The Gram-Positive Bacilli of Medical Importance: Group 5

Chapter 19
Microbiology and Parasitology
CHAPTER
19:
The Gram-Positive Bacilli of
Medical Importance
Group 5
Chapter 19 WOT
D
Word of the
Day
Don’t ever let someone tell you, you can’t do

something. Not even me. You got a dream, you got
to protect it. People can’t do something themselves,
they want to tell you you can’t do it. You want
something, go get it. Period.
Chapter 19 WOT Overview
D
OVERVIE
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Chapter 19 WOT Overview Case
D Study
Chapter 19 WOT Overview Case
D Study
CONT
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Chapter 19 WOT Overview Case 19.
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19.1 Medically Important Gram-Positive Bacilli

The gram-positive bacilli can be subdivided into three general groups based on the
presence or absence of endospores and the characteristic of acid-fastness. Further
levels of separation correspond to oxygen requirements and cell morphology.
Organization of the most important gram-positive pathogens can be seen in table 19.1
and Systems Profile 19.1.
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19.2 Gram-Positive Spore-Forming Bacilli

Most endospore-forming bacteria are gram-positive, motile, rod-shaped forms in the
genera Bacillus and Clostridium. An endospore is a dense survival unit that develops in
a vegetative cell in response to nutrient deprivation (figure 19.1; see figure 4.22). The
extreme resistance to heat, drying, radiation, and chemicals accounts for the survival,
longevity, and ecological niche of sporeformers, and it is also a significant factor in their
pathogenicity.
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General Characteristics of the Genus Bacillus

The genus Bacillus includes a large assembly of mostly saprobic bacteria widely
distributed in the earth’s habitats. Bacillus species are aerobic and catalase-positive,
and, though they have varied nutritional requirements, none is fastidious. The group is
noted for its versatility in degrading complex macromolecules, and it is also a common
source of antibiotics. Because the primary habitat of many species is the soil, spores are
continuously dispersed by means of dust into water and onto the bodies of plants and
animals. Despite their ubiquity, the two species with primary medical importance are B.
anthracis, the cause of anthrax, and B. cereus, the cause of one type of food poisoning.
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Bacillus anthracis and Anthrax

Bacillus anthracis is among the largest of all bacterial pathogens, composed of block-
shaped, angular nonmotile rods 3 to 5 μm long and 1 to 1.2 μm wide and central spores
that develop under all growth conditions except in the living body of the host (figure
19.1a). Its virulence factors include a polypeptide capsule and exotoxins that in varying
combinations produce edema and cell death. For centuries, anthrax* has been known
as a zoonotic disease of her bivorous livestock (sheep, cattle, goats). It has an
important place in the history of medical microbiology because it was Robert Koch’s
model for developing his postulates in 1877; and later Louis Pasteur used the disease
to prove the usefulness of vaccination.
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The anthrax bacillus is a facultative anaerobe that undergoes its cycle of vegetative
growth and sporulation in the soil. Animals become infected while grazing on grass
contaminated with spores. When the pathogen is returned to the soil in animal
excrement or carcasses, it can sporulate and become a long-term reservoir of in fection
for the animal population. The majority of anthrax cases are reported in livestock from
Africa, Asia, and the Middle East. Most recent human cases in the United States have
occurred in textile workers handling imported animal hair or hide or products made from
them. In 2008 a drum maker in London died of inhalational anthrax, contracted while
scraping goat hides to be used as drumheads. The hides had been imported from
Africa, where anthrax is endemic. Re markably similar incidents occurred in New York
in 2006 and Scotland in 2005. Because of effective control procedures, the number of
cases in the United States is extremely low (fewer than 10 a year).
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The circumstances of human infection depend upon the portal of entry. The most common
and least dangerous of all forms is cutaneous anthrax, caused by spores entering the skin
through small cuts and abrasions. Germination and growth of the pathogen in the skin are
marked by the production of a papule that becomes increasingly necrotic and later ruptures
to form a painless, black eschar* (figure 19.2).
A far more destructive infection is pulmonary anthrax (wool sorter’s disease) associated
with the inhalation of airborne spores, either from animal products or from contaminated
soil. The infec tious dose is relatively small—8,000 to 50,000 spores. Upon reaching the
lungs, the spores are phagocytosed and transported to lymph nodes, where they
germinate and secrete exotoxins that enter the circulatory system. The toxins attach to
membranes of macrophages and gain entry into these cells through engulfment. The
toxins are highly lethal, causing massive macrophage death and release of chemical
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Chapter WOTD Overview Case 19.
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The pathologic effect of these events are wide- capillary

cardiovascular s and rapid ranging: death in over thrombosis, untreated
shock,
gastrointestinal form of infection is a 99%
rare of
(1 U.S. case in the lastcases. The but deadly
70 years)
condition that follows a course similar to pulmonary anthrax but is acquired through the
ingestion of contaminated meat.
The terrorist attacks of 2001 focused a great deal of attention on the threat of
bioterrorism, but it was hardly the first time the virulent nature of anthrax had been
considered as a weapon of war (19.1 Making Connections).
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Methods of Anthrax Control Active cases of anthrax are treated with clindamycin,
doxycycline, or ciprofloxacin. Because drug therapy targeting the bacteria itself does
nothing to lessen the effects of toxemia, people can still die from it. Antibiotics are
generally given along with a second drug, Raxibacumab, which uses monoclonal
antibodies to bind to one of the toxins secreted by B. anthracis, preventing it from
entering cells and dramatically decreasing the severity of the disease. A vaccine
containing live spores and a toxoid prepared from a special strain of B. anthracis are
used to protect livestock in areas of the world where anthrax is endemic. A vaccine,
Biothrax, based on a purified toxoid, is recommended for people in high-risk occupations
and military personnel.
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Effective vaccination requires five inoculations given over 18 months, with yearly
boosters. The potential side effects reported for this vaccine have spurred research and
development of alternative vaccines. Animals that have died from anthrax must be
burned or chemically decontaminated before burial to prevent establishing the microbe
in the soil; and imported items containing animal hides, hair, and bone should be gas-
sterilized.
Other Bacillus Species Involved in Human Disease

Bacillus cereus is a common airborne and dust-borne contaminant that multiplies very
readily in cooked foods such as rice, potato, and meat dishes. The spores survive short
periods of cooking and reheating; when the food is stored at room temperature, the
spores germinate and release enterotoxins. Ingestion of toxin-containing food causes
nausea, vomiting, abdominal cramps, and diarrhea. There is no specific treatment, and
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For many years, most common airborne Bacillus species were dismissed as harmless
contaminants with weak to nonexistent pathogenicity. However, infections by these
species are increasingly reported in immunosuppressed and intubated patients and in
drug addicts who do not use sterile needles and syringes. Two important contributing
factors are the abundance of spores in the environment and how ineffective the usual
methods of disinfection and antisepsis are when it comes to spores.
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The Genus Clostridium

Another genus of gram-positive, spore-forming rods that is widely distributed in nature is
Clostridium.* It is differentiated from Bacillus on the basis of being anaerobic and
catalase- negative (table 19.2). The large genus (over 120 species) resides in a variety of
habitats. Saprobic members are frequently found in soil, sewage, vegetation, and organic
debris; and commensals inhabit the bodies of humans and other animals. Infections
caused by pathogenic species are not normally communicable but occur when spores are
introduced into injured skin.
Clostridia produce oval or spherical spores that often swell the vegetative cell (see figure
19.1b). Spores are produced only under anaerobic conditions. Their nutrient requirements
are complex, and they can decompose a variety of substrates. They can also synthesize
organic acids, alcohols, and other solvents through fermentation.
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The Genus Clostridium

This capacity makes some clostridial species essential tools of the biotechnology industry
(see chapter 27). Other extracellular products, primarily exotoxins, play an important role
in various clostridial diseases such as botulism and tetanus.
The Role of Clostridia in Infection and Disease

Clostridial disease can be divided into (1) wound and tissue infec tions, including
myonecrosis, antibiotic-associated colitis, and teta nus; and (2) food intoxication of the
perfringens and botulism varieties. Most of these diseases are caused by the release of
potent exotoxins that act on specific cellular targets. In fact, the exotoxins responsible for
these diseases are among the most poisonous sub stances on earth, being millions of
times more toxic than strychnine or arsenic.
19 Study 2
Gas
The majority of clostridial soft tissue and wound infections are caused by Clostridium
Gangrene/Myonecrosis
perfringens, C. novyi, and C. septicum. The spores of these species can be found in soil, on
human skin, and in the human intestine and vagina. The disease they cause has the common
name gas gangrene* in reference to the gas produced by the bacteria growing in the tissue. It is
technically termed anaerobic cellulitis or myonecrosis.* The conditions that predispose a
person to gangrene are surgical incisions, compound fractures, diabetic ulcers, septic
abortions, puncture and gunshot wounds, and crushing injuries contaminated by spores from
the body or the environment.
Because clostridia are not highly invasive, infection requires damaged or dead tissue that
supplies growth factors and an anaerobic environment. The low oxygen tension results from an
inter rupted blood supply and the growth of aerobic contaminants that deplete oxygen. Due to
this interaction, gas gangrene is considered a type of mixed infection.
19 Study 2
Gas Gangrene/Myonecrosis
These conditions stimulate spore germination, rapid vegetative growth in the dead tissue, and
release of exotoxins. Clostridium perfringens produces several physiologically active toxins; the
most potent one, alpha-toxin (lecithinase), causes red blood cell rupture, edema, and tissue
destruction (figure 19.3). Additional virulence factors that enhance tissue destruction are
collagenase, hyaluronidase, and DNase. The gas formed in tissues, due to fermentation of
muscle carbohydrates, can also destroy muscle structure.
Extent and Symptoms of Infection Two forms of gas gangrene have been identified. In
anaerobic cellulitis, the bacteria spread within damaged necrotic muscle tissue, producing toxins
and gas, but the infection remains localized and does not spread into healthy tissue. The
pathology of true myonecrosis is more destructive and mimics some aspects of necrotizing
fasciitis. Toxins produced in large muscles, such as the thigh, shoulder, and buttocks, diffuse
into nearby healthy tissue and cause local necrosis there.
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This damaged tissue then supports continued clostridial growth, toxin formation, and gas
production. The disease can progress through an entire limb or body area, destroying tissues as
it goes (figure 19.4). Initial symptoms of pain, edema, and a bloody exudate in the lesion are
fol owed by fever, tachycardia, and blackened necrotic tissue filled with bubbles of gas.
Gangrenous infections of the uterus due to septic abortions and clostridial septicemia are
particularly serious complications. If treatment is not initiated early, the disease is invariably fatal.
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Treatment and Prevention of Gangrene One of the most effective ways to prevent
clostridial wound infections is immediate and rigorous cleansing and surgical repair of deep
wounds, pressure sores (bedsores), compound fractures, and infected incisions. Debridement*
of diseased tissue eliminates the conditions that promote the spread of gangrenous infection.
This is most difficult in the intestine or body cavity, where only limited amounts of tissue can be
removed. Surgery is accompanied by antibiotic therapy to control the infection. The preferred
treatment is clindamycin, supplemented with penicillin for the 5% of clostridial species that are
clindamycin-resistant. Hyperbaric oxygen therapy, in which the affected part is exposed to an
increased oxygen tension in a pressurized chamber, can also lessen the severity of infection
(figure 19.5).
The increased oxygen content of the tissues blocks further bacterial multiplication and toxin
production, while simultaneously promoting healing. Extensive myonecrosis of a limb may call for
surgical removal, or amputation. Because there are so many different anti gen subtypes in this
group, active immunization is not possible.
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Chapter 19 Tenanus
Tenanus or
Lockjaw
Tetanus is a neuromuscular disease whose alternate name, lockjaw, refers to
an early effect of the disease on the jaw muscle. The etiologic agent,
Clostridium tetani, is a common resident of cultivated soil and the
gastrointestinal tracts of animals.
The incidence of neonatal tetanus—predominantly the result of an infected

umbilicus or circumcision—is higher in cultures that apply dung or mud to
these sites to arrest bleeding or as a customary ritual.
Chapter 19 Tenanus Course of Infection and
Disease
The Course of Infection and

The risk Disease
for tetanus occurs when spores of Clostridium tetani are forced into
injured tissue. It is also a strict anaerobe, and the spores cannot become
established unless tissues at the site of the wound are necrotic and poorly supplied
with blood, conditions that favor germination.
As the vegetative cells multiply, various metabolic products are released into the
infection site. Of these, the most serious is tetanospasmin, a potent neurotoxin that
accounts for the major symptoms of tetanus. The toxin spreads to nearby motor
nerve endings in the injured tissue, binds to them, and travels by axons to the
ventral horns of the spinal cord.
In the spinal column, the toxin binds to specific target sites on the spinal neurons
that are responsible for inhibiting skeletal muscle contraction.
Chapter 19 Tenanus Course of Infection and
Disease
Course of Infection and
Chapter 19 Tenanus
Disease
Tetanospasmin alters the usual

regulatory mechanisms for muscle
contraction. As a result, the muscles
are released from normal inhibition
and begin to contract uncontrollably.
Powerful muscle groups are most
affected, and the first symptoms are
clenching of the jaw, followed in
succession by extreme arching of the
back, flexion of the arms, and
extension of the legs
Course of Infection and
Chapter 19 Tenanus
Disease
Lockjaw confers the bizarre appearance of risus sardonicus (sarcastic grin)

that looks eerily as though the person is smiling.
Death is most often due to paralysis of the respiratory muscles and

respiratory failure. The fatality rate, ranging from 10% to 70%, is highest in
cases involving delayed medical attention, a short incubation time, or head
wounds. Full recovery requires a few weeks, and other than transient
stiffness, no permanent damage to the muscles usually remains.
Chapter 19 Tenanus Course of Infection and Treatment
Disease &
Prevention
Treatment and Prevention of Tetanus

Tetanus treatment is aimed at reducing the level of toxemia and providing
supportive care for the patient. A patient with a clinical appearance suggestive of
tetanus should immediately receive antitoxin therapy with human tetanus
immune globulin (TIG).
Other methods include thoroughly cleansing and removing the afflicted tissue,
controlling infection with metronidazole or penicillin, and administering muscle
relaxants. The patient may require a respirator, and a tracheostomy is sometimes
performed to prevent complications such as aspiration pneumonia or lung
collapse.
Disease &
Prevention
Tetanus is one of the world’s most preventable diseases, chiefly

because of effective vaccines (DTaP, Td) containing tetanus toxoid.
During World War II, only 12 cases of tetanus occurred among
2,750,000 wounded soldiers who had been previously vaccinated. The
recommended vaccination series for babies consists of three injections
given 2 months apart, followed by booster doses about 1 and 4 years
later.
Pathogen Profile
Disease &
#2
Prevention
Pathogen Profile Pathogen Profile
Disease & #2 #3
Prevention
Chapter 19 Clostridium difficile
Infection
Clostridium difficile Infection

A clostridial disease most commonly called C-diff infection, or CDI, is the second
most common intestinal disease after salmonellosis in industrialized countries. It is
caused by Clostridium difficile, a normal resident of the intestine that is usually
present in low numbers. Most instances of this infection are traced to therapy with
broad-spectrum drugs such as clindamycin, ceftriaxone, or ciprofloxacin.
Many cases today involve a strain that produces about 20 times the usual amount
of exotoxins. The use of gastric acid inhibitors such as famotidine (Pepcid) and
omeprazole (Prilosec) increase prevalence of the disease, as less gastric acidity may
improve survival of the pathogen in the stomach and intestine.
Infection
It produces enterotoxins that trigger

necrosis in the wall of the intestine. The
predominant symptom is diarrhea
commencing late in therapy or even after
therapy has stopped. More severe cases
exhibit abdominal cramps, fever, and
leukocytosis. The colon is inflamed and
gradually sloughs off loose, membrane-
like patches called pseudomembranes
consisting of fibrin and cells
Infection
More severe infections are treated with oral vancomycin or metronidazole

and replacement cultures to restore normal microbiota. Fecal microbiota
transplantation, a procedure in which feces from a healthy donor are
transferred via enema, swallowed capsules, or colonoscopy directly to the
colon of patients suffering C. difficile infection, has gained prominence. In
2016 the FDA began to increase oversight of fecal microbiota transplants,
tightening the regulations governing the procedure.
In the clinical setting, stringent precautions are necessary to prevent the

spread of the agent from infected persons to other patients who may be on
antimicrobic therapy. Immediate diagnosis is obtained by a rapid ELISA that
detects toxins in fecal samples.
Clostridium difficile Clostridial
Chapter 19
Infection Food
Poisoning
Clostridial Food
Poisoning
Two Clostridium species are involved in food poisoning:
1.Clostridium botulinum- produces a severe intoxication, usually
from home canned food.
2. Clostridium perfringens- type A, accounts for a mild intestinal illness that
is one of the most common forms of food poisoning worldwide.
Clostridium difficile Clostridial Epidemiology
Chapter 19
Infection Food of Botulinum
Poisoning
Epidemiology of Botulinum Food

Poisoning
Clostridium botulinum is a spore-forming anaerobe that commonly inhabits
soil and water and, occasionally, the intestinal tract of animals. The species
has eight distinctly different types (designated A, B, Cα and Cβ, D, E, F, and
G
Botulism is an intoxication usually associated with eating improperly

canned or poorly preserved foods, though it can occur as a result of
infection. However, botulism is a common cause of death in livestock that
Clostridium difficile Clostridial Epidemiology
Chapter 19
Infection Food of Botulinum
Poisoning
In the United States, the disease is often associated with low-acid vegetables
(green beans, corn) and, occasionally, meats, fish, and dairy products. Most
botulism outbreaks occur in home-processed foods, including canned
vegetables, smoked meats, and cheese spreads.
One of the most recent outbreaks of botulism traced to a commercial source

occurred in 2007 among people who had consumed canned chili sauce. The
cans were traced to a food plant that apparently had defects in its
sterilization procedures. The constant presence of C. botulinum spores in the
soil and on produce means that there is zero tolerance for errors in quality
control.
Clostridium difficile Clostridial Epidemiology Pathogenesis of
Chapter 19
Infection Food of Botulinum Botulinum
Poisoning
Pathogenesis of Botulism
Spores are present on the vegetables or meat at the time of gathering and are
difficult to remove by washing alone. When contaminated food is bottled
and steamed in a pressure cooker that does not reach reliable pressure and
temperature, some spores survive (botulinum spores are highly heat-
resistant). At the same time, the pressure is sufficient to evacuate the air and
create anaerobic conditions ideal for spore germination and vegetative
growth. One of the products of metabolism is botulinum toxin, the most
potent microbial toxin known
Chapter 19
Poisoning
Bacterial growth may not be evident in the

appearance of the bottle or can or in the
food’s taste or texture, and only minute
amounts of toxin may be present.
Swallowed toxin enters the small intestine
and is absorbed into the lymphatics and
circulation. From there, it travels to its
principal site of action, the neuromuscular
junctions of skeletal muscles
Chapter 19
Poisoning
Neuromuscular symptoms first affect the muscles of the head and

include double vision, difficulty in swallowing and dizziness, but there is
no sensory or mental lapse.
Later symptoms are descending muscular paralysis and respiratory

failure. In the past, death resulted from stoppage of respiration, but
mechanical respirators have reduced the fatality rate to about 10%. A
fascinating medical use for targeting unwanted muscle contractions with
the toxin.
Clostridium difficile Clostridial Epidemiology Pathogenesis of Infant and
Chapter 19
Infection Food of Botulinum Botulinum Wound Botulism
Poisoning
Infant and W ound Botulism

C. botulinum causes infections when endospores germinate in the body
and produce the toxin in vivo. Infant botulism was first described in the
late 1970s in children between the ages of 2 weeks and 6 months who had
ingested spores.
The immature state of the neonatal intestine and resident microbiota

allows the spores to gain a foothold, germinate, and produce neurotoxin.
As in adults, babies exhibit flaccid paralysis, usually with a weak
sucking response, generalized loss of tone (“floppy baby syndrome”),
and respiratory complications.
Clostridium difficile Clostridial Epidemiology Pathogenesis of Infant and
Chapter 19
Infection Food of Botulinum Botulinum Wound Botulism
Poisoning
In wound botulism, the spores enter a wound or puncture much as in

tetanus, but the symptoms are similar to those of food-borne botulism.
Increased cases of this form of botulism are being reported in injecting
drug users. The rate of infection is highest in people who inject black tar
heroin into the skin.
Chapter 19 Treatment and
Prevention of Botulism
Treatment and Prevention of Botulism

Differentiating botulism from other neuromuscular conditions usually involves
testing food samples, intestinal contents, and feces for evidence of toxin or C.
botulinum. Treatment involves administration of botulinum antitoxin, supplied by
the CDC, and which must be administered early for greatest effectiveness. Patients
are also managed with intensive respiratory and cardiac support care. Infectious
botulism is treated with penicillin to control the microbe’s growth and toxin
production.
Pressure cookers should be tested for accuracy in sterilizing, and home canners
should be aware of the types of food and conditions likely to cause botulism. Other
effective preventives include addition of preservatives such as sodium nitrite, salt,
or vinegar.
Treatment and Clostridial
Chapter 19
Prevention of Botulism Gastroenteriti
s
Clostridial Gastroenteritis
Clostridium perfringens spores contaminate many kinds of food, but those most
frequently involved in disease are animal flesh (meat, fish) and vegetables (beans)
that have not been cooked thoroughly enough to destroy the spores. When these
foods are cooled, spores germinate and the germinated cells multiply, especially if
the food is left unrefrigerated. When the food is eaten without adequate reheating,
live C. perfringens cells enter the small intestine and release enterotoxin. The
toxin, acting upon epithelial cells, initiates acute abdominal pain, diarrhea, and
nausea in 8 to 16 hours.
Clostridium perfringens also causes enterocolitis similar to that caused by C.

difficile. This infectious type of diarrhea is acquired from contaminated food, or it
may be transmissible by inanimate objects.
Treatment and Clostridial Differential Diagnosis of
Chapter 19
Prevention of Botulism Gastroenteriti Clostridial Species
s
Differential Diagnosis of Clostridial Species

Diagnosis frequently depends on the microbial load, the persistence of the isolate
on resampling, and the condition of the patient. Laboratory differentiation relies
on testing morphological and cultural characteristics, exoenzymes, carbohydrate
fermentation, reaction in milk, and toxin production and pathogenicity.
Other valuable procedures are direct ELISA testing of isolates, toxicity testing in
mice or guinea pigs, serotyping with antitoxin neutralization tests, and PCR
analysis of samples.
Treatment and Clostridial Differential Diagnosis of 19.2 Making
Chapter 19
Prevention of Botulism Gastroenteriti Clostridial Species
s Connection
s
Gram-Positive
Treatment and Clostridial 19.2 Making
Chapter 19 Regular Non-Spore-
Forming Bacilli
s Connection
s
19.3: Gram-Positive
Regular Non-Spore-
Forming Bacilli
Gram-Positive
Treatment and Clostridial 19.2 Making
Chapter 19 Regular Non-Spore-
Forming Bacilli
s Connection
s
The non-spore-forming gram-positive bacilli are a mixed group of genera

subdivided on the basis of morphology and staining characteristics. One loose
aggregate of seven genera is characterized as regular because they stain uniformly
and do not assume pleomorphic shapes.
Regular genera include:
1.Lactobacillus
2. Listeria
3. Erysipelothrix
4. Kurthia
5. Caryophanon
6.Brochothrix
7. Renibacterium.
Treatment and Clostridial 19.2 Making Gram-Positive Regular Non- Listeria
Chapter 19
Prevention of Botulism Gastroenteriti Spore-Forming Bacilli monocytogenes
s Connection
s
Listeria monocytogenes ranges in morphology

from coccobacilli to long filaments in palisades
formation. Cells show tumbling motility, with one
An Emerging to four flagella, and do not produce capsules or
spores.
Food-Borne
The bacterium is an intracellular pathogen during
Pathogen: part of its life cycle. It displays a unique
Listeria multiplication cycle in which it replicates within
the cytoplasm of a host cell after inducing its own
monoc ytogene phagocytosis. By moving directly from cell to cell,
Listeria is able to avoid the humoral immune
s system, enhancing its own virulence
Treatment and Clostridial 19.2 Making Gram-Positive Regular Non- Listeria
Chapter 19
Prevention of Botulism Gastroenteriti Spore-Forming Bacilli monocytogenes
s Connection
s
Chapter 19 Epidemiology and
Pathology of Listeriosis
Epidemiology and Pathology of Listeriosis

Although most cases of listeriosis are associated with ingesting
contaminated dairy products, poultry, and meat, a highly unusual
outbreak in 2011— responsible for 33 deaths and one miscarriage—was
linked to contaminated cantaloupes.
Recent epidemics have spurred an in-depth investigation into the

prevalence of L. monocytogenes from these sources. The pathogen has
been isolated in 12% of ground beef and in 15% of chicken carcasses. It
was also present in 6% of luncheon meats, hot dogs, and cheeses. Aged
cheeses made from raw milk are of special concern.
Chapter 19 Epidemiology and
Pathology of Listeriosis
A predisposing factor in listeriosis seems to be the weakened condition of

host defenses in the intestinal mucosa.
However, listeriosis in immunocompromised patients, fetuses, and

neonates usually affects the brain and meninges and results in
septicemia. Pregnant women are especially susceptible to infection,
which is transmitted to the infant prenatally when the microbe crosses
the placenta or perinatally through the birth canal. Intrauterine
infections are systemic and usually result in miscarriage and fetal death.
Epidemiology and Diagnosis and Control
Chapter 19
Pathology of Listeriosis of Listeriosis
Diagnosis and Control of Listeriosis

Isolation can be improved by using a procedure called cold enrichment,
in which the specimen is held at 4°C and periodically plated onto media,
but this procedure can take 4 weeks. Listeria monocytogenes can be
differentiated from the nonpathogenic Listeria and from other bacteria
to which it bears a superficial resemblance by comparing traits such as
cell shape, arrangement, motility, production of catalase, and positive
CAMP reaction. Rapid diagnostic kits using ELISA, immunofluorescence,
and DNA analysis are now available for direct testing of foods.
Epidemiology and Diagnosis and Control
Chapter 19
Pathology of Listeriosis of Listeriosis
Ampicillin and gentamicin are the first choices, followed by

trimethoprim/sulfamethoxazole. Prevention can be improved by
adequate pasteurization temperatures and by cooking foods that could
be contaminated with animal feces. The U.S. Department of Agriculture
implemented regulations designed to prevent the incorporation of
Listeria into processed meat and poultry products.
Epidemiology and Diagnosis and Control Erysipelothrix
Chapter 19
Pathology of Listeriosis of Listeriosis rhusiopathiae
Erysipelothrix
rhusiopathiae: A
Zoonotic Pathogen
Epidemiology and Diagnosis and Control Erysipelothrix Epidemiology, Pathogenesis,
Chapter 19
Pathology of Listeriosis of Listeriosis rhusiopathiae and Control
Epidemiology, Pathogenesis, and Control

Erysipelothrix rhusiopathiae is a gram-positive rod widely distributed in animals
and the environment. Its primary reservoir appears to be the tonsils of healthy
pigs. It is also a normal microbiota of other vertebrates and is commonly isolated
from sheep, chickens, and fish.
The pathogen causes epidemics of swine erysipelas and sporadic infections in other
domestic and wild animals. Humans at greatest risk for infection are those who
handle animals, carcasses, and meats, such as slaughterhouse workers, butchers,
veterinarians, farmers, and fishermen.
Chapter 19
The common portal of entry in human

infections is a scratch or abrasion
on hand or arm. The microbe
the
multiplies at the invasion site to
produce a disease known as
erysipeloid, characterized by
inflamed, dark red lesions that burn
and itch
Chapter 19
Although the lesions usually heal without complications, rare cases of

septicemia and endocarditis do arise. Inflamed red sores on the hands
of people in high-risk occupations suggest erysipeloid, but the lesions
must be cultured for confirmatory diagnosis. The condition is treated
with penicillin or erythromycin. Swine erysipelas can be prevented by
vaccinating pigs, but the vaccine does not protect humans. Animal
handlers can lower their risk by wearing protective gloves.
Chapter 19
CHAPTER
19.4
The Gram-Positive Bacilli of Medical Importance
19.4
Gram-Positive
Irregular Non-
Spore- Forming
Chapter 19
CHAPTER
19.4
The irregular non-spore-forming bacilli tend to be pleomorphic and to stain

unevenly. Of the 20 genera in this category, Corynebacterium, Mycobacterium,
and Nocardia have the greatest clinical significance. These three genera are
grouped together because of similar morphological, genetic, and biochemical
traits. They produce catalase and possess mycolic acids and a unique type of
peptidoglycan in the cell wall. The following sections discuss the primary diseases
associated with Corynebacterium, a similar genus called Propionibacterium,
Mycobacterium, Actinomyces, and Nocardia.
Chapter 19 CHAPTER Corynebacterium.....
19.4
Corynebacterium diphtheriae
Although several species of Corynebacterium* are found on the human body,

most human disease is associated with C. diphtheriae. In general morphology,
this bacterium is a straight or somewhat curved rod that tapers at the ends, but it
has many pleomorphic variants, including club, filamentous, and swollen shapes.
Older cells are filled with metachromatic (polyphosphate) granules and can occur
in side-by-side palisades arrangement (figure 19.12).
Chapter 19 CHAPTER Corynebacterium.....
19.4
Chapter 19 CHAPTER Corynebacterium..... Epidemiology ....
19.4
Epidemiology of Diphtheria
For hundreds of years, diphtheria* was a significant cause of morbidity and

mortality, but for more than five decades, both the number of cases and the
fatality rate have steadily declined throughout the world. The current rate for the
entire United States is 0.01 cases per million population with the last confirmed
case seen in 2003. Recent outbreaks of the cutaneous form of the disease have
occurred among Native American populations and the homeless. Because many
populations harbor a reservoir of healthy carriers, the potential for diphtheria is
constantly present. Most cases occur in nonimmunized children from 1 to 10
years of age living in crowded, unsanitary situations.
Chapter 19 CHAPTER Corynebacterium..... Epidemiology .... Pathology of Dip....
19.4
Pathology of Diphtheria
Exposure to the diphtheria bacillus usually results from close contact with the
droplets from human carriers or active infections and occasionally with fomites or
contaminated milk. The clinical disease proceeds in two stages: (1) local infection
by Corynebacterium diphtheriae and (2) toxin production and toxemia. The most
common location of primary infection is in the upper respiratory tract (tonsils,
pharynx, larynx, and trachea). Cutaneous diphtheria usually starts as a secondary
infection manifesting as deep, erosive ulcers that are slow to heal (figure
19.13a). The bacterium becomes established by means of virulence factors that
assist in its attachment and growth. The cells are not ordinarily invasive and
usually remain localized at the portal of entry. This form of the disease is on the
rise in the United States.
19.4
Figure 19.13 Clinical aspects of diphtheria. (a)

Cutaneous diphtheria appears as a deep erosive
ulcer that is slow to heal.
19.4
Diphtherotoxin and Toxemia Although infection is necessary for disease, the

cardinal determinant of pathogenicity is the production of diphtherotoxin. The
ability of some C. diphtheriae strains to produce toxin is the result of infection with
a lysogenic bacteriophage that carries the genes for the toxin. This cytotoxin
consists of two polypeptide fragments. Fragment B binds to and is endocytosed
by mammalian target cells in the heart and nervous system. Fragment A
interacts metabolically with factors in the cytoplasm and arrests protein synthesis
(see figure 13.13).
19.4
The toxin affects the body on two levels. The local infection produces an
inflammatory reaction, sore throat, nausea, vomiting, enlarged cervical lymph
nodes, severe swelling in the neck, and fever. One life threatening complication is
the pseudomembrane, a greenish-gray film that develops in the pharynx from
the solidification of fluid expressed during inflammation (figure 19.13b). The
pseudomembrane is so leathery and tenacious that attempts to pull it away result
in bleeding; and if it forms in the airways, it can cause asphyxiation
19.4
Figure 19.13 (b) Respiratory diphtheria

includes gross inflammation of the
pharynx and tonsils marked by grayish
patches (a pseudomembrane) and
swelling over the entire area.
19.4
The most dangerous systemic complication is toxemia, which occurs when the
toxin is absorbed from the throat and carried by the blood to certain target
organs, primarily the heart and nerves. The action of the toxin on the heart
causes myocarditis and abnormal EKG patterns. Cranial and peripheral nerve
involvement can cause muscle weakness and paralysis. Although toxic effects are
usually reversible, patients with inadequate treatment often die from
asphyxiation, respiratory complications, or heart damage
Chapter 19 CHAPTER Corynebacterium..... Diagnostic Metho......
19.4
Diagnostic Methods for Corynebacterium
Diphtheria has such great potential for harm that often the physician must make a
presumptive diagnosis and begin treatment before the bacteriologic analysis is
complete. A gray membrane and swelling in the throat are somewhat indicative of
diphtheria, although several diseases present a similar appearance.
Epidemiological factors such as living conditions, travel history, and immunologic
history (a positive Schick test) can also aid in initial diagnosis.
Chapter 19 CHAPTER Corynebacterium..... Diagnostic Metho......
19.4
Diagnostic Methods for Corynebacterium

A simple stain of C. diphtheriae isolates with alkaline methylene blue reveals
pleomorphic granulated cells. Other methods include the Elek test, an assay that
relies on antibodies to detect toxins, as well as amplification of specific DNA
sequences specific to C. diphtheriae. It is important to differentiate C. diphtheriae
from “diphtheroids”—similar species often present in clinical materials that are not
primary pathogens. Corynebacterium xerosis* normally lives in the eye, skin,
and mucous membranes and is an occasional opportunist in eye and
postoperative infections. Corynebacterium pseudodiphtheriticum,* a normal
inhabitant of the human nasopharynx, can colonize natural and artificial heart
valves.
Chapter 19 CHAPTER Corynebacterium..... Diagnostic Metho...... Treatment and Pr...
19.4
Treatment and Prevention of Diphtheria

The adverse effects of toxemia are treated with diphtheria antitoxin (DAT) derived
from horses. Prior to injection, the patient must be tested for allergy to horse
serum and be desensitized, if necessary. The infection is treated with antibiotics
from the penicillin or erythromycin family. Bed rest, heart medication, and
tracheostomy or bronchoscopy to remove the pseudomembrane may be
indicated. Diphtheria can be easily prevented by a series of vaccinations with
toxoid, usually given as part of a mixed vaccine against tetanus and pertussis
(DTaP). Five vaccines are recommended for children under 7 years of age
beginning at age 2 months, with boosters at 4 months, 6 months, 15 to 18
months, and 4 to 6 years. Children from ages 7 to 18 and adults who are not
immune to the toxin can be immunized with two doses of tetanus, diphtheria,
Chapter 19 Treatment and Pr... The Genus Prop.....
Corynebacterium..... Diagnostic Metho......
The Genus Propionibacterium
Propionibacterium* resembles Corynebacterium in morphology and

arrangement, but it differs by being aerotolerant or anaerobic and nontoxigenic.
The most prominent species is P. acnes,* a common resident of the
pilosebaceous* glands of human skin and occasionally the upper respiratory
tract. The primary importance of this bacterium is its relationship with the familiar
acne vulgaris lesions of adolescence. Acne is a complex disease influenced by
genetic and hormonal factors as well as by the structure of the epidermis, but it is
also an infection. Propionibacterium is occasionally involved in infections of the
eye and artificial joints
CHAPTER
19.5
19.5
Mycobacteria:
Acid- Fast Bacilli
CHAPTER
19.5
The genus Mycobacterium is distinguished by

its structure containing high-molecular-
complex layered
weight mycolic acids and waxes. The high lipid content
of the cell wall imparts the characteristic of acid-fastness
and is responsible for the resistance of the group to
drying, acids, and various germicides. The cells of
mycobacteria are long, slender, straight, or curved rods
with a slight tendency to be filamentous or branching
(figure 19.14). Although they usually contain granules
and vacuoles, they do not form capsules, flagella, or
spores.
CHAPTER 19.5
Most mycobacteria are strict aerobes that grow well on simple nutrients and
media. Compared with other bacteria, the growth rate is generally slow, with
generation times ranging from 2 hours to several days. Some members of the
genus exhibit colonies containing yellow, orange, or pink carotenoid pigments
that require light for development; others are nonpigmented. Many of the 50
mycobacterial species are saprobes living free in soil and water, and several
are highly significant human pathogens. Worldwide, hundreds of millions of
people are afflicted with tuberculosis and leprosy. Certain opportunistic species
loosely grouped into a category called NTM (nontuberculous mycobacteria)
have become an increasing problem in immunosuppressed patients.
Mycobacteriu
CHAPTER
m tuberculosis
19.5
Mycobacterium tuberculosis: The Tubercle Bacillus

The tubercle bacillus is a long,
thin rod that grows in sinuous
masses or strands called cords.
Unlike many pathogens, it
produces no exotoxins or
that contribute to
enzymes
infectiousness. Most strains
contain waxes and
complex
cord factor a
(figure 19.15)
contribute virulence that
to
preventing the mycobacteria from by
Their survival contributes to further invasion and persistence as
being destroyed by the
intracellular parasites.
lysosomes of macrophages.
Mycobacteriu
CHAPTER
m tuberculosis
19.5
Epidemiology and Transmission of Tuberculosis
Mummies from the Stone Age, ancient Egypt, and Peru provide
unmistakable evidence that tuberculosis (TB) is an ancient human disease. In fact,
it was such a prevalent cause of death that it was called “Captain of the Men of
Death” and “White Plague.”
Tuberculosis is an extraordinarily complex disease exerting profound effects on

the health and economy of much of the world’s population. People in developing
countries are often infected as infants and harbor the microbe for many years until
the disease is reactivated in young adulthood. Estimates indicate that possibly one-
third of the world’s population and 15 million people in the United States carry the
TB bacillus.
Mycobacteriu
CHAPTER
m tuberculosis
19.5
Epidemiology and Transmission of Tuberculosis

Cases in the United States show a strong correlation with the age, sex, and recent immigration
history of the patient. The highest case rates occur in people over 65 years of age, as well as in
new immigrant populations from certain areas of Southeast Asia, Latin America, and Africa and in
AIDS patients. For recent trends in the epidemiology of tuberculosis, see 19.3 Making
Connections.
The agent of tuberculosis is transmitted almost exclusively by fine droplets of respiratory

mucus suspended in the air. The tubercle bacillus is very resistant and can survive for 8 months
in fine aerosol particles. Although larger particles become trapped in the mucus and expelled,
tinier ones can be inhaled into the bronchioles and alveoli. This effect is especially pronounced
among people sharing closed, small rooms with limited access to sunlight and fresh air. Factors
that significantly affect a person’s susceptibility to tuberculosis are inadequate nutrition,
debilitation of the immune system, poor access to medical care, lung damage, and genetics.
19.3
MAKING
CONNECTIO
NS
Mycobacteriu
CHAPTER
m tuberculosis
19.5
The Course of Infection and Disease

A clear-cut distinction can be made between infection with the tubercle
bacillus and the disease it causes. In general, humans are rather easily infected
with the bacillus but are resistant to the disease. Estimates project that only
about 5% to 10% of infected people actually develop a clinical case of
tuberculosis. Untreated tuberculosis progresses slowly and is capable of lasting
a lifetime, with periods of health alternating with episodes of morbidity. The
majority (85%) of TB cases are contained in the lungs, even though
disseminated tubercle bacilli can give rise to tuberculosis in any organ of the
body. The major clinical manifestations are primary tuberculosis, latent
(reactivation) tuberculosis, and disseminated (extrapulmonary) tuberculosis,
covered in the following sections and figure 19.16a
Mycobacteriu
CHAPTER
m tuberculosis
19.5
Initial Infection and Primary Tuberculosis

The minimum infectious dose for lung infection is around 10 cells. As part of the body’s
immune response the bacilli are phagocytosed by alveolar macrophages where they multiply
intracellularly. This period of hidden infection is asymptomatic or accompanied by mild fever, but
some cells escape from the lungs into the blood and lymphatics. After 3 to 4 weeks, the immune
system mounts a complex, cell-mediated assault against the bacilli. The large influx of
mononuclear cells into the lungs plays a part in the formation of specific infection sites called
tubercles.
Tubercles are granulomas with a central core containing TB bacilli and enlarged
macrophages,
and an outer wall made of fibroblasts, lymphocytes, and neutrophils (figure 19.16b). Although
this response further checks spread of infection and helps prevent the disease, it also carries a
potential for lung damage. Frequently, the centers of tubercles break down into necrotic, caseous
lesions that gradually heal by calcification when lung tissue is replaced by calcium deposits. The
response of T cells to M. tuberculosis proteins also causes a cell-mediated immune response
Mycobacteriu
CHAPTER
m tuberculosis
19.5

Mycobacteriu
CHAPTER
m tuberculosis
19.5

Mycobacteriu
CHAPTER
m tuberculosis
19.5
Latent and Recurrent Tuberculosis
Although the majority of TB patients recover more or less completely from the
primary infection or disease, live bacilli can remain latent and become reactivated
weeks, months, or years later, especially in people with weakened immunity. In
reactivated tuberculosis, tubercles filled with masses of bacilli expand and drain into
the bronchial tubes and upper respiratory tract. Gradually, the patient experiences
more severe symptoms, including violent coughing, greenish or bloody sputum, low-
grade fever, anorexia, weight loss, extreme fatigue, night sweats, and chest pain. It
is the gradual wasting of the body that accounts for an older name for tuberculosis
— consumption. Untreated reactivated disease has nearly a 60% mortality rate.
Mycobacteriu
CHAPTER
m tuberculosis
19.5
Extrapulmonary Tuberculosis
During the course of reactivated TB, the bacilli disseminate rapidly to sites other than the lungs.
Organs most commonly involved in extrapulmonary TB are the regional lymph nodes, kidneys, long
bones, genital tract, brain, and meninges. Because of the debilitation of the patient and the high load of
tubercle bacilli, these complications are usually grave.
Renal tuberculosis results in necrosis and scarring of the renal medulla and the pelvis, ureters, and
bladder. Genital TB often damages the reproductive organs in both sexes. Tuberculosis of the bone and
joints is a common complication. The spine is a frequent site of infection, though the hip, knee, wrist, and
elbow can also be involved. Degenerative changes can collapse the vertebrae, resulting in abnormal
curvature of the thoracic or lumbar regions. Neurological damage stemming from compression on nerves
can cause extensive paralysis and sensory loss.
Tubercular meningitis is the result of an active brain lesion seeding bacilli into the meninges. Over a
period of several weeks, the infection of the cranial compartment can create mental deterioration,
permanent retardation, blindness, and deafness. Untreated tubercular meningitis is invariably fatal, and
even treated cases can have a 30% to 50% mortality rate.
Mycobacteriu Clinical Methods of
CHAPTER Detecting Tuberculosis
m tuberculosis
19.5
Clinical Methods of Detecting Tuberculosis

Clinical diagnosis of tuberculosis traditionally includes some combination of
these
techniques:
1.tuberculin or immunologic testing

2.radiography (X rays) of the chest
3.direct identification of acid-fast bacilli (AFB) in sputum or some other
specimen
4.cultural isolation and identification
Final diagnosis of overt or latent TB cannot be made on a single test alone

Mycobacteriu Clinical Methods of Tuberculin Sensitivity
CHAPTER Detecting Tuberculosis and Testing
m tuberculosis
19.5
Tuberculin Sensitivity and Testing

Becauseinfection with the TB bacillus leadto delayed hypersensitivity to
tuberculoproteins, can for been an important way to screen
testing
populations for tuberculosis hypersensitivity has
infection. The tuberculin test, called the Mantoux test, involves
local injection of tuberculin, a purified protein derivative (PPD), taken from culture fluids of
M. tuberculosis. The injection is done intradermally into the forearm to produce an immediate
small bleb. After 48 and 72 hours, the site is observed for a red wheal called an
induration, which is measured and classified according to size (figure 19.17).
The current practices for interpreting tuberculin tests are focused on selected groups
known to have higher risk for tuberculosis. It is no longer a routine screening method among
populations of children or adults who are not within the target groups. The reasoning behind
this change is to allow more focused screening and to reduce expensive and unnecessary
follow-up tests and treatments. Guidelines for test groups and methods of interpreting tests
are listed in the following summary.
m tuberculosis
19.5
Category 1. Induration (skin reaction) that is equal HIV-negative intravenous drug

to or greater than 5 mm is classified as positive in users
Persons with medical conditions that put
persons who them at risk for progressing from latent TB
Have had contact with actively infected TB infection to active TB
patients P ersons who live or work in high-
Are HIV positive risk residences
Have past history of tuberculosis as determined New immigrants from countries with
through chest X rays high rates of TB
Are organ transplant recipients Children who have contact with members of
Are immunosuppressed for other reasons high-risk adult populations
Mycobacteriology laboratory personnel
Category 2. Induration that is equal to or greater
than 10 mm is classified as positive in persons who Category 3. Induration that is equal to or
greater
risk groups: who
than do
15 not
mm meet
is criteriaasin positive
classified categories
in 1 or
persons
are not in category 1 but who fit the following high-
m tuberculosis
19.5

A positive reaction in a person from one of the categories is fairly reliable evidence of
recent infection or a latent infection, but a diagnosis of TB should not be made based on this
result alone. Vaccination with the tuberculosis vaccine (BCG) can also cause a TB positive
result, so clinicians must weigh a patient’s history, especially among individuals who have
immigrated from countries where the vaccine is routinely given. Another cause of a false
positive reaction is the presence of an infection with a closely related species of
Mycobacterium.
A negative skin test usually indicates that ongoing TB infection is not present. In
some
cases, it may be a false negative, meaning that the person is infected but is not yet
reactive. One cause of a false negative test may be that it is administered too early in the
infection, requiring retesting at a later time. Subgroups with severely compromised immune
systems, such as those with AIDS, advanced age, and chronic disease, may be unable to
mount a reaction even though they are infected. Skin testing may not be a reliable
Mycobacteriu Clinical Methods of Tuberculin Sensitivity The In Vitro TB
CHAPTER Detecting Tuberculosis and Testing Test
m tuberculosis
19.5
The In Vitro TB Test

The CDC has accepted two new tests for aiding in TB diagnosis and ruling
out most false positives. Both the QuantiFERON-TB Gold test and the T-
SPOT TB test are indirect methods of detecting infection based on a blood
test. A fresh sample of blood is incubated with synthetic M. tuberculosis
proteins for about a day. If the blood contains lymphocytes with a prior
sensitivity to the tuberculoproteins, the cells will release interferon gamma.
The amount of this substance can be measured by machine. The advantage
to this test is that it is rapid, it is easy to read, it does not sensitize the patient
to TB (which tuberculin can do), and it is not affected by prior B C G
vaccination. This will make it particularly useful in ruling out TB in immigrants
who have been vaccinated.
Mycobacteriu
CHAPTER
m tuberculosis
19.5
Radiography and Tuberculosis

Chest X rays may be suggestive of—but are never diagnostic
of—TB. They may, however, be used to rule out the possibility
of pulmonary TB in a person who has a positive reaction to
the tuberculin skin test and no symptoms of disease. X-ray
films reveal abnormal radiopaque patches whose appearance
and location can be very indicative. Primary tubercular
infection presents the appearance of fine areas of infiltration
and enlarged lymph nodes in the lower and central areas of
the lungs. Secondary tuberculosis films show more extensive
infiltration in the upper lungs and bronchi and marked
tubercles (figure 19.18). Scars from older infections often
show up on X rays and can furnish a basis for comparison
with which to identify newly active disease.
Mycobacteriu
CHAPTER
m tuberculosis
19.5
Acid-Fast
Staining
Acid-fast staining of sputum or other specimens
may be used to detect Mycobacterium, with
several variations of the technique currently in use.
The Ziehl-Neelsen stain produces bright red acid-
fast bacilli (AFB) against a blue background.
Fluorescence staining shows luminescent yellow-
green bacilli against a dark background (figure
19.19). The fluorescent acid-fast stain is becoming
the method of choice because it is easier to read
and provides a more striking contrast.
Mycobacteriu
CHAPTER
m tuberculosis
19.5
Laboratory Cultivation and Identification

Mycobacterium tuberculosis infection is most accurately diagnosed by isolating and
identifying the causative agent in pure culture. Because of the specialized expertise and
technology required, this is not done by most clinical laboratories as a general rule. In the
United States, the handling of specimens and cultures suspected of containing the pathogen is
strictly regulated by federal laws
Diagnosis that differentiates between M. tuberculosis and other mycobacteria must be
accomplished as rapidly as possible so that appropriate treatment and isolation precautions
can be instituted. Cultures are incubated under varying temperature and lighting conditions to
clarify thermal and pigmentation characteristics and are then observed for signs of growth.
Several newer cultivation schemes have shortened the time to several days instead of the 6 to
8 weeks once necessary. Other identification techniques use DNA probes to detect specific
genetic markers and can confirm positive specimens early in the infection. Rapid diagnosis is
particularly important for public health and treatment considerations.
Mycobacteriu
CHAPTER
m tuberculosis
19.5
Management and Prevention of Tuberculosis

Treatment of TB involves administering drugs for a sufficient period of time to kill the bacilli in
the lungs, organs, and macrophages, usually 6 to 9 months in uncomplicated cases (but as
long as 24 months in more complex infections). Because many strains of M. tuberculosis are
resistant to at least one of the drugs commonly used for treatment, the most commonly
followed anti-TB chemotherapeutic regimen begins with an initial phase of four drugs:
isoniazid (INH)
rifampin (RIF)
ethambutol (EMB)
pyrazinamide (PZA)
taken daily for eight
weeks. After this, a
continuation phase
involves daily doses of
INH and RIF
Mycobacteriu
CHAPTER
m tuberculosis
19.5

A one-pill regimen called Rifater combines isoniazid, rifampin, and pyrazinamide,
and may be supplemented with ethambutol if needed. The simplicity of the one pill
regimen increases the rate of patient compliance, a common problem with anti-TB
therapy. In 2012 the first new drug in 40 years—bedaquiline (Sirturo)—was introduced
primarily for cases of multi- and extensively-drug-resistant tuberculosis. Clinicians
expect it to significantly reduce the spread of these dangerous strains of TB, but
severe side effects limit its use to those instances where no other drug combination is
effective. When evaluating the effectiveness of chemotherapy, the presence of a
negative culture or a gradual decrease in the number of AFB on a smear indicates
success. However, a cure will not occur if the patient does not comply with drug
protocols, which accounts for many relapses.
Mycobacteriu
CHAPTER
m tuberculosis
19.5

Although it is essential to identify and treat people with active TB, it is equally
important to seek out and treat those in the early stages of infection or at high risk of
becoming infected. Treatment groups are divided into tuberculin-positive “converters,” who
appear to have a latent infection, and tuberculin-negative people in high-risk groups such
as the contacts of tubercular patients. The standard treatment is a daily dose of INH for 9
months or RIF for 4 months. An equally effective, and far simpler, treatment for patients
who fit a specific criteria is a single dose of INH and rifapentine (RPT) once weekly for 12
weeks. This treatment is recommended for patients older than 12 years who are not
receiving antiretroviral treatment for HIV, not infected with a resistant strain of M.
tuberculosis, and not pregnant or planning to become pregnant during the course of
treatment. In the hospital, the use of UV lamps in air-conditioning systems and negative
pressure rooms to isolate TB patients can help control the spread of infection.
Mycobacteriu
CHAPTER
m tuberculosis
19.5
A vaccine based on the attenuated “bacille Calmette-Guérin” (BCG) strain

of M. bovis is often given to children in countries that have high rates of
tuberculosis. Studies have shown that the success rate of vaccinations is around
80% in children and less than that (20% to 50%) in adults. The length of protection
varies from 5 to 15 years. Because the United States does not have as high an
incidence as other countries, B C G vaccination is not generally recommended
except among certain health professionals and military personnel who may be
exposed to TB carriers. Vaccine trials using an attenuated strain of M. tuberculosis
are currently under way.
Mycobacteriu PATHOGEN
CHAPTER
m tuberculosis PROFILE #5
19.5
PATHOGEN PROFILE #5 (MYCOBACTERIUM

TUBERCOLOSIS
Mycobacterium
CHAPTER
leprae: The Leprosy
19.5
Bacillus
Mycobacterium leprae: The Leprosy Bacillus

Mycobacterium leprae, the cause of leprosy, was first detected by a Norwegian
physician named Gerhard Hansen, and it is sometimes called the Hansen bacillus
in his honor. The general morphology and staining characteristics of the leprosy
bacillus are similar to those of other mycobacteria, but it is exceptional in two
ways: (1) It is a strict parasite that has not been grown in artificial media or
human tissue cultures, and (2) it is the slowest growing of all the species.
Mycobacterium leprae multiplies within host cells in large packets called globi at
an optimum temperature of 30°C. Mycobacterium lepromatosis, a species first
described in 2008, is thought to be responsible for a few cases of a unique form
of leprosy endemic to Mexico.
Mycobacterium
CHAPTER
leprae: The Leprosy
19.5
Bacillus
Leprosy* is a chronic, progressive disease of the skin and nerves known for its
extensive medical and cultural ramifications. From ancient times, leprosy victims
were stigmatized because of their severe disfigurement and the belief that leprosy
was a divine curse. As if the torture of the disease were not enough, leprosy
patients once suffered terrible brutalities, including imprisonment under the most
gruesome conditions. The modern view of leprosy is more enlightened. We know
that it is not readily communicated and that it should not be accompanied by
social banishment. Because of the unfortunate connotations associated with the
term leper (a person who is shunned or ostracized), more acceptable terms such
as leprosy patient, Hansen’s disease patient, or leprotic are preferred.
Epidemiology
CHAPTER
and
19.5
Transmission of
Leprosy
Epidemiology and Transmission of Leprosy

The incidence of leprosy has been declining due to a worldwide control effort.
World Health Organization (WHO) estimates about 175,000 cases, mostly in
endemic areas of Asia, Africa, Central and South America, and the Pacific
islands. Leprosy is not restricted to warm climates, however, because it has
been reported in Siberia, Korea, and northern China. The disease is also
reported in a few limited locales in the United States, including parts of Hawaii,
Texas, Louisiana, Florida, and California. The total number of new cases
reported nationwide is from 50 to
100 per year, many of which are associated with recent immigrants. The
mechanism of transmission among humans is yet to be fully verified. Theories
propose that the bacillus is directly inoculated into the skin through contact with a
leprosy patient, that mechanical vectors are involved, or that inhalation of droplet
Epidemiology
CHAPTER
and
19.5
Transmission of
Leprosy
Although the human body was long considered the sole host and reservoir of the
leprosy bacillus, it is now clear that armadillos also harbor M. leprae and may
develop a granulomatous disease similar to leprosy. Although the risk of contracting
leprosy from armadillos is exceedingly low, zoonotic infection is thought to be
responsible for the 30 to 40 new cases of leprosy seen each year in U.S.-born
citizens who have never traveled to regions where the disease is prevalent.
Because the leprosy bacillus is not highly virulent, most people who come into
contact with it do not develop clinical disease. . As with tuberculosis, it appears
that health and living conditions influence susceptibility and the course of the
disease. An apparent predisposing factor is some defect in the regulation of T
cells. Mounting evidence also indicates that some forms of leprosy are associated
with a specific genetic marker.
Epidemiology
CHAPTER
and
19.5
Transmission of
Leprosy
Long-term household contact with leprotics, poor nutrition, and crowded conditions
increase the risks of infection. Many people become infected as children and harbor
the microbe through adulthood.
The Course of
CHAPTER
Infection and Disease
19.5
The Course of Infection and Disease
Once M. leprae has entered a portal of entry, macrophages successfully destroy

the bacilli, and there are no initial manifestations of infection. But in a small
percentage of cases, a weakened or slow macrophage and T-cell response leads
to intracellular survival of the pathogen. The usual incubation period varies from
2 to 5 years, with extremes of 3 months to 40 years. The earliest signs of
leprosy appear on the skin of the trunk and extremities as small, spotty lesions
colored differently from the surrounding skin (figure 19.20). In untreated cases,
the bacilli grow slowly in the skin macrophages and Schwann cells of peripheral
nerves, and the disease progresses to one of several outcomes.
The Course of
CHAPTER
19.5
Figure 19.20 Leprosy. (a) Tuberculoid

(paucibacillary) Infection often appears as
hypopigmented patches, especially in dark skinned
persons. (b) Borderline (multibacillary) leprosy is
the most common form of the disease.
Tuberculoid-like are present in
lesion
numbers, and peripheral nerves in the area greate
are
affected, causing weakness and a loss r of
sensation.
The Course of
CHAPTER
19.5
A useful rating system for leprosy was developed by D. S. Ridley and W. H.

Jopling. At the two extremes are tuberculoid leprosy (TL) and lepromatous
leprosy (LL) (table 19.3); and in between are borderline tuberculoid (BT),
borderline (BB), and borderline lepromatous (BL) leprosy. Patients can have
more than one form of leprosy simultaneously, and one type can progress to
another. Currently, epidemiologists at the CDC and World Health Organization
are transitioning to a system in which leprosy is classified as paucibacillary
(few bacteria found in skin scrapings, otherwise classified as tuberculoid or
borderline tuberculoid leprosy) or multibacillary (many bacteria found in skin
scrapings, corresponding to borderline, borderline lepromatous, or lepromatous
leprosy).
The Course of
CHAPTER
19.5

The Course of
CHAPTER
19.5
Tuberculoid (Paucibacillary) leprosy, the most superficial form, is characterized by

asymmetrical, shallow skin lesions containing very few bacilli (figure 19.20). Microscopically,
the lesions appear as thin granulomas and enlarged dermal nerves. Damage to these
nerves usually results in local loss of pain reception and feeling. This form has fewer
complications and is more easily treated than other types of leprosy.
Lepromatous (Multibacillary) leprosy is responsible for the disfigurations commonly

associated with the disease. It is marked by chronicity and severe complications due to
widespread dissemination of the bacteria. Leprosy bacilli grow primarily in macrophages in
cooler regions of the body, including the nose, ears, eyebrows, chin, and testes. As growth
proceeds, the face of the afflicted person develops folds and granulomatous thickenings,
called lepromas, which are caused by massive intracellular overgrowth of M. leprae (figure
19.21)
The Course of
CHAPTER
19.5

The Course of
CHAPTER
19.5
Advanced LL causes a loss of sensitivity that predisposes the patient to trauma and
mutilation, secondary infections, blindness, and kidney or respiratory failure. Diffuse
lepromatous leprosy, a unique form of the disease endemic to Mexico, is thought to
be caused by M. lepromatosis, a species first described in 2008.
The condition of borderline (multibacillary) leprosy patients can progress in either

direction along the scale, depending upon their treatment and immunologic
competence. The most severe effect of intermediate forms of leprosy is early
damage to nerves that control the muscles of the hands and feet. The subsequent
wasting of the muscles and loss of control produce drop foot and claw hands
(figure 19.22). Sensory nerve damage can lead to trauma and loss of fingers and
toes.
The Course of
CHAPTER
19.5

CHAPTER Diagnosing Leprosy
19.5
Diagnosing Leprosy
Leprosy is diagnosed by a combination of symptomatology, microscopic

examination of lesions, and patient history. A simple yet effective field test in
endemic populations is the feather test. A skin area that has lost sensation and
does not itch may be an early symptom. Numbness in the hands and feet, loss of
heat and cold sensitivity, muscle weakness, thickened earlobes, and chronic
stuffy nose are additional evidence. Laboratory diagnosis relies upon the
detection of acid-fast bacilli in smears of skin lesions, nasal discharges, and
tissue samples. Knowledge of a patient’s prior contacts with leprotics also
supports diagnosis. Laboratory isolation of the leprosy bacillus is difficult and not
ordinarily attempted.
CHAPTER Treatment and
19.5 Prevention of Leprosy
Treatment and Prevention of Leprosy

Leprosy can be controlled by drugs, but therapy is most effective when started before
permanent damage to nerves and other tissues has occurred. Because of an increase in
resistant strains, multidrug therapy is necessary. Tuberculoid (paucibacillary) leprosy
can be managed with rifampin and dapsone for 12 months. Lepromatous (multibacillary)
leprosy requires a combination of rifampin, dapsone, and clofazimine until the number of
AFB in skin lesions has been substantially reduced (requiring up to 2 years).
Preventing leprosy requires constant surveillance of highrisk populations to discover

early cases, chemoprophylaxis of healthy persons in close contact with leprotics, and
isolation of leprosy patients. No vaccine for leprosy is currently available, but it is
thought that the bacille Calmette-Guérin (BCG) vaccine that is used in many countries
to prevent tuberculosis also provides some protection against infection with the leprosy
bacillus.
Infections by
CHAPTER Nontuberculous
19.5
Mycobacteria
(NTM)
Infections by Nontuberculous Mycobacteria (NTM)

For many years, most mycobacteria were thought to have low pathogenicity for humans.
Saprobic and commensal species are isolated so frequently in soil, drinking water, swimming
pools, dust, air, raw milk, and even the human body that both contact and asymptomatic
infection appear to be widespread. However, the recent rise in opportunistic and healthcare-
associated mycobacterial infections has demonstrated that many species are far from harmless.
Disseminated Mycobacterial Infection in AIDS Bacilli of the Mycobacterium avium complex

(MAC) frequently cause secondary infections in AIDS patients with low T-cell counts. These
common soil bacteria usually enter through the respiratory tract, multiply, and rapidly
disseminate. In the absence of an effective immune counterattack, the bacilli flood the body
systems, especially the blood, bone marrow, bronchi, intestine, kidney, and liver. Recommended
treatment is combined drug therapy using clarithromycin and ethambutol, occasionally
supplemented with rifabutin. This therapy usually has to be given for several months or even
Infections by
19.5
Mycobacteria
(NTM)
Nontuberculous Lung Disease Pulmonary infections caused by commensal mycobacteria

have symptoms like a milder form of tuberculosis, but they are not communicable.
Mycobacterium kansasii infection is endemic to urban areas in the midwestern and
southwestern United States and parts of England. It occurs most often in adult White males
who already have emphysema or bronchitis. Mycobacterium fortuitum complex causes
postsurgical skin and soft-tissue infection and pulmonary complications in
immunosuppressed patients.
A form of TB caused by M. bovis was once quite common but is now extremely rare due to
efforts to control the disease in cattle. Occasional clusters of cases have appeared, all
probably from imported cheese made with unpasteurized milk.
Infections by
19.5
Mycobacteria
(NTM)
Miscellaneous Mycobacterial Infections An infection by M. marinum has been labeled

fish tank granuloma because of the strong relationship between the disease and work
around aquariums. Interestingly, the same disease was referred to as swimming pool
granuloma for many years but consistent chlorination of pools has led to its eradication in
pools. The disease begins when M. marinum, found in both fresh and salt water, enters a
cut or scrape. A nodule begins to form, which then enlarges, ulcerates, and drains (figure
19.23). The granuloma can clear up spontaneously, but it can also persist and require long-
term treatment. Mycobacterium scrofulaceum causes an infection of the cervical lymph
nodes in children living in the Great Lakes region, Canada, and Japan Infection is
apparently associated with ingestion of food or milk and generally affects the oral cavity
and cervical lymph nodes. In most cases the infection is without complications but certain
children develop scrofula, in which the affected lymph nodes ulcerate and drain.
Infections by
19.5
Mycobacteria
(NTM)
Infections by
19.5
Mycobacteria
(NTM)
Research on a chronic intestinal syndrome called Crohn’s disease has uncovered a strong
association between the disease and a form of Mycobacterium paratuberculosis. When
technicians used a P C R technique to analyze the DNA of colon specimens, it was found
that 65% of Crohn’s disease patients tested positive for M. paratuberculosis. Further
studies have shown that this bacterium is found in cow’s milk, which may well be the
source of infection.
19.
6
19.6
Actinomycetes:
Filamentous
Bacilli
19.
6
A group of bacilli closely related to Mycobacterium are the

pathogenic
actinomycetes.
may be acid-fast.These
Certainare nonmotile
members filamentous
produce rods that growth
a mycelium-like
and spores reminiscent of fungi. They also produce chronic
granulomatous diseases. The main genera of actinomycetes involved
in human disease are Actinomyces and Nocardia.
19.
6
Actinomycosis
Actinomycosis is an endogenous infection of the cervicofacial,
thoracic, or abdominal regions by species of Actinomyces living
normally
in the human oral cavity, tonsils, and intestine. The cervicofacial form
of disease can be a common complication of tooth extraction, poor
oral hygiene, and rampant dental caries. The lungs, abdomen, and
uterus are also sites of infection.
19.6
Cervicofacial disease is caused by A.

israelii, which enters a damaged area of
the oral mucous membrane and begins
to multiply there. Diagnostic signs are
swollen, tender nodules in the neck or
jaw that give off a discharge containing
macroscopic (1–2 mm) sulfur
granules
19.
6
In most cases, infection remains localized, but bone invasion and

systemic spread can occur in people with poor health. Thoracic
actinomycosis is a necrotizing lung disorder that can project through the
chest wall and ribs.
Abdominal actinomycosis is a complication of burst appendixes, gunshot
wounds, ulcers, or intestinal damage. Uterine actinomycosis has been
increasingly reported in women using intrauterine contraceptive devices.
Infections are treated with surgical drainage and drug therapy with penicillin,
amoxicillin, erythromycin, or doxycycline.
19.
6
Compelling evidence indicates that oral actinomyces play a strategic role in

the development of plaque and dental caries. Studies of the oral environment
show that A. viscosus and certain oral streptococci are the first microbial
colonists of the tooth surface. Both groups have specific tooth-binding powers
and can adhere to each other and to other species of bacteria (see chapter
21).
19.
6
Nocardiosis
Nocardia* is a genus of bacilli widely distributed in the soil. Most species are
not infectious, but N. brasiliensis is a primary pulmonary pathogen, and N.
asteroides and N. caviae are opportunists. Nocardioses fall into the
categories of pulmonary, cutaneous, or subcutaneous infection. Most cases
in the United States are reported in patients with deficient immunity, but a
few occur in normal individuals.
19.6
Pulmonary nocardiosis is a form of bacterial

pneumonia with pathology and symptoms
similar to tuberculosis. The lung develops
abscesses and nodules and can
consolidate. Often, the lesions extend to
the pleura and chest wall and disseminate
to the brain, kidneys, and skin
Figure 19.25 Nocardiosis.
This case of pulmonary disease
has extended from the shoulders
and trunk to the skin of the
upper arm.
CASE
STUDY
CASE STUDY PART

2 investigation initiated in response to the illnesses was one of thousands, big and small, done every
The
year to track down the source of an outbreak. The first step in such an inquiry is decidedly low-tech, with
investigators quizzing ill persons as to their actions over the weeks leading up to the outbreak, searching
for behaviors that could have put them at risk for infection; with Listeria, the questioning centered on food
and drink. Investigators found that 93% of ill persons reported consuming fresh cantaloupe in the month
before falling ill. This was unusual, as Listeria is generally associated with unpasteurized milk, soft
cheeses, and processed meats, although outbreaks in 2009 and 2010 had been linked to sprouts and
celery.
Investigators from the Colorado Department of Public Health and Environment collected all available
cantaloupes from local markets and from patients’ homes. Several patients specifically reported eating
“Rocky Ford” cantaloupes, which are grown only in the Rocky Ford region of Colorado. These were
traced back to Jensen Farms and had been shipped from July 24 through September 10.
CASE
STUDY
CASE STUDY PART

2
A second front in the investigation centered on molecular typing of the Listeria bacterium, generating a
DNA profile—or fingerprint— of the strain responsible for infection. This phase of the effort was carried
out by PulseNet, a national network of laboratories that use a DNA profiling technique called pulsed-field
gel electrophoresis (PFGE) to distinguish strains at the molecular level. PulseNet analysis found five
strains of Listeria monocytogenes associated with the outbreak. A team headed by FDA inspectors began
an investigation of Jensen Farms, a fixture in southeastern Colorado, where four generations had grown
cantaloupe, hay, and alfalfa. The current owners, Ryan and Eric Jensen, had made a number of changes
to a packing shed just prior to the 2011 harvest. Investigators discovered several problems that may have
contributed to the outbreak. Among them were the following:
CASE
STUDY
CASE STUDY PART

■A refrigeration drain line allowed water to pool directly under packing facility equipment, and testing of
2 water revealed the presence of one of the outbreak strains of Listeria monocytogenes
the
■ The floor of the packing facility was not easily cleanable, creating a refuge for bacteria.
■Jensen Farms had recently installed packing equipment that had previously been used in the harvesting
of potatoes. This created a potential problem because potatoes, unlike cantaloupe, are generally cooked
prior to being consumed. The equipment had visible dirt and corrosion, and was also designed in a
manner that prevented adequate cleaning.
■Removal of an initial antimicrobial wash meant that a single contaminated melon could spread bacteria
to other packing equipment and potentially cross-contaminate every melon that passed through the
facility.
CASE
STUDY
CASE STUDY PART

2
Jensen Farms immediately halted sales of cantaloupes and a nationwide recall was instituted, but this
was of no help to those already affected. Nationwide, 147 persons reported illness, 143 of these were
hospitalized, and 33 deaths were attributed to the outbreak, making it the third deadliest food-related
outbreak in U.S. history. Mike Hauser and Paul Schwarz, along with Michelle and Kendall Wakely, fairly
represent those hit hardest by the outbreak. The median age of those infected was 78, and those who
died had a median age of 81. Seven cases were diagnosed in newborns or pregnant women, and one
miscarriage was reported. An onslaught of medical claims and civil suits related to the outbreak led
Jensen Farms to file for bankruptcy in May 2012; Eric and Ryan Jensen pleaded guilty to misdemeanor
charges in October 2013. Each received five years probation and six months home detention. Each also
was ordered to pay $150,000 in restitution and perform 100 hours of community service.
■ Explain the importance of P F G E subtyping of Listeria in this case.

■Milk and meat are kept cool during processing in order to slow the growth of E. coli. Would cooling be
an effective method of controlling Listeria ?
Chapter 19
THANK
YOU
Group 5
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Chapter 19

Microbiology and Parasitology

Don’t ever let someone tell you, you can’t do

Microbiology and Parasitology

19.1 Medically Important Gram-Positive Bacilli

19.2 Gram-Positive Spore-Forming Bacilli

General Characteristics of the Genus Bacillus

Bacillus anthracis and Anthrax

The pathologic effect of these events are wide- capillary

Other Bacillus Species Involved in Human Disease

The Genus Clostridium

The Genus Clostridium

The Role of Clostridia in Infection and Disease

The incidence of neonatal tetanus—predominantly the result of an infected

The Course of Infection and

Tetanospasmin alters the usual

Lockjaw confers the bizarre appearance of risus sardonicus (sarcastic grin)

Death is most often due to paralysis of the respiratory muscles and

Treatment and Prevention of Tetanus

Tetanus is one of the world’s most preventable diseases, chiefly

Clostridium difficile Infection

It produces enterotoxins that trigger

More severe infections are treated with oral vancomycin or metronidazole

In the clinical setting, stringent precautions are necessary to prevent the

Epidemiology of Botulinum Food

Botulism is an intoxication usually associated with eating improperly

One of the most recent outbreaks of botulism traced to a commercial source

Bacterial growth may not be evident in the

Neuromuscular symptoms first affect the muscles of the head and

Later symptoms are descending muscular paralysis and respiratory

Infant and W ound Botulism

The immature state of the neonatal intestine and resident microbiota

In wound botulism, the spores enter a wound or puncture much as in

Treatment and Prevention of Botulism

Clostridium perfringens also causes enterocolitis similar to that caused by C.

Differential Diagnosis of Clostridial Species

The non-spore-forming gram-positive bacilli are a mixed group of genera

Listeria monocytogenes ranges in morphology

Epidemiology and Pathology of Listeriosis

Recent epidemics have spurred an in-depth investigation into the

A predisposing factor in listeriosis seems to be the weakened condition of

However, listeriosis in immunocompromised patients, fetuses, and

Diagnosis and Control of Listeriosis

Ampicillin and gentamicin are the first choices, followed by

Epidemiology, Pathogenesis, and Control

The common portal of entry in human

Although the lesions usually heal without complications, rare cases of

The Gram-Positive Bacilli of Medical Importance

The Gram-Positive Bacilli of Medical Importance

The irregular non-spore-forming bacilli tend to be pleomorphic and to stain

The Gram-Positive Bacilli of Medical Importance

Although several species of Corynebacterium* are found on the human body,

The Gram-Positive Bacilli of Medical Importance

For hundreds of years, diphtheria* was a significant cause of morbidity and

The Gram-Positive Bacilli of Medical Importance

The Gram-Positive Bacilli of Medical Importance

Figure 19.13 Clinical aspects of diphtheria. (a)

The Gram-Positive Bacilli of Medical Importance

Diphtherotoxin and Toxemia Although infection is necessary for disease, the

The Gram-Positive Bacilli of Medical Importance

The Gram-Positive Bacilli of Medical Importance

Figure 19.13 (b) Respiratory diphtheria