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
  2. Pulmonary Macrophages transfer spores from the lung to the mediastinal Lymph Nodes
  3. Necrotizing Lymphadenitis results, followed by 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: 8,000-50,000 spores
    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)
  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. Headache
      3. Viral upper respiratory symptoms
      4. Cough
      5. 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. Shock
      7. Hemorrhagic mediastinitis
      8. Thoracic Lymphadenitis
      9. Hemorrhagic Meningitis

VIII. Findings: Intestinal Anthrax

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)
    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)

XII. Management: Suspected Anthrax Contact

  1. Suspicious item management
    1. See Biological and Chemical Weapon Exposure in Mail
  2. Decontamination
    1. Careful Hand Washing with soap and water
    2. No special Decontamination procedures
  3. 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. Hospitalized Patients with possible Anthrax findings
    1. Public Health to start epidemiologic evaluation
    2. Confirm diagnosis with lab testing (see above)

XIII. Management: Antibiotics for inhalational Anthrax

  1. General
    1. Combine antibiotic regimen with either Monoclonal Antibody (e.g. Rxibacumab) or Anthrax IgG
  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)

XIV. 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

XV. 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

XVI. Prognosis

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

XVII. 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

XVIII. 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

XIX. References

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

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Related Studies

Ontology: Anthrax disease (C0003175)

Definition (MEDLINEPLUS)

Anthrax is a disease caused by Bacillus anthracis, a germ that lives in soil. Many people know about it from the 2001 bioterror attacks. In the attacks, someone purposely spread anthrax through the U.S. mail. This killed five people and made 22 sick.

Anthrax is rare. It affects animals such as cattle, sheep, and goats more often than people. People can get anthrax from contact with infected animals, wood, meat, or hides. It can cause three forms of disease in people. They are

  • Cutaneous, which affects the skin. People with cuts or open sores can get it if they touch the bacteria.
  • Inhalation, which affects the lungs. You can get this if you breathe in spores of the bacteria.
  • Gastrointestinal, which affects the digestive system. You can get it by eating infected meat.

Antibiotics often cure anthrax if it is diagnosed early. But many people don't know they have anthrax until it is too late to treat. A vaccine to prevent anthrax is available for people in the military and others at high risk.

NIH: National Institute of Allergy and Infectious Diseases

Definition (NCI) An infection caused by Bacillus anthracis bacteria. It may affect the lungs, gastrointestinal tract, or skin. Patients with lung infection present with fever, headaches, cough, chest pain and shortness of breath. Patients with gastrointestinal infection present with nausea, vomiting and bloody diarrhea. Patients with skin infection develop blisters and ulcers.
Definition (MSH) An acute infection caused by the spore-forming bacteria BACILLUS ANTHRACIS. It commonly affects hoofed animals such as sheep and goats. Infection in humans often involves the skin (cutaneous anthrax), the lungs (inhalation anthrax), or the gastrointestinal tract. Anthrax is not contagious and can be treated with antibiotics.
Definition (CSP) infectious bacterial zoonotic disease usually acquired by ingestion of Bacillus anthracis; marked by hemorrhage and serous effusions in the organs and cavities and symptoms of extreme prostration.
Concepts Disease or Syndrome (T047)
MSH D000881
ICD9 022.9, 022
ICD10 A22 , A22.9
SnomedCT 17540007, 186304006, 187302001, 154295005, 409498004
LNC LA10432-5
English Anthrax, Anthrax, unspecified, [X]Anthrax, unspecified, anthrax (diagnosis), anthrax, Anthrax NOS, infection due to Bacillus anthracis, Anthrax [Disease/Finding], anthrax disease, splenic fever, charbon, Anthrax NOS (disorder), [X]Anthrax, unspecified (disorder), Anthrax disease, anthrax; infection, Anthrax, NOS, Charbon, Infection due to Bacillus anthracis, Milzbrand, Splenic fever, Anthrax (disorder)
Dutch Bacillus anthracis-infectie, anthrax niet-gespecificeerd, anthrax; infectie, Anthrax, niet gespecificeerd, anthrax, Anthrax, Miltvuur
French Anthrax, non précisé, Charbon, Charbon (maladie), Maladie du charbon, Fièvre charbonneuse, Infection à Bacillus anthracis, Maladie charbonneuse
German Anthrax, unspezifisch, Anthrax [Milzbrand], Milzbrand, nicht naeher bezeichnet, Anthrax, Milzbrand
Italian Carbonchio non specificato, Antrace, Carbonchio
Portuguese Carbúnculo NE, Infecção por Bacillus anthracis, Carbúnculo Gastrointestinal, Carbúnculo Inalacional, Carbúnculo Pulmonar, Septicemia Carbunculosa, Pústula Maligna, Toxi-Infecção por Bacillus anthracis, Antraz Cutâneo, Antraz Inalacional, Carbúnculo Hemático, Carbúnculo Meníngeo, Doença dos Cardadores de Lã, Infecção pelo Bacillus anthracis, Antraz Gastrointestinal, Antraz por Inalação, Antraz Meníngeo, Baceira, Carbúnculo Cutâneo, Carbúnculo por Inalação, Antraz Pulmonar, Carbúnculo Maligno, Doença dos Trapeiros, Antraz
Spanish Infección por carbunco, Carbuncosis no especificada, fiebre esplénica, carbunco, SAI (trastorno), [X]carbunco, no especificado (trastorno), [X]carbunco, no especificado, infección por Bacillus anthracis, carbunco, SAI, Carbunco Gastrointestinal, Carbunco Hematico, Carbunco Pulmonar, Carbunco Septicémico, Enfermedad de los Cardadores de Lana, Carbunco Cutáneo, Carbunco Maligno, Infección por Bacillus anthracis, Bacera, Carbunco Inhalacional, Carbunco Meníngeo, Carbunco por Inhalación, Enfermedad de los Traperos (Papeleros), Pústula Maligna, carbunco (trastorno), carbunco, Carbunco
Japanese 炭疽, 炭疽、詳細不明, 炭疽菌感染, タンソ, タンソキンカンセン, タンソショウサイフメイ
Swedish Mjältbrand
Czech sněť slezinná, antrax, Antrax, Antrax, blíže neurčený, Infekce způsobená Bacillus anthracis
Finnish Pernarutto
Korean 탄저병, 상세불명의 탄저병
Polish Wąglik, Czarna krosta
Hungarian anthrax, lépfene, k.m.n.
Norwegian Anthrax, Miltbrann, Antraks

Ontology: Bacillus anthracis (C0004589)

Definition (NCI) A species of aerobic or facultatively anaerobic, Gram-positive, rod shaped bacteria assigned to the phylum Firmicutes. This species is nonmotile, spore forming, and catalase positive, hydrolyzes casein, starch and gelatin, reduces nitrate, is penicillin susceptible but cephalosporin resistant, gamma phage sensitive, has absent or delayed hemolysis and the capsule can be visualized using M'Faydean's stain. B. anthracis is found in most soil, causes Anthrax in humans and animals, has been utilized as a biological weapon and both a veterinary and human vaccine exists.
Definition (NCI_CDISC) Any bacterial organism that can be assigned to the species Bacillus anthracis.
Definition (CSP) causes anthrax in humans and animals.
Definition (MSH) A species of bacteria that causes ANTHRAX in humans and animals.
Concepts Bacterium (T007)
MSH D001408
SnomedCT 21927003
LNC LP16672-5, MTHU002712
French Bacille du charbon, Bacillus anthracis, Bactéridie charbonneuse
Swedish Bacillus anthracis
English anthrax, Bacillus anthracis, B. anthracis, Bacillus anthracis Cohn 1872, bacillus anthracis, anthracis b, anthracis b., b. anthracis, anthracis bacillus, bacillus anthrax, Bacillus cereus var. anthracis, Bacteridium anthracis, anthrax bacterium, BACILLUS ANTHRACIS, Anthrax bacillus, Bacillus anthracis (organism)
Czech Bacillus anthracis
Finnish Bacillus anthracis
Polish Laseczki wąglika, Bacillus anthracis
Norwegian Bacillus anthracis
Spanish Bacillus anthracis (organismo), Bacillus anthracis
German Bacillus anthracis
Italian Bacillus anthracis
Dutch Bacillus anthracis, Miltvuurbacterie
Portuguese Bacillus anthracis

Ontology: Anthrax Vaccines (C0358297)

Definition (HL7V3.0) <p>anthrax vaccine</p>
Definition (CSP) vaccines or candidate vaccines used to prevent anthrax infection.
Definition (MSH) Vaccines or candidate vaccines used to prevent ANTHRAX.
Concepts Pharmacologic Substance (T121) , Immunologic Factor (T129)
MSH D022122
SnomedCT 333521006, 396420001
CPT 90581
HL7 24
English Anthrax Vaccine, Anthrax Vaccines [Chemical/Ingredient], anthrax vaccines, vaccine anthrax, Vaccines, Anthrax, anthrax vaccine (medication), anthrax vaccine, Anthrax vaccines, Anthrax vaccine, Anthrax vaccine (product), Anthrax vaccine (substance), anthrax, Anthrax, Anthrax Vaccines, ANTHRAX VACCINE
Czech antrax - vakcíny
Finnish Pernaruttorokotteet
Japanese 炭疽ワクチン, ワクチン-炭疽
Spanish vacuna contra el carbunclo, vacuna del ántrax, vacuna del ántrax (producto), vacuna contra el carbunco (producto), vacuna contra el carbunco, vacuna contra el carbunclo (sustancia), vacuna contra el carbunco (sustancia), Vacunas contra Bacillus Anthracis, Vacunas contra el Carbunco Maligno, Vacunas Anti Carbunco, Vacunas contra el Carbunco
Swedish Mjältbrandsvacciner
Polish Szczepionki przeciw wąglikowi
Portuguese Vacinas contra Bacillus Anthracis, Vacinas contra Carbúnculo Maligno, Vacinas contra Antraz, Vacinas contra Carbúnculo Hemático
German Impfstoffe, Milzbrand-, Milzbrandimpstoffe, Anthraxvakzinen, Vakzinen, Anthrax-
Italian Vaccini carbonchiosi
French Vaccins anti-anthrax, Vaccins anticharbonneux