Bacillus anthracis

Snapshot

• A 35-year-old woman presents to the emergency room for an ulcer on her arm. She reports that she recently completed a travel program in Africa, where she worked on the farms in exchange for room and board. She reports coming into contact with farm animals every day. She said she accidentally cut her left forearm on some wooden post a few days ago. Yesterday, she noticed a painless but pruritic lesion. On physical exam, there is a 4-mm papule with a dusky-looking central vesicle and surrounding edema. There is also axillary lymphadenopathy. She is started on antibiotics.

Introduction

• Classification 
  • Bacillus anthracis
    • spore- and exotoxin-forming gram + rod
    • capsule protects against phagocytosis 
      • the only bacteria with a polypeptide capsule (poly-D-glutamate) 
  • transmission
    • inhalation of spores
    • introduction of spores into a skin break
    • ingestion of spores
• Epidemiology
  • incidence
    • more common in areas where animal vaccination rates are low
    • bioterrorism
  • risk factors
    • intravenous drug use (e.g., heroin)
    • occupational exposure to unvaccinated animals
    • occupational exposure to animal hides
• Pathogenesis
  • anthrax toxin composed of 3 components
    • protective antigen
      • binds cell surface and mediates entry of edema and lethal factor
    • edema factor 
      • binds calmodulin and performs the same function as adenylate cyclase, ↑ cAMP and resulting in
        • black eschar with edematous borders
        • vasodilation and hypotension
    • lethal factor
      • a protease that cleaves the amino terminus of mitogen-activated protein kinase kinases (MAPKK), inhibiting this signalling pathway, and resulting in macrophage apoptosis
  • infection may spread via lymphatics
• Associated conditions
  • cutaneous anthrax
    • most common
  • pulmonary anthrax
    • “woolsorter’s disease”
  • gastrointestinal anthrax
• Prevention
  • post-exposure prophylaxis
    • 3 doses of anthrax vaccine
    • 60 days of a single antibiotic
      • ciprofloxacin or doxycycline are first line
• Prognosis
  • biphasic nature of pulmonary anthrax
    • prodromal symptoms
    • fulminant bacteremic phase
• often leads to death within days

Presentation

• Symptoms
  • pulmonary anthrax
    • flu-like syndrome with non-productive cough
    • nausea and vomiting
    • hemoptysis
    • chest pain
  • gastrointestinal anthrax
    • nausea and vomiting
    • dysentery
    • abdominal pain
• Physical exam
  • cutaneous anthrax   
    • initial lesion is a painless and pruritic papule with a central vesicle or bulla
    • this progresses to painless and necrotic black eschar
      • surrounded by edema 
    • eschar sloughs off at day 14
  • pulmonary anthrax
    • mediastinitis
    • shock
    • hypoxia
    • dyspnea
• lymphadenopathy

Imaging

• Chest radiography 
  • indication 
    • pulmonary anthrax
  • findings
    • pleural effusion
    • pulmonary consolidation
• widened mediastinum

Studies

• Labs
  • multiple methods of detection
    • “medusa head” appearance on microscopy
      • halo of projections
    • culture of blood, pleural fluid, or eschar
    • positive Gram stain of affected tissue 
    • polymerase chain reaction
    • anti-protective antigen immunoglobulin G on enzyme-linked immunosorbent assay
    • biopsy with immunohistochemistry staining
  • marked hemoconcentration
• Making the diagnosis
  • most cases are diagnosed clinically and confirmed with
    • positive culture, serology, or immunohistochemistry
• detection of Bacillus anthracis DNA in tissue

Differential

• Community-acquired pneumonia
  • distinguishing factor
• less likely to have nausea, vomiting, pallor, or unexplained mediastinal widening on chest radiography

Treatment

• Management approach
  • antibiotics should be given in the prodromal phase of the disease
  • cutaneous anthrax can be treated with 1 antibiotic
  • systemic anthrax can be treated with 2 antibiotics
• Medical
  • ciprofloxacin or doxycycline
    • indication
      • all patients
  • protein synthesis inhibitor
    • indications
      • systemic anthrax
      • combination therapy with fluoroquinolone or doxycycline
    • mechanism
      • reduces toxin production
    • drugs
      • clindamycin
      • linezolid
  • antitoxins
    • indication
      • all patients
    • drugs
      • monoclonal antibodies
        • raxibacumab
• anthrax immunoglobulin

Complications

• Bacteremia from cutaneous anthrax
• Death