Anthrax

Anthrax is a rare infectious disease caused by Bacillus anthracis, a gram-positive spore-forming bacterium that is found in soil. Human infection usually results from contact with infected livestock or infected animal products (e.g., wool or meat). B. anthracis spores have also been weaponized for biological warfare/terrorism. Depending on the route of entry, three distinct clinical syndromes can occur: inhalation anthrax, cutaneous anthrax, and gastrointestinal anthrax. Cutaneous anthrax (the most common form) presents initially as a papular lesion, which later becomes vesicular, and eventually forms a necrotic eschar. Inhalation anthrax results in hemorrhagic mediastinitis and presents with fever, acute, nonproductive cough, retrosternal chest pain, and/or pleural effusion. Gastrointestinal anthrax, which is very rare, causes gastrointestinal ulceration, which results in hematemesis and/or bloody diarrhea. The diagnosis of anthrax is confirmed by the microscopic evidence of B. anthracis. Mortality is high but swift treatment with antibiotics (e.g., fluoroquinolones, linezolid, meropenem) can increase survival. Prognosis of cutaneous anthrax is usually better than that of inhalation and gastrointestinal anthrax.

• Global distribution: Anthrax is endemic in agricultural regions of the USA, Canada, Central and South America, southern and eastern Europe, central and southwest Asia, and sub-Saharan Africa.
• Incidence: 0–2 cases per year
• Sex: ♂ > ♀

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Epidemiological data refers to the US, unless otherwise specified.

• Pathogen: Bacillus anthracis
  • Gram-positive, spore-forming, nonmotile rod
  • Edge of colony shows irregular comma-shaped outgrowths on blood agar (also referred to as Medusa head).
  • Spores of B. anthracis can remain viable for decades.
  • Anthrax is a zoonotic infection that primarily infects cows, goats, and sheep.
• Transmission
  • Human infection occurs following exposure to B. anthracis or its spores (e.g., inhalation), usually as a result of contact with infected animals or infected animal products (e.g., wool, hide, meat).
  • Bioterrorism or biological warfare: exposure to weaponized B. anthracis or its spores. An attack using aerosolized anthrax could infect a large number of individuals and cause many casualties, especially if an antibiotic-resistant strain was used.
  • Person-to-person transmission is rare, but cases of person-to-person transmission of cutaneous anthrax have been reported.

Anthrax infection is an occupational hazard for people who handle livestock and process potentially infected animal materials such as wool or meat.

Virulence factors

• Antiphagocytic capsule
  • B. anthracis is the only bacterium that is capable of forming a polypeptide capsule
  • Contains poly-D-glutamate
• Anthrax toxin: responsible for the local and systemic manifestations of anthrax; made up of A and B subunits
  • The A subunit has 2 components:
    • EF (edema factor); : binds to calcium and calmodulin and gains adenylate cyclase activity → ↑ cAMP → cell edema
    • LF (lethal factor): a metalloprotease that destroys MAPKK (mitogen-activated protein kinase kinase; ) → cell death
  • The B subunit (PA; anthrax toxin protective antigen); binds to endothelial receptors and facilitates entry of the A subunit into the host cell.

Infection

1. Local germination of B. anthracis spores and multiplication of bacteria
2. Spreading to local/regional lymph nodes
3. Bacteremia → systemic spread

Depending on the route/mechanism of infection, one or more of three anthrax subtypes may occur.

Systemic spread is common in inhalational and gastrointestinal anthrax. It is less common in cutaneous anthrax (5–10% of cases).

Perform a lumbar puncture in all patients with clinical features of systemic involvement to rule out meningitis.

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• Lethality
  • With antibiotic treatment: < 1% in cutaneous anthrax, ∼ 50% in inhalation anthrax, and ∼ 40% in gastrointestinal anthrax
  • Without antibiotic treatment: ∼ 20% in cutaneous and > 90% in inhalational anthrax

Gastrointestinal anthrax and inhalational anthrax are rare but have a particularly poor prognosis, even with antibiotic treatment!

• AVA (anthrax vaccine adsorbed) is the only FDA-approved vaccine that is available for active immunization against anthrax in the US.
  • Pre-exposure prophylaxis : AVA
  • Post-exposure prophylaxis : AVA along with antibiotics (ciprofloxacin or doxycycline)
• AVA is contraindicated in children < 18 years, adults > 65 years, and pregnant/lactating women. In these groups, antitoxin therapy with raxibacumab, obiltoxaximab, or anthrax immunoglobulin is indicated instead of AVA.

Anthrax is a notifiable disease. It is also categorized as a category A bioweapon hazard by the CDC.

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