Ministry of Agriculture of the Republic of Azerbaijan

Azerbaijan State Agrarian University

Faculty of veterinary medicine

Department of epizootology, microbiology and parasitology

Lecture: Enterotoxemia, Anaerobic dysentery,

Bradsot, Botulism and Necrobacteriosis

Lecturer: teaching assistant Narmin

 Enterotoxemia
Enterotoxemia, also known as overeating or pulpy kidney disease, is a
condition caused by Clostridium perfringens type D. These bacteria are
normally found in the soil and as part of the normal microflora in the
gastrointestinal tract of healthy sheep and goats. Under specific
conditions, these bacteria can rapidly reproduce in the animal’s intestine,
producing large quantities of toxins. The epsilon toxin produced by C.
perfringens Type D is the most significant toxin in producing the
disease. Young animals are most susceptible. Sudden and high mortality
rates may occasionally occur in lambs and kids. Although adult animals
are also susceptible to enterotoxemia, they develop immunity due to
frequent exposure to low doses of these toxins.

Factors Associated with Enterotoxemia Outbreaks

Overgrowth of Clostridium perfringens type D in the intestine of sheep

and goats resulting in enterotoxemia are more likely to occur during the
following conditions:

 Excessive consumption of milk or feed with high concentrations of

grain
 When natural immunity is compromised such as when ill,
recovering from an illness or stressed
 When animals are heavily parasitized with gastrointestinal
parasites, including nematodes, cestodes (tapeworms) and coccidia
 When the ration is rich in carbohydrates (grains) and low in
roughage
 When motility of the gastrointestinal tract is reduced
Common Signs of Enterotoxemia

 The peracute form is most frequent in young animals. It is characterized

by sudden death that occurs approximately 12 hours after the first signs
of the disease appear. Some kids or lambs may show signs of central
nervous disease, such as excitement or convulsions. Sudden death may
occur in only minutes in kids or lambs showing neurological disease.

Typical clinical signs include:

 Loss of appetite
 Abdominal discomfort
 Profuse and/or watery diarrhea that may be bloody

Diagnosis

Diagnosis is based on clinical signs, history of sudden death and

confirmation by necropsy examination. Diagnosis can be confirmed by
positive identification of enterocolitis, anaerobic culture, and
identification of Clostridium perfringens type D from the feces or
intestinal contents from clinical or necropsy specimens of affected
animals. The presence of hyperglycemia and glucosuria can strongly
suggest enterotoxemia in live or dead animals. Necropsy data is
important for the diagnosis of enterotoxemia. Therefore, dead animals or
a complete set of necropsy tissues, feces, etc., should be submitted to the
diagnostic laboratory for confirmation of the clinical diagnosis. A
postmortem examination of the large and small intestines can identify
watery contents, blood and fibrinous clots, and small ulcers on the
mucosa. The kidneys on gross examination may have a soft pulpy
consistency and encephalomalacia may occur within the brain (usually
only seen in sheep). On microscopic examination there may be
accelerated autolysis or diffuse acute necrosis of the proximal tubules in
the kidney. Microscopic ulcers and superficial mucosal necrosis with
numerous associated clostridial organisms and mild suppurative
inflammation may be present in intestinal specimens. Intestinal lumens
will often contain abundant clostridial organisms suggesting clostridial
enteritis/enterotoxemia. Advanced postmortem autolysis often prevents
definitive diagnosis of enterotoxemia at necropsy due to the extensive
overgrowth of clostridial organisms after death of the animal. Specific
DNA testing assays (PCR) for Clostridium perfringens type D may be
useful for confirmation of the diagnosis. An ELISA kit is also available
for the detection of several clostridial toxins including the epsilon toxin
and identification of the C. perfringens organism itself from intestinal
contents.

Treatment

 Recommended treatments can include the following:

 Clostridium perfringens C & D antitoxin according to the

manufacturer’s recommendations (5 mL of C & D antitoxin
subcutaneously)
 Antibiotics, especially penicillin
 Orally administered antacids
 Anti-bloating medication
 Pain reduction
 Intramuscular thiamine (vitamin B1) to prevent or treat the
encephalomalacia
 Supportive therapy such as intravenous or subcutaneous fluids and
corticosteroids
 Probiotics after antibiotic therapy to encourage repopulation of the
microflora in the GI tract

Prevention

Effective vaccines are commercially available to prevent enterotoxemia

in sheep and goats. All animals (especially young animals) within the
herd should be vaccinated as it will reduce the chances that the animals
will develop the disease. Use vaccines that are labeled for use in sheep
and goats and follow the manufacturer’s recommendations. Some of the
commercially available vaccines against enterotoxemia are also
combined with tetanus toxoid. Make sure the vaccine has been
refrigerated, stored properly, and is not expired. Young animals should
be vaccinated at 4 weeks of age and again one month later. All adults
including bucks should be vaccinated at least once per year. Do not
vaccinate animals that appear ill and keep good vaccination records for
future reference.

Anaerobic dysentery
Anaerobic dysentery (Latin - Dysenteria neonatorum anaerobica,
Dysetenteria anaerobica agnellorum; English - Lamb dysentery; white
diarrhea, anaerobic enterotoxemia of lambs) is an acute toxic-infectious
disease of newborn lambs, characterized by hemorrhagic diarrhea and
diarrhea.

Historical background, distribution, hazard and damage. Lamb dysentery

was first described as bloody diarrhea in 1885 by P. A. Kuleshov et al.
The etiology of the disease was studied by Delling and Geiger (1922),
who identified the pathogen and gave the name of the disease.
Anaerobic dysentery is recorded in many sheep-breeding countries (it
has no epizootic significance on the North American continent) and is
harmful due to the mortality of lambs.

The causative agent of the disease - Clostridium perfringens

type B
Epizootology- Anaerobic dysentery affects newborn lambs aged from
several hours to 10 days, usually 2 ... 5 days. At an older age, animals
rarely get sick.

The source of the causative agent of the infection is sick animals

secreting the causative agent with feces, as well as healthy adult
sheep-bacilli carriers, in the intestines of which the pathogen can
multiply and periodically stand out with feces, infecting the soil,
bedding, and care items. Spores can persist for a long time in the
soil, which determines the stationarity (enzooticity) of anaerobic
dysentery.
The disease is non-contagious. Infection of lambs occurs alimentary by
sucking an udder contaminated with secretions of sick animals, while
licking infected objects (feeder, litter, etc.). No less dangerous are the
uncleaned corpses of the fallen lambs, the places where they lay, left
uninfected, etc.
The disease is seasonal and manifests itself during the period of mass
lambing. One of the causes of the disease is the incomplete vaccination
coverage of the livestock of ewes, a decrease in the activity of the
formation of coloral immunity due to the low fatness of animals.
In some households, the disease is registered annually, in others it has
not been recorded for several years, which depends on the presence of
factors contributing to the disease (hypothermia, poor lambs, cramped
cattle, poor feeding of ewes). An increase in the epizootic outbreak from
isolated cases to a massive lesion of the lambs by the 15 ... 20th day
after the appearance of the first cases is characteristic.
In dysfunctional farms, the incidence varies from year to year — from
isolated cases to 15 ... 30% of lambs of dysfunctional flocks, mortality
can reach 100%.
Pathogenesis- The disease develops as intestinal intoxication. The
pathogen, once in the gastrointestinal tract, multiplies rapidly and
releases a large amount of a complex of toxins (mainly beta toxin),
which have a necrotizing effect on intestinal tissue, causing ulcers and
focal necrosis. Penetrating through damaged walls of the intestine into
other organs and tissues, the toxin causes general intoxication of the
body.
The occurrence of lamb dysentery only in the first days of life is
explained by a lower trypsin production during this period, as well as by
the presence of a trypsin inhibitor in the colostrum of sheep. Animals
older than 15 days of age do not get sick, as they produce enough
trypsin, which neutralizes beta toxin.
The course and clinical manifestation- The incubation period for
anaerobic dysentery is up to 5 ... 6 hours, rarely 2 ... 3 days. In most
cases, lambs fall ill in the first 3 days after birth. The course of the
disease is super-acute, acute, subacute and rarely chronic.
In a super-acute course, the lambs die unexpectedly, without pronounced
clinical symptoms, or the disease lasts no more than 2 ... 4 hours. At the
same time, the signs of damage to the nervous system are characteristic -
impaired coordination of movement, convulsions. Sometimes, shortly
before death, feces become thin and bloody. In an acute course, a
depressed state is noted, diarrhea with gas bubbles. The feces later
become thick, dark, mixed with mucus and often blood. A sick lamb is
bent over, with ruffled hair, an abdomen pulled in and weakly reacts to
the environment. The wool around the anus and on the tail is stained
with feces, glued. At the onset of the disease, it is possible to increase
body temperature to 41 ... 42 ° C, breathing and pulse become more
frequent. The disease lasts from several hours to several days, and the
lamb dies with the phenomena of rapidly growing general weakness.
With a subacute course, the disease takes a protracted nature with less
pronounced symptoms. In individual animals, it can last up to 2 weeks.
The sick lamb lies in a state of prostration, it is exhausted; there is
diarrhea, bowel movements are initially liquid, yellow or green, then
they become more dense, black, with an admixture of blood, gas bubbles
and mucus. Animals are pushing, the spine is arched, the stomach is
pulled in, the hair is disheveled. Sick lambs are oppressed, stale, refuse
to suck milk, pulse and breathing are quickened. At the onset of the
disease, body temperature can rise to 41 ° C. Depletion and death are
then noted.
In rare cases, in the chronic course of the disease, symptoms can be
mild, the disease drags on and the lambs recover. Recovery is very slow,
lambs lag behind in growth and development and often die from various
causes.
Pathological signs- Rigor mortis is well expressed. The anus area is
stained with feces. At autopsy, a yellow or reddish exudate, sometimes a
gelatinous mass, is found in the chest and abdominal cavities, as well as
in the cardiac shirt.
The heart is somewhat enlarged, the heart muscle is flabby, gray-red in
color, with punctate and striped hemorrhages under the epicardium and
endocardium. The liver is often enlarged, blood-filled, flabby
consistency. Spleen without visible changes. The lungs are swollen, the
kidneys are hyperemic. The most characteristic changes are found in the
gastrointestinal tract, especially in the thin section. The abomasum is
slightly inflamed, often filled with clotted milk. In some cases, the
intestines throughout are hemorrhagically inflamed, dark red in color,
filled with mucous-bloody contents. In other cases, individual segments
of the intestine are inflamed, covered with ulcerations and round
necrotic foci with a diameter of 3 to 6 mm, surrounded by a hemorrhagic
zone. Mesenteric lymph nodes are enlarged, juicy, sometimes with
hemorrhages. In a super-acute course, there are no visible pathological
changes.

Diagnostics and differential diagnostics- Preliminarily, the disease is

diagnosed on the basis of epizootological data, the clinical picture, and
pathological changes. The presence of hemorrhagic enteritis or necrotic
ulcers on the intestinal wall in the fallen lambs can be considered as a
diagnostic sign. The final diagnosis is based on the results of
bacteriological and serological studies.
The material for laboratory research is a fresh corpse or a bandaged
segment of the affected intestine, parts of the parenchymal organs,
mesenteric lymph nodes, tubular bone and sterilely taken contents of the
small intestine. Material is taken no later than 3 hours after the death of
the animal.
A laboratory diagnosis (microscopy, culture and biological research) is
established similarly to that for infectious enterotoxemia. If a toxin is
detected in the filtrate of the intestinal contents or the isolated culture, its
type is determined in pH on white mice with type-specific serums for C.
perfringens.
With differential diagnosis, it is necessary to exclude salmonellosis,
escherichiosis, coccidiosis.

Immunity and specific prevention. In dysentery, as in other

clostridioses, antitoxic immunity is formed - the sick animals become
resistant to the second disease. In lambs obtained from vaccinated ewes,
colostral immunity occurs, lasting up to 1.5 months.

To prevent dysentery, lambs vaccinate ewes before lambing. To do this,

use a multivalent concentrated hydroxyaluminium vaccine or a
polyvalent toxoid against sheep claus-tridiosis. For passive
immunization, antitoxic serum is used against anaerobic dysentery
of lambs and infectious enterotoxemia of sheep (see Infectious
enterotoxemia of sheep).
Treatment- Treatment is effective only at the beginning of the disease.
When dysentery occurs, sick lambs, together with the ewes, are isolated
and treated with antitoxic serum against anaerobic lambs dysentery and
sheep infectious enterotoxemia. Serum can be used in combination with
tetracycline antibiotics. Patients are kept in isolation (suckling lambs
with mothers) and served separately from a healthy livestock.
Control measures- In a dysfunctional farm, the entire number of sheep
is vaccinated, starting at 3 months of age, according to the instructions
for using the vaccine or polyanatoxin. In farms that are unfavorable for
lambs dysentery and sheep malignant edema, prophylactic vaccination
of ovarian queens is carried out 1.5. 2 months before lambing. Upon
reaching 6 months of age, the lambs are revaccinated twice in doses
prescribed for adult sheep. Forced vaccination in case of a disease
among an unvaccinated sheep population is carried out at any time.
During the vaccination period, castration and shearing of the sheep-head
is prohibited. In farms (flocks), permanently unfavorable for anaerobic
dysentery, antitoxic serum is administered to all born lambs.

Bradsot (Braxy)

Braxy is a disease which causes sudden death in sheep. It is caused by

the bacterium Clostridium septicum.
Braxy generally occurs in winter, when sheep eat frosted root crops, or
frosted grass. The frozen feed damages the mucosa (lining) of
the abomasum, allowing C. septicum to enter, causing abomasitis and a
fatal bacteremia.
Young sheep not protected with a vaccine are most commonly affected.
If sheep are not found dead, signs include abdominal pain and
recumbency.
There is no treatment, and sheep usually die within 36 hours of the
onset of signs.The carcass of sheep which died of braxy will often
decompose more rapidly than expected.

Botulism
 Clostridium botulinum is a bacterium that produces dangerous
toxins (botulinum toxins) under low-oxygen conditions.
 Botulinum toxins are one of the most lethal substances known.
 Botulinum toxins block nerve functions and can lead to respiratory
and muscular paralysis.
 Human botulism may refer to foodborne botulism, infant botulism,
wound botulism, and inhalation botulism or other types of
intoxication.
 Foodborne botulism, caused by consumption of improperly
processed food, is a rare but potentially fatal disease if not
diagnosed rapidly and treated with antitoxin.
 Homemade canned, preserved or fermented foodstuffs are a
common source of foodborne botulism and their preparation
requires extra caution.

Foodborne botulism is a serious, potentially fatal disease. However, it is

relatively rare. It is an intoxication usually caused by ingestion of potent
neurotoxins, the botulinum toxins, formed in contaminated foods.
Person to person transmission of botulism does not occur.

Spores produced by the bacteria Clostridium botulinum are heat-resistant

and exist widely in the environment, and in the absence of oxygen they
germinate, grow and then excrete toxins. There are 7 distinct forms of
botulinum toxin, types A–G. Four of these (types A, B, E and rarely F)
cause human botulism. Types C, D and E cause illness in other
mammals, birds and fish.

Botulinum toxins are ingested through improperly processed food in

which the bacteria or the spores survive, then grow and produce the
toxins. Though mainly a foodborne intoxication, human botulism can
also be caused by intestinal infection with C. botulinum in infants,
wound infections, and by inhalation.

Symptoms of foodborne botulism

Botulinum toxins are neurotoxic and therefore affect the nervous system.
Foodborne botulism is characterized by descending, flaccid paralysis
that can cause respiratory failure. Early symptoms include marked
fatigue, weakness and vertigo, usually followed by blurred vision, dry
mouth and difficulty in swallowing and speaking. Vomiting, diarrhoea,
constipation and abdominal swelling may also occur. The disease can
progress to weakness in the neck and arms, after which the respiratory
muscles and muscles of the lower body are affected. There is no fever
and no loss of consciousness.

The symptoms are not caused by the bacterium itself, but by the toxin
produced by the bacterium. Symptoms usually appear within 12 to 36
hours (within a minimum and maximum range of 4 hours to 8 days)
after exposure. Incidence of botulism is low, but the mortality rate is
high if prompt diagnosis and appropriate, immediate treatment (early
administration of antitoxin and intensive respiratory care) are not given.
The disease can be fatal in 5 to 10% of cases.

Exposure and transmission

Foodborne botulism

C. botulinum is an anaerobic bacterium, meaning it can only grow in the

absence of oxygen. Foodborne botulism occurs when C.
botulinum grows and produces toxins in food prior to consumption. C.
botulinum produces spores and they exist widely in the environment
including soil, river and sea water.

The growth of the bacteria and the formation of toxin occur in products
with low oxygen content and certain combinations of storage
temperature and preservative parameters. This happens most often in
lightly preserved foods and in inadequately processed, home-canned or
home-bottled foods. C. botulinum will not grow in acidic conditions (pH
less than 4.6), and therefore the toxin will not be formed in acidic foods
(however, a low pH will not degrade any pre-formed toxin).
Combinations of low storage temperature and salt contents and/or pH
are also used to prevent the growth of the bacteria or the formation of
the toxin.

The botulinum toxin has been found in a variety of foods, including low-
acid preserved vegetables, such as green beans, spinach, mushrooms,
and beets; fish, including canned tuna, fermented, salted and smoked
fish; and meat products, such as ham and sausage. The food implicated
differs between countries and reflects local eating habits and food
preservation procedures. Occasionally, commercially prepared foods are
involved.

Though spores of C. botulinum are heat-resistant, the toxin produced by

bacteria growing out of the spores under anaerobic conditions is
destroyed by boiling (for example, at internal temperature greater than
85 °C for 5 minutes or longer). Therefore, ready-to-eat foods in low
oxygen-packaging are more frequently involved in cases of foodborne
botulism.

Food samples associated with suspect cases must be obtained

immediately, stored in properly sealed containers, and sent to
laboratories in order to identify the cause and to prevent further cases.

Infant botulism

Infant botulism occurs mostly in infants under 6 months of age.

Different from foodborne botulism caused by ingestion of pre-formed
toxins in food, it occurs when infants ingest C. botulinum spores, which
germinate into bacteria that colonize in the gut and release toxins. In
most adults and children older than about 6 months, this would not
happen because natural defences in intestines that develop over time
prevent germination and growth of the bacterium.

C. botulinum in infants include constipation, loss of appetite, weakness,

an altered cry and a striking loss of head control. Although there are
several possible sources of infection for infant botulism, spore-
contaminated honey has been associated with a number of cases. Parents
and caregivers are therefore warned not to feed honey to the infants
before the age of 1 year.
Wound botulism

Wound botulism is rare and occurs when the spores get into an open
wound and are able to reproduce in an anaerobic environment. The
symptoms are similar to the foodborne botulism, but may take up to 2
weeks to appear. This form of the disease has been associated with
substance abuse, particularly when injecting black tar heroin.

Inhalation botulism

Inhalation botulism is rare and does not occur naturally, for example it is
associated with accidental or intentional events (such as bioterrorism)
which result in release of the toxins in aerosols. Inhalation botulism
exhibits a similar clinical footprint to foodborne botulism. The median
lethal dose for humans has been estimated at 2 nanograms of botulinum
toxin per kilogram of bodyweight, which is approximately 3 times
greater than in foodborne cases.

Following inhalation of the toxin, symptoms become visible between 1–

3 days, with longer onset times for lower levels of intoxication.
Symptoms proceed in a similar manner to ingestion of botulinum toxin
and culminate in muscular paralysis and respiratory failure.

If exposure to the toxin via aerosol inhalation is suspected, additional

exposure to the patient and others must be prevented. The patient's
clothing must be removed and stored in plastic bags until it can be
washed thoroughly with soap and water. The patient should shower and
be decontaminated immediately.

Other types of intoxication

Waterborne botulism could theoretically result from the ingestion of the

pre-formed toxin. However, as common water treatment processes (such
as boiling, disinfection with 0.1% hypochlorite bleach solution) destroy
the toxin, the risk is considered low.

Botulism of undetermined origin usually involves adult cases where no

food or wound source can be identified. These cases are comparable to
infant botulism and may occur when the normal gut flora has been
altered as a result of surgical procedures or antibiotic therapy.
Adverse effects of the pure toxin have been reported as a result of its
medical and/or cosmetic use in patients, see more on 'Botox' below.

'Botox'
The bacterium C. botulinum is the same bacterium that is used to
produce Botox, a pharmaceutical product predominantly injected for
clinical and cosmetic use. Botox treatments employ the purified and
heavily diluted botulinum neurotoxin type A. Treatment is administered
in the medical setting, tailored according to the needs of the patient and
is usually well tolerated although occasional side effects are observed.

Diagnosis and treatment

Diagnosis is usually based on clinical history and clinical examination

followed by laboratory confirmation including demonstrating the
presence of botulinum toxin in serum, stool or food, or a culture of C.
botulinum from stool, wound or food. Misdiagnosis of botulism
sometimes occurs as it is often confused with stroke, Guillain-Barré
syndrome, or myasthenia gravis.

Antitoxin should be administered as soon as possible after a clinical

diagnosis. Early administration is effective in reducing mortality rates.
Severe botulism cases require supportive treatment, especially
mechanical ventilation, which may be required for weeks or even
months. Antibiotics are not required (except in the case of wound
botulism). A vaccine against botulism exists but it is rarely used as its
effectiveness has not been fully evaluated and it has demonstrated
negative side effects.

Prevention

Prevention of foodborne botulism is based on good practice in food

preparation particularly during heating/sterilization and hygiene.
Foodborne botulism may be prevented by the inactivation of the
bacterium and its spores in heat-sterilized (for example, retorted) or
canned products or by inhibiting bacterial growth and toxin production
in other products. The vegetative forms of bacteria can be destroyed by
boiling but the spores can remain viable after boiling even for several
hours. However, the spores can be killed by very high temperature
treatments such as commercial canning.

Commercial heat pasteurization (including vacuum packed pasteurized

products and hot smoked products) may not be sufficient to kill all
spores and therefore the safety of these products must be based on
preventing bacterial growth and toxin production. Refrigeration
temperatures combined with salt content and/or acidic conditions will
prevent the growth of the bacteria and formation of toxin.

Necrobacteriosis
Fusobacterium necrophorum is an anaerobic, non-sporeforming, non-
motile, Gram-negative bacterium. There are
two subspecies, necrophorum and fundiliforme, the former being more
virulent. All members of the genus Fusobacterium produce butyrate as a
major end product of amino acid utilization and are poor fermenters of
carbohydrates. F. necrophorum morphology is variable, ranging from
coccobacillary to filamentous, but filamentous organisms are most
common, especially in new cultures. F. necrophorum produces several
toxins, the most important being leukotoxin. This is a high-molecular-
weight protein with specific activity against leukocytes. Leukotoxin has
been sequenced and shown to encode a protein of 3241 amino acids. The
gene sequence is markedly different from those of other bacterial
leukotoxins. Interestingly, F. necrophorum leukotoxin is substantially
more active against ruminant than rabbit leukocytes, which may explain
the difference in prevalence of infection among these species.

Fusobacterium necrophorum causes or is associated with a variety of

diseases in sheep and is likely to cause many similar diseases in goats. It
is best known as a cause of footrot and hepatic abscesses and also
appears to be important in lip-leg ulceration. It is an enteric gram-
negative anaerobe and as such can cause gram-negative sepsis after
entrance of the bacterium or its toxins into the circulation.
F. necrophorum has a poor ability to invade healthy tissue. However, it
readily colonizes regions damaged by trauma, persistent moisture, and
infection. In addition to endotoxin, the bacterium produces leukocidal
and cytolytic toxins that form zones of necrosis around bacterial
colonies. This tissue necrosis, as well as the foul-smelling waste gases
produced by the bacteria, are characteristic of necrobacillosis, or F.
necrophorum infection. Clinical signs include necrotic, fetid lesions,
usually of the mouth or feet, that can cause ingestion or lameness
problems. Efforts to maintain good hygiene are helpful in preventing
fecal contamination. Additionally, preventing trauma to foot and mouth
tissues through good surface choices and proper pasture drainage is
important

Clinical Signs

Varying degrees of lameness are observed in all ages of animals within

2–3 weeks of exposure to the organisms. Severely infected animals will
show generalized signs of weight loss, decreased productivity, and
anorexia associated with an inability to move. The interdigital skin and
hooves will be moist with a very distinct necrotic odor. Diagnosis is
based on clinical signs. Smears and cultures confirm the definitive
agents. Clinical signs of the milder disease, footscald, include mild
lameness, redness and swelling, and little to no odor.

Prevention and Control

These programs involve scrutiny of herd and flock

management; quarantine of incoming animals; vaccination; segregation
of affected animals; careful and regular hoof trimming; avoiding muddy
pens and holding areas; and culling individuals with chronic and
nonresponsive infections.