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Inhalational anthrax, part 2: prevention and treatment: strategies for preventing illness after exposure.

Article Excerpt
ABSTRACT: When untreated, inhalational anthrax typically results in a rapidly fatal illness. Evidence suggests that both the anthrax vaccine and prophylaxis with ciprofloxacin or doxycycline are effective in preventing illness after inhalational anthrax exposure. The current anthrax vaccine appears to have an adverse-effect profile that is similar to that of other adult vaccines. For patients with active infection, the CDC recommends a multi-antibiotic regimen that should include doxycycline or a fluoroquinolone and 2 additional antibiotics that have protein or RNA synthesis inhibition, such as rifampin and clindamycin. Monoclonal antibodies directed against anthrax toxins may also play a role in treating active infection.

KEY WORDS: Anthrax, Bioterrorism, Vaccines

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Early detection and rapid initiation of multidrug therapy during the 2001 US anthrax attack probably reduced mortality compared with historical reports. During a future bioterrorist attack, failure to detect anthrax in a timely manner will delay lifesaving therapy, resulting in increased anthrax-associated mortality. Because symptomatic patients will first present to primary care providers and to other outpatient medical settings, it is imperative that all clinicians have an awareness of the clinical signs and symptoms of inhalational anthrax.

In the May 2008 issue of The Journal of Respiratory Diseases, we reviewed the clinical course of inhalational anthrax and the diagnostic evaluation. In this article, we will address the strategies for prophylaxis and management.

TREATMENT

Preexposure vaccination

In the 1950s, the US army and the CDC developed and tested an acellular human anthrax vaccine (aluminum hydroxide--absorbed protective antigen vaccine) in placebo-controlled trials involving workers with high-risk exposure to anthrax particles. (1,2) These studies showed a 93% efficacy in preventing cutaneous infection. The vaccine is thought to be effective against inhalational anthrax because there have been no known cases of inhalational anthrax in immunized workers with high-risk occupations. (1) However, given the rarity of occupational inhalational anthrax, it is impossible to draw statistical conclusions from these experiments. (3)

Animal data suggest that the current US-licensed vaccine is highly effective in preventing anthrax infection after inhalational exposure. (4, 5) In humans, this vaccine induces an immune response in 83% after the first dose, 91% to 95% after the second dose, and 100% after the third dose. (6-9) After 2 doses, 95% to 100% of vaccinees have detectable anti--protective antigen (PA) IgG antibodies. (9) (Anti-PA antibodies developed in all of the survivors of inhalational anthrax during the 2001 attack. (10)

The duration of efficacy is unknown, but animal studies suggest that the vaccine is effective at least 2 years after the administration of 2 doses. (5, 11, 12) The CDC's Advisory Committee on Immunization Practices (ACIP) recommends that only civilian groups that are at high risk for repeated anthrax exposure (such as laboratory workers handling anthrax and high-risk veterinarian workers) be given preexposure vaccination. (13)

Concerns regarding the safety of the current US-licensed anthrax vaccine have been raised, (14, 15) but these concerns are not convincingly supported by the literature. Between January 1990 and August 2000, more than 1.8 million doses of anthrax vaccine were administered in the United States, mostly to military personnel. (16) Aside from injection site reactions, no serious adverse events were clearly associated with the anthrax vaccine.

Furthermore, no serious adverse events attributed to anthrax vaccination occurred in 1700 patients who were vaccinated and studied during the 2001 attack. (17) A National Academy of Sciences expert committee concluded that the current US-licensed anthrax vaccine has an adverse-effect profile that is similar to that of other adult vaccines. (18)

Prophylaxis

Animal studies suggest that ciprofloxacin and doxycycline are equally effective in preventing symptomatic infection after inhalational exposure. (19, 20) Other studies show ciprofloxacin, gatifloxacin, and moxifloxacin have similar prophylactic efficacy. (21) There is increasing evidence that antibiotic prophylaxis for persons exposed to anthrax particles during the 2001 attack prevented additional active infections...

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