• Clinical science

Anthrax

Abstract

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.

Epidemiology

  • 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: >

Epidemiological data refers to the US, unless otherwise specified.

Etiology

  • 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, usually as a result of contact with infected animals or infected animal products (e.g., wool, hide, meat)
    • Weaponized anthrax: infection resulting from exposure to weaponized anthrax spores (from an act of bioterrorism or biological warfare)
    • Person-to-person transmission typically does not occur.
  • The clinical manifestations of anthrax depend on the site of entry of B. anthracis. (see “Clinical features” below)

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

Pathophysiology

  • Virulence factors
    • Antiphagocytic capsule (containing poly-D-glutamate)
    • Anthrax toxin: responsible for the local and systemic manifestations of anthrax
      • Anthrax toxin is made up of A and B subunits.
        1. B subunit binds to endothelial receptors → A fragment of B subunit is removed by the host cell's protease enzyme → activation of B subunit → components of the A subunit bind to the B subunit bindsthe B subunit facilitates entry of the A subunit into the host cell.
        2. The A subunit has 2 components:
          • EF (edema factor): EF binds to calcium and calmodulin and gains adenylate cyclase activity → cAMP → cell edema
          • LF (lethal factor): : LF is a metalloprotease which destroys MAPKK (mitogen-activated protein kinase) cell death
  • Infection
    1. Local germination of B. anthracis spores and multiplication of bacteria
    2. Spread to local/regional lymph nodes
    3. Bacteremia → systemic spread

Clinical features

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

Cutaneous anthrax Inhalation anthrax Gastrointestinal anthrax
Relative frequency
  • ∼ 95%
  • ∼ 5%
  • < 1%

Route of entry

  • Skin contact
  • Inhalation
  • Ingestion
Incubation period
  • Typically 5–7 days
  • Typically 1–3 days
  • 2–5 days
Clinical features
  1. Prodromal phase (1–6 days): nonspecific symptoms
  2. Fulminant phase: substernal chest pain, high-grade fever, progressive dyspnea, hypoxia, shock, mediastinal widening due to hemorrhagic mediastinitis
  • Nausea, vomiting
  • Abdominal pain
  • Severe, bloody diarrhea
  • Hematemesis
  • Hemorrhagic lymphadenitis
  • Ascites

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

Diagnostics

Cutaneous anthrax Inhalation anthrax Gastrointestinal anthrax

Samples to collect

  • Pleural fluid
  • Swab of respiratory secretions
  • Blood
  • CSF
  • Oral and rectal swabs
  • Ascitic fluid
  • Splenic and/or mesenteric lymph node biopsy
  • Blood
  • CSF
Pathogen detection

Diagnosis of anthrax infection can be made if either the confirmatory test or at least two of the supportive microbiologic tests indicate an infection.

Additional findings

A lumbar puncture to rule out meningitis is indicated among all patients with clinical features of systemic involvement!

Treatment

Treatment Cutaneous anthrax Inhalation anthrax Gastrointestinal anthrax
Causative Without systemic spread - -
With systemic spread
Supportive General
Specific
  • None
Lethality
  • ∼ 40%

While gastrointestinal anthrax and inhalational anthrax are rare, they have a particularly poor prognosis, even with antibiotic treatment!

Prevention

  • 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 administered as 0.5 mL IM injections in a 3-dose primary schedule at 0, 1, and 6 months, followed by booster doses at 12 and 18 months, and annually thereafter.
    • Post-exposure prophylaxis : 3 doses of AVA over 4 weeks along with antibiotics (ciprofloxacin or doxycycline) for 60 days
  • AVA is contraindicated among 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.

  • Herold G. Internal Medicine. Cologne, Germany: Herold G; 2014.
last updated 08/24/2018
{{uncollapseSections(['vg0AC2', 'E3c84X0', 'Cg0qx2', 'u3cp4X0', 'yg0dB2', 'zg0rB2', '0S0ey2', 'bS0Hy2'])}}