Anthrax

Aka: Anthrax, Bacillus anthracis, Anthrax Vaccine

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II. History

  1. Bioterrorism attack with Anthrax spores sent via mail in 2001
    1. Resulted in 11 cutaneous cases, 11 inhalation cases (with 5 deaths)
    2. Postexposure Prophylaxis recommended for 10,000 exposures
    3. Cost >$300 Million for Decontamination
    4. Schmitt (2012) Biosecur Bioterror 10(1): 98-107 [PubMed]

III. Pathophysiology

  1. Organism: Bacillus anthracis
    1. Gram Positive rod
    2. Spore forming aerobic Bacteria
      1. Heat stable spores may survive 600-1000 years at room Temperature
      2. Spores are naturally found in soil
  2. Disease in Animals
    1. Domestic animals (e.g. cattle) are vaccinated against Anthrax
    2. Historically, animals inhaled spores from soil and human outbreaks occurred with exposure
  3. Disease in humans
    1. Pulmonary Macrophages transfer spores from the lung to the mediastinal Lymph Nodes
    2. Necrotizing Lymphadenitis results, followed by Septic Shock
  4. Anthrax Toxin (3 components)
    1. Protective Antigen (PA)
      1. B-Binding subunit allows EF entry in Target Cells
    2. Edema Factor (EF)
      1. Stimulates Calmodulin-dependent adenylate cyclase resulting in increased cAMP
      2. cAMP induces severe edema, and suppresses Neutrophil activity
    3. Lethal Factor (LF)
      1. Zinc metalloprotease blocks Protein kinase activity
      2. Triggers host inflammatory cell (e.g. Macrophage) release of TNF-a and IL-b, with resulting Septic Shock

IV. Transmission

  1. No transmission person to person
    1. Contrast with other Bioterrorism agents such as Plague, which do involve person-to-person spread
    2. Reservoir is in herbivores, with occasional human cases
  2. Cutaneous contact with hides of infected animals (wild and domestic herbivores)
    1. Cattle
    2. Sheep
    3. Camels
    4. Antelopes
  3. Ingestion of undercooked and contaminated meat
    1. Anthrax invades intestinal mucosa resulting in necrotic ulcers
    2. Maddah (2013) Caspian J Intern Med 4(2): 672-6 [PubMed]
  4. Inhalation of spores (most lethal)
    1. Infective aerosol dose: 8,000 to 50,000 spores (e.g. Bioterrorism)
    2. Spores may remain viable in soil for >40 years

V. Course

  1. Incubation: 4-6 days (range as broad as 1 to 42 days, even up to 2 months of latency)
  2. Duration of illness: 3-5 days

VI. Findings: Cutaneous ("Malignant Pustule")

  1. Inoculation at site of broken skin
  2. Painless pruritic Pustules develop at inoculation site
  3. Begins as erythematous Papule on exposed skin
  4. Vesiculates and then ulcerates within 1-2 days
    1. Surrounded by a ring of non-tender Brawny Edema
  5. Black eschar may form

VII. Findings: Inhalation Anthrax

  1. Malaise
  2. Regional Lymphadenopathy
  3. Two phases
    1. Initial Phase (Influenza-like illness) for 1-2 days
      1. Fever
      2. Chills
      3. Headache
      4. Viral upper respiratory symptoms
      5. Non-productive Cough
      6. Dyspnea
      7. Myalgias
      8. No Pharyngitis or Rhinorrhea (contrast with typical URI)
    2. Middle Phase
      1. Transient improvement for 1-2 days
    3. Later Phase: Rapid Deterioration
      1. High fever
      2. Drenching sweats
      3. Nausea and Vomiting
      4. Dyspnea and Hemoptysis during dissemination
      5. Cyanosis
      6. Septic Shock
      7. Hemorrhagic mediastinitis
        1. Alveolar Macrophages ingest Bacteria and carry to mediastinal Lymph Nodes
        2. Within the mediastinal Lymph Nodes, Bacteria release toxin that results in Hemorrhage and necrosis
      8. Thoracic Lymphadenitis
      9. Hemorrhagic Meningitis

VIII. Findings: Intestinal Anthrax

  1. Acute Gastroenteritis type symptoms
  2. Hematemesis
  3. Severe Diarrhea

IX. Differential Diagnosis

  1. Cutaneous Anthrax
    1. Spider Bite
    2. Ecthyma gangrenosum
    3. Ulceroglandular Tularemia
    4. Plague
    5. Staphylococcus or StreptococcusCellulitis
  2. Inhalational Anthrax
    1. Community Acquired Pneumonia (late phase Anthrax)
    2. Mycoplasma pneumonia (early phase Anthrax)
    3. Influenza (early phase Anthrax)
    4. Covid19
    5. Legionnaires' Disease
    6. Psittacosis
    7. Tularemia
    8. Q Fever
    9. Viral Pneumonia
    10. Histoplasmosis (fibrous mediastinitis)
    11. Coccidioidomycosis

X. Labs

  1. Rapid ELISA tests, PCR are now available
  2. Cultures
    1. Blood Culture (high sensitivity)
      1. Standard Blood Cultures will grow Anthrax
    2. Cultures of Vomitus or feces (Intestinal Anthrax)
    3. CSF Culture (Inhalational Anthrax)
    4. Nasal Swab (Epidemiologic tool to identify outbreak)
    5. Sputum Culture (Inhalational Anthrax)
    6. Vesicular fluid (Cutaneous Anthrax)
  3. Gram Stain of blood or vesicular fluid from lesion
    1. Large, Gram Positive bacilli
  4. Complete Blood Count
    1. Neutrophilic Leukocytosis in severe cases

XI. Imaging: Chest XRay

  1. Widened Mediastinum (hemorrhagic mediastinitis)
  2. Lymphadenopathy

XII. Diagnosis

  1. Rare diagnosis that will rely on multiple patients with atypical disease
  2. Consider in fulminant Influenza-like illness (without Pharyngitis or Rhinorrhea) with mediastinitis

XIII. Management: Suspected Anthrax Contact

  1. Suspicious item management
    1. See Biological and Chemical Weapon Exposure in Mail
  2. Decontamination
    1. Remove clothing and put in air tight bags
    2. Careful hand and exposed skin washing with soap and copious water
    3. Clean any grossly contaminated exposed skin with dilute bleach (1:10 dilution)
    4. No specific Decontamination procedures
  3. Personal Protective Equipment for first responders
    1. Full face respirators with HEPA filters or SCBA
    2. Splash-proof garment
    3. Gloves
  4. See Post-exposure Prophylaxis below
    1. Probability of exposure should be assessed
    2. See resources below to address probability
    3. Lab test all patients treated with prophylaxis
    4. Post-exposure quarantine is not needed after exposure
  5. Hospitalized Patients with possible Anthrax findings
    1. Public Health to start epidemiologic evaluation
    2. Confirm diagnosis with lab testing (see above)

XIV. Management: Antibiotics for Inhalational Anthrax

  1. General
    1. Combine Antibiotic regimen with either Monoclonal Antibody (e.g. Rxibacumab) or Anthrax IgG
    2. Naturally occurring Anthrax is susceptible to Penicillins and doxycyline
      1. However, Bioterrorism Anthrax may be engineered with Penicillin and Tetracycline resistance
  2. Initial IV management
    1. Start with IV preparations and then transition to oral when stable
    2. Meningitis (confirmed or suspected)
      1. Ciprofloxacin (or Levofloxacin or Moxifloxacin) AND
      2. Meropenem (or Imipenem or Doripenem, or if Penicillin sensitive, Penicillin G or Ampicillin) AND
      3. Linezolid (or Clindamycin or Rifampin or Chloramphenicol)
    3. Without Meningitis
      1. Ciprofloxacin AND
      2. Clindamycin (or Linezolid)
  3. Oral Antibiotics (after initial IV) to complete a total of 60 days of Antibiotics
    1. Ciprofloxacin or Doxycycline
  4. Antibiotic Dosing
    1. Ciprofloxacin
      1. IV: 7.6 mg/kg up to 400 mg every 8 hours
      2. PO: 15 mg/kg up to 500 mg orally twice daily
    2. Clindamycin
      1. IV: 7.6 mg/kg up to 900 mg every 8 hours
    3. Meropenem
      1. IV: 40 mg/kg up to 2 g every 8 hours
    4. Linezolid
      1. IV: 15 mg/kg up to 600 mg every 12 hours (or 30 mg/kg/day divided q8h if <12 years old)
    5. Doxycycline
      1. IV: 200 mg IV, then 100 mg IV every 12 hours
      2. PO: 4.4 mg/kg up to 200 mg orally once, then 2.2 mg/kg up to 100 mg twice daily
  5. Monoclonal Antibody or IgG Dosing (used with Antibiotic regimen)
    1. Obiltoxaximab (Anthim)
    2. Raxibacumab (coadminister with Diphenhydramine)
      1. Weight >50 kg: Give 40 mg/kg IV over 2 hours
      2. Weight >15-50 kg: Give 60 mg/kg IV over 2 hours
      3. Weight <15 kg: Give 80 mg/kg IV over 2 hours
    3. Anthrax Immunoglobulin (Anthrasil)
      1. Dosing in number of vials (2-7 each with 60 units) based on weight (10-60 kg)

XV. Management: Gastrointestinal Anthrax (Ingested)

  1. Same Antibiotics as for inhalational Anthrax, but total duration of treatment is 7-14 days (21 days for Meningitis)
    1. Contrast with 60 days for inhalational Anthrax

XVI. Management: Post-exposure Prophylaxis

  1. Regimen
    1. Anthrax Vaccine (BioThrax) at 0, 2 and 4 weeks post-exposure AND
      1. Approved for ages 18 to 65 years
      2. Emergency authorization for children, pregnancy, elderly
    2. Antibiotic course for 60 days
      1. Start with Ciprofloxacin or Levofloxacin (or Doxycycline)
      2. In pregnancy and children, if Anthrax tested as susceptible, may switch to Amoxicillin after 14 days
  2. Antibiotic Dosing
    1. Ciprofloxacin
      1. Adults: 500 mg orally twice daily
      2. Children: 10-15 mg/kg up to 500 mg orally twice daily
    2. Doxycycline
      1. Adults: 100 mg orally twice daily
      2. Children over age 8 years: 2.5 mg/kg up to 100 mg orally every 12 hours
    3. Amoxicillin (only if susceptible)
      1. Adults: 500 mg orally three times daily
      2. Children: 40 mg/kg up to 500 mg orally three times daily

XVII. Prognosis

  1. Inhalation Anthrax (inhaled spores)
    1. Bioterrorism (refined spores): 95% mortality (80% if treated)
    2. Naturally occurring: 30-45% mortality if treated
  2. Cutaneous Anthrax (skin contact)
    1. Untreated: 20% mortality
    2. Treated: Rare mortality
  3. Intestinal Anthrax (ingested contaminated meat)
    1. Mortality 25 to 60%

XVIII. Prevention: Anthrax Vaccine

  1. Anthrax Vaccine (preexposure) 93% effective
    1. Indications
      1. Deployed military to specific regions
      2. Lab personnel at risk for exposure
      3. Risk of infected animal handling (e.g. farmers, veterinarians)
    2. Contraindications
      1. Pregnancy (unless risk outweighs benefit)
    3. Dosing
      1. Initial: 0, 1 and 6 months
      2. Next Booster: 12 and 18 months
      3. Maintenance: Annually if high high risk
  2. Postexposure Prophylaxis as above
    1. Empiric prophylaxis for any suspected exposure
    2. Best prognosis with Antibiotics prior to symptoms

XIX. Resources

  1. Department of Defense Anthrax Vaccine Program
    1. http://www.anthrax.osd.mil
    2. Phone: 877-GETVACC
  2. CDC Bacterial and Mycotic Disease Information
    1. http://www.cdc.gov/ncidod/dbmd/diseaseinfo/
  3. CDC Bioterrorism Preparedness and Response
    1. http://www.bt.cdc.gov

XX. References

  1. Gary Malet, Correspondence
  2. (1998) Medical Management Biological Casualties, Army
  3. (2016) Sanford Guide Antimicrobial
  4. Charbonnet and Mace (2023) Crit Dec Emerg Med 37(4): 4-10
  5. Seeyave (2015) Crit Dec Emerg Med 29(5): 13-21
  6. Hendricks (2014) Emerg Infect Dis 20(2) +PMID:24447897 [PubMed]
  7. Inglesby (1999) JAMA 281(18):1735-45 [PubMed]
  8. Rathjen (2021) Am Fam Physician 104(4): 376-85 [PubMed]
  9. Sweeney (2011) Am J Respir Crit Care Med 184(12):1333-41 [PubMed]

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