The document provides a comprehensive overview of anthrax, a zoonotic disease caused by the bacterium Bacillus anthracis, including its history, epidemiology, transmission methods, and clinical features. It discusses the disease's pathogenesis, symptoms for its different forms (cutaneous, gastrointestinal, and inhalation anthrax), and the recommended treatments and preventive measures. Additionally, the document highlights the virulence factors of B. anthracis and outlines its diagnosis and the historical context of anthrax infections.

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Anthrax

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Contents
 1 History
 2 Etiology/Bacteriology
 2.1 Taxonomy
 2.2 Description
 3 Pathogenesis
 3.1 Transmission
 3.2 Infectious dose, incubation, and colonization
 3.3 Epidemiology
 3.4 Virulence factors
 4 Clinical features
 5 Diagnosis
 6 Treatment
 7 Prevention
 8 Host Immune Response
 9 Bioterrorism
 10 References

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Introduction
 Anthrax is a zoonotic disease (could be transferred from animals to
humans) caused by the spore-producing bacterium Bacillus anthracis.
 Bacillus anthracis bacterial spores are soil-borne.
 Because of their long lifespan, spores are present globally and remain at
the burial sites of animals killed by anthrax for many decades
 People can get anthrax if they are exposed to the spores.
 Is anthrax contagious?
Anthrax is not contagious, which
means it does not spread from
person to person the way the flu
can spread between family
members or classmates.
Variations in endospore
morphology: (1, 4) central
endospore; (2, 3, 5) terminal
endospore; (6) lateral
endospore

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Characteristics
Gram +
Rod
Spore forming
Obligate aerobic
Facultative intracellular
Encapsulated (Capsule could be demonstrated during growth in infected
animals)
Non-motile
Spores are formed in culture, dead animal's tissue but not in the blood of
infected animals.
Spores are oval and centrally located
 Spores remain viable in soil for decades.
· In World War II in Scotland spores were exploded.
· Survived for >40 years and were eradicated in 1987
· Changing environmental conditions (temp. rain etc.) help in survival
and multiplication.
Bacillus anthracis Reservoirs
 Humans (not normal flora)
 Animals (primarily horses, cattle,
sheep and swine)
 Soil (primarily spores)

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Anthrax has been described since antiquity. Stories of anthrax
plague appear in the Bible and the ancient Greeks described the
cutaneous infection as coal-like (anthrakites) in appearance. The
Roman poet Virgil also discussed the disease in domestic
animals. Anthrax continued to affect domestic animals and
humans in the Middle Ages and was referred as "woolsorters'
disease" in England due to mill workers contracting the disease
from sheep wool. Anthrax cases in the 20th century decreased
significantly due to vaccination of animals
The discovery of Bacillus anthracis is credited to Pollender,
Rayer and Davaine. Robert Koch proved that the anthrax bacillus
caused the disease. Koch did this by removing anthrax bacilli
from the spleens of mice that had died from the disease and
injected the blood into healthy mice, which killed the previously
healthy mice. This illustrated the disease could be passed by
blood from infected animals. He also created pure cultures of the
bacilli and showed that this also caused disease. These
experimnts served as the prototype for Koch's postulates.
History Taxonomy
 Domain: Bacteria
 Phylum: Firmicutes
 Class: Bacilli
 Order: Bacillales
 Family: Bacillaceae
 Genus: Bacillus
 Species: anthracis

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B. anthracis
pathogenesis
begins by the
spores entering a
skin abrasion,
lungs, or
intestines.
There, the spores
are ingested by
macrophages and
brought to lymph
nodes.
The bacteria
germinate in the
lymph nodes or
mediastinum, in
the case of
inhalation
anthrax.
Pathogenesis

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 The most common way a human
can contract anthrax is being in
contact with infected animal
products
 Herbivore grazing animals can
commonly contract anthrax
because anthracis lives in the
soil
 A person may get anthrax by
inhaling the spores from animal
products, such as wool, have an
open abrasion on the skin be
exposed to the spores, or eating
undercooked meat from an
animal that was infected
 Anthrax cannot be spread
person-to-person.
Transmission

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The infectious dose of B. anthracis is not entirely clear. Some suggest 100
spores will cause infection while other analyses have shown as few as 1-3
spores can cause infection. For inhalation anthrax, the infectious dose can be
8-50,000 spores.
 The incubation time also depends on what type of anthrax is contracted
a) For inhalation anthrax, the incubation period is 2-5 days.
b) Cutaneous anthrax will start to manifest symptoms within 2-3 days
with some cases being as short as 12 hours
c) Gastrointestinal anthrax is much more rare and the incubation time
isn't known.
Infectious dose,
incubation, and
colonization
If infected with inhalation anthrax, the
spores are deposited in the alveolar spaces
and then transported to mediastinal lymph
nodes. After the spores germinate the
vegetative bacteria will spread to the blood
and lymph and cause septecimia
For ingested and cutaneous anthrax,
the spores enter through a break in the
skin or a break in the mucosa of the
intestines. They are engulfed by
macrophages, where they germinate
and then extracellular replication will
occur. During this replication phase,
the capsule and toxin begin to be
secreted which will cause symptoms
and the disease

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 Most inhalation anthrax cases have occured in the
factory setting when workers are exposed to
contaminated animal products, like wool.
 Inhalation anthrax is very rare in the United States due
to vast vaccination of domesticated livestock.
 Gastrointestinal anthrax is the rarest form of anthrax,
and in the United States there has only been two reported
cases. In 2010, the Philippines had a 400 person outbreak
of gastrointestinal anthrax from eating meat from a dead
infected caribou
 The largest epidemic to date happened in Zimbabwae
between 1979-1985 when 10,000 people contracted
cutaneous anthrax.
Epidemiology

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 Bacillus anthracis has two components to
its virulence
 The toxin it secrets as well as its
capsule. The capsule is composed of D-
glutamyl polypeptide
 Plasmid pXO2 is involved in the formation
of the capsule
 The capsule prevents host phagocytosis
when B. anthracis is in its vegetative
form.
 Plasmid pXO1 is responsible for the toxin
released
 The toxin has three proteins: the edema
factor, lethal factor, and protective
antigen.
Virulence factors

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The protective antigen
is a binding domain that allows the toxins
(edema and lethal factors) to enter host
cells.
Lethal factor
 causes immunosuppressive effects as well
as damage endothelial cell function and
causes cell apoptosis
 also disrupts downstream signaling, which
is important in normal cell functioning.
Edema factor
is a potent adenyl cyclase and works additively
with lethal factor. EF causes increase cAMP
production in infected cells and also has
immunosuppressive effects like LF.
Virulence factors

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Symptoms
The symptoms of anthrax
depend on the type of
infection and can take
anywhere from 1 day to
more than 2 months to
appear
 small blisters or
bumps
 (ulcer) with a black
center
 Swelling of
abdomen(stomach)
 Diarrhea or bloody diarrhea
Bloody discharge from
body orifices

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Symptoms:
 A raised, itchy bump resembling an insect bite
that quickly develops into a painless sore with a
black center
 Swelling in the sore and nearby lymph glands
Types of Anthrax
Treatment:
Cutaneous anthrax is treated with antibiotics, most
often doxycycline or ciprofloxacin
http://www.nytimes.com/health/guides/disease/cutane
ous-anthrax/overview.html
A skin lesion caused by
anthrax

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 Gastrointestinal anthrax
 Gastrointestinal infection in humans is most often caused by
consuming anthrax-infected meat
 Lesions have been found in the intestines and in the mouth
and throat. After the bacterium invades the bowel system, it
spreads through the bloodstream throughout the body, while
also continuing to make toxins.
Treatment:
Antibiotics and supportive anthrax treatment can
cure the disease; however, gastrointestinal anthrax
results in death in 25 to 60 percent of cases.
Types of Anthrax
Symptoms:
Fever and chills
Swelling of neck or neck glands
Sore throat
Painful swallowing
Hoarseness
Nausea and vomiting, especially bloody
vomiting
Diarrhea or bloody diarrhea
Headache
Flushing (red face) and red eyes
Stomach pain
Fainting
Swelling of abdomen (stomach)

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 Inhalation form :
Inhalation anthrax is an uncommon type of anthrax caused by breathing
in the anthrax bacteria or spores. Inhalation anthrax is also known as:
 Pulmonary anthrax
 Pneumonic anthrax
 Respiratory anthrax.
Types of Anthrax
Symptoms
Flu-like symptoms, such as sore throat,
mild fever, fatigue and muscle aches,
which may last a few hours or days
Mild chest discomfort
As the disease progresses, you may
experience:
High fever
Trouble breathing
Shock
Meningitis — a potentially life-
threatening inflammation of the brain
and spinal cord

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Mechanism of Anthrax Toxins:
 Anthrax toxin is a three-protein exotoxin secreted by virulent strains of
the bacterium Bacillus anthracis
 Anthrax toxin is composed of a cell-binding protein, known as
protective antigen (PA), and two enzyme components, called edema
factor (EF) and lethal factor (LF).
 These three protein components act together to impart their
physiological effects.
 The entry of toxin into cells begins with the recognition of a recently
identified cellular receptor in the plasma membrane by PA. Proteolytic
cleavage of cell-bound PA creates a smaller fragment that then
multimerizes into a pore-like structure in the plasma membrane.
 The LF and EF proteins bind to the PA pre-pore, followed by
internalization of the entire structure through receptor-mediated
endocytosis
 In the endosomal compartment, the acidic pH causes a
conformational change that inserts PA fragments and releases LF and
EF into the cytoplasm
 In the cytoplasm, LF acts as a protease that cleaves MAP kinase
kinase (MAPKK 1 and MAPKK 2), inhibiting pathways that rely on this
kinase family and causing cell death
 Edema factor is an adenylate cyclase that inhibits the immune
response, including phagocytosis by macrophages.
 Several potential mechanisms could be used to block anthrax toxin
action, one of which was demonstrated by the design of a multivalent
protein inhibitor of toxin interaction with PA.

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Mechanism of Anthrax Toxins

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I. Cultural Characteristics:
•Blood Agar and Nutrient Agar are commonly used to
cultivate the bacilli. Plates are incubated aerobically at
37 oC
Diagnosis
On blood agar plates
•Colonies have irregular borders and are non-hemolytic.
On nutrient agar
•They are described as "Medusa head" or "Comet tail".

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Cutaneous
Anthrax
• Swab samples
from cutaneous
lesions
Pulmonary
Anthrax
• Sputum and blood
Gastrointestinal
Anthrax
• . Gastric aspirate,
feces and blood
Microscopy
Diagnosis Samples
Gram stain for Bacilli demonstration
MacFadyean's stain,
showing capsulate B.
anthracis
Spore stain for spore
demonstration

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Laboratory PicturesB.anthracis capsule production
on bicarbonate agar
B.anthracis close up of
colonies on blood agar India ink visualisation ofB.anthracis capsule
Histopathology slide
ofB.anthracis in the
meninges

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Treatment
 If anthrax is confirmed, antibiotics
should be administered.
 The CDC recommends
ciprofloxacin and doxycycline
 f anthrax meningitis is suspected,
doxycycline shouldn't be used
because it does not penetrate the
central nervous system very well.
 Pregnant or breastfeeding women
can use amoxicillin.
 For inhalation anthrax, it is
recommended to use multi-drug
therapy, such as vancomycin, with
the chosen antibiotic

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Prevention

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 http://microbewiki.kenyon.edu/index.php/Anthrax
 https://sites.google.com/site/allmicrobiologysite/medic
al-microbiology-ii/summary-of-bacterial-
pathogens/bacillus-anthracis
 http://www.cdc.gov/anthrax/
 http://www.hpa.org.uk/webw/HPAweb&Page&HPAwebAut
oListName/Page/1204619483853
References