anthrax (woolsorter's disease)

Introduction

Infection with Bacillus anthracis. The name anthrax from the Greek for 'coal' refers to the black eschar seen on affected skin.

Etiology

• transmission from wild or domestic animals
• contact with animal hides
• ingestion or inhalation* of Bacillus anthracis spores

* even a single case of inhalation anthrax should raise suspicion of bioterrorism

Epidemiology

• endemic in Iran, Turkey, Pakistan, Sudan
  • natural resistance of humans is > than that of livestock
• cutaneous form of anthrax is most common in humans
  • 3 cases in 9 years in USA (1984-1993)
• gastrointestinal anthrax is rare (never documented in USA)
• large epidemics have occurred in the former Soviet Union
• exposure of 84 workers to live anthrax at CDC in June 2014, due to safety protocol breach

Pathology

• infections are initiated by endospores (see B anthracis)
  • in the cutaneous form, endospores enter through cuts or abrasions
  • a few cases of transmission by insect bites
• all known anthrax virulence genes are expressed by the vegetative form of B anthracis that results from the germination of spores within macrophages
• after release from macrophages, the vegetative form of B anthracis multiplies with the lymphatics, then enters the blood stream
• regional hemorrhagic lymphadenitis may occur
  • migration of inhaled spores to mediastinal lymph nodes results in tissue destruction & hemorrhage
  • pulmonary lymphatic drainage may be compromised contributing to pulmonary edema
• massive septicemia may result (10E07-10E08 organisms/mL)
• there is no evidence that an immune response is initiated against the vegetative bacilli

* histopathology images

Clinical manifestations

• cutaneous form
  • malaise
  • painless pruritic pustule on skin (images
    • begins as erythematous papule
    • later vesiculates & ulcerates (painless cutaneous ulcer)
    • surrounding non-tender edema
    • a black eschar may form
    • lesions most commonly on upper extremities, less commonly on face & neck
  • hemorrhagic & necrotic progression may occur
  • regional lymphadenopathy may occur
  • dyspnea & hemoptysis may occur during dissemination
• inhalation anthrax (woolsorter's disease)
  • 1-3 day incubation period
  • constituional symptoms
    • fever, malaise, myalgia, headache
  • pulmonary:
    • dyspnea*, stridor, hypoxia
    • cough is generally non-productive
    • pleuritic chest pain
    • hemorrhagic mediastinitis
    • abnormal chest auscultation*
  • sepsis
    • hypotension
    • tachycardia, tachypnea
    • rapidly progressive systemic infection
  • neurologic manifestations
    • headache
    • confusion*
    • dizziness*
    • blurry vision*
  • nausea/vomiting*
  • very high mortality rate within 24 hours
• gastrointestinal anthrax
  • fever
  • nausea/vomiting, abdominal pain, bloody diarrhea
  • rapidly-developing ascites
  • high mortality
  • oropharyngeal anthrax
    • primary lesion on palatine tonsil
    • pharyngitis, dysphagia, regional lymphadenopathy
• anthrax meningitis is an uncommon complication of disseminated anthrax

* less common in viral respiratory tract infection rhinorrhea & sore throat less common with inhalation anthrax No clinical features reliably distinguish anthrax from community-acquired pneumonia

Laboratory

• direct staining of cutaneous lesions
  • organism may be present in large numbers
  • Gram stain
  • direct fluorescent staining
  • consider punch biopsy (submit in formalin to CDC)
• culture of lesion
• blood cultures
• complete blood count (CBC)
  • generally reveals normal WBC, but leukocytosis with neutrophil predominance may be observed in severe cases
• serology: Bacillus anthracis antibody in serum
  • ELISAs showing 4X increase in titer of antibodies against capsular antigen & exotoxins
    • capsular components (95-100% sensitive)
    • protective antigen (72% sensitive)
  • enzyme-linked immunoelectrotransfer blotting
  • indirect microhemagglutination
  • serologic testing available at CDC
• Bacillus anthracis DNA
  • polymerase chain reaction (PCR) under investigation
  • vrrA - marker
  • Ba813 - marker
• nasal swabs most useful for exposure
• pleural fluid
  • gram stain, culture, Bacillus anthracis DNA
  • cytospin for immunohistochemistry (cytology)
• CSF analysis

Diagnostic procedures

• thoracentesis for pleural effusion
• lumbar puncture for CSF analysis if meningeal signs

Radiology

• chest X-ray:
  • mediastinal widening resulting from hemorrhagic mediastinitis
  • bloody pleural effusion
  • pulmonary infiltrate
• consider computed tomography (CT) if chest X-ray is normal

Differential diagnosis

(see differential diagnosis of anthrax)

Management

• inhalation anthrax
  • ciprofloxacin, levofloxacin, or moxifloxacin or doxycycline# IV plus 1 or 2 other active drugs for 60 days
• other antibiotics with good in vitro activity
  • penicillin, ampicillin, chloramphenicol, rifampin, clindamycin, clarithromycin, vancomycin, linezolid, imipenem. meropenem
• penicillin monotherapy no longer recommended by CDC
  • 2 million units of penicillin G IV
    • every 6 hours for cutaneous lesions
    • every 2 hours for inhalation anthrax
    • continue until symptoms resolve
  • switch to oral penicillin to complete 7-10 day course
  • streptomycin is synergistic with penicillin in experimental models
  • amoxicillin 80 mg/kg/day, up to 500 mg TID (children)
• postexposure: prophylaxis for aerosol exposure
  • positive nasal swabs
  • 60 days of ciprofloxacin or doxycycline in conjunction with 3 doses of anthrax vaccine (AVA) for previously unvaccinated persons
  • raxibacumab, investigational monoclonal antibody
• passive immunization with anthrax antitoxin
  • no commercially available antitoxin
  • raxibacumab may be commercially available
• cutaneous lesions
  • should be cleaned & covered & used dressings should be decontaminated
  • viable organisms disappear from lesions within 5 hours of administration of parenteral penicillin G
  • oral ciprofloxacin
  • treat as inhalation anthrax if severe cutaneous disease
• gastrointestinal anthrax
  • treat as inhalation anthrax
  • consider raxibacumab, obiltoxaximab or IV anthrax immune globulin
• prognosis
  • mortality of cutaneous anthrax is 10-20% without treatment
  • mortality of inhalation anthrax approaches 100% despite treatment
  • mortality for gastrointestinal anthrax is 50%
• prevention:
  • veterinary anthrax vaccination
  • anthrax vaccine adsorbed for people at risk
  • no treatment or separation from potentially infected persons indicated if no risk of direct exposure
• Notify Public Health Department

# levofloxacin & ofloxacin also seem to be effective

* doxycycline is the preferred agent in this class

Notes

• aerosolized release of Bacillus anthracis spores over densely populated areas (bioterrorism) could result in mass casualty

More general terms

• bacterial infection

More specific terms

• cutaneous anthrax
• inhalation anthrax

Additional terms

• anthrax vaccine adsorbed (AVA)
• Bacillus anthracis
• differential diagnosis of anthrax