.
The major structural components are an outer enve-
lope, which surrounds a cell wall or peptidoglycan com-
plex, and two polar endoflagella (originating subtermi-
nally at each end).
The taxonomy of the leptospires has been through a
period of change which continues to cause considerable
confusion to those not intimately acquainted with the
subject. Until recently a single genus Leptospira was rec-
ognized in the family Leptospiraceae. Two groupings were
recognized within the genus: those found in animal
species (the parasitic strains) and those found in water
(the saprophytic strains). These two groupings, which
were referred to as the interrogans and biflexa complexes,
can be differentiated by their growth requirements and
biochemical reactions. Only the parasitic strains are of
medical and veterinary interest.
For taxonomic purposes and as an aid to epidemio-
logical studies, the parasitic leptospires were divided in-
to serogroups on the basis of antigenic relationships as
determined by cross-agglutination reactions and were
further subdivided into serovars by agglutination-ab-
sorption patterns. About 23 serogroups are recognized,
containing approximately 212 serovars.
The advent of genetic typing methods has provided
rapid, reproducible typing protocols. The current recom-
mendations on the taxonomy of leptospires (Ellis 1995)
recognized eight species of pathogenic leptospires with-
in the family Leptospiraceae. They are Leptospira interro-
gans, L. borgpetersenii, L. inadai, L. kirschneri, L. noguchii,
L. meyer, L. weilii, and L. santarosai.
The species definition is based on a level of DNA-
DNA homology of at least 70% and 5% or less divergence
in DNA relatedness. Taxonomy at the subspecific level
continues to be based on serovars as defined by Dikken
and Kmety (1978), but other valid methods which give
results comparable to conventional serotyping can be
used for their identification. Such methods include mon-
oclonal antibody agglutination profiles, factor analysis,
and analyses in which restriction-fragment length poly-
morphisms or rRNA gene restriction patterns are used in
pulsed-field gel electrophoresis analyses. The term “type”
is used to indicate strain differences at the subserovar
level (Ellis 1995).
Molecular Biology
The genus Leptospira is characterized by a guanine plus
cytosine (G + C) ratio of 35–41 mol% in its chromosomal
483
484 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
DNA, depending on species. The published genome size
has varied between 3100 and 5000 kb depending on the
techniques used to measure it and reflecting differences
between strains. The Leptospira interrogans serovars
icterohaemorrhagiae and pomona have two circular chro-
mosomes: the large (4400–4600 kb) and the small (350
kb) replicons are regarded as chromosomal because the
essential asd gene is located on the smaller unit. Leptospi-
ra interrogans strains contain two 23S and 16S rRNA
genes but only one 5S rRNA gene. The 5S rRNA gene is
highly conserved among the pathogenic leptospires.
There are differences in the global distribution of
some of the Leptospira species: L. interrogans, L. borg-
petersenii, and L. kirschneri have a worldwide distribu-
tion, whereas L. noguchii and L. santarosai are found
mainly in North and South America, and L. weilii is
found mainly in China and eastern Asia. Strains that
cause disease in pigs are found mainly in the L. interro-
gans and L. borgpetersenii species.
EPIDEMIOLOGY
The epidemiology of swine leptospirosis is potentially
very complicated, since swine can be infected by any of
the pathogenic serovars. Fortunately, only a small num-
ber of serovars will be endemic in any particular region
or country. Furthermore, leptospirosis is a disease that
shows a natural nidality, and each serovar tends to be
maintained in specific-maintenance hosts. Therefore, in
any region, pigs will be infected by serovars maintained
by pigs or by serovars maintained by other animal
species present in the area. The relative importance of
these incidental infections is determined by the opportu-
nity that prevailing social, management, and environ-
mental factors provide for contact and transmission of
leptospires from other species to pigs.
Pigs act as maintenance hosts for serovars belonging
to the Pomona, Australis, and Tarassovi serogroups,
while strains belonging to the Canicola, Icterohaemor-
rhagiae, and Grippotyphosa serogroups are among the
more commonly identified incidental infections in
swine.
Pomona Infection
Serovar pomona has been the most common serovar iso-
lated from pigs worldwide. Infection with this serovar
has been extensively studied and it provides a suitable
model with which to illustrate general concepts of swine
leptospirosis. Many strains of serovar pomona, especially
those of type kennewicki found in the United States and
Canada, are adapted to swine. Serovar pomona has been
the cause of widespread clinical disease in swine in
North and South America, Australia, New Zealand, parts
of Asia, and Eastern and Central Europe and is endemic
in many of these regions. Such strains are apparently ab-
sent from the more westerly parts of Europe. Further-
more, not all strains of serovar pomona are adapted to
pigs nor are the other serovars of the Pomona serogroup,
but they have rodent hosts (Sebek et al. 1983).
In parts of North America, the prevalence of pomona
infection in pigs has fallen from the high levels observed
in the 1950s and early 1960s: no carriers were detected in
a 1989 meat-plant survey carried out in Iowa (Bolin and
Cassells 1992). In contrast, Baker et al. (1989) recovered
serovar pomona (type kennewicki) from almost 10% of
pigs in a small survey in Canada.
Leptospires have a particular affinity for the kidneys
of infected pigs, where they persist, multiply, and are
voided in urine. This characteristic is very important in
the transmission of infection.
Infection is introduced into a susceptible herd by
three possible routes: the introduction of infected stock,
exposure to a contaminated environment, or contact
with an alternative infected animal vector (Hathaway
1983). Carrier pigs are probably the most common route
of introduction. Replacement gilts (Edwards and Daines
1979) or infected boars (Kemenes and Suveges 1976)
have been identified as important means of introducing
infection.
The importance of free-living species as possible
sources of pomona infection of pigs depends on geo-
graphical location. In North America, the skunk has
been incriminated as a source of pomona outbreaks in
pigs (Mitchell et al. 1966).
Once pomona has been introduced into a pig popula-
tion, a high prevalence of infection is established. Only
low infective doses are required to transmit infection
(Chaudhary et al. 1966a, b). If direct contact is prevent-
ed, indirect contact through contaminated effluent, wa-
ter, or soil ensures transmission (Michna 1970; Buddle
and Hodges 1977; Kingscote 1986). The presence of
moisture is critical for indirect transmission; the organ-
isms cannot withstand dessication, but when infected
urine is deposited in damp soil or water with a pH
around or slightly on the alkaline side, the organisms
may survive for extended periods (Mitscherlich and
Marth 1984).
During the initial herd infection, clinical disease may
occur in all ages of sows.
Following the initial establishment of infection, an
endemic cycle typical of that in a maintenance host pop-
ulation is set up (Hathaway 1981). Piglets are passively
protected in the first weeks of life by colostrum-derived
immunoglobulins from infected dams (Fish et al. 1963;
Bolt and Marshall 1995a). The duration of this passive
protection depends primarily on the quantity of im-
munoglobulins received in colostrum (Chaudhary et al.
1966b). A study of grower pigs in New Zealand has
shown that leptospiral infection becomes apparent in
piglets from 12 weeks of age, and by slaughter up to 90%
may be infected. The intensity of leptospiruria is greatest
in the first 3–4 weeks of infection, after which it declines
 CHAPTER 35 LEPTOSPIROSIS Ellis
and becomes intermittent (Bolt and Marshall 1995a, b).
Infection between groups of fattening pigs is often by
urine-contaminated effluent from a common drainage
system (Buddle and Hodges 1977).
In herds with endemic infection, clinical disease is
usually restricted to gilts that either have been reared in
isolation since weaning and reintroduced into the herd
or, more commonly, have been brought in from an unin-
fected herd.
Tarassovi Infection
There is much less information available on the epidemi-
ology of tarassovi infection in pigs. The pig acts as a
maintenance host for some strains of tarassovi found in
Eastern Europe and Australia. In these regions, it does
not spread as rapidly in a pig population as does pomona
(Kemenes and Suveges 1976), but endemic infection is
readily maintained (Ryley and Simmons 1954b;
Kemenes and Suveges 1976).
Many strains of tarassovi have been recovered from
free-living animals (Anon. 1966, 1975) and these may
give rise to incidental pig infections. For example,
tarassovi has not been recovered from swine in the Unit-
ed States, but there is serologic evidence of infection in
pigs (Cole et al. 1983) in the southeastern states, where it
has been isolated from racoons, skunks, and opossums
(McKeever et al. 1958; Roth 1964).
Australis Infection
Serovar bratislava and to a lesser extent the closely relat-
ed serovar muenchen have emerged as major swine-main-
tained leptospiral infections in the last few years. Sero-
logic data have indicated widespread bratislava infection
in Germany (Weber and Fenske 1978), the United King-
dom (Hathaway and Little 1981; Hathaway et al. 1981),
Czechoslovakia (Propopcakova et al. 1981), the Nether-
lands (Bercovich et al. 1983), Sweden (Sandstedt and
Engvall 1985), Denmark (Jensen and Binder 1989;
Nissen 1989), the United States (Hanson 1985, 1987),
Canada (Kingscote 1988), Austria (Loimayr 1990), Aus-
tralia (Chappel et al. 1992), Brazil (Oliveira et al. 1994),
and South Africa (Potts et al. 1995). There is, as yet, no
information from Russia but it would be reasonable to
assume that infection is now present in all major pig-
rearing countries.
Serovar bratislava was first recovered from a pig in
the Netherlands by Hartmann et al. (1975) (Ellis 1992)
and has now been recovered from pigs in the United
Kingdom (Ellis et al. 1986a, b, c), the United States (Ellis
and Thiermann 1986; Bolin and Cassells 1990, 1992),
and Germany (Schonberg et al. 1992).
The epidemiology of these strains is poorly under-
stood. There are specific pig-adapted strains, strains that
are maintained by pigs, dogs, horses, and hedgehogs,
and strains that are found only in wildlife.
Two very distinct serologic profiles may be seen in en-
485
demically infected herds. In indoor sow units infected
with pig-adapted strains of bratislava, the prevalence of
sows with antibody titers of greater than 1:100 in the mi-
croscopic agglutination test (MAT) is usually very low, al-
though many sows will have titers of less than 1:100.
This is thought to result from infection being primarily
due to venereal transmission. In contrast, in units where
the sows are kept outside, the seroprevalences (≥1:100)
may be greater than 50%. This is thought to be due to the
sows being infected systemically as a result of exposure
to infected rodent urine.
Although the renal-carrier state does become estab-
lished, urinary excretion is poor compared with pomona
excretion, and transmission within the fattening house is
inefficient. Important additional carrier sites have been
identified, namely, the upper genital tracts of sows and
boars (Ellis et al. 1986b, c; Power 1991; Bolin and Cassells
1992). Venereal transmission is thought to play an im-
portant role in the spread of bratislava infection.
Canicola Infection
Although organisms belonging to the Canicola sero-
group have been recovered from swine in at least 11
countries (Hanson and Tripathy 1986), little is known of
the epidemiology of canicola infection in pigs. The dog is
the recognized maintenance host for this serovar and is
the probable vector whereby this serovar enters a pig-
gery, although a report from Peru (Paz-Soldan et al.
1991) incriminates wildlife as the source of an outbreak
in sows. The long period of leptospiruria observed in in-
fected pigs (at least 90 days) (Michna 1962) and the abil-
ity of canicola to survive for up to 6 days in undiluted pig
urine (Michna 1962) suggest that there would be an op-
portunity for intraspecies transmission, but no studies
have been done on this subject (Hathaway 1983).
Icterohaemorrhagiae Infection
Serologic evidence of Icterohaemorrhagiae serogroup in-
fection has been reported in many countries but few iso-
lations have been made from pigs (Hathaway 1985). It
appears that both serovars copenhageni and icterohaemor-
rhagiae may be involved. The maintenance host for these
serovars is the brown rat (Rattus norvegicus), and it is
probable that copenhageni and icterohaemorrhagiae are in-
troduced to susceptible stock via an environment conta-
minated with infected rat urine. Field investigation sug-
gests that transmission between swine is inefficient
(Hathaway 1985). Schnurrenberger et al. (1970) found
that urinary excretion lasted less than 35 days in natural-
ly infected pigs, while Fennestad and Borg-Petersen
(1966) failed to demonstrate leptospiruria in experimen-
tally infected pigs. Low prevalences of renal infection
have been found in those microbiological surveys in
which Icterohaemorrhagiae strains have been recovered;
Hathaway et al. (1981) reported a 0.7% prevalence in
England, and McErlean (1973) found a 0.4% prevalence
486 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
in Ireland. It is believed, in the absence of supporting
isolation data, that vaccine-induced antibodies are re-
sponsible for the seroprevalences of icterohaemorrhagiae
observed in the United States.
Grippotyphosa Infection
Serovar grippotyphosa infection is maintained by wildlife
hosts, and incidental infection of pigs gives rise to low
prevalences of antibodies in swine in various regions,
particularly Eastern and Central Europe and the United
States. It has been recovered from pigs in the former
USSR (Gorshanova 1964) and the United States (Hanson
et al. 1965, 1971).
Sejroe Infection
Serovar hardjo infection is maintained by cattle world-
wide, and where cattle and pigs come in close contact,
the opportunity arises for infection in pigs to occur.
There are now reports of the isolation of hardjo from
pigs in the United Kingdom (Hathaway et al. 1983; Ellis
et al. 1986a) and the United States (Bolin and Cassells
1992). Persistence in renal tissue was not a feature of ex-
perimental infection (Hathaway et al. 1983); therefore,
intraspecies transmission is unlikely.
Serovar sejroe, which is maintained by small rodents,
has also been isolated from swine in Europe (Brandis
1956; Fuzi et al. 1957; Combiesco et al. 1958), and an-
other serovar in this group (serovar balcanica) has been
recovered from swine in the former USSR (Matveeva et
al. 1977).
PATHOGENESIS
The most important route of natural infection has not
been determined; however, it is thought to be via the mu-
cous membranes of the eye, mouth, or nose (Alston and
Broom 1958; Alexander et al. 1964; Michna and Camp-
bell 1969). Infection via the vaginal route is also possible
(Ferguson and Powers 1956; Chaudhary et al. 1966a).
Transmission of leptospires through milk from an in-
fected dam has been demonstrated experimentally (Tri-
pathy et al. 1981). A period of bacteremia, which may
last for a week, begins 1 or 2 days after infection. During
this period leptospires can be isolated from most organs
of the body and also from cerebrospinal fluid. This pri-
mary bacteremic phase ends with the appearance of cir-
culating antibodies, which are detectable usually after
5–10 days (Hanson and Tripathy 1986). A secondary bac-
teremic period (after 15–26 days) has been reported in
experimental hardjo infection (Hathaway et al. 1983).
Antileptospiral agglutinins appear at detectable lev-
els in the blood at approximately 5–10 days after infec-
tion and reach maximum levels at around 3 weeks (Ryley
and Simmons 1954b; Ferguson and Powers 1956; Morse
et al. 1958). Peak titers vary considerably (1:1000 to
1:100,000 in the MAT), and these may be maintained for
up to 3 weeks, after which a gradual decline occurs. Low
titers may be detectable for several years in many ani-
mals.
Following the period of leptospiremia, the lep-
tospires localize in the proximal renal tubules, where
they multiply and are voided in the urine. The duration
and intensity of urinary shedding vary from pig to pig
and with the infecting serovar. In the case of pomona in-
fection, the intensity of excretion is highest during the
first month of shedding, when more than a million lep-
tospires may be present in each milliliter of urine (Morse
et al. 1958); leptospiruria is very constant during this pe-
riod (Hodges et al. 1979). A variable period of intermit-
tent, low-intensity leptospiruria then ensues, and this
may last for up to 2 years in some cases (Ryley and Sim-
mons 1954a; Morse et al. 1958; Mitchell et al. 1966). Low
levels of antibody may be detected in the urine of pigs
(Morse et al. 1958), but the immunologic mechanism
whereby infection is ultimately eliminated from the kid-
neys is not known.
Leptospires also localize in the uterus of pregnant
sows, and abortion, production of stillborn pigs, and
neonatal disease frequently result from intrauterine in-
fections occurring in the last half of the gestation period.
Abortions and stillbirths usually occur 1–4 weeks follow-
ing infection of the gilt or sow (Hanson and Tripathy
1986), by which time most sows have developed de-
tectable antibody titers. Since pig fetuses are capable of
producing antibodies during the latter stages of gesta-
tion, some stillborn piglets will have detectable titers.
The pathogenesis of reproductive disease is poorly
understood, but some authors believe that transplacen-
tal infection, occurring during the very limited period of
maternal leptospiremia, is the sole cause (Fennestad and
Borg-Petersen 1966). While this may be true for systemic
infections such as pomona, the low antibody titers detect-
ed in sows aborting bratislava-infected fetuses has led to
the hypothesis that infection occurs as a result of waning
uterine immunity being unable to prevent transplacental
infection by leptospires present in the genital tract. The
possibility of transplacental infection during lep-
tospiremia appears to increase with the stage of preg-
nancy (Wrathall 1975). From midpregnancy onward, it
is likely that the majority of fetuses in a litter at risk will
become infected. Fennestad and Borg-Petersen (1966)
have suggested that horizontal transmission to litter-
mates not infected during the period of maternal lep-
tospiremia may also occur. Once the placental barrier is
breached, septicemia results in large numbers of lep-
tospires in all fetal tissues (Preston and Morter 1960). It
is unlikely that placental insufficiency plays a role in fetal
death (Wrathall 1975); abortion is probably initiated by
toxic products released from dead and autolyzing fetus-
es.
An additional feature seen in bratislava infection but
not reported for the other swine leptospiral infections is
 CHAPTER 35 LEPTOSPIROSIS Ellis
the persistence of leptospires in the oviduct and uterus
of nonpregnant sows (Ellis et al. 1986c; Ellis and Thier-
mann 1986; Bolin and Cassells 1992) and in the genital
tracts of boars (Ellis et al. 1986b).
CLINICAL SIGNS
The vast majority of swine leptospiral infections are sub-
clinical. Two groups of pigs are most likely to experience
clinical infections: the young piglet and the pregnant
sow.
Acute Leptospirosis
This phase usually coincides with the period of bac-
teremia (Morse et al. 1958; Sleight and Lundberg 1961;
Chaudhary et al. 1966a, b). In experimental infections,
many pigs exhibit transient anorexia, pyrexia, and list-
lessness at this time (Hanson and Tripathy 1986). How-
ever, the mild nature of these signs means that in natur-
al infections, especially in endemically infected herds
where perhaps only one or two animals may be affected,
this phase of infection usually goes unrecognized.
There have been a few reports of jaundice and hemo-
globinuria in naturally occurring outbreaks (Ferguson et
al. 1956), particularly in cases of infection in piglets un-
der 3 months of age by strains belonging to the Ictero-
haemorrhagiae serogroup (Klarenbeek and Winsser
1937; Field and Sellers 1951; Urban and Androsov 1976).
A high proportion of these undergo spontaneous recov-
ery within a week of when symptoms develop. The small
number of such reports suggests that this more severe
form of disease is rare.
Chronic Leptospirosis
Abortions, stillbirths, and the birth of weak piglets of re-
duced viability are primary signs of chronic leptospiro-
sis, particularly pomona infection, in pigs (Bohl et al.
1954; Fennestad and Borg-Petersen 1966) and it is this
aspect of leptospirosis that can cause considerable eco-
nomic loss. Weak litters have been reported as a feature
of Icterohaemorrhagiae infection (Neto et al. 1997).
Information as to the importance of leptospirosis as
a cause of abortion in national swine herds is not avail-
able, and if it were, it must vary from country to country
depending on prevalence, epidemiological, and manage-
ment factors, including the implementation of control
measures. From the limited information available, it
would appear that even in countries where vaccination
has been widely practiced, leptospirosis is a common
cause of swine abortion. In Ontario, for example, 6% of
swine abortions were attributed to pomona infection
(Anon. 1986). Endemic tarassovi infection was consid-
ered to be the cause of a 3% abortion rate in herds in
Poland investigated by Wandurski (1982). Acute out-
breaks can still give rise to severe losses; Saravi et al.
(1989) described an outbreak in a herd in which 19% of
487
pregnant sows aborted, while the number of dead
piglets/sow rose from 8% prior to the outbreak to 28%
during the outbreak. Differences in strain pathogenicity
also contribute to different prevalences of clinical abor-
tion in infected herds (Nagy 1993).
A very high prevalence of serovars belonging to the
Australis serogroup has been observed in aborted pig lit-
ters in part of the United Kingdom. Ellis et al. (1986a)
isolated either serovar bratislava or muenchen from 71%
of the litters they examined. Similar strains have also
been recovered from aborted piglets in the United States
(Bolin and Cassells 1990), where a high prevalence in
aborted fetuses has also been noted (Bolin et al. 1991).
Rehmtulla et al. (1992) reported fetal bratislava infection
following abortions in 16% of sows in a herd in Ontario.
Egan (1995) reported fluorescent antibody test (FAT)–
positive prevalences ranging from 5% to 23% in diagnos-
tic submissions in Ireland. Published experimental eval-
uations of the significance of such microbiological find-
ings are not available. There has, however, been an
absence of significant isolations of other abortifacient
agents from these cases, and the farrowing rate and the
number of live piglets born/sow improve significantly
following either bratislava vaccination (Frantz et al.
1989) or the use of an antibiotic medication program (El-
lis 1989). Van Til and Dohoo (1991) failed to demon-
strate a relationship between positive serology and still-
births.
Following abortions due to pomona, there does not
appear to be any subsequent limitation on reproductive
performance, even in pigs that remain infected for long
periods (Ferguson and Powers 1956; Mitchell et al. 1966;
Kemenes and Suveges 1976).
Infertility is a feature of bratislava infection. An
analysis of serologic and clinical data by Hathaway and
Little (1981) has shown a statistically significant relation-
ship between Australis serogroup titers and infertility in
sows. Similar associations have been observed by Jensen
and Binder (1989) and Van Til and Dohoo (1991). Split-
herd trials, carried out using a bratislava bacterin, have
demonstrated significant improvements in sow fertility
(Frantz et al. 1989).
LESIONS
The main pathological changes are essentially the same
for all infections, with the primary lesion being damage
to the membranes of the endothelial cells of small blood
vessels.
In acute leptospirosis there are no pathognomonic
gross changes. Pathological changes in acute pomona in-
fection are very limited, reflecting the mild nature of
acute clinical disease. Hanson and Tripathy (1986) re-
ported little gross or histopathological change in swine
killed during the acute phase of leptospirosis. Burnstein
and Baker (1954) reported that petechial and ecchymot-
488 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
ic hemorrhages could be seen in the lungs of some pigs,
and histological examinations have revealed minor renal
tubular damage, focal liver necrosis, lymphocytic infil-
tration of the adrenal glands, and meningoencephalitis
with perivascular lymphocytic infiltration (Burnstein
and Baker 1954; Sleight et al. 1960; Chaudhary et al.
1966a).
In chronic leptospirosis, lesions are confined to the
kidneys and consist of scattered small gray foci, often
surrounded by a ring of hyperemia. Microscopic exami-
nation shows these lesions to be a progressive focal in-
terstitial nephritis (Burnstein and Baker 1954; Langham
et al. 1958; Cheville et al. 1980). The interstitial leukocyt-
ic infiltrations, which consist mainly of lymphocytes,
macrophages, and plasma cells, may be extensive in
some areas. Focal damage may also involve glomeruli
and renal tubules. Some affected glomeruli are swollen,
some atrophic, and others are replaced by fibrosis. The
Bowman’s capsule may be thickened, containing
eosinophilic granular material (Langham et al. 1958).
Tubular changes involve atrophy, hyperplasia, and the
presence of necrotic debris in the lumen in some areas.
Occasionally, petechial hemorrhages may be present in
interstitial spaces.
Older lesions mainly consist of fibrosis and intersti-
tial infiltration. Chronic lesions with accompanying
acute inflammatory changes are still noticeable as long
as 14 months postinfection (Morter et al. 1960).
Experimental studies indicate leptospires can invade
the mammary gland of pigs and produce a mild, focal
nonsuppurative mastitis (Tripathy et al. 1981).
The gross pathology of fetuses aborted as a sequela of
pomona infection is nonspecific and includes edema of
various tissues, serous or bloodstained fluid in body cav-
ities, and sometimes petechial hemorrhages in the renal
cortex (Ryley and Simmons 1954b; Fennestad and Borg-
Petersen 1966; Wrathall 1975). These changes are proba-
bly the result of intrauterine autolysis. Jaundice may be
seen in some aborted piglets (Hathaway et al. 1983). Fo-
cal necrosis, presenting as small grayish-white spots, is a
frequent finding in the liver (Ryley and Simmons 1954b;
Fish et al. 1963; Fennestad and Borg-Petersen 1966). His-
tological examination may reveal small foci of interstitial
nephritis.
Placentas from aborted fetuses are grossly normal
(Fish et al. 1963; Fennestad and Borg-Petersen
1966).
DIAGNOSIS
A diagnosis of leptospirosis in swine may be required
not only for the clinician to confirm leptospirosis as a
cause of clinical disease but also for other reasons, such
as (1) the assessment of the infection and/or the im-
mune status of a herd for the purposes of a control or
eradication program on either a herd or a national basis;
(2) epidemiological studies; or (3) a determination of the
infectivity status of an individual animal to assess its
suitability for international trade or for introduction in-
to an uninfected herd.
The mild, often inapparent, clinical signs of acute
leptospirosis make clinical diagnosis difficult; therefore,
diagnosis is usually based on the results of laboratory
procedures.
Laboratory diagnostic procedures for leptospirosis
fall into two groups. The first group consists of tests for
antibody detection; the second contains the tests for the
demonstration of leptospires in pig tissues. The selection
of tests to be carried out depends on the purpose for
which a diagnosis is to be made and the resources avail-
able.
Serologic Tests
Serologic testing is the most widely used method for di-
agnosing leptospirosis, and the MAT (Cole et al. 1980;
Faine 1982) is the standard serologic test. The minimum
antigen requirements are that the test should employ
representative strains of all the serogroups known to ex-
ist in the particular country, plus those known to be
maintained by pigs elsewhere.
The MAT is used primarily as a herd test. To obtain
useful information, at least 10 animals or 10% of the
herd, whichever is the greater (Cole et al. 1980), should
be tested. A retrospective diagnosis of both acute lep-
tospirosis and pomona abortion may be made when the
majority of affected animals have titers of 1:1000 or
greater. Increasing the sample size and sampling a num-
ber of different cohorts markedly improve epidemiolog-
ical information, investigations of clinical disease, as-
sessments of vaccination needs, and public health
tracebacks.
As an individual-animal test, the MAT is very useful
in diagnosing acute infection; rising antibody titers in
paired acute and convalescent serum samples are diag-
nostic. The presence of antibody in fetal serum is diag-
nostic of leptospiral abortion.
The MAT has severe limitations in the diagnosis of
chronic infection in individual pigs, both in the diagno-
sis of abortion and in the identification of renal or geni-
tal carriers. Infected animals may have MAT titers below
the widely accepted minimum significant titer of 1:100
(Ellis et al. 1986b, c).
Other serologic tests have been described for use in
pigs, especially ELISA-based tests, but none of these have
gained widespread acceptance for use as diagnostic tests.
Demonstration of Leptospires in Pig Tissues
The isolation of leptospires from, or their demonstration
in, the internal organs (such as liver, lung, brain) and
body fluids (blood, cerebrospinal, thoracic, and peri-
 CHAPTER 35 LEPTOSPIROSIS Ellis
toneal) of clinically affected animals gives a definitive di-
agnosis of acute clinical disease or, in the case of a fetus,
a diagnosis of leptospiral abortion and probable chronic
infection of its mother.
Their presence in the male or female genital tract, the
kidney, or urine, in the absence of evidence of general-
ized infection, is diagnostic of chronic infection. Failure
to demonstrate leptospires in the urine of a pig does not
rule out the possibility of the animal being a chronic re-
nal carrier; it merely indicates that the pig was not ex-
creting detectable numbers of leptospires at the time of
testing.
ISOLATION. Isolation, especially from clinical mater-
ial, is difficult and time-consuming and is a job for labo-
ratories specializing in the identification of isolates. Iso-
lation from renal carriers is very useful in
epidemiological studies to determine which serovars are
present in an animal species or in a particular group of
animals or geographic location.
The isolation of leptospires is the most sensitive
method of demonstrating their presence, provided that
antibiotic residues are absent, that tissue autolysis is not
advanced, and that tissues for culture have been stored at
a suitable temperature (4˚C) and, in the case of urine, at
a suitable pH since collection.
Culture should be carried out in a semisolid
(0.1–0.2% agar) bovine serum-albumin medium contain-
ing either Tween 80 (Johnson and Harris 1967) or a com-
bination of Tween 80 and Tween 40 (Ellis 1986), and
preferably a small amount of fresh rabbit serum
(0.4–2%) if the more fastidious leptospires such as
bratislava are to be isolated. A dilution culture method
should be used (Ellis 1986). Contamination may be con-
trolled by a variety of selective agents (e.g., 5-fluo-
rouracil, nalidixic acid, fosfomycin, and a cocktail of ri-
famycin, polymyxin, neomycin, 5-fluorouracil,
bacitracin, and actidione). The use of selective agents
will reduce the chance of isolation where there are only
small numbers of viable leptospires. Culture media con-
taining 5-fluorouracil at levels between 200 and 500
µg/mL should be used as transport media for the sub-
mission of samples (Ellis 1990).
Cultures should be incubated at 29–30˚C for at least
12 weeks, preferably for 26 weeks (Ellis 1986). They
should be examined by dark-ground microscopy every
1–2 weeks.
OTHER METHODS OF DEMONSTRATING LEPTO-
SPIRES. Leptospires do not stain satisfactorily with
the aniline dyes, and silver-staining techniques lack sen-
sitivity and specificity (Baskerville 1986). Dark-ground
microscopy of fetal fluids or urine has been widely used
in the diagnosis of leptospirosis and can be a useful tool
in the hands of an experienced diagnostician, but many
489
tissue artifacts can be mistakenly identified as lep-
tospires.
The demonstration of leptospires by immunochemi-
cal tests (immunofluorescence, immunoperoxidase, and
immunogold) is more suited to most laboratory situa-
tions; however, these tests are “number-of-organisms”
dependent and lack the sensitivity of culture. They pro-
vide no information as to the infecting serovar (Ellis
1990) and require high-IgG-titer antileptospire sera,
which are not available commercially. Immunofluores-
cence is the method of choice for the diagnosis of fetal
leptospirosis. There have been a number of polymerase
chain reaction methods published, but so far these have
failed to deliver the promised increase in sensitivity
which the underlying technology should theoretically de-
liver (Taylor et al. 1997).
PREVENTION AND CONTROL
Interruption of transmission from an infected pig or oth-
er host to a pig is the critical factor in control. Control of
leptospirosis depends on the combined use of three
strategies: antibiotic therapy, vaccination, and manage-
ment. Unfortunately, not all these options are available
in every country; for example, vaccines are not available
in many Western European countries, including the
United Kingdom, and problems of antibiotic residues
may make the use of antibiotic therapy difficult in other
situations. In the United States, the most useful antibiot-
ic for leptospiral control/treatment programs, strepto-
mycin, is no longer available for veterinary use. Control
programs must therefore be modified to meet local con-
ditions.
Vaccination induces immunity of relatively short du-
ration. Immunity to infection is probably never 100%
and, at best, lasts little more than 3 months (Kemenes
and Suveges 1976; Ellis et al. 1989); immunity to clinical
disease is believed to last somewhat longer, although the
exact duration is not known. Vaccination will markedly
reduce the prevalence of infection in a herd (Wrathall
1975; Kemenes and Suveges 1976) but will not eliminate
infection (Hodges et al. 1976; Edwards and Daines 1979;
Cargill and Davos 1981). Given the widespread use of
tetracycline medication of feed in parts of Europe to con-
trol bratislava infection and all the attendant residue
problems, there is an urgent need for the marketing of
an effective bratislava vaccine in Europe.
Antibiotics alone will not eliminate pig-maintained
leptospiral infections from the individual carrier animal
or control infection in herds. Despite claims by some au-
thors that either systemic streptomycin at 25 mg/kg
body weight (Dobson 1974; Alt and Bolin 1996) or oral
tetracyclines at levels of 800 g/ton of feed (Stalheim
1967) will eliminate carriers, others have reported that
these regimes do not work (Doherty and Baynes 1967;
490 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
Hodges et al. 1979). Recent work into the use of alterna-
tive antibiotic therapy regimes indicates that oxytetracy-
cline (40 mg/kg for 3 or 5 days), tylosin (44 mg/kg for 5
days), or erythromycin (25 mg/kg for 5 days) may be ef-
fective in eliminating pomona from the kidneys of exper-
imentally infected pigs (Alt and Bolin 1996).
The main management factor in the control of lep-
tospirosis is the prevention of direct or indirect contact
with free-living vectors or other domestic stock. Strict
biosecurity should be implemented and rodent control
programs instigated in and around the production com-
plex. When faced with an outbreak of clinical disease,
the best option is to treat both affected and at-risk stock
with streptomycin at 25 mg/kg body weight, to immedi-
ately vaccinate the at-risk stock, and then to introduce a
regular vaccination program. If vaccination is not an
available option, then a feed medication program, using
either chlor- or oxytetracycline at 600–800 g/ton of feed,
should be introduced. This ration is fed either continu-
ously or on a 1-month-on/1-month-off basis. Alterna-
tively, it may be fed for two periods of 4 weeks in the
year, preferably one in the spring and the other in the au-
tumn.
The use of artificial insemination is an important
tool in the control of bratislava infection.
ZOONOSIS
Leptospirosis is an important occupational zoonosis of
those who work with pigs, especially farmers and those
involved in slaughtering pigs. Pigs are now being pro-
duced for intended xeno grafting. It is important to re-
member the potential risk to recipients posed by pig-as-
sociated leptospirosis (Bjoersdorff et al. 1995).
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 Mycoplasmal Diseases
36 R. F. Ross
Mycoplasmal pneumonia of swine (MPS), or enzootic
pneumonia, is caused by Mycoplasma hyopneumoniae and
is one of the most important contributors to disease-as-
sociated loss in swine production. Recently, the infection
has been attributed increased importance as part of a
composite infection with porcine reproductive and respi-
ratory syndrome virus (PRRSV) and other agents in U.S.
swine. This syndrome, known as the porcine respiratory
disease complex (PRDC), has emerged in spite of the
continuing adoption of strategies for rearing high-
MYCOPLASMAL PNEUMONIA OF SWINE
Mare and Switzer (1965) and Goodwin et al. (1965) were
the first to report the isolation of a mycoplasma from
pneumonic lung and the experimental reproduction of
the disease. The isolates, named M. hyopneumoniae and
M. suipneumoniae, were shown to be identical, and the
former name was given priority. Enzootic pneumonia
has been reported from many countries and has long
been believed to be one of the most common and eco-
nomically important diseases occurring in swine. Loss
associated with disease is the result of a complex interac-
tion between the mycoplasma and other infections, poor
management, and poor environmental conditions.
ETIOLOGY
Isolation of the organism is complicated by its extremely
fastidious growth requirements and the frequent pres-
ence of M. hyorhinis in the swine respiratory tract. The
most widely used growth medium is that described by
Friis (1975). Media and methods for isolation of M. hy-
opneumoniae were reviewed by Ross and Whittlestone
(1983).
In primary broth cultures, M. hyopneumoniae grows
slowly, producing a faint turbidity and an acid color shift
after 3–30 days’ incubation. Generally, cultures are pas-
saged several times in broth, then inoculated on agar
medium and incubated in a 5–10% carbon dioxide at-
mosphere. Colonies of the organism become barely visi-
ble after 2–3 days’ incubation, and they increase in size
to about 0.25–1 mm diameter in about 10 days. Infor-
health-status swine and widespread availability of M. hy-
opneumoniae and PRRSV vaccines. Mycoplasma hyorhinis
is another common inhabitant of the respiratory tract of
swine, is not a primary cause of pneumonia, but occa-
sionally causes polyserositis and arthritis in young pigs.
Another mycoplasma, Mycoplasma hyosynoviae, causes
arthritis in growing-finishing swine. Other swine iso-
lates, not known to be pathogenic or not common, in-
clude M. flocculare, M. sualvi, M. hyopharyngis, and sever-
al species of acholeplasmas.
mation concerning the biological and biochemical prop-
erties of M. hyopneumoniae and methods for specific
identification were reviewed by Ross and Whittlestone
(1983). M. flocculare, a nonpathogen common in swine
lungs, has many morphological, growth, and antigenic
similarities to M. hyopneumoniae. Finally, a very impor-
tant attribute of mycoplasmas, with potential pathogen-
ic and control implications, is their marked propensity to
switch surface antigens. Artiushin and Minion (1996) re-
cently provided evidence of heterogeneity existing
among isolates of M. hyopneumoniae.
EPIDEMIOLOGY
Field observations have strongly implicated carrier swine
as a major source of infection with M. hyopneumoniae. In
an early report Pullar (1948) summarized data on out-
breaks of pneumonia in 190 Australian swine herds; 80%
of outbreaks were associated with introduction and
commingling of store (feeder) pigs with swine already
present on the farm, and 20% were associated with intro-
duction of adult breeding stock.
Transmission of M. hyopneumoniae is apparently ef-
fected mainly by direct contact with respiratory tract se-
cretions from infected swine. Goodwin (1972a) demon-
strated that the organism could be isolated from nasal
samples from affected pigs. Farrington (1976) and
Etheridge et al. (1979) demonstrated that transmission
of the organism occurs among penmate swine; however,
transmission does not always take place even among
495
496 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
commingled penmates (Goodwin 1972b). Because of the
fastidious nature of the organism and the large inoculum
required for experimental transmission of the disease,
dogma has held that it could not be easily transmitted
between herds unless carrier swine were involved. How-
ever, many breakdowns have occurred in pneumonia-
free herds that were thought to be rather strictly isolated
(Whittlestone 1979). In Britain, Goodwin (1985) found
that breakdowns occurred most frequently when herds
were less than 3.2 km apart. Jorsal and Thomsen (1988)
found that reinfections occurred most frequently in Dan-
ish herds during the autumn and winter and when spe-
cific-pathogen-free (SPF) herds were close to non-SPF
herds. Transmission was especially likely when the latter
contained more than 500 swine. Further work by the
same group (Thomsen et al. 1992) and work in Switzer-
land (Stark et al. 1992) support the conclusion that air-
borne transmission is a mechanism for reinfection of
SPF herds with M. hyopneumoniae.
MPS is maintained in many herds by sow-to-pig
transmission of M. hyopneumoniae. Once infection is es-
tablished in a few pigs, transmission among penmates
occurs, especially after animals are pooled together at
weaning time. In continuous-production systems, M. hy-
opneumoniae and a number of other important respira-
tory pathogens may be transmitted in large numbers
from older to younger pigs. Overt signs of MPS usually
are not seen until piglets are 6 weeks of age or older. Al-
though M. hyopneumoniae infections are commonly
thought to begin in the nursing pig, microbiological evi-
dence that the organism is common in such lesions has
not been presented. Kott (1983) found no evidence of M.
hyopneumoniae in lungs of 55 baby pigs with pneumonia.
Predominant organisms isolated were Haemophilus para-
suis, M. hyorhinis, and Bordetella bronchiseptica. Pigs of
various ages seem to be equally susceptible to the organ-
ism. Undoubtedly, the long incubation period, slow
spread of the organism in litters, increased animal den-
sity, spread of other infectious agents, and environmen-
tal factors that develop following weaning contribute to
the peak prevalence of M. hyopneumoniae disease in
growing-finishing swine.
Surveys conducted in a variety of countries in the
past indicated that lesions typical of those seen with
MPS occur in 30–80% of slaughter-weight swine (Whit-
tlestone 1979; Switzer and Ross 1975). A more recent
Minnesota survey for gross lesions at slaughter indicated
that 100% of 125 herds had typical “enzootic pneumo-
nia” lesions and 75% of the pigs were affected (Pointon et
al. 1990). Guerrero (1990) reported on surveys conduct-
ed at slaughter in seven countries; the prevalence of
pneumonia ranged from 38% to 100%. However, Tielen
(1995) indicated that the prevalence of pneumonia at
slaughter in the Netherlands has decreased from 23% in
1981 to 5.8% in 1990. It is conceivable that during the
past 10 years, where improved control measures such as
age-segregated rearing have been implemented, the over-
all prevalence of pneumonia at slaughter may have de-
creased. In some areas, however, pulmonary disease has
increased in complexity and severity because of in-
creased involvement of viruses such as PRRSV with M.
hyopneumoniae (Halbur et al. 1993).
The frequency of isolation of M. hyopneumoniae from
chronic swine pneumonia varies. In a survey of Iowa
breeding swine of various ages, Young et al. (1983) found
that animals in 60% of 597 herds had complement-fixing
(CF) antibodies to M. hyopneumoniae. In another survey
of Iowa swine, primarily slaughter-weight swine, Owen
(1990) found CF antibodies to the organism in sera from
80% of 88 herds and 32% of 2077 animals in these
herds.
Economic loss attributable to MPS has long been as-
sociated with reduced rate of gain and feed efficiency
(Switzer and Ross 1975). Pointon et al. (1985) reported
that the growth rate of pigs held in contact with MPS-af-
fected pigs was reduced by 12.7% between 50 and 85 kg
body weight. In another trial, they found that the growth
rate of pigs exposed to infected dams was reduced by
15.9% (between 8 and 85 kg body weight), and feed con-
version was decreased by 13.8% (between 10 and 25 kg
body weight). Losses were estimated to be approximate-
ly $2.80 (Australian) for each pig produced.
Much information about the prevalence of MPS and
the related economic loss has been based on evaluation
of lungs at slaughter; however, caution must be exercised
when using data collected at slaughter. Scheidt et al.
(1990a) found no correlation between average daily gain
and severity of pneumonia at slaughter, and Noyes et al.
(1990) found little correlation between extent of lesions
detected at slaughter and those detected radiologically
earlier in life. In a study of pigs from two Danish con-
ventional farrow-to-finish herds, Paisley et al. (1993a,
1993b) reported that mycoplasma-like pneumonia, as
well as several other respiratory lesions found at slaugh-
ter, were related to reduced mean daily gain. However,
they also concluded that lesions present at slaughter
could be related to only 9–27% of the variation in mean
daily gain. They suggested that the remaining 20–90% of
variation was due to factors such as environment, feed,
genetics, and management systems.
PATHOGENESIS
The incubation period of MPS was reported by Betts
(1952) to be 10–16 days under natural conditions; how-
ever, other reports have indicated considerable variabili-
ty in duration. Onset of disease is probably dependent
on the intensity of infection with the organism on the
tracheal and bronchial mucosal surfaces. Disease has
been reported in pigs 2 weeks of age (Holmgren 1974),
 CHAPTER 36 MYCOPLASMAL DISEASES Ross
but it generally spreads slowly and many pigs do not evi-
dence disease until they are 3–6 months old.
In the early stages of infection, large numbers of my-
coplasmas have been detected by electron microscopy as
well as by immunofluorescence (IF) tests, primarily on
the surfaces of the trachea, bronchi, and bronchioles.
Very few organisms have been found in the small bron-
chioles and alveoli. Scanning (Mebus and Underdahl
1977) and transmission (Blanchard et al. 1992) electron
microscopy of MPS-affected lungs revealed a close asso-
ciation of mycoplasmas with the cilia as well as extensive
loss of cilia. No evidence of a specialized attachment or
orientation of the organism to the epithelial cells has
been demonstrated. The microscopic changes, especially
peribronchial and perivascular lymphoreticular hyper-
plasia, are widely thought to reflect significant involve-
ment of the immune response in lesion development.
Mycoplasma pathogens generally are known to uti-
lize a very complex virulence process; this involves at-
tachment/colonization, cytotoxicity, competition for
substrates, and evasion and modulation of the host im-
mune response. Such processes are not measured by a
single effect but by the expression of a multitude of gene
products (adhesins, nutrient receptors, mitogens, poly-
saccharide polymers, and metabolic intermediates). Re-
cent efforts have been directed toward elucidation of the
specific pathogenetic mechanisms utilized by M. hyo-
pneumoniae in induction of pneumonia. We have demon-
strated that M. hyopneumoniae attaches to a variety of
porcine cells in vitro (Zielinski et al. 1990); however, the
most meaningful was the demonstration of the attach-
ment of the organism to ciliary tufts of single ciliated tra-
cheal cells (Zielinski and Ross 1993). An in vitro mi-
crotiter system for studying attachment of the organism
to cilia was used to partially characterize the attachment
process and to demonstrate that at least two proteins, 97
and 145 kDa, in the organism’s membrane, were possibly
involved in the attachment process (Zhang et al. 1995).
Two additional proteins of 28.5 and 57 kDa were shown
by Chen et al. (1996) to compete for binding of M. hyo-
pneumoniae to porcine cilia. The attachment process in
M. hyopneumoniae disease is undoubtedly a multifaceted
and complex process.
Infected airways evidence ciliary and epithelial cell
damage. Similar damage has been produced in vitro with
tracheal ring cultures inoculated with pneumonic lung
homogenate containing M. hyopneumoniae by DeBey and
Ross (1994). Another potentially important event in the
pathogenesis of the disease is the interaction of the my-
coplasma with lymphoid cells. Membranes of the organ-
ism were mitogenic for porcine lymphocytes in vitro
(Messier and Ross 1991), and swine infected with the or-
ganism have altered alveolar macrophage function
(Caruso and Ross 1990) and are immunosuppressed
(Wannemuehler et al. 1988; Weng and Lin 1988).
497
Virtually all naturally occurring cases of MPS are
mixed infections involving mycoplasmas, bacteria, virus-
es, or nematodes. Experimentally induced M. hyopneu-
moniae pneumonia has been shown to predispose swine
to pneumonia caused by P. multocida (Ciprian et al. 1988;
Amass et al. 1994) and Actinobacillus pleuropneumoniae
(Yagihashi et al. 1984). The PRRSV, in interaction with
M. hyopneumoniae and other agents, has been strongly
implicated in the emergence of a widespread complicat-
ed pneumonia known as PRDC in many U.S. (Halbur et
al. 1993; Halbur 1996) and Canadian finishing units
(Moore 1996). The importance of environmental factors
in respiratory disease losses is discussed in Chapter 61.
CLINICAL SIGNS
Betts (1952) described MPS as a chronic disease with a
high morbidity and a low mortality. The principal clini-
cal sign is a chronic, nonproductive cough. Onset of the
disease is gradual, with coughing continuing for a few
weeks or even months, although some affected pigs evi-
dence little or no coughing. Intensity of coughing is of-
ten greatest in growing-finishing swine. Respiratory
movements are normal unless extensive lung involve-
ment, especially secondary bacterial infection, develops.
Death loss associated with secondary bacterial infection
and stress may occur at 4–6 months of age. Animals with
this “secondary breakdown” may evidence inappetence,
labored breathing or “thumping,” increased coughing,
elevated temperatures, and prostration. Most pigs with
MPS evidence no malaise but appear unthrifty, their hair
coat lacking a normal “bloom.” Growth may be retarded
and stunting may occur, although appetites are usually
normal.
LESIONS
Gross lesions in lungs of swine with MPS consist of pur-
ple to gray areas of consolidation. The lesions are virtu-
ally always in the ventral portions of the cranial and mid-
dle lobes, the accessory lobe, and the cranial portion of
the caudal lobes of the lungs (Fig. 36.1). The gross ap-
pearance of the involved lung resembles that of at-
electatic lung, particularly during the chronic stages of
disease. When the affected lung is incised, the consisten-
cy is “meaty” but not excessively firm. In early- and mid-
dle-stage disease there is usually a catarrhal exudate in
the airways. Bronchial and mediastinal lymph nodes are
often enlarged.
Microscopic changes in the lungs of pigs with exper-
imentally induced MPS have been described by Whittle-
stone (1972). The lesions are very similar to those de-
scribed in reports on the naturally occurring disease.
Early lesions consist of small accumulations of neu-
trophils in the lumina and around airways as well as in
498 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
36.1. The lung of a
pig with M. hyopneu-
moniae pneumonia.
the alveoli. Infiltrating lymphocytes are seen in adventi-
tia of arterioles and venules and around airways. As the
disease progresses there are increased numbers of lym-
phocytes in perivascular, peribronchial, and peribron-
chiolar tissues as well as in the lamina propria of the air-
ways. Alveoli may contain eosinophilic edema fluid and
increased numbers of mononuclear, septal, and poly-
morphonuclear cells (Fig. 36.2). By about 15–20 days
there are appreciable cuffing or lymphoid hyperplasia
around the airways, more extensive accumulations of
edema fluid, large mononuclear and other inflammatory
36.2. The lung of a pig with M. hyopneumoniae
disease. Early stage with mixed alveolar exudate and
some peribronchiolar lymphocytic infiltration (H&E).
cells in alveoli, and thickening of interalveolar septa.
More advanced lesions, 17–40 days postinfection as de-
scribed by Whittlestone (1972), consist of extensively
proliferated lymphoreticular tissue in perivascular and
peribronchiolar areas (Fig. 36.3). In recovering lesions
described by Whittlestone there were collapsed alveoli,
alveolar emphysema, and rather extensive hyperplastic
lymphoid nodules (Fig. 36.4), especially in association
with the airways. MPS lesions are markedly influenced
by secondary bacterial infections, stress, poor air quality,
and bad management (see Chapter 61).
36.3. The lung of a pig with M. hyopneumoniae
disease. More advanced lesion with resolving alveolar
inflammation and peribronchiolar lymphocytic
hyperplasia (H&E; ×287).
 CHAPTER 36 MYCOPLASMAL DISEASES Ross
36.4. The lung of a pig with M. hyopneumoniae
disease. Advanced lymphocytic hyperplasia, including
obliteration of bronchioles (H&E; ×287).
DIAGNOSIS
Clinical signs that are helpful and lead one to suspect
MPS include a chronic nonproductive cough, retarded
growth and stunting, low mortality, slow onset and
spread, and repeated occurrence of the disease. Lesions
of MPS, described in the previous section, are character-
istic for MPS but are not specific in that similar lesions
may be seen in pneumonias caused by other agents. Re-
cently, Ross and Stemke (1996) reviewed traditional and
new molecular approaches to diagnosis of MPS in swine.
Serologic methods found useful for diagnosis of MPS
include indirect hemagglutination (IHA), CF, and en-
zyme-linked immunosorbent assay (ELISA) (Ross and
Whittlestone 1983). Other tests that have been evaluated
include agglutination, latex agglutination, and indirect
IF tests.
Nicolet et al. (1980) and Bommeli and Nicolet (1983)
developed an indirect ELISA using a Tween 20 extract for
detection of antibodies to M. hyopneumoniae. Cross-reac-
tions resulting from M. flocculare infections were mini-
mized using a slight modification of the Tween 20 ELISA
(Bereiter et al. 1990). Additional tests for detection of
antibody to M. hyopneumoniae, including a blocking
ELISA, have been reported in recent years (Feld et al.
1992); their reliability and usefulness on a wide scale
need to be determined. In a comparison of ELISA tests,
Wallgren et al. (1996) found earlier detection with the in-
direct (Tween 20) ELISA, whereas they found less cross-
reactivity with other mycoplasmas with a blocking
ELISA.
499
ELISA antibodies develop in susceptible pigs by 3
weeks (Bereiter et al. 1990) after exposure to M. hyopneu-
moniae and persist for as long as 52 weeks postexposure
(Armstrong et al. 1983; Bereiter et al. 1990). In the study
by Bereiter et al., optical density (OD) values with the
Tween 20 ELISA peaked about 5–7 weeks postexposure,
and animals were still seropositive 1 year after exposure.
Using the Tween 20 ELISA, Zimmermann et al. (1986)
found 65% of animals positive between 4 and 8 months
of age, with numbers positive declining to 26–28% by
8–12 months of age. Yagihashi et al. (1993) found that
72% of sows from conventional herds were positive with
the Tween 20 ELISA; the seropositive rate declined with
increasing parity of sows. Utilizing sera from a large far-
row-to-finish herd with a history of respiratory disease,
we found that colostral antibodies declined from sample
1 (17 days of age) to sample 3 (52 days of age); mean
ODs then increased until sample 8 (132 days of age),
when a sharp increase occurred (Young and Ross, un-
published data—1993). Yagihashi et al. (1993) further
reported that in 3267 growing-finishing swine ranging in
age from 1 to 6 months, the seropositive rate increased
sharply from the age of 4 months to 6 months.
Zimmermann et al. (1989) and Zimmermann (1990)
reported that evaluation of colostrum was a useful strat-
egy for monitoring infection in attempts to eradicate M.
hyopneumoniae from Swiss swine herds. Morris et al.
(1994) reported that the median half-life of passively ac-
quired ELISA antibodies against M. hyopneumoniae in
suckling piglets was 15.8 days. They further indicated
that estimates of the time at which passive antibodies
waned were 30, 45, and 63 days for piglets with initial an-
tibody concentrations classified as low, medium, or high,
respectively.
Direct, as well as indirect, modifications of the IF test
have been used to detect M. hyopneumoniae in lung tis-
sues, and positive results obtained have correlated well
with positive findings obtained by other methods. IF
seems particularly suited for acute-stage disease, when
larger numbers of mycoplasmal cells are present. The or-
ganism can be found principally on the bronchial and
bronchiolar lining of affected lung. M. hyopneumoniae
has also been detected in pneumonic lungs by use of an
enzyme-linked immunoperoxidase technique (Brug-
gmann et al. 1977). Mattsson et al. (1995) and Blanchard
et al. (1996) reported very promising developments us-
ing the polymerase chain reaction (PCR) for rapid, spe-
cific detection of M. hyopneumoniae in nasal swabs and
tracheobronchial washings from infected pigs.
M. hyopneumoniae is one of the most difficult my-
coplasmas to isolate and identify. It grows slowly and is
often overgrown by M. hyorhinis, a common secondary
invader in swine pneumonia. Although methods for iso-
lation have been improved and more laboratories have
developed the capability to isolate the organism, diagno-
sis by culture is not feasible in most situations.
500 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
TREATMENT
Early evidence that M. hyopneumoniae disease could be
controlled at least in part by medication with tetracycline
antibiotics has been reviewed by Switzer and Ross
(1975). Tetracycline antibiotics do not prevent establish-
ment of infection, and lesions apparently develop after
cessation of medication. Repeated administration of
long-acting oxytetracycline during the suckling and early
nursery periods may have potential for reduction of
pneumonias occurring at later stages (Scheidt et al.
1990b). Inamoto et al. (1994), using an in vitro assay, re-
ported that a comparison of strains of M. hyopneumoni-
ae isolated in Japan between 1970–81 and 1989–90 indi-
cated decreasing susceptibility to chlortetracycline.
Feed medication with 1000 g/ton tylosin phosphate
(Mare and Switzer 1966) and water medication with 2
g/gallon (530 g/L) tylosin tartrate (Huhn 1971) did not
prevent MPS. Goodwin (1972a) presented evidence that
intramuscular injection of 10 mg/kg tylosin daily, start-
ing the day before exposure and continuing for 3 addi-
tional days, reduced the severity of the disease. However,
intramuscular inoculation with tylosin at 8.8 mg/kg for 5
days beginning 14 days after intratracheal challenge had
no effect on incidence or severity of experimentally in-
duced MPS (Ross, unpublished data—1981). In another
study Ross and Skelly (unpublished data—1982) found
that tylosin phosphate at 100 g/ton fed for 8 weeks had
no effect on severity of lung lesions in pigs with natural-
ly acquired MPS.
Evidence has been presented that lincomycin fed at
200 g/ton for 3 weeks reduces the incidence and severity
of MPS and results in improved performance (Van Bu-
ren 1983). However, Ross (unpublished data—1985)
found that continuous medication with lincomycin at
500 g/ton of feed did not prevent transmission of M. hy-
opneumoniae from pigs with clinically overt MPS to in-
contact susceptible pigs, nor did it reduce the severity of
pneumonia in pigs with early-stage established disease.
Tiamulin at 200 ppm in feed for 10 days reduced the
severity of experimentally induced (Schuller et al. 1977a)
and naturally occurring (Martineau et al. 1980) MPS.
Tiamulin at 200 ppm in the feed for 10 days (Martineau
et al. 1980) improved growth rates; given at 30 ppm con-
tinuously (Burch 1984b), it improved weight gains and
feed efficiency in the presence of MPS. Administration of
0.006% tiamulin in the drinking water (Johnson et al.
1978) or parenterally at 15 mg/kg for 3 days (Burch
1984a) was reported to result in clinical improvement
and improved growth in the presence of naturally occur-
ring MPS. However, in spite of the many published re-
ports on the efficacy of tiamulin, we were unable to de-
tect a beneficial effect when the drug was administered in
the drinking water at 60, 120, or 180 ppm for 10 days to
pigs with experimentally induced MPS (Ross and Cox
1988). Two developments seem noteworthy with respect
to the issue of tiamulin and its value for treatment of en-
zootic pneumonia. Where acceptable, use of a combina-
tion of tiamulin with chlortetracycline or oxytetracycline
may be beneficial in reducing the severity of the disease
(Burch et al. 1986; Koh et al. 1996). The second develop-
ment is that SDZ PMD 296 (Econor, Sandoz), a new
pleuromutilin derivative, appears to have exceptional ac-
tivity against M. hyopneumoniae (Hannan and Ripley
1996; Windsor et al. 1996), with promise that it will be
more effective in treatment of enzootic pneumonia than
tiamulin.
Newer quinolone antibiotics have good in vitro activ-
ity against M. hyopneumoniae (Hannan et al. 1989; Coop-
er et al. 1993). At least four quinolones—enrofloxacin
(Simon et al. 1990), danofloxacin (Ross et al. 1990), nor-
floxacin (Hannan and Goodwin 1990), and ofloxacin
(Kuwano et al. 1992)—have been reported to be effective
in treating the disease.
Sulfonamides have long been known to have little in-
fluence on M. hyopneumoniae, although they are widely
used for control of bacterial infections responsible for a
great part of the economic loss associated with MPS.
Penicillin, streptomycin, and erythromycin are of no val-
ue in treatment of MPS.
PREVENTION
Early methods for prevention of MPS were reviewed by
Switzer and Ross (1975). Effective control of the disease
depends on providing an optimal environment, includ-
ing air quality, ventilation, and temperature, and proper
stocking density. Use of a strict all-in/all-out production
scheme is possibly the most effective way to control the
disease in infected herds (Clark et al. 1990; Scheidt et al.
1990c). Clark et al. (1989) have recommended no more
than 3 weeks’ variation in age in stocking a room. The
strategy of using repopulation to gain improved perfor-
mance may be in part related to reduction in the severity
of, or complete elimination of, the retarding effects of
MPS.
Various health control schemes have been developed
which emphasized certification of herds free of MPS and
other diseases. Methods used included on-farm inspec-
tion, rigid isolation, and periodic examination of lungs
from slaughter pigs reared in close confinement (Good-
win and Whittlestone 1967). Whittlestone (1979) has re-
viewed problems attendant to breakdowns in various
systems for maintenance of MPS-free herds.
It has been known for many years that older sows that
have recovered from MPS are less likely to carry M. hyo-
pneumoniae. A number of systems have been devised to
take advantage of this natural adjunct to disease control.
 CHAPTER 36 MYCOPLASMAL DISEASES Ross
Serotesting of older sows to detect those that are
seropositive, with the objective of culling them to estab-
lish an MPS-free herd, has been attempted with variable
success (Schuller et al. 1977b). Renewed efforts to use a
serotest and cull strategy for controlling MPS should uti-
lize the Tween 20 ELISA discussed earlier. In work with
the Tween 20 ELISA, Zimmermann et al. (1986) found
substantially more positive animals when colostrum was
tested rather than serum.
The SPF pig program has found wide application in
the control of MPS. Producers that have repopulated ac-
cording to this system or with second-generation stock
derived from primary herds have benefited greatly,
although breakdowns have posed a problem. Monitor-
ing for continued freedom from MPS should include
use of the most sensitive and specific tests, such as
ELISA, for detection of subclinical M. hyopneumoniae in-
fections.
Alexander et al. (1980) developed the medicated ear-
ly-weaning (MEW) system, wherein intensive medica-
tion of the sow during late gestation and immediately
following parturition and of the newborn piglet is used
to derive pigs free of M. hyopneumoniae. Pigs derived
were free of MPS, and monitoring revealed no evidence
of M. hyopneumoniae or Bordetella bronchiseptica in repre-
sentative pigs examined from 5 weeks of age to slaugh-
ter. Harris (1990) has devised a similar strategy
(IsoweanTM) utilizing early weaning and rearing in three
isolated sites to prevent transmission of a variety of dis-
eases, including M. hyopneumoniae, from the sow to the
piglet. Pigs reared using the IsoweanTM strategy gained
substantially better than those reared in the traditional
manner (Harris et al. 1990). Zimmermann et al. (1989)
reported that a control program based on removal of all
young swine and gilts, coupled with feeding of tiamulin
or chlortetracycline/tylosin/sulfadimidine to the re-
maining older sows, resulted in elimination of M. hyo-
pneumoniae from 16 out of 17 Swiss herds. Continued
surveillance to ensure that the organism had not reen-
tered the herd was accomplished with a four-prong pro-
M. HYORHINIS POLYSEROSITIS AND ARTHRITIS
Respiratory tract infection with M. hyorhinis has been re-
ported in swine from many different countries. It is usu-
ally the first mycoplasma isolated when an investigator
begins searching for these organisms in swine tissue. The
organism is an extremely common contaminant in cell
culture lines.
501
gram of clinical observation, commingling of progeny
with known susceptible swine during growing and fin-
ishing, slaughter examination of lungs, and milk and
blood serology with the Tween 20 ELISA.
Dee (1994) reported use of a modified MEW pro-
gram to eliminate M. hyopneumoniae from two swine op-
erations. He reported that the program resulted in im-
provements in pig growth rate, reduced mortality,
reduced medication, and reduced vaccination costs per
pig weaned. Clark et al. (1994) also assessed variations
on the MEW approach and demonstrated that the pro-
cedure appeared to eliminate M. hyopneumoniae com-
pletely, along with several other important swine
pathogens. Similar results were obtained by Dritz et al.
(1996) using a segregated early-weaning procedure in
which no medication was used. Additional information
regarding application of various high-health-status rear-
ing strategies and their implications for M. hyopneumoni-
ae disease can be obtained in Dial et al. 1992.
Protective immunity develops in swine recovered
from MPS. M. hyopneumoniae vaccines consisting of ad-
juvanted whole-cell preparations have been shown to in-
duce at least partial protection against development of
gross lesions of experimentally induced MPS (Goodwin
and Whittlestone 1973; Ross et al. 1984). Commercial
development of adjuvanted whole-cell vaccines has been
reported recently (Dayalu and Ross 1990; Peterson et al.
1990; Kobisch et al. 1994). Field evaluations have been
carried out with these vaccines (Lium et al. 1994; Dayalu
1994). The utility of mycoplasma vaccines in the field de-
pends on clear evidence that the mycoplasma vaccine
will significantly reduce losses caused by pneumonia in a
given swine herd. The PRDC has evolved in spite of the
use of mycoplasma vaccines. Whether current vaccines
contain the appropriate mycoplasma antigens has not
been determined. As demonstrated by Morrow et al.
(1994), use of M. hyopneumoniae vaccines should be
based upon evaluation of the severity of disease in the
herd; in their study, use of a M. hyopneumoniae vaccine in
a herd with a low prevalance of infection had no demon-
strable effect on average daily gain.
ETIOLOGY
Media and methods for isolation and growth of M. hy-
orhinis have been summarized by Ross and Whittlestone
(1983).
502 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
EPIDEMIOLOGY
M. hyorhinis infections are transmitted to young pigs
from infected sows or from older pigs in a nursery or
grower unit. The organism can be isolated from the nasal
or sinus secretions of about 10% of sows (Ross and Spear
1973) and from the nasal secretions of about 30–40% of
weanling swine. The organism is also common in pneu-
monic lungs of slaughter swine. Nasal and tracheo-
bronchial infections with M. hyorhinis appear to spread
rapidly once one pig in a group becomes infected. Many
infected pigs evidence no clinical disease, although ex-
perimental work with gnotobiotic pigs and a field study
by Kott (1983) suggest that it may play an important role
in pneumonias of baby pigs.
PATHOGENESIS
M. hyorhinis is very common in nasal and tracheo-
bronchial secretions of young swine. It seems likely that
other diseases such as pneumonia or stress facilitate
septicemic infection of pigs already colonized with the
organism. When this occurs, the organism may localize
in the joints and the serous-membrane-lined body cavi-
ties, where it then elicits acute serofibrinous inflamma-
tion.
M. hyorhinis can be isolated from acute-stage lesions
of polyserositis or arthritis. During the subacute disease
(i.e., 2 weeks to 3 months after onset) it can still be iso-
lated but is present in a decreasing number of sites. The
organism persists for as long as 6 months in some affect-
ed joints.
Some strains of the organism produce pneumonia in
gnotobiotic pigs (Gois and Kuksa 1974). Less clear is its
capability to act as a primary cause of pneumonia in nat-
36.5. Lesions in a pig with
acute M. hyorhinis polyserositis
(12 days postinfection).
Fibrinopurulent exudate on the
liver and heart. Pericardium is
thickened. (By permission, New
York Academy of Sciences.)
urally born pigs. It is possible that the pulmonary patho-
genicity of M. hyorhinis is strain variable. Although M.
hyorhinis is a frequent isolate from pneumonia with lym-
phoreticular hyperplasia characteristic of that produced
by M. hyopneumoniae, it is also frequent in lesions of oth-
er bronchopneumonias. No difference has been detected
in severity between pneumonias with or without M. hy-
orhinis.
CLINICAL SIGNS
Outbreaks of polyserositis generally occur in swine 3–10
weeks of age, although occasionally the disease occurs in
young adult swine. The first clinical evidence of illness
occurs 3–10 days after exposure or after a precipitating
stress. Acute-phase signs consist of a roughened hair
coat, moderate temperature elevations, listlessness,
moderate inappetence, reluctance to move, labored
breathing, tucked-up appearance, abdominal tender-
ness, lameness, and swollen joints. The duration and de-
gree of clinical change during the acute phase vary, de-
pending on the severity of the lesions. Acute-phase signs
begin to abate 10–14 days after onset, and the main clin-
ical signs thereafter consist of lameness and swollen
joints. Joint involvement is most severe during the suba-
cute stage of the disease. Lameness and joint swelling
may become less severe 2–3 months after onset, al-
though some pigs are still lame 6 months later.
LESIONS
Acute-stage lesions consist of acute serofibrinous and
fibrinopurulent pericarditis, pleuritis, and to a lesser ex-
tent peritonitis (Fig. 36.5). Acute joint lesions consist of
swelling and hyperemia of the synovial membranes and
 CHAPTER 36 MYCOPLASMAL DISEASES Ross
increased amounts of serosanguineous synovial fluid.
Subacute-phase serosal membrane lesions consist of
organized fibrous adhesions and thickened, cloudy
serosal membranes. Synovial membranes may be quite
thickened, and villous hypertrophy is evident. Synovial
fluid is serosanguineous and increased markedly in
amount. In later stages, 3–6 months, lesions appear less
active, although cartilage erosion and pannus formation
may be seen. Serosal lesions consist of organized fibrous
adhesions.
Japanese workers have demonstrated that M. hyorhi-
nis infection is very common in the eustachian tube of
young pigs. Morita et al. (1995) studied the pathology of
the ears of 479 pigs ranging in age from 1 day to 1 year.
Histological evidence of otitis was found in 76% of the
pigs. Immunohistochemical examination revealed M. hy-
orhinis on the eustachian epithelia in 14 of 28 pigs exam-
ined. All pigs with this infection had an acute eustachitis.
Mycoplasmas were also demonstrated among the cilia of
the eustachian tube using electron microscopy. The au-
thors suggested that porcine otitis media may be caused
primarily by M. hyorhinis infection.
In addition to eustachian tube infection, M. hyorhinis
has been associated with conjunctivitis in swine (Friis
1976). Rogers et al. (1991) demonstrated a mycoplasma-
like organism in association with conjunctivitis in swine
based upon ultrastructural examination but did not
identify the mycoplasma.
M. HYOSYNOVIAE ARTHRITIS
Arthritis associated with M. hyosynoviae infection has
been reported principally in the United States, although
the disease also has been reported in England (Roberts et
al. 1972; Blowey 1993) and Germany (Ross et al. 1977).
Nielsen (1988) reported severe outbreaks of bursitis as-
sociated with M. hyosynoviae infection in Danish slaugh-
ter pigs. Buttenshon et al. (1995) reported isolation of
M. hyosynoviae from 8–9% of synovial fluid samples col-
lected from nonpurulent arthritis of Danish slaughter
pigs.
ETIOLOGY
M. hyosynoviae can be isolated best in mycoplasma medi-
um containing mucin (Ross and Karmon 1970). A selec-
tive procedure for isolation of M. hyosynoviae in the pres-
ence of M. hyorhinis has been reported (Friis et al. 1990).
503
DIAGNOSIS
Gross lesions of serofibrinous to fibrinopurulent poly-
serositis and arthritis in 3- to 10-week-old swine are sug-
gestive of M. hyorhinis disease, although similar lesions
are also caused by Haemophilus parasuis and other
agents. The organism generally can be isolated from
acute- and early-subacute-phase lesions. Animals exam-
ined for diagnosis should be killed in the acute stage of
the disease. Autolytic changes in dead animals may re-
duce the chances of isolating M. hyorhinis.
TREATMENT
Although M. hyorhinis is generally quite sensitive to ty-
losin or lincomycin in vitro, antibiotic therapy of swine
clinically ill with M. hyorhinis disease is not very satisfac-
tory. The inflammatory response seems to either prevent
antibiotic penetration or be self-perpetuating. Treatment
with tylosin or lincomycin on a herd basis may be bene-
ficial.
PREVENTION
Control programs should emphasize control of other
conditions such as respiratory or enteric disease or stress
that might predispose to M. hyorhinis disease. No data
are available on the efficacy of prophylactic feed medica-
tion with tylosin, lincomycin, or other antibiotics.
EPIDEMIOLOGY
The organism is common in nasal and pharyngeal secre-
tions of sows (Ross and Spear 1973), apparently persist-
ing in such carrier swine indefinitely. Transmission from
adult carrier swine to young piglets generally does not
occur until the pigs are 4–8 weeks of age. Shedding of
large numbers of the organism in mucosal secretions oc-
curs during the acute stage of the disease.
Nasal and pharyngeal infection with M. hyosynoviae
occurs first in a few pigs at 4–8 weeks of age (Ross
and Spear 1973). The spread among penmates has
not been studied thoroughly; however, it seems that in
some herds most pigs have experienced nasal and/or
pharyngeal infection by 12 weeks of age. The rate of
spread might be related to population density and envi-
ronment.
504 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
PATHOGENESIS
M. hyosynoviae can be isolated from the blood 2–4 days
following intranasal exposure. The septicemia persists
for 8–10 days, and during this time joint infection may
occur. The duration and severity of joint infection are
variable. Many infected joints do not have lesions of
arthritis and are infected for only a few days. Other joints
evidence acute arthritis; the organism probably grows to
higher titers and persists longer in these joints. M.
hyosynoviae has been isolated as long as 24 days postinoc-
ulation.
Factors that contribute to development of lesions in
joints have not been determined. The arthritis is espe-
cially severe in heavily muscled swine that have poor leg
action and conformation (i.e., stilted gait with especially
straight legs). Osteochondrosis, a degenerative disease of
the epiphyseal and subchondral osteoid tissue, is also
extremely common in the same type of pig. It seems
likely that joint lesions developing as a result of osteo-
chondrosis or trauma-induced bursal lesions (Nielsen
1988) might predispose to arthritis caused by M. hyo-
synoviae.
CLINICAL SIGNS
Clinical evidence of M. hyosynoviae disease occurs princi-
pally in pigs 12–24 weeks of age. Lameness appears sud-
denly and may occur in one or more limbs. Temperature
elevations generally are not detected. Severely affected
pigs may have slight to moderate inappetence and loss of
weight. Animals with the disease usually have difficulty
rising or in some instances are not able to rise. Joint
swelling is usually not observed because joints covered
with muscle are most often involved. Pseudocysts or cal-
luses on the cranial surface of the carpal joint or the
plantar and lateral surface of the tarsal joint may become
swollen (Nielsen 1988).
Acute-phase signs persist for 3–10 days, and follow-
36.6. Femorotibial joint of a pig
with M. hyosynoviae arthritis
(14 days postinfection). Synovial
membrane is darkened and
hypertrophied. Articular cartilage
is normal. (By permission, New
York Academy of Sciences.)
ing that, severity of lameness generally decreases. Many
animals recover and evidence no further lameness, or on-
ly stiffness. Some pigs may be lame for several weeks or
months; however, clinical signs in such animals are often
a reflection of osteochondrosis as well. Morbidity of M.
hyosynoviae arthritis varies from 1% to 50% in affected
herds. Mortality is very low, occurring only when affect-
ed animals cannot eat, are killed by penmates, or devel-
op complicating suppurative arthritis or bursitis
(Nielsen et al. 1996).
LESIONS
Synovial membranes in acute M. hyosynoviae arthritis are
swollen, edematous, and hyperemic (Fig. 36.6). Synovial
fluid is increased markedly in volume and is serofibri-
nous to serosanguineous. Periarticular tissues may be
edematous. Pigs with subacute disease have yellow to
brown, thickened hyperemic membranes. Mild villous
hypertrophy may be seen. In chronic stages the mem-
branes are more thickened, and pannus formation may
be seen. Articular cartilage changes may be seen, but
these are usually focal and are very likely the result of os-
teochondrosis. The periarticular fibrosis seen in
erysipelas is not observed.
DIAGNOSIS
An outbreak of acute lameness in 10- to 20-week-old
swine that is not responsive to penicillin is suggestive of
M. hyosynoviae arthritis. Definitive diagnosis of the dis-
ease should be based on isolation of the organism from
typical lesions. Animals examined should be representa-
tive of the herd problem, be in the acute stage of the dis-
ease, and be unmedicated. Fluids may be aspirated from
joints of live animals or from slaughtered or necropsied
animals (Nielsen et al. 1996). It is best to examine sever-
al representative fluids, since some will be culture-nega-
tive.
 CHAPTER 36 MYCOPLASMAL DISEASES Ross
Antibodies detectable by means of the CF test devel-
op quickly during M. hyosynoviae disease (Zimmermann
and Ross 1982). Many pigs have subclinical disease and
develop antibodies to the organism; therefore, such tests
should be used with paired serums collected during the
acute and early convalescent stages of the disease to as-
certain that an antibody rise coincides with the clinical
problem. Serologic testing for M. hyosynoviae is not gen-
erally available.
TREATMENT
Successful treatment of M. hyosynoviae disease is best
achieved by use of injectable tylosin, lincomycin, or tia-
mulin, possibly in combination with a corticosteroid.
Burch (1984a) reported that intramuscular treatment
with 10 mg/kg tiamulin or lincomycin for 3 days result-
ed in reduced lameness and improved gains in swine
with naturally occurring mycoplasmal arthritis. Blowey
(1993) indicated that single injections of tiamulin hydro-
gen fumarate (15 mg/kg) reduced severity of the disease
but did not totally suppress the condition. The same au-
OTHER MYCOPLASMAS FROM SWINE
Switzer and Ross (1975) and Whittlestone (1979) have
reviewed information on mycoplasmas isolated from
swine other than M. hyorhinis, M. hyopneumoniae, and M.
hyosynoviae. Isolates reported include mycoplasmas that
normally are isolated from some other animal species;
previously unreported strains that represent new species
but are not yet associated with disease in swine; and
acholeplasmas, saprophytic organisms that are common
in a wide variety of animal and plant sources.
M. flocculare is a species that has been isolated from
lungs and nasal cavities of swine in Denmark (Meyling
and Friis 1972), England, and the United States (Arm-
strong and Friis 1981). Friis (pers. comm.—1978) indi-
cated that it is widespread in the upper respiratory tracts
of Danish swine, including SPF swine. Friis (1973) pre-
sented evidence that M. flocculare produced lymphocytic
infiltration in the nasal mucosa and peribronchial areas
of gnotobiotic pigs inoculated with the organism. Evi-
dence that it is of significance in naturally occurring res-
piratory disease has not been presented.
The genitourinary tract is a common site of infection
with mycoplasmas in several animal species. Evidence
for a consistent mycoplasma flora in the genitourinary
tracts of swine has not been presented.
Other mycoplasmas reported as occasional or inci-
dental isolates from swine include M. sualvi, M.
hyopharyngis, M. arginini, M. bovigenitalium, M. buccale,
M. gallinarum, M. iners, M. mycoides, and M. salivarium.
Acholeplasmas have many characteristics in common
505
thor indicated some success through feed medication
with 100 ppm of tiamulin hydrogen fumarate for 21 days
or water medication with 8.8 mg/kg per day with tia-
mulin hydrogen fumarate. Pigs with bone and joint dam-
age caused by osteochondrosis will not respond well to
any treatment.
PREVENTION
Preventive measures should include selecting breeding
stock with good leg action and conformation, preventing
stress during the susceptible age, and allowing new
young breeding stock time to adjust to a new location.
Protective immunity results from infection with M.
hyosynoviae. Previous speculation that pigs experiencing
the infection prior to 12 weeks of age might be protected
against the clinical disease at an older age has been dis-
puted by Blowey (1993). The author found that CF titers
to M. hyosynoviae increased with age and that serocon-
version was not associated with onset of clinical disease.
Vaccines have been shown to be efficacious (Ross 1978)
but have not been made available commercially.
with members of the genus Mycoplasma. They differ in
having a larger genome and being capable of growth in
medium not containing sterols. These organisms are oc-
casionally isolated from respiratory disease in swine,
from nasal and pharyngeal secretions of swine, or from
environmental sources such as fecal material or recycled
effluent used to remove manure from swine facilities.
Convincing evidence that these organisms are important
in naturally occurring swine respiratory disease has not
appeared. Gois et al. (1969) demonstrated that achole-
plasmas may be the only mycoplasmas isolated from res-
piratory tracts of swine in respiratory-disease-free herds.
REFERENCES
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Gush, A. F. 1980. Medicated early weaning to obtain
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 Pneumonic Pasteurellosis
37 C. Pijoan
Pneumonic pasteurellosis, the result of Pasteurella multo-
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pleuritis in a sample of 6634 pigs inspected, with all
herds studied showing some animals with lesions (Bahn-
son 1994), which highlights pneumonia as the most fre-
quent lesion seen at slaughter.
Pneumonia in pigs also appears to be a very costly
disease, although the actual cost has been difficult to cal-
culate and has varied widely in published results. Noyes
et al. (1990) performed a radiographic study of pigs’
lungs in a commercial herd in order to evaluate lifetime
pneumonia and found a significant correlation between
the extent of lifetime pneumonic lesions and the weight
of the animals at 180 days. Bahnson (1994) compared
batches of finishing pigs sent to slaughter. The batch
with the highest pneumonia scores had a 7.8% lower rate
of gain than the batch with the lowest score, a difference
that has considerable economic impact.
Pneumonic pasteurellosis occurs worldwide and in
all climates and husbandry conditions. Specific-
pathogen-free (SPF) schemes, especially at the national
level, do achieve a degree of control, presumably
through the eradication of Mycoplasma hyopneumoniae.
However, P. multocida, which is a common inhabitant of
the pig’s nasal flora, is extremely difficult to eradicate
and can be found in most high-health-status herds, such
as SPF or minimal-disease herds. Since pasteurellae can
interact directly with other agents, elimination of my-
coplasmas does not give an absolute guarantee of con-
trolling pneumonia.
A more recent strategy for raising high-health-status
pigs has been to use a combination of segregation of the
offspring together with early weaning. This program of
segregated early weaning (SEW) has been extremely suc-
cessful in controlling and minimizing most of the com-
mon diseases that affect the pig. However, its impact on
pneumonic pasteurellosis has been variable. In most
farms and groups of pigs, pneumonia at slaughter has
decreased to negligible levels. However, some farms have
presented with severe pneumonia during the late finish-
ing stages, around 16–18 weeks of age. This late pneu-
monia has been attributed mostly to infection by M. hy-
opneumoniae, but P. multocida is also commonly isolated.
SEW, at least when used with weaning at 15 days, does
not eliminate P. multocida from the offspring. Elimina-
tion of M. hyopneumoniae is more variable and unpre-
dictable, probably dependent on sow immunity, and is
most probably the predisposing trigger for pneumonia
in these systems.
ETIOLOGY
P. multocida is a gram-negative coccobacillus, 0.5–1 ×
1–2 µm in size. The organism is a facultative anaerobe,
growing well in most enriched media. It is oxidase posi-
tive, nonmotile, indole positive, and urease negative. It
does not grow well in MacConkey and is nonhemolytic
and does not require X and V factors. These reactions are
helpful in differentiating P. multocida from a group of
closely related bacteria that are also involved in pul-
monary diseases of pigs, namely, P. haemolytica, Acti-
nobacillus suis, and A. pleuropneumoniae.
P. multocida has five capsular serotypes, A, B, D, E,
and F of which A, B, and D have been reported in swine.
Serotype B however, is atypical in that it produces a
much more severe disease. It is also rare, confined to re-
gions of Southeast Asia, China, and India (Verma 1988).
It has not been reported from natural outbreaks in pigs
in North America or Europe. The most common
serotype isolated from pneumonic lungs is A, although a
variable proportion of serotype D strains is also found
(Pijoan et al. 1983a, 1984; Kielstein 1986; Hoie et al.
1991; Rubies et al. 1996). P. multocida also has 16 somat-
ic serotypes; strains of serotypes 3 and 5 are commonly
detected in pigs, with strains A:3, A:5, D:5, and D:3 be-
ing the most prevalent, in that order.
Virulence Factors
The virulence factors of P. multocida are not well defined.
In particular, the importance of the dermonecrotic toxin
(DNT) is unresolved. This toxin is central to the produc-
tion of atrophic rhinitis (see Chapter 27) when only tox-
511
512 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
igenic strains of P. multocida are involved in the disease.
Toxigenic strains of P. multocida from lungs were first re-
ported by Pijoan et al. (1984). Since then, a number of
authors have found increasing numbers of toxigenic
strains (both type A and type D) in pneumonic lungs.
Some reports (Kielstein 1986; Iwamatsu and Sawada
1988) show that between 25% and 45% of strains isolat-
ed from lungs are toxigenic. Kielstein (1986) found that
toxigenic strains were frequently isolated from acute cas-
es but not from slaughterhouse lungs, suggesting en-
hanced virulence. However, Baekbo (1988) postulated
that toxigenicity was not important in determining the
virulence of P. multocida in experimentally infected ani-
mals.
The role, if any, of toxigenicity in pneumonic pas-
teurellosis is still under debate. For example, Hoie et al.
(1991) found that 94% of serotype A and 90% of serotype
D isolates from pneumonic lungs were toxigenic. In con-
trast, Rubies et al. (1996) found no toxigenic strains (ei-
ther A or D) in 218 isolates from pneumonic lungs in
Spain.
The capsule appears to be an important virulence fac-
tor, especially in serotype A, for it may help the organism
avoid phagocytosis by alveolar macrophages, at least in
vitro. Maheswaran and Thies (1979) reported that P.
multocida uptake by swine alveolar macrophages was
very low, even in the presence of opsonins. Similar re-
sults were found by Fuentes and Pijoan (1986). More re-
cent work, however, suggests that little capsule is ex-
pressed when the organisms are grown under
iron-restricted conditions (Jacques et al. 1994). These
growth conditions mimic the scenario found in vivo.
Thus, the relevance of the capsule to virulence may have
been overestimated in the past.
Some strains of P. multocida are able to produce pleu-
ritis and abscessation in experimentally infected pigs (Pi-
joan and Fuentes 1987). The virulence factors that dis-
tinguish these strains from less virulent pneumonic
strains are not defined. However, Iwamatso and Sawada
(1988) found that strains of serotype D or toxigenic
strains (of both serotypes) were associated with abscess-
es but not with pleuritis.
Mucosal Colonization
The colonization of mucous surfaces by P. multocida has
received some attention lately, as it is of paramount im-
portance in understanding the pathogenesis of this or-
ganism. Jacques (1987) found that both serotypes A and
D adhered poorly to isolated tracheal epithelial cells, al-
though serotype A strains were more adherent. He later
showed that serotype A strains adhered mostly to ciliat-
ed epithelial cells. Pijoan and Trigo (1989) also found
sparse colonization by serotype A and D strains but
found that serotype D strains adhered mostly to noncili-
ated cells. Trigo and Pijoan (1988) and later Issacson and
Trigo (1995) found that some strains, in particular toxi-
genic ones, had detectable pili on their surface, although
the role of these structures in adhesion is still under de-
bate. In contrast to their poor attachment to epithelial
surfaces, P. multocida strains have been shown to attach
readily to nasal mucus, raising questions as to where nor-
mal attachment and colonization take place.
The presence of capsule has been shown to decrease
the attachment of P. multocida to respiratory tract mu-
cus, as well as to cultured tracheal rings (Jacques et al.
1993). On the other hand, the same group has reported
that preinfection of tracheal rings with Bordetella bron-
chiseptica enhanced subsequent attachment by P. multo-
cida (Dugal et al. 1992). Some other authors, however,
have had difficulties in confirming that P. multocida
attached to immobilized mucus (Issacson and Trigo
1995).
Mucosal colonization of suckling pigs is becoming a
very important issue in SEW systems. It has been postu-
lated (Pijoan 1995) that pigs weaned early (at 15 days of
age or less) are not homogeneously colonized with or-
ganisms such as P. multocida and M. hyopneumoniae. As a
result, pigs are weaned into isolated nurseries in popula-
tions that have a variable prevalence of colonized ani-
mals. Populations with low prevalence of colonization
are at risk of developing severe clinical disease, because
some pigs in the population will become infected very
late, at a time when no maternal immunity is available.
This could explain why SEW systems sometimes present
with delayed PRDC (the “18-week wall”) (Dee 1997).
EPIDEMIOLOGY
The epidemiology of P. multocida is not well understood.
The organism is present in practically all herds and can
be readily isolated from the nose and tonsils of normal,
healthy individuals. Transmission of the disease by
aerosols has been postulated but is unlikely to be of im-
portance. Baekbo and Nielsen (1988) measured airborne
P. multocida in herds suffering from atrophic rhinitis.
They were able to isolate the organism in 29 of 44 herds
studied. However, the low number of organisms isolated
(144 CFU/mL) led them to conclude that there was no re-
lationship between the number of organisms recovered
and the severity of the clinical problem.
Although aerosol transmission may occasionally oc-
cur within the herd, it is probable that nose-to-nose con-
tact is the common route of infection. Both vertical and
horizontal transmission occur, although within farms
most transmission appears to be horizontal, with one
strain predominating in pneumonic lungs (Zhao et al.
1993). This suggests the existence of P. multocida strains
of variable virulence, with one of the more virulent
strains producing most of the disease within a popula-
tion. External sources of the organism include mice and
 CHAPTER 37 PNEUMONIC PASTEURELLOSIS
other rodents, although chickens and chicken manure
have also been postulated as sources. These are probably
not common sources of the organism in modern swine
farms, however.
PATHOGENESIS
Experimental infections with P. multocida are very diffi-
cult to produce. Healthy pigs will readily tolerate large
doses of organisms instilled intranasally or even intra-
tracheally. Pulmonary clearance is very effective, and the
bacteria cannot be reisolated 30 minutes after challenge.
Recent work demonstrating that little capsule is present
in vivo has clarified the apparent disparity between the
poor phagocytosis observed in vitro and the ready clear-
ance of bacteria found in healthy animals. Experimental
models of the disease have used serotype B organisms
(Farrington 1986), previous infections with immunosup-
pressive virus or mycoplasmas (Fuentes and Pijoan 1986;
Ciprian et al. 1988), or massive instillation of infected
fluids into the lung (Hall et al. 1988). This has led to the
conclusion that P. multocida is not a primary agent of
pneumonia but rather follows infections with other
agents. Vaccination against hog cholera virus (Pijoan and
Ochoa 1978) and infection with Aujezsky’s virus
(Fuentes and Pijoan 1987) or M. hyopneumoniae (Ciprian
et al. 1988) have all been shown to predispose the pig to
superinfections with P. multocida. In contrast, porcine re-
productive and respiratory syndrome (PRRS) virus could
not be shown to interact with P. multocida in the produc-
tion of pneumonia (Carvalho et al. 1997).
Once established, the organism stimulates a rapid
suppurative reaction, characterized by neutrophil infil-
tration. This is probably a host reaction to bacterial
lipopolysaccharide, which stimulates the release of in-
flammatory cytokines. Death is uncommon, probably
the result of endotoxic shock and respiratory fail-
ure.
CLINICAL SIGNS
The clinical signs vary in severity depending on the strain
of P. multocida involved, together with the immune sta-
tus of the animals.
Acute Form
This form is most commonly associated with serotype B
strains. It is rare and is never seen in Europe or North
America. The animals show dyspnea, labored breathing
with abdominal “thumps” (sudden contractions of the
abdomen), prostration, and high fever (up to 42.2˚C,
108˚F). Mortality may be high (5–40%) in these cases;
dead and moribund animals may show purplish discol-
oration of the abdominal region, suggesting endotoxic
shock.
Pijoan 513
Subacute Form
This is associated with P. multocida strains that produce
pleuritis. In these cases, cough and abdominal breathing
can be detected in grower or finishing pigs up to market
weight. Cough in this age pig is usually the hallmark of
severe disease. Clinically, this form of the disease is very
similar to pleuropneumonia due to A. pleuropneumoniae
(see Chapter 26). The main distinguishing feature is that
pleuritic pasteurellosis rarely results in sudden death.
Rather, pigs become extremely emaciated but may sur-
vive for a long time. Recently, outbreaks of PRDC in fin-
ishing pigs (about 16–18 weeks of age) on farms using
SEW methods has resulted in cough and abdominal
breathing in pigs but usually not pleuritis (Dee 1997).
Chronic Form
This is the most common form of the disease, character-
ized by occasional cough, thumping, and low or nonexis-
tent fever. Animals affected are usually in the later stages
of the nursery or are growers (10–16 weeks of age). The
signs are indistinguishable from those following M. hy-
opneumoniae infections, for P. multocida causes the con-
tinuation and exacerbation of primary mycoplasmosis.
LESIONS
Lesions of P. multocida are confined to the thoracic cavi-
ty and are superimposed on those of M. hyopneumoniae.
Typically, anteroventral consolidation of the lung is
seen, together with froth in the trachea. There is a clear
line of demarcation between affected and healthy lung
tissue. The affected portion of the lung will have discol-
oration ranging from red to grayish-green, depending on
the course of the infection (Fig. 37.1).
Severe cases may present varying degrees of pleuritis
and abscessation. Pleural adhesions to the thoracic wall
are common in these cases, and the pleura has a translu-
cent, dry appearance (Figs. 37.2, 37.3). This is useful in
differentiating pneumonic pasteurellosis from acti-
nobacillus pleuropneumonia, in which moist, yellowish
pleural adhesions with massive fibrin infiltration are
more common (Pijoan 1989).
Histologically, a lobular, exudative bronchopneumo-
nia is found. Severe bronchopneumonia, alveolar epithe-
lial hyperplasia, and the presence of abundant neu-
trophils are seen with mucopurulent exudate in the
bronchial lumen and in alveolar spaces. These lesions are
not specific to P. multocida infections and are similar for
most bacterial pneumonias.
Evidence has also been presented for a relationship
between pasteurella-induced bronchopneumonia and
the presence of disseminated focal nephritis (Butten-
schon 1991). The author concluded that the two diseases
are connected by a process of dissemination from the
pulmonary lesions.
514 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor

37.1. Pneumonic pasteurellosis. Lung consolidation is anteroventral with a clear demarcation

line between affected and healthy tissue.
 CHAPTER 37 PNEUMONIC PASTEURELLOSIS
37.2. Pleural adhesions of lung to the thoracic wall in a case of pleuritic pasteurellosis.
Note that the pleura has a translucent, dry aspect.
DIAGNOSIS
Since the lesions of P. multocida infection are not pathog-
nomonic, they cannot be used as the only criteria to es-
tablish a definite diagnosis. The history of the outbreak,
histopathology, and isolation of the organism should be
used to confirm the original presumptive diagnosis.
Serology has not proven effective for diagnosis, and no
serologic test is routinely available for P. multocida infec-
tions.
P. multocida is a relatively easy organism to culture,
provided proper specimens are submitted to the labora-
tory. Specimens yielding the best isolations include
swabs of tracheobronchial exudate and affected lung tis-
sue obtained from the border area between affected and
normal tissue. Nasal swabs have also been shown to be
good samples for isolation of P. multocida (Schoss
and Alt 1995). Swabs should be immersed in an ap-
propriate transport medium, such as Stuart’s. Lung sam-
ples should be obtained as aseptically as possible. All
samples should be refrigerated (but not frozen) until cul-
tured.
Culture of P. multocida can be successfully achieved in
laboratories with minimal facilities. Good-quality speci-
mens will yield the organism on direct culture onto
blood agar or glucose agar plates. If the samples are
more contaminated, they can be serially diluted tenfold
Pijoan 515
in brain-heart infusion (BHI) broth, grown overnight,
and then plated (Pijoan et al. 1983b). Alternatively, se-
lective media can be used: Ackermann et al. (1994) suc-
cessfully isolated P. multocida from tonsils and turbinates
of adult pigs using blood agar with 3.75 U/mL of baci-
tracin, 5 µg/mL clindamycin, 0.75 µg/mL gentamicin,
and 2.25 µg/mL of amphotericin B. Isolation can also be
enhanced by injecting the specimen intraperitoneally in-
to mice and then recovering the pasteurellae 24 hours
later from liver and ascitic fluid.
Differential diagnosis must include influenza virus,
A. pleuropneumoniae, B. bronchiseptica, Salmonella choler-
aesuis, and pure M. hyopneumoniae infections. Accurate
clinical differentiation based on the epidemiology and le-
sions can be readily achieved for some of these condi-
tions but may be difficult in cases of influenza, B. bron-
chiseptica, or M. hyopneumoniae. In these cases, histology
and bacterial culture will be needed. Ramirez and Pijoan
(1982) and Straw (1986a) have published tables for the
differential diagnosis of these conditions.
TREATMENT
Treatment of P. multocida field infections with antibi-
otics is usually difficult or unsuccessful. This is partly due
to widespread antibiotic resistance in P. multocida iso-
lates in the United States and also to difficulties in achiev-
516 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
37.3. Lung from a case of
pleuritic pasteurellosis. Note
anteroventral, well-demarcated
lesions, together with the presence
of multiple abscesses. There is
extensive interlobar adhesion.
ing adequate antibiotic concentrations in consolidated,
pneumonic lung.
A variety of antibiotics and antibiotic combinations
have been commonly used (Farrington 1986). These in-
clude parenteral antibiotics such as oxytetracycline, 11
mg/kg; long-acting oxytetracycline, 20 mg/kg; procaine
penicillin, 66,000 units/kg; benzathine penicillin, 32,000
units/kg; tiamulin, 10–12.5 mg/kg; and ampicillin, 6.6
mg/kg. Many of these drugs, however, are becoming in-
creasingly less efficient due to widespread antibiotic re-
sistance. Treatment via feed antibiotics has also been
suggested, although, as in the case of other pneumonias,
it is probably not very effective.
Cote et al. (1991) found some plasmid-mediated re-
sistance to streptomycin and sulfonamides among 29
field isolates investigated. Gutierrez Martin and Ro-
driguez Ferri (1993) studied 59 Spanish isolates, finding
good activity with penicillins, aminoglycosides, tetracy-
clines, erythromycin, colistin, and rifampicin, with some
resistance to tylosin, vancomycin, and tiamulin. They re-
ported that third-generation cephalosporins and fluori-
nated quinolones were the most effective drugs. Raem-
donck et al. (1994) found good minimum inhibitory
concentrations (MIC) for danofloxacin, ceftiofur, and
trimethoprim-sulfonamide; they found variable to high
resistance to erythromycin, gentamicin, lincomycin,
 CHAPTER 37 PNEUMONIC PASTEURELLOSIS
oxytetracyclines, and spectinomycin. Finally, Salmon et
al. (1995) tested isolates from several countries and
found the best activity with cephalosporins and en-
rofloxacin, with poor activity shown in vitro by ery-
thromycin, sulfamethazine, spectinomycin, and lin-
comycin.
The effectiveness of all these antimicrobials will vary
considerably depending on strain susceptibility. Since P.
multocida readily exhibits resistance to various antimi-
crobials, antibiograms should be performed before insti-
tuting treatment.
As in other respiratory infections, antibiotics are
more effective when used as prophylactic, rather than
therapeutic, agents. Tetracyclines alone, tetracyclines
combined with sulfamethazine or sulfathiazole or peni-
cillin, and tylosin combined with sulfamethazine have
been recommended for this purpose. It is probable that
the most effective compound in these mixtures is sul-
famethazine. This antimicrobial has been the focus of
controversy over residues. Because of this, its use has
been severely limited and monitored. Tiamulin (40 ppm
in feed) has been shown, in a number of trials, to im-
prove average daily gain. However, since pneumonic le-
sions are not significantly reduced by this antibiotic (Pott
and Edwards 1990), the mode of action by which these
improvements are obtained is unclear. Tiamulin has
been found to be of variable effectiveness against P. mul-
tocida. It is therefore probable that its main effect in
pneumonia lies in the control of M. hyopneumoniae.
Some new antibiotics with claims for P. multocida
treatment are not available in the United States but are
used extensively in other countries. These include in-
jectable lincomycin-spectinomycin, some cephalo-
sporins, and various quinolones including enrofloxacin
and danofloxacin. Injectable ceftiofur is available in the
United States, however, and it has been shown by a num-
ber of authors to have good activity against P. multocida.
PREVENTION
Management Approaches
Since antibiotic therapy is often unsuccessful and even
when successful may not prove cost-effective, prevention
of pneumonia has received much attention. Prevention
is usually obtained through changes in management.
The management techniques that result in decreased
pneumonia have been reviewed by several authors (Pi-
joan 1986; Straw 1986b). Caution must be taken when
implementing these recommendations, since they derive
mostly from retrospective epidemiological studies and
not from experimental data. Also, they are intended to
reduce pneumonia as a whole (and other respiratory
problems) and do not differentiate between conditions
of different etiology.
Management changes can be directed either at modi-
fying the pigs’ environment or at reducing the possibili-
Pijoan 517
ties of spreading the organism.
Environmental changes such as increasing ventila-
tion flow rate, decreasing ammonia, and minimizing
temperature fluctuations and dust are usually recom-
mended. Some of these recommendations are antago-
nistic; increasing airflow, especially in winter, results in a
decrease of both temperature and humidity, with an in-
crease in dust. Most of these changes have not proven
valuable in controlled, experimental conditions. Noyes
et al. (1986) found that decreasing ventilation below
minimal recommended levels (0.5 CFM/pig) had no ef-
fect on weaned pigs inoculated with both B. bronchisepti-
ca and P. multocida. Similarly, Rafai et al. (1987) found
that cold stress, even though it reduced immune function
in suckling pigs, had no effect on the course of an exper-
imental P. multocida infection. Environmental changes
frequently entail extensive remodeling. They are, there-
fore, expensive to institute and maintain. It is not clear
that these changes are cost-effective in terms of reducing
respiratory disease.
On the other hand, considerable improvement may
be obtained by instituting management changes that re-
duce the spread of the organism. These include the fol-
lowing:
1. Segregated early weaning: SEW has a major impact
on pneumonia and, when properly done, will reduce or
eliminate pneumonia from most groups of pigs. This is
probably based on the control of M. hyopneumoniae,
which in many herds is virtually eliminated. Early wean-
ing probably has less effect on P. multocida, since it has
been shown that pigs are colonized as early as 10 days of
age. Occasional farms or groups of pigs will experience
acute outbreaks of pneumonia.
2. All-in/all-out production: In farms where SEW is
not possible, efforts should be made to institute an all-
in/all-out production program. Several workers have
shown that this type of production system markedly de-
creases the incidence of pneumonia.
3. Closed herds: Minimizing the purchase of outside
pigs, especially fatteners, will result in a decrease of
pneumonia and other respiratory conditions. However,
the pressure to improve genetics in modern farms has
forced most producers to purchase their breeding ani-
mals. It has become increasingly important to evaluate
the health status of the farm from which these animals
are purchased, in order to minimize the probability of
introducing disease.
4. Minimal mixing and sorting: This is a source of
stress to the pigs, while also intensifying the probabilities
of disease transmission. Pigs should be mixed as few
times as possible during their productive life.
5. Reduction in building and pen size: Smaller rooms
and smaller pens both have been shown to reduce levels
of pneumonia. Rooms should have a maximum of 250
pigs, and pens a maximum of 20–25 pigs each. This
518 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
again is difficult to achieve in modern farms. However,
the recent trend of building wean-to-finish barns, where
pigs are only mixed once, at weaning, will probably have
a positive effect in decreasing pneumonia.
6. Reduction in animal density: Decreasing animal
density has been shown by many authors to reduce levels
of pneumonia. It is important therefore to find a reason-
able compromise between densities that are appropriate
for the animals’ health and those that maximize returns
on the building’s cost.
Vaccination
Although several killed vaccines for the prevention of
pneumonic pasteurellosis are available, their effective-
ness is questionable. Since no reliable model of experi-
mental disease exists, potency testing is usually per-
formed in mice. It is doubtful, therefore, that this model
truly replicates the disease in the pig. Under field condi-
tions, clinicians frequently have disappointing results
with these vaccines, and they do not appear to be cost-ef-
fective.
Some modern approaches to vaccination against P.
multocida have been reported recently. The use of puri-
fied lipopolysaccharide (LPS) antigen and the use of aro
A gene deletion mutants both resulted in protection
against homologous, but not heterologous, challenge
(Adler et al. 1996). The use of a cloned, 87 kDa outer-
membrane protein had similar limitations (Ruttolo and
Adler 1996). Cross-protection has been reported in
chickens with the use of a protein preparation from cells
grown under iron-deprived conditions, which mimic the
in vivo environment (Wang and Glisson 1994). However,
none of these fraction vaccines are commercially avail-
able or have been tested in pigs, where the disease is not
septicemic as it is in chickens and mice. Therefore, there
is at present no successful commercial vaccine against P.
multocida in the pig.
OTHER PASTEURELLA INFECTIONS
IN PIGS
Several authors have sporadically isolated P. haemolyt-
ica–like organisms from cases of severe necrotizing pleu-
ropneumonia. The lesions seen are similar to those
found in A. pleuropneumoniae infections but tend to be
less severe. In this regard, they are also similar to lesions
reported from A. suis. A new nicotinamide adenine dinu-
cleotide (NAD)-independent biotype of A. pleuropneu-
moniae has now been recognized, and it is very probable
that many of these severe pneumonias are related to
these two organisms rather than to P. hemolytica.
All these organisms are very similar and differ in mi-
nor biochemical reactions such as indole formation or V-
factor requirement. Bisgaard (1984) did a comprehen-
sive study of these strains and concluded that they
differed from P. haemolytica sensu stricto. Since the le-
sions produced (and the serologic reactions) are indistin-
guishable from A. pleuropneumoniae, it is possible that
some field outbreaks have been misdiagnosed. At
present, it is very difficult to assess the true prevalence
and economic impact of these strains.
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 Porcine Proliferative
38 Enteropathies
S. McOrist and C. J. Gebhart
Proliferative enteropathies (PE; also known as prolifera-
tive ileitis) are a group of acute and chronic conditions of
widely differing clinical signs but with a common under-
lying pathological change visible at necropsy: a thicken-
ing of the mucosa of the small intestine and colon. His-
tologically, the affected tissues show marked
proliferation of immature epithelial cells of the intesti-
nal crypts, forming a hyperplastic to adenoma-like mu-
cosa. These proliferating cells invariably contain numer-
ous intracytoplasmic Lawsonia intracellularis, an obligate
intracellular bacterium.
In growing pigs with uncomplicated proliferation of
the mucosa, the condition is chronic proliferative en-
teropathy, also known as porcine intestinal adenomato-
sis (PIA) or ileitis. In some pigs, additional changes may
be superimposed on this basic lesion, including a necrot-
ic enteritis, a granulomatous regional ileitis, or an acute
hemorrhagic proliferative enteropathy (Rowland and
Lawson 1975). Both the chronic and acute hemorrhagic
forms of PE are now important enteric diseases in the
modern pig industry.
The lesions of PE were first described in pigs in
Ames, Iowa, by Biester and others in the 1930s (Biester
and Schwarte 1931; Biester et al. 1939) and were subse-
quently found to occur in other major pig-raising areas
throughout the world, but it was not until 1973 that
Rowland and others investigating major outbreaks oc-
curring in the United Kingdom developed a productive
research program (Rowland and Rowntree 1972; Row-
land and Lawson 1974). They found that whenever these
proliferative changes in pigs were studied either ultra-
structurally or using silver stains, intracellular bacteria
were consistently present within the abnormal prolifer-
ating cells (Rowland and Lawson 1974). These bacteria
are curved to straight rods with either tapered or round-
ed ends and measure 1.25–1.75 µm in length by
0.25–0.43 µm in width. The bacteria lie free in the apical
cytoplasm of infected epithelial cells and are not mem-
brane-bound during the important stages of infection.
The identity of these bacteria and their etiologic role in
PE were finally resolved in 1993 with successful culture of
the intracellular organism and the reproduction of the
disease in pigs using a pure culture of this agent (Lawson
et al. 1993; McOrist et al. 1993). Also in 1993, its taxo-
nomic position was clarified (Gebhart et al. 1993); its de-
finitive name is Lawsonia intracellularis, within the fami-
ly Desulfovibrionaceae (McOrist et al. 1995a).
The disease is worldwide in distribution and has been
recently described in Australia, Belgium, Brazil, Canada,
Denmark, France, Greece, Holland, Ireland, Japan, Mex-
ico, New Zealand, Poland, South Africa, Sweden, Tai-
wan, Thailand, the United Kingdom, and the United
States (Rowland and Lawson 1992). While there are
some local differences, surveys conducted in several of
these countries have estimated that approximately 30%
of pig herds are likely to be affected. It is possible that
there has been an increase in the incidence of acute PE in
modern multisite production systems in the United
States in the past 5 years (Winkelman 1996a).
Pathological changes closely resembling porcine PE
have been described in a number of other mammalian
species, including some rodents, such as the hamster
(Frisk and Wagner 1977) and rat, (Vandenberghe et al.
1985), but not the mouse. PE has been described occa-
sionally in carnivores, such as the fox (Eriksen and
Landsverk 1985) and ferret (Fox and Lawson 1988), in
herbivores, such as the horse (Duhamel and Wheeldon
1982; Williams et al. 1996), rabbit (Schoeb and Fox
1990), and deer (Drolet et al. 1996), and also in ratite
birds, the emu and ostrich (Cooper 1996), but not in oth-
er birds. In all these species, intracellular bacteria resem-
bling Lawsonia species have been observed within the cy-
toplasm of epithelial cells of proliferative portions of
intestinal mucosa. Experimental transmission studies, in
situ immunostaining, and DNA analysis have suggested
that one agent may be able to infect the intestinal cells of
a wide variety of host species. However, there is current-
ly no evidence to link these other hosts with the onset of
disease in pigs.
ETIOLOGY
The primary agent that causes PE is the obligately intra-
cellular bacterium L. intracellularis, which preferentially
grows within intestinal epithelial cells. It has not as yet
been cultivated in cell-free media. Its morphology and
entry processes into host epithelial cells resemble some
other obligately intracellular bacteria, particularly Rick-
ettsia species (McOrist et al. 1995b); however, these two
genera are not related taxonomically. The reliance on
host cells for growth, probably for preformed triphos-
phates or another energy source, is readily apparent
521
522 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
when the bacteria are observed in the natural lesions.
Unfortunately, between 1973, when the bacteria were
first observed, and 1993, when they were first cultured
and identified, a variety of curved gram-negative bacte-
ria and other putative agents were cultured from the in-
testines of affected pigs, leading to considerable confu-
sion at the time.
A variety of Campylobacter species, particularly C.
mucosalis (Lawson and Rowland 1974), C. hyointestinalis
(Gebhart et al. 1983), C. hyoilei, a C. jejuni variant, and
C. coli, can be recovered from proliferative lesions. How-
ever, neither specific proliferative lesions nor intracellu-
lar colonization have occurred when pigs are inoculated
with any of these bacteria (Kashiwazaki et al. 1971; Mc-
Cartney et al. 1984; Boosinger et al. 1985; Alderton et al.
1992). This indicates that these are secondary agents tak-
ing advantage of the altered conditions in the gut for col-
onization. Similar colonization by other secondary bac-
teria is a feature of other enteric diseases, such as swine
dysentery (Robinson et al. 1984). Much of the published
literature on PE does refer to the intracellular bacterium
being a Campylobacter-like organism; however, the desig-
nation was only based on its morphologic similarity to
that genus. Other agents cultured from affected in-
testines are enteroviruses and intestinal Chlamydia
species (Joens et al. 1987; Fox et al. 1993). However, these
are probably present in many unaffected pigs, and inoc-
ulation studies with these agents were unrewarding.
Exposure of pigs to crude, or partially filtered, ho-
mogenized diseased mucosa resulted in reproduction of
specific intestinal lesions and clinical disease in some
early challenge trials (Roberts et al. 1977; Mapother et al.
1987; McOrist and Lawson 1989a), first indicating the
etiologic role of the intracellular bacteria.
Experimental transmission studies using pure cul-
tures of British or American strains of L. intracellularis as
oral-challenge inocula for conventional pigs and using
gnotobiotic pigs predosed with a minimal bacterial flora
of nonpathogenic enteric species have resulted in repro-
duction of the specific lesions of PE. Three weeks follow-
ing oral inoculation of postweaned pigs with 108 L. intra-
cellularis bacteria, numerous L. intracellularis bacteria
were recovered from the affected proliferative intestines
of challenged pigs, with numerous intracytoplasmic L.
intracellularis bacteria visible in sections of these in-
testines (McOrist et al. 1993, 1994). No such recovery or
lesions occurred in control pigs inoculated with unin-
fected cell cultures or media. Several isolates derived
from natural lesions of acute or chronic forms of PE have
proved pathogenic in these and several subsequent chal-
lenge studies, indicating the ability of any single L. intra-
cellularis strain to be involved in both types of lesions. L.
intracellularis isolates from American and Australian pigs
have been identical to British isolates with respect to cul-
tural and morphological characteristics (Knittel et al.
1996; Collins et al. 1996). Intestinal lesions that develop
as a result of artificial exposure to British or American
isolates have had all the characteristics of the field dis-
ease, including the presence of mucosal proliferation
and intracellular bacteria (McOrist et al. 1993; Knittel et
al. 1996).
Early attempts to identify the intracellular agent in
the tissues by immunological techniques produced con-
flicting results (Rowland and Lawson 1974; Chang et al.
1984), probably due to the presence of a “natural” rabbit
antibody reactive with the intracellular organism (Law-
son et al. 1985). Preparation of specific hyperimmune
sera and monoclonal antibodies eliminated this source
of confusion. These react with L. intracellularis and do
not react with cells of any of the cultivated Campylobac-
ter species or other bacteria (Lawson et al. 1985; McOrist
et al. 1987). Specific reactivity of monoclonal and poly-
clonal antibody raised to the L. intracellularis organism
mainly lies in a 25–27 kDa fragment present on its outer
surface (McOrist et al. 1989a).
EPIDEMIOLOGY
Documented information on the occurrence and epi-
demiological features of the PE disease complex in pig
herds of the world remains basic. The main reason for
this deficiency is that in many instances clinical signs are
not dramatic and that, until recently, specific tools for
the diagnosis of the disease in the live animal have not
been available. Abattoir or on-farm mortality monitor-
ing has been used to assess the presence and possible im-
pact of the disease. The extent to which the incidence at
slaughter may reflect the occurrence of disease on the
farm is largely unknown and may be a considerable un-
derestimate. As with other postweaning enteric diseases,
moderate lesions may resolve by the time of slaughter.
Various authors have noted lesions in pigs at normal
slaughter, but in some reports the incidence of animals
with lesions has been low, 0.7–2.0% (Emsbo 1951; Row-
land and Hutchings 1978; Kubo et al. 1984; Christensen
and Cullinane 1990). Other reports have indicated much
higher levels of occurrence of lesions. Studies by Pointon
in Australia and in the United States found that around
30% of herds had pigs with lesions at slaughter, and the
incidence of lesions in particular herds reached 40%
(Pointon 1989). These differences may be partly due to
differences in the age and origin of animals at slaughter,
making routine slaughter checks a somewhat unreliable
guide to prevalence.
Surveys of the cause of mortality on pigs farms and
estimates of clinical occurrence of acute hemorrhagic PE
suggest that an average of 1.0–5.0% of older growing
pigs are affected (Lawson et al. 1979; Duran 1994; Chris-
tensen et al. 1995). Clinically important outbreaks of
this condition are now reasonably frequent, however,
and may affect a high proportion of animals in a herd.
Reported attack rates of 12–50% of susceptible pigs on
 CHAPTER 38 PORCINE PROLIFERATIVE ENTEROPATHIES
affected farms are still representative (Love et al. 1977;
Lomax and Glock 1982; Holyoake and Cutler 1995). Par-
ticular management situations are thought to lend them-
selves to outbreaks of acute hemorrhagic PE. Young
adults (4–12 months old) within boar and gilt perfor-
mance testing stations, gilts within breeding programs
that involve transport to new units, and the movement
and mixing of boars and gilts into breeding groups are
commonly associated with PE outbreaks. While this may
partly reflect changes in use of antibiotics at these times,
the occurrence of major stressors is a consistent feature
of herd history prior to outbreaks. White breeds, partic-
ularly the Landrace and Large White breeds, and syn-
thetic commercial breeds incorporating the white breeds
are thought to exhibit an increased breed susceptibility;
however, the disease has been regularly diagnosed in
Duroc and other colored pig breeds. Outbreaks have also
been noticed in association with extreme weather condi-
tions, particularly periods of extreme differentials be-
tween night and day temperatures, or hot, humid weath-
er. Lawsonia sp. may have a relatively long survival time
in the environment for an obligate intracellular bacteri-
um. Some strains have remained viable at 5˚C for 1–2
weeks outside the host cells, and only quaternary ammo-
nium compounds and iodine-based compounds, of 6
disinfectants tested, showed complete bactericidal activ-
ity (McOrist and Gebhart, unpublished data—1996).
Development of specific polymerase chain reaction
(PCR) and immunologic detection methods has recently
enabled some measurement of the excretion of L. intra-
cellularis in the feces of pigs. Where clinical disease is
present in a group, the organism is present in the feces of
all affected, and some subclinically affected animals can
be found to be excreting at this time (McOrist and Law-
son 1989b). Fecal excretion of L. intracellularis can per-
sist for at least 10 weeks, and enumeration of L. intracel-
lularis in the feces of experimentally affected pigs found
up to 108 organisms per gram, further indicating that the
feces of infected pigs may contain ample infective doses
for other pigs (Smith and McOrist 1997). These methods
have also enabled surveys of the prevalence and risk fac-
tors for chronic PE in growing pigs. Recent surveys in
Spain, Denmark, United States, and the United Kingdom
have indicated that 20–40% of farms are infected (Lanza
and Pozo 1996; Moller et al. 1996; Bane et al. 1997;
Smith 1997). These surveys have also indicated that a
wide age range of pigs can be infected, with the detection
of fecal excretion in boars, gilts, pre-, and postweaned
pigs. Preliminary analysis of PE-positive farms by PCR
and serologic methods has further indicated that the ma-
jority of infections occur in later postweaning areas of
farms (where pigs are 8–16 weeks old). It is possible that
these finisher pigs could act as a potent source of infec-
tion to other areas of affected farms, especially if fecal
contamination of boots and equipment occurs.
In herds with endemic chronic PE, feces from infect-
McOrist, Gebhart 523
ed pigs provide the likely source of new infections. Rig-
orous removal of feces between batches of pigs in build-
ings capable of complete “all-in/all-out” was demon-
strated to be more effective at control of PE than reliance
on slatted floors and sunken pits for feces removal (Bane
et al. 1997; Smith 1997). It is possible that feces from in-
fected gilts are responsible for transmission of the infec-
tion to their progeny of preweaned piglets. However, the
replacement of stock with those derived from the early
weaning of piglets, at 10–14 days old, has not proved an
effective method of eradicating PE from herds (Winkel-
man 1996a). The relevance of the occurrence of diseases
similar in etiology and pathology to PE in several species
other than pigs is not yet clear. Modern pig farms are
generally capable of excluding other mammals, except
mice, and these are not known to suffer from naturally
occurring PE. Experimental inoculations of rodents oth-
er than hamsters (i.e., rats and mice) with pig-derived
isolates of L. intracellularis has not resulted in persistent
infection (McOrist and Gebhart, unpublished data—
1996). The close adaptation of L. intracellularis to life
within pig epithelial cells suggests that the introduction
of infection generally occurs with new pigs carrying the
infection, particularly in high-health-status herds. Sur-
veys have indicated that boars and gilts within nucleus
herds are potential sources of infection that can lead to
outbreaks of acute disease (Smith 1997).
Examination of diagnostic records in several Danish
high-health herds indicated that introduction of PE oc-
curred following import of British boars of white breeds
(McOrist and Gebhart, unpublished data—1996).
PATHOGENESIS
PE can be reproduced by exposing susceptible pigs to L.
intracellularis or to diseased mucosa containing these in-
tracellular bacteria (Roberts et al. 1977; Mapother et al.
1987; McOrist and Lawson 1989a; McOrist et al. 1993,
1994). Intracellular bacteria and histological changes of
PE are first evident 8–10 days after exposure, and lesions
reach their maximum around 21 days postchallenge, in-
dicating a relatively long incubation period of 2–3
weeks. Experimental infection of postweaned piglets
usually leads to moderate diarrhea in 50% of challenged
animals 2–3 weeks after challenge. L. intracellularis
strains associated with one type of PE (acute or chronic)
appear capable of initiating the range of pathological se-
quelae. The pigs exposed to diseased mucosa from the
chronic form may develop the necrotic or acute hemor-
rhagic form of the disease (Mapother et al. 1987). Also,
pigs challenged with L. intracellularis isolates derived
from acute hemorrhagic PE regularly develop lesions of
chronic PE (McOrist et al. 1993) and occasionally
progress to acute hemorrhagic PE. Pigs of a wide age
range are susceptible to oral challenge. Pathogenic infec-
tions have developed in neonatal piglets aged 7 or 14
524 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
days and in weaned pigs aged 4 or 10 weeks (McOrist
and Lawson 1989a; McOrist et al. 1993; Jones et al.
1993a).
PE develops as a progressive proliferation of imma-
ture epithelial cells populated by numerous intracellular
bacteria. In order to persist and multiply within the ep-
ithelium, the L. intracellularis organisms must penetrate
into the dividing crypt cells. In vivo and in vitro studies
have elucidated the early events in bacteria-cell interac-
tion (McOrist et al. 1989b, 1995b; Lawson et al. 1995).
Bacteria associate with the cell membrane and then
quickly enter the enterocyte via an entry vacuole. This
rapidly breaks down (within 3 hours) and the bacteria
flourish and multiply free (not membrane-bound) within
the cytoplasm. The entry of bacteria into cells is depen-
dent on cell, but not necessarily bacterial, viability, that
is, a type of induced phagocytosis (Lawson et al. 1995).
The mechanism whereby the bacteria cause infected cells
to fail to mature, continue to undergo mitosis, and form
hyperplastic crypts is not yet understood. Intestinal
glands can become enormously elongated and often
branched. Loss of body protein into the feces and the
blocking of nutrient absorption by the thickened intesti-
nal mucosa are the likely causes of the reduction in
weight gain and altered feed conversion in pigs affected
with chronic uncomplicated PE lesions.
Degenerative and reparative changes may be super-
imposed on the basic enterocyte proliferation. Inflam-
matory changes range from a superficial fibrinous reac-
tion to extensive, deep, coagulative necrosis, which is the
lesion of necrotic enteritis. Early lesions contain very few
infiltrating inflammatory cells, probably not above the
normal for pig intestines (McOrist et al. 1992). In more
developed lesions a mainly mononuclear leukocyte infil-
tration of the lamina propria, particularly CD8 cells,
may occur. In some pigs a substantial granulation tissue
reaction may occur, leading to fibrous tissue infiltration
and muscular hypertrophy, which is the lesion of region-
al ileitis (Rowland and Lawson 1992).
Acute hemorrhagic PE is marked by severe bleeding
into the lumen of the intestine, but with underlying le-
sions of chronic PE. The hemorrhage occurs concurrent-
ly with the widespread degeneration and desquamation
of many epithelial cells and leakage from the capillary
bed (Rowland and Lawson 1992). The exact trigger for
this hemorrhagic crisis is not yet known, but it has been
observed in pigs challenged once with L. intracellularis
and also subjected to an acute stressor (Mapother et al.
1987; McOrist and Gebhart, unpublished data—1996),
indicating a direct antiprotective effect of the stressor.
CLINICAL SIGNS
Clinical cases of chronic PE are observed most common-
ly in the postweaned pig between 6 and 20 weeks of age.
In many cases of chronic PE in growing pigs, the clinical
signs are slight, and little more is seen than failure to sus-
tain growth despite normal feed intake. Ileal lesions are a
consistent feature of these pigs. In some pigs there may
be a degree of anorexia, characterized by curiosity about
food but refusal to eat. Thus, affected animals vary from
the clinically unremarkable to those showing marked
dullness and apathy. Diarrhea, when present, is general-
ly moderate, with loose stools of normal color; this is
probably a feature of only one-half of pigs affected with
chronic PE. Diarrhea may occur when significant large-
intestinal lesions are present. When chronic PE is sus-
pected in a herd, milder cases can be relatively common
but difficult to detect. Therefore, such farms should be
inspected for apparent wasting of well-grown animals
with anorexia and irregular diarrhea, possibly seen as
“slab-sided” pigs. Records should be carefully examined
to detect changes in average weight gains and feed con-
version efficiency in the postweaned group (Roberts et al.
1979; Gogolewski et al. 1991). More severely affected cas-
es are often associated with varying degrees of inflam-
matory or necrotic change in the affected mucosa, and
those that develop necrotic enteritis or the “hose pipe”
ileum of regional ileitis show severe loss of condition
and often scour persistently. Death in regional ileitis is
not uncommon and is usually associated with perfora-
tions of the hypertrophied ileal wall, leading to a gener-
alized terminal peritonitis.
Unlike chronic PE, cases of acute hemorrhagic PE oc-
cur more commonly in young adults 4–12 months old
and present a clinical picture of acute hemorrhagic ane-
mia. Black tarry feces are often the first visible clinical
sign and these may become loose. However, some ani-
mals die without fecal abnormality and show only
marked pallor. Probably around half of the animals clin-
ically affected will die, the remainder recovering over a
short period of time, without marked loss of body con-
dition. Pregnant animals that are clinically affected may
abort, the majority within 6 days of the onset of clinical
signs (Beers 1984).
In most cases of uncomplicated chronic PE, recovery
occurs abruptly 4–10 weeks after the onset of clinical
signs with a return of appetite and growth rate to normal
levels. However, although progress to slaughter weight
can take place despite extensive lesions (Emsbo 1951;
Rowland and Hutchings 1978), there will be a reduction
in average weight gain, causing a significant extension of
the time pigs take to reach market weight, with a conse-
quent burden on the costs of maintaining the facilities.
The increase in feed required per unit weight gain in af-
fected pigs is also a major cost in extra feed require-
ments. Careful feed and weight measurements during re-
peated challenge studies have established that average
weight gains are reduced 6–20% in affected pigs, and the
increase in feed required per unit gain is 6–25%, com-
 CHAPTER 38 PORCINE PROLIFERATIVE ENTEROPATHIES McOrist, Gebhart 525

pared to normal pigs (Gogolewski et al. 1991; McOrist et

al. 1996b, 1997). Other costs associated with reduced
weight gains in growing pigs include reduced lean-meat
gain and increased “variation” in pigs destined for mar-
ket or breeding programs.

LESIONS

Chronic PE in growing pigs occurs most commonly in

the terminal 50 cm of the small intestine and the upper
third of the proximal colon. The magnitude of the pro-
liferation varies widely, but in the developed lesions the
wall is visibly thickened and the overall diameter in-
creased. In minor lesions, the area of the terminal ileum
that is 10 cm proximal from the ileocecal valve should be
carefully examined as the most likely site of infection.
Care is needed to distinguish minor lesions from con-
tracted mucosa over the Peyer’s patches. Some subseros-
al and mesenteric edema is common, and the normal
reticulated pattern of the serosal surface is emphasized.
The mucosal surface is moist but not mucoid, sometimes
with flecks of inflammatory exudate loosely adherent.
The affected mucosa itself is thrown into deep folds, lon-
gitudinal or transverse (Fig. 38.1); similar changes in the
large intestine may result in apparent plaque or polyp 38.1. Chronic PE. Ileum showing thickened, ridged
formation. mucosa.
Histologically, the mucosa is composed of enlarged,
branching crypts lined with immature epithelial cells. ing elongated spindles. Goblet cells are absent, and their
Compared to normal crypts, which are 1 cell layer thick, reappearance in deep glands is an indication of impend-
affected crypts are often 5, 10, or more cells thick (Fig. ing resolution. In uncomplicated disease, the lamina pro-
38.2). Numerous mitotic figures occurring throughout pria is normal.
the crypt are evident. Other nuclei of affected cells may Electron microscopy reveals intracellular bacteria, of-
appear as enlarged vesicular structures or densely stain- ten in considerable numbers, lying in the apical cyto-

38.2. Chronic PE, ileum.

High-power micrograph
showing marked enlargement
of affected intestinal crypts,
5–10 epithelial cells thick,
compared with adjacent nor-
mal crypt (H&E; ×400).
526 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor

plasm of the affected epithelial cells (Fig. 38.3). In recov-
ering lesions, the organisms become aggregated and may
be extruded in degenerate cells into the lumen or be con-
sumed by macrophages in the lamina propria. Many cas-
es show little evidence of inflammatory reaction. The re-
covering lesions are notable for the resumption of
epithelial cell apoptosis with the development of a popu-
lation of mature epithelium, with goblet cells in the deep
crypts, and a rapid disappearance of the adenomatous
cells from the surface (McOrist et al. 1996a).
Necrotic Enteritis
This is evident as coagulative necrosis with marked in-
flammatory exudation superimposed on an established
lesion of PE. Yellow-gray cheesy masses that adhere
tightly to the mucosa are present and may closely follow
the original thickened mucosal architecture. Histologi-
cally, the coagulative necrosis is clearly defined, with fib-
rin deposits and degenerative inflammatory cells. Diag-
nosis is confirmed by the presence of remnants of the
proliferative epithelium observed in the deep layers. In
long-standing cases, granulation tissue may become
prominent.
Regional Ileitis
This is recognized as a smoothly contracted, almost rigid
length of lower small intestine; hence the traditional
name “hose pipe gut” is appropriate (Fig. 38.4); the af-
fected portion of intestine often may be stood on end.
When the lumen is opened, ulceration, usually linear,
can be seen, with islands or strips of surviving mucosa
adjacent. Granulation tissue may be prominent, but the
most striking feature is hypertrophy of the outer muscle
coats. Both necrotic enteritis and regional ileitis lesions
are now relatively rare occurrences in some diagnostic
laboratories, for reasons that are not certain.

38.3. Chronic PE. Intestinal epithelial cell of ileum. Apical cytoplasm containing several L.
intracellularis organisms lying free in the cytoplasm and undergoing division (arrow) (uranyl
acetate and lead citrate; ×10,000).
 CHAPTER 38 PORCINE PROLIFERATIVE ENTEROPATHIES McOrist, Gebhart 527

38.4. Regional ileitis. Small intestine showing marked muscular hypertrophy. Normal intestine
adjacent.

Acute Hemorrhagic PE
Hemorrhagic PE generally affects the terminal ileum and
colon. The affected intestine is thickened and somewhat
turgid with serosal edema. The lumen of the ileum and
colon usually contains one or more formed blood clots,
but often with no other bloody fluids or feed contents ev-
ident. The rectum may contain black, tarry feces of
mixed blood and digesta (Fig. 38.5). The mucosal surface
of the affected portion of intestine shows little gross
damage except for the marked hyperplastic thickening.
Bleeding points, ulcers, or erosions are not observed.
Histological examination demonstrates extensive degen-
eration and hemorrhage within the proliferative epitheli-
um. There is marked accumulation of cellular debris

38.5. Acute hemorrhagic PE.

Small intestine showing thickened
mucosa and blood clot in lumen.
528 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor

containing numerous L. intracellularis organisms above
the affected mucosa and in the lumina of affected in-
testinal crypts (Fig. 38.6).
DIAGNOSIS
Because of the difficulty of culturing L. intracellularis (see
below), it has been necessary to develop alternative
methods for its detection. Confirmation of a clinical di-
agnosis of PE may be obtained by demonstration of L.
intracellularis in feces, either by a PCR assay using L. in-
tracellularis–specific primers or by using specific hyper-
immune rabbit serum or, preferably, a specific anti–L. in-
tracellularis monoclonal antibody (McOrist et al. 1987)
incorporated into immunofluorescence assay tech-
niques. In both test systems, pigs with active lesions are
usually found to be excreting the agent (McOrist et al.
1987; McOrist and Lawson 1989b; Jones et al. 1993b);
however, neither test is likely to prove sufficiently sensi-
tive for the diagnosis of all infections. The sensitivity of

38.6. Acute hemorrhagic PE,

ileum. Micrograph of mucosa
showing widespread degeneration
of mucosal crypts with hemor-
rhage on the surface.
 CHAPTER 38 PORCINE PROLIFERATIVE ENTEROPATHIES
the PCR assay is considered to be 102–105 organisms per
gram of feces, depending on the DNA extraction method
and type of assay used. Collection of feces for either test
is relatively easy to perform, and organisms within feces
are probably robust for the test procedures. Animals
6–10 weeks old usually have the highest prevalence rates
for screening of farms. Older animals are usually only
sampled during outbreaks of acute PE. Feces should be
stored at 4˚C or below for either test. However, both tests
require specialized reagents and equipment and are ex-
pensive to perform.
Methods described for the serologic diagnosis of PE
have employed whole bacterial antigen incorporated in-
to an indirect immunofluorescence assay (Lawson et al.
1988; Knittel et al. 1997) or an ELISA (Holyoake et al.
1994). Those assays used bacteria extracted from affect-
ed intestines or cultured L. intracellularis. Results from
serologic assays suggest that the serum antibody re-
sponse in pigs to L. intracellularis is specific and involves
IgM and IgG. While detectable antibody responses relate
well to the presence of lesions, exposure to infection may
not induce significant seroconversion in all cases. Al-
though blood collection is considerably more time-con-
suming than feces collection, the serotests are probably
cheaper to perform and more amenable to high through-
puts. Development of sensitive methods for antibody de-
tection may improve detection of low-level infections
(Knittel et al. 1997).
At necropsy, the use of modified Ziehl-Neelsen stain
or the Giminez stain on mucosal smears to demonstrate
the intracellular organisms is a simple presumptive tech-
nique, requiring minimal time and equipment (Love et
al. 1977). Histopathological examination of affected tis-
sues will reveal the distinctive morphology of the prolif-
erative lesions. Specific identification of L. intracellularis
in these lesions can be achieved by immunohistochemi-
cal staining of fixed embedded tissues (Lawson et al.
1985; McOrist et al. 1987). In the absence of specific im-
munological reagents, silver-staining techniques will
clearly show the presence of intracellular bacteria (Fig.
38.7). Modifications of the Warthin-Starry silver im-
pregnation technique (Young 1969) are satisfactory for
routine use. The affected crypts need to be examined
carefully at high magnifications due to the small size of
L. intracellularis. Where electron microscopic facilities
are available, the presence of the intracellular organism
can be confirmed. The organisms are straight or curved
bacteria with a wavy trilaminar outer coat typical of
gram-negative bacteria.
Cocultivation of the obligate intracellular L. intracel-
lularis in the laboratory requires establishment of a suit-
able cell line, such as IEC-18 rat enterocytes or IPEC-J2
pig enterocytes and the addition of purified L. intracellu-
laris from pig intestines in the presence of antibiotics to
retard the growth of other bacteria (Lawson et al. 1993;
McOrist et al. 1995b). Maintenance and passage of the
organism in coculture require suitable microaerobic at-
McOrist, Gebhart 529
mospheres and cell lysis conditions, respectively (Law-
son et al. 1993). Most cells in a monolayer are typically
infected with around 50 cytoplasmic bacteria (Fig. 38.8),
causing no apparent cytopathic effect.
TREATMENT AND PREVENTION
Some understanding of the antimicrobial agents likely to
be effective against L. intracellularis within pigs’ in-
testines has been gained. However, full correlation of in
vitro data, challenge trial data, and field trial data is not
yet finalized. Previously, speculative clinical impressions
of field treatments, without relevant controls, pointed
out many possible treatments (Connor 1991). Controlled
field studies suggested that PE may be prevented by
treatment with high doses of tylosin (100 ppm, Fleck and
Jones 1994) or oxytetracycline (400 ppm, Beers 1984).
In vitro evaluations of the minimum inhibitory con-
centration (MIC) of 20 antimicrobial agents and the
minimum bactericidal concentration (MBC) of 10 of
these suggested a rather broad range of antibiotic groups
with in vitro activity against L. intracellularis (McOrist et
al. 1995c; McOrist and Gebhart 1995). These included
macrolides (erythromycin and tylosin), tetracyclines,
pleuromulins (tiamulin), penicillins, and fluoro-
quinolones. The aminoglycosides and aminocyclitols
(neomycin, gentamicin, apramycin) were found to be in-
effective, with the bacteria being fully resistant. Follow-
ing these results, the evaluations of treatment and pre-
vention measures in experimentally challenged pigs have
indicated that macrolides, lincosamides, chlortetracy-
cline, and tiamulin are effective drugs in vivo (McOrist et
al. 1996b, 1997; Winkelman 1996b).
Various approaches to medication are possible, de-
pending on the age and type of pigs involved. Treatment
of acute PE in breeding herds previously thought to be
free of PE requires a vigorous approach. Treatment
needs to include both the clinically affected and the in-
contact animals (which may be the whole herd). The pre-
ferred treatment would be tiamulin (120 ppm), tylosin
(100 ppm), or chlortetracycline (400 ppm) for 14 days,
delivered orally via a water-soluble formulation or an in-
feed premix or by intramuscular injection of an equiva-
lent dose to affected and in-contact pigs.
Animals such as replacement breeding stock which
are to be introduced into infected transport situations or
into infected premises could be allowed a period of ex-
posure followed by therapeutic levels of antimicrobial
agents to impede the occurrence of clinical disease. The
preferred treatment would be tiamulin (120 ppm), ty-
losin (100 ppm), lincomycin (110ppm), or chlortetracy-
cline (300 ppm) for 14 days, delivered orally via a stabi-
lized in-feed premix. Following the transport or on-farm
period of exposure, no more than 2–3 weeks should
elapse before the introduction of antibiotics (Love and
Love 1977). Such an approach is most suited to the man-
agement of acute PE in young adult animals. However,
530 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor

38.7. Chronic PE, ileum. Micro-

graph of enlarged mucosal crypt
showing numerous intracellular
bacteria (arrows) in the apical
cytoplasm of epithelial cells
(Warthin-Starry silver stain;
×2000).

even with this type of program, PE may occur in med-
icated animals following the end of therapy. It is possible
that treatment of pregnant gilts 1–2 weeks prior to far-
rowing may reduce transmission of the infection to their
progeny.
Where PE is endemic in growing and fattening pigs,
another approach to treatment is continuous medica-
tion, to minimize the severe production losses caused by
the disease. Tiamulin (50 ppm), chlortetracycline (200
ppm), lincomycin (110 ppm), and tylosin (100 ppm) are
probably effective for this purpose in most cases, al-
though reduced dose rates or inadequate compliance
would be likely to undermine proper performance of
these drugs. However, the continuous medication of
young breeding animals may result in the medicated an-
imals remaining susceptible to infection, with the danger
of reoccurrence of PE following withdrawal of the med-
ication. These drugs should be delivered orally via a sta-
bilized in-feed premix. The description of ineffective
drugs is less certain, but recurrence or failure of preven-
 CHAPTER 38 PORCINE PROLIFERATIVE ENTEROPATHIES
38.8. Culture of L. intracellularis. Micrograph of
IPEC-J2 pig intestinal epithelial cells, one of which con-
tains numerous intracellular bacteria in the cytoplasm.
Immunoperoxidase stain incorporating Lawsonia-
specific monoclonal antibody.
tion of the disease has been reported in pigs receiving
penicillin, bacitracin, neomycin, virginiamycin, salino-
mycin, or olaquindox (Pointon 1989; Winkelman
1996a). Despite the apparent usage of these drugs at ap-
propriate levels, intestinal lesions still developed in some
pigs.
Severe chronic clinical disease manifest as wasting
pigs with or without necrotic enteritis will often appear
to be moderated by the use of tylosin, lincomycin,
chlortetracycline, or tiamulin. If sufficient numbers of
clinical cases are occurring in growing pigs, then the re-
moval of affected animals to separate accommodation,
with supportive therapy, may limit losses. Preliminary
field trials suggest that incorporation of in-feed antibi-
otics for control achieves best results at 4–8 weeks of age,
that is, just prior to the peak period of Lawsonia infection
on most farms. These trials also suggest that medication
of older pigs, such as breeding stock, is not likely to elim-
inate the infection from their progeny or from other
groups. Inherent bacterial resistance to tetracycline or
other groups of drugs has not been proven and is not
common in other obligately intracellular bacteria.
Because PE is rarely observed in apparently recovered
pigs or in pigs over 2 years old, it is likely that some nat-
ural immunity exists. Also, specific cell-mediated and hu-
moral antibody responses to infection have been detect-
ed, albeit at a low level (Lawson et al. 1988; McOrist and
Lawson 1993). However, the common occurrence of the
disease and the wide age range of susceptible pigs sug-
gest that natural immunity in field situations may not
occur regularly.
Estimates of the financial costs of the disease suggest
that the costs in extra feed, extra facility time, and possi-
ble loss of carcass leanness are substantial (U.S.$5–10
per affected pig), especially considered together with the
high prevalence of the disease. Sustained isolation of the
herd with rigorous control of access appears the most
McOrist, Gebhart 531
appropriate absolute precaution.
It remains a matter of concern that acute and chron-
ic PE continue to be serious problems in high-health-sta-
tus, minimal-disease herds, often with early weaning and
high-quality commercial breeding lines in place. It can-
not be overemphasized that in most conventional herds,
the absence of clinical PE, even over a period of years, is
no guarantee of freedom from the infection and disease.
Apparently clean animals from such herds may be re-
sponsible for the introduction of PE into a hitherto un-
contaminated environment, often followed by an explo-
sive outbreak of acute hemorrhagic PE and later by a low
level of endemic chronic PE.
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 Salmonellosis
39 K. J. Schwartz
Members of the genus Salmonella are notorious for their
ability to infect a broad range of hosts, which is a major
factor in their success as pathogens. Taylor and McCoy
(1969) observed that salmonellae have been isolated
from virtually all vertebrate hosts from which they have
been sought, with the possible exception of fish in un-
polluted waters. Although many of the more than 2400
salmonella serotypes have a broad host range and are
widely distributed, several serotypes are quite adapted to
a single host species, most notably S. typhi (humans), S.
dublin (bovine), and S. choleraesuis (swine). Many
serotypes are not associated with overt disease and ap-
pear to have limited host and geographical range.
Salmonella infections of swine are of concern for two
major reasons. The first is the clinical disease (salmonel-
losis) in swine that may result, and the second is that
swine can be infected with a broad range of salmonella
serotypes that can be a source of infection of pork prod-
ucts.
Salmon and Smith (1886) first associated salmonel-
lae with disease when they described S. choleraesuis as the
putative cause of classical swine fever (hog cholera). The
identification and, in many swine-producing areas, erad-
ication of the viral etiology of classical swine fever, rele-
gated S. choleraesuis to an opportunistic pathogen in
swine. The dramatic increase in salmonellosis during the
1980s in North America underscored the pathogenic po-
tential of S. choleraesuis for swine.
Disease associated with host-adapted S. choleraesuis is
referable to septicemia, enterocolitis, or bacteremic lo-
calization as pneumonia and hepatitis (Baskerville and
Dow 1973) or occasionally as meningitis (Reynolds et al.
1967; McErlean 1968), encephalitis (Wilcock and Olan-
der 1977c), and abortion (Schwartz and Daniels 1987).
Only a handful of other serotypes are associated with
disease in swine, usually as a cause of enterocolitis, the
most notable being S. typhimurium. Reported rarely, S.
typhisuis is associated with caseous lymphadenitis
(Barnes and Bergeland 1968).
ETIOLOGY
The genus Salmonella is a morphologically and biochem-
ically homogeneous group of gram-negative, motile,
non-spore-forming, facultatively anaerobic bacilli with
peritrichous flagella. The reservoir for salmonellae is,
typical of the family Enterobacteriaceae, the intestinal
tract of warm-blooded and cold-blooded animals.
Salmonellae are hardy and ubiquitous bacteria. They
multiply at 7–45˚C; survive freezing and desiccation
well; and persist for weeks, months, or even years in suit-
able organic substrates. Salmonellae were reported to
survive in meat-meal fertilizer for 8 months (Mittermey-
er and Foltz 1969) and in manure oxidation ditches for
47 days (Will et al. 1973). Survival is greatly shortened
below pH 5.0 (Henry et al. 1983). Numerous reports of
prolonged survival in water have been cited (Williams
1975; Wray and Sojka 1977; Pokorny 1988). The bacteria
are readily inactivated by heat and sunlight as well as by
common phenolic, chlorine, and iodine-based disinfec-
tants (Rubin and Weinstein 1977). Ability to survive in
the environment, as well as prolonged carrier states in in-
numerable hosts, ensures the widespread distribution of
this genus worldwide.
Techniques for isolation of salmonellae vary widely,
depending on the nature of the suspect material and
sometimes with the specific serotypes sought. In sewage,
feed, and polluted water, where salmonella numbers are
likely to be low compared to other organisms, well-docu-
mented and sometimes elaborate techniques of preen-
richment, selective enrichment, and selective plating are
commonly used (Groves et al. 1971; Edwards and Ewing
1972; Skovgaard et al. 1985; Vassiliadis et al. 1987). Oc-
casionally these methods may be necessary for the isola-
tion of salmonellae from tissues or feces of carrier ani-
mals in which numbers are low, but in clinically affected
animals the populations are such that direct plating of
internal organs on routine selective and differential en-
teric media such as brilliant green agar and MacConkey
agar are usually adequate (Committee on Salmonella
1969). The isolation of salmonellae is not sufficient for
definitive diagnosis of salmonellosis, particularly if elab-
orate isolation techniques are required, since subclinical
infections and environmental contamination are com-
mon. Isolation techniques for various types of specimens
are detailed in most standard texts on clinical microbiol-
ogy. Epidemiological investigations of zoonotic out-
breaks occasionally demand more sophisticated tech-
niques of phage typing, plasmid characterization,
mapping of outer-membrane proteins (OMP), or DNA
analysis to trace a specific isolant.
S. choleraesuis is the type species for the genus Salmo-
535
536 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor

nella as described by Salmon, although it is now more
commonly isolated as the hydrogen sulfide–producing
variant kunzendorf. Some authors suggest that there are
only two actual species of salmonellae with well over
2400 serotypes. Convention, however, is to refer to each
of the serologically distinct serotypes, usually named by
the geographic site of first isolation, as a species.
Serotype identification uses the Kauffmann-White
schema, based on antigenic differences in somatic (O),
surface or capsular (Vi), phase 1 flagellar, and phase 2 fla-
gellar antigens determined by agglutination serology.
Complete serotyping is laborious and is available at only
a few reference laboratories. Most laboratories use com-
mercially available polyvalent antisera to determine the
O antigen groups of isolates for rapid and preliminary
identification. The serogroup designation will help pre-
dict the serotype present or, at least, can be used to rule
out those serotypes found in other serogroups (Table
39.1).
In contrast to the large number of serotypes isolated
from carcasses and pork products, disease in swine is al-
most always caused by either the hydrogen sulfide–pro-
ducing variant of S. choleraesuis variety kunzendorf or by
S. typhimurium. The former has been and continues to be
the most frequent serotype causing disease in swine
(Levine et al. 1945; Lawson and Dow 1966; Morehouse
1972; Wilcock et al. 1976; Mills and Kelly 1986;
Schwartz and Daniels 1987; Schwartz 1997a), generally
manifested as septicemia.
S. typhimurium is the second most frequently isolated
serotype from diseased swine, usually associated with en-
terocolitis. Disease caused by S. typhimurium occurs with
greater than expected frequency in what could be con-
sidered unusually clean herds: university research herds,
testing stations, closed specific-pathogen-free (SPF)
herds, or purebred breeding herds (Heard et al. 1965;
Gooch and Haddock 1969; Lynn et al. 1972). Presum-
ably, this is because of introduction to a previously im-
munologically naive population, a situation occurring
with increasing frequency in modern production units
using age-segregated rearing. This organism is also fre-
quently isolated as a sequel to other enteric or debilitat-
ing diseases.
Localized epizootics of disease caused by the bio-
chemically atypical S. typhisuis have been reported in the
American Midwest (Barnes and Bergeland 1968; An-
drews 1976) and at least historically in Europe (Barnes
and Sorensen 1975). This organism grows poorly in stan-
dard selective media for salmonella isolation, but the dis-
ease produced by S. typhisuis is so characteristic that out-
breaks are not likely to remain unnoticed (Barnes and
Bergeland 1968).

Table 39.1. Serogroups of selected salmonella serotypes and ranking of frequency of isolation from diseased
pigs, swine sources, and humans
Isolations from Isolations from Isolations from
Diseased Pigs Swine Sources Humans
Serogroup Serotype (Schwartz 1997a) (Ferris and Frerichs 1996) (CDC 1996)
A S. paratyphi A
B S. typhimurium 3 5 3
S. typhimurium var. copenhagen 2 3 2
S. derby 1
S. agona 4 6
S. schwarzengrund 10
S. hadar 7
S. saint paul
S. heidelberg 4 6 4
C1 S. choleraesuis 7
S. choleraesuis var. kunzendorf 1 2
S. mbandaka 9
S. typhisuis
S. montevideo 8
S. oranienburg 9
S. infantis
S. thompson 10
C2 S. newport 5
S. muenchen
D1 S. dublin
S. typhi
S. enteritidis 1
S. pullorum
E1 S. anatum 8
E2 S. newington
E4 S. senftenberg
G2 S. worthington
 CHAPTER 39 SALMONELLOSIS Schwartz
Other serotypes are occasional causes of disease in
swine but are usually transient and associated with pre-
disposing factors, including other intestinal distur-
bances or disease; circumstances which allow immuno-
logically naive pigs to be exposed to very large doses; or
debilitated and immunologically compromised pigs. A
variety of serotypes may be isolated from diarrheic
piglets in the immediate postweaning period, but most
are usually associated with concurrent enteric
pathogens, inappropriate diets, poor hygiene and envi-
ronment, or debilitation. The isolation of uncommon
serotypes of salmonellae from diarrheic pigs generally
warrants further diagnostic investigation. Salmonella hei-
delberg has been associated with postweaning diarrhea,
with lesions more typical of enterotoxigenic diarrheal
disease than typical salmonellosis (Reed et al. 1985). Re-
ports of naturally occurring disease, such as those for S.
dublin (Lawson and Dow 1966; McErlean 1968) and S.
enteritidis (Reynolds et al. 1967), should support the iso-
lation of the offending serotype with clinical and patho-
logic evidence of salmonellosis. In the case of both S.
dublin and S. enteritidis, the reports were of meningitis in
suckling pigs.
EPIDEMIOLOGY
The reservoir for salmonellae is the intestinal tract of
warm- and cold-blooded animals. Salmonellae have mas-
tered virtually all of the attributes necessary to ensure
wide distribution, including abundant reservoir hosts,
efficient fecal shedding from carrier animals, persistence
within the environment, and the effective use of trans-
mission vectors (feed, fomites, vehicles, etc.). Inappar-
ent, long-term carriers that can shed salmonellae in feces
continuously or intermittently, often in high numbers,
are common in most host species. Shedding of the or-
ganism can be exacerbated by a long list of stressors, in-
cluding commingling of pigs, transportation, concur-
rent diseases, and food deprivation.
The epidemiology of salmonella infections in swine is
two relatively separate problems: salmonella infection of
pork carcasses and retail products and infections that
cause salmonellosis in swine. Infection of swine by one
or more serotypes is common, but primary clinical dis-
ease caused by serotypes other than S. choleraesuis or S.
typhimurium is uncommon. It is important to under-
stand that swine can be infected with a variety of
serotypes that do not cause disease in swine but do rep-
resent a source of infection for pork products.
Extrapolation of epidemiological data from experi-
mental studies where a single serotype with predeter-
mined dose is administered to naive healthy pigs is not
likely to represent field situations, where there are multi-
ple serotypes, varying doses, intermittent exposures,
variable host resistance, many management variables,
and various intercurrent infections and diseases. Similar-
537
ly, disease prevalence surveys must be carefully scruti-
nized to be sure that infection is not equated with dis-
ease, and that a source of infection is not inaccurately
implicated.
Salmonellae in Pork
Data collected from various countries indicate salmonel-
lae to be present in 0–48% of carcasses (Riley 1970; Not-
tingham et al. 1972; McCaughey et al. 1973; Gustafson et
al. 1976; Tacal and Lawrence 1980; Morse and Hird
1984; Jayarao et al. 1989; Carr et al. 1996) and 0–30% of
retail pork products (Gooch and Goo 1971; Surkiewicz et
al. 1972; Roberts et al. 1975; Banks and Board 1983; Silas
et al. 1984; Fukushima et al. 1987; Anon. 1994). The
marked variation is probably due, in part, to real varia-
tion in contamination and, in part, to differences in
methods of survey and methods of meat processing. The
high level of infection demonstrated in some of the stud-
ies is likely the result of abattoir cross-contamination in
crowded holding pens prior to slaughter as well as me-
chanical transfer of contamination among carcasses by
dehairing machines, scalding tanks, and polishers (Gal-
ton et al. 1954; Hansen et al. 1964; Kampelmacher et al.
1965; Williams and Newell 1970; Michaud 1978; Mor-
gan et al. 1987). Although much of the salmonella
contamination of pork products occurs within abattoirs
during processing, infected pigs leaving the farm are con-
sidered the original source of abattoir infections. The
stress of transport and feed deprivation increases shed-
ding from inapparent carriers, which then contaminate
the environment of the truck and abattoir (Williams and
Newell 1970). The prevalence of infection within the
group continues to increase with increasing length of
stay in the pens prior to slaughter, rising by about 50%
for each 24-hour period (Craven and Hurst 1982; Mor-
gan et al. 1987). It should be noted that S. choleraesuis is
rarely associated with contamination of carcasses and
pork products, and although unusual as a cause of hu-
man disease, it is particularly severe when it does occur
(Cherubin 1980).
There is currently an explosion of investigational ac-
tivity related to issues of food safety, including salmonel-
la contamination of a variety of foods. Salmonellosis is
considered to be the most common food-borne illness in
humans, with increasing incidence reported worldwide.
Reasons include improved monitoring, increased public
awareness of microbiological hazards of food, wide-
spread distribution of virulent serotypes such as S. enter-
itidis or S. tyhimurium definitive type 104 (DT 104) in an-
imal populations, increasing consumption of foods of
animal origin, and changes in consumer eating habits.
Although salmonella contamination of poultry and beef
products exceeds that of pork, salmonella control pro-
grams in swine will continue to be a primary focus of
food safety initiatives. Salmonella reduction programs
are becoming commonplace, with long-range goals to in-
538 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
clude the production and marketing of salmonellae-free
pork products. Already, numerous, dynamic programs
are in place utilizing hazard analysis and critical control
point (HACCP) principles. Those programs that have
been in place for a sufficient period of time, such as the
Danish program, have significantly reduced the rate of
salmonella infection in pork products (Nielsen et al.
1995). Fortunately, most of the methods useful for pre-
harvest salmonella reduction in swine populations are
related to sound management practices that also im-
prove the overall health of a swine operation.
Salmonellosis in Swine
Most salmonellosis outbreaks occur in intensively reared
weaned pigs, and although disease in adults and suckling
pigs is infrequent, infection is not (Gooch and Haddock
1969; Wilcock et al. 1976). The low frequency of salmo-
nellosis in suckling pigs presumably results from lacto-
genic immunity, since neonatal swine are susceptible to
oral challenge with salmonellae and develop a disease
comparable to that in weaned pigs (Wilcock 1978). Dis-
ease occurs worldwide but varies markedly in estimated
prevalence, morbidity, and mortality. This may be from
incautious extrapolation of data gathered from microbi-
ological surveys applied to actual disease incidence. In
one correlative study in Indiana in 1974–75, salmonel-
losis accounted for 19% of 327 consecutive porcine
necropsies (Wilcock et al. 1976). In contrast, Hooper and
Troutt (1971) reported that salmonella infection was
considered the major disease process in only 2% of sam-
ples submitted in Missouri between 1967 and 1969. Dur-
ing a 4-year period in Ireland, salmonellosis was the di-
agnosis in 4.4% of 2180 swine necropsies (Lawson and
Dow 1966). In Taiwan, salmonellae were isolated from
about 10% of scouring pigs and 48% of fatal diarrheas or
septicemias in weaned pigs (Hsu et al. 1983). A survey of
diagnostic submissions to the Iowa State University Vet-
erinary Diagnostic Laboratory from 1994 through 1996
revealed salmonellae to be present in 11% of 9109
porcine pneumonia cases, 9% of 3320 enteric cases, and
58% of 1612 cases of porcine bacterial septicemia
(Schwartz 1997a).
Host-adapted S. choleraesuis is isolated almost exclu-
sively from diseased swine, is the most common cause of
salmonellosis in swine, and is usually manifested as sep-
ticemia. Midwestern U.S. diagnostic laboratories and
veterinarians reported an increasing frequency of salmo-
nellosis due to S. choleraesuis from 1981 to 1990 and a de-
creasing frequency from 1991 to 1997 (Schwartz 1997b).
The recent decrease in the Midwest is likely due to im-
provements in swine management and husbandry and
the advent of efficacious attenuated live vaccines. Re-
gional variation in salmonellosis incidence is loosely cor-
related to pig density, husbandry practices, and, in par-
ticular, commingling of pigs of different ages and/or
origins.
S. typhimurium accounts for most of the remaining
cases of salmonellosis in swine. This serotype has world-
wide distribution and is not host-specific. Enterocolitis is
the primary disease referable to this serotype, most com-
monly seen in pigs with concurrent debilitating illnesses,
in conditions of poor hygiene that allow exposure to
high doses of the organism, or where immunologically
naive pigs are exposed to sufficiently large doses. The lat-
ter situation appears to be more frequently encountered
with modern production systems utilizing age-segregat-
ed production.
The attribution of primary pathogenic status to oth-
er serotypes should be made with caution. Most other
serotypes are transient, sporadic causes of disease and
often cannot be associated with disease experimentally
without unique, qualifying criteria. S. heidelberg has been
associated with catarrhal enterocolitis in young pigs,
with enterotoxigenic properties leading to accumula-
tions of large amounts of fluid in the small intestine and
colon as a rather unusual presentation of salmonellosis
(Reed et al. 1985).
Sources of Infection
The number of potential sources of salmonella infection
for a population of swine is seemingly endless. A task
force study in the United States did not reach a consen-
sus as to the most important source of salmonellae for
pigs (Bixler 1978), in large part due to the diversity and
the biology of the genus Salmonella. In general, the
source of salmonellae virulent for swine is most likely to
be other swine or environments contaminated by swine.
S. choleraesuis is the most frequent porcine isolate from
clinically ill pigs, but it is a very infrequent isolate from
pig feeds or nonporcine salmonella reservoirs. The con-
clusion seems clear that infected, shedding pigs and con-
taminated environments are the major sources of new
infections of S. choleraesuis. Vertical (dam to offspring)
and horizontal transmission both occur. Feed contami-
nation and nonporcine species have not been implicated
as a source of S. choleraesuis infection of swine.
The source of infection for other serotypes is less
clear, since the host and vector range for salmonellae is
broad and they have amazing capability to persist in en-
vironments outside the host. For serotypes other than S.
choleraesuis, pigs should be thought of as biological fil-
ters for the low numbers of various salmonella serotypes
present in feed, water, or litter contaminated by birds,
rodents, or other animals. Evidence linking these sources
of contamination to primary clinical outbreaks, without
other concurrent diseases or predisposing conditions, is
generally lacking. Feed containing ingredients of animal
origin is widely accepted as a source of salmonella infec-
tion to herds, but it should be emphasized that ingredi-
ents of vegetable origin can also be a source of salmonel-
lae-contaminated feed. Water is not as likely a source of
infection unless surface water is used for consumption or
 CHAPTER 39 SALMONELLOSIS Schwartz
pigs have access to recycled lagoon water. Birds, insects,
rodents, and pets can all act as carriers, as can bedding
and litter (Allred et al. 1967; Williams et al. 1969; Nape
and Murphy 1971). In a recent survey in the United
States, salmonellae were isolated from feed or feed ingre-
dients from 14 of 30 farms and 36 of 1228 samples (Har-
ris et al. 1997). The isolation of salmonellae from feed
was significantly associated with the lack of bird-proof-
ing, with on-farm feed preparation, and with the housing
of pigs in facilities other than total confinement, for all
stages of production. Interestingly, salmonella isolation
from complete feeds was more frequent from pelleted
feeds than from ground feed. No S. typhimurium was iso-
lated from feed samples in this study.
Transmission, Shedding, and Carrier State
Because of the dynamic relationship between salmonel-
lae, host, and environment, and because infection does
not equate with disease, definitive statements regarding
transmission, shedding, and carrier states are apt to be
misinterpreted, if not erroneous. Salmonella transmis-
sion and shedding within differing populations of ani-
mals in an endless variety of environmental, feeding, and
management situations result in countless unique situa-
tions that cannot be experimentally reproduced. The
sensitivity of most current detection methods is not ade-
quate to define these parameters in field situations. In
general, fecal-oral transmission is the most likely mode
of transmission of virulent salmonellae. This can occur
from pig to pig, contaminated environment to pig, or
dam to offspring. Oral-pharyngeal secretions may con-
tain salmonellae, which may allow nose-nose transmis-
sion. Aerolized secretions, feces, or contaminated dust
particles make the potential for aerosol transmission for
short distances quite real.
Salmonella infection of swine herds is much more
common than disease. Longitudinal Dutch studies sug-
gest that about 25% of herds are never infected, 24% are
constantly infected, and 50% are infected most of the
time. There appear to be infection cycles, with the en-
demic salmonellae having an ecological advantage over
newly introduced salmonella serotypes. Infection occurs
in the first weeks after arrival or commingling and reach-
es a maximum of 80–100% prevalence within another
2–3 weeks. About 5–30% of the pigs are still excreting
salmonellae at the end of the finishing period. In 1995,
the National Animal Health Monitoring Service
(NAHMS) reported 30–60% of U.S. herds infected with
at least one serotype of Salmonella, with the greatest per-
centage of postive herds found in the southeastern Unit-
ed States and in herds marketing greater than 10,000
head annually.
During acute disease, pigs will shed up to 106 S.
choleraesuis/g feces (Smith and Jones 1967) or 107 S. ty-
phimurium (Gutzmann et al. 1976). The minimum dis-
ease-producing dose of either serotype has not been es-
539
tablished in field situations, but disease is difficult to re-
produce experimentally at low doses. There is one report
of moderate disease following oral inoculation of 106
cells (Dawe and Troutt 1976), but most authors report
successful experimental disease production with doses of
108–1011 cells unless pigs are artificially stressed by injec-
tion of dexamethasone or in some other manner. Pigs in-
fected with 103 organisms remained clinically normal but
uninoculated pigs in the same pen did become clinically
ill (Gray et al. 1996). It is likely that dose (and perhaps
virulence) is magnified when pigs are infected and se-
quential (pig-to-pig) transmission occurs in field situa-
tions, so that the initial infective dose in the field is con-
siderably less than that required in experimental
situations. High animal density, stress of transport, and
intercurrent nutritional or infectious disease are as-
sumed to increase the shedding by carriers as well as the
susceptibility of exposed pigs (Committee on Salmonel-
la 1969). Pigs with nondetectable shedding of salmonel-
lae can become detectable within hours of an applied
stress. The transmission demonstrated between feeder
pigs also occurs between pigs during market transport
and lairage at abattoirs, with infection rates proportion-
al to time spent in transport and lairage. It is likely that
catecholamines are released in association with stress, re-
sulting in decreased gastric acid production and in-
creased intestinal motility. Increases in stomach pH in-
crease the likelihood that salmonellae will survive
passage through the stomach and will access and repli-
cate in the intestine and colon.
Outbreaks of salmonellosis are usually characterized
by spread from pen to pen. Situations of spread from
pen to distant pen are likely because of vectors or care-
taker transmission. When all animals sicken simultane-
ously, a common source such as feed, bedding, water, or
a contaminated environment should be suspected. Sal-
monella infections tend to be more prevalent in continu-
ous-flow systems than in barns managed by principles of
all-in/all-out. Prevalence is also higher in barns with
open flush-gutters than in those with slotted floors, with
the highest rates of infection observed in outdoor finish-
ing systems (Davies et al. 1997).
Numerous studies in a variety of host species with a
potpourri of serotypes have demonstrated prolonged
carrier states following infection. The pattern of shed-
ding and the duration of the carrier state after clinically
apparent disease have been studied only in group-
housed pigs with no barrier to repeated reinfection
(Wilcock and Olander 1978; Wood et al. 1989). After ex-
perimental infection, S. typhimurium was isolated from
feces daily during the first 10 days postinfection and fre-
quently during the next 4–5 months. When slaughtered
4–7 months after initial infection, over 90% of pigs were
positive for S. typhimurium in the mesenteric lymph
node, tonsil, cecum, or feces (Wilcock and Olander 1978;
Wood et al. 1989; Wood and Rose 1992; Fedorka-Cray et
540 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
al. 1994). S. newport has been shown to persist in mesen-
teric lymph nodes for 28 weeks. Infection of individual
animals may be relatively short-lived (less than 8 weeks),
but organisms may circulate within a population and be-
tween pigs and the environment for extended periods of
time.
S. choleraesuis given by either the intranasal or the in-
tragastric route has been demonstrated to persist within
ileocolic junction, lymph nodes, tonsils, lungs, and colon
for at least 12 weeks (Gray et al. 1995). Infection with low
doses of S. choleraesuis produced a shorter period of in-
fection than infection with moderate or high doses. S.
choleraesuis has been shown to persist for at least 3
months in wet feces and 6 months in desiccated feces.
The influence of antibiotics on the frequency and du-
ration of shedding of salmonellae in pigs has received lit-
tle attention. In human enteric salmonellosis, the use of
antibiotics has long been recognized to prolong the car-
rier state (Dixon 1965; Aserkoff and Bennett 1969). In
pigs with enterocolitis, antibiotics do not reduce the du-
ration or the magnitude of fecal shedding, but neither
are they reported to prolong or intensify shedding (Fin-
layson and Barnum 1973; DeGeeter et al. 1976; Gutz-
mann et al. 1976; Wilcock and Olander 1978; Jones et al.
1983; Jacks et al. 1988). In contrast, vigorous antibacter-
ial therapy early in the course of septicemia caused by S.
choleraesuis may significantly reduce the magnitude and
duration of fecal shedding (Jacks et al. 1981).
PATHOGENESIS
The clinical and pathological features of salmonella in-
fections are extremely variable. Severity is influenced by
serotype, virulence, natural and acquired host resistance,
and route and quantity of the infective dose. Over 200
virulence factors have been associated with salmonellae
but few have been completely characterized. Generally,
those that promote virulence in pathogenic salmonellae
are involved in adhesion, invasion, cytotoxicity, and re-
sistance to intracellular killing, often working in combi-
nation to promote disease. Despite distinct differences in
clinical signs, many parallels can be drawn between S.
choleraesuis and S. typhimurium when discussing patho-
genesis.
Although large doses (greater than 107) are required
to induce disease experimentally, intraluminal replica-
tion may be important with small inocula from contami-
nated feed or water. Disease is facilitated by factors such
as peristaltic impairment, interference with intestinal
flora, and elevation of gastric pH (Clarke and Gyles
1993). Replication to about 107 organisms/g of intestinal
content is required for lesion production in pigs infected
with S. typhimurium, a finding that probably also applies
to other serotypes causing enterocolitis. Alterations in
normal intestinal defenses by antibiotic-induced
changes in normal flora or cold-induced alteration in in-
testinal motility may reduce the amount of replication
required for disease or increase the ease of salmonella
replication (Bohnhoff et al. 1954). Infection with S.
choleraesuis may not require such massive luminal prolif-
eration as prerequisite for disease, because it is inherent-
ly more invasive than other serotypes, can infect via the
pharyngeal tonsil, and regularly causes signs of sep-
ticemia 24–72 hours before the onset of diarrhea (Smith
and Jones 1967; Cherubin et al. 1974; Wilcock 1979;
Reed et al. 1986).
Most pathogenic S. typhimurium organisms have type
1 fimbriae and flagella, both of which appear to be in-
volved in attachment and invasion. Phenotypic shifts
may occur in salmonellae to produce adhesive pili (Isaac-
son 1996). Flagella may also be important in allowing
survival inside macrophages. The ability to invade is a re-
quirement for pathogenesis and is encoded by a
serotype-specific plasmid (Helmuth et al. 1985). Re-
moval of this plasmid results in a lack of ability to invade
but has no effect on ingestion or killing by murine
macrophages, LPS production, or serum resistance
(Gulig and Curtiss 1987). During the invasion process
there is induction of synthesis of new proteins that prob-
ably enhance intracellular survival (Finlay et al. 1989).
Peroxidase-antiperoxidase immunoenzymatic labeling
and immunogold labeling techniques have demonstrat-
ed that S. typhimurium has a low tendency to invade the
enteric mucosa and does not have a predilection for any
specific intestinal location, whereas S. choleraesuis locates
preferentially in the colon on the luminal surface of ileal
M cells of Peyer’s patches (Pospischil et al. 1990). Inva-
sion is by endocytosis by M cells of gut-associated lym-
phoid tissue as well as enterocytes. Attachment of the
bacteria to epithelial receptors triggers microfilament-
controlled uptake, vacuole formation, vacuole transport
through the cell cytoplasm, and entry to the lamina pro-
pria via exocytosis through the basement membrane
(Takeuchi 1967; Takeuchi and Sprinz 1967). Passage
through the epithelium results in mild and transient en-
terocyte damage. Salmonellae can synthesize over 30
proteins which are selectively induced during infection
of macrophages, making them facultative intracellular
bacteria (similar to Brucella, Mycobacteria, and Listeria
organisms) that can survive within macrophages and
neutrophils in the lamina propria (Roof et al. 1992a, b).
Spread to mesenteric lymph nodes is rapid, occurring
within 2 hours of inoculation of ligated intestinal loops
or 24 hours after oral challenge (Reed et al. 1985, 1986).
Macrophages are the most likely disseminators of infec-
tion systemically to other sites of infection and patholo-
gy. Concurrent with bacillary spread is the appearance of
an acute, predominantly macrophagic, inflammatory re-
action and prominent microvascular damage with
thrombosis within the lamina propria and submucosa.
 CHAPTER 39 SALMONELLOSIS Schwartz
When administered intranasally to esophagatomized
pigs, S. choleraesuis demonstrated primary colonization
of the lung within 4 hours (Fedorka-Cray et al. 1995;
Gray et al. 1995).
The pathogenesis of the diarrhea typical of enteric
salmonellosis and of later stages of salmonella sep-
ticemia has traditionally been attributed to malabsorp-
tion and net fluid leakage by a necrotic, inflamed bowel.
Several studies using rabbits, monkeys, calves, or pigs
have demonstrated fluid secretion independent of mu-
cosal necrosis or inflammation (Giannella et al. 1973;
Rout et al. 1974; Kinsey et al. 1976; Clarke and Gyles
1987). These studies present evidence that, at least early
in the disease, the diarrhea is the result of decreased
sodium resorption and increased chloride secretion due
to cholera-like and shiga-like enterotoxins. Secretion
stimulated by prostaglandins elaborated by endotoxin-
stimulated neutrophils may also be important (Stephen
et al. 1985). Most of the experimental work has been
done using small intestine of rabbits or monkeys, species
in which the lesions of salmonellosis are quite different
from those in pigs. Toxic effects of certain OMPs, as well
as lipid A associated with the LPS, are also important me-
diators of cell damage. Survival within phagocytes is an
important attribute of virulent salmonellae, the mecha-
nism of which is not clear. Salmonellae which possess
smooth LPS, O side chains, and a complete LPS core are
more resistant to phagocyte killing.
Mucosal inflammation and necrosis, as well as sep-
ticemia, occur in concert with the diarrhea but perhaps
independently of it. Microvascular thrombosis and en-
dothelial necrosis in the submucosa and lamina propria
are consistent early lesions in porcine salmonellosis
(Lawson and Dow 1966; Wilcock et al. 1976; Jubb et al.
1993; Reed et al. 1986), probably in response to locally
produced endotoxin. Salmonellae are not directly associ-
ated with the damaged vessels but direct the events from
the protected intracellular niche of macrophages in the
surrounding submucosa or lamina propria (Takeuchi
and Sprinz 1967). Mucosal ischemia as a result of the mi-
crovascular thrombosis is probably a major contributor
to the mucosal necrosis so typical of salmonellosis in all
species. The second major contribution to mucosal
necrosis is probably from the chemical products of mu-
cosal inflammation. The systemic signs and lesions of
septicemic salmonellosis, in swine almost exclusively S.
choleraesuis infection, are most commonly attributed to
endotoxemia from bacterial dissemination. The complex
biology of endotoxin is beyond the scope of this chapter,
and readers should consult Wolff 1973, Elin and Wolff
1976, or Cybulsky et al. 1988. Briefly, endotoxin interacts
with plasma and with leukocytes to initiate inflamma-
tion and fever. Most of the effects are mediated by inter-
leukin-1, a lymphokine produced by macrophages stim-
ulated by the endotoxin (Rubin and Weinstein 1977).
541
Endotoxins have either direct effects on tissue or effects
via an array of cytokine mediators.
CLINICAL SIGNS, PATHOLOGICAL
FINDINGS, AND DIAGNOSIS
The clinical signs of porcine salmonellosis are referable
to septicemia or to enterocolitis, and this section de-
scribes each syndrome separately. Pigs surviving acute
septicemia may develop clinical signs due to bacteremic
localization: pneumonia, hepatitis, enterocolitis, and,
occasionally, meningoencephalitis. Pigs initially suffer-
ing from enterocolitis may later develop chronic wasting
disease or, occasionally, rectal stricture.
The most available salmonella diagnostic method is
bacterial isolation and identification, which, along with
compatible lesions, remains the basis for diagnosis. Oth-
er tests using more sophisticated technology, including
polymerase chain reaction (PCR), are not required for
routine diagnosis. PCR currently has value as a screening
tool but has a relatively high cost and currently lacks sen-
sitivity without preenrichment. Detection of salmonel-
lae does not constitute diagnosis of salmonellosis.
Serology is becoming increasingly available, usually
in the form of an ELISA test. Most tests use surface anti-
gens such as OMP or LPS. These tests, some of which use
mixed antigens containing both OMP and LPS or anti-
gens from several serotypes, thus far appear to lack speci-
ficity and sensitivity for individual-animal diagnosis but
are useful for herd screening (Baum et al. 1996). A mixed-
ELISA test using meat juice at slaughter to detect anti-
body to a broad range of serotypes has been useful in cat-
egorizing the level of salmonella infection in herds in
Denmark (Nielsen et al. 1995; Mousing et al. 1997).
Septicemic Salmonellosis
This form of disease, usually caused by S. choleraesuis, oc-
curs mainly in weaned pigs less than 5 months of age but
may be seen occasionally in market swine, suckling
piglets, or adult breeding stock either as a septicemia or
as a cause of abortion.
CLINICAL SIGNS. Pigs ill with S. choleraesuis are in-
appetent, lethargic, febrile with temperatures of
105–107˚F (40.5–41.6˚C) and may have a shallow, moist
cough with slight expiratory dyspnea. Icterus may be ap-
parent. The first evidence of disease may be finding pigs
reluctant to move, huddled in the corner of a pen, or
even dead, with cyanosis of extremities and abdomens.
Diarrhea is not usually a feature of septicemic salmonel-
losis until the third or fourth day of disease, when watery
yellow feces may be seen. In most outbreaks, the case fa-
tality rate is high; morbidity is variable but is usually less
than 10%. Outbreaks are frequently associated with
stressful situations. The duration of the disease in indi-
542 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
vidual pigs, as well as the duration and severity of each
epizootic, is unpredictable but will be prolonged without
successful intervention. Evaluation of therapeutic regi-
mens in naturally occurring outbreaks is difficult, mak-
ing response to therapy a poor diagnostic criterion. Dis-
ease spread is by ingestion of contaminated feces or
nasopharyngeal secretions, with an incubation period
ranging from 2 days to at least several weeks. Surviving
pigs may remain carriers and fecal shedders for at least
12 weeks.
GROSS LESIONS. Lesions at necropsy include cyano-
sis of ears, feet, tail, and ventral abdominal skin; conges-
tion progressing to infarction of gastric fundic mucosa;
splenomegaly with less severe hepatomegaly; and moist,
swollen gastrohepatic and mesenteric lymph nodes.
Lungs are firm and resilient, diffusely congested, often
with interlobular edema and perhaps hemorrhage; cran-
ioventral bronchopneumonia is not uncommon. Icterus
can be severe, although not consistently present (Fig.
39.1). An inconsistent, subtle lesion is miliary, random
white foci of necrosis in the liver. In pigs surviving the
first few days of disease there may be serous to necrotic
enterocolitis. The features of the intestinal lesion are de-
scribed more fully in the section on salmonella entero-
colitis. Petechial hemorrhages, when present, are usually
best seen in the renal cortex or on the epicardium.
MICROSCOPIC LESIONS. The most diagnostic le-
sion of systemic salmonellosis is the presence of paraty-
39.1. Splenomegaly, hepatomegaly, and swollen mesenteric lymph nodes from S. choleraesuis
infection.
phoid nodules in the liver. These are clusters of histio-
cytes amid foci of acute coagulative hepatocellular necro-
sis, corresponding to the white foci seen grossly. These
lesions are often present (Lawson and Dow 1966) and
unique for this disease, although other agents can pro-
duce suppurative or necrotic foci in liver. Other lesions
typical of salmonellosis include fibrinoid thrombi in
venules of gastric mucosa, in cyanotic skin, in glomeru-
lar capillaries, and less regularly in pulmonary vessels.
There is hyperplasia of reticular cells of spleen and
lymph nodes as well as generalized swelling of endothe-
lial cells and histiocytes typical of gram-negative sepsis.
A similar diffuse histiocytic interstitial pneumonia is pre-
sent in lung. A complete discussion of the pathology of
septicemic salmonellosis can be found in Lawson and
Dow 1966 and Jubb et al. 1993.
DIAGNOSIS. The diagnosis of septicemic salmonel-
losis cannot be made on the basis of clinical signs alone,
which are similar to those of other causes of septicemia
in pigs, particularly Erysipelothrix rhusiopathiae, Strep-
tococcus suis, Actinobacillus suis, or death due to classical
swine fever or Actinobacillus pleuropneumoniae. Gross le-
sions of splenomegaly, hepatomegaly, lymphadenopa-
thy, interstitial pneumonia, or focal hepatic necrosis are
very suggestive of septicemic salmonellosis, but are not
seen in every case. In most situations, definitive diagno-
sis requires the isolation of large numbers of salmonel-
lae from tissues of affected pigs, almost invariably S.
choleraesuis var. kunzendorf. Samples of lung, liver, or
 CHAPTER 39 SALMONELLOSIS Schwartz
spleen often yield pure cultures of the organism on bril-
liant green, bismuth sulfite, blood agar, or MacConkey
agar. Enrichment techniques are seldom required unless
the organs have been contaminated by feces or careless
handling or have autolysis, in which case tetrathionate
broth at 42–43˚C is the enrichment medium of choice.
Selenite broth is inhibitory for S. choleraesuis and should
be avoided (Edwards and Ewing 1972). Attempts to iso-
late salmonellae from animals that have received antimi-
crobial therapy are often unrewarding. Intestine or feces
are not reliable specimens for isolation of the organism
in pigs with acute septicemia. Differential diagnosis
must include agents associated with the particular sys-
tems affected, including those that may cause sep-
ticemia, pneumonia, hepatitis, encephalitis, or entero-
colitis (Schwartz 1991).
Salmonella Enterocolitis
Salmonellosis manifested as enterocolitis is most fre-
quent in pigs from weaning to about 4 months of age.
Disease may be acute or chronic and can usually be as-
cribed to S. typhimurium (including variety copenhagen)
or, less frequently, to S. choleraesuis. Although isolation
of other serotypes of salmonellae from pigs with diar-
rhea occurs with some frequency, implication of
serotypes other than S. choleraesuis, S. typhimurium, and
perhaps S. heidelberg as primary pathogens should be
with caution.
CLINICAL SIGNS. The initial clinical sign is watery yel-
low diarrhea, initially without blood or mucus. The dis-
ease may spread rapidly to involve most pigs in a pen
within a few days. The initial diarrhea in an individual
pig usually lasts 3–7 days, but it typically may recur for
second and third bouts, giving the impression of a wax-
ing and waning diarrheal disease of several weeks’ dura-
tion. Blood may appear sporadically in the feces but
543
rarely with the profuseness typical of swine dysentery or
hemorrhagic porcine proliferative enteropathy (PPE).
Affected pigs are febrile, have decreased feed intake, and
are dehydrated, paralleling the severity and duration of
the diarrhea. Mortality usually is low and occurs only af-
ter several days of diarrhea, presumably as the result of
hypokalemia and dehydration. Most pigs make complete
clinical recovery but a portion may remain as carriers
and intermittent shedders for at least 5 months. A few
pigs may remain unthrifty and, occasionally, may devel-
op rectal strictures.
GROSS LESIONS. In pigs that have died of diarrhea,
the major lesion is focal or diffuse necrotic enteritis, col-
itis, or typhlitis. The lesion is seen as adherent gray-yel-
low debris on the red, roughened mucosal surface of an
edematous spiral colon, cecum, or ileum (Fig. 39.2).
Colon and cecal contents are bile stained and scant, often
with black or sandlike gritty material. Mesenteric lymph
nodes, especially ileocecal nodes, are greatly enlarged
and moist. The gross lesion may extend to involve the de-
scending colon and rectum. The necrosis may be seen as
sharply delineated button ulcers, particularly in resolv-
ing lesions. Necrotic ileitis has historically been attrib-
uted to several agents, including Salmonella, but in con-
firmed cases of salmonellosis, ileal involvement usually
is seen as reddening and slight roughening of the mu-
cosa, suggesting mild superficial necrosis. Salmonellae
associated with necrotic enteritis may be a sequel to PPE.
Lesions of septicemia may be present in those cases in-
volving S. choleraesuis. In cases of S. typhimurium entero-
colitis, the liver and spleen are not enlarged except by
terminal congestion.
MICROSCOPIC LESIONS. The typical enteric lesion
is necrosis of cryptal and surface enterocytes that varies
from focal to diffuse. The lamina propria and submucosa
39.2. Coalescing colonic ulcers
from S. typhimurium infection.
544 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
contain numerous macrophages and moderate numbers
of lymphocytes; neutrophils are numerous only in the
very early lesions. Thrombi containing fibrin, platelets,
and leukocytes are numerous (Fig. 39.3). The necrosis
frequently extends to involve muscularis mucosa, sub-
mucosa, and lymphoid follicles. Balantidium coli is com-
monly present in necrotic debris of chronic cases. In the
ileum, necrosis is usually quite superficial and is often
seen as villous atrophy. The Peyer’s patches may be
necrotic in acute disease, but in pigs dying of the natu-
rally occurring disease, lymphoid hypertrophy or even
regenerative hyperplasia is more common. The liver may
contain paratyphoid nodules but not with the consisten-
cy or the necrosis usually seen in the septicemic disease.
A more complete discussion of the pathology can be
found in Wilcock et al. 1976, Reed et al. 1986, and Jubb
et al. 1993.
DIAGNOSIS. The differential diagnosis of diarrhea in
weaned pigs must include salmonellosis, swine dysen-
tery, and PPE due to Lawsonia intracellularis. Other viral,
bacterial, or parasitic diseases capable of causing diar-
rhea include rotaviral and coronaviral enteritis, post-
weaning colibacillosis, trichuriasis, and coccidiosis. Sal-
monellosis concurrently present with other diseases is
not uncommon.
Typical acute swine dysentery is distinguished from
salmonellosis on the basis of the mucoid and bloody di-
arrhea in otherwise alert swine with dysentery, contrast-
ed with depression and profuse yellow diarrhea of sal-
monellosis. PPE may be seen as acute intestinal
hemorrhage or acute to chronic diarrhea with mucosal
proliferation or necrosis. Differentiation among the
three diseases at necropsy is primarily by recognition of
differences in lesion distribution rather than by differ-
ences in character. Salmonellosis is usually in colon and
occasionally small intestine, may be focal, and always in-
39.3. Histological section show-
ing deep colonic ulceration and
inflammation from S. typhimuri-
um infection.
volves marked mesenteric lymphadenopathy. The lesion
of swine dysentery is diffuse, shallow, and restricted to
large intestine; lymph node enlargement is absent or
mild. In PPE ileal involvement usually overshadows the
milder colonic lesions, and the mucosa underlying the
necrotic membrane is markedly hyperplastic (Table
39.2). Whipworms (Trichuris suis) may also cause diffuse
mucohemorrhagic colitis.
The diagnosis of salmonellosis is confirmed by mi-
crobiological and histological examination. The wide dis-
tribution of environmental salmonellae makes isolation
alone unreliable for disease diagnosis, and a positive iso-
lation should always be supported by appropriate lesions
before a diagnosis of salmonellosis is made. A pool of
ileum and ileocecal lymph node should enable detection
of virtually all active or recently recovered cases, al-
though tissues such as tonsil or cecal wall will usually
yield positive cultures as well (Wilcock et al. 1976; Wood
et al. 1989). From live animals, large (10 g) aliquots of fe-
ces or pharyngeal tonsil scrapings are preferable to rectal
swabs for isolation, with tetrathionate enrichment the
method of choice.
Other Syndromes
Salmonellae are occasionally involved in disease out-
breaks in which the clinical signs may not suggest salmo-
nellae as the etiologic diagnosis. Outbreaks of neurolog-
ic disease resembling classical swine fever or
pseudorabies have been reported (Wilcock and Olander
1978), and brain lesions sometimes occur with sep-
ticemic salmonellosis. The lesion in the brain is necrotic
vasculitis and perivascular granulomatous lesions resem-
bling typical paratyphoid nodules (Fig. 39.4). Rectal
strictures in growing pigs have been ascribed to defective
healing of ulcerative proctitis caused by S. typhimurium
(Wilcock and Olander 1977a, b). The stricture reported-
ly represents fibrosis in an area of persistent ischemia,
 CHAPTER 39 SALMONELLOSIS Schwartz 545

Table 39.2. Differential diagnosis of enterocolitis in swine at necropsy

Extraintestinal
Condition Ileal Lesion Colonic Lesion Ileocecal Nodes Lesions
Salmonellosis Mild, usually no Focal to diffuse, Always enlarged Variable, gastric
pseudomembrane deep necrotic two to five infarction,
lesions times normal interstitial
pneumonitis,
miliary hepatic
necrosis
Swine dysentery Absent Superficial and Often normal, None except
usually diffuse slight gastric fundic
necrosis, blood enlargement infarction in
and/or mucus natural deaths
Porcine proliferative Varies from Milder than in the Variable with None
enteritis hemorrhagic to ileum, usually stage of disease
necrotic or only the
proliferative proximal spiral
colon

with the rectum predisposed because of a normally pre- TREATMENT

carious blood supply (Fig. 39.5).
Infection with the fastidious, swine-adapted serovar
S. typhisuis causes a relatively specific chronic syndrome
of diarrhea and wasting in which caseous lymphadenitis,
histiocytic interstitial pneumonia, or suppurative bron-
chopneumonia is added to the typical necrotic colitis
(Barnes and Bergeland 1968; Andrews 1976; Fenwick
and Olander 1987). In some pigs the intestinal lesions
may have healed, leaving the lymphoid and pulmonary
lesions to be distinguished from tuberculosis and infec-
tion with Arcanobacterium pyogenes (Barnes and Sorensen
1975).
With either septicemic or enteric salmonellosis, the goals
of treatment in an outbreak of salmonellosis are to min-
imize the severity of clinical disease, prevent spread of
infection and disease, and prevent recurrence of the dis-
ease in the herd. With salmonellosis the attainment of
these goals is particularly difficult. Both S. choleraesuis
and S. typhimurium are often resistant in vitro to many
antibacterial agents used in swine (Barnes and Sorensen
1975; Wilcock et al. 1976; Blackburn et al. 1984; Schultz
1989; Fales et al. 1990; Schwartz 1997a). During clinical
disease, the organism inhabits a protected intracellular

39.4. Histological section show-

ing vasculitis and perivascular
granulomatous inflammation in
the brain stem from S. cholerae-
suis encephalitis.
546 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
39.5. Rectal stricture at
necropsy.
niche inaccessible to many common antibacterials. The
use of various antibiotics to treat enteric salmonellosis is
widely advocated (Morehouse 1972; Barnes and
Sorensen 1975; Blood et al. 1979), but much of the in-
formation to support this recommendation has been tak-
en from trials designed to test the prophylactic efficacy of
drugs, not their therapeutic efficacy. Thus, pigs on med-
icated feed, when inoculated orally with salmonellae,
have the antibiotic already present in the gastrointestinal
tract to interact with the salmonellae, resulting in milder
disease because of what amounts to a decreased inocu-
lum. In the few trials designed specifically to test an-
tibacterial drug efficacy against clinical enteric salmonel-
losis, such therapy was considered to have little merit
(Heard et al. 1968; Gutzmann et al. 1976; Olson et al.
1977; Wilcock and Olander 1978). Although not thera-
peutic, oral medications may decrease efficiency of
transmission and have a prophylactic effect on pigs not
yet affected. Antimicrobials are ordinarily administered
at maximum permissible levels in feed or, preferably, wa-
ter. Ideally, the choice of antibacterial agent should be
based on in vitro susceptibility testing of isolates from
each outbreak. Since medication often must be initiated
before such results are available, choices must be based
on previous experience and results of controlled trials.
In contrast, vigorous therapy early in the course of
septicemia caused by S. choleraesuis has been reported to
significantly reduce the duration and severity of disease
(Jacks et al. 1981). In that report, therapy was initiated
after inoculation but prior to the onset of clinical signs.
Evaluation of efficacy under field conditions is difficult
because of the unpredictability of the disease and be-
cause husbandry changes often accompany the use of
antibacterials in an outbreak. Reports and practitioner
communications from the American Midwest, however,
suggest that visibly affected animals respond to aggres-
sive therapy with parenteral antimicrobials (Schwartz
1991). Mass medication of the population at risk to de-
crease severity of disease and transmission of salmonel-
lae is also widely practiced. The choice of an appropriate
antimicrobial is aided by antibiograms and previous
herd experience. In the absence of either, amikacin, gen-
tamicin, neomycin, apramycin, ceftiofur, and trimetho-
prim-sulfonamide are effective in vitro against most iso-
lates (Barnes and Sorensen 1975; Wilcock et al. 1976;
Mills and Kelly 1986; Schultz 1989; Evelsizer 1990; Fales
et al. 1990, Schwartz 1997b). Antiinflammatory agents
are sometimes administered to critically ill animals to
combat the effects of endotoxin (Schwartz and Daniels
1987; Schultz 1989; Evelsizer 1990).
Most salmonella antimicrobial resistance is plasmid-
mediated, and removal of selective pressure of an an-
timicrobial allows for reversion to susceptibility. Of con-
cern is the recent emergence of a S. typhimurium phage
type or definitive type 104 (DT 104), isolated primarily
from bovine and human populations, that has chromo-
somally integrated multiple antimicrobial resistance
(Low et al. 1997). This isolate has a higher morbidity and
mortality in humans than other S. typhimurium organ-
isms and is increasing in prevalence in human and
bovine populations. Carrier swine are generally asymp-
tomatic. Although evidence linking emergence of such
isolates to veterinary medical practices is generally lack-
ing, the impact will affect public health initiatives as well
as the availability of therapeutic agents for food-produc-
ing animals. It should be emphasized that salmonella
control programs that rely strictly on antimicrobials are
doomed to failure.
In addition to antimicrobial therapy, the successful
treatment of salmonellosis relies heavily on routine hus-
bandry procedures recommended for control of infec-
tious diseases. The diarrheic pig massively contaminates
its environment and is the single most important source
of infection for other pigs. Removal and isolation of sick
 CHAPTER 39 SALMONELLOSIS Schwartz
animals, minimizing exposure to infective material by
scrupulous pen sanitation, frequent cleaning of water
bowls, and restriction of animal or staff movement from
potentially contaminated to clean areas are necessary. Ef-
forts to modify management and environment to de-
crease stress and increase pig comfort are essential ad-
juncts to specific therapy.
PREVENTION
Prevention of infection of swine with salmonellae is not
currently possible. Infection does not necessarily result
in disease, and pigs may not sicken with disease until se-
verely stressed long after initial exposure. The control of
disease expression rests on efforts to minimize the expo-
sure dose and to maximize pig resistance. The carrier pig
and contaminated feed or environment are the most sig-
nificant sources of infection to pigs, and pigs are most
likely to develop disease during periods of stress or when
exposed to massive numbers of salmonellae. The com-
mingling and transport of weanling pigs from different
sources to finishing farms enhance activation of latent
carriers and ensure exposure of stressed pigs to salmo-
nellae (Allred 1972). The source of host-adapted S.
choleraesuis, which is rarely, if ever, isolated from feed or
feed ingredients, would seem to be limited to carrier pigs
and facilities previously contaminated with this
serotype. The fact that many outbreaks occur in facilities
with good sanitation suggests that other stresses proba-
bly contribute to occurrence of the disease. Management
practices that allow filling of grower and finishing rooms
with single-source and single-age pigs are beneficial.
Minimizing the variety of stresses often involved in acute
outbreaks requires constant attention to details of man-
agement and husbandry, including proper animal densi-
ty; dry, comfortable pens and temperatures; and ade-
quate ventilation. On farms with enzootic disease,
modifications to the facility and environment and imple-
mentation of management practices that emphasize all-
in/all-out production should precede a prophylactic
drug program. Antibiotics are probably useful as aids in
preventing occurrence of disease when used prophylacti-
cally, but their use will not prevent infection and when
relied upon for prevention of disease will eventually fail.
Nutritional approaches to prevent or alleviate swine
salmonellosis include feeding of propionic or other
volatile fatty acids, mannose, lactose, probiotics, and
heavy metals. Although all of these practices are based
on a sound theoretical basis and are reported to be suc-
cessful experimentally or in other species, evidence for
their efficacy in swine is lacking. Anecdotal reports sug-
gest acidification of rations or water to be of some bene-
fit.
As with other facultative intracellular bacteria, live
vaccines that stimulate cell-mediated immunity are the
most likely to be protective for salmonellae in swine. His-
547
torically, an attenuated live S. choleraesuis vaccine was
used widely in the United Kingdom for many years but
was withdrawn when S. choleraesuis infection decreased
in that country to negligible proportions. Recently, the
introduction of effective and safe modified live attenuat-
ed vaccines for S. choleraesuis has had a major impact on
the occurrence of systemic salmonellosis in North Amer-
ica. The isolates used in these vaccines are either natural-
ly occurring avirulent S. choleraesuis or are derived from
repeated passage through porcine neutrophils, the prod-
uct of which was demonstrated to have been cured of a
50 kb virulence plasmid necessary for intracellular sur-
vival (Roof et al. 1992b; Kramer et al. 1987, 1992). When
given at weaning, vaccine protected pigs for at least 20
weeks (Roof and Doitchinoff 1995) against homologous
serotypes, with some cross-protection suggested with
heterologous serotypes.
Partial protection can be obtained with bacterins,
primarily because of the nonspecific mitogenic and im-
munostimulant effect of LPS (Fenwick et al. 1986). Killed
vaccines for S. typhimurium are safe, but the bulk of the
evidence suggests that they have little efficacy in prevent-
ing disease following strong challenge because resistance
to disease rests primarily on cell-mediated immunity
(Collins 1974; Davies and Kotlarski 1976). Extrapolation
of information from experience in humans (Hornick et
al. 1970; Welliver and Ogra 1978) and calves (Bairey
1978) suggests, however, that use of a potent killed vac-
cine may increase the dose necessary to cause disease and
may offer some protection from septicemic salmonel-
losis, in which humoral immunity may play a role.
Monitoring herds for salmonellae has not been com-
monly practiced. The detection of carrier animals is dif-
ficult because of the unpredictability of fecal shedding.
The detection of salmonellae by bacterial culture of feces
and tonsils of diarrheic pigs in the nursery would likely
be the most rewarding for identification of infected
herds. However, even repeated negative fecal or tonsilar
cultures do not guarantee that a herd or individual is not
a salmonella carrier and thus a potential shedder. The
use of salmonella serology can determine if an animal
has had previous exposure to salmonellae, but this has
little relevance to the carrier status or to the probability
of shedding. Food safety concerns have stimulated re-
newed interest in serology as a method to determine the
salmonella infection status of groups of market swine.
This technology offers the possibility of sensitive and
specific methods to identify infected herds, but it is not
yet useful for determining the infection status of individ-
ual pigs.
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 Spirochetal Diarrhea/Porcine
40 Intestinal Spirochetosis
D. J. Hampson and D. J. Trott
The term “spirochetal diarrhea” has been used to de-
scribe a colitis of growing pigs associated with infection
with a weakly hemolytic intestinal spirochete distinct
from Serpulina hyodysenteriae (the agent of swine dysen-
tery) (Taylor 1980, 1992). The causal agent in the original
study of this condition (Taylor et al. 1980) recently has
been shown to be a distinct species of spirochete, now of-
ficially named Serpulina pilosicoli (Trott et al. 1996e). S.
pilosicoli previously has been described in the literature
as “Anguillina coli” (Lee et al. 1993), “Serpulina coli”
(Duhamel et al. 1993a), and group IV weakly hemolytic
intestinal spirochetes (Fellström and Gunnarsson
1994).
Infection with S. pilosicoli is characterized by a mild
to moderate typhlocolitis resulting in the passage of wa-
tery to mucoid feces and consequently loss of condition
and reduced growth rate. The most striking histological
feature of the condition is the presence of large numbers
of intestinal spirochetes attached by one cell end to the
surface of the colonic epithelium. This characteristic at-
tachment also has been observed in humans (Lee and
Hampson 1994), primates (Duhamel et al. 1996), dogs
(Duhamel et al. 1995b), chickens (McLaren et al. 1997),
and ducks (Trott et al. 1996a).
Prior to the classification of S. pilosicoli and its recog-
nition as a cause of diarrhea in the pig and other host
species, the attachment of intestinal spirochetes by one
end to the colonic epithelium of humans was referred to
as “intestinal spirochetosis” (Harland and Lee 1967). For
this reason, when S. pilosicoli was named, we used the
term “porcine intestinal spirochetosis” (PIS) rather than
“spirochetal diarrhea” to describe the disease it caused in
pigs (Trott et al. 1996e). In North America the infection
also has been called “porcine colonic spirochetosis” (Gi-
rard et al. 1995), but the preferred term “porcine intesti-
nal spirochetosis” will be used for the condition in the re-
mainder of this chapter.
PIS was first described by Taylor and coworkers
(1980), who challenged experimental pigs with a weakly
beta-hemolytic strain of intestinal spirochete
(P43/6/78), inducing a colitis associated with mucoid di-
arrhea containing flecks of blood. This strain initially
Recently the genus name Brachyspira has been suggested for Serpulina
hyodysenteriae, Serpulina innocens, and Serpulina pilosicoli.
was thought to be S. innocens but is now recognized as
the type strain of S. pilosicoli. The condition has since
been experimentally reproduced in pigs on a number of
occasions using other strains of S. pilosicoli (Andrews
and Hoffman 1982; Thompson et al. 1996; Trott et al.
1996c). PIS is now increasingly becoming recognized as a
major cause of colitis in growing pigs, particularly since
the adoption of more intensive production strategies
that have limited other major intestinal diseases such as
salmonellosis and swine dysentery (Duhamel 1996). It is
likely that at least some of the cases of “nonspecific coli-
tis” reported in the United Kingdom may have been
caused by S. pilosicoli, although a noninfectious, diet-re-
sponsive colitis also does exist (Wood 1991). PIS has
been reported in most major pig-producing countries,
including the United Kingdom (Taylor et al. 1980), Cana-
da (Girard and Higgins 1989; Girard et al. 1995; Jacques
et al. 1989; Spearman et al. 1988), Australia (Hampson
1991; Hampson and Trott 1995), the United States
(Duhamel et al. 1993b; Ramanathan et al. 1993), Sweden
(Fellström et al. 1996), and Denmark (Møller et al.
1996). Much of the research concerning PIS has only
been undertaken recently, and many important aspects
of the disease are still poorly understood, including
pathogenicity, host immunity, and detailed epidemiolo-
gy.
ETIOLOGY
Serpulina pilosicoli takes its name from the histological
appearance of PIS, where the end-on attachment of
spirochetes to the colonic epithelium resembles a hairy
covering on the surface of the colon (Serpulina pilosicoli is
Latin for “little serpent of the hairy colon”) (Trott et al.
1996e). S. pilosicoli has a characteristic spirochete mor-
phology and an appearance similar to other species in
the genus Serpulina, except that it is generally shorter
(6–10 µm in length) and thinner (0.25–0.30 µm in
width), has fewer periplasmic flagella (4–7 attached at
each cell end), and has pointed, instead of rounded, ends
(Fig. 40.1). These differences can only be confirmed by
electron microscopy; however, using phase contrast mi-
croscopy, S. pilosicoli cells generally appear thinner and
shorter than cells of the other species of Serpulina. S. pi-
losicoli grows as a thin streak of weak beta-hemolysis on
trypticase soy blood agar and is cultured under the same
553
554 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
conditions as those described for S. hyodysenteriae, except
that it may take up to 6 days for hemolysis to appear, and
the inclusion of additional antibiotics (rifampicin
and spiramycin) normally recommended for the isola-
tion of S. hyodysenteriae may inhibit the growth of the
more sensitive organism (Trott et al. 1996d). Slicing the
agar prior to primary inoculation, as reported for S.
hyodysenteriae by Olson (1996), may help improve the re-
covery of S. pilosicoli free of other contaminating organ-
isms.
The taxonomy of the porcine intestinal spirochetes is
a rapidly developing field (Hampson and Stanton 1997),
and in addition to S. innocens and S. pilosicoli, two new
species of weakly beta-hemolytic spirochete have been
formally proposed: Serpulina intermedia and Serpulina
murdochii (Stanton et al. 1997). All four species of weak-
ly hemolytic intestinal spirochete have a similar appear-
ance on blood agar and can only be differentiated from
one another by biochemical and genetic typing tech-
niques. S. innocens, S. intermedia, and S. murdochii have
never been shown to cause disease in experimentally in-
fected conventional pigs and are generally considered to
be nonpathogens (Hudson and Alexander 1976; Kinyon
40.1. (A) Electron micrograph of
whole cell of P43/6/78T. Marker
bar = 0.5 µm. (B) Electron micro-
graph of magnified cell end of
Serpulina pilosicoli strain
P43/6/78T showing pointed tip,
five periplasmic flagella, and
insertion disks. Marker bar = 0.1
µm.
B
et al. 1977; Lee et al. 1993). However, strains of S. inter-
media have been shown to be pathogens in commercial
chickens (McLaren et al. 1997), have caused lesions when
inoculated into isolated porcine colonic loops (Binek and
Szynkiewicz 1984), and on rare occasions have been as-
sociated with diarrhea in pigs in the field (Fellström and
Gunnarsson 1995). Additionally, some strains of S. inno-
cens isolated from pigs with diarrhea have been shown to
cause diarrhea and lesions when inoculated into gnoto-
biotic pigs (Neef et al. 1994). The occurrence of colitis
and diarrhea in pigs colonized by S. intermedia has previ-
ously been termed “spirochetal colitis” (Hampson and
Trott 1995; Taylor and Trott 1997). Little is known about
this condition; however, it appears to be much less fre-
quently encountered than PIS and therefore will only be
mentioned briefly as a differential diagnosis.
EPIDEMIOLOGY
The detailed epidemiology of PIS has not been fully de-
termined. Infection is believed to occur by the fecal/oral
route, and disease in nonimmune herds may be facilitat-
ed by the introduction of carrier pigs. Infection has been
 CHAPTER 40 SPIROCHETAL DIARRHEA
demonstrated in specific-pathogen-free (SPF) herds free
of swine dysentery (Atyeo et al. 1996c). The organism is
believed to survive in feces for a length of time similar to
that previously demonstrated for S. hyodysenteriae (Chia
and Taylor 1978). Using culture techniques, the preva-
lence in individual piggeries has been demonstrated to
range from 5% (Atyeo et al. 1996c) to 37.5% (Duhamel
1996). However, these figures are often influenced by the
concurrent administration of antibiotics, the age of the
pigs examined, the limits of detection using culture, and
the degree of contamination with other fecal organisms
which may inhibit the growth of the spirochetes. In Swe-
den, S. pilosicoli was isolated from 6 of 8 herds with
diarrhea but only from 1 of 11 herds with no clinical
signs (Fellström et al. 1996). S. pilosicoli may be isolated
from pigs during any period of the growing stage, but
infection is most common and more severe in weaner
and grower pigs. Specific serologic tests are not yet
available for determining antibody titers in exposed ani-
mals.
Unlike the situation with S. hyodysenteriae, where in-
fection throughout a piggery is usually caused by a single
strain of the organism, S. pilosicoli is a genetically diverse
species (Atyeo et al. 1996a; Lee and Hampson 1994), and
often more than one type of strain of the organism may
be isolated from a single pen of pigs (Atyeo et al. 1996c).
The demonstration of multiple strains within piggeries
may help explain the common recurrence of PIS in con-
valescent animals or in those that have been treated with
antimicrobials.
Unlike S. hyodysenteriae, strains of S. pilosicoli colo-
nize a range of animal species (Atyeo et al. 1996a). Typi-
cal clinical signs and lesions associated with PIS have
been demonstrated in all host species, including hu-
mans. Isolates from pigs, dogs, and humans have been
shown to be genetically closely related (Lee and Hamp-
son 1994), but direct evidence for zoonotic transmission
has only been demonstrated between dogs and humans
(Trott et al. 1996b). Nevertheless, human strains of S. pi-
losicoli have been shown to cause disease when inoculat-
ed into conventional pigs (Trott et al. 1996c), and the po-
tential for cross-transmission between humans and pigs
cannot be discounted. Because humans colonized with S.
pilosicoli tend to be either immunocompromised or live
in developing communities, healthy pig industry work-
ers are unlikely to be at risk of developing disease from
pigs infected with PIS.
Other host species, particularly birds, may represent
continual sources of transmission for pigs. Although ro-
dents have been demonstrated to be carriers of S. hyo-
dysenteriae and may be colonized with weakly beta-he-
molytic spirochetes, all other rodent isolates examined
by us to date have been shown to be members of the non-
pathogenic species S. murdochii (Trott et al. 1996a). De-
spite this, strain P43/6/78 has been shown to colonize
experimentally infected mice, thus demonstrating poten-
tial for mice to act as carriers (Sacco et al. 1996).
Hampson, Trott 555
PATHOGENESIS
The pathogenesis of PIS is not well understood but is
thought to differ from swine dysentery in several impor-
tant ways. Cells of S. pilosicoli are not attracted to porcine
mucin in the same way as are virulent strains of S. hyo-
dysenteriae (Milner and Sellwood 1994), and infection is
often associated with the presence of large numbers of
spirochetes attached by one cell end to the luminal sur-
face of colonic and cecal epithelial cells. Additionally, the
colitis associated with PIS is much less severe than swine
dysentery and only resembles the very early stages of
that disease.
Oral infection is followed by colonization of the
colonic mucosa, and the organism can be demonstrated
in fecal swabs within 2–7 days postinoculation; however,
the incubation period may range up to 20 days. In the ini-
tial stages of infection, S. pilosicoli cells adhere in large
numbers to the surface of cecal and colonic epithelial
cells, resulting in effacement of the microvilli and dis-
ruption of the terminal web cytoplasm. Attachment on-
ly occurs to mature apical enterocytes on the villous tips,
and spirochetes do not attach to immature cells within
intestinal crypts (Trott et al. 1995). Epithelial cell degen-
eration results in an increase in the crypt cell mitotic
rate, crypt elongation, and the production of an imma-
ture epithelium consisting of squamous or cuboidal
cells. Necrosis of the epithelium is evident grossly as
small adherent nodules on the surface of the mucosa
(Fig. 40.2).
S. pilosicoli cells have been observed within dilated in-
testinal crypts (Trott et al. 1996c), invading through tight
junctions between epithelial cells, within goblet cells
(Thompson et al. 1996), and within the lamina propria.
The presence of S. pilosicoli within crypts and the lamina
propria is associated with neutrophilic exocytosis (crypt
abscesses) and colitis characterized by edema, with a
mixed infiltrate of neutrophils and lymphocytes within
the mucosa, lamina propria, and occasionally muscularis
layers. In chronic infections, neutrophils may be absent
and the lamina propria is infiltrated with monocytes and
lymphocytes (Duhamel 1996). Invasion has been ob-
served both concurrent with and independent of attach-
ment of spirochete cells to the epithelium. The damaged
mucosa is often colonized by large numbers of Balantid-
ium coli cells. S. pilosicoli has been isolated from the
blood of humans with severe clinical disease or impaired
immunity (Trott et al. 1997). Although a systemic spiro-
chetemia has not been directly observed in pigs, its oc-
currence cannot be excluded. Occasionally some animals
are found dead with the only lesions being suggestive of
mucohemorrhagic colitis caused by S. pilosicoli. To date,
there has been no reported attempt to culture the blood
of such animals using media appropriate for the isola-
tion of S. pilosicoli.
Colonization of the epithelium, local invasion, and
subsequent colitis combine to cause an increase in the
556 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
40.2. Colonic mucosa of a
chronic case of porcine intestinal
spirochetosis. Note the isolated
areas of necrotic material.
water content of the cecal and colonic digesta, together
with excess mucus production and occasionally flecks of
blood. The resulting damaged or immature epithelium
may result in a reduction in surface area of the colon, re-
duced absorption of volatile fatty acids, and consequent-
ly poor feed conversion and weight gain (Duhamel
1996).
The host immune mechanisms that are directed
against S. pilosicoli have not been determined. Circulat-
ing antibodies have been demonstrated in convalescent
experimentally infected pigs, but the immune response
has not be characterized in detail (Taylor et al. 1980).
Gnotobiotic pigs (Neef et al. 1994), day-old chicks
(Adachi and Minato 1986; Duhamel et al. 1995a; Trott et
al. 1995), and mice (Sacco et al. 1996) have successfully
been used as models of experimental infection. In exper-
imental infections of conventional pigs, only a small pro-
portion (33%) of challenged animals became colonized
and developed disease (Trott et al. 1996c). Adachi et al.
(1982) infected pigs with weakly hemolytic spirochetes
(most likely to be S. pilosicoli) and demonstrated that
those animals with the highest titers of complement-fix-
ing antibody shed the least number of organisms in their
feces.
CLINICAL SIGNS
PIS has a clinical presentation similar to other forms of
colitis and to the early stages of swine dysentery. It is
commonly seen in the immediate postweaning period
and in recently mixed growers placed on a new ration but
can be observed in finishers and occasionally pregnant
sows and recently introduced breeding stock. PIS may af-
fect groups of pigs of the same age in a unit or be present
in pigs of mixed age within a house. It is not uncommon
to observe various manifestations of PIS in weaners,
growers, and finishers at the same piggery. Because of
the large functional capacity of the cecum and colon, not
all infected animals will develop diarrhea; however, sub-
clinical infections will still result in depressed growth
rates.
The first clinical signs that tend to be observed are
hollowing of the flanks and the passage of loose, sticky
feces that adhere to the pen floor. The consistency of the
feces then changes to that of wet cement or porridge and
may take on a glistening appearance. These may be the
only clinical signs observed in finishers. Weaner and
grower pigs usually develop a watery to mucoid diarrhea
which is green or brown in color and occasionally char-
acterized by thick tags of mucus and flecks of blood. Di-
arrhea is usually self-limiting and lasts between 2 and 14
days, although some animals may relapse and develop
clinical signs after convalescence or treatment.
Affected pigs appear ill-thrifty, have fecal staining of
the perineum, have a tucked-up appearance, and are
sometimes febrile, but usually continue to eat. Pigs with
PIS may have concurrent illness such as pneumonia, and
pigs with other, more severe gastrointestinal diseases
such as swine dysentery, salmonellosis, or intestinal
adenopathy may also be colonized with S. pilosicoli. Pigs
with uncomplicated PIS that develop loose feces may not
show any reduction in liveweight gain, but the condition
is generally characterized by significant loss of condi-
tion, decreased feed conversion, and delays in reaching
market weight. Mortality is generally not a feature of
PIS.
LESIONS
Gross Lesions
Gross lesions associated with PIS are limited to the ce-
cum and colon and may be very subtle, particularly in
 CHAPTER 40 SPIROCHETAL DIARRHEA
the early stages of the disease. Postmortem examina-
tion soon after the onset of clinical signs often reveals
a flaccid, fluid-filled cecum and colon with an edema-
tous serosal surface and enlarged mesenteric and
colonic lymph nodes. The contents are abundant and
watery green or occasionally yellow and frothy. The
severity and clinical stage of the disease are reflected
in the appearance of the mucosal surface. There may
be few changes in the early stages of the disease, al-
though mild congestion and hyperemia may be ap-
parent, with occasional ulcerations and necrotic foci.
Inflammation in the later stages may result in multi-
focal ulcerative or mucohemorrhagic colitis, but it is
never as severe as that observed in swine dysentery.
The mucosa becomes thickened, and local ecchymot-
Hampson, Trott 557
ic or petechial hemorrhages may be apparent on the sur-
face. In chronic cases and in resolving lesions, the hem-
orrhages are covered by small tags of adherent fibrin,
necrotic material, and digesta, which appear as conical
scales adherent on the surface of the mucosa (Fig. 40.2).
This material may be dislodged by rinsing and can be
found as a deposit after decanting the washings.
Microscopic Lesions
PIS has been described as a catarrhal, multifocal, erosive
or ulcerative colitis (Andrews and Hoffman 1982; Girard
and Higgins 1989). Lesions are generally confined to the
mucosa and submucosa but may extend into the muscu-
laris. The mucosa is thickened, edematous, and occa-
sionally hyperemic and is characterized by the presence
40.3. Photomicrograph of
hematoxylin eosin–stained section
of porcine colon infected with a
Serpulina pilosicoli strain.
Neutrophilic exocytosis (crypt
abscess material) is present in
dilated intestinal crypts (arrows).
The lamina propria is diffusely
infiltrated with inflammatory
cells. Marker bar = 37 µm.
40.4. Photomicro-
graph of the colonic
epithelium. Note false
brush border of spiro-
chetes (arrow) (×400).
558 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
of dilated, elongated intestinal crypts filled with mucus,
cellular debris, and degenerate inflammatory cells gener-
ally referred to as crypt abscesses (Fig. 40.3). Subepithe-
lial capillary dilatation is a noteworthy finding. The
crypt cell mitotic rate is increased, often with immature,
cuboidal, or squamous epithelium present on the tips of
the villi. Where columnar epithelium is still present on
the surface of the colon, it is often covered by a dark
fringe of spirochetes attached by one cell end (Fig. 40.4).
The use of silver stains will confirm the presence of
spirochete-shaped bacteria attached to the surface of
colonic enterocytes, within dilated intestinal crypts, and
occasionally within the lamina propria. Balantidium coli
bacteria are often seen in large numbers on the surface of
the colon (Taylor et al. 1980; Trott et al. 1996c).
Electron Microscopy
Using transmission electron microscopy, polar-attached
spirochetes with 4–7 periplasmic flagella attached to
each cell end are observed invaginated into the terminal
web cytoplasm, effacing microvilli and disrupting micro-
filaments without penetration of the host cell plas-
malemma (Fig. 40.5). Scanning electron microscopy re-
veals the adherent spirochetes as a patchy fringe on the
surface of colonic epithelial cells. Spirochetes also may
be observed invading between epithelial cells in the ex-
trusion zone between adjacent crypt units (Duhamel
1996).
40.5. Transmission electron
micrograph of porcine colon infect-
ed with a strain of Serpulina
pilosicoli. Note attachment of
large numbers of spirochetes to
the epithelium and disruption of
terminal web microfilaments
(arrow). Marker bar = 2 µm.
Bacteriology
Large numbers of spirochetes can be seen in wet smears
viewed by phase contrast microscopy or in fixed Gram-
stained smears. Swabs should be taken directly from the
colonic wall rather than collecting colonic contents.
DIAGNOSIS
A tentative diagnosis of PIS can be made when typical
clinical signs of mucoid diarrhea without blood and no
mortality are found in weaned pigs not previously re-
ceiving medication in the feed. The clinical signs of PIS
are difficult to differentiate from those associated with
the proliferative enteropathies caused by Lawsonia intra-
cellularis. Additionally, PIS may occur concurrently with
a number of gastrointestinal diseases, including prolifer-
ative enteritis, salmonellosis, postweaning colibacillosis,
swine dysentery, and trichuriasis. All of these should be
considered in the differential diagnosis of PIS, as well as
“nonspecific colitis,” an apparently dietary condition as-
sociated with a form of hypersensitivity to pelleted feed
(Connor 1992; Smith and Nelson 1987). Additionally,
Clostridium perfringens type A enterotoxemia (Taylor et
al. 1987) and Yersinia pseudotuberculosis infection (Neef
and Lysons 1994) must be considered as causes of colitis.
To obtain a diagnosis, postmortem examination of
several affected pigs, including routine histological and
bacteriological examination, should be undertaken. Fe-
 CHAPTER 40 SPIROCHETAL DIARRHEA
cal samples for culture for Serpulina spp. and other
pathogens also should be obtained from a cross section
of affected pigs. While waiting for confirmation of re-
sults, water medication should be initiated, as it may
take up to 2 weeks to obtain a definitive diagnosis from
culture. In histological sections from the cecum and par-
ticularly the colon, the presence of spirochetes attached
to the colonic mucosa is diagnostic for PIS but will not be
observed in every case of the disease. Other typical his-
tological lesions associated with PIS, including the
demonstration of spirochetes within intestinal crypts
and the lamina propria by silver staining or the demon-
stration of spirochetes in smears, should be confirmed
by the results of culture.
The four species of weakly beta-hemolytic spiro-
chetes can be differentiated from one another and from
S. hyodysenteriae using a number of biochemical tests
outlined in Table 40.1. Unfortunately, these tests require
the growth of pure cultures of Serpulina organisms in liq-
uid medium, a process which may take several weeks to
achieve, particularly if the initial plates are heavily con-
taminated with other fecal flora. Consequently, the tests
are currently performed only in several specialized labo-
ratories. For S. pilosicoli, examination of ultrastructural
morphology under the transmission electron micro-
scope, hippurate hydrolysis, metabolism of ribose, and
lack of beta-glucosidase activity in the API-ZYM profile
are diagnostic (Fellström and Gunnarsson 1995; Trott et
al. 1996d).
A polymerase chain reaction (PCR) test based on a
unique 16S rRNA DNA sequence is completely specific
for S. pilosicoli (Park et al. 1995). Although not sensitive
enough for use directly on feces, the technique is more
sensitive than culture alone (Atyeo et al. 1996b). When
applied to DNA harvested from 4-day-old bacteriological
plates containing the organism, it can significantly re-
duce the time taken for a diagnosis, even if there is a
large amount of contamination with other fecal flora
(Atyeo et al. 1996b). A second PCR also based on the S.
pilosicoli 16S signature sequence but producing a slightly
smaller product has been reported but did not signifi-
cantly improve the sensitivity of the initial procedure
(Fellström et al. 1997).
Table 40.1. Differentiation of the five recognized groups of porcine intestinal spirochetes by their hemolysis
pattern on trypticase soy blood agar, biochemical reactions, and utilization of sugars
Test S. hyodysenteriae S. intermedia
Hemolysis strong weak
Indole + +
Hippurate − −
API-ZYM 1 1
d-ribose − −
Note: + = positive reaction; − = negative reaction; 1 = alpha-glucosidase positive, alpha-galactosidase negative; 2 = alpha-glucosidase
negative, alpha-galactosidase positive; 3 = alpha-glucosidase negative, alpha-galactosidase negative; 4 = variable reactions, including positive
reactions for both enzymes, beta-glucosidase negative.
Hampson, Trott 559
The four recognized species of weakly hemolytic in-
testinal spirochetes can be differentiated without the
need for culture by digestion of PCR-amplified 16S rRNA
DNA with restriction enzymes. Characteristic DNA frag-
ments produced are identified after separation by elec-
trophoresis (Stanton et al. 1997). An indirect fluorescent
antibody test using a monoclonal antibody (MAB) raised
against a specific outer-membrane protein of S. pilosicoli
also shows considerable potential for diagnostic use on
feces, and with suitable modification the MAB may be
applied to tissue sections for immunoperoxidase stain-
ing (Lee and Hampson 1995). There is significant sero-
logic cross-reactivity among the intestinal spirochetes,
and to date no specific tests are available to measure
serum antibody titers.
If weakly beta-hemolytic spirochetes distinct from S.
pilosicoli are cultured from pigs with colitis, spirochetal
colitis should be suspected, particularly if the organisms
are indole positive and have API-ZYM profiles consistent
with S. intermedia. Spirochetal colitis should respond to
treatment in a manner similar to PIS.
TREATMENT AND CONTROL
Treatment and control of PIS are largely modeled on
procedures developed for swine dysentery. No effective
vaccines have been produced to date. Affected pigs
should be treated by water or feed medication at similar
levels and lengths of time as recommended in Chapter
42 for the treatment of swine dysentery. Parenteral treat-
ment may sometimes be warranted for individual ani-
mals. A number of antimicrobials that are effective
against S. hyodysenteriae, including tiamulin, carbadox,
dimetridazole, lincomycin, and tylosin, have been shown
to have low minimum inhibitory concentration (MIC)
values when tested against S. pilosicoli isolates in vitro
(Trott et al. 1996d). Tetracyclines also have low MIC val-
ues, which suggests their effectiveness against S. pilosicoli
(Trott et al. 1996d). Olaquindox has been shown to have
MIC values of less than 1.0 µg/mL against S. pilosicoli
(group IV spirochetes), and the organism could not be
isolated from herds previously receiving olaquindox in
the feed at 100 ppm (Fellström et al. 1996). However, de-
S. innocens S. murdochii S. pilosicoli
weak weak weak
− − −
− − +
2 3 4
− − +
560 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
spite its preventive qualities, olaquindox is not suitable
as a therapeutic agent (Fellström et al. 1996): olaquindox
is insufficiently active; at the level required for effective-
ness, the pig would die.
Resistance to single antimicrobials or combinations
has been recorded in our laboratory. In the field, the oc-
currence of reinfection after medication has ceased is
common. Adjunctive therapy such as improved manage-
ment and pen hygiene has given inconsistent results
(Wilkinson and Wood 1987), whereas reducing the ener-
gy and protein content of the ration has often alleviated
the problem (Spearman et al. 1988; Wilkinson and
Wood 1987). It has been reported that the addition of
zinc oxide in the feed at 3 kg/tonne helps control PIS
(Love 1996). This method also has been effective in con-
trolling uncomplicated cases of “nonspecific colitis” (Ka-
vanagh 1992).
The methods described for the control of swine
dysentery in Chapter 42 may be effective at eliminating
PIS, but the severity of PIS generally does not warrant
such drastic procedures. Medicated early weaning, as
proposed by Alexander et al. (1980), and discussed else-
where for swine dysentery, is the only recorded practice
that has eliminated intestinal spirochetes from a group
of animals. Where PIS becomes endemic in a herd, regu-
lar periods of treatment with antimicrobials in the feed
or water may be required to prevent sudden increases in
morbidity due to recent introduction of nonimmune
pigs, change of diet, or other periods associated with
stress.
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 Streptococcal Diseases
41 R. Higgins and M. Gottschalk
Several streptococcal species can be found in tonsils, in-
testines, or feces of clinically healthy pigs, and some of
them are potential pathogens. Among species consid-
ered part of the intestinal microflora in swine, there are
Streptococcus intestinalis (Robinson et al. 1988), S. hyoin-
testinalis (Devriese et al. 1988), S. suis, S. alactolyticus,
and S. bovis (Devriese et al. 1994b). In tonsils, S. suis, S.
porcinus, and S. dysgalactiae are members of the mi-
croflora (Devriese et al. 1994b). Members of the genus
Enterococcus (formerly Streptococcus) such as E. faecalis, E.
faecium, E. durans, E. hirae, and E. cecorum are also pres-
ent in the intestinal microflora.
In this chapter, the different pathological conditions
associated with streptococci and enterococci are present-
ed. A particular emphasis was put on the infections
INFECTIONS CAUSED BY S. SUIS
ETIOLOGY AND PREVALENCE
New alpha-hemolytic streptococci from septicemic infec-
tions in pigs were first biochemically and serologically
characterized by de Moor between 1956 and 1963 as new
Lancefield groups R, S, RS, and T (de Moor 1963). In
England, Elliott (1966) suggested that de Moor’s group S
was similar to his PM Streptococcus and that both be-
longed to Lancefield’s group D; he proposed the name
Streptococcus suis capsular type 1. In 1975, Windsor and
Elliott isolated other porcine streptococci which corre-
sponded to de Moor’s group R and named them S. suis
type 2. Type 1 was associated with meningitis in baby
piglets, whereas type 2 occurred at any age. Isolates re-
acting with both antisera against types 1 and 2 were des-
ignated capsular type 1⁄2 (originally RS group). Isolations
of streptococci belonging to group T from tonsillar, vagi-
nal, and preputial swabs were reported by Clifton-
Hadley in 1984. The group T reference strain was desig-
nated S. suis capsular type 15 in 1989 (Gottschalk et al.
1989).
Between 1983 and 1995, a total of 32 new capsular
types were described, out of a total number of 35 strains
(Perch et al. 1983; Higgins et al. 1995). Reference strains
caused by S. suis because of their emergence in the swine
industry during the last decade. Efforts were made to
synthesize the more recent knowledge about the differ-
ent aspects of these infections, particularly pathogene-
sis, clinical signs, diagnosis, and prevention. Importance
was also given to the fact that S. suis is a zoonotic agent
with severe consequences, and that its presence in a wide
range of animal species and birds may influence the epi-
demiology and the control of the infection in swine.
Comments about infections caused by other streptococ-
ci, such as S. porcinus (groups E, P, U, and V), S. dysgalac-
tiae subsp. dysgalactiae (group C, formerly S. equisimilis,
and group L), and S. agalactiae, have been included, as
well as a discussion of diarrhea associated with entero-
cocci.
originated from diseased pigs except for capsular type
14, a human isolate, capsular types 17, 18, 19, and 21 iso-
lated from clinically healthy pigs, capsular types 20 and
31 from diseased calves, and type 33 from a diseased
lamb (Gottschalk et al. 1989; Higgins et al. 1995). The
designation of S. suis as a new bacterial species was made
official in 1987 by Kilpper-Balz and Schleifer. This
species appeared genetically distinct and displayed no
specific relationship with other streptococcal species ex-
amined (Bently et al. 1991). Genetic diversity among
members of the S. suis species is important (Hampson et
al. 1993; Harel et al. 1994), and this should be taken into
account in diagnosis, surveillance, and control of the dis-
ease.
Initial reports of S. suis infections were published by
Jansen and Van Dorssen in the Netherlands (1951) and
by Field et al. (1954) in England. Since then, S. suis has
been reported in all countries where the swine industry is
important, and for more than a decade, infections asso-
ciated with this microorganism have been observed in
both traditional and modern intensive swine operations.
In diseased pigs, capsular type 2 predominates in almost
all countries. In Scandinavia capsular type 7 predomi-
nated for several years (Perch et al. 1983; Sihvonen et al.
563
564 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
1988), but in the 1990s, capsular type 2 outnumbered
type 7 (J. P. Nielsen, pers. comm.—1997). In Japan, cap-
sular type 2 was also the most prevalent serotype (28%),
followed by capsular type 7 (11%) (Kataoka et al. 1993).
Most S. suis organisms isolated from diseased pigs be-
long to a limited number of capsular types, often those
between 1 and 8 (Galina et al. 1992; Higgins and
Gottschalk 1996; Hogg et al. 1996; Kataoka et al. 1993;
Prieto et al. 1994; Reams et al. 1996).
Some strains belonging to less common capsular
types have been associated with severe cases of infection.
S. suis capsular type 9 was associated with outbreaks of
septicemia, meningitis, and pneumonia in weaned pigs
(Orr et al. 1989; Gogolewski et al. 1990). In 1996,
MacLennan et al. reported the first isolation of serotype
14 in the United Kingdom. They indicated that although
capsular type 2 still predominated (62%), 25% of isolates
belonged to serotype 14, which affected piglets aged 2–4
weeks and caused arthritis, meningitis, and septicemia.
The same year, also in the United Kingdom, Heath et al.
(1996) reported the isolation of capsular type 14 in 22
farms with clinicopathological findings similar to those
associated with serotype 2.
Capsular type 2 can also be isolated from clinically
healthy pigs, but its prevalence may be low. British au-
thors reported that in four herds without any history or
clinical signs of the disease, two were negative for the
presence of type 2, one had a prevalence of 1.5%, and an-
other a prevalence of 20% (Clifton-Hadley et al. 1984).
This is in accordance with Canadian studies that demon-
strated the presence of this serotype in 12% of herds
without clinical signs of infection and in 4% of piglets in
these herds (Brisebois et al. 1990). Also, serotype 2 was
found in 8 out of 19 nurseries without clinical signs of
infection; in these herds, only 1.5% of piglets were carri-
ers in their nasal cavities, whereas capsular types 19 and
21 were found in 24% and 19% of the piglets, respective-
ly (Monter Flores et al. 1993).
Hogg et al. (1996) noted a higher prevalence of
serotypes 9–34 from nasal and vaginal swabs than from
tissues taken from diseased pigs. It is noteworthy that
several capsular types may be present in the same ani-
mal. In one study, 31% of pigs had only one serotype of
S. suis in their nasal cavities, 38% had two or three
serotypes, and 6% had more than four serotypes (Monter
Flores et al. 1993). Isolation of multiple serotypes also
has to be taken into consideration in diseased animals
(see the section on diagnosis).
EPIDEMIOLOGY
Natural Habitat
The natural habitat of S. suis is the upper respiratory
tract (particularly the tonsils and nasal cavities) and the
genital and alimentary tracts of pigs (Clifton-Hadley et
al. 1986b; Devriese et al. 1991; Robertson et al. 1991;
Hogg et al. 1996). S. suis is also increasingly isolated from
a wide range of animal species and birds, and this may
affect some epidemiological aspects of this infection (see
the section on infection in other animal species and
birds). Its presence in the environment is transitory (see
the next section).
Transmission
Transmission of the infection between herds usually oc-
curs by the movement of healthy carrier pigs. The intro-
duction of healthy carriers pigs (breeding gilts, boars,
weaners) into a noninfected herd usually results in the
subsequent onset of disease in weaners and/or growing
pigs in recipient herds. Sows presumably infect their own
piglets via the respiratory route (Clifton-Hadley et al.
1986b), but because S. suis is found in the genital and al-
imentary tracts, piglets are also exposed during the birth
process and while suckling (Robertson and Blackmore
1989a; Robertson et al. 1991; Dee et al. 1993). It appears
that although most weaned piglets carry S. suis strains,
only a few of them carry strains capable of inducing the
disease after weaning (Pijoan 1996).
S. suis also appears to be easily transmitted via
fomites (Robertson et al. 1991; Dee and Corey 1993). S.
suis types 1 and 2 were isolated from the feed troughs of
piglets and sows (Robertson et al. 1991). Enright et al.
(1987) demonstrated that flies can carry S. suis type 2 for
at least 5 days and can contaminate materials on which
they feed for at least 4 days. Thus, flies could spread in-
fection within farms and between farms. The importance
of other animal species or birds as reservoirs or vectors
of the infection has still to be determined. Carriage by
humans also seems possible (Sala et al. 1989).
Survival in the Environment
Studies of the survival of S. suis in the environment have
only been carried out with capsular type 2. This organ-
ism survived in water at 4˚C for 1–2 weeks. In experi-
mentally inoculated feces, it survived at 0˚C, 9˚C, and
22–25˚C for 104, 10, and 8 days, respectively, and in dust
for 54, 25, and 0 days, respectively. Thus, at a summer-
time or weaner-accommodation temperature of
22–25˚C, the organism could survive about 8 days in fe-
ces but less than 24 hours in dust (Clifton-Hadley and
Enright 1984). S. suis capsular type 2 was shown to sur-
vive in pig carcasses left rotting on farms. Survival time
was 6 weeks at 4˚C and 12 days at 22–25˚C, potentially
providing a source of infection for indirect spread by, for
example, birds, rats, mice, or dogs (Clifton-Hadley et al.
1986c).
With regard to the cleaning of infected pens, disin-
fectants and cleansers commonly used in piggeries can
kill S. suis type 2 in less than 1 minute, even at concen-
trations in distilled water less than those recommended
by the manufacturers (Clifton-Hadley and Enright 1984;
Robertson et al. 1991). The presence of dirt and organic
 CHAPTER 41 STREPTOCOCCAL DISEASES
material protects some organisms from the action of
chemical disinfectants, and hence, removal of surface
dirt from pens is an important part of the disinfection
procedure. S. suis type 2 has survived for up to 2 hours at
50˚C, but only 10 minutes at 60˚C. Hot water may be
used, but water from heated pressure washers cools
rapidly on pen surfaces and is usually below 50˚C. Thus,
its value is in diluting contaminating microorganisms
and washing away surface dirt rather than in killing by
heat (Clifton-Hadley and Enright 1984).
CLINICAL SIGNS AND LESIONS
Even when the pig carrier rate is near 100%, the incidence
of the disease varies from period to period and is usually
less than 5%. According to Clifton-Hadley et al. (1984),
affected animals are generally between 5 and 10 weeks of
age. In 1996, a report from the United States described
cases in pigs aged between 1 and 32 weeks, but 75% of
them were 16 weeks of age or less (Reams et al. 1996).
The earliest sign is usually a rise in rectal temperature
to as high as 42.5˚C. This may occur initially without any
other obvious signs. It is accompanied by a detectable
bacteremia or pronounced septicemia, which, if untreat-
ed, may persist for up to 3 weeks. During this period,
there is usually a fluctuating fever and variable degrees of
inappetence, depression, and shifting lameness (Clifton-
Hadley et al. 1984).
In peracute cases, pigs may be found dead with no
premonitory signs. Meningitis is the most striking fea-
ture and the one on which a presumptive diagnosis is
usually based. Early nervous signs include incoordina-
tion and adoption of unusual stances, which soon
progress to inability to stand, paddling, opisthotonus,
convulsions, and nystagmus. The eyes are often staring,
with reddening of mucous membranes (Clifton-Hadley
et al. 1986a). Septicemia, arthritis, and pneumonia are
less remarkable manifestations of the disease, and a ten-
tative diagnosis may be difficult to make. Among other
manifestations of S. suis infections, there are endocardi-
tis, rhinitis, abortions, and vaginitis (Sanford and Tilker
1982; Sihvonen et al. 1988). In North America, S. suis is,
by far, the infectious agent most frequently isolated from
cases of endocarditis in pigs. Affected pigs may die sud-
denly or show various levels of dyspnea, cyanosis, and
wasting.
In the United Kingdom, infections due to S. suis cap-
sular type 2 were primarily associated with septicemia
and meningitis in weaned pigs (Windsor and Elliott
1975). In North America, early reports indicated that S.
suis was predominantly isolated from cases of pneumo-
nia (Koehne et al. 1979; Sanford and Tilker 1982; Erick-
son et al. 1984). Years later, reports from the United
Kingdom mentioned septicemia, meningitis, and pol-
yarthritis, but rarely pneumonia (MacLennan et al. 1996;
Heath et al. 1996), whereas pulmonary lesions still pre-
Higgins, Gottschalk 565
dominated in North America (Reams et al. 1994, 1996;
Hogg et al. 1996). In the Netherlands, S. suis type 2 was
associated with pneumonia in 42% of the cases, followed
by meningitis, endocarditis, and polyserositis in 18%,
18%, and 10%, respectively (Vecht et al. 1985). In Japan,
between 1987 and 1991, 38% of S. suis isolates were from
cases of meningitis and 33% from cases of pneumonia
(Kataoka et al. 1993).
S. suis isolates belonging to capsular types other than
2 have been recovered from cases of bronchopneumonia
in Denmark (Perch et al. 1983), the Netherlands (Vecht
et al. 1985), Belgium (Hommez et al. 1986), Finland (Sih-
vonen et al. 1988), Australia (Gogolewski et al. 1990),
Canada (Higgins et al. 1990a; Gottschalk et al. 1991a, b),
and the United States (Reams et al. 1994). In a retrospec-
tive study of 256 cases associated with S. suis serotypes
1–8 and 1⁄2, Reams et al. (1996) indicated that neither
clinical signs nor gross lesions were associated with spe-
cific serotypes. This is in accordance with a report by
Heath et al. (1996). Nevertheless, in an outbreak due to
S. suis type 9, 100% of weaned pigs dying from the dis-
ease had arthritis, 91% had meningitis, 73% had intersti-
tial pneumonia, and 42% had endocarditis, and accord-
ing to the authors, this serotype produced a different
distribution of lesions from that reported for serotype 2
(Vasconcelos et al. 1994). Some strains of certain
serotypes seem to have particular virulence characteris-
tics. This could explain cases of severe pneumonia due to
serotype 3 in Argentina (Vena et al. 1991) or the recent
diffusion of capsular type 14 in the United Kingdom
(Heath et al. 1996). It is noteworthy that type 14 has al-
ready infected humans (Gottschalk et al. 1989).
Significant microscopic lesions are usually limited to
the lung, brain, heart, and joints (Reams et al. 1994). The
predominant lesions are suppurative bronchopneumo-
nia, neutrophilic meningitis or encephalitis, and fibrino-
purulent or suppurative epicarditis (Sanford and Tilker
1982; Erickson et al. 1984; Reams et al. 1994, 1996). In-
terstitial pneumonia is also seen and is considered a le-
sion secondary to septicemia (Reams et al. 1994). Micro-
scopic lesions do not seem to be associated with serotype
(Reams et al. 1994). Rare cases of fibrinohemorrhagic
pneumonia and septal necrosis have been seen, and it is
suggested that certain strains of S. suis may cause vascu-
lar lesions (Reams et al. 1995). Unusual lesions of hem-
orrhagic and necrotizing myocarditis and subacute
meningoencephalitis and meningoencephalomyelitis
have also been reported by Sanford (1987a, b).
PATHOGENESIS
The mechanisms that enable S. suis to disseminate
throughout the animal are not well understood. The bac-
terium could spread systemically from the nasopharynx,
occasionally resulting in septicemia and death (Windsor
1977). Most studies have focused on capsular type 2 and
566 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
on meningitis. Possible steps involved in the pathogene-
sis are entry of the bacterium into blood from tonsils,
uptake of bacteria by monocytes, transport of bacteria
to the cerebrospinal fluid (CSF) via the choroid plexus,
and stimulation of cytokine production by mono-
cytes/macrophages, which leads to an inflammatory in-
filtrate from the blood to the CSF (Williams 1990;
Chanter et al. 1993). Studies have pointed out that the in-
flammatory exudate itself may be detrimental in some
cases and have recommended treatment with antiinflam-
matory medications (Tunkel et al. 1990).
In spite of the prevalence of cases of pneumonia in
which S. suis was isolated in pure culture or in associa-
tion with other microorganisms, the pathogenesis of this
condition has not been investigated. To our knowledge,
there is no report of experimental induction of pneumo-
nia in swine using S. suis alone. It is likely that the infec-
tion occurs via the respiratory route, then colonization
takes place along with multiplication of the bacteria. A
study has demonstrated that all S. suis type 2 isolates
from diseased pigs adhered to cryostat sections of new-
born piglet lung tissue, and that isolates from cases of
pneumonia adhered in greater number than isolates
from cases of meningitis (Gottschalk et al. 1991c). Bind-
ing of hemagglutinating S. suis strains to frozen sections
of pig pharyngeal tissue was also demonstrated by
Haataja et al. (1993). Another explanation is that some
pneumonic infections result from bacteremia, either by
direct infection of the alveoli or by transport to the alve-
oli in monocytes (Alexander 1995).
The pathogenesis of an infection is influenced by the
immune status of the host, environmental factors, and
virulence attributes of the infectious agent. Researchers
have studied different possible virulence factors of S. su-
is: fimbriae (Jacques et al. 1990), hemagglutinins
(Gottschalk et al. 1990; Haataja et al. 1993), capsular ma-
terial (Elliott and Tai 1978; Quessy et al. 1994c; Salasia et
al. 1994; Charland et al. 1996; Katsumi et al. 1996), cell-
wall and extracellular proteins (Vecht et al. 1991, 1996),
and hemolysin (Gottschalk et al. 1995; Jacobs et al.
1996).
In several bacterial species, fimbriae and hemagglu-
tinins have been associated with adhesion. Haataja et al.
(1993) indicated that the S. suis activity detected by
hemagglutination may account for binding of bacteria to
pig tissues, but the presence of other binding mecha-
nisms is suggested. Studies on the S. suis capsular mater-
ial have led to different conclusions, but although the
capsule is one of the important virulence factors (re:
phagocytosis), it does not appear to be a good virulence
marker.
Two proteins of S. suis type 2 were identified as viru-
lence markers: a muramidase-released protein (MRP)
and an extracellular factor (EF) (Vecht et al. 1991). Vari-
ants of these proteins were later described by Vecht et al.
(1996), who proposed a series of phenotypes which can
be found in several serotypes. Since these proteins are
not present in all virulent S. suis isolates, it is now ac-
cepted that these strains possess other virulence factors
(Quessy et al. 1994a; Galina et al. 1996).
A hemolysin, designated suilysin, has been associated
with virulence in some capsular type 2 strains. Antibod-
ies against it induced protection in mice and pigs against
an experimental challenge (Jacobs et al. 1996). As for
MRP and EF, the suilysin is not produced by all virulent
isolates. Finally, an IgG-binding protein (Serhir et al.
1993), a galactosyl-(alpha 1-4)-galactose-binding adhesin
(Tikkanen et al. 1996), and an albumin-binding protein
(Quessy et al. 1997) were described as possible virulence
factors. These binding proteins may participate in the es-
tablishment of the infection, but their role is still not
considered essential in the pathogenesis of S. suis infec-
tions.
It is likely that concomitant viral infections could po-
tentiate the development of lesions in infections due to
S. suis. Iglesias et al. (1992) concluded that clinical dis-
ease associated with S. suis type 2 was enhanced by con-
comitant infection with pseudorabies virus. Later, it was
suggested that the porcine reproductive and respiratory
syndrome virus (PRRSV) predisposes specific-pathogen-
free (SPF) pigs to infection and disease caused by virulent
S. suis serotype 2 (Galina et al. 1994). Swine practitioners
generally agree with this statement. However, Cooper et
al. (1995) have obtained different results, and they con-
cluded that the NEB-1 PRRSV did not potentiate com-
mon bacterial pathogens while inducing consistent clini-
cal signs, viremia, seroconversion, and microscopic
lesions.
DIAGNOSIS
Presumptive diagnosis of S. suis infections is generally
based on clinical signs, age of animals, and macroscopic
lesions. Confirmation is achieved by the isolation of the
infectious agent and microscopic lesions in tissues.
When feasible, collection of more than one alpha-he-
molytic colony from different tissues of the same animal
or from different animals in the same herd is recom-
mended, because multiple serotypes and strains of S. su-
is can be involved (Reams et al. 1996). Amass (1997) sug-
gested periodic culture of CSF from pigs with meningitis
to ensure that the strain(s) of S. suis causing meningitis
in the herd have not changed. This could be very helpful
when vaccination is considered. Since S. suis may be re-
covered even from healthy lung tissues (Mwaniki et al.
1994), isolates from tissues other than lungs should be
preferred in septicemic cases. In respiratory case acces-
sions, isolation of other infectious agents such as Pas-
teurella multocida, Actinobacillus pleuropneumoniae, or
Arcanobacterium pyogenes is frequent, but pure cultures of
S. suis are also isolated (Higgins et al. 1990a; Galina et al.
1992).
 CHAPTER 41 STREPTOCOCCAL DISEASES
Biochemical identification of S. suis isolates is possi-
ble with a minimum of tests when serotyping is available
(Higgins and Gottschalk 1990). Devriese et al. (1991)
suggested the use of only two tests on pig isolates: amy-
lase positive and Voges-Proskauer (acetoin) negative. It
has to be noted that isolates from the genital tract of
sows form a distinct ecovar with several unusual charac-
teristics such as CO2-dependency (Devriese et al. 1991).
Also, isolates from dogs have been shown to differ from
the common porcine isolates in fermenting mannitol
(Devriese et al. 1992).
Serotyping is still an important part of the routine di-
agnostic procedure. It can be carried out by different
techniques, but many laboratories have adopted the co-
agglutination technique. Since the majority of typeable
isolates belong to capsular types 1–8 and 1⁄2, it is advis-
able for diagnostic laboratories to only use antisera cor-
responding to those serotypes and to send untypeable
isolates to a reference laboratory (Higgins and
Gottschalk 1996; Hogg et al. 1996). Some isolates cross-
react with more than one antiserum using the coaggluti-
nation, as well as the capsular reaction, tests. Some cross-
reactions can be removed by absorption of antisera, but
others will remain, as for type 1⁄2 (Gottschalk et al. 1989;
Hampson et al. 1993).
Genetic tools could be of valuable help in distin-
guishing individual isolates of S. suis, in establishing the
origin of the infection in a given herd, in monitoring the
kinetics of an outbreak, or in ensuring that the right
strain is included in a vaccine. Plasmid analysis allowed
the differentiation of some bacterial isolates belonging
to capsular type 2 (Cantin et al. 1992). It was demon-
strated that an important diversity existed among S. suis
isolates even for those belonging to the same serotype
(Mogollon et al. 1990). Genomic fingerprinting has al-
lowed the identification of outbreak isolates of S. suis
(Mogollon et al. 1991). Beaudoin et al. (1992) confirmed
the genetic diversity between isolates and explained that
although isolates from clinically healthy animals were
very heterogeneous, that was not the case for most iso-
lates from cases of septicemia. Hampson et al. (1993) in-
dicated that genetic diversity was greater than anticipat-
ed on the basis of a previous DNA-DNA hybridization
study (Kilpper-Balz and Schleifer 1987) and estimated
that the species, as currently defined, was diverse. The
same authors did not find any tendency for isolates re-
covered from healthy pigs to be genetically distinct from
those from diseased animals, nor were there consistent
differences between isolates recovered from animals with
different disease syndromes. They concluded that viru-
lence, as well as tissue tropism within the species, does
not appear to be confined to narrow genetic groupings of
the bacteria. At present, there are no known common
virulence markers for all S. suis serotypes (Vecht et al.
1996).
Different serologic tests for the detection of antibod-
Higgins, Gottschalk 567
ies against S. suis have been evaluated. Recent studies
have shown that an ELISA using purified capsular anti-
gens had the best specificity (del Campo Sepulveda et al.
1996; Kataoka et al. 1996). However, serology is more
useful in vaccination studies or as a surveillance tool in
high-health-status swine herds than as a diagnostic tool.
TREATMENT
The choice of the best antibacterial agent against S. suis
infections must be based on several criteria such as the
susceptibility of the organism, the type of infection, and
the mode of administration. Using the Kirby-Bauer
method, susceptibility of S. suis isolates to penicillin ap-
peared to be between 80% and 95% (Sanford and Tilker
1989; Dee et al. 1993; Tarradas et al. 1994). The determi-
nation of minimal inhibitory concentrations allowed the
demonstration of a large number of isolates moderately
susceptible to penicillin, but the sensitivity rate to amox-
icillin and ampicillin was around 90% (Shryock et al.
1992; Dee et al. 1993; Turgeon et al. 1994; Tarradas et al.
1994). It is now recommended that penicillin be used on-
ly in cases where sensitivity tests have shown that S. suis
is sensitive (Sanford 1989). Different authors have re-
ported a high degree of resistance of S. suis isolates to
some antibacterial agents such as tetracycline, clin-
damycin, erythromycin, kanamycin, neomycin, and
streptomycin (Estoepangestie and Lämmler 1993; Dee et
al. 1993; Reams et al. 1993; Tarradas et al. 1994; Prieto et
al. 1994; Turgeon et al. 1994; Salmon et al. 1995). Sus-
ceptibility to trimethoprim-sulfamethoxazole appeared
to be variable (Sanford and Tilker 1989; Shryock et al.
1992; Turgeon et al. 1994; Tarradas et al. 1994). Other re-
ports have mentioned that the most active in vitro an-
timicrobial agents against S. suis were enrofloxacin and
ceftiofur (Dee et al. 1993; Salmon et al. 1995).
Prompt recognition of the early clinical signs of
streptococcal meningitis followed by immediate par-
enteral treatment of affected pigs with an appropriate
antibiotic is currently the best method to maximize pig
survival (Amass 1997). Pigs in the early stages of menin-
gitis may be difficult to detect, and groups of pigs should
be checked 2–3 times daily. Affected pigs hold their ears
back, squint their eyes, or exhibit dog-sitting (Amass
1997). Based on data from studies on the treatment of S.
pneumoniae meningitis in children (Tuomanen 1993), ad-
junctive therapy with an antiinflammatory agent is rec-
ommended for treatment of S. suis meningitis in pigs
(Amass 1997). In a segregated early-weaning (SEW) pro-
gram where postweaning meningitis associated with S.
suis was observed, excellent results were obtained when
piglets, in the very early stages of the disease, were in-
jected with both penicillin and dexamethasone (Clark
1995). In human medicine, the use of antiinflammatory
agents in cases of bacterial meningitis seems nonetheless
controversial (Canadian Pediatric Society 1990).
568 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
Gentamicin appeared very active against S. suis, and
a combination with penicillin is recommended in human
cases of endocarditis due to this agent (Trottier et al.
1991).
PREVENTION
Control of Predisposing Factors
S. suis is an example of an emerging infection associated
with the intensification of the swine industry. Multiple
factors are involved, and among them are the health sta-
tus of the herd (such as concomitant infections and im-
munosuppression), the degree of virulence of the S. suis
strains involved, and the quality of the environment and
of the management.
Overcrowding, poor ventilation, excessive tempera-
ture fluctuations, and mixing of pigs with an age spread
of more than 2 weeks seem to be the most important
stress factors involved in the development of S. suis in-
fection in susceptible pigs (Dee et al. 1993). Management
practices such as all-in/all-out pig flow can help reduce
the incidence of the disease. Dividing large buildings in-
to smaller rooms can help minimize temperature fluctu-
ations and the age spread between pigs. Cleaning each
room between groups of pigs reduces buildup of mi-
croorganisms and improves health status, average daily
gain, and feed conversion (Dee et al. 1993).
Production Technologies
Medicated early weaning and SEW have been used to im-
prove the health status of pigs and to eliminate some in-
fectious organisms (Alexander et al. 1980). It is now ac-
cepted that although early weaning can succeed in
controlling diseases such as pleuropneumonia and swine
dysentery, its capacity to reduce or eliminate early colo-
nizers, such as S. suis, Haemophilus parasuis, and Acti-
nobacillus suis, is questionable (Pijoan 1996). Control of
these problems requires aggressive use of new diagnostic
techniques, such as serum profiling, together with some
manipulation of sow immunity and disease transmission
in the nursery (Pijoan 1996). Other procedures, such as
nursery depopulation, are under evaluation (Dee and Joo
1997).
Antimicrobial Preventive Medication
Antimicrobial preventive medication of groups of pigs
via feed or water against S. suis infections must be based
on several considerations. Bioavailability, route of ad-
ministration (feed or water), competition (overcrowded
pens), and serum concentration needed to kill S. suis
have to be considered prior to prophylactic antimicro-
bial treatment (del Castillo et al. 1995; Amass 1997).
Procaine penicillin incorporated into the feed was re-
ported to significantly reduce the prevalence of strepto-
coccal meningitis within a herd (McKellar et al. 1987).
Oral administration of procaine penicillin G resulted in
measurable systemic concentrations, although it is
known that in humans, only about one-third of an orally
administered dose is absorbed from the intestinal tract.
Higher plasma concentrations are obtained with an
equivalent dose of phenoxymethyl penicillin (McKellar
et al. 1987). Del Castillo et al. (1995) indicated that of all
types of oral treatments with penicillins, only penicillin
V in water given to fasted piglets could reach serum con-
centrations greater than the target concentrations select-
ed for S. suis isolates. In the same conditions, penicillin G
concentrations were much lower and hardly stayed
above the target serum level. In the presence of food, on-
ly penicillin V reached the target level, but only in a few
piglets. Thus, penicillins should exclusively be orally ad-
ministered through drinking water to reduce the inter-
ference in absorption due to feed (del Castillo et al.
1995).
Amoxicillin has advantages over natural penicillins
for mass medication. Its bioavailability is similar, but its
body clearance is lower than that of penicillin V. Thus,
higher serum concentrations can be obtained (J. del
Castillo, pers. comm.—1997).
Immunization
Until now, most vaccines used to protect against S. suis
infections have been autogenous bacterins and results
have been inconsistent. The exact reasons for vaccine
failure are still unknown, but possible explanations are
degradation of protective antigens or loss of antigenicity
of the bacteria caused by heat or formalin processing
(Holt et al. 1990a), weak immunogenicity of the capsu-
lated bacteria (del Campo Sepulveda et al. 1996), pro-
duction of antibodies to antigens not associated with
virulence factors (Holt et al. 1988), and absence of some
strains or serotypes involved in the pathological process.
Reams et al. (1996) focused on this last argument; they
mentioned that the presence of multiple serotypes in a
single herd may account for poor response to vaccina-
tion. Some strains of S. suis can be primary pathogens,
causing conditions such as septicemia, meningitis, or
arthritis, but the majority of isolates are considered op-
portunistic or secondary pulmonary pathogens, which,
nonetheless, should probably be taken into account in a
vaccination program (Reams et al. 1996).
Different types of vaccines have been or presently are
under investigation. Whole-cell bacterins do not appear
to be good immunogens and vaccine failures are com-
mon (Reams et al. 1996). None of the sera from vacci-
nated piglets and sows were protective for mice chal-
lenged with a virulent strain, whereas sera from
hyperimmunized pigs induced a strong passive protec-
tion (Blouin et al. 1994). This is in accordance with data
from Holt et al. (1990a).
Live attenuated vaccines, such as a temperature-sen-
sitive mutant of S. suis capsular type 1⁄2, provided protec-
tion of various degrees in mice against challenge by types
 CHAPTER 41 STREPTOCOCCAL DISEASES
1, 2, or 1⁄2 (Kebede et al. 1990). Vaccination of mice with
a streptomycin-dependent mutant of serotype 1⁄2 result-
ed in complete protection against challenge with
serotypes 1 and 1⁄2 and partial protection against chal-
lenge with a capsular type 2 strain (Foster et al. 1994). Al-
though described as low, the reversion rate of these mu-
tants represents a risk difficult to evaluate.
Live avirulent strains have also been tested. Protec-
tion was obtained in mice and/or pigs following the in-
oculation of live S. suis capsular type 2 strains (Holt et al.
1988; Quessy et al. 1994b; Kobisch et al. 1995; del Cam-
po Sepulveda et al. 1996). Since live avirulent S. suis
strains appear to induce a protection similar to that pro-
duced by live virulent strains, it is suggested that the im-
portant immunogens may be different from S. suis viru-
lence factors. The importance of humoral immunity was
well established by Holt et al. (1988), who succeeded in
passively transferring protection against S. suis type 2.
Nonetheless, S. suis was shown to survive a period of
time in leukocytes, and the use of live vaccines could,
along with the induction of humoral immunity, stimu-
late an active cellular immunity.
Studies have shown that different S. suis type 2 cell-
wall proteins could induce a good protection (Holt et al.
1990b; Quessy et al. 1994a). However, some proteins
which have a good immunogenic potential, such as the
136 kDa (MRP), are not present in all virulent strains
(Quessy et al. 1994a; Galina et al. 1996).
Vaccines against extracellular proteins were tested in
pigs by Jacobs et al. (1996). One was made of purified
suilysin and the other contained most of the extracellu-
lar proteins produced by S. suis, particularly the EF, a 110
kDa protein, described by Vecht et al. (1991) and essen-
tially free of suilysin. Results in pigs were comparable to
those already reported with mice (Jacobs et al. 1994).
Complete protection was obtained with the purified
suilysin and only partial protection with the EF. Al-
though the suilysin is produced by a large number of
serotypes and field isolates from diseased pigs (Jacobs et
al. 1995), there are virulent strains in North America that
do not produce a detectable hemolysin (M. Gottschalk,
unpublished data).
Some authors have suggested that capsular antigens
are most important in the protection of mice against a
challenge with S. suis (Kebede et al. 1990). On the other
hand, it was demonstrated that pigs experimentally or
naturally infected with S. suis type 2 only produced low
levels of antibodies against the capsular polysaccharide
(del Campo Sepulveda et al. 1996), and that a monoclon-
al antibody directed against the capsule of S. suis type 2
was not protective for mice (Charland et al. 1996).
ERADICATION
Attempts to eradicate the infection have focused only on
capsular type 2. According to Clifton-Hadley et al.
Higgins, Gottschalk 569
(1986b), only depopulation and restocking with clean
pigs will ensure eradication of the infection, and in most
herds this is not economic. Mills (1996) has recently de-
scribed the procedures that were used to establish a pure-
bred minimal-disease herd from gilts found to be carriers
of a virulent strain of S. suis type 2. Amass et al. (1996),
on the other hand, did not recommend such an ap-
proach. They emphasized optimization of management
and environment of pigs coupled with strategic medica-
tion of clinically ill animals for control and prevention of
mortality caused by streptococcosis.
Cesarean section can be used to derive pigs free of S.
suis from infected dams. Strict biosecurity measures are
needed and they must include eliminating rodents and
flies (Amass 1997).
Considering that the disease is often associated with
respiratory problems and with multiple S. suis capsular
types, that some less common serotypes are more and
more involved in severe outbreaks, that reliable diagnos-
tic or monitoring tools such as serology will not be avail-
able in the short term, and, finally, that S. suis is now iso-
lated from a wide range of animal species and birds, it
would appear reasonable to direct research efforts to-
ward control measures rather than eradication.
INFECTION IN HUMANS
S. suis is a zoonotic agent which deserves attention. De-
spite its high prevalence in pigs, human cases are rare,
but serious. Over 110 cases have been reported world-
wide, mostly from northern Europe and Southeast Asia
(Dupas et al. 1992; Kay et al. 1995). Meningitis is the
most common manifestation, followed by septicemia
and endocarditis. Clinical cases were reported as early as
1968 in the Netherlands and Denmark (Zanen 1970;
Perch et al. 1968). In Europe, cases have been reported
from the Netherlands, Denmark, Sweden, France, United
Kingdom, Belgium, Italy, and Germany (Colaert et al.
1985; Lütticken et al. 1986; Walsh et al. 1992; Perseghin
et al. 1995). Cases have occurred in Hong Kong (Ho et al.
1990; Kay et al. 1995), Taiwan (Yen et al. 1994), New
Zealand (Robertson and Blackmore 1989b), and Canada
(Trottier et al. 1991; Michaud et al. 1996). During the
past two decades, S. suis infection has become common
in swine, and it is likely that the disease in humans is un-
derdiagnosed. Unfortunately, because many laboratories
are unaware of this organism, it can easily be mistaken
for an enterococcus, Streptococcus bovis, pneumococcus,
or even Listeria species (Chattopadhyay 1979; Arends
and Zanen 1988).
The vast majority of human cases have been attrib-
uted to capsular type 2 of S. suis. Only one case each was
associated with capsular types 4 (Arends and Zanen
1988) and 14, which was designated as the reference
strain of this serotype (Gottschalk et al. 1991a). In near-
ly all reported cases, patients had close contact with
570 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
pigs—as farmers, butchers, abattoir workers, or veteri-
narians—or handled pork products. The most frequent
transmission route is through skin abrasions or cuts, al-
though in many cases, no skin laceration can be shown
(Michaud et al. 1996). The finding that liquid soap inac-
tivates S. suis type 2 in less than 1 minute at a dilution in
water of 1 in 500 suggests that washing with soap and
water would be a satisfactory way of removing skin con-
tamination (Clifton-Hadley and Enright 1984). Since S.
suis type 2 can survive in carcasses at 4˚C for 6 weeks,
chilled or frozen meat could be a hazard long after being
butchered. A case has been reported in a woman who en-
joyed eating raw meatballs (Chattopadhyay 1979).
S. suis capsular type 2 has been isolated from the ton-
sils of two clinically healthy abattoir workers, confirm-
ing a higher risk for persons in close contact with pigs
(Sala et al. 1989). However, the possible role of other an-
imal species and birds as reservoirs or as sources of in-
fection for humans has still to be determined.
INFECTION IN OTHER ANIMAL
SPECIES AND BIRDS
Formerly reported from pigs and humans only, S. suis is
now recovered from a variety of different animal species
and birds. In 1983, Keymer et al. reported isolation of S.
suis type 2 from a raccoon dog fed raw pig meat in a
wildlife park. Isolates belonging to serotypes 2 and 5
have been recovered from extramammary suppurative
lesions in cattle, sheep, and goats. All cases were sporadic
INFECTIONS CAUSED BY S. PORCINUS
In 1984, the name Streptococcus porcinus was proposed
for a species that would include streptococci of groups E,
P, U, and V, mostly because they shared biochemical
properties (Collins et al. 1984a). S. porcinus has a unique
phenotypic profile in addition to serologic differences
that can be used to help identify the species. By rRNA se-
quencing, S. porcinus is closely related to the other beta-
hemolytic streptococci, such as groups A, B, and C (Fack-
lam et al. 1995). S. porcinus is easily differentiated from S.
suis by the fact that the former is beta-hemolytic and is
positive to cyclic AMP (cAMP), esculin, and Voges-
Proskauer tests (Lämmler and Bahr 1996).
S. porcinus group E was associated, particularly in the
United States, with a contagious clinical entity in grow-
ing pigs known as streptococcal lymphadenitis, jowl ab-
scesses, or cervical abscesses. Transmission is possible by
contact, drinking water, or ingestion of food contami-
nated by abscess discharge or infected feces. The organ-
isms enter the swine host through the mucosa of the
and only one was related to the presence of pigs on the
farm (Hommez et al. 1988). In 1990, a case of meningitis
in a horse, in contact with cattle only, was reported in
Belgium; the authors indicated that S. suis appears to be
a member of the intestinal flora of cattle, sheep, goats,
and horses (Devriese et al. 1990). In Canada, capsular
type 2 was isolated in pure culture from an aborted
bovine fetus, capsular type 16 from a lung of a 6-week-
old calf affected with chronic purulent bronchopneumo-
nia, capsular type 31 from a calf with a cerebral edema,
and type 33 from a lamb affected with arthritis (Higgins
et al. 1990b, 1995). Devriese and Haesebrouck (1992) re-
ported the isolation of S. suis from three horses, a zebra,
and cats. The same group also confirmed the presence of
S. suis in 20% of dog tonsils (Devriese et al. 1992). Cap-
sular types 1⁄2, 4, 9, 20, 22, and 26 were also isolated from
the tonsils and the anal flora of dogs and cats by Salasia
et al. (1994). In 1993, S. suis was isolated from a peri-
toneal abscess in a fallow deer (Devriese et al. 1993).
Meningitis due to capsular types 9 and 20, pneumonia
due to types 9 and 18 in cattle, and a case of pneumonia
in a horse were reported by Japanese authors in 1993
(Kataoka et al. 1993). More recently, the group from Bel-
gium reported the isolation of S. suis from psittacine
birds, zebra finches, bullfinches, and a duck (Devriese et
al. 1994a). Finally, capsular type 2 was isolated from the
lung of a young wild boar affected with pneumonia (Hig-
gins et al. 1997). More studies are needed to evaluate the
importance of these findings for the epidemiology of S.
suis infection not only in swine but also in humans.
pharyngeal or tonsillar surfaces and are carried to the
lymph nodes, primarily of the head and neck region,
where abscesses are formed (Wessman 1986). Losses due
to this disease in the United States were important in the
1960s, but its incidence has since declined. The disease is
not recognized as an important economic entity in other
countries, where the bacterium represents only a few
percent of the microorganisms isolated from abscesses
in swine (Wessman 1986). A report of an outbreak from
Spain mentioned that 80% of 50 feeder pigs had
mandibular and retropharyngeal purulent lymphadeni-
tis (Real et al. 1992).
Antibiotic treatment is not usually successful in ab-
scessed swine or in elimination of carriers. However, re-
duction in the prevalence of abscesses was achieved by
feeding 138 g chlortetracycline/metric ton (125 g/ton) to
pigs for 4–6 weeks after weaning (Schmitz and Olson
1973). Resistance to tetracycline has been recently re-
ported (Facklam et al. 1995; Lämmler and Bahr 1996).
 CHAPTER 41 STREPTOCOCCAL DISEASES
Vaccination is possible but has not been widely used
since the condition is not widespread. The vaccine is ob-
tained from a chemically derived mutant of the group E
streptococcus and is sprayed directly onto the tonsillar
area, producing an immunological efficacy of more than
90% (Wessman 1986). It has to be noted that abscesses in
pigs may also be caused by a variety of streptococcal and
nonstreptococcal bacteria.
S. porcinus group E can be isolated from tonsils, phar-
ynx, and nasal cavities of clinically healthy pigs. It is also
occasionally found in the vaginal mucus of sows and in
the semen and prepuce of boars. It is considered to be
more of a secondary invader than a primary pathogen in
conditions such as pneumonia, enteritis, encephalitis,
and arthritis (Wessman 1986). It was isolated in Canada
from the lungs of a 2-year-old pig affected with an ab-
scessative pneumonia, along with other bacterial agents
(A. Désilets, pers. comm.—1995).
INFECTIONS CAUSED BY STREPTOCOCCI BELONGING TO
GROUPS C AND L
ETIOLOGY AND EPIDEMIOLOGY
In 1984, Farrow and Collins, using DNA-DNA hybridiza-
tion, DNA base composition, and biochemical tests, in-
dicated that Streptococcus dysgalactiae, S. equisimilis, and
streptococci of Lancefield serologic groups C, G, and L
were a single species. Then group C S. equi and S. zooepi-
demicus were each classified as a subspecies of the species
S. equi. In 1996, Vandamme et al. proposed that the name
S. dysgalactiae subsp. dysgalactiae be used for strains of
animal origin, and the name S. dysgalactiae subsp. equi-
similis be used for human isolates. S. dysgalactiae subsp.
dysgalactiae strains belong to groups C, G, and L; are al-
pha-, beta-, or nonhemolytic; do not exhibit streptoki-
nase activity on human plasminogen; and are found in
the respiratory and genital tracts of various animal
species. S. dysgalactiae subsp. equisimilis strains belong to
groups C and G; are beta-hemolytic; exhibit streptoki-
nase activity on human plasminogen; and are found in
the respiratory and genital tracts of humans.
In swine, the S. dysgalactiae group C “equisimilis” and
the S. dysgalactiae group L serobiovars are all beta-he-
molytic streptococci. Although members of the normal
flora, they are considered the most important beta-he-
molytic streptococci involved in lesions in pigs, and
these agents were judged to be of etiological significance
in autopsy reports (Jones 1976; Hommez et al. 1991). S.
dysgalactiae group C streptococci are common in nasal
and throat secretions, tonsils, and vaginal and preputial
Higgins, Gottschalk 571
S. porcinus groups P, U, and V were isolated by Hom-
mez et al. (1991) from pig lungs, genital organs, and
brains. However, no histological lesions could be associ-
ated with their presence. More recently, S. porcinus
groups P and V were associated with abortions in pigs
(Plagemann 1988; Lämmler and Bahr 1996). Hommez et
al. (1991) cited a report of Hinterdorfer et al. (1990) in
which, S. porcinus group P was associated with hemor-
rhagic tracheitis in pigs.
According to Wessman (1986), group E streptococci
were isolated from cases of enteritis and infertility in cat-
tle and sheep, mastitis in cattle, pneumonia in guinea
pigs, abscesses in rabbits, and skin and respiratory infec-
tions in dogs. Finally, these beta-hemolytic streptococci
were found in the genitourinary tract of humans (Fack-
lam et al. 1995). There is, as yet, no evidence that S. porci-
nus has a zoonotic potential.
secretions (Jones 1976). Vaginal secretions and milk
from postparturient sows are the most likely sources of
infection for the piglets (Woods and Ross 1977). Strepto-
cocci enter the bloodstream via skin wounds, the navel,
and tonsils. A bacteremia or septicemia occurs, and the
organisms then settle in one or more tissues, giving rise
to arthritis, endocarditis, or meningitis. Insufficient con-
sumption of colostrum or milk or inadequate levels of
antibodies, especially in gilts, may predispose to disease
(Windsor 1978).
CLINICAL SIGNS, LESIONS,
AND DIAGNOSIS
Infection is usually first seen in pigs between 1 and 3
weeks of age. Joint swelling and lameness are the most
obvious and persistent clinical signs. Elevated tempera-
tures, lassitude, roughened hair coat, and inappetence
may also be noted. Early lesions consist of periarticular
edema; swollen, hyperemic synovial membranes; and
turbid synovial fluid. Necrosis of articular cartilage may
be seen 15–30 days after onset and may become more se-
vere. Fibrosis and multiple focal abscessation of periar-
ticular tissues and hypertrophy of synovial villi also oc-
cur. In lame pigs, up to 12 weeks of age, the causative
agents of arthritis were, in decreasing order, “S. equisim-
ilis” (26.3%), Staphylococcus hyicus subsp. hyicus (24.6%),
Arcanobacterium pyogenes (13.2%), S. aureus (7.9%), and
Haemophilus parasuis (7.9%). Most of the pigs culled for
572 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
arthritis were under 6 weeks of age (Hill et al. 1996). In
Denmark, polyarthritis due to hemolytic streptococci
and staphylococci was shown to be common in suckling
pigs, 17.8% of litters born being affected (Nielsen et al.
1975).
Endocarditis is another condition associated with S.
dysgalactiae infection, but it is difficult to diagnose in live
animals. Lesions consist of yellow or white vegetations of
different sizes, often covering the entire surface of the af-
fected valve (Jones 1980).
Diagnosis of streptococcal septicemia, arthritis, or
endocarditis is best accomplished by necropsy and bac-
teriological examination of representative affected pigs.
Rather small numbers of organisms or no organisms
may be isolated from affected joints, especially when the
inflammatory process is advanced. Use of large inocu-
lums and enrichment media will enhance the isolation of
the organism. Bacteria grow readily from portions of the
vegetations in cases of endocarditis (Sanford and Hig-
gins 1992).
DIARRHEA ASSOCIATED WITH ENTEROCOCCUS DURANS IN PIGLETS
Diarrhea associated with Enterococcus durans (formerly
Streptococcus durans) was described in piglets between 2
and 20 days of age (Johnson et al. 1983; Drolet et al.
1990; Cheon and Chae 1996). Most cases are sporadic,
but a recently reported outbreak included 90% of the pig-
lets in 16 of 20 litters. Diarrhea was observed during a 2-
week period, but mortality was negligible. No other in-
fectious agent was identified, and E. durans was con-
sidered to be strongly associated with diarrhea in piglets
(Cheon and Chae 1996). Collins et al. (1984b) have pub-
lished details about the characterization and identifica-
tion of E. durans. Devriese et al. (1994b) have indicated
that some strains identified as E. durans were in fact E. hi-
rae.
Enterococci are known as part of the intestinal flora,
but it seems that some strains have the capacity to colo-
nize the mucosal surface of the small intestine extensive-
OTHER STREPTOCOCCI IN SWINE
Other streptococcal species have been isolated from pigs.
Hommez et al. (1991) reported the isolation of beta-he-
molytic group B streptococci (S. agalactiae) from the ton-
sils, brain, and intestinal mucosa of pigs, and according
TREATMENT AND CONTROL
Since baby pigs are virtually assured of being exposed to
group C and/or group L streptococci, effective preven-
tive measures should be followed. Adequate intake of
colostrum may ensure that the piglets receive protective
antibodies. Traumatic injuries to the feet and legs should
be minimized by reducing the abrasiveness of the floor
surface in the nursing area.
Beta-hemolytic streptococci are recognized to be sen-
sitive to beta-lactam antibiotics. Long-acting antibacteri-
al agents may be beneficial, and treatment should be giv-
en before the inflammatory process is well advanced
(Sanford and Higgins 1992). There are no recent reports
about vaccination against groups C or L streptococci. Au-
togenous bacterins have been used, and a reduction in
incidence of arthritis has been reported when sows were
vaccinated before farrowing. Woods and Ross (1977) re-
ported that extract vaccines induced higher levels of
complement-fixing antibodies than did whole-cell bac-
terins.
ly. The pathogenesis of enteric disease associated with
adherent enterococci is unclear. Adherence occurs with
the help of fibrillar projections (Tzipori et al. 1984). Di-
arrhea is not associated with enterotoxin production or
substantial mucosal injury (Cheon and Chae 1996).
Alone or in conjunction with other agents, they interfere
with digestion and absorption at the brush border (Tzi-
pori et al. 1984). Because of the natural resistance of en-
terococci to some antibacterial agents, antimicrobial sus-
ceptibility testing is advised before the institution of a
treatment. Due to the lack of knowledge about the clini-
cal and epidemiological aspects of this infection, preven-
tive measures are difficult to establish. This condition
has also been reported in foals (Tzipori et al. 1984),
calves (Rogers et al. 1992), and puppies (Collins et al.
1988; Jergens et al. 1991).
to these authors, the etiological significance of the S.
agalactiae strains in the lesions was beyond doubt. They
also suggested that the rare porcine S. agalactiae cases
had cattle or humans as the infection source. However, a
 CHAPTER 41 STREPTOCOCCAL DISEASES
more recent study has indicated that group B streptococ-
ci from pigs and nutrias differ from bovine and human
group B streptococci and seem to play no role in cross-in-
fections between animals (Wibawan et al. 1993).
S. bovis, S. alactolyticus, S. hyointestinalis, and S. in-
testinalis are not considered potential pathogens in
pigs.
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42 Swine Dysentery
D. L. Harris, D. J. Hampson, and R. D. Glock

Swine dysentery (SD) is a severe mucohemorrhagic diar-

rheal disease that primarily affects pigs during the grow-
ing-finishing period. This enteric disease is also referred
to as vibrionic dysentery, bloody scours, bloody dysen-
tery, black scours, or mucohemorrhagic diarrhea. SD
was originally described in 1921 and since that time has
been reported to occur in most swine-rearing areas of
the world. An anaerobic spirochete, Serpulina hyodysen-
teriae is considered to be the primary etiologic agent of
SD, and diagnostic tests are based on demonstrating the
presence of this organism. However, other indigenous
microbiota of the intestinal tract may also contribute to
lesion production.
For veterinary practitioners familiar with SD and de-
siring specific directions concerning the formulation of
advice to producers on minimizing the detrimental eco-
nomic effects of the disease, we suggest that the section
Practical Veterinary Advice to Producers (later in chap-
ter) be studied prior to referring to the other sections in
42.1. Pure culture of Serpulina (Treponema) hyo-
the chapter.
dysenteriae, carbol fuchsin stain, as viewed by light
microscopy (Kinyon 1974).
ETIOLOGY

Although SD was first described in 1921 by Whiting et
al., the etiology remained unknown for 50 years. In 1971
Taylor and Alexander at Cambridge University reported
the successful propagation of a pathogenic anaerobic
spirochete from an infected pig. Their work was simulta-
neously confirmed at Iowa State University, and the or-
ganism was named Treponema hyodysenteriae (Glock and
Harris 1972; Harris et al. 1972a). The organism is now
classified in the new genus Serpulina, which also includes
the species S. innocens (Stanton 1992) and S. pilosicoli
(Trott et al. 1996c). A number of other species in the
genus are in the process of being described and
named.
The organism is a gram-negative, oxygen-tolerant,
anaerobic spirochete. It is 6–8.5 µm in length, 320–380
nm in diameter, loosely coiled (Fig. 42.1), motile, and he-
molytic on blood agar. S. hyodysenteriae has 7–14
periplasmic flagella inserted at each cell end, and these
overlap at the middle of the protoplasmic cylinder. The
whole cell, including the periplasmic flagella, is covered
Recently the genus name Brachyspira has been suggested for Serpulina
hyodysenteriae, Serpulina innocens, and Serpulina pilosicoli.
by a loose outer membrane (Fig. 42.2).
S. hyodysenteriae produces typical signs and lesions of
SD when orally inoculated into conventional or specific-
pathogen-free (SPF) pigs (Taylor and Alexander 1971;
Glock and Harris 1972; Harris et al. 1972a). Several ani-
mal models have been developed for the study of SD. Le-
sions closely resembling those of SD can be produced
with pure cultures of S. hyodysenteriae in a colonic seg-
ment of pigs prepared by surgical anastomosis (Hughes
et al. 1975), in isolated ligated colonic loops of pigs
(Whipp et al. 1978), and by oral inoculation of guinea
pigs (Joens et al. 1978a), mice (Joens and Glock 1979),
and young chicks (Adachi et al. 1985). The organism also
has been recovered from naturally infected rheas in the
United States, where it causes a necrotizing typhlocolitis
(Jensen et al. 1996; Trott et al. 1996a).
Initial studies on the pathogenicity of S. hyodysenteri-
ae in gnotobiotic pigs indicated that the organism could
not establish itself in the gut when inoculated orally in
the absence of other anaerobic bacteria (reviewed by
Harris and Glock 1981). Studies in gnotobiotic mice
(Joens et al. 1982) and pigs (Whipp et al. 1982) clearly
showed that S. hyodysenteriae is not dependent upon oth-

579
580 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor

42.2. Electron micrographs of S.

hyodysenteriae. (A) S. hyodysen-
teriae from the intestinal mucosa of
a pig acutely affected with SD. The
organism is negatively stained with
potassium phosphotungstate. Ar-
rows indicate areas of flagellar
crossover (A. E. Ritchie and L. N.
Brown, unpublished data—1974).
(B) S. hyodysenteriae, isolate 3166
(Norway), in thin section. Trans-
verse aspect illustrating flagellar di-
ameters and apposition to the outer
envelope. The differences in flagellar
diameter are presumably due to dif-
ferent stages of morphogenetic as-
sembly (A. E. Ritchie and L. A.
Joens, unpublished data—1978).
(C) Bacteriophages ubiquitously as-
sociated with S. hyodysenteriae, in
potassium phosphotungstate nega-
tive stain illustrating uniform mor-
phology and close proximity of the
receptor sites on a fragment of the
outer envelope (Ritchie et al. 1978).

er microorganisms for the production of lesions in the
colon and cecum, although the disease produced in gno-
tobiotic pigs was less severe than in conventional pigs.
Anaerobic indigenous bacteria of the colon and cecum
are synergistic with S. hyodysenteriae by facilitating colo-
nization and by augmenting lesion production. There is
no doubt that S. hyodysenteriae is the only transmissible
agent in natural outbreaks of SD. Its ability to colonize
can be inhibited by feeding diets that are highly di-
gestible in the small intestine, so that little fermentable
substrate reaches the large intestine (Pluske et al. 1996;
Siba et al. 1996).
In their original work, Taylor and Alexander (1971)
demonstrated a second type of anaerobic spirochete in
the feces of normal swine, which morphologically re-
sembled pathogenic S. hyodysenteriae. It is now clear that
there are a number of species of weakly beta-hemolytic
spirochetes which can be differentiated from pathogenic
S. hyodysenteriae either by hemolytic pattern on blood
agar plates (Fig. 42.3) or by enteropathogenicity testing
in pigs or mice. The weakly hemolytic S. pilosicoli, how-
ever, is also capable of causing colitis in experimentally
infected pigs (Trott et al. 1996b). Nonpathogenic spiro-
chetes probably exist in all pig herds (Hudson et al. 1976;
Kinyon et al. 1976; Joens et al. 1979b). Kinyon and Har-
ris (1979) originally proposed that nonpathogenic spiro-
chetes isolated from the pig gut be named Treponema
(Serpulina) innocens. Other nonpathogenic porcine spiro-
chete species now include Serpulina murdochii and Ser-
pulina intermedia—although the latter has been suspect-
ed of being pathogenic under some circumstances
(Hampson and Trott 1995; Chapter 40, this volume).
Kinyon et al. (1977) and Kinyon and Harris (1979)
showed that 25 of 25 strongly beta-hemolytic isolates (S.
hyodysenteriae) caused SD when orally inoculated into
SPF pigs, whereas 13 weakly beta-hemolytic isolates were
not pathogenic.
It became evident that these organisms were not typ-
ical of the genus Treponema (Sellwood 1991). Analysis of
16S RNA sequence data from strains of T. hyodysenteriae
and T. innocens and data from other spirochetes and oth-
er bacteria enabled genetic relationships to be estab-
 CHAPTER 42 SWINE DYSENTERY Harris, Hampson, Glock
42.3. Zones of beta hemolysis (S. hyodysenteriae)
and weak beta hemolysis (S. innocens) produced on
bovine blood agar.
lished. Taking this RNA homology, DNA-DNA reassocia-
tion, and SDS-PAGE profiles of whole-cell proteins,
Stanton et al. (1991) proposed the new genus “Serpula”
(Latin for “little serpent”) for both T. hyodysenteriae and
T. innocens strains. These were closely related to each oth-
er but only distantly related to treponemes and other
bacteria. The genus name Serpula was found to duplicate
the name of a fungal genus and has subsequently been
changed to Serpulina (Stanton 1992).
In 1982, Lysons et al. described three isolates of S. hy-
odysenteriae, cultured from three different pig herds in
the United Kingdom without previous histories of SD,
that were strongly beta-hemolytic on blood agar but
lacked pathogenicity for conventional experimental pigs
by oral inoculation. They were indistinguishable from S.
hyodysenteriae in biochemical, slide agglutination, and
disk growth-inhibition tests but could be differentiated
from a pathogenic isolate of S. hyodysenteriae by agglu-
tinin cross-absorption tests. These isolates appear to be
avirulent strains of S. hyodysenteriae, and their existence
may confuse the laboratory diagnosis of SD. Lee et al.
(1993) subsequently described another avirulent isolate
which they recovered from a pig in an Australian herd.
Both the British and Australian isolates have reduced
motility in porcine mucus (Milner and Sellwood 1994).
Initially, S. hyodysenteriae could not be grown in a liq-
uid medium, so solid agar was used. In 1974 Kinyon and
Harris reported propagating the organism in a liquid
medium consisting of trypticase soy broth without dex-
trose but with 10% fetal calf serum, under O2-free H2 and
CO2. Lemcke et al. (1979) described a procedure for
growth of S. hyodysenteriae in trypticase soy broth with
10% rabbit serum under O2-free N2 and CO2. Lemcke and
Burrows (1980) propagated the organism in serum-free
medium containing bovine serum albumin and choles-
terol. Other useful media have been described by Kunkle
et al. (1986) and also by Stanton and Lebo (1988), who
used 1% O2 in the culture atmosphere (S. hyodysenteriae
can utilize oxygen with the aid of enzymes such as nicoti-
namide adenine dinucleotide, reduced [NADH], oxidase
[NOX]; Stanton 1989). Kent et al. (1988) described a sim-
581
ple laboratory flask apparatus in which enhanced growth
of the organism was demonstrated. Kinyon (1974), Kin-
yon and Harris (1979), and Lemcke and Burrows (1981)
compared the cultural characteristics of S. hyodysenteriae
and strains of weakly hemolytic spirochetes (S. innocens).
The organisms produced acid from a limited number of
carbohydrates, usually glucose and maltose; the end
products of fermentation were acetate, small amounts of
butyrate, H2, and CO2. The organisms degraded pyruvate
but not lactate and were negative in tests for catalase, cy-
tochrome oxidase, hydrogen sulfide, gelatin hydrolysis,
meat hydrolysis, glycine tolerance, starch hydrolysis, and
urease. They were positive in tests for bile tolerance, es-
culin hydrolysis, and iodoacetic acid tolerance. S. hyo-
dysenteriae may be separated from most but not all
strains of weakly hemolytic spirochetes by differences in
fructose fermentation and indole production; more reli-
able is the hemolytic pattern (although in recent years
occasional strains of non–S. hyodysenteriae spirochetes
have been reported to be strongly hemolytic: Neef et al.
1994). Enteropathogenicity for conventional pigs is the
ultimate test. A fuller description of the metabolic activ-
ities of S. hyodysenteriae has been given by Stanton
(1997).
Miao et al. (1978) found that S. hyodysenteriae and S.
innocens have an extremely low guanine-plus-cytosine
content (25.8%), as does S. pilosicoli (Trott et al. 1996c).
The different Serpulina spp. have only low (<50%) de-
oxyribonucleic acid (DNA) sequence homology, whereas
different isolates of S. hyodysenteriae exhibit greater than
75% DNA sequence homology. A physical and genetic
map of the chromosome of the type strain of S. hyo-
dysenteriae (B78T) has been prepared (Zuerner and Stan-
ton 1994). The chromosome is circular and about 3.2 Mb
in size. Ritchie et al. (1978) demonstrated several differ-
ent types of bacteriophages on the surfaces of pure cul-
tures of S. hyodysenteriae and S. innocens. A generalized
transducing bacteriophage from S. hyodysenteriae has
been purified and characterized (Humphrey et al. 1997).
A hemolysin produced by S. hyodysenteriae has been
demonstrated in filtrates of cultures; the amount was en-
hanced when Na RNA was added (Picard et al. 1978).
Lemcke et al. (1982) used washed cells in a buffer with
various “carriers”; yeast RNA core was more efficient
than Na RNA, while bovine serum albumin fraction V
and Tween 80 were worse. They also determined that the
hemolysin of S. hyodysenteriae was oxygen-stable and re-
sembled another carrier-dependent toxin, streptolysin S.
It is a small peptide with a molecular weight of 19 kDa
(Kent et al. 1988), which has proved difficult to separate
from the carrier. The hemolysin is cytotoxic for a number
of tissue culture cells and also primary pig cells, lympho-
cytes being particularly sensitive (Kent and Lemcke
1984). It has also been shown to damage epithelial cells
in pig ligated intestinal loops (Lysons et al. 1991). The
role of hemolysins in virulence has been emphasized by
the fact that hemolysin-negative mutants of S. hyodysen-
582 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor

teriae have reduced virulence in pigs (Hyatt et al. 1994). printing” of individual strains, including restriction en-
Recently it has become apparent that there are at least donuclease analysis (Combs et al. 1989, 1992; Harel et al.
three different genes encoding hemolysins of S. hyo- 1994), DNA restriction fragment polymorphism analysis
dysenteriae (Ter Huurne et al. 1994), and their relative im- (Duhamel et al. 1992; Jensen et al. 1992), pulsed field gel
portance is still not clear. electrophoresis (Trott et al. 1996a), and random amplifi-
Baum and Joens (1979a) serologically characterized cation of polymorphic DNA (Dugourd et al. 1996), have
phenol extracts of S. hyodysenteriae and S. innocens. Wa- been developed and are useful tools for epidemiological
ter-phase material (lipopolysaccharide, LPS) from phe- studies.
nol extracts of S. hyodysenteriae was utilized to classify LPS from S. hyodysenteriae has been shown to resem-
isolates into four serotypes by agar gel diffusion tests. ble endotoxin by in vitro tests. Studies using LPS extract-
Mapother and Joens (1985) found three more LPS ed by phenol/water (Nuessen et al. 1982) and endotoxin
serotypes, designated 5, 6, and 7 (Table 42.1). Lemcke extracted by butanol/water (Greer and Wannemuehler
and Bew (1984) meanwhile found three new serotypes, 1989a) showed that it acts as a mitogen for murine
which have not been compared with those of Mapother splenocytes, generates a chemotoxin in fresh swine
and Joens. Having studied LPS antigens of North Amer- serum, causes an increase in uptake of red blood cells by
ican, European, and Australian isolates, Hampson et al. murine peritoneal cells via Fc and C3 receptors, and is cy-
(1989a, b, 1990) proposed that LPS serologic typing totoxic to murine peritoneal cells. The butanol/water
should be modified to a system describing serogroups preparation was also able to stimulate production of in-
(currently 11: Hampson et al. 1997), each of which may terleukin-1 (IL-1) and tumor necrosis factor (TNF) from
contain several distinct serovars. The situation in the murine peritoneal exudate cells. However, the differ-
United States appears relatively simple; most isolates be- ences in virulence between S. hyodysenteriae and S. inno-
long to serotypes 1 and 2 of Baum and Joens (1979a). In cens could not be attributed to the biological properties
Quebec “serotypes 8 and 9” predominate (Li et al. 1991), investigated. Oral inoculation of two types of conven-
whereas isolates from Europe and Australia are more tional mice with S. hyodysenteriae has shown that the LPS
serologically diverse. There is no indication that the viru- may be involved in lesion production. Lesions were pro-
lence of an isolate correlates with its serotype. duced in the colons of endotoxin-sensitive mice but not
Other typing methods suggested for S. hyodysenteriae in endotoxin-resistant mice (Nuessen et al. 1983).
have been agglutinin cross-absorption (Lemcke and Bew Other morphologic types of spirochetes are present
1984), which was likely to be very complex, and multilo- in colons of normal pigs and those affected with SD.
cus enzyme electrophoresis (Lymbery et al. 1990; Lee et These may be confused with S. hyodysenteriae when using
al. 1993). Using the latter technique, S. hyodysenteriae iso- dark-field or phase-contrast microscopy. A commonly
lates have been divided into four broad genetic groups, recognized type is the small spirochete, or pig feces spiro-
one of which contains the avirulent Australian isolate chete (Harris et al. 1972b). It has a corkscrew shape and
SA3. A number of DNA-based techniques for “finger- is approximately 220 nm in diameter with 2–4 periplas-
mic flagella. These should not be confused with the much
larger and snakelike S. hyodysenteriae and S. innocens.
Table 42.1. Serotypes of S. hyodysenteriae based on Cwyk and Canale-Parola (1979) characterized the mor-
water-soluble antigens as revised by Mapother and phology and general physiological characteristics of a
Joens (1985)
small corkscrew-shaped anaerobic spirochete that had
Serotype Origin Isolate been isolated from the colon of a pig (Harris et al. 1972b)
1 Iowa Strain B78a and named it T. succinifaciens. This organism is nonpath-
Missouri Dys 7, Den 191 ogenic for pigs by oral inoculation.
Missouri B234b
Denmark Dys 7, Den 191 EPIDEMIOLOGY
Mexico Strain G
Iowa T6
Minnesota T7 Mapother (1993) reported that 11% of herds in the Unit-
Minnesota B140 ed States were infected with S. hyodysenteriae based on an
2 Iowa B204c LPS-ELISA test. Egan et al. (1982) had previously deter-
Iowa T3, T4, T5 mined that 40% of all pig herds in Iowa, Illinois, and Mis-
Iowa B9605
3 Canada B169 souri were affected with SD by testing sera collected at
4 England A-1 slaughter plants. In comparison, Mapother (1993) indi-
5 Illinois B6933 cated that 33% of Iowa farms were positive for SD. Total
6 Missouri B8044 national losses to the U.S. swine industry have been esti-
7 Netherlands Ack 300/8
mated to be $115.2 million (Duhamel and Joens 1994). A
a
Type species: ATCC 27164; CCM 6063. serologic survey in Western Australia indicated a preva-
b
ATCC 31287. lence of 33% (Mhoma et al. 1992). Taylor (1984) con-
 CHAPTER 42 SWINE DYSENTERY Harris, Hampson, Glock
ducted a veterinary practitioner survey that indicated
that 27% of the feeder pig–producing herds were affect-
ed with the disease. SD is the second most commonly di-
agnosed pig disease (after enteric colibacillosis) in U.K.
Veterinary Investigation Centers, and the incidence has
not dropped noticeably, despite some successful at-
tempts at eradication by depopulation or cleaning/med-
ication plus the availability of disease-free replacement
breeding stock (Lysons 1992). Roncalli and Leaning
(1976) reported that SD was present in most pig-produc-
ing countries of the world. It appears to continue to be
prevalent but at a reduced frequency in most countries.
SD is most commonly observed in 15–70 kg pigs, but
the disease may also occur in adults, particularly in sows
reared outdoors, and occasionally in suckling piglets.
Transmission of the disease occurs primarily by inges-
tion of fecal material either from clinically affected pigs
or from clinically normal pigs that carry the disease. Ex-
perimentally, transmission has been accomplished by ex-
posure of susceptible pigs to previously infected animals
that have had no clinical signs for 70 days. SD has also
been transmitted by animal caretakers who did not
change clothing or footwear between isolation units con-
taining diseased and healthy pigs. It is believed that the
use of improperly designed load-outs which allow pigs to
return to the production unit from a contaminated trans-
port vehicle has resulted in transmission of SD. Differ-
ences in susceptibility due to breed have not been re-
ported.
SD causes a tremendous financial loss due to mortal-
ity, decreased rate of growth, poor feed conversions, and
expenses for chemotherapy. Lysons (1983) calculated
that in-feed medication for SD could cost £1.50–£5.00
($2.60–$8.60)/pig. Wood and Lysons (1988) demon-
strated that the feed-conversion efficiency ratio in a herd
deteriorated by 0.58 while it had SD, a cost increase of
£7.31 ($12.60)/pig sold, and the cost of medication was
£1.38 ($2.40)/pig. Although there were pigs with clinical
SD in the herd, the poor feed-conversion efficiency ratio
was attributed mainly to subclinical disease. Walter and
Kinyon (1990) found that the cost of medicating an in-
fected herd was $8.30/pig marketed and that medication
costs were reduced to $.08 per pig after eradication.
Polson et al. (1992) projected the financial impact of
SD via four simulation scenarios: SD-free, endemic SD,
eradication by medication and disinfection, and total de-
population/repopulation. Net present value, internal
rate of return, and benefit/cost ratio were calculated for
each simulation scenario over a 10-year period. The prof-
it margin per 100 kg liveweight produced was as follows:
SD-free, $7.44; endemic SD, $1.67; eradication, $4.93;
and depopulation/repopulation, $.07 (Polson et al.
1992).
In field cases, morbidity of SD in weanling pigs may
approach 90% and mortality may be 30%, depending on
the effectiveness of treatment. The severity in chronical-
583
ly affected herds may be mild, and disease may not be
clinically evident. This situation is due to the protection
afforded suckling pigs by the milk of chronically affected
dams and the common use of drugs in nursery and grow-
er rations. Under experimental conditions in which pigs
are not treated, mortality is often 50%. The severity of ex-
perimentally induced SD is related to the amount of
stress on the pig, the quantity of infectious inoculum ad-
ministered, and the size of the pig.
Clinical signs of SD seem to occur in a cyclic manner.
In large groups of pigs affected with the disease, symp-
toms may reappear at 3- to 4-week intervals. This reap-
pearance of symptoms often occurs only after removal of
therapeutic levels of drugs from the water or feed. Be-
cause S. hyodysenteriae survives in the rearing environ-
ment, some pigs may become reinfected and show symp-
toms of the disease. By contrast, many pigs that survive
the acute phase of the disease do recover from SD and
are capable of resisting subsequent challenge. However,
chemotherapy during the acute phase may not allow the
pig to initiate an immune response.
Pigs that have recovered from SD may be asympto-
matic but shed S. hyodysenteriae in their feces. Songer and
Harris (1978) reported that pigs that had not had clinical
signs of SD for 70 days would transmit the disease to sus-
ceptible sentinel pigs. S. hyodysenteriae shed in the feces
of asymptomatic sows can cause infection of suckling
pigs. Depending on the immune status of the sow, the
suckling pigs may not show clinical symptoms until re-
moval from the sow. Glock et al. (1975) showed that la-
goon water containing effluent of a herd affected with
SD would produce the disease when administered to sus-
ceptible pigs. The organism has been isolated from the
pit of a slotted-floor building that housed pigs affected
with the disease. S. hyodysenteriae was isolated from a dog
that frequented pens containing pigs affected with SD
(Songer et al. 1978). Similarly, the organism has been
isolated by Joens and Kinyon (1982) from field mice cap-
tured on three farms on which there were pigs affected
with the disease. Hampson et al. (1991) isolated S. hyo-
dysenteriae from a wild rat living on an Australian pig-
gery.
Experimentally, Glock et al. (1978) showed that oral
inoculation of dogs and birds (starlings) resulted in fecal
shedding of S. hyodysenteriae for 13 days and 8 hours, re-
spectively. Flies may carry the organism for at least 4
hours (J. G. Songer, pers. comm.—1978). Experimental-
ly inoculated mice shed S. hyodysenteriae in feces for over
180 days (Joens 1980), while rats shed it for only 2 days
(Chia 1977). Conventional pigs exposed to the feces of
infected mice developed clinical symptoms of SD within
11 days after the first contact with mouse feces (Joens
1980). Chia and Taylor (1978) demonstrated that S. hyo-
dysenteriae will survive in dysenteric feces diluted in wa-
ter for 61 days at 5˚C. The organism survives in feces for
7 days at 25˚C. I. T. Egan (pers. comm.—1980) found
584 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
that S. hyodysenteriae would survive in soil for 18 days at
4˚C. However, her attempts to transmit the disease to
susceptible pigs by placing them on contaminated dirt
lots were unsuccessful. In pure culture, S. hyodysenteriae
survives at −80˚C for more than 10 years. The above ob-
servations indicate that although S. hyodysenteriae is an
anaerobic bacterium, it may have the potential to survive
under a wide range of environmental conditions.
The origin of most epizootics of SD can be explained
by the fact that carrier pigs were introduced into a herd.
However, outbreaks of the disease do occur in herds with
no history of introduction of new animals. Robertson et
al. (1992) found a high odds ratio for both allowing visi-
tors onto farms and the presence of rodents. Other fac-
tors that play a role in the induction of symptoms of SD
in infected pigs are stresses, including a change in feed,
shipping, castration, overcrowding, and exposure to ex-
treme changes in environmental temperatures. Where
antibiotic medication is routine, any cause of loss of ap-
petite, such as pneumonia, stops the intake of drug; the
animal can then succumb to SD. The disease seems to oc-
cur frequently in the late summer and fall.
The incubation period of SD is variable. Specific re-
ports range from 2 days to 3 months, but the disease usu-
ally occurs within 10–14 days in naturally exposed pigs.
Olson (1974) showed that treatment with preventive lev-
els of sodium arsanilate may be a factor in prolonging
the incubation period.
Experimental oral inoculation of starvation-stressed
pigs with colonic mucosa from acutely affected donors
has resulted in lesion formation within 24 hours. Varia-
tion in incubation time occurs with varied doses of in-
oculum. Unfortunately, some animals may carry the in-
fection for days with no clinical signs. Unknown
circumstances usually described as “stress” may induce
the active disease and spread of infection to other ani-
mals.
PATHOGENESIS
Swine dysentery is associated with the proliferation of S.
hyodysenteriae and perhaps other synergistic supporting
organisms within the large intestine. Although S. hyo-
dysenteriae can be seen within epithelial cells and the
lamina propria of tissues with typical lesions, invasion
may not be essential for lesion production (Glock et al.
1974). The organism is motile due to the presence of
periplasmic flagella, and motility is essential for viru-
lence (Rosey et al. 1994, 1995). Due to its motility, S. hy-
odysenteriae is efficient at moving through viscous mater-
ial such as mucus and has been shown to be attracted to
hog gastric mucin by chemotaxis (Kennedy et al. 1988;
Milner and Sellwood 1994). It is thus able to get close to
epithelial cells in the colon (Wilcock and Olander 1979a,
b). Knoop et al. (1979) and Bowden et al. (1989) demon-
strated attachment of S. hyodysenteriae to animal cells in
vitro. Bowden et al. (1989) concluded that binding ad-
hesins on S. hyodysenteriae for cultured Henle intestinal
epithelial (HIE 407) cells may contain sialic acid residues.
Cellular damage and invasion did not occur. Whether at-
tachment is an important feature in the disease has not
been clearly demonstrated. S. hyodysenteriae is an oxy-
gen-tolerant anaerobe and is able to chemically reduce
molecular oxygen to water via NOX (Stanton and Jensen
1996). Kennedy et al. (1996) prepared nox mutant strains
of the organism that were less pathogenic for pigs and
appeared to have less ability to colonize the colon. There-
fore, wild-type S. hyodysenteriae may be able to associate
with the oxygen-rich colonic epithelium and thus exert
its pathogenicity.
Although the mechanism of tissue destruction has
not been fully elucidated, two toxins (hemolysin and
lipooligosaccharide [LOS]) of S. hyodysenteriae have been
described and characterized that may play a role in lesion
production. The hemolysin produced by S. hyodysenteri-
ae as extracted by Kent et al. (1988) is cytotoxic for sev-
eral types of cell cultures and is a major virulence factor
in the disease (Hyatt et al. 1994). By contrast, hemolysin
prepared from the avirulent strain of S. hyodysenteriae
VS1 was less toxic for cell cultures (Kent and Lemcke
1984). Lysons et al. (1991) demonstrated damage to ep-
ithelial cells in germfree pig ligated ileal and colonic
loops injected with hemolysin. Damage occurred after
0.5–1 hour when cell organelles were disrupted; swelling
and shedding of cells had occurred after 3 hours. The
pattern of damage was similar to that observed by Kang
and Olander (1990) when following early changes at in-
tervals after injecting pig colonic loops with cultures of S.
hyodysenteriae. Definitive work on the importance of he-
molysin followed the cloning of the RNA-core hemolysin
gene (tlyA) by Muir et al. (1992). Hyatt et al. (1994) pro-
duced tlyA mutants and compared them to parent strains
of S. hyodysenteriae by oral inoculation of pigs. The mu-
tant strains of the organism were able to colonize pigs
but did not produce disease. The LOS described origi-
nally by Baum and Joens (1979a) has endotoxic activity
that may have a direct effect on the epithelial cells of the
large intestine (Nuessen et al. 1983) and may elicit an in-
flammatory response via the stimulation of production
of IL-1 and TNF (Greer and Wannemuehler 1989b).
However, treponemal endotoxin was less potent than Es-
cherichia coli endotoxin at stimulating IL-1 and TNF and
causing death in galactosamine-sensitized BALB/ByJ
mice (Greer and Wannemuehler 1989a, b).
Whipp et al. (1978) reported that sterile filtrates of
broth cultures of S. hyodysenteriae caused no fluid accu-
mulation in ligated colonic loops of pigs or in sucking
mice. Furthermore, sterile filtrates did not produce
changes in Y-1 adrenal cells. Inactivated whole cells and
sonically disrupted suspensions of S. hyodysenteriae do
not cause lesions or fluid accumulation in ligated colonic
segments of pigs.
 CHAPTER 42 SWINE DYSENTERY Harris, Hampson, Glock
The causative organisms do not invade beyond the
lamina propria of the large intestine, and the lack of S.
hyodysenteriae and significant lesions in other organs im-
plies that the entire pathogenesis of the disease can be di-
rectly attributed to the enteric lesions (Kinyon et al.
1980). The primary systemic effects of typical SD are the
result of fluid and electrolyte imbalance induced by en-
teritis. The pathogenesis of peracute deaths is not known
but could be attributable to endotoxin.
The pathophysiology of the disease has been studied
by Argenzio et al. (1980), Argenzio (1981), and Schmall
et al. (1983). In contrast to what would be expected from
histological interpretations, the diarrhea observed is not
the result of increased mucosal permeability and leakage
of protein and extracellular fluid from blood to lumen
because of increased tissue hydrostatic pressures. In-
stead, the fluid loss appears to be the result of colonic
malabsorption as a consequence of the failure of the ep-
ithelial transport mechanisms to actively transport sodi-
um and chloride ions from lumen to blood. Further-
more, cyclic adenosine monophosphate (cAMP) and
cyclic guanosine monophosphate (cGMP) levels in
colonic mucosa of infected pigs were normal, but their
response to a stimulus (theophylline) was markedly at-
tenuated. Thus, these studies strongly suggest that an en-
terotoxin and/or prostaglandins released from the in-
flamed mucosa are not involved in the production of
diarrhea. Therefore, the pathogenesis of dysentery is un-
like the diarrhea induced by enterotoxigenic E. coli or
Salmonella spp.
Studies of small-intestine function in infected pigs in-
dicated that the glucose-stimulated fluid-absorptive
mechanism was intact and that no additional small-in-
testinal secretory component was present. Therefore, the
fluid losses are exclusively the result of failure of the
colon to reabsorb the animals’ own endogenous secre-
tions. Because as much as 30–50% of the extracellular
fluid volume of these animals, in the form of endoge-
nous secretions, is presented daily to the colon for ab-
sorption, colonic absorptive failure alone is sufficient to
explain the progressive dehydration and death associat-
ed with the disease. These studies also imply that oral
glucose-electrolyte solutions would be useful as a thera-
peutic measure in restoring these extracellular fluid loss-
es.
CLINICAL SIGNS
Diarrhea is the most consistent sign of SD, but the sever-
ity may be quite variable. The disease usually spreads
gradually through an infected herd, with new animals
being affected each day. The course varies not only be-
tween individual animals within a herd but also between
herds.
Occasional animals are peracutely affected and die af-
ter a period of only a few hours with little or no evidence
585
of diarrhea. This syndrome is, however, uncommon. The
first evidence of the disease in most animals is soft, yel-
low to gray feces. Partial anorexia and increased rectal
temperature of 104–105˚F (40–40.5˚C) may be evident
in some animals, but not uniformly so. After a few hours
to a few days following infection, there are large amounts
of mucus and often flecks of blood in the feces. As the di-
arrhea progresses, watery stools containing blood, mu-
cus, and shreds of white mucofibrinous exudate are seen
with concurrent staining of the rear quarters. An arched
back and occasional kicking at the abdomen suggest ab-
dominal pain. Prolonged diarrhea leads to dehydration
with increased thirst, and affected animals become
gaunt, weak, incoordinated, and emaciated.
Most pigs follow the same general sequence of clini-
cal signs, but the time involved may vary from hours to
weeks, and arbitrary separation into acute, subacute,
and chronic categories is often made. The feces in chron-
ic forms often contain well-mixed dark blood leading to
so-called black scours. A walk through the facilities hous-
ing an infected herd may permit the observation of soft,
yellow or gray feces, some mucoid feces with partially
mixed blood, and uniformly dark red or brown feces of
variable consistency.
The ultimate cause of death in most animals is asso-
ciated with dehydration, acidosis, and hyperkalemia,
which are discussed in greater detail below. The cause of
the occasional peracute deaths is not known.
Suckling pigs are not commonly affected and are an
exception to the typical form of SD in that they may have
catarrhal enteritis without hemorrhage.
LESIONS
Gross Lesions
The first obvious signs noted in pigs that have died from
SD are emaciation and a hair coat that is often rough and
stained with feces. Dehydration is usually evident. A con-
sistent characteristic of the disease is the presence of le-
sions in the large intestine but not in the small intestine,
often with a sharp line of demarcation at the ileocecal
junction.
Typical changes in the acute stages of SD include hy-
peremia and edema of the walls and mesentery of the
large intestine. Inflammation may also induce swelling of
mesenteric lymph nodes and formation of small
amounts of clear ascitic fluid. Colonic submucosal
glands are often more prominent than normal and ap-
pear as white, slightly raised foci on the serosa, particu-
larly in subacute or chronic infections. There is obvious
swelling of the mucosa, with loss of the typical rugose
appearance. The mucosa is usually covered by mucus
and fibrin with flecks of blood, and the colonic contents
are soft to watery and contain exudate.
As the condition progresses, the amount of edema
within the wall of the large intestine may decrease. Mu-
586 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
cosal lesions may become more severe with increased fib-
rin exudation and may form thick, mucofibrinous
pseudomembranes containing blood. As lesions become
more chronic, the mucosal surface is usually covered by a
thin, dense, fibrinous exudate, often giving the appear-
ance of marked necrosis, which is quite superficial. Le-
sions can be found in clinically healthy pigs and appear
as discrete areas of reddening of the mucosa, usually
covered with some mucus, but with colon contents of
normal consistency.
Distribution of lesions within the large intestine
varies. In some instances the entire organ may be in-
volved, while at other times only certain segments may
be affected. Lesions tend to become more diffuse in the
later stages of the disease.
Other lesions may include hepatic congestion and hy-
peremia or congestion of the gastric fundus. However,
these lesions are also associated with other diseases and
are not specific for SD. The fact that the stomach may be
full is often interpreted as meaning the appetite was nor-
mal prior to death. It is probably more reasonable to as-
sociate the full stomach with gastric stasis. Pigs with en-
teritis also frequently ingest materials with a high fiber
content.
Microscopic Lesions
The only significant microscopic lesions are found in the
cecum, colon, and rectum. Typical acute lesions include
obvious thickening of the mucosa and submucosa due to
vascular congestion and extravasation of fluids and
leukocytes. There is also hyperplasia of goblet cells, and
the epithelial cells at the base of the crypts may be elon-
gated and hyperchromic in appearance. Increased num-
bers of various types of leukocytes may be present in the
lamina propria, but quantitative evaluation of this lesion
is difficult because of the relatively numerous leukocytes
present in normal animals. However, excessive accumu-
lation of neutrophils in and around capillaries near the
lumen is commonly observed.
Groups of epithelial cells on the luminal surface may
separate from the lamina propria early in the course of
the disease, resulting in exposure of capillaries. Focal ar-
eas of hemorrhage result and blood is trapped in the
overlying mucus, producing the typical blood-flecked ap-
pearance of the colonic contents in the acute stages of
the disease.
Later changes include accumulation of large
amounts of fibrin, mucus, and cellular debris in mucos-
al crypts and on the luminal surface of the large intes-
tine. Superficial necrosis of the mucosa may be exten-
sive, but deep ulceration is not typical. Increased
numbers of neutrophils may be seen throughout the
lamina propria. Large spirochetes with the appearance of
S. hyodysenteriae are found in the lumen and within
crypts at all stages of the disease but are most numerous
42.4. S. hyodysenteriae in colonic crypt and epitheli-
um (Warthin-Starry; ×750).
in the acute phase (Fig. 42.4). Invasion of crypt epitheli-
um is common.
Chronic changes are not very specific, with less hy-
peremia and edema. There is often more advanced su-
perficial necrosis of the mucosa, which usually has a
thick, fibrinous pseudomembrane. Ulceration is uncom-
mon unless there are secondary infections with Salmo-
nella spp.
Ultrastructural changes of the intestine during the
early stages of SD have been characterized. Large num-
bers of spirochetes with the appearance of S. hyodysen-
teriae are found at the luminal surface and within crypts
(Fig. 42.5). Adjacent epithelial cells have lesions, includ-
ing destruction of microvilli, swelling of the mitochon-
dria and endoplasmic reticulum, loss of other or-
ganelles, and decreased density. As damage becomes
more pronounced, the epithelial cells often shrink and
become dark. S. hyodysenteriae invade epithelial cells,
goblet cells, and the lamina propria and may be found in
large clusters within some epithelial cells, suggesting
that intracellular multiplication may occur (Glock 1971;
Taylor and Blakemore 1971; Taylor 1972; Glock et al.
1974).
Hematology
Hematologic changes in SD include marked alterations
in many measurable factors. Total leukocyte counts may
increase, but not consistently. However, a marked left
shift usually occurs, with high numbers of immature
neutrophils in circulation.
Other changes include early transient increases in
erythrocyte sedimentation rates and fibrinogen levels.
Packed-cell volumes vary but do not indicate significant
blood loss, and total plasma protein may be elevated as a
result of dehydration. Serum glutamic-oxaloacetic
transaminase levels remain normal.
 CHAPTER 42 SWINE DYSENTERY Harris, Hampson, Glock
The most significant changes occur in blood elec-
trolytes. Serum sodium, chloride, and bicarbonate levels
decrease, and a marked metabolic acidosis develops,
which may be fatal. Terminal hyperkalemia may be not-
ed and may be a significant cause of death along with
acidemia (Glock 1971).
DIAGNOSIS
The diagnosis of SD depends primarily on differentiat-
ing the condition from other potential causes of diar-
rhea. Factors that should be considered include history,
clinical signs, gross lesions, microscopic lesions, as well
as isolation and identification of S. hyodysenteriae.
SD may occur as a persistent problem within a herd,
with phases of increased or decreased severity. Diagnos-
tic problems are most likely to occur in a herd in which
the disease has not been previously diagnosed. History
may be helpful, as it is not unusual to have an outbreak
following the introduction of new animals, presumably
carriers, into the herd. Other situations that disrupt the
normal environment may also precipitate outbreaks in
herds that have been exposed to S. hyodysenteriae but in
which the overt disease has not been detected.
Clinical signs such as depression, dehydration, and
diarrhea with mucus and/or blood in the feces are quite
suggestive but offer only presumptive evidence. Temper-
ature increases are too moderate and inconsistent to be
of any diagnostic benefit. Hematologic changes as previ-
ously described are characteristic but not sufficiently
unique to be of any great differential value.
Further evidence may be obtained by necropsy. Only
acutely affected animals should be examined, since in a
chronically affected animal various secondary infectious
agents may cause confusion. The essential finding is a
587
42.5. Electron photomicrograph
of S. hyodysenteriae invading a
colonic epithelial cell (Glock and
Harris 1972).
diffuse enteritis limited to the large intestine. Mucofibri-
nous exudate and free blood in the lumen are character-
istic but do not eliminate some differential questions.
Typical microscopic lesions of mucosal edema and mi-
crofibrinous enteritis with superficial erosion are helpful
but not very definitive as diagnostic criteria.
Confirmation of a diagnosis of SD requires isolation
and identification of S. hyodysenteriae from the colonic
mucosa or feces, or demonstration of S. hyodys-
enteriae–specific proteins or nucleic acid sequences. Early
isolation studies involved passage of mucosal extracts
through filters of decreasing pore size, but this technique
is no longer routinely used. Songer et al. (1976) devel-
oped a selective isolation medium that utilized 400
µg/mL spectinomycin hydrochloride incorporated in
trypticase soy agar and 5% bovine or horse blood. Other
antibiotics are often added to the medium to increase its
selectivity in terms of inhibition of other fecal microflo-
ra, including colistin and vancomycin, both at 25 µg/mL
(Jenkinson and Wingar 1981), or lower concentrations
of the previous three antimicrobials with 25 µg/mL spi-
ramycin and 12.5 µg/mL rifampin also added (Kunkle
and Kinyon 1988). Lemcke and Williams (1984) showed
that the addition of Na RNA (1%) to the selective medi-
um containing spectinomycin increased the degree of
hemolysis around colonies of S. hyodysenteriae and en-
hanced the viable counts of the organism. Fastidious
anaerobe agar (Lab M) gives a more lush surface growth
of S. hyodysenteriae (M. R. Burrows, pers. comm.—
1988).
Swabs may be used to collect samples of colonic mu-
cosa or feces. The samples should be stored at 4˚C and
kept moist in phosphate-buffered saline or a transport
medium until streaked onto the selective agar medium.
The selective medium should be utilized within 3 days of
588 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
preparation if stored at room temperature. Pure cultures
are more readily obtained if the agar surface is kept free
of moisture. Recently it has been recommended that S.
hyodysenteriae be separated from other fecal microflora
by cutting the agar in parallel cuts and streaking perpen-
dicular to the cuts (Olson 1996). The spirochete grows
out along the cut lines, and if motile contaminants are
present, these migrate farther along the cuts.
Whatever technique is used, after streaking, the
plates should be placed in an anaerobic container, typi-
cally containing a cold palladium catalyst and a mixture
of N2 or H2 and CO2. The anaerobic container should
contain an indicator (methylene blue) to ensure that a re-
duced atmosphere has been obtained within 2–3 hours
of closure. The plates should be incubated at 37˚C or
preferably 42˚C for at least 24–48 hours prior to their ini-
tial observation. On primary isolation, S. hyodysenteriae
produces zones of strong beta hemolysis in which
colonies are hard to distinguish, but a film of growth in
the hemolytic zone is grossly visible. As a routine, plates
without evidence of beta hemolysis should be further in-
cubated anaerobically and observed at 48-hour intervals
for at least 144 hours of incubation. Great care must be
taken to distinguish the weakly beta-hemolytic zones of
growth produced by S. innocens and other Serpulina spp.
from those produced by S. hyodysenteriae. To adequately
distinguish S. hyodysenteriae from more weakly hemolyt-
ic organisms, serial passage on trypticase soy agar with
5% blood may be required. Serial passage is readily ac-
complished by removing plugs of agar from within the
hemolytic zones (free of other colony-forming bacteria)
and transferring the agar to fresh medium. The plugs of
agar should be dispersed on fresh medium with a trans-
fer loop to free the spirochetes from the agar.
Once a strongly hemolytic spirochete is isolated, a va-
riety of other methods have been described that may
help to confirm its identity. As discussed earlier, spiro-
chete isolates can be tested for pathogenicity in pigs or
mice, looking for pathological changes typical of SD.
Other, more practical methods for distinguishing be-
tween S. hyodysenteriae and other spirochetes include a
fluorescent antibody test with absorbed antiserum, a
growth-inhibition test (Lemcke and Burrows 1979), en-
zyme analysis (Hunter and Wood 1979), rapid slide ag-
glutination (Burrows and Lemcke 1981), and biochemi-
cal differential tests, such as the production of indole.
None of these tests are completely specific by themselves
but are useful in conjunction with information on
strength of hemolysis.
Improved identification methods include the demon-
stration of S. hyodysenteriae–specific antigens or nucleic
acid sequences. Some candidate antigens have been iden-
tified. Baum and Joens (1979b) described a protein iso-
lated and purified from phenol-phase material of a phe-
nol/water extraction of isolate B169 of S. hyodysenteriae
by starch-block electrophoresis. In agar gel diffusion
tests this protein reacted with antisera prepared against
all isolates of S. hyodysenteriae but not with those pre-
pared against isolates of S. innocens. Sellwood et al.
(1989) identified a prominent 16 kDa protein band pres-
ent on the outer membrane of S. hyodysenteriae, but un-
fortunately this lipoprotein is no longer considered to be
species specific (Turner et al. 1995). A 30 kDa outer-
membrane protein of S. hyodysenteriae, to which a mon-
oclonal antibody has been generated, appears to be a bet-
ter species-specific target (Lee and Hampson 1996). The
monoclone can be used to identify S. hyodysenteriae in
immunofluorescence and agglutination assays, as well as
in Western blot analysis.
The direct culture of S. hyodysenteriae from colonic
tissue or feces is central in confirming the diagnosis of
the disease. But, as with other enteric diseases, the sensi-
tivity of this procedure is dependent upon the number of
organisms present in the sample. Pigs acutely affected
with SD possess large numbers (108–109/g) of S. hyo-
dysenteriae in their colonic mucosa and feces. By contrast,
pigs that are asymptomatic may only shed the organism
periodically at detectable levels in their feces (Harris et
al. 1978). Furthermore, medications commonly used to
treat or prevent SD may reduce the number of organ-
isms below culturally detectable levels. Therefore, great
caution must be used in interpreting the results of nega-
tive culture results, particularly from fecal samples. In an
attempt to increase the sensitivity of detection, nucleic
acid probes (Jensen et al. 1990; Combs and Hampson
1992; Sotiropoulos et al. 1993) and polymerase chain re-
action (PCR) amplification of specific sequences (Combs
et al. 1994; Elder et al. 1994; Harel and Forget 1995;
Atyeo et al. 1996) have been developed for S. hyodysente-
riae. Probes have been used to detect 105 cells per gram of
pig feces (Jensen et al. 1990), but the technique is quite
technically difficult and time-consuming. The PCR is a
simpler technique and can detect much fewer organisms,
but unfortunately there often are substances in porcine
fecal samples which inhibit the reaction. For this reason
the PCR is usually used on growth from the primary iso-
lation plate. Even under these circumstances, PCR offers
a more rapid and sensitive approach to diagnosis than
does the more routine isolation and biochemical identifi-
cation of the spirochetes (Atyeo et al. 1996).
The identification by Lysons et al. (1982) of avirulent
strains of S. hyodysenteriae poses a problem for the diag-
nosis of SD. To date, such organisms have been identi-
fied only in the United Kingdom and Australia, but diag-
nostic laboratories throughout the world should be
aware of their existence. Until we have simple laborato-
ry-based assays to detect virulence determinants, it is ul-
timately necessary to conduct in vivo tests to determine
if strongly beta-hemolytic isolates from herds without
typical signs and lesions of SD are pathogenic S. hyo-
dysenteriae.
It is common practice to conduct direct examination
of smears prepared on slides from colonic mucosa or fe-
ces of pigs suspected of being affected with SD. Workers
 CHAPTER 42 SWINE DYSENTERY Harris, Hampson, Glock
in the United Kingdom have utilized an absorbed anti-
serum in an indirect fluorescent antibody test to detect S.
hyodysenteriae (Hunter and Saunders 1977). Joens et al.
(1978b) in the United States and Lysons and Lemcke
(1983) in the United Kingdom questioned the specificity
of this test. However, improvements have been made to
the procedure in the United Kingdom by cross-absorbing
the serum with a number of strains of weakly hemolytic
spirochetes to increase its specificity. The use of specific
monoclonal antibodies, as described by Lee and Hamp-
son (1996), will improve this situation further. The ex-
amination of smears for the presence of S. hyodysenteriae
is less sensitive than isolation and identification of the
organism (Lysons and Lemcke 1983). Direct microscopic
examination revealing large numbers of organisms re-
sembling S. hyodysenteriae in samples from diseased pigs
can be used as presumptive evidence of SD, at least until
completion of cultural examination. In such cases the
possibility of the condition being porcine intestinal
spirochetosis (PIS) caused by S. pilosicoli (see Chapter 40)
also must be considered. Mucosal or fecal smears may be
examined as wet mounts by phase-contrast or dark-field
microscopy or stained with crystal violet, dilute carbol
fuchsin, or Victoria blue 4-R stains and viewed by light
microscopy. Serpulina spp. are easily recognized by these
techniques but cannot be differentiated. Electron micro-
scopic examination of negative-stained preparations of
intestinal or fecal fluids may detect the organisms but
does not distinguish between the species. The organisms
can also be demonstrated by light microscopy in sections
of the colonic mucosa by staining with Warthin-Starry,
Victoria blue 4-R, or Goodpasture stains.
Campylobacter (synonym Vibrio) spp. may appear in
increased numbers in some affected animals, but such
organisms are often numerous in normal animals. There-
fore, no diagnostic significance should be associated with
the observation or isolation of Campylobacter spp.
Several serologic tests have been reported that detect
antibodies to S. hyodysenteriae in serum of experimental-
ly affected pigs. To date, these tests have not been based
on species-specific antigens and consequently have had
low specificity and/or sensitivity. Tests include macro-
scopic agglutination (Joens et al. 1978c), indirect fluores-
cent antibody, passive hemolysis (Jenkins et al. 1976),
enzyme-linked immunosorbent assays (ELISAs) using
various plate-coating antigens (P. Høgh, pers. comm—
1979; Burrows et al. 1984), and agar gel diffusion (L. A.
Joens, pers. comm.—1979). Egan et al. (1983) designed a
method for determining the accuracy of serologic testing
for SD as a means of determining the prevalence of the
disease and the usefulness of serology for diagnosis.
They compared the accuracy and sensitivity of the mi-
crotitration agglutination test and an LPS-based ELISA
(Joens et al. 1981) by evaluating the level of antibodies in
the sera of three age groups of swine from 22 farms; 14
of the farms had a previous history of SD and 8 had no
history that the disease had ever occurred. Egan et al.
589
(1983) concluded that this ELISA could be used for de-
termination of the prevalence of SD but not for detec-
tion of individual pigs affected with the disease. LPS-
based ELISA systems also have the disadvantage that
they require a knowledge of the serotypes of organisms
present in the herds to be tested (Mhoma et al. 1992).
Further research must be done before national con-
trol schemes or import-export regulations are formulat-
ed based on serologic tests. The specificity of such tests
could be improved by the identification and use of an S.
hyodysenteriae–specific antigen that is recognized by in-
fected pigs: the 30 kDa outer-membrane protein de-
scribed by Lee and Hampson (1996) is one possible can-
didate.
Proliferative enteritis (porcine intestinal adenomato-
sis) may clinically resemble the symptoms of SD. How-
ever, SD does not affect the small intestine, whereas pro-
liferative enteritis usually occurs primarily in the small
intestine. Necrotic debris and blood that originated in
the anterior intestine will often be present in the large in-
testine and feces of pigs affected with proliferative en-
teritis. Weakly hemolytic spirochetes are commonly iso-
lated from cases of proliferative enteritis, although they
are not known to play a role in the disease. A definitive
diagnosis of proliferative enteritis depends on the lack of
isolation of S. hyodysenteriae, lesions characteristic of
proliferative enteritis, and the presence of organisms
with the appearance of Lawsonia intracellularis in the in-
testinal epithelium.
Salmonellosis, in particular Salmonella choleraesuis
infection, can be easily confused with SD because symp-
toms and lesions may be quite similar. It should be kept
in mind that hemorrhage or necrosis in parenchymatous
organs and lymph nodes may be expected with salmo-
nellosis but not with SD. Mucosal lesions may be found
in the small intestine with salmonellosis but not with un-
complicated SD. Deep ulcerative enteric lesions are also
much more typical of salmonellosis. The definitive diag-
nosis depends on lack of S. hyodysenteriae in the mucosa
of the large intestine and the isolation of Salmonella spp.
from the intestine or other organs such as lymph nodes
or spleen. The mere isolation of Salmonella spp. does not
constitute a positive diagnosis, since both normal ani-
mals and animals with SD may harbor Salmonella spp.
Trichuriasis may be differentiated on the basis of the
presence of numerous Trichuris suis in the large intestine
and the lack of S. hyodysenteriae. It should be noted that
concurrent infections can occur, and possible potentia-
tion of SD by T. suis has been postulated. Here again,
demonstration of the absence of S. hyodysenteriae is nec-
essary to eliminate the possibility of both infections be-
ing present.
Gastric ulcers and other hemorrhagic conditions may
cause the presence of blood in the feces and confusion
with SD. These conditions are easily differentiated at
necropsy since they generally involve the anterior diges-
tive tract.
590 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
“Colitis” is a diet-related disease syndrome of grow-
ing pigs that can resemble SD both in clinical signs and
in postmortem appearance (Lysons et al. 1988). There
has been some confusion over this condition, and some
reported cases actually may have been spirochetal diar-
rhea/PIS, caused by infection with Serpulina pilosicoli
(Taylor et al. 1980; Hampson and Trott 1995; Chapter
40, this volume). Typically, pigs aged 7 weeks or more are
affected. They have a watery scour, or sometimes just soft
feces, and lose body condition. Some pigs will have mu-
cus and/or blood in the feces. Lesions are confined to the
colon. In the early stages of the disease, the entire large
intestine is filled with liquid contents and there is a mild
reddening of the colon. Pigs in which the disease persists
can become thin, excrete mucus, and have a mucofibri-
nous exudate on the mucosal surface of the colon. To
eliminate SD from the diagnosis, it is necessary to autop-
sy pigs in the early stages of the disease and to carry out
extensive screening for the presence of S. hyodysenteriae.
In some laboratories samples from such cases are rou-
tinely subjected to PCR for both S. hyodysenteriae and S.
pilosicoli (Atyeo et al. 1996). Clearly, PIS represents the
most difficult differential diagnosis, since it so closely re-
sembles mild cases of SD. Although it responds to simi-
lar treatment, an accurate diagnosis is important be-
cause, in general, PIS has much less economic impact in
individual herds than SD does. Furthermore, it appears
that aspects of the epidemiology of PIS may differ from
those described here for SD (Hampson 1997).
TREATMENT
Pigs acutely affected with SD should be medicated via the
water. Usually, animals in the early stages of the disease
consume very low amounts of feed. This precludes plac-
ing therapeutic levels of drugs in the feed as a method of
treatment. Occasionally moribund animals may require
systemic injection of drugs, but this is usually impracti-
cal in large-herd situations. Medication is often added to
the feed as a method of preventing SD.
Table 42.2 lists the dosage levels, duration of admin-
istration, and withdrawal times of various drugs used for
the treatment and/or prevention of SD as approved by
the U.S. Food and Drug Administration. Harris and
Glock (1975, 1981, 1986) have reviewed other drugs that
have been used to either treat and/or prevent SD. Treat-
ment of SD is usually accomplished by administering ei-
ther chemotherapeutics or antibiotics, sometimes sup-
plemented with electrolytes.
Chemicals that have been reported to be effective for
the treatment and/or prevention of SD are sulfon-
amides, nitrofurans, quinoxalines, ionophores, mutilins,
and the nitroimidazoles.
The following antibiotics have been reported to be ef-
fective for the treatment and/or prevention of SD: strep-
tomycin, bacitracin, neomycin, tylosin, gentamicin,
chlortetracycline, virginiamycin, and lincomycin (Harris
and Glock 1975).
Methods for in vitro sensitivity testing of antimicro-
bials have been developed utilizing either liquid or solid
media (Kitai et al. 1979; Kinyon and Harris 1980). Iso-
lates resistant to certain antimicrobials have been re-
ported from various parts of the world. In general, iso-
lates resistant to carbadox or tiamulin are uncommon
while resistance to other antimicrobials is reported more
frequently. Walter and Kinyon (1990) found that 38 iso-
lates of S. hyodysenteriae from the United States were ful-
ly susceptible to carbadox, dimetridazole, and tiamulin
while many isolates were resistant to bacitracin MD, gen-
tamicin, and lincomycin. Isolates resistant to sodium ar-
sanilate, lincomycin, and tylosin have also been reported
from the United States (Kinyon and Harris 1980). Iso-
lates resistant to (in order of increasing frequency of re-
sistance) carbadox, dimetridazole, ronidazole, and lin-
comycin have been reported from Canada (Messier et al.
1990), and all isolates were found to be susceptible to tia-
mulin. Ronne and Szancer (1990) found 25 Danish iso-
lates to be fully susceptible to tiamulin and most or all
isolates resistant to lincomycin, dimetridazole, and ty-
losin. Buller and Hampson (1994) tested 30 Australian
isolates and found 2 resistant to dimetridazole and 1 re-
sistant to tiamulin; 90% of isolates were resistant to lin-
comycin and tylosin. Molnar (1996) tested 332 Hungari-
an isolates of S. hyodysenteriae isolated between 1978 and
1992 and found all isolates to be susceptible to carbadox,
but isolates resistant to dimetridazole, lincomycin, and
tiamulin were reported. Binek et al. (1994) tested 83 Pol-
ish isolates of S. hyodysenteriae isolated from 1982 to
1993, finding all isolates remained susceptible to tia-
mulin while complete reistance had developed for lin-
comycin, ronidazole, and metronidazole during the peri-
od.
As with the treatment of any infectious disease, suc-
cessful therapy is dependent on an accurate differential
diagnosis distinguishing SD from other enteric bacterial
or parasitic diseases. Government regulatory approval
(drug availability), antimicrobial resistance patterns,
and cost typically dictate drug selection and usage. Po-
tential effectiveness against concurrent infections, either
enteric or respiratory, and the goal of treatment (con-
trolling vs. eradicating the disease) are also important
considerations in drug selection. Ensuring adequate con-
sumption (dosage and duration) of properly medicated
feed and/or water is essential to achieve desired results
with those routes of administration.
Elimination of SD by Medication
and Cleaning
The use of drugs on all ages of pigs on the premises and
careful cleanup and disinfection procedures have been
successfully utilized to eradicate SD from affected herds
without depopulation. Songer and Harris (1978) report-
 CHAPTER 42 SWINE DYSENTERY Harris, Hampson, Glock 591

Table 42.2. Dosage level, duration of administration, and withdrawal times for various drugs used for the
treatment and prevention/control of SD as approved by the U.S. Food and Drug Administration
Dosage by Dosage in Dosage in Duration Withdrawal
Drug Injection Water Feed (days) (days)
Treatment of SD
Bacitracin 1000 mg/gal, 7–14a None
264 mg/L
Gentamicin 50 mg/gal, 3 3 (oral solution)
13.2 mg/L 10 (sol. powder)
Lincomycin 3.8 mg/lb/day, 5–10a None
8.4 mg/kg/day
(250 mg/gal,
66 mg/L)
100 g/t 21a None
Tiamulin 3.5 mg/lb/day, 5a 3
7.7 mg/kg/day
(227 mg/gal,
60 mg/L)
200 g/t 14a 7
Tylosin 4 mg/lb IM ≤3 14
(8.8 mg/kg)
twice daily
250 mg/gal, 3–10 2
66 mg/kg
Virginiamycin 100/g/t 14 None

Prevention of SD
Bacitracin 250 g/t None
Carbadox 50 g/t 42

Lincomycin 40 g/ta None

Tiamulin 35 g/ta 2
Tylosin 100 g/t ≥3 weeks None
Followed by To market None
40 g/t
Virginiamycin 25–50 g/t Not over None
120 lbs
(54 kg) BW
Note: The information in this table is an abbreviated summation of product labeling. For more complete information review the prod-
uct label. BW = body weight. IM = intramuscular.
a
Not approved for use in swine over 250 lbs (109 kg) body weight.

ed that S. hyodysenteriae could be completely eliminated
from pigs by treatment with dimetridazole or ronidazole
when pigs were housed in conditions minimizing expo-
sure to their feces. Rainier et al. (1980) showed that car-
badox would also eliminate the organism from pigs un-
der similar conditions. Taylor (1980) has also eliminated
SD using tiamulin. Veterinarians from several countries
have reported the successful elimination of SD from af-
fected herds by medication of all pigs on the premises
(Glock 1979). During the medication period the facilities
should be cleaned and disinfected frequently to mini-
mize the environmental survival of S. hyodysenteriae. In
addition, the rodent population on the farm should be
reduced and, in the pig buildings, should be eliminated.
The regimes for eradication have varied greatly. The
medication period has been as short as 5 days (Moller
1984) or as long as 6 months (Wood and Lysons 1988).
The former approach depended on intensive, high-level
medication to all pigs via drinking water or oral dosing;
the latter concentrated on elimination of S. hyodysenteri-
ae from sows as they came into the farrowing house.
General guidelines for eradicating swine dysentery
from a herd without depopulation are given below (Har-
ris and Glock 1981):
1. A warm season in which temperatures are higher
than 15˚C (59˚F) is preferable.
2. The number of animals in the herd should be de-
creased to as few as possible.
3. If farrowings occur in batches, the recommended
time to eradicate the disease is when no suckling pigs are
on the farm.
4. An effective rodent control program, including
renovation of buildings, should be instituted.
592 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
5. All liquids should be removed from pits within
buildings in which pigs are housed.
6. Any buildings that do not contain pigs should be
cleaned and disinfected.
7. All pigs on the farm should be medicated simulta-
neously with drugs known to eliminate S. hyodysenteriae
from the pig intestinal tract. Care should be taken to en-
sure that inclusion rates of antibacterials in the diet of
animals, such as adult stock, on restricted feeding is ad-
justed so that the animals receive the correct dose/kg of
body weight.
8. After 1 week of medication, all equipment used
for handling pigs, feed, and manure should be cleaned
and disinfected.
9. During the medication period, an attempt should
be made to clean and disinfect floors of buildings fre-
quently. Animals should not be housed in overcrowded
conditions.
This method of elimination of the disease without
depopulation is not always successful. Muirhead (1984)
reported 11 attempts to eliminate SD from six herds; that
is, the success rate for any one attempt was 54%. With
careful selection of herds, including an assessment of the
ability and commitment of the workforce, and pretreat-
ment antimicrobial susceptibility testing of the endemic
isolate to ensure proper drug selection, the chances of
success are likely to reach 80–90% (Wood and Lysons
1988). To determine if the disease has been eliminated, it
is recommended that for 3–6 months following medica-
tion no antimicrobials be used that are efficacious for SD.
Clinical evidence of the disease will usually reappear if
the organism is still present. The increased feed-conver-
sion efficiency of SD-free pigs means that the cost of the
eradication program will usually be recovered in 6–12
months.
PREVENTION
The economically devastating effects of SD justify a seri-
ous effort to keep the disease from being introduced into
a noninfected herd. Infectious materials may be carried
into a herd by fomites such as workers’ boots, farm im-
plements, and trucks. Isolation of a herd and rigid sani-
tation are essential to reduce this potential hazard.
Introduction of new stock is an even greater hazard.
A reliable history of the source herd is the only assurance
of safety. Research efforts are being directed at various
methods of identification of carrier animals, and it is
hoped that serologic tests or other detection methods
will soon be available for use in screening potential herd
additions. Quarantine of all new animals is an excellent
procedure, especially since clinical signs often appear in
subclinically affected animals as a result of transporta-
tion. Furthermore, during quarantine, the newly pur-
chased animals could be placed on a drug(s) known to
eliminate S. hyodysenteriae from the intestinal tract to
preclude the introduction of the disease into the herd.
It is well accepted that although SD is very prevalent,
the disease may be readily eliminated by surgical proce-
dures used for repopulation. Once a herd is established
in the absence of the disease, such precautions as those
taken by the SPF or minimal-disease associations, the Pig
Health Control Association in the United Kingdom
(Goodwin and Whittlestone 1984), and the Health Con-
trol Programs of certain breeding-stock companies
(Alexander 1985) can prevent recurrence of S. hyodysen-
teriae. For example, newly established surgically derived
herds in some locales may eventually become infected
with such agents as Bordetella bronchiseptica and My-
coplasma hyopneumoniae but often can be maintained
free of S. hyodysenteriae. The introduction of S. hyodysen-
teriae into a susceptible farm primarily occurs with carri-
er pigs. Mice are considered only as reservoir hosts be-
cause mice do not usually migrate from farm to farm.
Rats are also considered reservoir hosts but do tend to
migrate from farm to farm. Thus rats may be the source
of introduction in some cases (Hampson et al. 1991;
Robertson et al. 1992). Such mechanical vectors of in-
fected feces as boots, coveralls, vehicles, migratory ani-
mals, and birds are also possible modes of introduction.
Losses in affected herds can also be reduced or pre-
vented by various management procedures. Outbreaks
of SD are often associated with conditions that produce
stress such as handling, transportation, severe weather,
or dietary changes. Minimizing stress or using preven-
tive levels of various efficacious compounds may be use-
ful aids. Sanitation is also extremely important, since the
severity of the disease within an individual or a herd is
directly related to the quantities of contaminated feces
that are ingested. Reducing crowded conditions and pro-
viding a clean, dry environment can produce dramatic
results. Conversely, poor sanitation will greatly enhance
the distribution and severity of the disease within a herd.
An example of this may be seen in occasional herds in
northern latitudes where severe outbreaks have followed
overfilling of waste pits under slatted-floor systems
when outlets became frozen.
Depopulation is a rather drastic but frequently neces-
sary measure to eliminate chronic SD. Because the
causative agent is anaerobic and susceptible to heat, oxy-
gen, drying, and disinfectants, it is recommended that
depopulation be done during warm, dry weather if pos-
sible. Thorough cleaning, disinfection and rodent exter-
mination should be followed by enough time to reduce
hazards of reinfection.
S. hyodysenteriae may survive in feces (pits and la-
goons) for 60 days. The organism does not survive for
long periods of time in feces-contaminated soil during
seasonal temperatures of 15˚C (59˚F) or above (Egan
1981). Therefore, dirt lots that have held pigs affected
with SD should remain free of pigs for at least 30 days
 CHAPTER 42 SWINE DYSENTERY Harris, Hampson, Glock 593

during a warm period of the year. Any liquid feces such
as in pits and lagoons should be considered to contain S.
hyodysenteriae for 90 days during periods of warm weath-
er. Therefore, lagoon water used for recycling should not
be utilized for several months after depopulation of the
affected pigs.
Repopulation is extremely critical because any pre-
ventive procedures are for naught if carrier pigs are in-
troduced into the herd. Only surgically derived pigs or
animals from reliable sources should be considered as re-
placement stock.
Serious losses may be prevented even in exposed
herds by use of preventive levels of various therapeutic
compounds. Judicious use of these compounds as de-
scribed in the section on treatment may be very benefi-
cial, but they should not be relied upon as a substitute for
good management.
Among veterinarians and producers, there has been
confusion regarding whether or not pigs that recover
from SD are subsequently immune. Pigs with experi-
mentally induced SD that recover without drug treat-
ment can be immune to rechallenge (Joens et al. 1979a),
or they may require more than one episode of disease be-
fore acquiring protective resistance (Rees et al. 1989).
Pigs that develop SD and recover without treatment
usually continue to excrete S. hyodysenteriae in their feces
(i.e., the immune status could be an infection immunity).
This immunologic state can be maintained under condi-
tions of good management. If some management stress
is applied, clinical symptoms of the disease can reap-
pear. If pigs that are acutely affected with the disease are
given effective pharmaceuticals for treatment, the devel-
opment of immunity may be impaired. Once the drug is
withdrawn, the pig may be readily reinfected by S. hyo-
dysenteriae present in the environment and exhibit clini-
cal symptoms of SD.
Sows that have been exposed to S. hyodysenteriae pro-
tect their suckling piglets. The feces of these immune
sows are the source of S. hyodysenteriae for the suckling
pigs. Pigs that are not weaned until 8–10 weeks of age
perhaps have a better chance to develop immunity than
pigs weaned at a younger age. Since a natural infected-
immune state can exist for SD involving a secretory im-
mune response (Joens et al. 1984; Rees et al. 1989), it is
possible that a vaccine could be developed to prevent the
disease. Several researchers have published information
about experimental attempts to prevent SD by active im-
munization. Most use a parenteral administration of
killed whole cells of S. hyodysenteriae (Fernie et al. 1983;
Parizek et al. 1985; Coloe and Gerraty 1988) or subunits
(Joens et al. 1990; Wannemuehler et al. 1990). Cloned
endoflagella antigens were demonstrated to confer pro-
tection in the CF-1 mouse model (Boyden et al. 1989) but
did not immunize pigs (Gabe et al. 1995). A combination
of killed whole cells given intramuscularly followed by
an oral vaccination with live avirulent S. hyodysenteriae
was a novel approach that gave better protection than in-
tramuscular vaccination alone (Lysons et al. 1986).
Hampson et al. (1993, 1994) reported that protection
with whole-cell bacterins may be serotype specific, which
may be important for bacterins marketed either region-
ally or globally.
A killed whole-cell vaccine was marketed until re-
cently in the United States, but with minimal sales. A
subunit vaccine (Wannemuehler et al. 1990) containing
both serotypes 1 and 2 of S. hyodysenteriae and a metab-
olizable adjuvant was licensed and marketed in the Unit-
ed States in mid-1997.
PRACTICAL VETERINARY ADVICE
TO PRODUCERS
The most important mode of transmission of SD from
farm to farm is the asymptomatic carrier pig. Reservoir
hosts for S. hyodysenteriae are pigs, rats, and mice. The or-
ganism also survives readily in feces, particularly in
waste pits (Table 42.3).
In herds known to be free of SD, the practitioner
should determine that replacement breeding stock and
purchased feeder pigs are free of the disease. In produc-
tion facilities where the disease is endemic, reduction in
production costs can be attained by eradication of the

Tabe 42.3. Survival time of S. hyodysenteriae in animals and the environment

Temp.
Location Condition °F °C Survival Time
Pigs − − − 60 days
Mice − − − 1 year
Rats − − − 2 days
Dogs − − − 13 days
Feces
Pits Moist 45 7 60 days
Hog lots Dry 65 18 7 days
Hog lots Cold or frozen 45 7 Until temp. increases
Lagoons − − − 60 days
Source: Harris et al. 1990.
594 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
organism without depopulation; by two-site production
with partial depopulation; or by total depopulation,
cleanup, disinfection, and repopulation with SD-free
stock (Polson et al. 1992).
Establishing a Diagnosis of SD
A diagnosis of SD based on clinical signs and/or gross
and histological lesions should be confirmed by isolation
and identification of S. hyodysenteriae. If no clinical signs
of SD have been observed in the herd, the veterinarian
must be assured by the farmer that drugs and vaccines
known to be effective for the treatment and prevention of
SD are not being used and thus masking the disease.
Clinical signs of SD should become apparent in 3–6
months, particularly in confinement facilities in the ab-
sence of drugs and vaccines.
Preventing Introduction of S. hyodysenteriae
into SD-Free Herds
Herds that have been established as free of SD and are ei-
ther closed or maintained in a closed pyramid will re-
main free of SD if situated in an isolated locale and pre-
cautions are taken to prevent contamination by feces
from carrier pigs. If breeding stock or feeder pigs are in-
troduced into the herd, care should be taken to limit the
introductions to as few sources as possible and to pro-
cure the pigs from herds known to be free of SD. Pigs
should be purchased from herds that do not use drugs or
vaccines known to prevent the occurrence of SD. In ad-
dition, the source herd should not have made recent in-
troductions of pigs from questionable or SD-positive
herds. It is not recommended that tests be conducted to
ascertain the SD status, because cultural tests lack sensi-
tivity (Harris et al. 1978) and serologic tests often have
false-positive reactions (Egan et al. 1983). A fecal ELISA
has been developed but it appears to be no more sensi-
tive than culture, and false-positive reactions also occur
(Taylor and Stevenson 1986).
If the SD status of the source herd(s) cannot be as-
certained, then it is imperative that pigs be placed in
quarantine prior to entry into the SD-free herd. In quar-
antine, the pigs should either be nonmedicated and ob-
served for signs of SD or be appropriately medicated to
eliminate carriers of S. hyodysenteriae. It is more practical
to medicate, since it has been reported that unmedicated
pigs may remain asymptomatic carriers of the disease
for at least 60 days (Songer and Harris 1978).
Herd Elimination Programs
In some situations, pig producers must continually use
medications and vaccines for control of SD (Harris et al.
1990). Quite often, however, the cost of such programs is
prohibitive due to poor profitability. If the producer is
capable of maintaining a herd free of SD, then consider-
ation should be given to eliminating S. hyodysenteriae
from the herd/facilities. Polson et al. (1992) reported a
definite financial advantage to eradication of S. hyo-
dysenteriae without depopulation versus either endemic
disease with constant medication/vaccination or total
depopulation/repopulation. The options are as follows:
1. Eradication of S. hyodysenteriae without depopula-
tion. S. hyodysenteriae can be eliminated from endemic
herds without depopulation, but the procedure is not al-
ways successful. Several drugs used either alone or in
combination have been reported to eliminate the infec-
tion from endemic herds when used in conjunction with
a sanitation program and rodent control (Blaha et al.
1986; Coulson 1986; Larsen 1987; Wetzel 1987; Olson
1988). Drugs that are recommended for this procedure
are lincomycin, carbadox, and tiamulin. The principle
applied for elimination without depopulation is to med-
icate all pigs in the herd via feed, water, and/or injection
for a period of several days to months. During this med-
ication period, a sanitation program is conducted to
eliminate the organism from the facility. In addition, the
rodent population is exterminated. The reason for failure
to eliminate the organism in this manner is believed to
be survival of S. hyodysenteriae in either slurry (Glock et
al. 1975) or mice (Joens and Kinyon 1982). More re-
search is needed to determine if vaccines could be of
benefit in such programs.
2. Isowean two- or three-site production with partial
depopulation. Endemic SD is often not difficult or costly
to control in the adult population. Dams previously re-
covered from SD confer resistance to their young during
the suckling period (Harris and Glock 1986). The cost of
medication to control SD to 18–32 kg body weight is not
prohibitive, since certain drugs at growth-promotion lev-
els often control SD in this age of pig. Therefore, if pigs
are removed from either the farrowing rooms after re-
ceiving colostrum as in isowean (see Chapter 72) or the
nursery accommodation up to 30 kg body weight, it is
possible that the pigs will be free of S. hyodysenteriae at
this time. Prior to removal from farrowing rooms or the
nursery, medications should be administered to the
piglets to eliminate S. hyodysenteriae. The SD-free pigs
should be isolated from the adult herd and moved to fa-
cilities not contaminated with S. hyodysenteriae. The use
of an SD vaccine in the sow herd may also be helpful in
this procedure.
3. Total depopulation, cleanup, disinfection, and re-
population with SD-free stock. The decision to totally de-
populate an ongoing pig operation should not be made
without serious deliberation and accurate financial cal-
culations (Wood and Lysons 1988). However, in some
situations, this alternative is the only method available to
eliminate S. hyodysenteriae from the herd/facilities. At
warm temperatures, the organism does not survive well
in soil (less than 7 days) (Egan 1981). Therefore, the most
important reservoirs for the organism in a depopulated
facility are the slurry and rodents. At temperatures above
 CHAPTER 42 SWINE DYSENTERY Harris, Hampson, Glock
60˚F (16˚C), facilities can be cleaned, disinfected, and re-
populated very rapidly.
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 Tuberculosis
43 C. O. Thoen

During fiscal year 1995 in the United States, 35,681,290 Table 43.1. Prevalence of tuberculosis in swine in
the United States as determined by inspection in
cattle (exclusive of tuberculin reactors) were slaughtered abattoirs under federal supervision
under federal inspection; of these, 136 carcasses
(0.0003%) were designated as being tuberculous. In con- Number Percent Percent
Year Slaughtered Tuberculosisa Condemnedb
trast, of 94,490,329 swine slaughtered during the same
period, 196,944 (0.21%) had lesions attributed to tuber- 1912 34,966,378 4.69 0.12
culosis (USDA 1996). The number of swine carcasses 1917 40,210,847 9.89 0.19
1922 34,416,439 16.38 0.20
with lesions attributed to tuberculosis is more than 1400 1927 42,650,443 13.54 0.14
times greater than that for cattle, and this is cause for 1932 45,852,422 11.38 0.08
concern. 1937 36,226,309 9.48 0.08
The processing of tuberculous swine carcasses is cost- 1942 50,133,871 7.96 0.026
1947 47,073,370 8.50 0.023
ly and results in significant economic losses. Regulations 1952 63,823,263 4.40 0.015
of the Meat and Poultry Inspection Program of the US- 1956 66,781,940 4.76 0.010
DA require that unaffected portions of swine carcasses 1962 67,109,539 2.25 0.008
with tuberculous lesions in more than one primary site, 1968 72,325,507 1.35 0.005
such as cervical and mesenteric lymph nodes, be cooked 1972 83,126,396 0.85 0.007
1978 71,805,911 0.75 0.006
at 170˚F (76.7˚C) for 30 minutes before being approved 1983 79,992,743 0.41 0.003
for human food (National Archives and Records Services 1989 82,110,688 0.67 0.002
1973). 1995 94,490,329 0.21 0.003
The public health significance of Mycobacterium avi- Sources: Data compiled from USDA 1922, 1973, 1979, 1984,
um complex infections has been recognized. Of special 1990, 1996; Feldman 1963.
a
interest are reports on the isolation of M. avium complex Includes all carcasses with evidence of tuberculosis, varying
from patients with acquired immune deficiency syn- in extent from only small foci in cervical lymph nodes to general-
ized involvement.
drome (Chin et al. 1994). b
Includes carcasses with evidence of generalized tuberculo-
There has been no direct campaign to eradicate tu- sis.
berculosis in swine. It was once believed that the cam-
paign to eradicate bovine tuberculosis, which was started
in 1917, would result in a reduction of the disease in France and Germany (Meissner et al. 1978), Hungary
swine in the United States. However, the percentage of (Szabo et al. 1975), Japan (Nishimori et al. 1995; Yugi et
swine with tuberculous lesions continued to increase for al. 1972), and South Africa (Kleeberg and Nel 1973).
a number of years (Table 43.1). These reports indicate the worldwide distribution of tu-
berculosis in swine due to M. avium. The similarity of M.
ETIOLOGY avium and so-called M. intracellulare has led to the pro-
posal that the latter be considered serovars of M. avium
Swine are susceptible to infection with Mycobacterium tu- complex (M. avium–M. intracellulare) (Wolinsky and
berculosis, M. avium, and M. bovis. The investigations of Schaefer 1973; Thoen et al. 1984); this has been done in
Van Es and Martin (1925) showed that in the United this chapter.
States most of the tuberculosis in swine was caused by A numbering scheme has been developed for report-
avian tubercle bacilli. M. avium serovars 1, 2, 4, and 8 are ing M. avium serovars (Wolinsky and Schaefer 1973).
the most common isolates from tuberculous lesions in Serovars 1, 2, and 3 occur mainly in animals but also in
swine in the United States (Mitchell et al. 1975; Thoen et humans, whereas serovars 4–8 are found in human pa-
al. 1975b). At least 15 other M. avium complex serovars tients and less commonly in animals. A micromethod
have been isolated from swine in the United States has been developed for identifying serovars of M. avium
(Thoen et al. 1975b) as well as in other countries: Aus- that saves time and materials (Thoen et al. 1975a). DNA
tralia (Tammemagi and Simmons 1971), Brazil (Pestana hybridization using probes for M. avium and M. intracel-
de Castro et al. 1978), Denmark (Jorgensen 1978), lulare has been shown to provide a rapid and reliable

601
602 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
method for identifying M. avium complex isolated from
swine (Thorensen and Saxegaard 1993).
The decrease in prevalence of tuberculosis in swine in
the United States is largely attributable to a lowering of
the incidence of tuberculosis in poultry, which in turn is
the result of the increasing practice of maintaining all-
pullet flocks of chickens. The control of tuberculosis in
swine is thus incidental to and a beneficial but secondary
effect of a changing practice of poultry husbandry. Per-
haps a more rapid decline in tuberculosis among swine
will occur if a direct and effective attack is made on tu-
berculosis in poultry.
Tuberculosis has been observed in large confined
swine herds, in which the infection is caused by M. avium
serovars 4 and 8. Outbreaks usually result in large losses
involving 30–60% of slaughter swine (Pritchard et al.
1977). The problem has been associated with the use of
sawdust and peat for litter (Dalchow and Nassal 1979;
Songer et al. 1980).
EPIDEMIOLOGY
Because swine are not routinely tested with tuberculin,
the only sources of information on the prevalence and
geographic distribution of tuberculosis in this species
are the data obtained from meat inspection records. On
this basis an increase in the rate of infection occurred in
the United States until 1922 (Table 43.1). During 1922,
16.38% of all swine slaughtered under federal supervi-
sion had tuberculous lesions; in 0.2%, the disease was so
extensive that the entire carcass was condemned. Since
1922, there has been a gradual decline; by 1995, the
prevalence had decreased to 0.21%, with only 0.003%
having evidence of generalized tuberculous disease.
Since most of the tuberculosis in swine in the United
States is of avian origin, the disease among swine is ex-
pected to be greater in the north central states, where tu-
berculosis among chickens is greater (Thoen 1997).
However, data from meat inspection records may be mis-
leading because in the United States swine may be
shipped great distances from the state of origin for
slaughter. Data on the prevalence of tuberculosis in
swine from meat inspection records may also be mis-
leading because the diagnoses are made on the basis of
the macroscopic appearance of lesions (Fig. 43.1). A cer-
tain number of tuberculous infections will escape detec-
tion because the lesions are not grossly visible. Avian tu-
bercle bacilli have been isolated from tonsils (Feldman
and Karlson 1940) and lymph nodes of apparently nor-
mal swine (Langenegger and Langenegger 1981).
In studies in the United States and Canada, where
presumably tuberculous lymph nodes of swine were col-
lected at abattoirs and examined bacteriologically, a
varying percentage failed to yield tubercle bacilli (Table
43.2). Similar observations have been made by workers
43.1. Tuberculous lesions in a mesenteric lymph node
of a pig at slaughter (Thoen 1994).
in Australia (Clapp 1956), Denmark (Plum 1946; Jor-
gensen et al. 1972), England (Cochin 1943), Finland
(Vasenius 1965), France (LaFont and LaFont 1968), and
Germany (Retzlaff 1966; Dalchow and Nassal 1979). The
failure to demonstrate tubercle bacilli in lesions that ap-
pear grossly to be tuberculous may be due to inadequacy
in present-day methods for isolating tubercle bacilli, oc-
currence of healed processes that contain no viable tu-
bercle bacilli, or cause of the lesions by some microor-
ganism other than tubercle bacilli, such as Rhodococcus
equi or R. sputi (to be discussed later).
Sources of Infection and Their Control
Swine are susceptible to infection with M. tuberculosis, M.
bovis, M. avium, and M. intracellulare. The occurrence of
tuberculosis in swine, therefore, is related to the oppor-
tunity for direct or indirect contact with tuberculous cat-
tle, humans, and fowl and to the prevalence of tubercu-
losis in all of these species.
The bovine tubercle bacillus is not a frequent cause of
tuberculosis in swine in localities where the disease in
cattle is controlled by a campaign of eradication. In the
United States and Canada, for example, bovine tubercle
bacilli are rarely found in lesions of swine (Table 43.2).
In Great Britain during 1952–55, the bovine type of tu-
berculosis in swine gradually declined concurrently with
the eradication of the disease in cattle. The percentage of
avian-type infection increased from 44% during the first
5 years of the study to 92% for the last 5 years (Lesslie et
al. 1968). However, the occasional finding of bovine tu-
bercle bacilli in swine is a reminder that the disease in
cattle is a constant threat. Efforts to eradicate bovine tu-
berculosis should not be diminished.
Where tuberculosis does occur in cattle, the infection
may be transmitted to swine by the feeding of unpas-
teurized milk and dairy by-products. Feces of tubercu-
lous cattle may contain viable tubercle bacilli; this pro-
vides an obvious hazard where swine and cattle are
maintained in a common feedlot.
The practice of feeding swine the offal from abattoirs
 CHAPTER 43 TUBERCULOSIS Thoen 603

Table 43.2. Summary of data compiled from reports in North America on the occurrence of tubercle bacilli in
tuberculous lymph nodes of swine
Type of Tubercle Bacillus (%)
Mammalian
Reference Datea Origin of Swine Specimens Avian only only Mixed Noneb
Van Es 1925b Nebraska 248 74.6 4.4 5.6 15.4
Van Es and Martin 1925b Michigan 14 92.9 None 7.1 None
Mitchell et al. 1934b Canada 96 38.5 None None 61.5
Feldman 1938b Southeastern 30 c 80.0 6.6 (bovine) None 13.3
Minnesota
Feldman 1939b Minnesota 75d 46.6 16.0 (human) None 37.3
Feldman and Karlson 1940b Minnesota 89 61.8 None None 38.2
Pullin 1946b Eastern Canada 232 44.8 0.9 (bovine) None 54.3
Bankier 1946b Alberta, Canada 102 88.0 1.0 (bovine) None 11.0
Karlson and Thoen 1971b Minnesota 36 72.0 None None 28.0
Thoen et al. 1975b United States 2036 76.0 <1.0 <1.0 22.0
Pritchard et al. 1977b Idaho 31 80.0 None None None
Cole et al. 1978b Georgia 112 53.6 None None 46.4
Margolis et al. 1994b Pennsylvania 125 70 None None 26
Note: Specimens obtained from abattoirs under federal supervision.
a
Several papers indicated that the work was done from 1 to 2 years before publication.
b
Tubercle bacilli not demonstrated by cultural or animal inoculation tests.
c
Selected cases of generalized tuberculosis; some of the specimens were portions of lung, liver, or spleen.
d
Garbage-fed swine.

or uncooked garbage is obviously unwise, because such
material may contain tuberculous material from beef
carcasses. Fichandler and Osborne (1966) described an
epizootic of tuberculosis in a herd of swine in Connecti-
cut that was fed improperly cooked offal from tubercu-
lous cattle. A serious outbreak of avian tuberculosis in a
swine-feeding establishment in Denmark was traced to
the improper cooking of offal from poultry plants (Bier-
ing-Sorensen 1959). The human type of bacillus is occa-
sionally isolated from tuberculous lesions in swine. No
person known to have active tuberculosis should be per-
mitted to have contact with swine or other animals.
Uncooked garbage is a potential means of transmit-
ting tuberculosis to swine. Feldman (1939) recorded that
75 (28.4%) of 264 garbage-fed swine were found to have
tuberculous lesions at the time of slaughter. Of these, 47
contained tubercle bacilli, of which 35 were avian type
and 12 were human type. It was concluded that garbage
may contain the offal of tuberculous chickens and that
material from tuberculous human patients is not proper-
ly disposed of. The frequent occurrence of avian tubercle
bacilli in lesions limited to the cervical and mesenteric
lymph nodes in naturally infected swine indicates that
infection usually occurs by ingestion. Janetschke (1963)
found that the primary complex involved the alimentary
tract in 97.3% of 1000 carcasses with tuberculous lesions;
a pulmonary route of infection was noted in only 2.7%,
as indicated by involvement of the bronchial lymph
nodes.
Schalk et al. (1935) found that swine contracted tu-
berculosis when placed on ground that had not been oc-
cupied by tuberculous chickens for the previous 2 years.
Viable and pathogenic avian tubercle bacilli were found
in the soil and litter of a chicken cage after 4 years.
Schalk and coworkers concluded that soil contaminated
by feces of tuberculous fowl is the most important source
of infection for swine. No success was obtained in con-
trolling the disease merely by use of the tuberculin test
and elimination of reactors, because the soil remained
contaminated. They recommended that an ideal pro-
gram to control avian tuberculosis is to rear young birds
on clean ground and to dispose regularly of all fowl more
than 1 year old.
Schliesser and Weber (1973) studied the survival of
M. avium in sawdust. At 18–22˚C, the survival time of
two virulent strains was 153–160 days, and the survival
time of two avirulent strains was 169–214 days. The sur-
vival times were greatly reduced when the contaminated
sawdust was maintained at 37˚C.
Wild birds may be incriminated as a source of M. avi-
um infections in swine. Tuberculosis was found in star-
lings on a farm with a high incidence of tuberculosis in
the swine but where no poultry had been kept for 8 years
(Bickford et al. 1966). Tuberculosis due to M. avium has
been found in various wild birds, some of which fre-
quent feedlots (Thoen 1997).
The close contact of sows and slaughter pigs in yards
and feeding pens provides opportunity for transmission
of tuberculosis from animal to animal (Alfredsen and
Skjerve 1993). The occurrence of intestinal lesions (Fig.
43.2) allows spread of tubercle bacilli in feces. Feldman
and Karlson (1940) and Pullar and Rushford (1954)
604 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
43.2. Submucosal tuberculous lesion
due to avian tubercle bacilli in the
intestinal tract of the pig. The lesion
appears to be extending toward the
surface, where it may ulcerate and
discharge bacilli into the lumen. Diffuse
cellular proliferation with little necrosis
is typical of avian tubercle bacillus
infection in swine (H&E; ×50).
demonstrated avian tubercle bacilli in the tonsils of pigs.
The latter workers suggested that this may be a source of
infection for other animals. Smith (1958) found avian tu-
bercle bacilli in apparently normal lymph nodes of 7% of
swine, 5% of sheep, and 5% of cattle but was unable to
find them in adult normal chickens; he suggested, there-
fore, that domestic mammals may contract M. avium
from each other as well as from tuberculous fowl.
Pulmonary, uterine, and mammary tuberculous le-
sions in swine constitute sources of infection for other
animals. Jorgensen et al. (1972) described an enzootic of
pulmonary tuberculosis resulting from M. avium in pigs.
Lesslie and Birn (1967) found M. avium in the udder or
milk of 18 cows and concluded that such animals may be
a source of M. avium in pigs. Bille and Larsen (1973) re-
ported congenital infection in swine caused by avian tu-
bercle bacilli, suggesting that infected pregnant sows
may have a role in the transmission of this infection. Sig-
urdardottir et al. (1994) reported granulomatous enteri-
tis due to M. avium in a pig.
Where sawdust is used for bedding, various serovars
of M. avium have been isolated from lesions in swine as
well as from the sawdust. Reactions to avian and bovine
tuberculin have been reported in boars exposed to saw-
dust from which M. avium or other nonphotochro-
mogenic mycobacteria were isolated (Fodstad 1977).
Schliesser and Weber (1973) found that M. avium would
survive as long as 214 days in sawdust. In Hungary,
Szabo et al. (1975) found that the incidence of tubercu-
lous adenitis in swine was greater when sawdust was
used as litter; when the use of sawdust was discontinued,
the occurrence of such lesions decreased significantly.
Dalchow and Nassal (1979) recorded that the same
serovars of avian tubercle bacilli as found in swine could
be isolated from sawdust. These workers also reported
that sawdust could contain infectious mycobacteria even
after 4 years of storage. Songer et al. (1980) investigated
herds of swine in Arizona and found in at least one herd
that the source was sawdust and wood shavings.
PATHOGENESIS
The development of disease in swine depends on the
ability of the tubercle bacillus to multiply within tissues
of the host and to induce a host response. Although acid-
fast bacilli initially encounter granulocytes and humoral
components, activated mononuclear macrophages are
considered to be more important in protection of the
host against mycobacteria.
The capacity of M. avium to produce progressive dis-
ease may be related to certain complex lipids present in
the cell wall, such as the glycopeptidolipids (previously
referred to as C-mycosides) localized in the exterior por-
tion of the cell envelope (Rastogi and Barrow 1994).
However, it appears that the effect of these components
alone or together on phagolysosome fusion cannot ac-
count for virulence. Available information suggests that a
combination of toxic lipids and factors released by viru-
lent tubercle bacilli may cause disruption of the phago-
some, interfere with phagolysosome formation, alter the
release of hydrolytic enzymes from the attached lyso-
somes, and/or inactivate the lysosomal enzymes released
into the cytoplasmic vacuole (Thoen and Bloom 1995).
Certain serovars of M. avium are susceptible to bacterici-
dal mechanisms of macrophages; however, the impor-
tance of reactive nitrogen intermediates and oxygen rad-
icals in macrophages of swine exposed to virulent
tubercle bacilli remains to be elucidated (Thoen and
Chiodini 1993). Although the mechanisms by which my-
cobacteria produce disease in swine have not been clear-
ly defined, experimental studies in piglets revealed that
nonspecific esterase activity was elevated in mononu-
clear macrophages of lymph nodes 7 days following in-
oculation of M. avium complex (M. intracellulare) serovar
 CHAPTER 43 TUBERCULOSIS Thoen
8 (Momotani et al. 1980). Granulomas of varying stages
were observed in mesenteric and mandibular lymph
nodes and intestinal mucosa at 14 days postinoculation.
In other investigations, sensitized lymphocytes and de-
tectable mycobacterial antibodies have been reported to
occur at 14–28 days postexposure to M. avium or M. bo-
vis (Muscoplat et al. 1975; Thoen et al. 1979a).
LESIONS
Tubercle Bacilli
Detailed discussions of the pathological anatomy of tu-
berculosis in swine may be found in Pallaske (1931),
Feldman (1938a), Francis (1958), and Kramer (1962). As
seen in the abattoirs, tuberculous lesions in swine are
usually limited to lymph nodes of the cervical and the
mesenteric regions. The lesions vary in appearance from
small, yellowish white, caseous foci a few millimeters in
diameter to diffuse enlargement of the entire node (Fig.
43.1). The disease may be localized in one group of
nodes or may involve a number of lymph nodes along
the digestive tract.
Gross differentiation between tuberculous adenitis
caused by avian tubercle bacilli and that caused by mam-
malian tubercle bacilli is difficult, but in general, some
features are characteristic of each. In an infection of
avian origin the lymph nodes may be enlarged and firm
with no discrete purulent foci, or there may be one or
more soft caseous areas with indistinct borders. Calcifi-
cation is seldom demonstrable. The cut surface of the le-
sion has a neoplastic appearance with a few caseous foci.
Although there may be diffuse fibrosis, there is little ten-
dency to encapsulation. Relatively large areas of
caseation may be present and occasionally will involve
the entire lymph node. The lesions due to tubercle bacil-
li of the avian type are generally not easily enucleated. In
contrast, when the infection is of mammalian origin (ei-
ther bovine or human), the lesions tend to be well encap-
sulated and are relatively easy to separate from the sur-
rounding tissue. In addition, calcification is usually
prominent in lesions caused by infection with mam-
malian tubercle bacilli. The individual foci appear to be
discrete and caseous. These distinctions are by no means
absolute, and there are many variations in the gross ap-
pearance of tuberculous lesions in lymph nodes of
swine.
Clapp (1956) examined, by bacteriological proce-
dures, 420 lymph nodes (mostly submaxillary) designat-
ed as tuberculous upon meat inspection. There was some
association between the gross appearance and the cause.
Localized lesions that were not easily enucleated and
large, dry calcareous processes involving an entire lymph
node were usually due to M. avium. Indistinctly mottled
and streaked lesions, large encapsulated purulent ab-
scesses, and lesions that could be easily enucleated were
usually not caused by tubercle bacilli. Some of these
605
yielded Corynebacterium equi, now reclassified as
Rhodococcus equi (Goodfellow et al. 1982), which Clapp
considered important in producing tuberculosis-like
lymphadenitis in swine. In the series of 420 specimens,
only 5 were from swine with generalized tuberculosis,
and all of these were associated with M. bovis and M. avi-
um. Microscopically, the changes induced in swine tis-
sues are characterized by diffuse proliferation of epithe-
lioid cells and giant cells. There may be some necrosis
and calcification, especially in older lesions, but calcifica-
tion is not usually prominent. Similar changes are ob-
served in sows and slaughter pigs (Thoen et al. 1976b).
Proliferation of connective-tissue elements accompanies
the process. Lesions caused by mammalian tubercle
bacilli have a tendency to become encapsulated by a well-
developed zone of connective tissue (Fig. 43.3). In addi-
tion, there is often early caseation and marked calcifica-
tion (Karlson and Thoen 1971). However, consistent
histopathological differentiation between lesions caused
by mammalian and avian tubercle bacilli is not possible
(Himes et al. 1983).
Generalized tuberculosis in swine is not commonly
seen. In most instances it is from infection with M. bovis,
but it may also result from the avian type (Feldman
1938b; Jorgensen et al. 1972). The extent and character
of generalized involvement vary from the occurrence of
a few small foci in several organs to extensive nodular
processes involving the liver, spleen, lungs, kidneys, and
many lymph nodes. Generalized lesions from infection
with M. avium tend to be diffuse. The cut surface is usu-
ally smooth, and there is no great tendency toward en-
capsulation by fibrosis. There may be foci of caseation,
but calcification is not pronounced. Lesions resulting
from infection with mammalian tubercle bacilli, howev-
er, are likely to be discrete, caseous, and well circum-
scribed by fibrosis. Calcification is prominent.
Bacteria Other than Tubercle Bacilli
Various species of mycobacteria other than tubercle
bacilli have been isolated from swine and other animals
in different countries, but reports of such are few and
usually concern only sporadic cases (Schliesser 1976).
The significance of finding M. kansasii, M. xenopi, or M.
fortuitum is not clear. It may be important, however, to
learn if animals and humans become infected from the
same sources (Thoen and Williams 1994). Of potential
importance is the recovery of M. chelonei from swine be-
cause this bacterium has been isolated from prosthetic
heart valves that were prepared from swine (Thoen and
Himes 1977).
In Norway, M. paratuberculosis was isolated by cul-
ture from lesions in the mesenteric lymph nodes of
swine as well as from normal swine that were closely as-
sociated with a herd of cattle in which Johne’s disease
was present (Ringdal 1963). This microorganism was
isolated in the United States from a slaughter pig (Thoen
606 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor

A B

43.3. Tuberculous changes in cervical lymph nodes of swine. (A) Mammalian tubercle bacillus
infection. Peripheral fibrosis, necrosis, and calcification are typical of lesions due to bovine or
human types of tubercle bacilli (H&E; ×40). (B) M. avium infection. Diffuse cellular proliferation
with little necrosis (H&E; ×95).

et al. 1975b). Jorgensen (1969) and Larsen et al. (1971)
found that swine may be infected with M. paratuberculo-
sis after oral administration of the organism. M. xenopi
was isolated from tissues of slaughtered swine that orig-
inated in the southeastern region of the United States
(Jarnagin et al. 1971). Another rare finding was the isola-
tion of the vole bacillus, M. microti, from lymph nodes of
three swine (Huitema and Jaartsveld 1967).
Mention must be made of the occurrence of R. equi
in localized lesions that cannot be easily differentiated
from tuberculous processes either macroscopically or
histologically (Feldman et al. 1940). Holth and Amund-
sen (1936) in Norway reported that of 162 tuberculous
lymph nodes from swine, only 103 yielded tubercle bacil-
li (97 were typed, with 80 avian and 16 human strains
and 1 bovine strain). Of the other 59, 38 contained a
variably acid-fast “coccobacillus.” The acid-fastness,
however, was not constant and was lost on subculture.
The presence of this microorganism in localized tuber-
culosis-like lesions in swine was soon confirmed by other
Scandinavian workers. Ottosen (1945) has shown that R.
equi occurs more frequently in the soil of hog pens than
elsewhere. In Denmark, Plum (1946) studied a large
number of tuberculous lymph nodes from swine and
concluded that it is difficult for inspectors in abattoirs to
differentiate between tuberculosis and R. equi infection.
Barton and Hughes (1980) recorded 32 reports of R. equi
infection in swine. R. equi expressing a 20 kDa antigen
has been observed in all pig isolates, and 2 of 5 plasmids
from pig isolates were the same as those from human
isolates, suggesting that the source of infection for hu-
mans may be pigs or the pig environment (Takai et al.
1996).
Rhodococcus sputi has been isolated from tuberculosis
lesions in the mesenteric lymph nodes of swine (Tsuka-
mura et al. 1988).
DIAGNOSIS
A clinical diagnosis of tuberculosis in swine is presump-
tive at best. Generally, the tuberculous lesions are limit-
ed to small foci in a few lymph nodes of the digestive
tract. It is difficult to conceive that such nonprogressive
morbid changes may elicit signs detectable by physical
examination. In extensive tuberculous infection, signs
may be suggestive of an infectious disease, but the symp-
toms and changes are not sufficiently characteristic to es-
tablish a diagnosis of tuberculosis.
 CHAPTER 43 TUBERCULOSIS Thoen
The necropsy and histopathological appearance of
tuberculosis in swine has been described. Although the
morbid changes are sufficiently characteristic to permit a
tentative diagnosis of tuberculosis, they are not specific.
The great similarity between localized tuberculous le-
sions and those associated with R. equi and other bacte-
ria has already been discussed. Also, chronic granuloma-
tous lesions may be difficult to differentiate grossly
because of parasitic nodules and neoplasms.
Enzyme-linked immunosorbent assay (ELISA) has
been described for detecting antibodies in swine infected
with M. avium (Thoen et al. 1979a, b). Positive ELISA re-
actions were observed in pigs experimentally infected
and in those naturally infected. The ELISA is a rapid test
that can be automated and may be of value in testing re-
placement breeding animals.
The mere demonstration of acid-fast bacilli in exu-
dates or in lesions may be misleading. Some workers
have recorded that R. equi is acid-fast in smears of
necrotic material from lymph nodes of swine (Ottosen
1945). Acid-fast microorganisms other than tubercle
bacilli have been isolated from swine (Karlson and Feld-
man 1940; Brandes 1961).
The characteristic pathological features of tuberculo-
sis in swine and the presence of acid-fast microorgan-
isms in such lesions provide important indications on
which to base a diagnosis of tuberculosis. However, an
unequivocal diagnosis can be made only on the basis of
bacteriological procedures designed for the isolation,
identification, and typing of the tubercle bacillus.
Tuberculin Test
The tuberculin test for the diagnosis of tuberculosis in
swine appears to be a useful procedure on a herd basis.
Of the various techniques described for this test in
swine, the operator should select the method that proves
by experience to be most suitable. Separate simultaneous
tests with avian and mammalian types of tuberculin
must be made (Thoen and Karlson 1970). A number of
investigators have found that some tuberculous swine
may fail to react to the intradermal tuberculin test.
Therefore, tests should be repeated in a herd in which an-
imals with positive reactions have been found and ex-
cluded.
The intradermal test, usually on the ear or vulva, may
be employed. Because swine are susceptible to infection
with avian and mammalian tubercle bacilli, avian and
mammalian tuberculin should be used. The tuberculins
may be diluted (1:100) to minimize nonspecific cross-re-
actions (Meyn et al. 1959). Fichandler and Osborne
(1966) described an extensive outbreak of bovine tuber-
culosis in swine in which animals reacted to mammalian
tuberculin by developing erythema and swelling of the
ear, compared with slight reactions to the avian tuber-
culin.
Feldman (1938a) recommended the use of 0.2 mL
607
25% Old Tuberculin applied into the dermis on the dor-
sal surface of the ear, slightly anterior to the base. A pos-
itive reaction is indicated in 24 hours by a flat, reddish
swelling up to 3 cm in diameter, which in 48 hours reach-
es its maximal intensity. At this time the erythema and
swelling are more pronounced; the central area becomes
hemorrhagic, and ulceration may occur. McDiarmid
(1956) described a means of testing swine in which re-
straint is not necessary. While the animals are feeding
from a trough, 0.1 mL tuberculin is injected at a right an-
gle into the skin at the junction of the ear and neck using
a needle only 3.5 mm long. With this short needle, most
of the tuberculin is deposited in the skin. By using a sy-
ringe in each hand, avian tuberculin can be injected on
one side and mammalian tuberculin on the other. Reac-
tions are recorded in 48 hours. A positive reaction varies
from “puffy” edema to inflammation, with purple discol-
oration and necrosis. McDiarmid used Weybridge puri-
fied protein derivative (PPD), which, according to Pater-
son (1949), has 3 mg protein/mL for mammalian
tuberculin and 0.8 mg protein/mL for avian.
Lanz (1955) recommended injecting the tuberculin in
the skin of the back about 10–20 cm caudal to the shoul-
ders and slightly to the right of the midline. This was eas-
ier and less time-consuming than trying to use the ear. A
dose of 0.1 mL PPD (as used for cattle in Switzerland) is
injected intradermally. A positive reaction reaches its
peak in 72 hours and consists of a painful erythematous
swelling 22–35 mm in diameter. As determined by
necropsy, no false-negative or atypical reactions were
found among 316 animals.
Luke (1952) described observations on the tuberculin
test in 100 sows, 3 years old or older, using avian and
mammalian tuberculin intradermally in the ear and
recording the results in 24 hours. A positive reaction was
ascribed when there was an increase of 2 mm in thick-
ness of the skin at the site of injection. Of 39 reactors,
only 22 had visible lesions, chiefly of lymph nodes of the
digestive tract. Tubercle bacilli were demonstrable in on-
ly 3 of the 22 animals with lesions, and each was a mam-
malian strain. Lesions considered to be tuberculous were
found in 8 animals that were nonreactors, but tubercle
bacilli were apparently not demonstrable in these. In
Luke’s opinion, there is a large percentage of error in the
tuberculin test in swine because of nonspecific sensitivi-
ty or residual sensitivity from healed tuberculous lesions.
Negative reactions in animals with lesions may, accord-
ing to Luke (1958), be ascribed to the ability of the pig to
overcome and apparently sterilize existing lesions. Luke
(1953) studied various aspects of the tuberculin test in
swine, including the specific effect of tuberculin on the
leukocyte count.
Lesslie et al. (1968), using Weybridge PPD, tested 84
White pigs from a herd known to have tuberculosis. The
avian tuberculin was given in injections of 0.1 mL, each
containing 2500 tuberculin units (TU); and the mam-
608 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
malian tuberculin was given in injections of 0.1 mL, each
containing 10,000 TU. The injections were made simul-
taneously, each at the base on an ear; in 48–72 hours a
positive reaction was recorded when the reaction con-
sisted of edema and erythema. Guinea pigs experimen-
tally sensitized with M. avium serovars 3, 4, 5, 6, 8, and 9
each reacted similarly to tuberculin prepared from
serovars 2 and 7 (Anz et al. 1970). Swine experimentally
infected with M. avium serovars 4 and 8 reacted well to
the USDA avian Old Tuberculin and to PPD prepared
from M. avium serovar 1 (Thoen et al. 1976a; Thoen et al.
1979b). Further studies must be made in swine to deter-
mine whether the serovar of the infecting strain will in-
fluence the specificity of the tuberculin test.
At present, intradermal injection of PPD tuberculin
in the dorsal surface of the ear is the recommended pro-
cedure for applying the tuberculin test in swine. The in-
jection site should be observed at 48 hours.
PREVENTION
The eradication of tuberculosis in swine, as well as in
other species, is dependent on the availability of an eco-
nomical and specific means of detecting infected ani-
mals. Additional information is needed to determine ad-
equate measures for cleaning and disinfecting the
premises where M. avium persists in the soil, in build-
ings, or on equipment. Also, we need to know how long
these organisms will remain viable in the environment.
Investigations also should be made to determine the
sources and modes of transmission of the different
serovars of M. avium. Information is needed on the sta-
bility of the serovars and the genetic relationships of the
M. avium isolated from tuberculous swine and those that
cause disease in humans. This is of increased importance
since serovars 1, 4, and 8, which are most commonly iso-
lated from patients with acquired immune deficiency
syndrome, are also isolated from tuberculous lesions in
swine.
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 Miscellaneous Bacterial
44 Infections
D. J. Taylor
ANTHRAX
Anthrax is relatively rare in swine compared to sheep
and cattle, which are highly susceptible. Swine may be-
come infected, however, along with other species of farm
animals and may become important as a reservoir of in-
fection.
Since anthrax is a zoonosis, infections in swine are a
threat to human health. Infected swine represent a haz-
ard to the farmworker and veterinarian, to the abattoir
worker, and to those preparing and eating contaminated
pig products. The importance of this relatively rare dis-
ease in swine is increased by the public health require-
ment for abattoir disinfection and the disposal of car-
casses after the discovery of an infected animal at meat
inspection. Meat processors are becoming unwilling to
slaughter pigs from infected farms, retailers are increas-
ingly concerned about their duty to consumers, and the
safe disposal of manures can be a major problem. These
factors add a wider importance to the disease.
Anthrax is present throughout the world, and the
FAO-WHO report (1973) indicates that the disease oc-
curred in swine in every continent during 1972. The inci-
dence remains low and sporadic, but the disease presents
a local problem in some areas.
ETIOLOGY
Anthrax is caused by Bacillus anthracis, a large gram-pos-
itive, aerobic, spore-forming, nonmotile rod. The indi-
vidual bacilli are 1–5 µm in diameter and 3–8 µm long.
When observed in tissue from an infected animal, the or-
ganisms are commonly in short chains surrounded by a
well-developed capsule. Under suitable aerobic condi-
tions, spores highly resistant to disinfectants, heat, and
desiccation may be produced.
B. anthracis grows very luxuriantly on most common
laboratory media. On blood agar plates, colonies can
usually be detected within 12 hours. After 24 hours at
37˚C, the colonies have a “ground glass” appearance,
with irregular, wavy borders that give them the “medusa
head” characteristic. No hemolysis is produced on blood
agar; this is useful in distinguishing the colonies from
those of certain nonpathogenic species of the genus
(Norberg 1953). The colony of B. anthracis growing on
blood agar on primary isolation possesses a stickiness
that can be readily detected by touching with the bacte-
riological loop. The colonial growth tends to adhere to
the loop and forms tenacious threads.
Bacteria in these colonies do not produce capsules
unless grown on special media or in 5% carbon dioxide
but do produce spores. B. anthracis may be distinguished
from other members of the genus by biochemical tests.
Those of use in differentiating the organism from related
bacilli are listed in the section on diagnosis below. B. an-
thracis is pathogenic to laboratory animals and humans.
Culture should not be attempted unless appropriate safe-
ty precautions such as safety cabinets and adequate dis-
posal facilities are available. Personnel handling the or-
ganism should be vaccinated.
EPIDEMIOLOGY
Anthrax is generally considered a soilborne infection in
cattle, sheep, and horses. Animal-to-animal spread does
not commonly occur, but rather, B. anthracis is deposited
in the soil or the environment by the infected animal at
the time of or following death. Spores are formed by
some of the organisms, and these highly resistant bodies
may remain viable for years, even under adverse condi-
tions. Subsequently, the spores may be ingested by sus-
ceptible animals and anthrax may develop.
Swine can presumably become infected in this man-
ner; however, because of the small number of spores
likely to be picked up and the higher degree of resistance
in swine, infection probably occurs only rarely. Rather,
anthrax in swine generally occurs following ingestion of
feed that contains a large number of B. anthracis or vi-
able spores. Swine that are permitted to eat the carcass of
an animal dead of anthrax may consume large numbers
of organisms and may therefore become infected. The
use of bonemeal or other animal products containing
spores of B. anthracis in feed is the most common source
of infection in swine. Davies and Harvey (1955) isolated
B. anthracis from 5 of 41 cargoes of bonemeal shipped to
England from the Near and Middle East. Direct cultural
613
614 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
methods were unsuccessful, but the authors isolated the
organism from guinea pigs that were first protected from
the various anaerobic species common in bonemeal by
means of clostridial antisera and antitoxins and that
were then injected with a concentrated infusion from the
bonemeal specimen.
The role of feed contaminated with spores of B. an-
thracis in the transmission of anthrax can be illustrated
by a brief account of the 1952 outbreak that occurred in
the midwestern United States (Ferguson 1986). Anthrax
was confirmed on a farm in southern Ohio in February
1952, and further outbreaks occurred in rapid succession
in widely separated areas. Within a week of the recogni-
tion of the first case, feed was incriminated as the source
of infection. A number of feed companies were involved,
but all had incorporated bonemeal obtained from a com-
pany in Columbus, Ohio, which had processed part of a
shipment of 100 tons of raw bonemeal obtained from
Belgium into a meat scrap concentrate. The companies
purchased the concentrate and included it in many hun-
dreds of tons of swine feed sold throughout Ohio and
adjoining states. The organism was isolated from the raw
bonemeal and from the meat scrap concentrate but not
from any of the finished feeds.
The organism appears to be spread in wet-feed sys-
tems but rarely affects more than 1–2 animals in an in-
fected herd. This was the classic picture, but accounts of
continuing outbreaks exist (Jackson 1967; Jackson and
Taylor 1989; Edgington 1990). The outbreak referred to
by Jackson and Taylor (1989) and Edgington (1990) oc-
curred in a 500-sow unit and persisted for 14 weeks, re-
sulting in at least 18 cases in sows, suckling pigs, and
weaned pigs. The development of disease in weaners
may have been delayed by maternal immunity in this
continuing outbreak. The origin of the outbreak was
considered to be feed, but the disease persisted within
the herd in spite of antimicrobial treatment. Persistence
may have been in carrier pigs or as spores in slurry and
housing. The role of flies in persistence and transmission
was not clear, although recent studies in the United
States indicate that biting flies (Stomoxys calcitrans) and
mosquitoes (Aedes aegyptii and A. taeniorhynchus) trans-
mit the disease experimentally 4 hours after feeding
(Turell and Knudson 1987). Ticks (Dermacentor margina-
tus) were shown to harbor the organism for 76 days at
4˚C and for 35 days at 22–25˚C in the former Soviet
Union (Akhmerov et al. 1982).
PATHOGENESIS
B. anthracis has two major sets of pathogenic determi-
nants: a protective capsule composed of a polymer of
d-glutamic acid and the complex exotoxin. Molecular bi-
ology studies have shown that toxin production results
from the possession of a 110 MDa plasmid and that cap-
sulation is related to the possession of a smaller 60 MDa
plasmid (Uchido et al. 1985; Mikesell et al. 1983). The ex-
otoxin (Smith et al. 1955; Harris-Smith et al. 1958; Davis
et al. 1973) is composed of three fractions and is pro-
duced when bacteria reach 5–10 × 106 organisms per
milliliter of blood. The toxins share the same binding
unit—the protective antigen (PA)—and are binary tox-
ins. PA binds to cell surfaces and is activated by a host
protease, allowing edema factor (EF) and lethal factor
(LF) to enter cells. EF is a calmodulin-dependent adeny-
late cyclase and affects neutrophils, preventing the respi-
ratory burst and thus protecting the organisms. It is also
responsible for the progressive hyperglycemia and the
severe terminal hypoglycemia seen in animals with the
septicemic form. LF appears to be a zinc-dependent pro-
tease affecting macrophages. All three toxins are needed
to produce typical anthrax.
The organism appears to enter the pig through the
gut or tonsil. Septicemic disease is rare, and the organ-
ism multiplies locally, resisting phagocytosis by means of
the polyglutamic acid capsule. Edema is commonly pro-
duced locally. Neutrophils and other phagocytes are
killed by EF, and organisms multiply until LF is pro-
duced, resulting in the death of the animal as a result of
its effect on the mitochondria. Immunity against anthrax
is associated with antibodies against the exotoxin (PA)
(Sargeant et al. 1960; Thorne et al. 1960). Antibody to
the cell wall may be produced but is not protective.
CLINICAL SIGNS
The first indications of an outbreak of the disease may
be an increase in mortality. Investigation of these extra
deaths may indicate the presence of anthrax and the clin-
ical signs described below may be identified. Three forms
of anthrax have been observed in swine: pharyngeal, in-
testinal, and septicemic. The usual portal of entry is the
oral cavity, and invasion occurs in the tonsils or mucosa
of the pharynx. In some cases the infection may remain
localized in the lymph nodes of this region, and the dis-
ease is classified as pharyngeal. In other cases the organ-
isms may pass into the intestinal tract, where primary in-
vasion may also occur. When B. anthracis is not localized
but gains access to the general circulation, the septicemic
form of the disease develops.
The clinical signs commonly observed in pharyngeal
anthrax are cervical edema and dyspnea. General de-
pression, inappetence, and vomiting are commonly seen.
Fever with temperatures to 41.7˚C may occur, but it is
not consistent, and in some affected swine the tempera-
ture may be subnormal. Death follows in many of the
swine within 24 hours after the cervical edema is noticed.
It is not uncommon for swine to recover even in the ab-
sence of treatment. The swelling may disappear gradual-
ly, and complete recovery appears to occur; however,
 CHAPTER 44 MISCELLANEOUS BACTERIAL INFECTIONS
such animals may continue to remain carriers of B. an-
thracis.
Clinical signs of intestinal anthrax are not as obvious
as those in the pharyngeal form. In severe cases an acute
digestive disturbance may be evident, with vomiting,
complete loss of appetite, and diarrhea with bloody fe-
ces. Death may follow in the most severely affected
swine; however, recovery occurs in many affected with
the milder forms (Brennan 1953). When 50 pigs were in-
fected in an experimental study (Redmond et al. 1997),
33 developed anorexia, lethargy, dullness, shivering,
constipation, loose feces, blood in the feces, and ataxia at
some point between 1 and 8 days after infection. Only 2
died. Fever did not exceed 41.9˚C, peaking 48 hours after
infection.
Intestinal anthrax has been reported only rarely in
the United States. Many cases may be unrecognized be-
cause of the usual practice of avoiding a complete
necropsy of animals suspected of anthrax. It is possible
that some of the animals dying of pharyngeal anthrax
may also have had lesions in the intestinal tract. Brennan
(1953) reported that intestinal anthrax was the most
common form of the disease seen in the 1952 outbreak
of anthrax in England.
Septicemic anthrax is the highly acute form that re-
sults from the entrance of B. anthracis into the blood-
stream, followed by rapid reproduction of the organisms
throughout the body. Death frequently occurs in animals
so affected, without any period of illness being noticed
by the owner. In swine it is the uncommon form of the
disease. Walker et al. (1967) reported the presence of vi-
able spores of B. anthracis in the lungs of dwarf swine for
as long as 7 days following respiratory exposure. These
authors suggested that resistance of swine may be relat-
ed to some mechanism that inhibits germination of the
spores. Of 30 swine examined at necropsy during the an-
thrax outbreak of 1952 in Ohio, only 3 had the enlarged,
dark spleen so characteristically seen in cattle. It is possi-
ble that young pigs develop septicemia more frequently
than older swine (Ferguson 1986).
LESIONS
In the interests of controlling anthrax, complete necrop-
sy of animals is strongly discouraged. Pigs with anthrax
may not be identified before necropsy because the dis-
ease is relatively rare. Large pigs which have died from
the disease may have a bloody discharge from the nose
(Edgington 1990), and small ones may appear very pale
and dehydrated. The cervical region is edematous, but
otherwise no superficial lesions are evident. Incision of
the region reveals an extensive infiltration of the tissues
with fluid, which is usually straw colored but may appear
pink or hemorrhagic. The tissue, containing large
amounts of fluid, may appear to possess a gelatinous
Taylor 615
consistency. The tonsils are usually covered with a fibri-
nous exudate, or extensive necrotic changes may be evi-
dent. The pharyngeal mucosa is frequently inflamed and
swollen.
The mandibular and suprapharyngeal lymph nodes
are enlarged to several times their normal size. The cut
surface of the affected node may vary in color from deep
brick red to strawberry red. In more chronic cases the
color may be grayish yellow, indicative of necrotic
changes in the node. In cases of the septicemic and in-
testinal forms the carcass may be opened before anthrax
is suspected. The intestinal form is more common and
there is usually copious pinkish peritoneal fluid, which
may clot on exposure to air. The small intestine is usual-
ly inflamed, with fibrinous adhesions on the serous sur-
face. The mesenteric lymph nodes may be swollen, hem-
orrhagic, or necrotic, and edema of the mesentery is
common. The intestinal mucosa is covered with a diph-
theritic membrane and may be hemorrhagic. The intesti-
nal wall may be grossly thickened. In the septicemic form
little may be seen other than the presence of blood-
stained fluid in the peritoneal cavity and local petechia-
tion. In some cases the spleen is enlarged and there may
be marked petechiation of the kidney. Small abscesses
may be present in the lymph nodes of recovered pigs
(Redmond et al. 1997).
Microscopic lesions in the lymph nodes usually con-
sist of hemorrhage and necrosis with encapsulated bacil-
li. These may also be seen in the necrotic diphtheritic le-
sions of the intestinal mucosa and in the capillaries of
any organ in septicemia.
DIAGNOSIS
Anthrax should be suspected when swine show cervical
edema and dyspnea. However, erysipelas or malignant
edema from Clostridium septicum may also provoke simi-
lar clinical signs. In malignant edema, the edema will of-
ten be more prominent in the shoulders or axillary
spaces. The edematous fluid and enlarged cervical or
mesenteric lymph nodes, as seen on necropsy, are very
suggestive of anthrax. When the carcass has been
opened, the presence of bloodstained fluid in the peri-
toneum, petechiation of the kidney or serosal surfaces,
enlargement of the spleen, and thickening and inflam-
mation of the small intestine should lead to suspicion of
anthrax. A history of the type of feed products eaten by
the affected swine is always of value.
The accurate diagnosis of anthrax is very important
and in most cases is dependent upon the isolation and
identification of B. anthracis.
Microscopic Examination
Impression smears and cultures should be made from
the cut surfaces of the cervical lymph nodes, spleen,
616 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
mesenteric lymph nodes, intestinal mucosa, or kidney as
appropriate, and peritoneal fluid should also be sampled
when present. Smears should be fixed in Zenker’s fluid,
which kills spores, or by low heat, which does not, and
then stained by polychrome methylene blue for 2 min-
utes and washed with water. The bacilli of anthrax ap-
pear as square-ended blue rods in a pinkish capsule. In
smears made from decayed carcasses, other bacilli may
be present, and where antimicrobial treatment has been
given, the bacilli may be present only as capsules or in
aberrant forms. The failure to find anthrax bacilli imme-
diately should not rule out the disease, as up to 30 min-
utes’ examination may be required. Peritoneal fluid is
more often positive than splenic smears in septicemia.
Slides and reagents used for diagnosis should be dis-
posed of by incineration or formaldehyde fixation.
Spores are not observed in slides prepared from fresh
tissue or from freshly cut surfaces. Spore-forming anaer-
obes are frequently encountered in tissues of animals
that have been dead several hours prior to necropsy. Dif-
ferentiation is important in such cases, and the following
points are helpful. Spores are rarely seen in B. anthracis
in fresh-tissue preparations, whereas spores are regularly
seen in clostridia. In the latter organism the rod is usual-
ly slightly enlarged by the spore. Capsules are very rarely
observed in the clostridia, and any capsules seen do not
stain purple with polychrome methylene blue.
Cultural Studies
B. anthracis grows readily on many common media and
is characterized by very rapid colonial development.
Typical colonies can be observed after 12–18 hours of
incubation. This rapid growth is useful in differentiating
B. anthracis from other pathogens.
B. anthracis is readily cultured from the enlarged
lymph nodes, and it may also be demonstrated from the
surrounding connective tissue in some cases. In the occa-
sional septicemic case the organisms can be isolated
from the blood, spleen, or liver—in fact, from essentially
any tissue of the body. Since B. anthracis grows more
rapidly than most of the saprophytic bacteria likely to be
encountered, except other species of Bacillus, one should
always examine the cultures after incubation for 12–18
hours.
Suspect colonies can be identified as B. anthracis by
their biochemical characters using API systems or by the
absence of hemolysis, lack of motility, growth on chloral
hydrate agar, and susceptibility to anthrax phage. Final
confirmation of pathogenic B. anthracis depends on the
inoculation of culture into scratches on the footpad of a
guinea pig or mouse under strict containment. All cul-
tures and any experimental animals should be fixed in
formaldehyde and incinerated.
Serology
A competitive enzyme immunosorbent assay (EIA) has
been described (Turnbull et al. 1986, 1992) to identify
the presence of IgG antibody to PA, and PA may be as-
sayed in serum in pigs which have died using the capture
EIA (Turnbull 1990).
CONTROL
Control of the spread of anthrax differs significantly
from control of most of the other important animal dis-
eases. The highly resistant spore formed by B. anthracis
accounts for this difference. Some swine may become in-
apparent carriers, but there is little evidence to indicate
that this forms an important source of infection to sus-
ceptible animals. Otherwise, animals that become infect-
ed do show clinical signs and generally develop an acute
disease that terminates in death within a few days. Trans-
mission from animal to animal rarely occurs, but soil
contaminated by the organisms serves as a source from
which susceptible animals subsequently ingest the
spores. Because of this common form of transmission,
anthrax can be controlled by preventing susceptible ani-
mals from contacting viable spores of B. anthracis.
Van Ness and Stein (1956) pointed out the impor-
tance of soil types in the survival of anthrax spores. The
principal areas of enzootic anthrax are regions charac-
terized by soils high in nitrogen and with adequate calci-
um. Where such soil types are lacking (e.g., central and
eastern United States), anthrax does not appear to per-
sist.
The spores can survive for years under a variety of en-
vironmental conditions. In the unopened carcasses of
animals dead of anthrax, few spores are formed except at
the body openings. When the animal is opened for a
complete necropsy or when carnivorous animals are per-
mitted to eat the carcass, there is usually extensive spore
formation as the heavily infected blood and viscera are
exposed to the oxygen of the air. For this reason, the ori-
fices and any cuts in a carcass should be covered with dis-
infectant-soaked cotton wool to prevent sporulation and
spread of infection. The most productive control mea-
sures include the complete destruction of the carcasses
of animals dead of anthrax by incineration or deep bur-
ial.
When an animal dies in the open, it is generally rec-
ommended that it be burned on the spot. If the animal
must be moved, the carcass must be placed on a sled or
some other vehicle that can be thoroughly disinfected
and then hauled, not dragged, to an area for disposal. If
burning is not an option, deep burial can be used. The
carcass should be covered with lime and at least 4 feet
(1.25 m) of soil. When carefully completed, these meth-
ods will minimize the chances of transmission of the in-
fection.
Disinfection can be achieved with 5% freshly pre-
pared sodium hydroxide or, more controllably, with 10%
formaldehyde and the use of appropriate respirators.
 CHAPTER 44 MISCELLANEOUS BACTERIAL INFECTIONS
Only disinfectants capable of inactivating anthrax
spores, such as those containing glutaraldehyde and
formaldehyde, should be used. Disinfectants should be
used prior to clearing up infected premises, and contam-
inated articles should be burned. Exposed surfaces
should be scrubbed or pressure washed with the disin-
fectant.
Edgington (1990) gives an account of the procedure
adopted in depopulating and disinfecting a chronically
infected 500-sow unit from which purchasers would no
longer take pigs. All 5000 pigs were slaughtered and
burned, all 300,000 gallons (1,364,000 L) of slurry were
disinfected with 10% formaldehyde and disposed of in an
approved toxic-waste site, and the buildings were
formaldehyde-fumigated and cleaned—at a cost of
£1,000,000 (U.S.$1,700,000). Similar precautions may
have to be adopted in contaminated meat plants to safe-
guard public health.
Following the outbreaks of anthrax in the midwest-
ern United States in 1952, which were conclusively
traced to imported bonemeal, regulations were estab-
lished that prohibit the importation of raw bonemeal in-
to the United States (Stein 1953). Comparable preventive
legislation was adopted in Canada (Moynihan 1963).
Bonemeal processed by an acceptable steam treatment
may be imported under these regulations. In addition to
this federal regulation, some states have laws pertaining
to the operation of rendering plants and the use of ani-
mal products in feed. These regulations have proved ef-
fective. Similar regulations apply in most developed
countries.
TREATMENT
Treatment of animals infected with B. anthracis is possi-
ble. Since swine may develop a chronic form of the dis-
ease, treatment can be successfully administered in some
cases. In the outbreak in Ohio in 1952, penicillin in oil
was used at a dosage level of 10,000 units/lb (22,000
units/kg) body weight. According to Ferguson (1986),
pigs that were showing clinical signs of anthrax recov-
ered completely after this treatment, and the losses were
reduced considerably when the disease was recognized
early in its course. Anthrax antiserum in doses of 20–75
mL was also used in treatment of a limited number of
animals. The results were comparable to those following
treatment with penicillin in that the pigs in the early
stages of anthrax recovered promptly. Oxytetracycline is
effective against B. anthracis and may be used parenteral-
ly in daily doses of 4.4–11.0 mg/kg body weight. Edging-
ton (1990) reported the successful use of penicillin,
oxytetracycline, and chlortetracycline:sulfonamide:peni-
cillin combinations to treat or suppress infection but had
to withdraw treatment from animals intended for
slaughter. Following the study of Redmond et al. (1997),
it is clear that infection may persist for up to 21 days af-
Taylor 617
ter infection in a population, and this factor must be con-
sidered before carcasses are submitted for human con-
sumption.
PREVENTION
Kaufmann et al. (1973) evaluated the Sterne strain an-
thrax vaccine, an avirulent spore vaccine, in an outbreak
of the disease in Louisiana. The results supported the ef-
ficacy of the vaccine in swine, but the number involved
was too small to provide significant data for this species.
Similar findings were obtained by Jackson (1967) in a
continuing outbreak in the United Kingdom. Immuniza-
tion of swine would probably reduce incidence of infec-
tion when they are exposed to massive doses of B. an-
thracis. Immunization on a large scale has not been
recommended, however, since swine possess a level of
natural resistance adequate to prevent the disease except
following heavy exposure to B. anthracis.
Human infection can be prevented by the safe dis-
posal of all contaminated carcasses, articles, and fluids
on the farm by the methods outlined above. Persons ex-
posed to the infection can be given prophylactic antimi-
crobials such as penicillin and tetracyclines, and any cas-
es can be treated with them. Where longer-term
exposure is likely, vaccination should be carried out.
REFERENCES
Akhmerov, D. S.; Kusov, V. N.; and Chernova, A. A. 1982.
Survival of Bacillus anthracis in the tick Dermacentor
marginalis. Rep Kaganskii Vet Inst, pp. 101–103.
Brennan, A. D. J. 1953. Anthrax, with special reference to
the recent outbreak in pigs. Vet Rec 65:255.
Davies, D. G., and Harvey, R. W. S. 1955. The isolation of
Bacillus anthracis from bones. Lancet 2:86.
Davis, B. D.; Dulbecco, R.; Eisen, N. H.; Ginsberg, H. S.;
Wood, W. B.; and McCarty, M. 1973. Microbiology, 2d
ed. New York: Harper & Row.
Edgington, A. B. 1990. An outbreak of anthrax in pigs: A
practitioner’s account. Vet Rec 127:321–324.
FAO/WHO. 1973. Animal Health Yearbook for 1972. Rome:
FAO.
Ferguson, L. C. 1986. Anthrax. In Diseases of Swine, 6th ed.
Ed. A. D. Leman, B. Straw, R. D. Glock, W. L. Mengeling,
R. H. C. Penny, E. and Scholl, E. Ames: Iowa State Univ
Press, pp. 622–627.
Harris-Smith, P. W.; Smith, H.; and Keppie, J. 1958. Produc-
tion in vitro of the toxin of Bacillus anthracis previously
recognised in vivo. J Gen Microbiol 19:91.
Jackson, W. T. 1967. Anthrax in pigs—A series of deaths.
State Vet J 22:67–71.
Jackson, W. T., and Taylor, K. C. 1989. Anthrax in pigs—A
series of deaths. State Vet J 43:119–125.
Kaufmann, A. F.; Fox, M. D.; and Kolb, R. C. 1973. Anthrax
in Louisiana, 1971: An evaluation of the Sterne strain
618 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
anthrax vaccine. J Am Vet Med Assoc 163:442.
Mikesell, P.; Ivins, B. E.; Ristroph, J. D.; and Dreier, T. M.
1983. Evidence for plasmid mediated toxin production
in Bacillus anthracis. Infect Immun 39:371–376.
Moynihan, W. A. 1963. Anthrax in Canada. Can Vet J 4:283.
Norberg, B. K. 1953. Continued investigations of some im-
portant characteristics in anthrax-like microorganisms
as viewed from a point of view of differential diagnosis.
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Redmond, C.; Hall, G. A.; Turnbull, P. C. B.; and Gillgan, J.
S. 1997. Experimentally assessed public health risks as-
sociated with pigs from farms experiencing anthrax. Vet
Rec 141:244–247.
Sargeant, K.; Stanley, J. L.; and Smith H. 1960. The serolog-
ical relationship between purified preparations of fac-
tors I and II of the anthrax toxin produced in vivo and in
vitro. J Gen Microbiol 22:219.
Smith, H.; Keppie, J.; and Stanley, J. L. 1955. The chemical
basis of the virulence of Bacillus anthracis. V. The specif-
ic toxin produced by B. anthracis in vivo. Br J Exp Pathol
36:460.
Stein, C. D. 1953. A review of anthrax in livestock during
1952 with reference to outbreaks in the first eight
months of 1953. In Proc US Livest Sanit Assoc,
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duction of toxin in vitro by Bacillus anthracis and its sep-
MELIOIDOSIS (BURHOLDARIA PSEUDOMALLEI INFECTION)
Melioidosis is a chronic bacterial infection of pigs in
tropical and subtropical regions such as those of Asia
and northern Australia. Pigs may become infected by
Burholdaria (formerly Pseudomonas) pseudomallei, which
is a short, gram-negative rod, 0.8 by 1.5 µm, that pro-
duces rough or mucoid colonies on a wide variety of lab-
oratory media. It is present in water and soil in tropical
and subtropical areas and may infect pigs when water
supplies are contaminated. Infection is often clinically
inapparent but has been associated with clinical signs
(Olds and Lewis 1955; Omar et al. 1962; Laws and Hall
1964; Rogers and Andersen 1970; Veljanov et al. 1994).
Clinical signs include a raised rectal temperature
(40–42˚C, 104–108˚F) for up to 4 days, unsteady gait,
lameness or weakness, slight nasal discharge, and subcu-
taneous swellings of the limbs. Deaths may occur but are
rare in adults, in which abortions and uterine discharges
have been recorded.
Lesions are found in slaughter pigs in which clinical
signs have not been seen and in those that have died from
the disease. They consist of large abscesses in the lungs,
liver, spleen, kidney, and mesenteric and subcutaneous
lymph nodes. The organism can be isolated from them.
aration into two components. J Bacteriol 79:450.
Turell, M. J., and Knudson, G. B. 1987. Mechanical trans-
mission of Bacillus anthracis by stable flies (Stomoxys cal-
citrans) and mosquitoes (Aedes aegyptii and Aedes tae-
niorhynchus). Infect Immun 55:1859–1861.
Turnbull, P. C. B. 1990. Salisbury Medical Bulletin. In Proc
Int Workshop on Anthrax, Apr 11–13, 1989, Winches-
ter. 68. Special Suppl, p. 53.
Turnbull, P. C. B.; Broster, M. G.; Carman, J. A.; Manchee, R.
J.; and Melling, J. 1986. Development of antibodies to
protective antigen and lethal factor components of an-
thrax toxin in humans and guinea pigs and their rele-
vance to protective immunity. Infect Immun
52:356–363.
Turnbull, P. C. B.; Doganay, M.; Lindeque, P. M.; Aygen, B.;
and McLaughlin, J. 1992. Serology and anthrax in hu-
mans, livestock, and Etosha National Park wildlife. Epi-
demiol Infect 108:299–313.
Uchido, I.; Sekizaki, T.; Hashimoto, K.; and Terakado, N.
1985. Association of the encapsulation of Bacillus an-
thracis with a 60 Megadalton plasmid. J Gen Microbiol
131:363–367.
Van Ness, G., and Stein, C. D. 1956. Soils of the United
States favorable for anthrax. J Am Vet Med Assoc 128:7.
Walker, J. S.; Klein, F.; Lincoln, R. E.; and Fernelius, A. L.
1967. A unique defense mechanism against anthrax
demonstrated in dwarf swine. J Bacteriol 93:2031.
Melioidosis may be suspected on clinical grounds espe-
cially when prolonged raised rectal temperatures and un-
steady gait are associated with subcutaneous swellings of
the limbs. More frequently, diagnosis is based on the
creamy abscesses found at slaughter or on the bacterio-
logical results needed to confirm the presence of B.
pseudomallei (Ketterer et al. 1986; Veljanov et al. 1994). A
hypersensitivity test resembling a tuberculin test (the
melioidin test) and serum-agglutination and comple-
ment-fixation tests have all been described and can be
used to confirm a diagnosis in the live pig.
Treatment with tetracyclines has been described, and
the disease can be prevented by use of clean or chlori-
nated water supplies and preventing access to contami-
nated soil. As the disease is of public health importance,
infected carcasses should be disposed of safely.
REFERENCES
Ketterer, P. J.; Webster, W. R.; Shield, J.; Arthur, R. J.; Black-
all, P. J.; and Thomas, A. D. 1986. Melioidosis in inten-
sive piggeries in South Eastern Queensland. Aust Vet J
63:146–149.
 CHAPTER 44 MISCELLANEOUS BACTERIAL INFECTIONS
Laws, L., and Hall, W. T. K. 1964. Melioidosis in animals in
North Queensland. IV. Epidemiology. Aust Vet J
40:309–314.
Olds, R. J., and Lewis, F. A. 1955. Melioidosis in a pig. Aust
Vet J 31:273–274.
Omar, A. R.; Cheah, K. K.; and Mahendranathan, T. 1962.
Observations on porcine melioidosis in Malaya. Br Vet J
118:421–429.
CHLAMYDIAE
Chlamydiae are small intracellular bacteria that cause
disease in many mammalian species and are widespread
in birds. They have been demonstrated in cases of con-
junctivitis, enteritis, pneumonia, pleurisy, pericarditis,
arthritis, orchitis, uterine infections, and abortion in
pigs. Recent work on chlamydiae in pigs has shown that
at least three species are involved (C. psittaci, C. tra-
chomatis, and C. pecorum); the development of reliable
tissue culture methods and the use of immunoperoxi-
dase staining of tissue sections, DNA probes, and, more
recently, polymerase chain reaction (PCR) methods have
demonstrated that the organisms are relatively common
in pig populations. The literature prior to 1983 was re-
viewed comprehensively by Stellmacher et al. (1983),
and the account in the present chapter draws on
Taylor 619
Rogers, R. J., and Andersen, D. J. 1970. Intrauterine infec-
tion of a pig by Pseudomonas pseudomallei. Aust Vet J
46:292.
Veljanov, D.; Vesselinova, A.; Nicolova, S.; Kussovski, V.; and
Najdenski, H. 1994. Experimental Pseudomonas pseudo-
mallei infection of pigs. Proc Int Congr Pig Vet Soc
13:236.
earlier work only where it is relevant to current knowl-
edge.
ETIOLOGY
Chlamydiae are gram-negative bacteria that can multiply
only inside living cells. They are unusual among bacteria
in that they exist outside the cell only as an inactive,
trypsin-resistant, infectious particle 0.2–0.3 µm
(200–300 nm) in diameter known as an elementary body
(Fig. 44.1). This body has an electron-dense core packed
with DNA and surrounded by a trilaminar cytoplasmic
membrane, outside which lies a further trilaminar enve-
lope and then a cell wall with projections that may be as-
sociated with attachment to cells. The outer-membrane
44.1. Electron micrograph of
elementary body (arrow) of
Chlamydia sp. in an aborted
placenta (×52,500).
620 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
proteins of the chlamydiae have been studied in consid-
erable detail, and sequences of the genes coding for out-
er-membrane protein A (ompA) have been obtained
(Kaltenbroeck and Storz 1992; Kaltenbroeck et al. 1993;
Anderson et al. 1996). These sequences have contributed
to the current species classification and are now widely
used in diagnosis. C. psittaci contains a plasmid, and
DNA sequences of it have also been identified in C. peco-
rum.
Within 6–9 hours after an elementary body has en-
tered a cell, it forms a reticulate body 1 µm (1000 nm) in
diameter. This body divides by binary fission to form fur-
ther reticulate bodies in an inclusion within the host cell.
At this stage the infected host cell may divide to give in-
fected daughter cells, which may account for latent infec-
tions seen in animal hosts. Within 20 hours of the first
division of the reticulate body, some begin to mature in-
to elementary bodies. The chlamydial inclusions may oc-
cupy up to three-quarters of the cell volume and contain
up to 10,000 elementary bodies. C. trachomatis produces
glycogen inclusions in cells at this stage; C. psittaci and C.
pecorum do not. Infected cells may lyse to release the ele-
mentary bodies or these may be budded from persistent-
ly infected cells.
Chlamydiae can be grown in the laboratory by inocu-
lation of the yolk sac of 6- to 8-day-old embryonated hen
eggs and in neonatal mice. Most laboratories now use
cell cultures, usually McCoy or L929 cells, in which the
chlamydiae grow readily. Some strains and species can
be maintained in Vero cells. In some cases, isolation can
be improved by treatment of the cells, using irradiation
or cycloheximide (1 µm/mL), and by centrifugation of
the chlamydiae onto the cells.
The different species of chlamydiae and biotypes
within them can be distinguished by their differential
growth in cell cultures in the presence of tissue culture
medium supplemented with amino acids such as argi-
nine, isoleucine, and methionine (Johnson 1984) and by
the presence of inclusions or the time taken to develop in
a particular cell line. The main methods of differentia-
tion are now (1) antigenic, based on differences between
the outer-membrane proteins detected using monoclon-
al antibodies in immunoperoxidase, immunofluores-
cence, or ELISA methods, and (2) nucleic acid based, us-
ing genomic and ompA sequences for PCR (Anderson et
al. 1996; Kaltenbroek and Storz 1992; Kaltenbroeck et al.
1993).
EPIDEMIOLOGY
The recent development of methods to differentiate the
three species of chlamydiae present in pigs has raised a
number of questions about the epidemiology of infec-
tions with these species in the pig. All three species are
found in other animals or birds, and experimental infec-
tions show that C. psittaci from species such as sheep can
be transmitted to pigs and sometimes produces lesions
(Harris et al. 1984; Vasquez-Cisneros et al. 1994). C.
psittaci occurs in many avian species and is particularly
common in pigeons and doves but may occur in almost
any bird. Some mammals such as sheep, cattle, and ro-
dents may be infected. All these species may form a reser-
voir of C. psittaci infection for the pig. The relationship
between C. pecorum and C. trachomatis infections of oth-
er mammalian species and the pig has not yet been ex-
plored in detail. All chlamydiae can survive for consider-
able lengths of time as elementary bodies in the
environment, where they are resistant to drying. The ma-
jor routes of transmission of C. psittaci to pigs are by in-
halation of aerosols of elementary bodies, either fresh or
in dust, from respiratory, genital tract, or enteric infec-
tions; by ingestion of contaminated feed; and by contact,
particularly venereal in the case of genital tract infec-
tions. The exact methods by which C. pecorum and C. tra-
chomatis are transferred are not yet clear but are proba-
bly similar, with the fecal-oral route being of importance
for enteric infections and transmission by flies or dust
being involved in C. trachomatis conjunctivitis (Rogers et
al. 1993).
Chlamydial infection in the pig has been reported
from the United States (Willigan and Beamer 1955;
Pospischil and Wood 1987), Britain (Wilson and Plum-
mer 1966; Harris 1976), Rumania (Sorodoc et al. 1961),
Germany (Stellmacher et al. 1983), and more recently
from other countries. The early serologic surveys sug-
gested that complement-fixing and microagglutinating
antibodies were present in up to 23% of slaughter pigs
(Wilson and Plummer 1966). Most antibody titers were
low (1:8–1:128), but titers as high as 1:1024 were record-
ed (Wilson and Plummer 1966). More recent surveys us-
ing immunoperoxidase staining of histological sections
of gut suggest that chlamydial inclusions can be found in
up to 67% of piglets (Zahn et al. 1995) and 99% of fin-
ishing pigs (Szeredi et al. 1996). Serum antibody surveys
of the same finishing animals using an ELISA method
confirmed antibody in 82.6%, but the complement-fixa-
tion test (CFT) detected antibody in only 28.6%, a figure
similar to that of Wilson and Plummer (1966). It is clear,
therefore, that infection with chlamydiae is widespread
among pigs.
Studies of the distribution of infection within infect-
ed herds suggest that infection can occur in animals of
every age group. Samples from which chlamydiae have
been isolated include semen samples from boars; fetuses,
both live and aborted; sows; lungs, joints, and organs
such as liver and spleen from piglets; store pigs; and pigs
at slaughter. Enteric infection is uncommon in piglets of
less than 4 weeks of age (6.9%) and more common
(41.8%) in piglets aged more that 4 weeks (Zahn et al.
1995), and conjunctival infection was recorded by
 CHAPTER 44 MISCELLANEOUS BACTERIAL INFECTIONS
Rogers et al. (1993) as associated with clinical signs be-
tween 2 and 8 weeks of age. The presence of low levels of
antibody in piglets may suggest maternal antibody trans-
fer. The possibility of transmission of intestinal chlamy-
diae to humans from slaughter pigs was raised by Szere-
di et al.(1996).
PATHOGENESIS
Experimental infections were carried out with “C.
psittaci” or “chlamydiae” prior to the identification of the
presence of three species of chlamydiae in pigs. The ac-
count which follows uses the term “C. psittaci” unless
there is evidence that the organisms were of the other
species.
Elementary bodies of C. psittaci enter by the respira-
tory, oral, or genital routes and enter epithelial cells, in
which they multiply or are taken up by macrophages and
distributed to lymph nodes. Infection may be local at the
portal of infection and remain inapparent or latent; may
cause local disease such as pneumonia, enteritis, or dis-
turbances of reproduction; or may become generalized.
C. psittaci isolates of avian, bovine, ovine, and porcine
origin have been used in experimental infections; but
strains of porcine origin appear to be most virulent for
the pig, provided they have not become yolk sac or tissue
culture adapted.
There appears to be some adaptation of strains to the
method of transmission, in that strains of genital origin
(Kielstein et al. 1983) do not appear to cause severe pneu-
monia, and parenteral inoculation was found necessary
to reproduce arthritis with an arthritis isolate. Pneumo-
nia has been consistently produced by intranasal or in-
tratracheal inoculation with porcine strains (Kielstein et
al. 1983; Martin et al. 1983; Stellmacher et al. 1983;
Rogers et al. 1996), but infection was found to spread
consistently to other organs. An acute exudative or inter-
stitial pneumonia with peribronchiolar cellular cuffing
and a lobular distribution occurs within 4–8 days of in-
fection. Lesions are fully developed by 8–12 days postin-
fection and are largely resolved by 4 weeks after infec-
tion, although infection may still be present in the lungs.
Similar lesions were produced in germfree pigs by Rogers
et al. (1996) using a C. trachomatis–like isolate from a
case of pneumonia. They identified mild multifocal
rhinitis and diarrhea in addition to the pneumonic
changes. Rogers and Anderson (1996) infected gnotobi-
otic piglets with isolates from diarrheic pigs to produce
diarrhea after 4–5 days which lasted for 8 days. The api-
cal part of the villus appeared to be colonized in the dis-
tal jejunum and ileum, with little or no infection in the
colon. Villous atrophy developed and this was later fol-
lowed (7–10 days postinfection) by mild focal serositis.
Contact infections suggest that natural infection is
normally less severe and that reinfection after 3–4 weeks
Taylor 621
results in little or no further disease. This development of
immunity is accompanied by development of comple-
ment-fixing antibodies to C. psittaci, which appear with-
in 2 weeks and remain detectable for a variable period.
Information on the time course of antibody detectable
by ELISA and indirect immunofluorescence is lacking.
In genital infections, infected semen given to sows
has resulted in the birth of weak piglets and continued
shedding of chlamydiae for up to 20 months.
CLINICAL SIGNS
Many chlamydial infections are inapparent, but consis-
tent features of respiratory tract and generalized infec-
tions include an incubation period of 3–11 days followed
by inappetence and a rise in rectal temperature to
39–41˚C. Dyspnea, pneumonia and conjunctivitis may
occur and may persist for 4-8 days. Evidence of pleurisy
or pericarditis may be detected by auscultation, and ar-
ticular involvement by lameness in one or more joints. In
slaughter pigs, polyarthritis associated with synovitis has
been reported. Other disturbances of gait include weak-
ness in piglets and nervous signs in pigs of all age
groups. Fatal infections are most commonly reported in
younger animals.
Diarrhea has been reported to be associated with
chlamydial infection (Pospischil and Wood 1987) and
can be produced experimentally in gnotobiotic pigs with
isolates from diarrheic animals (Rogers and Anderson
1996), but retrospective analysis of cases by Nietfeld et
al. (1997) failed to confirm that infection (demonstrated
by immunoperoxidase staining of the intestinal epitheli-
um) was statistically associated with diarrhea. Many re-
ports deal with genital tract infection and disturbances
in reproduction. In the boar, infection is associated with
orchitis, epididymitis, and urethritis; while infections in
gilts and sows have resulted in late abortions and the
birth of dead or weak piglets. Serologic and isolation
studies suggest that many genital tract infections are
clinically inapparent.
LESIONS
Lesions in which C. psittaci has been demonstrated often
contain other agents, and many descriptions of the le-
sions found in field cases may not take into account the
presence of agents such as mycoplasmas or viruses. The
large body of work on respiratory disease suggests that
lung lesions are distributed posteriorly in most cases, al-
though occasional patches of pneumonia may occur in
the anterior lobes (Harris et al. 1984).
Lesions are irregular and raised, are of firm consis-
tency, extend deep into the lung tissue, are limited by
lobular boundaries, and are clearly demarcated from ad-
jacent grossly normal tissue. Early lesions are pale red,
622 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
becoming grayish as they age. Enlarged bronchial lymph
nodes may be present. The microscopic findings include
thickening of the alveolar septae by capillaries, septal
edema, and neutrophils in peribronchial and subepithe-
lial sites. Neutrophils and macrophages are common in
the alveolar lumina, and in some areas this exudate oc-
cludes terminal bronchioles. Edema and massive epithe-
lial cell shedding have been reported in severely affected
lung lobules (Martin et al. 1983). Foci of type II pneu-
mocyte hypertrophy and hyperplasia and vacuolated
pneumocytes and bronchial epithelium have been re-
ported in C. trachomatis–like experimental infection
(Rogers et al. 1996). Peribronchiolar accumulations of
plasma cells, lymphocytes, and macrophages are also
common. There appears to be no pleurisy in experimen-
tal infections, and no gross changes in other organs were
reported beyond enlargement of the bronchial lymph
nodes. Antigen can be demonstrated in bronchial and
bronchiolar epithelial cells and in pneumocytes in exper-
imental studies (Rogers et al. 1996) and in field cases
(Done et al. 1992).
The other lesions reported to occur in field cases in-
clude pericarditis, pleurisy, hemorrhages of kidney and
bladder, and enlargement of the spleen. There is little
doubt that synovitis accompanies the arthritic changes
and that orchitis in boars is accompanied by interstitial
edema and tubular degeneration. Aborted piglets may be
mummified; stillborn or weak piglets may have lung, liv-
er, or enteric lesions. The organism has been isolated
from pseudomembranous colitis in experimental S. ty-
phimurium infections (Pospischil and Wood 1987), and
extensive studies of pig intestines by immunoperoxidase
(Zahn et al. 1995; Pospischil et al. 1996; Szeredi et al.
1996; Nietfeld et al. 1997) confirm the distribution of the
inclusions in the small-intestinal villi in piglets and in the
large-intestinal intercrypt epithelium in finisher pigs. Le-
sions in experimentally infected gnotobiotic piglets in-
cluded watery colon contents with flakes of undigested
curd, villous atrophy, lymphangitis, and multifocal
necrosis of the apical portion of the villi (Rogers and An-
derson 1996).
DIAGNOSIS
The clinical signs of chlamydial infection are not distinc-
tive, but it must be considered as a possible cause of
pneumonia, polyarthritis, enteritis, late abortion, still-
births, mummified piglets, and orchitis. The gross le-
sions in the lung may be suggestive of chlamydial infec-
tion, but any firm diagnosis involves laboratory tests.
These are serologic: complement fixation using heat-sta-
ble C. psittaci antigen, and ELISA using tissue culture
antigen (Szeredi et al. 1996); microscopic agglutination
(Wilson and Plummer 1966); and indirect immunofluo-
rescence. Complement-fixing antibodies should ideally
be found to rise in paired serum samples, but the pres-
ence of high levels of antibody (1:256) may be sufficient.
As only low levels of complement-fixing antibodies may
arise from infections in sites such as the respiratory, en-
teric, and genital tracts, the absence of high levels of
complement-fixing antibody does not rule out chlamydi-
ae as a cause of disease.
Chlamydiae may be detected in smears of discharges
or postmortem specimens and in histological specimens
after staining by Giemsa’s method. The organisms are
tiny (0.2–1.0 µm) and are present in large numbers in
cells. A more satisfactory method is to use Koster’s stain
in which a fixed smear is stained for 5 minutes with car-
bol fuchsin, decolorized for 30 seconds with 0.25% acetic
acid, and counterstained for 1 minute with 1% aqueous
Loeffler’s methylene blue. The chlamydiae appear as
clusters of intracellular red dots against a blue back-
ground (Fig. 44.2). Most specific of all is the immunoflu-
orescence test using specific fluorescein-conjugated anti-
body to C. psittaci to demonstrate infected cells.
Immunoperoxidase tests have been described (Chasey et
al. 1981), and the immunoperoxidase staining of fixed
tissue sections is now standard and appears to be the
most sensitive method of detection (Szeredi et al. 1996)
in tissue. Many laboratories are using PCR tests to con-
firm the presence of the three species in feces and tissue
specimens. Primers include genomic DNA sequences,
16S rRNA gene sequences, ompA gene sequences, and
plasmid sequences.
Isolation can also be carried out by the inoculation of
young mice and of 6- to 8-day fertile hen eggs. More than
one subculture may be necessary before infection can be
detected. Cell cultures using L929 or McCoy cell lines
treated with cycloheximide (1 µg/mL) may be inoculated
by centrifugation (Farmer et al. 1982) in tissue culture
medium at pH 7.0. Inclusions are at a maximum after 48
hours of incubation at 35–37˚C.
Transport media for chlamydiae should contain
streptomycin (50–100 mg/L) or gentamicin (10–20
mg/L) with vancomycin (100 µg/mL) and nystatin (25
mg/L). Samples can be stored at 4˚C or at −70˚C. Han-
dling C. psittaci is dangerous, and severe human infec-
tions and death can result. Appropriate safety precau-
tions should be observed.
TREATMENT
A number of antimicrobials have some effect on C.
psittaci in vitro, but the most satisfactory compounds for
treatment are the tetracyclines. Treatment for inade-
quate times may result in relapse; for complete elimina-
tion or suppression of infection to the latent state, 21-
day treatment should be given at the therapeutic level.
Tetracycline, oxytetracycline, and chlortetracycline can
all be used in drinking water or feed. Long-acting oxyte-
tracycline injections are useful for treating individual in-
fected animals.
 CHAPTER 44 MISCELLANEOUS BACTERIAL INFECTIONS
PREVENTION
Pigs should be prevented from coming into contact with
infected pigs, other mammalian species, and bird drop-
pings. Infected pigs should be maintained in separate air
and drainage spaces from susceptible animals. Any in-
fected breeding stock should be used only after tetracy-
cline treatment or kept with other infected stock in isola-
tion until sufficient uninfected animals are available to
replace them. Disinfection with phenols and formalin fu-
migation will eliminate elementary bodies from build-
ings.
REFERENCES
Anderson, I. E.; Baxter, S. I. F.; Dunbar, S.; Rae, A. G.;
Philips, H. L.; Clarkson, M. J.; and Herring, A. J. 1996.
Analyses of the genomes of chlamydial isolates from ru-
minants and pigs support the adoption of the new
species Chlamydia pecorum. Int J Syst Bacteriol
46:245–251.
Chasey, D.; Davis, P.; and Dawson, M. 1981. Immunoperox-
idase detection of Chlamydia ovis in experimentally in-
fected cell culture. Br Vet J 137:634–638.
Done, S. H.; McGill, I.; Spencer, Y.; and Simmons, J. 1992.
Chlamydia psittaci and necrotizing interstitial pneumo-
nia. Proc Int Congr Pig Vet Soc 12:341.
Farmer, H.; Chalmers, W. S. K.; and Woolcock, P. R. 1982.
Taylor 623
44.2. Photomicrograph of
elementary bodies of
Chlamydia sp. (arrow) in
aborted placenta (×1200).
Chlamydia psittaci isolated from the eyes of domestic
ducks (Anas platyrhynchos) with conjunctivitis and rhini-
tis. Vet Rec 110:59.
Harris, J. W. 1976. Chlamydial antibodies in pigs in Scot-
land. Vet Rec 98:505–506.
Harris, J. W.; Hunter, A. R.; and Martin, D. A. 1984. Experi-
mental chlamydial pneumonia in pigs. Comp Immun
Microbiol Infect Dis 7:19–26.
Johnson, F. W. A. 1984. Isolation of C. psittaci from nasal
and conjunctival exudate of a cat. Vet Rec 114:342–344.
Kaltenbroeck, B., and Storz, J. 1992. Biological properties
and genetic analysis of the ompA locus in chlamydia iso-
lated from swine. Am J Vet Res 53:1482–1487.
Kaltenbroeck, B.; Kousoulas, K. G.; and Storz, J. 1993. Struc-
tures of and allelic diversity and relationships among
the major outer membrane protein (omp A) genes of the
four chlamydial species. J Bacteriol 175:487–502.
Kielstein, P.; Stellmacher, H.; Horsch, F.; and Martin, J.
1983. Zur ChlamydienInfektion des Schweines. I. Mit-
teilung zur experimentellen Chlamydien-Pneumonie
des Schweines. Arch Exp Veterinärmed 37:569–586.
Martin, J.; Kielstein, P.; Stellmacher, P.; and Horsch, F. 1983.
Zur Chlamydien Infektion des Schweines. II. Mitteilung:
Pathologische-histologische Besonderhect der experi-
mentellen Chlamydien Pneumonie des Schweines. Arch
Exp Veterinärmed 37:939–949.
Nietfeld, J. C.; Leslie-Steen, P.; Zeman, D. H.; and Nelson, D.
1997. Prevalence of intestinal chlamydial infection in
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pigs in the Midwest as determined by immunoperoxi-
dase staining. Am J Vet Res 58:260–264.
Pospischil, A., and Wood, R. L. 1987. Intestinal Chlamydia
in pigs. Vet Pathol 24:568–570.
Pospischil, A.; Thoma, R.; Schiller, I.; Sydler, T.; and
Guscetti, F. 1996. Chlamydia in pigs. Pig J 37:9–13.
Rogers, D. G., and Anderson, A. A. 1996. Intestinal lesions
caused by two swine chlamydia isolates in gnotobiotic
pigs. J Vet Diagn Invest 8:433–440.
Rogers, D. G.; Anderson, A. A.; Hogg, A.; Nielson, D. L.; and
Huebert, M. A. 1993. Conjunctivitis and keratoconjunc-
tivitis associated with chlamydias in swine. J Am Vet
Med Assoc 203:1321–1323.
Rogers, D. G.; Anderson, A. A.; and Hunsaker, B. D. 1996.
Lung and nasal lesions caused by a swine chlamydial iso-
late in gnotobiotic pigs. J Vet Diagn Invest 8:45–55.
Sorodoc, G.; Surdan, C.; and Sarateanu, D. 1961. Cercetari
asupra identificarii virusului pneumoniei enzootice a
porcilor. Stud Cerc Inframicrobiol 12 (Suppl):355–
364.
Stellmacher, H.; Kielstein, P.; Horsch, F.; and Martin, J.
ACTINOBACILLUS SUIS
Septicemia and death caused by Actinobacillus suis and
occasionally by A. equuli in suckling and recently weaned
pigs have been reported sporadically from several pig-
rearing countries (Van Dorssen and Jaartsveld 1962; Cut-
lip et al. 1972; Windsor 1973; Mair et al. 1974; MacDon-
ald et al. 1976). A. suis outbreaks resembling erysipelas
have been reported in older pigs and sows in Canada
(Miniats et al. 1989), and the organism has also been the
cause of disease resembling pleuropneumonia in older
pigs in the United States (Yaeger 1996) and the United
Kingdom. Most outbreaks occur as sudden death of one
or several piglets in one, two, or, rarely, multiple litters in
individual herds. Infection with A. suis is probably wide-
spread but disease is seldom reported.
ETIOLOGY
A. suis is a gram-negative, nonmotile, nonencapsulated,
aerobic, and facultative anaerobic coccobacillus, 0.5–3
µm long and about 0.8 µm in diameter. Filamentous
forms occur. Grayish, adherent, circular, translucent
colonies measuring 1–2 mm form on blood agar within
24 hours. On horse blood agar, colonies are surrounded
by a narrow but distinct zone of alpha hemolysis, and on
calf and sheep blood agars, by a wide zone of beta (com-
plete) hemolysis. The organism grows on MacConkey
agar. Biochemically, A. suis can be differentiated from
other related bacteria isolated from pigs by its ability to
1983. Zur Bedeutung der Chlamydien-Infektion des
Schweines unter besonder Berucksichtigung der Pneu-
monien. Monatsh Veterinärmed 38:601–606.
Szeredi, L.; Schiller, I.; Sydler, T.; Guscetti, F.; Heinen, E.;
Corboz, L.; Eggenberger, E.; Jones, G. E.; and Pospischil,
A. 1996. Intestinal chlamydia in finishing pigs. Vet
Pathol 33:369–374.
Vasquez-Cisneros, C.; Wilsmore, A. J.; and Bolle, E. 1994.
Experimental infections of pregnant sows with ovine
chlamydia strains. Vet Microbiol 42:383–387.
Willigan, D. A., and Beamer, P. D. 1955. Isolation of trans-
missible agent from pericarditis of swine. J Am Vet Med
Assoc 126:118–122.
Wilson, M. R., and Plummer, P. A. 1966. A survey of pig
sera for the presence of antibodies to the P.L.V. group of
organisms. J Comp Pathol 76:427–433.
Zahn, I.; Szeredi, L.; Schiller, I.; Straumann Kunz, U.; Buer-
gi, E.; Guscetti, F.; Heinen, E.; Corboz, L.; Sydler, T.; and
Pospischil, A. 1995. Immunologischer nachweis von
Chlamydia psittaci/pecorum und Chlamydia trachomatis
im Ferkel Darm. J Vet Med Series B 42:266–276.
produce catalase, oxidase, and urease; hydrolysis of es-
culin; and acid production without gas from arabinose,
lactose, salicin, and trehalose, but not from mannitol or
sorbitol. Its biochemistry and antigenicity have recently
been studied by Bada et al. (1996). Distinction from iso-
lates of A. pleuropneumoniae biotype II is difficult but can
be achieved biochemically and using DNA analysis. A.
equuli differs from A. suis by being nonhemolytic; pro-
ducing acid from mannitol but not from arabinose, cel-
lulose, and salicin; and not splitting esculin. A. suis is
pathogenic for mice; A. equuli is not. A. suis and A. equuli
are killed within 15 minutes at 60˚C and are sensitive to
most disinfectants. They die out within a few days in cul-
ture and pathologic material.
EPIDEMIOLOGY
A. suis can be carried in the tonsils and nostrils of
healthy pigs of any age and in the vaginas of apparently
healthy sows (Ross et al. 1972). Clinical disease occurs in
neonates and suckling pigs up to and just after weaning
age, and less commonly in sows and mature swine (Mini-
ats et al. 1989; Sanford et al. 1990). With the separation
of pigs and horses in modern farming systems, infection
in pigs by A. equuli seems to have diminished.
Outbreaks of clinical disease associated with A. suis
infection occur more frequently in minimal-disease and
other high-health-status herds (Miniats et al. 1989; San-
 CHAPTER 44 MISCELLANEOUS BACTERIAL INFECTIONS
ford et al. 1990), possibly because the lack of immunity
in these pigs allows virulent A. suis organisms to express
their pathogenic potential, but the organism can be re-
covered from herds in which disease is not apparent.
PATHOGENESIS
The pathogenesis of A. suis infection has not been de-
fined. Infection probably occurs via the upper respirato-
ry tract, and the disease has been reproduced by in-
tranasal inoculation (Fenwick et al. 1996), although
invasion through abrasions in the skin and mucous
membranes is also likely. In susceptible animals, septic
emboli then spread rapidly to multiple organs and tis-
sues throughout the body and either are trapped in ves-
sels or adhere to vessel walls, forming microcolonies sur-
rounded by areas of hemorrhage and necrosis. Virulence
factors of A. suis have not been specifically determined,
but lipopolysaccharide, polysaccharides in the cell wall,
outer-membrane proteins, and, in some strains, a 104
kDa hemolysin (ApxI) are all potential virulence factors
likely to be involved in pathogenesis. Antibodies to ApxI
have been demonstrated in the sera of pigs which have
recovered from experimental infection (Fenwick et al.
1996). Pigs may die within 15 hours of infection.
CLINICAL SIGNS
Sudden death of suckling piglets, 2 days to 4 weeks old,
in one or more litters is often the first indication of an
outbreak of actinobacillosis. Deaths in piglets are some-
times mistakenly attributed to crushing. Cyanosis, pe-
techial hemorrhages, fever (up to 40˚C, 104˚F), and
panting, sometimes accompanied by shaking and/or
paddling, may be seen prior to death in suckling pigs.
Congestion of extremities (leading to necrosis of feet,
tail, and ears) and swollen joints may occur. In weaned
44.3. Lung of 3-day-old piglet with actinobacillosis. Note the hemorrhages.
Taylor 625
pigs, anorexia, fever, a persistent cough, respiratory dis-
tress (Yaeger 1996) and pneumonia are reported; recov-
ered animals may remain unthrifty. In outbreaks in ma-
ture animals, fever, round and rhomboid erythematous
skin lesions, inappetence, and sudden deaths are charac-
teristic, but mortality is usually low. Metritis, meningitis,
and abortion have been reported in sows. The disease
may be confused with erysipelas, especially when skin le-
sions develop, and with pleuropneumonia when respira-
tory signs are present.
LESIONS
The most striking gross lesions are petechial to ecchy-
motic hemorrhages in any of the following organs: lung,
kidney, heart, liver, spleen, skin, and intestines. The le-
sions are especially prominent and most frequently seen
in the lung, where lobular necrosis and serofibrinous ex-
udates also occur (Fig. 44.3). Increased serous or serofib-
rinous exudates may occur in the thorax and the peri-
cardium. Pleurisy, pericarditis, and miliary abscesses in
the lung, liver, skin, mesenteric lymph nodes, and kidney
may be seen in older suckling or weaned pigs. The pneu-
monic lesions may resemble those of pleuropneumonia.
Arthritis (Van Dorssen and Jaartsveld 1962; Odin 1994)
and valvular endocarditis (Jones and Simmons 1971)
have been reported. In mature animals, numerous
round, rhomboid, or irregular skin lesions are com-
mon.
Histologically, bacterial thromboemboli with accom-
panying fibrinohemorrhagic necrosis in randomly scat-
tered vessels in the lung, liver, kidney, skin, spleen, heart,
pericardium, meninges, and brain are characteristic (Fig.
44.4). Bacterial emboli may be surrounded by radiating
eosinophilic clublike colonies. These are most obvious in
the lung, where there may be large coalescing areas of
necrosis.
44.4. Photomicrograph of a microabscess in the lung as shown in Fig. 44.3. Note the
microcolonies of bacteria (H&E; ×110).
DIAGNOSIS
Sudden mortality in suckling pigs in individual litters in
herds with previous A. suis outbreaks usually indicates a
new outbreak. The gross lesions of hemorrhages and
necrosis in the lung and/or skin and kidney and splenic
enlargement are suggestive of A. suis infection. In mature
pigs, fever, inappetence, and skin lesions resembling
erysipelas, especially in herds already vaccinated against
erysipelas, should raise a suspicion of A. suis. Micro-
scopic lesions consisting of bacterial emboli, necrosis,
and inflammatory cells in the lung and other organs are
also suggestive. Diagnosis, however, depends on isola-
tion of A. suis or A. equuli from the lesions. A. suis infec-
tion should be considered when pleuropneumonia is sus-
pected in herds thought to be free from that disease. In
these herds it may cause mild or atypical lung lesions and
give rise to antibody to ApxI but not to the cytotoxin of
A. pleuropneumoniae or to its somatic antigens (Fenwick
et al. 1996). A suis can usually be isolated from the tonsils
of piglets aged 2–10 days in such herds.
TREATMENT
A. suis is sensitive to most commonly used antibiotics.
Since outbreaks in suckling pigs are so acute and unpre-
dictable, however, treatment is usually too late. In older
pigs, responses to treatment with ampicillin (5 mg/kg)
orally or parenterally, injectable benzathine-procaine
penicillin G (2.25–3.0 × 106 IU) intramuscularly (IM),
injectable procaine penicillin (1.8–2.4 × 106 IU) IM, or
in-feed medication with oxytetracycline hydrochloride
(550 g/ton) and/or streptomycin for periods up to 1
week have all been excellent.
PREVENTION
Autogenous bacterins have not been critically evaluated
but have been used in herds with repeated A. suis out-
breaks with apparent success.
REFERENCES
Bada, R.; Mittal, K. R.; and Higgins, R. 1996. Biochemical
and antigenic relationships between porcine and equine
strains of Actinobacillus suis. Vet Microbiol 51:393–396.
Cutlip, R. C.; Amtower, W. C.; and Zinober, M. R. 1972. Sep-
tic embolic actinobacillosis of swine: A case report and
laboratory reproduction of the disease. Am J Vet Res
33:1621–1626.
Fenwick, B.; Rider, M.; Chengappa, M.; and Montarz, J.
1996. Cross protective immunity between Actinobacillus
suis and A. pleuropneumoniae. Proc Int Congr Pig Vet Soc
14:373.
 CHAPTER 44 MISCELLANEOUS BACTERIAL INFECTIONS
Jones, J. E. T., and Simmons, J. R. 1971. Endocarditis in the
pig caused by Actinobacillus equuli: A field and an exper-
imental case. Br Vet J 127:25–29.
MacDonald, D. W.; Hewitt, M. P.; Wilton, G. S.; Rawluk, S.;
and Childs, L. 1976. Actinobacillus suis infections in Al-
berta swine, 1973–1975: Pathology and bacteriology.
Can Vet J 17:251–254.
Mair, N. S.; Randall, C. J.; Thomas, G. W.; Harbourne, J. F.;
McCrea, C. T.; and Cowl, K. P. 1974. Actinobacillus suis
infection in pigs: A report of four outbreaks and two
sporadic cases. J Comp Pathol 84:113–119.
Miniats, O. P.; Spinato, M. T.; and Sanford, S. E. 1989. Acti-
nobacillus suis septicemia in mature swine: Two out-
breaks resembling erysipelas. Can Vet J 30:943–947.
Odin, M. 1994. Les infections a Actinobacillus suis au Que-
bec: une étude retrospective de 22 cas. Méd Vét du Que-
YEASTS
Yeasts are fungi that are normally single celled but can
form filaments (or pseudohyphae). Some can sporulate
to produce resistant spores. They occur in the food of the
pig and in dusts. Some species are commonly found on
the skin and mucous membranes. In certain situations,
yeasts of a number of species (but principally Candida
albicans) may be isolated from inflammatory lesions of
the oral cavity, gastrointestinal tract, urogenital tract,
and skin. Their isolation from such lesions is often asso-
ciated with use of therapeutic antimicrobials, especially
in piglets. Yeasts belonging to the genus Malassezia, pos-
sibly M. pachydermatis, are present in the ears and on the
skin of pigs, but their role in disease at these sites is not
known. They can reach high numbers when skin or ear
lesions develop, but so little is currently known about
them and their role in disease that they will not be con-
sidered further.
Yeasts may also form a major part of the diet of the
pig, as either yeast wastes from brewing or distilling or
yeast grown and treated specifically as a component of
rations. These yeasts can provide high protein and, in
particular, high lysine. Traces of paraffin waxes have
been found in the fat of pigs fed on yeasts grown on that
substrate, and there are some reports of diarrhea and in-
creased kidney weights in yeast-fed pigs. Most reports in-
dicate that inclusion of yeasts in the ration does not ad-
versely affect the health of pigs.
ETIOLOGY
Yeasts identified in infections in pigs belong to a number
of genera. Those of the genus Candida are most com-
monly isolated, although species of Torulopsis, Tri-
chosporon, Rhodotorula, Pichia, Pityrosporum, and Crypto-
Taylor 627
bec 24:61–65.
Ross, R. F.; Hall, J. E.; Orning, A. P.; and Dale, S. E. 1972.
Characterization of an Actinobacillus isolated from the
sow vagina. Int J Syst Bacteriol 22:39–46.
Sanford, S. E.; Josephson, G. K. A.; Rehmtulla, A. J.; and
Tilker, A. M. E. 1990. Actinobacillus suis infection in pigs
in southwestern Ontario. Can Vet J 31:443–447.
Van Dorssen, C. A., and Jaartsveld, F. H. J. 1962. Acti-
nobacillus suis (novo species), a bacterium occurring in
swine. Tijdschr Diergeneeskd 87:450–458.
Windsor, R. S. 1973. Actinobacillus equuli infection in a litter
of pigs and a review of previous reports on similar in-
fections. Vet Rec 92:178–180.
Yaeger, M. J. 1996. An outbreak of Actinobacillus suis sep-
ticemia in grow/finish pigs. J Vet Diagnost Invest
8:381–383.
coccus have been recorded. Cryptococcus neoformans has
been isolated from cryptococcosis in pigs, but the disease
is rare in this species and occurs only where the organism
is commonly found in other livestock.
Candida albicans is the species of Candida most fre-
quently reported; but C. tropicalis, C. pseudotropicalis, C.
brumptii, C. sloofii, C. rugosa, C. lipolytica, C. krusei, and C.
scottii have been isolated from lesions or feces of appar-
ently healthy pigs. Since C. albicans is associated most
frequently with specific lesions, both it and its relation-
ship to these lesions will be described here.
Candida spp. are spherical cells, 2.5–6 µm in diame-
ter. They reproduce by budding (blastospores) and
chlamydospores, which bud from filaments (or pseudo-
hyphae) on chlamydospore agar, particularly under re-
duced oxygen tension at 25˚C (Carter 1979). Pseudohy-
phae and oval yeast forms are found in lesions. Candida
spp. grow readily on Sabouraud agar, malt agar, and of-
ten on blood agar incubated aerobically. They form 1–2
mm, creamy white, opaque, circular colonies within
24–48 hours at 37˚C and within 2–4 days at 25˚C. C. al-
bicans produces chlamydospores and germ tubes but no
pellicle when grown in broth and ferments glucose, mal-
tose, and galactose but not sucrose or lactose. It is not
known to produce toxins, although there have been sug-
gestions that it can produce keratolytic enzymes in the
presence of glucose.
EPIDEMIOLOGY
C. albicans has been identified in the bedding, feed, and
water supplies of pigs. It occurs on the skin and in the
oral cavity, stomach, and intestines of normal pigs in
small numbers. It can be shed in the feces and exhaled in
628 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
droplets by animals with oral infections. It may be isolat-
ed from the feces of birds, rodents, and other animal
species and may cause disease in those species, which
may become sources of the organism for pigs. Organ-
isms in the environment may multiply in moist condi-
tions in the presence of suitable substrates such as
spilled meal or garbage.
PATHOGENESIS
C. albicans appears to colonize debilitated skin surfaces
and lesions on other mucous surfaces. The predisposing
factors appear to include the effects of artificial rearing
of piglets (Osborne et al. 1960) and chronic enteritis of-
ten associated with treatment with broad-spectrum an-
timicrobials. Gastric ulcers appear to be colonized by
yeasts rather than initiated by them, and cutaneous can-
didiasis often results from exposure to continually warm
moist conditions that are accompanied by poor hygiene
and food residues (Reynolds et al. 1968).
Invasion of mucous surfaces appears to follow accu-
mulation of yeast forms on the debilitated surface and
develops with pseudohyphal invasion of the superficial
layers of the epithelium. Systemic invasion is rare and
the inflammatory response to infection is slight.
CLINICAL SIGNS
Yeasts have been implicated in chronic gastroenteritis in
piglets, gastric ulceration, and cutaneous and oropha-
ryngeal infections. Piglets are often 3–5 days old (more
commonly, 7–14 days) before yeast infection complicates
the underlying problem. The clinical signs of gastroen-
teritis complicated by yeasts are not specific, but there is
often a history of dullness, inappetence, vomiting, and
chronic diarrhea that may be grayish or blackish de-
pending on the diet and has failed to respond to the use
of broad-spectrum antibiotics such as tetracyclines.
Piglets may die after 10–14 days of illness. In many cases
there are characteristic yellowish white, circular, 2–5 mm
lesions on the tongue and hard palate, which resemble
colonies of C. albicans on artificial media. When scraped
off, no macroscopic changes are seen beneath them. Cu-
taneous candidiasis often presents as a moist gray exu-
date on the surface of the skin of the abdomen with little
or no effect on the hair in early lesions, but later resulting
in hair loss and thickening of the skin. Affected animals
are often kept in moist conditions and exposed to food
residues.
LESIONS
Piglets with candidiasis are often in poor condition with
chronic diarrhea. There may be lesions in the oral cavity
and throughout the gastrointestinal tract. These consist
of white specks and circular patches 2–5 mm in diameter
on the dorsum of the tongue, less frequently on the phar-
ynx, and sometimes on the soft or hard palate. These
patches may coalesce to form larger areas of
pseudomembranous material that may occlude the lu-
men of the esophagus. The lesions may extend down the
esophagus and may be seen on the gastric mucosa. There
may be small hemorrhages in the cardiac area and white
pseudomembranous lesions in the esophageal area. De-
scriptions of the lesions distal to the stomach are rarely
published, but in heavily infected animals they resemble
those of chronic enteritis, with villous atrophy and thick-
ening of the mucosa. When the white pseudomembra-
nous material is removed, congestion of the mucosal sur-
face may be seen, but ulceration is rare. In older pigs, C.
albicans may be isolated from gastric ulcers, but these do
not differ grossly from uninfected ones. Gross lesions
may be seen in cutaneous candidiasis and include a gray-
ish surface deposit, thickening of the skin, and hair
loss.
Microscopic lesions include the presence of numer-
ous yeasts on the epithelial surface, with pseudohyphal
filaments visible as 1.5–2.0 µm deeply staining threads in
the epithelium. In lesions on the tongue, yeast cells and
pseudohyphae may be seen in cavities beneath the papil-
lae. They may also be present in large numbers in the pe-
riphery of infected gastric ulcers. Degenerative changes
are frequently present in the infected epithelium. They
include desquamation of epithelial cells, capillary dila-
tion, edema of the submucosa or dermis (depending on
the epithelial surface attached), and presence of inflam-
matory cells. These are neutrophils in the early lesions,
later (in 4- to 5-day-old lesions) accompanied by
eosinophils, macrophages, plasma cells, and lympho-
cytes.
DIAGNOSIS
In piglets the appearance of the white 2–5 mm lesions in
the oral cavity may suggest that candidiasis is present,
but diarrhea and association of infection with gastric ul-
ceration may not be identified on clinical grounds. Skin
changes may also suggest a diagnosis of candidiasis. A
history of chronic enteritis and broad-spectrum antibi-
otic use or housing in moist conditions is often sugges-
tive of candidiasis.
Confirmation of diagnosis is based on demonstra-
tion of the organism concerned in the lesions or, in life,
isolation of large numbers from the feces. The presence
of yeasts in lesions of the intestine may be established by
their demonstration in Gram-stained smears in which
oval or round, gram-positive, often budding, 2.5–6 µm
cells may be seen (Fig. 44.5). Similar bodies may be seen
in histological sections stained by hematoxylin and eosin
or, more easily, stained by periodic acid-Schiff or silver
stains such as Grocott’s (Fig. 44.6). None of these allow
the complete identification of the organism.
Yeasts may be isolated using Sabouraud’s agar with or
without chloramphenicol (Carter 1979). Some, such as
CHAPTER 44 MISCELLANEOUS BACTERIAL INFECTIONS Taylor 629

44.5. Photomicrograph of
yeast cells (arrow) from the
ileal mucosa in a 10-day-old
piglet (Gram; ×1200).

44.6. Photomicrograph of
yeast cells and pseudohyphae
adjacent to the ileal mucosa
in a 10-day-old piglet
(Grocott; ×400).
630 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
C. albicans, will grow readily on horse blood agar. Incu-
bation at 25˚C yields colonies 1–2 mm in diameter after
3–4 days, but incubation at 37˚C can allow colonies to be
identified within 24–48 hours. The genera can be sepa-
rated using characters such as shape of the cells, pres-
ence or absence of pseudomycelium, presence or ab-
sence of capsule, production of chlamydospores, ability
to split urea, and other characters (Carter 1979). Many
yeast species may be identified in culture using commer-
cial biochemical strips such as the API Yeast series.
Isolation of large numbers of yeasts from lesions may
confirm a diagnosis of candidiasis, but their isolation in
small numbers from the skin, vagina, or feces and in-
testines of clinically normal pigs may not be significant.
TREATMENT
C. albicans and other yeasts are sensitive in vitro to a
number of compounds such as nystatin, miconazole,
and amphotericin B, but only nystatin and amphotericin
B have been used in treatment (Osborne et al. 1960).
Nystatin suppressed the clinical signs but did not elimi-
nate infection. Amphotericin B may be effective in young
piglets given at a rate of 0.5 mg/kg twice daily. In many
instances, correction of underlying disease or husbandry
factors is sufficient. Cleaning up waste food and provid-
ing a dry environment caused resolution of cutaneous
candidiasis (Reynolds et al. 1968). Treatment should also
YERSINIAS
A number of species of Yersinia have been isolated from
pigs, and reports of association between infection and
clinical disease are increasing. Y. enterocolitica has in-
creasingly become recognized as a cause of human food
poisoning and enteritis since the late 1960s, and the pig
is an important source. There are reports in the literature
of many surveys of pig carcasses, offal, and feces for the
presence of Y. enterocolitica (Doyle et al. 1981; Schie-
mann and Fleming 1981; Hunter et al. 1983). Results of
these surveys show that infection is distributed world-
wide in pigs, and serotypes considered pathogenic to hu-
mans are commonly present. This relationship to human
disease has stimulated a number of reports of pathogen-
ic determinants (Mosimbale and Gyles 1982) that have
been demonstrated in Y. enterocolitica in both porcine
and human isolates, and it seems clear from the work of
Kwaga and Iversen (1993) that the pig and human strains
are identical. Further reports deal with the antigenic re-
lationships between Yersinia spp. and Brucella spp., since
infections with certain strains of the former can cause in-
terference with serologic tests for both B. abortus and B.
include discontinuation of the use of broad-spectrum
antibiotics and their replacement with narrow-spectrum
ones if they are a factor in yeast colonization. Animals
with cutaneous candidiasis may also be scrubbed with
suitable detergent or with hexetidine-based shampoos.
PREVENTION
Pigs should be maintained in warm, dry, clean condi-
tions, and accumulations of moist fermenting food
should be prevented. Enteric diseases in piglets should
be treated with appropriate antimicrobials, and lengthy
treatment with broad-spectrum antibiotics should be
avoided. Disinfection of pens and pen fittings can be car-
ried out using formaldehyde vapor or 2% formaldehyde;
cleaning and drying of the pens will reduce levels of
yeasts to normal background levels.
REFERENCES
Carter, G. R. 1979. Diagnostic Procedures in Veterinary Bac-
teriology and Mycology, 3d ed. Springfield: Charles C.
Thomas, chap. 30.
Osborne, A. D.; McCrae, M. R.; and Manners, M. J. 1960.
Moniliasis in artificially reared pigs and its treatment
with nystatin. Vet Rec 72:237–241.
Reynolds, I. M.; Miner, P.; and Smith, R. E. 1968. Cutaneous
candidiasis on swine. J Am Vet Med Assoc 152:182–186.
suis. This interference is described in Chapter 28.
Infection in pigs is usually inapparent, but Y. pseudo-
tuberculosis and Y. enterocolitica have been isolated from
pigs with fever, enteritis, and diarrhea.
ETIOLOGY
Yersinias are aerobic or facultatively anaerobic, gram-
negative coccobacilli (or short rods), 1.2 µm in length
and 0.5–1.0 µm in diameter. They are nonmotile at 37˚C,
but some are motile at lower temperatures. Species iso-
lated from pigs include Y. pseudotuberculosis, Y. pseudotu-
berculosis subsp. pestis (the plague bacillus), Y. enterocolit-
ica, Y. intermedia, Y. fredrikensii, and Y. kristensenii. Only
two species (Y. pseudotuberculosis and Y. enterocolitica)
have yet been associated with clinical disease in pigs.
Yersinias may be isolated in routine media, upon
which they appear as grayish 1–2 mm colonies within
24–48 hours and as similar-sized non-lactose-fermenting
colonies on MacConkey agar. The species are distin-
guished by biochemical tests. Y. pseudotuberculosis is
 CHAPTER 44 MISCELLANEOUS BACTERIAL INFECTIONS
motile at 22˚C, grows on citrate media at 22˚C, splits
urea, and does not ferment sucrose or raffinose but does
ferment mannose. Y. pseudotuberculosis subsp. pestis is
negative for all these characters. Y. enterocolitica is also
motile and splits urea but ferments sucrose and does not
grow on citrate or ferment mannose. Individual species
can be divided into biotypes and serotypes. Capsules, at-
tachment antigens, and enterotoxins have been de-
scribed in organisms of this genus.
Y. enterocolitica has been subdivided into at least 46 O
groups and at least 5 biotypes. Of these, most human in-
fections are associated with biotype 2, O9 and biotype 4,
O3. Biotype 1, O8 is also associated with some human in-
fections. Y. enterocolitica organisms of a number of O
groups have been recorded from pigs. The actual O
groups isolated may vary from one part of a country to
another (Schiemann and Fleming 1981) but include O3,
O5, O6, O7, O8, O9, O13, O18, and O46.
EPIDEMIOLOGY
Y. enterocolitica is found throughout the world and has
been recorded from pigs in many countries (Bockemuhl
et al. 1979; Cantoni et al. 1979; Barcellos and Castro
1981; Doyle et al. 1981; Schiemann and Fleming 1981;
Hunter et al. 1983). Infection may not be general, since
not all herds are infected (Christensen 1980). It persists
on the tonsils of infected pigs for long periods and is
shed in the feces of infected pigs for up to 30 weeks. It
has been shown to be transmitted to human food and
elsewhere on farms by flies (Fukushima et al. 1979). Feed
has been found to be infected, and studies of the dissem-
ination of infection in pig facilities (Fukushima et al.
1983) indicate that infection is transmitted from conta-
minated pens, in which infection can persist for 3 weeks.
Other studies suggest that feces can remain infected for
up to 12 weeks and that, in suitable substrates, the or-
ganism may multiply at 20–22˚C. It appears that trans-
mission from pig to pig is via fecal contamination of ac-
commodation, water, and feed.
Y. pseudotuberculosis is less commonly demonstrated
in America than in Europe or Japan and is less common-
ly identified in pigs than Y. enterocolitica. It is commonly
found in rodents, which probably represent the main
source of infection for pigs.
Y. pseudotuberculosis subsp. pestis may infect wild pigs
in California, presumably from infection present in ro-
dents (Clark et al. 1983).
PATHOGENESIS
Y. enterocolitica has been shown to infect pigs orally, to
multiply and be found in the feces within 2–3 weeks of
infection, and to disappear from the feces within 30
weeks (Fukushima et al. 1984). No clinical signs or le-
sions were described and none were found following in-
Taylor 631
fection of 6 pigs with the isolate obtained from the clini-
cal outbreak described above. Experimental studies by
Nielsen et al. (1996) have confirmed that infection of the
feces may be found between 5 and 21 days after infection
and that tonsillar carriage persists longer. A serum anti-
body response develops by 19 days after infection and
has disappeared by 70 days postinfection. Studies in
suckling mice have indicated that 10 of the 12 pig iso-
lates tested produced enterotoxin and that one isolate
could produce fluid in piglet gut loops. The Sereny test
for invasiveness was negative in typical pig strains
(Mosimbale and Gyles 1982). Pig isolates harbor the vir-
ulence plasmid (Kwaga and Iversen 1993) and possess
the capsular material considered essential for patho-
genicity and detected using the congo red magnesium
oxalate test. Studies by Erwerth and Natterman (1987)
suggest that oral infection is followed by establishment
of infection in the tonsils and the development of enteri-
tis in the ileum and large intestine. Similar colonization
was reported by Schiemann (1988) and has also been re-
produced by Shu et al. (1995a, b) and Shu et al. (1997),
who demonstrated that small-intestinal infection in
piglets led to microabscesses at the base of the villi and
to reductions in the levels of intestinal lactases (Shu et al.
1997) and depressed growth (Shu et al. 1995b).
CLINICAL SIGNS
Clinical disease has been associated only with Y. enteroco-
litica and Y. pseudotuberculosis. Y. pseudotuberculosis sub-
sp. pestis is clearly capable of producing serologic reac-
tions (Clark et al. 1983), but no clinical disease has been
described.
Y. enterocolitica was isolated in profuse culture from
outbreaks of diarrhea in weaned pigs from which no oth-
er infectious agents could be recovered. Mild fever (to
39.4˚C, 103˚F) was present, and the diarrhea contained
no blood or mucus and was blackish in color. Clinical
signs resembling those described above have been seen
in animals receiving tylosin or lincomycin. Bloodstained
mucus may also be found in some diarrheic feces and on
solid feces passed by penmates. The organism has been
isolated from the rectal mucosa in cases of rectal stric-
ture. Experimental infections in suckling piglets result in
anorexia, vomiting, diarrhea, and reduction in weight
gain (Shu et al. 1995a).
Y. pseudotuberculosis has been associated with clinical
signs by Morita et al. (1968), who described an outbreak
in Japan. Affected pigs were dull and showed inappe-
tence; bloodstained diarrhea; and edema of eyelids, low-
er face, and dependent parts of the abdomen. Diarrhea
was also observed by Barcellos and Castro (1981). Neef
and Lysons (1994) were able to reproduce diarrhea in 4
of 9 pigs infected with a colitis isolate of Y. pseudotuber-
culosis. The organism has been isolated from pigs with
the rectal stricture syndrome.
632 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
LESIONS
The lesions caused by Y. enterocolitica infection have been
described in detail by Erwerth and Natterman (1987)
and consist of catarrhal enteritis in the small and large
intestines. Microcolonies of the organism can be seen in
the disrupted intestinal epithelium, and in pigs with rec-
tal lesions, bacterial penetration and inflammation reach
the muscularis mucosae. Shu et al. (1995a) confirmed
this finding for the small intestine and describe the pres-
ence of microabscesses at the bases of the villi.
Lesions of Y. pseudotuberculosis have been described
(Morita et al. 1968). They resembled those of pseudotu-
berculosis in other species, with miliary gray-white spots
on the liver and spleen and swollen gray-white mesen-
teric lymph nodes. A catarrhal and diphtheritic change
was described in the colon and rectum, as edema and as-
cites also occurred. Microscopic lesions included necrot-
ic foci containing masses of bacteria surrounded by a
thin layer of granulation tissue in the lung, liver, spleen,
mesenteric lymph nodes, and lymphoid follicles of the
large intestine. Similar findings were made by Neef and
Lysons (1994), who noted the penetration of the mi-
croabscesses into the lamina propria. Y. pseudotuberculo-
sis was isolated from the liver, spleen, lungs, duodenum,
rectum, and mesenteric lymph nodes by Morita et al.
(1968). Y. pseudotuberculosis can also be isolated from in-
flammatory lesions of the rectal mucosa similar to those
described above.
DIAGNOSIS
The clinical signs are not distinctive, but the occurrence
of mild fever and blood and mucus on solid feces can in-
dicate yersinia infection in the absence of swine dysen-
tery. Where rectal stricture is common, the organism
may be responsible for diarrhea in younger age groups,
and the organism may be involved in the “colitis” syn-
drome of mild diarrhea in growing pigs. Diagnosis of in-
fection with most Yersinia spp. in pigs depends upon iso-
lation of the organism and its identification. Serology
has been used to identify Y. pseudotuberculosis subsp.
pestis (Clark et al. 1983), but most accounts of yersinia
infections suggest that although agglutinating antibody
may result from infection, isolation methods are ade-
quate for diagnosis. The indirect ELISA developed by
Nielsen et al. (1996) for Y. enterocolitica O3 may be of val-
ue in the field but may not detect infections by other
serotypes. Y. pseudotuberculosis can readily be isolated at
37˚C on blood and MacConkey agar from lesions of the
type described by Morita et al. (1968) and so may Y. en-
terocolitica. Most isolation methods for all yersinias in-
volve use of a cold enrichment technique in which tis-
sues or samples under investigation are placed in
phosphate-buffered saline M/15 at pH 7.6 at 4˚C for 6
weeks, with subculture at 3 and 6 weeks onto a selective
medium (Hunter et al. 1983). The selective medium may
be MacConkey agar incubated at 30˚C or a specific
medium for Y. enterocolitica. These methods may be used
for direct isolation. Media are described by Hunter et al.
(1983) and six are reviewed by Catteau et al. (1983). Re-
cent studies by food microbiologists have resulted in a
range of tests, such as the immunomagnetic separation
and polymerase chain reaction technique of Rasmussen
et al. (1995), which can detect as few as 200 cells per
gram of feces.
TREATMENT
There is at present no general indication for the treat-
ment of yersinia infections, since clinical signs are so
rare. In vitro studies suggest that isolates are often sensi-
tive to oxytetracycline, furazolidone, neomycin, sulfon-
amides, and spectinomycin. Tetracyclines have been
used in feed to eliminate infection and clinical signs.
PREVENTION
Since spread of Y. enterocolitica from pig to pig appears to
occur from contact with feces, hygiene coupled with
housing groups of pigs in separate drainage areas will re-
duce infection. Control of flies and rodents and disinfec-
tion of pens before restocking will reduce transmission.
Morita et al. (1968) found that pseudotuberculosis could
be prevented by excluding birds and rodents. Current re-
quirements for the control of Y. enterocolitica in pig meat
concentrate on the removal of the tonsil at slaughter, so
control programs have not been developed for the live
animal. Control may be required when serologic cross-re-
action in the brucellosis test is identified in herds selling
breeding stock. The findings of Nielsen et al. (1996) sug-
gest that serologic reactions peak at 33 days postinfec-
tion and have disappeared by 70 days postinfection, so
pigs may be treated or managed at the time of infection
to prevent the development of antibody or held and
retested after antibody levels have declined.
REFERENCES
Barcellos, D. E. S. N. de, and Castro, A. F. P. de. 1981. Isola-
tion of Yersinia pseudotuberculosis from diarrheas in pigs.
Br Vet J 137:95–96.
Bockemuhl, J.; Schmitt, H.; Roth, J.; and Saupe, E. 1979. Die
jahreszeitliche Haufigkeit der Ausscheidung von Yersinia
enterocolitica im Kot gesunder Schlachtschweine. Zen-
tralbl Bakteriol (Orig A) 224:494–505.
Cantoni, C.; D’Aubert, S.; Buogo, A.; and Guizzardi, F. 1979.
Yersinia enterocolitica nelli feci di suino. Arch Vet Ital
30:134–136.
 CHAPTER 44 MISCELLANEOUS BACTERIAL INFECTIONS
Catteau, M.; Krembel, C.; and Wauters, G. 1983. Isolement
de Yersinia enterocolitica de langues de porc. Rec Méd Vét
159:89–94.
Christensen, S. G. 1980. Yersinia enterocolitica in Danish
pigs. J Appl Bacteriol 48:377–382.
Clark, R. K.; Jessup, D. A.; Hird, D. W.; Rupanner, R.; and
Meyer, M. E. 1983. Serologic survey of California wild
hogs for antibody against selected zoonotic disease
agents. J Am Vet Med Assoc 183:1248–1259.
Doyle, M. P.; Hugdahl, M. B.; and Taylor, S. L. 1981. Isola-
tion of Yersinia enterocolitica from porcine tongues. Appl
Environ Microbiol 41:661–666.
Erwerth, W., and Natterman, H. 1987. Histopathologische
Untersuchengen bei der experimentellen oralen Yersinia
enterocolitica Infektion des Jung-schweines. Monatsh Vet
42:319–324.
Fukushima, H.; Ito, Y.; Saito, K.; Tsubokura, M.; and Otsuki,
K. 1979. Role of the fly in the transport of Yersinia ente-
rocolitica. Appl Environ Microbiol 38:1009–1010.
Fukushima, H.; Nakamura, R.; Ito, Y.; Saito, K.; Tsubokura,
M.; and Otsuki, K. 1983. Ecological studies of Y. entero-
colitica in pigs. I. Dissemination of Y. enterocolitica in
pigs. Vet Microbiol 8:469–483.
Fukushima, H.; Nakamura, R.; Ito, Y.; and Saito, K. 1984.
Ecological studies of Yersinia enterocolitica. II. Experi-
mental infection with Y. enterocolitica in pigs. Vet Micro-
biol 9:375–389.
Hunter, D.; Hughes, S.; and Fox, E. 1983. Isolation of
Yersinia enterocolitica from pigs in the United Kingdom.
Vet Rec 112:322–323.
Kwaga, J., and Iversen, J. O. 1993. Plasmids and outer mem-
brane proteins of Yersinia enterocolitica and related
species of swine origin. Vet Microbiol 36:205–214.
Morita, M.; Nakamatsu, M.; and Goto, M. 1968. Pathologi-
cal studies on pseudotuberculosis rodentium. III. Spon-
taneous swine cases. Jpn J Vet Sci 30:233–239.
STAPHYLOCOCCI
Staphylococci are ubiquitous. They are present on every
pig farm and involved in a wide range of lesions in pigs
of all ages. The most easily recognized are those of ex-
udative epidermitis caused by Staphylococcus hyicus and
described in Chapter 33. Few, if any, of the other lesions
can be unequivocally identified as being staphylococcal
on clinical grounds; in the majority, staphylococcal in-
volvement must be confirmed by laboratory means. In
addition to their association with pig disease, some of
the staphylococci that infect the pig, notably S. aureus,
may be involved in human food poisoning if carcasses
are contaminated or abscesses are present.
Taylor 633
Mosimbale, F., and Gyles, C. L. 1982. The pathogenicity of
Yersinia enterocolitica strains isolated from various
sources for four test systems. Can J Comp Med
46:70–75.
Neef, N. A., and Lysons, R. J. 1994. Pathogenicity of a strain
of Yersinia pseudotuberculosis isolated from a pig with
porcine colitis syndrome. Vet Rec 135:58–63.
Nielsen, B.; Heisel, C.; and Wingstrand, A. 1996. Time
course of the serological response to Yersinia enterocolit-
ica O:3 in experimentally infected pigs. Vet Microbiol
48:293–303.
Rasmussen, H. N.; Rasmussen, O. F.; Christensen, H.; and
Olsen, J. E. 1995. Detection of Yersinia enterocolitica O:3
in fecal samples and tonsil swabs from pigs using im-
munomagnetic separation and polymerase chain reac-
tion. J Appl Bacteriol 78:563–568.
Schiemann, D. A. 1988. The pathogenicity of Yersinia ente-
rocolitica for piglets. Can J Vet Res 52:325–330.
Schiemann, D. A., and Fleming, C. A. 1981. Yersinia entero-
colitica isolated from throats of swine in eastern and
western Canada. Can J Microbiol 27:1326–1333.
Shu, D.; Simpson, H. V.; Xu, R. J.; Mellor, D. J.; Reynolds, G.
W.; Alley, M. R.; Fenwick, S. G.; and Marshall, R. B.
1995a. Impact of Yersinia enterocolitica enteritis on
disaccharidase activity and small intestinal morphology
in colostrum-deprived newborn piglets. New Zealand
Vet J 45:27–36.
Shu, D.; Simpson, H. V.; Xu, R. J.; Mellor, D. J.; Reynolds, G.
W.; and Marshall, R. B. 1995b. Effects of Yersinia entero-
colitica infection on growth of the body and internal or-
gans in newborn colostrum-deprived piglets. Biology of
the Neonate 67:360–369.
Shu, D.; Simpson, H. V.; Xu, R. J.; Mellor, D. J.; Reynolds, G.
W.; and Marshall, R. B. 1997. Experimental infection of
newborn piglets with Yersinia enterocolitica: An animal
model of enteritis. New Zealand Vet J 43:50–56.
ETIOLOGY
Staphylococci are gram-positive, 0.5–1.5 µm in diameter,
forming grapelike clusters when grown in serum broth
or seen in pus. They grow primarily in aerobic conditions
but can also grow anaerobically, are oxidase-negative but
produce catalase, and metabolize a wide variety of sug-
ars. They produce a wide range of enzymes and some
toxins. The species are distinguished by the presence of
enzymes such as coagulase, DNAase, hemolysins, and
phosphatase and by the ability to utilize a variety of sug-
ars. Major species reported from the pig are S. aureus, S.
634 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
hyicus, and S. epidermidis, although S. saprophyticus has
also been described.
S. aureus is the only species apart from S. hyicus to be
consistently isolated from lesions in pigs. It forms yel-
lowish-white, opaque, circular, domed colonies, 1–2 mm
in diameter, on blood agar after 24 hours of incubation.
These colonies may be surrounded by a zone of complete
hemolysis, caused by alpha hemolysins, on horse blood
agar. On sheep blood agar, the ring of complete hemoly-
sis is surrounded by a wider area of incomplete hemoly-
sis caused by beta hemolysins; this becomes complete on
cooling of the plate. In addition to these hemolysins, the
organism produces coagulase, DNAase, proteinases,
hyaluronidase, and toxins that include the alpha toxin
and the enterotoxins. Both have been demonstrated in
strains of porcine origin (Engvall and Schwan 1983);
protein A (Takeuchi et al. 1995) and polysaccharide cap-
sules are also present. Isolates of S. aureus can be identi-
fied by phage typing and plasmid profiling, and those of
public health significance may readily be traced. S. aureus
is fairly resistant to drying but is readily inactivated by
heat. It is sensitive to a wide range of disinfectants, such
as phenols, hypochlorites, iodine, and iodophors.
EPIDEMIOLOGY
S. aureus is widely distributed in the environment and
has been recovered from pig feces, food, water following
contamination of drinkers, pen floors and walls, and the
air in pig facilities. The organism can be isolated from a
wide range of hosts, including birds, rodents, dogs, cats,
and humans. The extent to which isolates from lesions in
pigs are of nonporcine origin is not yet known. Porcine
strains capable of enterotoxin production have been
identified on carcasses and represent a source of infec-
tion or possible food poisoning to humans (Engvall and
Schwan 1983).
The pig is probably the major source of infection for
other pigs; S. aureus can be isolated from the skin, oral
cavity, upper respiratory tract, prepuce, vagina, and gut
of healthy pigs on a very wide scale. Transmission of the
organism may be by aerosol to the upper respiratory
tract, directly by skin contact, or indirectly by contact
with contaminated walls or fittings. Ingestion of S. au-
reus from food, contaminated water, or litter is common.
Venereal contact may be responsible for some genital in-
fections; local invasion of the mammary gland, navel,
and skin lesions is common.
PATHOGENESIS
S. aureus appears to multiply on damaged mucosal sur-
faces or skin and can invade to cause bacteremia. In some
cases, such as neonatal septicemia, animals may become
fevered and die, but bacteremia usually leads to forma-
tion of multiple abscesses. These may occur in bones to
give osteomyelitis; in joints; on the heart valves to give
vegetative endocarditis; and in the liver, kidney, or
lymph nodes. Vegetative endocarditis may give rise to
septic emboli that cause abscess formation and infarc-
tion in the kidney. Most of these systemic infections oc-
cur in neonates or piglets and take 7–10 days to develop.
They are also present in apparently normal pigs at
slaughter. Abscesses contain neutrophils and micro-
colonies of bacteria in all stages of multiplication and
heal by fibrosis.
Mastitis, vaginitis, and metritis appear to result from
ascending infection. Abortion has been associated with
the demonstration of serum antibody to alpha he-
molysin in the sow (Kohler and Wille 1980), but the im-
portance of this and other toxins in abortion is not
known.
In enteric infection, experimental studies have shown
that staphylococcal enterotoxin A will cause emesis with-
in 90–180 minutes when given orally in doses of 40–50
µg (Taylor et al. 1982). Larger doses can cause behavioral
changes, including inappetence, restlessness, and stag-
gering. The piglet is clearly susceptible, but the ability of
enteric staphylococcal infections to produce enterotoxin
in vivo is not known.
CLINICAL SIGNS
The presence of S. aureus infection cannot readily be sus-
pected on clinical grounds. S. aureus has been isolated
from a wide variety of syndromes. Most of these occur in
individual animals, and disease rarely spreads from ani-
mal to animal. It can cause neonatal septicemia and is of-
ten identified in small, hairy, stunted piglets of 7–10
days of age with umbilical abscesses, polyarthritis, and
signs of cardiac enlargement due to vegetative endo-
carditis. It is a cause of subcutaneous abscesses associat-
ed with abrasions and foot lesions, especially in piglets.
These often result in arthritis of the distal phalangeal
joints, enlargement of the hoof, and sinus formation at
the coronary band. Creamy pus is often seen to exude
from the abscesses.
S. aureus has been isolated from enteritis in piglets
and in older animals and from the rectal mucosa of ani-
mals with lesions of rectal stricture. No particular fea-
tures of diarrhea are associated with staphylococci ex-
cept that the enteritis is often chronic and antibiotic
treatment may have been given. The organism is also
present in a small percentage of cases of mastitis and has
been isolated from pigs with metritis and agalactia. The
only reason to suspect staphylococcal involvement may
be the presence of a creamy white or bloodstained pus,
but this often contains other organisms. It has also been
isolated from aborted fetuses and placentas (Kohler and
Wille 1980).
 CHAPTER 44 MISCELLANEOUS BACTERIAL INFECTIONS
LESIONS
No gross lesions may be seen in piglet septicemia. In
chronic infections, an inflamed mucosa may be associat-
ed with staphylococcal infection, but there is no specific
feature that allows their identification with staphylococ-
cal infection. Abscesses may occur in the umbilicus, liver,
lungs, lymph nodes, spleen, kidneys, joints, and bones in
osteomyelitis; bone abscesses may give rise to pathologic
fractures, especially when in the vertebrae. Body cavities
(peritoneal cavity, pericardial cavity, uterine lumen) may
contain pus, especially in young animals, following um-
bilical infection. S. aureus is only one cause of such le-
sions. Both gross and microscopic lesions of mastitis
may be found in the mammary glands, and in some cas-
es fibrosis may be considerable. Occasionally, a granulo-
matous mass with fibrosis may be found in the abdomi-
nal cavity of piglets that have died after castration. In all
cases, confirmation that the lesions are staphylococcal
depends on demonstration of the organisms.
DIAGNOSIS
The clinical signs resulting from multiple abscess forma-
tion in individual pigs may be suggestive, and similar
suspicions may arise from the postmortem findings.
Confirmation of involvement of staphylococci rather
than Arcanobacterium pyogenes or streptococci in abscess-
es and arthritis is obtained from Gram-stained smears of
the pus in which gram-positive cocci may be seen singly
or in clusters. Only the isolation of staphylococci in cul-
ture confirms that they are involved. S. aureus can be iso-
lated readily on blood and MacConkey agar, and its iden-
tity can be confirmed by coagulase and DNAase tests and
by its ability to ferment mannitol. Isolates may be phage
typed if this is considered relevant, and any toxins pro-
duced may be identified.
In most abscesses the absence of other bacteria must
ACTINOBACULUM (ACTINOMYCES–EUBACTERIUM–
CORYNEBACTERIUM) SUIS
Soltys and Spratling (1957) isolated, anaerobically, a
diphtheroid bacterium from the urine and diseased tis-
sue of adult pigs in the United Kingdom affected with
cystitis and pyelonephritis and named it Corynebacterium
suis. Soltys (1961) described the characteristics of C. suis
in more detail. C. suis was subsequently assigned to the
genus Eubacterium (Wegienek and Reddy 1982), Actino-
myces (Ludwig et al. 1992), and finally Actinobaculum
Lawson et al. 1997).
A. suis infection associated with urinary tract disease
Taylor 635
be confirmed before S. aureus is considered to be the sole
cause; exclusion of other agents is even more important
in diseases at mucous surfaces.
TREATMENT
Individual abscesses may be opened surgically after skin
cleaning and disinfection, but most treatments rely on
antimicrobial treatment. Since S. aureus infection is an
individual-animal problem, there is usually no need to
treat the whole group. Parenteral treatment with an ap-
propriate formulation and prompt treatment at any age
can prevent the development of large and potentially ex-
tensive and fatal abscesses. The use of feed medication as
a prophylactic cannot be justified unless a severe prob-
lem has been identified, since the development of an-
timicrobial resistance in staphylococci is likely to favor
them over other organisms after a brief period during
which they are suppressed. The use of bacterins has been
described, but they are not widely available or extensive-
ly used.
REFERENCES
Engvall, A., and Schwan, O. 1983. Isolation and partial char-
acterization of bacteria recovered from abscesses of nor-
mally slaughtered pigs. Acta Vet Scand 24:74–83.
Kohler, B., and Wille, H. 1980. Bakteriologische Unter-
suchungen bei abortierten Schweinfeten unter Beruck-
sichtigung der ätiologischen Bedeutung von Staphylococ-
cus aureus. Monatsch Veterinärmed 35:506–510.
Takeuchi, S.; Matuda, K.; and Sasano, K. 1995. Protein A in
Staphylococcus aureus isolates from pigs. J Vet Med Sci
57:581–582.
Taylor, S. L.; Schlunz, L. R.; Beerey, J. T.; Cliver, D. O.; and
Bergdoll, M. S. 1982. Emetic action of staphylococcal
enterotoxin A on weanling pigs. Infect Immunol
36:1263–1266.
in sows has been reported from Canada (Percy et al.
1966), Norway (Aalvik 1968), Holland (Dijkstra 1969;
Frijlink et al. 1969; Narucka and Westendorp 1972),
Denmark (Larsen 1970, 1973), Hong Kong (Munro and
Wong 1972), Australia (Glazebrook et al. 1973), Switzer-
land (Schallibaum et al. 1976), Finland (Kauko et al.
1977), Malaysia (Too et al. 1985), Germany (Muller et al.
1986; Waldmann 1987), Brazil (De Oliveira et al. 1988),
and the United States (Walker and MacLachlan 1989).
Disease caused by A. suis occurs in small outbreaks or in-
636 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
dividual sows, but carriage is much more widespread.
The main features of the organism and the disease are
described below.
ETIOLOGY
A. suis is a gram-positive pleomorphic rod, 2–3 µm long
and 0.3–0.5 µm wide; the organism tends to be larger in
tissues than in cultures. In tissues and cultures it occurs
in the form of so-called Chinese letters and in a palisade
fashion. It is nonmotile and does not form spores.
A. suis grows well on blood agar under anaerobic con-
ditions. Colonies are evident at 2 days, having a diameter
of 2–3 mm; they then begin to flatten and develop a
characteristic dry, gray, opaque surface with a crenated
edge; some colonies attain a size of 4–5 mm in 5–6 days.
There is no hemolysis. Growth on nutrient agar, even af-
ter subculture, is poor. In liquid media such as cooked
meat broth and brain-heart infusion, slight turbidity is
produced in 2–4 days; growth is more luxuriant in tryp-
ticase soy broth and is further enhanced by the addition
of urea to a final concentration of 1.2% (w/v). The addi-
tion of maltose to either solid or liquid media improves
growth. Although A. suis has always been described as an
anaerobic organism, prolonged aerobic incubation on
blood agar results in the development of colonies within
5–10 days; on subculture, aerobically, colonies are evi-
dent in 1–3 days.
The organism is relatively inactive when subjected to
conventional biochemical tests. Most strains ferment
maltose and xylose and hydrolyze starch but do not at-
tack other commonly used “sugars”; all produce urease.
Catalase, methyl red, Voges-Proskauer, indole, and ni-
trate-reduction tests are negative. Coagulated serum and
egg medium are not liquefied. A slight alkalinity is pro-
duced in litmus milk.
EPIDEMIOLOGY AND PATHOGENESIS
Most male pigs aged 6 months or more harbor A. suis in
the preputial diverticulum, which may become colonized
when pigs are only a few weeks old. Uninfected males are
readily infected when they are housed with carrier males
(Jones and Dagnall 1984). The organism may be found
on the floors of pens occupied by male pigs. Carr and
Walton (1990) have isolated A. suis from the footwear of
handlers working with boars but not from those working
in the farrowing area. Only rarely is it found in the vagi-
na of healthy females, but it may be that existing cultur-
al techniques are insufficiently sensitive to demonstrate
its presence there. There are no reports of A. suis being
isolated from any sites in the pig other than the urogeni-
tal tract.
Cystitis and pyelonephritis caused by A. suis mainly
affect adult females. Infection of the bladder and kidneys
is by the ascending route. Most cases occur within 1–3
weeks of mating, suggesting that predisposing factors
are operating at this time. Wendt et al. (1994) suggest
that these may include infection with other organisms,
because of a requirement for erosion of mature vesical
epithelial cells to allow attachment by A. suis. Water re-
striction and the presence of crystalluria may also pre-
dispose to infection (Wendt and Sobestiansky 1995).
The disease may become clinically evident at any time in
the breeding cycle of the sow (e.g., after parturition), and
in such cases it is not always clear whether infection of
the urinary tract is recent or whether there has been a re-
crudescence of previously existing disease.
Studies on the adhesive properties of A. suis have
been reported by Larsen et al. (1986). They have demon-
strated that some strains are heavily fimbriated and are
able to adhere to the epithelial cells of the porcine blad-
der; their findings support the hypothesis that glycocon-
jugates are specific receptor sites for the attachment of A.
suis. Infection of the ureters and kidneys follows infec-
tion of the bladder.
CLINICAL SIGNS AND LESIONS
Hematuria is the main sign in the acute phase. As the dis-
ease progresses, there is loss of weight. Some sows may
die suddenly, apparently from acute renal failure.
Inflammatory reactions in the mucosa of the urethra,
bladder, and ureters may be catarrhal, fibrinopurulent,
hemorrhagic, or necrotic. Affected kidneys often have ir-
regular yellow areas of degeneration in the parenchyma
that are visible on the surface. The renal pelvis may be di-
lated and contain mucoid fluid in which flakes of necrot-
ic debris and altered blood are present. The medullary
pyramids often show yellow or dark green to black foci of
necrosis. The ureters are often dilated and filled with red-
dish purulent urine. There are no related lesions else-
where in the body.
DIAGNOSIS
Diagnosis is based on clinical signs and bacteriological
examination of urine. A. suis is easily seen in Gram-
stained films, often with other bacteria, notably strepto-
cocci. For cultural examination it is essential to incubate
the medium (e.g., blood agar), which has been inoculat-
ed with urine or other appropriate material, anaerobical-
ly for 4 days. Results of cultural procedures should not
be reported as negative before that time. Rapid diagnosis
can be achieved by the use of immunofluorescent tech-
niques (Schallibaum et al. 1976; Kauko et al. 1977). A se-
lective medium for the isolation of A. suis has been de-
scribed by Dagnall and Jones (1982). Wendt and
Amstberg (1995) evaluated the possibility of using serol-
ogy to detect infection and tested indirect immunofluo-
rescence in diagnosis. They found that antibody did not
appear until 3 weeks after hemorrhagic cystitis had oc-
 CHAPTER 44 MISCELLANEOUS BACTERIAL INFECTIONS
curred and that when a titer of ++ at 1/16 was used as an
endpoint to give 100% specificity, the sensitivity was on-
ly 79%. There was no relationship between antibody lev-
el and the degree of renal damage.
TREATMENT AND PREVENTION
A. suis is sensitive in vitro to several antibiotics, including
penicillin and tetracyclines. Administration of antibi-
otics is frequently effective, at least in the short term.
However, relapses commonly occur, and often it is best to
advise early slaughter of affected animals. Prolonged
treatment for 20 days with ampicillin given at 20 mg/kg
may be used (Wendt and Sobestiansky 1995), and en-
rofloxacin given for 10 days at 10 mg/kg may also be ef-
fective. In Wendt and Sobestiansky’s studies (1995), pigs
with lesions confined to the bladder recovered with an-
timicrobial treatment alone, but those with renal dam-
age required infusion therapy for recovery.
There are no proven methods of prevention. A. suis
may be transmitted from boars to sows at the time of
mating. Culling of carrier boars has been suggested as a
method of preventing infection of sows; this does not
seem worthwhile, because replacement boars will almost
certainly be infected. Culling might be of value if there
are “pathogenic” and “nonpathogenic” strains of A. suis,
but there is no evidence that such different strains exist.
Currently, the only means of attempting prevention of
the disease is to administer antibiotics to sows immedi-
ately after service or, if outbreaks of the disease are eco-
nomically serious, to use artificial insemination.
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Dagnall, G. J. R., and Jones, J. E. T. 1982. A selective
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De Oliveira, S. J.; Barcellos, D. E. S. N.; and Borowski, S.
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Dijkstra, R. G. 1969. Cysto-pyelonefritis bij varkens ver-
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Frijlink, G. P. A.; Van Dijk, J. E.; and Goudswaard, J.
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Glazebrook, J. S.; Donaldson-Wood, C.; and Ladds, P. W.
1973. Pyelonephritis and cystitis in sows associated
Taylor 637
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Jones, J. E. T., and Dagnall, G. J. R. 1984. The carriage of
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93:381–388.
Kauko, L.; Schildt, R.; and Sandholm, M. 1977.
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tajana suomessa. Suom Elainl 83:489–492.
Larsen, J. L. 1970. Corynebacterium suis infektioner hos
svin. Nord Vet Med 22:422–431.
———. 1973. Et enzootisk udbrud af cystitis og
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Larsen, J. L.; Hogh, P.; and Hovind-Hougen, K. 1986.
Haemagglutinating and hydrophobic properties of
Corynebacterium (Eubacterium) suis. Acta Vet Scand
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47:899–903.
Ludwig, W.; Kirchof, G.; Weizenegger, M.; and Weiss, N.
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Eubacterium suis to the genus Actinomyces as Actino-
myces suis comb nov. Int J Syst Bacteriol 42:161–165.
Muller, E.; Pozvari, M.; and Merkt, M. 1986. Zum
Vorkommen von blutig-eitrigen Harnblasen und
Nierenentzundungen bei Zuchtsauen in Verbindung
mit Corynebacterium suis. Prakt Tierärztl 67:1081–
1083.
Munro, R., and Wong, F. 1972. First isolation of
Corynebacterium suis in Hong Kong. Br Vet J
128:29–32.
Narucka, U., and Westendorp, J. F. 1972. Corynebacteri-
um suis in pigs. Neth J Vet Sci 4:86–92.
Percy, D. H.; Ruhnke, H. L.; and Soltys, M. A. 1966.
A case of infectious cystitis and pyelonephritis of
swine caused by Corynebacterium suis. Can Vet J
7:291–292.
Schallibaum, M. von; Hani, H.; and Nicolet, J. 1976. In-
fektion des Harntraktes beim Schwein mit Corynebac-
terium suis: Diagnosis met Immunofluoreszenz.
Schweiz Arch Tierheilkd 118:329–334.
Soltys, M. A. 1961. Corynebacterium suis associated with
specific cystitis and pyelonephritis in pigs. J Pathol
81:441–446.
Soltys, M. A., and Spratling, F. R. 1957. Infectious cysti-
tis and pyelonephritis of pigs: A preliminary commu-
nication. Vet Rec 69:500–504.
Too, H. L.; Chooi, K. F.; and Bahaman, A. R. 1985. Cysti-
tis in a sow due to Corynebacterium suis. Kajian Veteri-
nar 17:155–156.
Waldmann, K. H. 1987. Die Pyelozystitis der Zuchtsau.
Tierärztl Prax 15:263–267.
638 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
Walker, R. L., and MacLachlan, J. J. 1989. Isolation of Eu-
bacterium suis from sows with cystitis. J Am Vet Med
Assoc 195:1104–1107.
Wegienek, J., and Reddy, C. A. 1982. Taxonomic study of
Eubacterium suis (nom. rev.) Comb. nov. Int J Syst
Bacteriol 32:218–228.
Wendt, M., and Amstberg, G. 1995. Untersuchungen
zum Nachweis von Antikorpen gegen Eubacterium su-
is beim Schwein. Schweiz Arch für Tierheilkd
RHODOCOCCUS EQUI
Rhodococcus equi is associated with granulomatous lym-
phadenitis affecting the lymph nodes of the head and
neck of the pig. The lesions can be confused at slaughter
with those of tuberculosis, and the organism is impor-
tant for this reason rather than as a cause of clinical dis-
ease.
ETIOLOGY
The organism was first isolated from the pneumonic
lungs of a foal by Magnusson (1923) and was given the
name Corynebacterium equi; it is now called Rhodococcus
equi. This gram-positive coccobacillus is a member of the
nocardioform actinomycete group (Goodfellow et al.
1982). In common with other members of Rhodococcus,
R. equi produces pinkish colonies on solid media. The
mycolic acids of R. equi have a chain length of 34–48 C,
and the DNA base composition is 66–72 mol% guanine
plus cytosine. Chemical properties used in defining the
species were summarized by Goodfellow (1987).
Isolation of R. equi from clinical samples is easily
achieved by aerobic culture on routine media at 37˚C, al-
though the optimum temperature is 28–30˚C. Selective
media, such as that developed by Woolcock et al. (1979),
are required for fecal isolation. Colonies are slow grow-
ing, requiring 48 hours to reach a size of 2–4 mm. The
typical colony is irregularly round, buff-pink, smooth,
and mucoid, although colonial variation is common
within and between strains (Mutimer and Woolcock
1981). R. equi is biochemically unreactive. It is not prote-
olytic and does not ferment carbohydrates. R. equi is
catalase positive, usually urease positive, and oxidase
negative. The API ZYM system has been found helpful in
bacterial identification (Mutimer and Woolcock 1982).
R. equi is not hemolytic but, in conjunction with the
phospholipase D of Corynebacterium pseudotuberculosis
or the beta toxin of Staphylococcus aureus, produces com-
plete hemolysis of sheep and cattle erythrocytes
(Prescott et al. 1982). Semipurification of this factor,
known as “equi factor,” has indicated that cholesterol ox-
137:129–136.
Wendt, M., and Sobestiansky, J. 1995. Untersuchungen
zur Therapie von Harnwegs-infektionen bei Sauen.
Dtsch Tierärztl Wochenschr 102:21–22.
Wendt, M.; Liebhold, M.; and Drommer, W. 1994.
Rasterelektronenmikroskopische Untersuchungen
an der Harnblase von Sauen unter besonderer
Berucksichtigung einer Eubacterium suis-Infektion. J
Vet Med Ser B 41:126–138.
idase is the major constituent (Linder and Bernheimer
1982).
R. equi possess an abundant acidic polysaccharide
capsule, which is the basis for several serotyping
schemes. Prescott (1981) has identified 7 serotypes, of
which serotype 1 is the most frequently isolated in Cana-
da, Australia, and India. Japanese workers have identi-
fied 27 serotypes, with the most common being equiva-
lent to Prescott serotype 1 (Nakazawa et al. 1983). There
is no relationship between capsular serotype and origin
of the isolates. The capsular polysaccharides of 4
Prescott serotypes have been purified.
Recent studies of this species have confirmed that
isolates from pigs possess a virulence-associated protein
(vapA) that is encoded by a virulence plasmid. Takai et
al. (1996) confirmed the presence of 79–95 kb plasmids
coding for a 20 kDa virulence protein.
EPIDEMIOLOGY AND PATHOGENESIS
R. equi is primarily a soil resident. Environmental distri-
bution favors soils enriched with herbivore manure,
since fecal matter potentiates bacterial multiplication
(Barton and Hughes 1984). R. equi is also a transient in
the intestinal tract of many species, including pigs, cat-
tle, deer, horses, sheep, goats, and wild birds (Woolcock
et al. 1979; Carman and Hodges 1987). Being an obligate
aerobe, R. equi is not likely to be a member of the normal
flora. The bacterium is found in soil samples collected
from arable land that has not pastured animals for many
years, emphasizing its durability. R. equi is present in
dust and even in cobwebs of farm buildings in areas
where it occurs. R. equi is relatively resistant to chemical
disinfectants, such as treatment with 2.5% oxalic acid
and 0.5% sodium hydroxide over periods of 15–60 min-
utes (Karlson et al. 1940).
Little is known of the epidemiology or pathogenesis
of the naturally occurring disease in swine. As in horses,
R. equi infection is likely to be acquired from the envi-
ronment (Woolcock et al. 1980). Ingestion is the normal
 CHAPTER 44 MISCELLANEOUS BACTERIAL INFECTIONS
mode of exposure in foals (Takai et al. 1986a), leading to
the development of solid protective immunity in the ma-
jority of animals (Prescott et al. 1980; Chirino-Trejo et al.
1987). A similar situation probably occurs in swine
housed on pasture or in yards contaminated with R. equi,
as the bacterium is readily isolated from the feces of such
pigs (Barton and Hughes 1984). Several slaughterhouse
studies have also demonstrated recovery of R. equi from
normal cervical and submaxillary lymph nodes at rates
varying from 7% to 35% (Mutimer and Woolcock 1980;
Takai et al. 1986b), although the organism may now be
less common, as Takai et al. (1996) recovered it from on-
ly 3.1% of 1832 swine in Japan. However, no epidemio-
logical studies have been carried out to correlate infec-
tion rates, disease prevalence, and environmental
contamination of R. equi on pig farms, as has been done
for horses. There have been suggestions that isolates
from pigs differ somewhat from those from horses and
that some pig isolates resemble those from humans.
Takai et al. (1996) speculated that some human cases
may be of porcine origin.
The way in which R. equi causes granulomatous lym-
phadenitis of the head and neck in the pig is not clear. R.
equi can be recovered from normal nodes, and there are
accounts of failure to reproduce the nodal lesions exper-
imentally (Karlson et al. 1940; Cotchin 1943). Mycobac-
terium spp. may also be recovered in some cases. It is pos-
sible that the severity of the lesions reflects the
possession of the virulence-associated protein, which
may vary from strain to strain, the degree of immunity
present when infection took place, or the duration of the
infection at sampling. However, R. equi typically pro-
duces a granulomatous tissue reaction in lymph nodes of
other species, consistent with its action as a facultative
intracellular pathogen (Yager 1987).
R. equi has been associated with serious clinical dis-
ease, including one outbreak of oral abscesses and one of
pneumonia (Thal and Rutqvist 1959; Rao et al. 1982),
but pigs are extremely resistant to experimental infec-
tion. Following aerosolization, R. equi is cleared from the
lungs very slowly, but clinical signs and pathological le-
sions of pneumonia are minimal despite exposure to 107
organisms on 7 consecutive days (Zink and Yager 1987).
Pneumonia has, however, been induced by intratracheal
inoculation of fluid inocula (Thal and Rutqvist 1959).
LESIONS
Lymphadenitis causes no significant clinical signs; le-
sions are detected only at slaughter. Affected sub-
mandibular and cervical nodes are enlarged, containing
multiple yellow-tan foci, often in a subcapsular location.
Caseation and calcification of these foci sometimes oc-
cur. Histologically, the lesion is a granulomatous lym-
phadenitis. Similar lesions reported in the mesenteric
lymph nodes have yielded Rhodococcus sputi on culture
(Tsukamura et al. 1988).
Taylor 639
DIAGNOSIS
Diagnosis is at postmortem. Microbiological identifica-
tion of R. equi is necessary for it is not possible to differ-
entiate the gross lesions of R. equi–induced lymphadeni-
tis from those caused by Mycobacterium spp.
TREATMENT AND PREVENTION
R. equi–induced disease is not sufficiently important to
necessitate antemortem diagnosis and treatment in
swine. Therapy, which in foals requires long-term ad-
ministration of rifampicin and erythromycin, is not fea-
sible on economic grounds. While some economic loss
may accrue from condemnation at slaughter, there are no
studies that indicate the extent of this loss and there ap-
pears to be no incentive to institute control measures.
These would in any case be difficult; an effective vaccine
is presently unavailable.
REFERENCES
Barton, M. D., and Hughes, K. L. 1984. Ecology of Rhodococ-
cus equi. Vet Microbiol 9:65–76.
Carman, M. G., and Hodges, R. T. 1987. Distribution of
Rhodococcus equi in animals, birds and from the environ-
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Chirino-Trejo, J. M.; Prescott, J. F.; and Yager, J. A. 1987. Pro-
tection of foals against experimental Rhodococcus equi
pneumonia by oral immunization. Can J Vet Res
51:444–447.
Cotchin, E. 1943. Corynebacterium equi in the submaxillary
lymph nodes of swine. J Comp Pathol 53:298–309.
Goodfellow, M. 1987. The taxonomic status of Rhodococcus
equi. Vet Microbiol 14:205–209.
Goodfellow, M.; Beckham, A. R.; and Barton, M. D. 1982.
Numerical classification of Rhodococcus equi and related
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Karlson, A. G.; Moses, H. R.; and Feldman, W. H. 1940.
Corynebacterium equi (Magnusson, 1923) in the submax-
illary lymph nodes of swine. J Infect Dis 67:243–
251.
Linder, R., and Bernheimer, A. W. 1982. Enzymatic oxida-
tion of membrane cholesterol oxidase in relation to lysis
of sheep erythrocytes by corynebacterial enzymes. Arch
Biochem Biophys 213:395–404.
Magnusson, H. 1923. Spezifische Infektiose Pneumonie
beim Fohlen: Ein neurer Eitererreger beim Pferde. Arch
Wiss Prakt Tierheilk 50:22–38.
Mutimer, M. D., and Woolcock, J. B. 1980. Corynebacterium
equi in cattle and pigs. Vet Q 2:25–27.
———. 1981. Some problems associated with the identifi-
cation of Corynebacterium equi. Vet Microbiol
6:331–338.
———. 1982. API ZYM for identification of Corynebacteri-
um equi. Zentralbl Bakteriol Hyg Abt (Orig C3):410–
415.
640 SECTION 3 BACTERIAL DISEASES D. J. Taylor, Editor
Nakazawa, M.; Kubo, M.; Sugimoto, C.; and Isayama, Y.
1983. Serogrouping of Rhodococcus equi. Microbiol Im-
munol 27:837–846.
Prescott, J. F. 1981. Capsular serotypes of Corynebacterium
equi. Can J Comp Med 45:130–134.
Prescott, J. F.; Ogilvie, T. J. H.; and Markham, R. J. F. 1980.
Lymphocyte immunostimulation in the diagnosis of
Corynebacterium equi pneumonia of foals. Am J Vet Res
41:2073–2075.
Prescott, J. F.; Lastra, M.; and Barksdale, L. 1982. Equi fac-
tors in the identification of Corynebacterium equi Mag-
nusson. J Clin Microbiol 16:988–990.
Rao, M. S.; Zaki, S.; Keshavamurthy, B. S.; and Singh, K. C.
1982. An outbreak of an acute Corynebacterium equi in-
fection in piglets. Indian Vet J 59:487–488.
Takai, S.; Ohkura, H.; Watanabe, Y.; and Tsubaki, S. 1986a.
Quantitative aspects of fecal Rhodococcus (Corynebacteri-
um) equi in foals. J Clin Microbiol 23:794–796.
Takai, S.; Takeuchi, T.; and Tsubaki, S. 1986b. Isolation of
Rhodococcus (Corynebacterium) equi and atypical my-
cobacteria from the lymph nodes of healthy pigs. Jpn J
Vet Sci 48:445–448.
ARCANOBACTERIUM (ACTINOMYCES–CORYNEBACTERIUM)
PYOGENES
Arcanobacterium pyogenes, previously known as Actino-
myces pyogenes, and even earlier as Corynebacterium
pyogenes, is a common cause of suppurative lesions in
pigs throughout the world. Infection is opportunistic, re-
sulting from the invasion of skin or mucous membranes
by resident A. pyogenes. Clinical disease can result from
vertebral osteomyelitis, arthritis, pneumonia, endocardi-
tis, mastitis, and subcutaneous and deep-tissue ab-
scesses.
ETIOLOGY
A. pyogenes is a small gram-positive pleomorphic rod.
There is marked morphologic variation between and
within strains. Growth is enhanced by the addition of
serum or blood to media and occurs under both aerobic
and anaerobic conditions. The optimal temperature for
growth is 37˚C. Colonies are translucent and small, tak-
ing 48 hours to reach a diameter of 1 mm. A. pyogenes
colonies are surrounded by a narrow zone of complete
hemolysis after 24 hours on blood agar. Strains isolated
from pigs are more hemolytic than those isolated from
cattle. A. pyogenes produces a hemolysin and an exotoxin
that is dermonecrotic in rabbits and guinea pigs and
lethal following intravenous injection in rabbits and
mice (Lovell 1944). Glucose is fermented by all strains,
but other carbohydrate reactions are variable. In general,
Takai, S.; Fukunaga, N.; Ochiai, S.; Imal, Y.; Sasaki, Y.; Tsub-
aki, S.; and Sekizaki, T. 1996. Identification of interme-
diately virulent Rhodococcus equi isolates from pigs. J
Clin Microbiol 34:1034–1037.
Thal, E., and Rutqvist, L. 1959. The pathogenicity of
Corynebacterium equi for pigs and small laboratory ani-
mals. Nord Vet Med 11:298–304.
Tsukamura, M.; Komatsuzaki, C.; Sakai, R.; Kane-da, K.; Ku-
do, T.; and Seino, A. 1988. Mesenteric lymphadenitis of
swine caused by Rhodococcus sputi. J Clin Microbiol
26:155–157.
Woolcock, J. B.; Farmer, A. M. T.; and Mutimer, M. D. 1979.
Selective medium for Corynebacterium equi isolation. J
Clin Microbiol 9:640–642.
Woolcock, J. B.; Mutimer, M. D.; and Farmer, A. M. T. 1980.
Epidemiology of Corynebacterium equi in horses. Res Vet
Sci 28:87–90.
Yager, J. A. 1987. The pathogenesis of Rhodococcus equi
pneumonia in foals. Vet Microbiol 14:225–232.
Zink, M. C., and Yager, J. A. 1987. Experimental infection of
piglets by aerosols of Rhodococcus equi. Can J Vet Res
51:290–296.
porcine strains are more biochemically active than
bovine strains (Roberts 1968; Tainaka et al. 1983). A. pyo-
genes is proteolytic, a series of serine proteases with mol-
ecular masses of 69, 59, and 55 kDa being produced
along with one of 108 kDa that is only produced by pig
strains (Takeuchi et al. 1995).
A. pyogenes had been classified into the genus Actino-
myces by Collins and Jones (1982), chiefly on the basis of
cell wall composition. The guanine-cytosine content of
DNA is 58 mol%. Identification of Arcanobacterium
pyogenes is rapid and reliable with the API 20 Strep sys-
tem (Morrison and Tillotson 1988). Recent studies of
vaginal isolates have allowed the differentiation of
Arcanobacterium hyovaginalis (Collins et al. 1993).
EPIDEMIOLOGY AND PATHOGENESIS
Arcanobacterium pyogenes is common on the mucous
membranes of the upper respiratory tract and genital
tract of several animal species, including the pig. Disease
is therefore the result of endogenous infection and is
sporadic, requiring some predisposing event, such as
trauma, to initiate the process. For A. pyogenes to cause
subcutaneous lesions, devitalized or inflamed tissue is an
apparent prerequisite, since the inoculation of A. pyo-
genes subcutaneously does not, per se, lead to abscesses.
Infection is often secondary. Tail biting may lead to ab-
 CHAPTER 44 MISCELLANEOUS BACTERIAL INFECTIONS
scessation and suppurative osteomyelitis, retention of
the fetal membranes may lead to endometritis and infer-
tility, lacerations of the mammary gland may lead to
mastitis and arthritis, umbilical cord contamination may
lead to omphalophlebitis, and iatrogenic abscesses may
result from faulty injection or castration techniques. Lo-
cal extension may produce pelvic lymphadenitis and
peritonitis. A. pyogenes may act as a secondary invader in
preexisting pneumonia.
Bacteremic spread from infective foci results in a va-
riety of lesions, including embolic pneumonia, endo-
carditis, arthritis, and vertebral osteomyelitis. Experi-
mental intravenous inoculation of A. pyogenes shows
bacterial localization within the marrow of vertebral
body epiphyses, initiating osteolysis, abscessation, and
the formation of osteophytes (Vladutiu et al. 1982).
Valvular endocarditis may result from bacteremia follow-
ing tail-biting lesions (Van den Berg et al. 1981). A. pyo-
genes is occasionally recovered from fetuses and fetal
membranes, but its role in abortion has not been estab-
lished. Some of these isolates may be A. hyovaginalis.
A. pyogenes, as denoted by its name, causes suppura-
tive lesions. Surprisingly little, however, is known of the
virulence factors important in disease causation. Both
the hemolytic protein exotoxin and protease have been
proposed as toxic factors (Kume et al. 1983). A. pyogenes
also binds alpha-2 macroglobulin (Lammler et al. 1985),
a property that could interfere with local regulation of
inflammation.
CLINICAL SIGNS AND LESIONS
The clinical signs are very variable, since A. pyogenes is re-
sponsible for a range of pathological lesions. Some, such
as endocarditis and adhesive peritonitis, may be fatal.
Others, such as vertebral osteomyelitis leading to poste-
rior paralysis, may necessitate euthanasia. Suppurative
osteomyelitis generally affects the vertebral bodies, lead-
ing to transverse pathological fractures, vertebral col-
lapse, and compression of the spinal cord. Lameness re-
sults from polyarthritis or from cellulitis and
periarthritis. However, many lesions, including subcuta-
neous and intramuscular abscesses, are clinically inap-
parent and are discovered only at postmortem or slaugh-
ter. Such abscesses vary from a few millimeters to several
centimeters in size, usually have a thick fibrous capsule,
and contain a yellow-green pus of variable consistency.
Mastitis may be confined to one gland or may involve
several.
DIAGNOSIS
Diagnosis in individual cases requires the demonstration
of the organism in lesional material and confirmation by
laboratory culture and identification. Carcass abscesses
typically yield mixed cultures, including clostridia,
Bacteroides spp., Propionibacterium granulosum, Pasteurel-
Taylor 641
la multocida, and unidentified anaerobes (Hara 1980;
Jones 1980). Diagnosis of infection within a herd has
been attempted serologically using an immunodiffusion
test for antibody to A. pyogenes protease (Takeuchi et al.
1979). However, in a slaughterhouse survey, only 34.4%
of pigs with abscesses had an antiprotease titer (Hara
1980).
TREATMENT
A. pyogenes is sensitive to a wide range of antimicrobial
agents, including penicillin, tetracycline, and ery-
thromycin. Some strains have been shown to be resistant
to sulfonamides and trimethoprim. In vivo sensitivity
does not necessarily reflect in vitro sensitivity, for the
physicochemical properties of chronic abscesses tend to
protect the bacteria from the action of antimicrobial
drugs. Abscesses may be removed surgically.
PREVENTION
Surveys of serum antibodies to A. pyogenes protease
show that approximately one-third of pigs are positive
(Hara 1980). Antitoxin antibodies are also demonstrable
and may increase with age. However, mice vaccinated
with preparations of whole cells with or without toxoid
or even given live organisms are not adequately protect-
ed against subsequent challenge (Derbyshire and
Matthews 1963; Durner and Werner 1983). There is no
effective vaccine available for swine. Prevention requires
management of the environment to reduce or abolish
the various conditions that predispose the development
of A. pyogenes lesions. The treatment of sows with an-
timicrobials such as tetracyclines in the food prior to far-
rowing and throughout weaning can eliminate infection
and reduce vulval discharges (Taylor 1984).
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