II. History
-
Bioterrorism attack with Anthrax spores sent via mail in 2001
- Resulted in 11 cutaneous cases, 11 inhalation cases (with 5 deaths)
- Postexposure Prophylaxis recommended for 10,000 exposures
- Cost >$300 Million for Decontamination
- Schmitt (2012) Biosecur Bioterror 10(1): 98-107 [PubMed]
III. Pathophysiology
- Organism: Bacillus anthracis
-
Gram Positive Spore-Forming Rod
- Anthrax spores are resistant to heat, drying, UV light and disinfection
- Heat stable spores may survive 600-1000 years at room Temperature
- Spores are naturally found in soil
- Spores are 1-2 microns in diameter and are easily inhaled
- Unique Poly-D Glutamic Acid Capsule
- Found only in Bacillus anthracis organisms
- Protein capsule protects against Phagocytosis
- Encoded by 3 genes on the pXO2 Plasmid (1 of two B. anthracis capsules)
- Spore Germination
- Two Plasmids (pXO1, pXO2) encode genes related to germination and virulence
- Germination is triggered by Temperature increase to 37 C, CO2 concentration and Serum Proteins
- Disease in Animals
- Domestic animals (e.g. cattle, sheep, goats) are vaccinated against Anthrax
- Historically, animals inhaled spores from soil and human outbreaks occurred with exposure
- Transmission to Humans (Zoonosis)
- Humans acquire Anthrax via spore exposure from infected animals or soil, animal hides or wool
- No cases of Anthrax human to human transmission has ever been reported
- Spore entry may be via inhalation, ingestion or open Skin Wound
- Anthrax Activation in humans
- Spores are phagocytosed by Macrophages (e.g. in lung after inhalation)
- Spores germinate within Macrophages
- Germinated B. anthracis is resistant to Phagocytosis due to Poly Glutamic Acid Capsule
- Macrophages transfer B. anthracis to regional Lymph Nodes (e.g. mediastinum)
- B. anthracis is released and reproduces in the lymph system in high concentrations
- Necrotizing Lymphadenitis results, followed by intense bacteremia and Septic Shock
- Anthrax Toxin (3 components found on Plasmid pXO1)
- Protective Antigen (PA)
- B-Binding subunit allows EF entry in Target Cells
- Edema Factor (EF)
- A-Active subunit (of A-B Toxin), with the B-Binding subunit PA
- EF stimulates Calmodulin-dependent adenylate cyclase resulting in increased cAMP
- cAMP induces severe edema, and suppresses Neutrophil activity
- Lethal Factor (LF)
- Zinc metalloprotease blocks Protein kinase activity
- Triggers host inflammatory cell (e.g. Macrophage) release of TNF-a and IL-b, with resulting Septic Shock
- Protective Antigen (PA)
IV. Transmission
- No transmission person to person
- Contrast with other Bioterrorism agents such as Plague, which do involve person-to-person spread
- Reservoir is in herbivores, with occasional human cases
- Cutaneous contact with hides of infected animals (wild and domestic herbivores)
- Cattle
- Sheep
- Goats
- Camels
- Antelopes
- Ingestion of undercooked and contaminated meat
- Anthrax invades intestinal mucosa resulting in necrotic ulcers
- Maddah (2013) Caspian J Intern Med 4(2): 672-6 [PubMed]
- Inhalation of spores (most lethal)
- Infective aerosol dose: 8,000 to 50,000 spores (e.g. Bioterrorism)
- Spores may remain viable in soil for >40 years
V. 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
VI. 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
- Surrounded by a ring of non-tender Brawny Edema
- Malignant Pustule forms (classic lesion)
- Painless, round black eschar with surrounding edema
- Skin lesions may resolve spontaneously in 80-90% of cases
- However, lethal Anthrax systemic infection may also occur
VII. Findings: Inhalation Anthrax ("Woolsorter's Disease")
- Malaise
- Regional Lymphadenopathy
- Two phases
- Initial Phase (Influenza-like illness) for 1-2 days
- Fever
- Chills
- Headache
- Viral upper respiratory symptoms
- Non-productive Cough
- Dyspnea
- Myalgias
- No Pharyngitis or Rhinorrhea (contrast with typical URI)
- Middle Phase
- Transient improvement for 1-2 days
- Later Phase: Rapid Deterioration
- High fever
- Drenching sweats
- Nausea and Vomiting
- Dyspnea and Hemoptysis during dissemination
- Cyanosis
- Septic Shock
- Hemorrhagic mediastinitis
- Alveolar Macrophages ingest Bacteria and carry to mediastinal Lymph Nodes
- Within the mediastinal Lymph Nodes, Bacteria release toxin that results in Hemorrhage and necrosis
- Thoracic Lymphadenitis
- Hemorrhagic Meningitis
- Initial Phase (Influenza-like illness) for 1-2 days
VIII. Findings: Intestinal Anthrax
- Acute Gastroenteritis type symptoms
- Hematemesis
- Severe bloody Diarrhea
IX. Differential Diagnosis
- Cutaneous Anthrax
- Spider Bite
- Ecthyma gangrenosum
- Ulceroglandular Tularemia
- Plague
- Staphylococcus or StreptococcusCellulitis
- Inhalational Anthrax
- Community Acquired Pneumonia (late phase Anthrax)
- Mycoplasma pneumonia (early phase Anthrax)
- Influenza (early phase Anthrax)
- Covid19
- Legionnaires' Disease
- Psittacosis
- Tularemia
- Q Fever
- Viral Pneumonia
- Histoplasmosis (fibrous mediastinitis)
- Coccidioidomycosis
X. Labs
- Rapid ELISA tests, PCR are now available
- Cultures
- Blood Culture (high sensitivity)
- Standard Blood Cultures will grow Anthrax
- Cultures of Vomitus or feces (Intestinal Anthrax)
- CSF Culture (Inhalational Anthrax)
- Nasal Swab (Epidemiologic tool to identify outbreak)
- Sputum Culture (Inhalational Anthrax)
- Vesicular fluid (Cutaneous Anthrax)
- Blood Culture (high sensitivity)
-
Gram Stain of blood or vesicular fluid from lesion
- Large, Gram Positive bacilli
-
Complete Blood Count
- Neutrophilic Leukocytosis in severe cases
XI. Imaging
-
Chest XRay or Chest CT
- Widened Mediastinum (hemorrhagic mediastinitis)
- Lymphadenopathy
- Pleural Effusions
XII. Diagnosis
- Rare diagnosis that will rely on multiple patients with atypical disease
- Consider in fulminant Influenza-like illness (without Pharyngitis or Rhinorrhea) with mediastinitis
XIII. Management: Suspected Anthrax Contact
- Suspicious item management
-
Decontamination
- Remove clothing and put in air tight bags
- Careful hand and exposed skin washing with soap and copious water
- Clean any grossly contaminated exposed skin with dilute bleach (1:10 dilution)
- No specific Decontamination procedures
-
Personal Protective Equipment for first responders
- Full face respirators with HEPA filters or SCBA
- Splash-proof garment
- Gloves
- See Post-exposure Prophylaxis below
- Probability of exposure should be assessed
- See resources below to address probability
- Lab test all patients treated with prophylaxis
- Post-exposure quarantine is not needed after exposure
- Hospitalized Patients with possible Anthrax findings
- Public Health to start epidemiologic evaluation
- Confirm diagnosis with lab testing (see above)
XIV. Management: Antibiotics for Inhalational Anthrax
-
General
- Combine Antibiotic regimen with either Monoclonal Antibody (e.g. Rxibacumab) or Anthrax IgG
- Naturally occurring Anthrax is susceptible to Penicillins and doxycyline
- However, Bioterrorism Anthrax may be engineered with Penicillin and Tetracycline resistance
- Initial IV management
- Start with IV preparations and then transition to oral when stable
- Meningitis (confirmed or suspected)
- Ciprofloxacin (or Levofloxacin or Moxifloxacin) AND
- Meropenem (or Imipenem or Doripenem, or if Penicillin sensitive, Penicillin G or Ampicillin) AND
- Linezolid (or Clindamycin or Rifampin or Chloramphenicol)
- Without Meningitis
- Ciprofloxacin AND
- Clindamycin (or Linezolid)
- Oral Antibiotics (after initial IV) to complete a total of 60 days of Antibiotics
-
Antibiotic Dosing
- Ciprofloxacin
- IV: 7.6 mg/kg up to 400 mg every 8 hours
- PO: 15 mg/kg up to 500 mg orally twice daily
- Clindamycin
- IV: 7.6 mg/kg up to 900 mg every 8 hours
- Meropenem
- IV: 40 mg/kg up to 2 g every 8 hours
- Linezolid
- IV: 15 mg/kg up to 600 mg every 12 hours (or 30 mg/kg/day divided q8h if <12 years old)
- Doxycycline
- IV: 200 mg IV, then 100 mg IV every 12 hours
- PO: 4.4 mg/kg up to 200 mg orally once, then 2.2 mg/kg up to 100 mg twice daily
- Ciprofloxacin
-
Monoclonal Antibody or IgG Dosing (used with Antibiotic regimen)
- Obiltoxaximab (Anthim)
- Raxibacumab (coadminister with Diphenhydramine)
- Weight >50 kg: Give 40 mg/kg IV over 2 hours
- Weight >15-50 kg: Give 60 mg/kg IV over 2 hours
- Weight <15 kg: Give 80 mg/kg IV over 2 hours
- Anthrax Immunoglobulin (Anthrasil)
- Dosing in number of vials (2-7 each with 60 units) based on weight (10-60 kg)
XV. Management: Gastrointestinal Anthrax (Ingested)
- Same Antibiotics as for inhalational Anthrax, but total duration of treatment is 7-14 days (21 days for Meningitis)
- Contrast with 60 days for inhalational Anthrax
XVI. Management: Post-exposure Prophylaxis
- Regimen
- Anthrax Vaccine (BioThrax) at 0, 2 and 4 weeks post-exposure AND
- Approved for ages 18 to 65 years
- Emergency authorization for children, pregnancy, elderly
- Antibiotic course for 60 days
- Start with Ciprofloxacin or Levofloxacin (or Doxycycline)
- In pregnancy and children, if Anthrax tested as susceptible, may switch to Amoxicillin after 14 days
- Anthrax Vaccine (BioThrax) at 0, 2 and 4 weeks post-exposure AND
-
Antibiotic Dosing
- Ciprofloxacin
- Adults: 500 mg orally twice daily
- Children: 10-15 mg/kg up to 500 mg orally twice daily
- Doxycycline
- Adults: 100 mg orally twice daily
- Children over age 8 years: 2.5 mg/kg up to 100 mg orally every 12 hours
- Amoxicillin (only if susceptible)
- Adults: 500 mg orally three times daily
- Children: 40 mg/kg up to 500 mg orally three times daily
- Ciprofloxacin
XVII. Prognosis
- Inhalation Anthrax (inhaled spores)
- Bioterrorism (refined spores): 95% mortality (80% if treated)
- Naturally occurring: 30-45% mortality if treated
- Cutaneous Anthrax (skin contact)
- Untreated: 20% mortality
- Treated: Rare mortality
- Intestinal Anthrax (ingested contaminated meat)
- Mortality 25 to 60%
XVIII. Prevention: Anthrax Vaccine
- Anthrax Vaccine (preexposure) 93% effective
- Indications
- Deployed military to specific regions
- Lab personnel at risk for exposure
- Risk of infected animal handling (e.g. farmers, veterinarians)
- Contraindications
- Pregnancy (unless risk outweighs benefit)
- Dosing
- Initial: 0, 1 and 6 months
- Next Booster: 12 and 18 months
- Maintenance: Annually if high high risk
- Indications
-
Postexposure Prophylaxis as above
- Empiric prophylaxis for any suspected exposure
- Best prognosis with Antibiotics prior to symptoms
XIX. Resources
- Department of Defense Anthrax Vaccine Program
- http://www.anthrax.osd.mil
- Phone: 877-GETVACC
- CDC Bacterial and Mycotic Disease Information
- CDC Bioterrorism Preparedness and Response
XX. 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]
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Related Studies
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
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 |
Russian | SIBIRSKAIA IAZVA, СИБИРСКАЯ ЯЗВА |
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 |
Russian | SIBIRSKAIA IAZVA, VOZBUDITEL', BACILLUS ANTHRACIS, BACTERIDIUM ANTHRACIS, СИБИРСКАЯ ЯЗВА, ВОЗБУДИТЕЛЬ |
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 |
Russian | VAKTSINY SIBIREIAZVENNYE, VAKTSINY PROTIV SIBIRSKOI IAZVY, ВАКЦИНЫ ПРОТИВ СИБИРСКОЙ ЯЗВЫ, ВАКЦИНЫ СИБИРЕЯЗВЕННЫЕ |
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 |