Anthrax

See Also

Biological Weapon (Bioterrorism)

History

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]

Pathophysiology

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
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
Disease in humans
1. Pulmonary Macrophages transfer spores from the lung to the mediastinal Lymph Nodes
2. Necrotizing Lymphadenitis results, followed by Septic Shock
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

Transmission

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
Cutaneous contact with hides of infected animals (wild and domestic herbivores)
1. Cattle
2. Sheep
3. Camels
4. Antelopes
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]
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

Course

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

Findings
Cutaneous ("Malignant Pustule")

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

Findings
Inhalation Anthrax

Malaise
Regional Lymphadenopathy
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

Findings
Intestinal Anthrax

Differential Diagnosis

Cutaneous Anthrax
1. Spider Bite
2. Ecthyma gangrenosum
3. Ulceroglandular Tularemia
4. Plague
5. Staphylococcus or Streptococcus Cellulitis
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

Labs

Rapid ELISA tests, PCR are now available
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)
Gram Stain of blood or vesicular fluid from lesion
1. Large, Gram Positive bacilli
Complete Blood Count
1. Neutrophilic Leukocytosis in severe cases

Imaging
Chest XRay

Widened Mediastinum (hemorrhagic mediastinitis)
Lymphadenopathy

Diagnosis

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

Management
Suspected Anthrax Contact

Suspicious item management
1. See Biological and Chemical Weapon Exposure in Mail
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
Personal Protective Equipment for first responders
1. Full face respirators with HEPA filters or SCBA
2. Splash-proof garment
3. Gloves
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
Hospitalized Patients with possible Anthrax findings
1. Public Health to start epidemiologic evaluation
2. Confirm diagnosis with lab testing (see above)

Management
Antibiotics for Inhalational Anthrax

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
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)
Oral Antibiotics (after initial IV) to complete a total of 60 days of Antibiotics
1. Ciprofloxacin or Doxycycline
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
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)

Management
Gastrointestinal Anthrax (Ingested)

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

Management
Post-exposure Prophylaxis

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
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

Prognosis

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

Prevention
Anthrax Vaccine

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
Postexposure Prophylaxis as above
1. Empiric prophylaxis for any suspected exposure
2. Best prognosis with Antibiotics prior to symptoms

Resources

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

References

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