November 8, 2001

Anthrax is an infection caused by Bacillus anthracis, an aerobic, gram-positive, spore-forming, nonmotile bacillus species. The three primary clinical manifestations of the disease are: cutaneous, inhalational and gastrointestinal.

Cutaneous: This is the most common presentation, accounting for 95% of naturally occurring infections. The organisms' portal of entry is a cut or abrasion on the skin. The areas of greatest exposure are the hands, arms, face or neck. Potential sources of the organism include wool, hides, leather or hair products of infected animals, particularly goats. Exposure may also result from a bio-terrorist act (e.g., contaminated letter). Incubation periods may be as long as 12 days. Skin infection begins as a raised pruritic papule, resembling an insect bite. Within 1-2 days a vesicle develops, followed by a painless ulcer 1-3 cm in diameter with a characteristic black necrotic eschar in the center. Localized lymphangitis and painful lymphadenopathy may occur. Although antibiotic therapy does not appear to change the course of eschar formation and healing, it does decrease the risk of systemic disease. Mortality rates are 20% if untreated, but <1% with antibiotic therapy.

Inhalational: This is the most serious presentation, resulting from deposition of spore-bearing particles of 1 to 5 microns into the alveolar spaces. Macrophages ingest the spores that are then transported to the pulmonary lymphatics where they germinate. The asymptomatic incubation period is usually 1-7 days after exposure, but spores may germinate in the mediastinal lymphatics for up to 60 days. Once germination occurs, replicating bacteria release toxins leading to hemorrhage, edema and necrosis. Initial symptoms resemble a flu-like illness with fever, cough, and headache, but without rhinitis, followed by progressive dyspnea that rapidly progresses to respiratory failure and death within hours. Case-fatality estimates are extremely high, even with supportive care and appropriate antibiotics.

Gastrointestinal: The relatively rare intestinal form of anthrax follows ingestion, deposition and subsequent germination of spores in the upper or lower gastrointestinal tract. The former leads to the oral-pharyngeal form of the disease marked by oral-esophageal ulcers and regional lymphadenopathy. The latter results in acute inflammation of the intestinal tract with symptoms that include: anorexia, malaise, nausea, vomiting, and fever. Subsequently patients develop abdominal pain, hematemesis, severe, bloody diarrhea and sepsis. Intestinal anthrax may be fatal in 25% to 60% of cases; the effect of early antibiotic therapy is unknown.

Evaluation and Management of Possible Anthrax Exposure Due to Bio-terrorist Acts

The risk of exposure is remote for people not in direct contact with the contaminated object/site and greatest for those present in the immediate vicinity of contamination. The disease is not spread by casual contact or by coughing and sneezing.

Active Infection

Anthrax infections are diagnosed by isolating B. anthracis from the blood, cerebrospinal fluid, skin lesions, or respiratory secretions or by measuring specific antibodies in the blood of persons with suspected cases. Rapid diagnostic immunoassays and PCR are available at national reference laboratories. Strategies of antimicrobial treatment of active anthrax infection are evolving. For the latest recommendations see http://www.cdc.gov/mmwr and http://www.bt.cdc.gov.

Exposure

For asymptomatic individuals with low risk exposure, antimicrobials are not warranted until there is an evident risk of actual exposure based on microbiologically documented anthrax as determined by law enforcement and public health authorities. The woman's healthcare provider is not the party to validate a threat.

In the current crisis, when screening for exposure is deemed necessary, it is conducted by nasal swab. The resultant secretions can be examined by gram stain and culture. However, given the lack of reliability of nasal swab screening, post-exposure prophylaxis is indicated after confirmed or high risk suspected exposure. In the latter cases, treatment can be stopped if anthrax is not documented.

For adult post-exposure prophylaxis against anthrax infections the CDC currently recommends ciprofloxacin 500 mg p.o. every 12 hours for 60 days or doxycycline 100 mg p.o. every 12 hours for 60 days.

Management of Exposed Asymptomatic Pregnant or Lactating Women

At this time the Committee on Obstetric Practice recommends that prophylaxis of asymptomatic pregnant and lactating women be limited to those women who have had exposure to a confirmed environmental contamination or who are exposed to a high risk source as determined by the local Department of Health. Prophylaxis for asymptomatic pregnant or lactating women is as follows:

• ciprofloxacin 500 mg p.o. every 12 hours x 60 days (6).

If a woman has been prescribed ciprofloxacin and is found to be pregnant, she should continue her course of antibiotics for the full 60 days (6) unless the bacteria is shown to be penicillin-sensitive she should then be switched to amoxicillin. A 1999 expert review of published data on experiences with ciprofloxacin concluded that therapeutic doses during pregnancy are unlikely to pose substantial teratogenic risk but the data are insufficient to state that there is no risk (1). In the case of penicillin and ciprofloxacin-allergic patients, treatment should consist of doxycycline or consider penicillin desensitization if the organism is proven sensitive (6). In this situation, the risks of anthrax would far out weigh the risks of doxycycline to the fetus (i.e., dental staining of the primary teeth and possible depressed bone growth and defective dental enamel).

Because these guidelines are continually evolving, please refer to http://www.bt.cdc.gov and http://www.cdc.gov/mmwr for any updates in treatment guidelines.

Sincerely,

Ralph W. Hale, MD, FACOG
Executive Vice President

Stanley Zinberg, MD, MS, FACOG
Vice President, Practice Activities

1) Friedman JM, Polifka JE. Ciprofloxacin. In: Teratogenic effects of drugs: resource for clinicians (TERIS). 2nd ed. Baltimore: The Johns Hopkins University Press, 2000[a]:149-150.

2) Friedman JM, Polifka JE. Doxycyclicne. In: Teratogenic effects of drugs: a resource for clinicians (TERIS). 2nd ed. Baltimore: The Johns Hopkins University Press, 2000[b]: 238-239.

3) Center for Drug Evaluation and Research. U.S. Food and Drug Administration. CIPRO (Ciprofloxacin) use by pregnant and lactating women. Available at http://www.fda.gov/cder/drug/infopage/cipro/cipropreg.htm. Retrieved November 2, 2001.

4) Center for Drug Evaluation and Research. U.S. Food and Drug Administration. Drug preparedness and response to bio-terrorism. Available at http://www.fda.gov/cder/drugprepare/default.htm. Retrieved November 2, 2001.

5) Center for Drug Evaluation and Research. U.S. Food and Drug Administration. Doxycycline (Vibramycin, Monodox, Doryx, Doxy, Atridox, Periodox, Vibra-Tabs) use by pregnant and lactating women. Available at http://www.fda.gov/cder/drug/infopage/penG_doxy/doxypreg.htm. Retrieved November 2, 2001.

6) Updated recommendations for antimicrobial prophylaxis among asymptomatic pregnant women after exposure to bacillus anthracis. MMWR Morb Mortal Wkly Rep 2001[b];50:960.

1) Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, et al. Anthrax as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA 1999;281:1735-1745[erratum JAMA 2000; 283:1963].

2) Update: investigation of anthrax associated with intentional exposure and interim public health guidelines, October 2001. MMWR Morb Mortal Wkly Rep 2001[a];50:889-893.

3) Use of anthrax vaccine in the United States. MMWR Morb Mortal Wkly Rep 2000;49(RR-15):1-20.