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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 +RodSpore formingObligate aerobicFacultative intracellularEncapsulated (Capsule could be demonstrated

during growth in infected animals)Non-motileSpores 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 animalsThe 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 antigenis 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 factoris 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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Cutaneous Forms : Cutaneous anthrax is typically caused when Bacillus

anthracis spores enter through cuts on the skin. This form of Anthrax is found most commonly when humans

handle infected animals and/or animal products Cutaneous anthrax is rarely fatal if treated because the infection

area is limited to the skin, preventing the lethal factor, edema factor, and protective antigen from entering and destroying a vital organ.

Without treatment, about 20% of cutaneous skin infection cases progress to toxemia and death.

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/cutaneous-anthrax/overview.html

A skin lesion caused by anthrax

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Cutaneous Forms

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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 chillsSwelling of neck or neck glandsSore throatPainful swallowingHoarsenessNausea and vomiting, especially bloody vomitingDiarrhea or bloody diarrheaHeadacheFlushing (red face) and red eyesStomach painFaintingSwelling 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

SymptomsFlu-like symptoms, such as sore throat, mild fever, fatigue and muscle aches, which may last a few hours or daysMild chest discomfortAs the disease progresses, you may experience:High feverTrouble breathingShockMeningitis — 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

Gastrointestina

l 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 Pictures

B.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/medical-microbiology-ii/summary-of-bacterial-pathogens/bacillus-anthracis

http://www.cdc.gov/anthrax/ http://www.hpa.org.uk/webw/HPA

web&Page&HPAwebAutoListName/Page/1204619483853

References