Basics
Description
Bacillus anthracis is a spore-forming, gram-positive rod that can cause acute infection (anthrax) in humans and animals.
Epidemiology
- Anthrax is primarily zoonotic. Most naturally acquired anthrax infections are cutaneous (95%). Inhalational (5%) and GI (<1%) forms are particularly rare.
- Prior to October 2001, only 18 cases of inhalational anthrax were reported in the United States during the 20th century.
- No human-to-human spread of inhalational anthrax has been reported.
- Rare cases of human-to-human transmission of cutaneous anthrax have been reported after direct contact with infected skin lesions.
- Anthrax has been used as an agent of bioterrorism.
General Prevention
- Antibiotics are effective against germinating B. anthracis but not against the spores. Therefore, if prophylactic antibiotics are stopped prematurely, remaining spores can cause disease when they germinate. This phenomenon of delayed-onset disease does not occur with cutaneous or GI exposures.
- Where the threat of transmission of B. anthracis spores is deemed credible, decontamination of skin and potential fomites (e.g., clothing) may be considered to reduce the risk for cutaneous and GI forms of the disease.
- Anthrax vaccine absorbed (AVA) is the only licensed human anthrax vaccine in the United States. Primary vaccination consists of subcutaneous injections at 0, 2, and 4 weeks and 3 booster vaccinations at 6, 12, and 18 months. Annual booster injections are required to maintain immunity. The most common adverse event is injection-site discomfort (e.g., edema, pain, local hypersensitivity).
- Infection control
- Immediately notify the hospital epidemiologist, infection control department, or local health department of suspected cases.
- No data suggest that patient-to-patient transmission of inhalational anthrax occurs. Standard barrier isolation precautions are recommended for all hospitalized patients with all forms of anthrax infection. High-efficiency particulate air-filter masks or other measures for airborne precautions are not indicated.
- There is no need to immunize or provide prophylaxis to patient contacts unless they, like the patient, were exposed to the aerosol.
- If anthrax is used as a bioweapon, spores may be detected on environmental surfaces. Inhalational anthrax is unlikely to be caused by secondary aerosolization of these spores.
Alert
Pulmonary disease caused by anthrax is a hemorrhagic mediastinitis with pleural effusions and not a bronchopneumonia.
Pathophysiology
- After inhalation, wound inoculation, or ingestion, B. anthracis spores infect macrophages, germinate, and proliferate.
- Proliferation occurs at the site of infection and in regional lymph nodes.
- Replicating bacteria release toxins, leading to edema, hemorrhage, and necrosis.
- Incubation period depends on the route of transmission.
- Inhalational anthrax: Infection requires inhalation of >8,000 spores; incubation period is 2-60 days.
- Cutaneous anthrax: Spores enter a cut or abrasion in the skin; incubation period is 1-12 days.
- GI anthrax: Spores are ingested in undercooked, infected meat; incubation period is 1-7 days; infection occurs in the upper (oropharyngeal lesions) or lower (intestinal lesions) GI tract.
- Hematogenous spread of the bacteria causes infection at other sites, including the CNS, liver, spleen, and kidney.
Commonly Associated Conditions
If anthrax is intentionally released, physicians must be alert for diseases caused by other potential biologic warfare agents (e.g., plague, tularemia, Q fever, smallpox, and botulism).
Diagnosis
History
- Inhalational anthrax
- Clinical presentation is a 2-stage illness.
- Initial symptoms are nonspecific and last 1-3 days. They include low-grade fever, dry cough, headache, vomiting, chills, weakness, abdominal pain, and substernal discomfort. This stage may be followed by a brief period of apparent recovery.
- 2nd-stage symptoms develop abruptly 2-5 days later: fever, hemoptysis, dyspnea, chest pain, and profuse diaphoresis. Death may occur within 1-2 days.
- Cutaneous anthrax
- Painless lesions develop on affected areas soon after exposure.
- Systemic symptoms of fever, malaise, and headache may occur.
- GI anthrax
- Oropharyngeal form causes sore throat, dysphagia, and fever.
- Intestinal form also causes nausea, vomiting, anorexia, severe abdominal pain, and bloody diarrhea.
Physical Exam
- Clinical presentation of anthrax in children is varied; rapid diagnosis and effective treatment require recognition of the broad spectrum of clinical presentations.
- Inhalational anthrax
- Tachypnea, hypoxia, cyanosis
- Stridor, rales, signs of pleural effusion
- Hemoptysis, hematemesis, melena
- Cutaneous anthrax
- Initial painless, pruritic macule or papule enlarges into a 1-3-cm round ulcer by the second day.
- 1-3-mm vesicles with clear or serosanguineous fluid surround the ulcer.
- A painless, depressed, black eschar follows, often with extensive local edema.
- Over 1-2 weeks, the eschar dries, loosens, and falls off, occasionally with scarring.
- Painful, regional lymphadenopathy may occur.
- GI anthrax
- Unilateral oral or esophageal ulcers, cervical lymphadenopathy
- Cecal or terminal ileal ulcers (Intestinal anthrax progresses to massive ascites and acute abdomen.)
- Disseminated anthrax (potential complication of any of the above forms of anthrax):
- Sepsis syndrome: tachycardia, hypotension, septic shock
- Meningitis: meningismus, delirium, obtundation
Diagnostic Tests & Interpretation
Lab
- Gram stain smear and culture from vesicular fluid
- Diagnose cutaneous anthrax
- Gram stain reveals large, gram-positive, boxcar-shaped bacilli.
- Capsule is visible on polychrome methylene blue stain.
- B. anthracis grows readily on blood agar.
- Anthraxin skin test
- Measures anthrax cell-mediated immunity
- It is positive in 80% of patients within 72 hours of infection and in >95% of cases within 3 weeks.
- The test was positive in 72% of patients >16 years after recovery.
- Serologic enzyme-linked immunosorbent assay (ELISA):
- Measures antibodies to the lethal and edema toxins of B. anthracis
- Positive if a single acute-phase titer is >1:32 or if there is a 4-fold or greater rise between acute and convalescent titers collected 4 weeks apart
- Polymerase chain reaction, immunohistochemical staining
- Nasopharyngeal swab or induced respiratory secretion culture
- Used for epidemiologic investigation
- The sensitivity, specificity, and predictive value of nasal swab testing are unknown; therefore, this test should not be used to guide the use of postexposure prophylactic antibiotics.
- Blood culture: Patients with cutaneous anthrax may have bacteremia with B. anthracis even without significant signs of systemic disease.
- CBC
- Serum electrolytes, glucose, and calcium
- Hypokalemia, acidosis, hypoglycemia, and hypocalcemia occurred during experimental anthrax infection in animals.
- Hemorrhagic meningitis
Imaging
Chest x-ray (or chest CT scan)
- Inhalational anthrax causes a hemorrhagic mediastinitis.
- May show a widened mediastinum and pleural effusions
- No infiltrates are present.
Differential Diagnosis
- The prodromal illness of inhalational anthrax may resemble a lower respiratory tract infection, although upper respiratory infection symptoms are characteristically absent.
- Patients with inhalational anthrax may have a widened mediastinum on chest radiograph which may resemble an aortic aneurysm or bacterial mediastinitis.
- Necrotic skin lesions may resemble plague, tularemia, ecthyma gangrenosum, and brown recluse spider bite.
- GI anthrax may be confused with other infectious enteritides (e.g., Shigella, Salmonella, Yersinia, Campylobacter, enterohemorrhagic Escherichia coli, Clostridium difficile, colitis), intussusception, Meckel diverticulum, and inflammatory bowel disease.
Treatment
Medication
- Postexposure prophylaxis
- Ciprofloxacin 15 mg/kg (up to 500 mg) ordoxycycline 2.2 mg/kg (up to 100 mg) or levofloxacin 8 mg/kg (up to 250 mg) PO b.i.d. for 60 days.
- Pediatric: Use ciprofloxacin for initial prophylaxis. Switch to amoxicillin or penicillin if susceptibility testing permits.
- Treatment
- For all forms of anthrax, begin with IV therapy and switch to oral therapy when clinically appropriate. Treat for 60 days (IV and PO combined).
- Inhalational or GI anthrax: ciprofloxacin 15 mg/kg (up to 400 mg) ordoxycycline 2.2 mg/kg (up to 100 mg) IV q12h plusclindamycin or rifampin
- Cutaneous anthrax: ciprofloxacin or doxycycline IV. (Pediatric: Begin therapy with ciprofloxacin [plus clindamycin or rifampin for inhalational/GI anthrax] and convert to penicillin G IV if susceptibility testing permits and when clinical improvement is documented.)
General Measures
Direct physical contact with a substance alleged to be anthrax:
- Wash exposed skin and articles of clothing with soap and water.
- Administer postexposure prophylaxis until the substance is proved not to be anthrax.
- Contact the public health department or the Centers for Disease Control and Prevention (CDC).
- For severe anthrax, anthrax-specific hyperimmune globulin 5% should be considered in consultation with CDC.
Ongoing Care
Prognosis
- Inhalational anthrax
- Case fatality rates were previously estimated to be >85% after symptoms develop. However, early use of appropriate antibiotic therapy appears to improve survival.
- Survival rate is higher if symptoms develop >30 days after exposure.
- Cutaneous anthrax
- Case fatality rate is 20% without antibiotic treatment and <1% with antibiotic treatment.
- GI anthrax: Case fatality rate is 25-60%.
Complications
- Antibiotic therapy of cutaneous anthrax limits the likelihood of developing systemic symptoms but does not change the course of the eschar formation.
- Systemic dissemination of inhalational, cutaneous, or GI anthrax may lead to sepsis, meningitis, and death.
Additional Reading
- Akbayram S, Dogan M, Akgun C, et al. Clinical findings in children with cutaneous anthrax in Eastern Turkey. Pediatr Dermatol. 2010;27(6):600-606. [View Abstract]
- Alexander JJ, Colangelo PM, Cooper CK, et al. Amoxicillin for postexposure inhalational anthrax in pediatrics: rationale for dosing recommendations. Pediatr Infect Dis J. 2008;27(11):955-957. [View Abstract]
- Bravata DM, Holty JE, Wang E, et al. Inhalational, gastrointestinal, and cutaneous anthrax in children: a systematic review of cases: 1900 to 2005. Arch Pediatr Adolesc Med. 2007;161(9):896-905. [View Abstract]
- Centers for Disease Control and Prevention. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2000;49(RR-15):1-20. MMWR. 2001;50(42):909-919. Erratum in: MMWR. 2001;50(43):962.
- Hendricks KA, Wright ME, Shadomy SV, et al. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis. 2014;20(2). [View Abstract]
- Kyriacou DN, Adamski A, Khardori N. Anthrax: from antiquity and obscurity to a front-runner in bioterrorism. Infect Dis Clin North Am. 2006;20(2):227-251. [View Abstract]
- Li F, Nandy P, Chien S, et al. Pharmacometrics-based dose selection of levofloxacin as a treatment for postexposure inhalational anthrax in children. Antimicrob Agents Chemother. 2010;54(1):375-379. [View Abstract]
- Scorpio A, Blank TE, Day WA, et al. Anthrax vaccines: Pasteur to the present. Cell Mol Life Sci. 2006;63:2237-2248.
- Stocker JT. Clinical and pathological differential diagnosis of selected potential bioterrorism agents of interest to pediatric health care providers. Clin Lab Med. 2006;26(2):329-344. [View Abstract]
Codes
ICD09
- 022.9 Anthrax, unspecified
- 022.0 Cutaneous anthrax
- 022.1 Pulmonary anthrax
- 022.2 Gastrointestinal anthrax
- 022.3 Anthrax septicemia
- 022.8 Other specified manifestations of anthrax
ICD10
- A22.9 Anthrax, unspecified
- A22.0 Cutaneous anthrax
- A22.1 Pulmonary anthrax
- A22.2 Gastrointestinal anthrax
- A22.8 Other forms of anthrax
- A22.7 Anthrax sepsis
SNOMED
- 409498004 Anthrax (disorder)
- 84980006 Cutaneous anthrax (disorder)
- 11389007 Inhalational anthrax (disorder)
- 111798006 Gastrointestinal anthrax (disorder)
- 14972006 Anthrax septicemia
FAQ
- Q: Does the government have a plan in place if there were mass exposure to anthrax?
- A: Yes. Under emergency plans, the federal government would ship appropriate antibiotics from its stockpile to wherever they are needed.
- Q: Should individuals ask their physicians to write a prescription for ciprofloxacin (or other antibiotic) so they have prophylaxis available?
- A: No. Ciprofloxacin and other antibiotics should not be prescribed unless there is a clearly indicated need. In addition, indiscriminate prescribing and widespread use of ciprofloxacin could hasten the development of drug-resistant organisms.
- Q: Can a person get screened or tested for anthrax?
- A: No screening test is available to determine whether anthrax exposure has occurred. The only way exposure can be determined is through a public health investigation.
- Q: What are the clues to differentiate pulmonary or inhalational anthrax from RSV in children?
- A: Children with pulmonary anthrax display a high WBC count with left shift compared to the relatively normal WBC of those with RSV. Blood O2 levels may be severely depressed in inhalational anthrax.