Treatment and Vaccination for Anthrax
Anthrax disease is rapidly progressive, thus treatment should be initiated at the earliest sign or suspicion of disease. The following recommendations are based on the Consensus Statement published by the American Medical Association in 1999 1. (It should be understood that these recommendations are made based on a limited number of animal studies, and no human data.)
Treatment for Anthrax Disease
Until the actual spectrum of sensitivity to drugs is made, anthrax should be treated with ciprofloxocin or other fluoroquinolones. Adults treated for presumed inhalational anthrax infections should ideally receive intravenous (IV) cipro: 400 mg every 12 hours. However, if IV cipro is not readily available, oral cipro: 500 mg every 12 hours should be used. Penicillin or doxycycline may be substituted for cipro if and when the anthrax is found to be sensitive to them.
Prophylactic Treatment After Exposure
There are no FDA-approved post-exposure antibiotic regimens following exposure (but no clinical disease) to an anthrax aerosol. The AMA Consensus Statement recommends that post-exposure prophylaxis include oral cipro (500 mg every 12 hours) initially. Amoxicillin or doxycycline may be substituted if and when the anthrax is found to be sensitive to these antibiotics.
Experimental evidence2 has demonstrated that treatment with antibiotics beginning 1 day after exposure to a lethal aerosol challenge with anthrax spores can provide significant protection against death. All three drugs used in this study—ciprofloxacin, doxycycline, and penicillin—were effective. The optimal protection was afforded by combining antibiotics with active immunization.
Currently there are only a limited number of available anthrax vaccinations which are controlled by the Department of Defense. No vaccinations are available to the public at large. The only licensed human vaccine against anthrax is produced by the Michigan Department of Public Health. This vaccine is made from sterile filtrates of microaerophilic cultures of an attenuated, unencapsulated, nonproteolytic strain (V770-NP1-R) of B anthracis.
Some vaccine lots contain very small amounts of lethal factor and lesser amounts of edema factor, as determined by antibody responses in vaccinated animals,3,4,5 although this antibody response has not been reported in the limited observations in human vaccinees.6 Although protective antigen by itself is an effective immunogen,7 it is unknown whether the small amounts of lethal or edema factor that are present in some lots of the vaccine contribute to its protective efficacy. The potency of vaccine lots is determined by showing protection of parenterally challenged guinea pigs. There is no characterization of the amount and form of the protective antigen or other toxin components in the vaccine.
The recommended schedule for vaccination is at 0, 2, and 4 weeks, followed by boosters of 0.5 mL at 6, 12, and 18 months. Annual boosters are recommended if the potential for exposure continues. In the United States, immunization with the licensed vaccine induced an immune response in 91% of those tested after receiving two or more doses.9
Vaccination is indicated for protection against the use of anthrax in biological warfare. Approximately 150,000 service members received this licensed MDPH vaccine between 11 January and 28 February 1991 (25%–30% of the total U.S. forces deployed during the Persian Gulf War).
A live, attenuated, unencapsulated, spore vaccine is used for humans in the former USSR. The vaccine is given by scarification or subcutaneously. Its developers claim it to be reasonably well tolerated and to show some degree of protective efficacy against cutaneous anthrax in clinical field trials.7
Side Effects of Vaccination
In two different studies, the incidence of significant local and systemic reactions to the vaccine used in the placebo-controlled field trial was 2.4% to 2.8% and 0.2% to 1.3%.12 The vaccine currently licensed in the United States is reported to have a similar incidence of reactions. Local reactions considered significant consist of induration, erythema in an area larger than 5 cm in diameter, edema, pruritus, warmth, and tenderness. These reactions peak at 1 to 2 days and usually disappear within 2 to 3 days. Very rare reactions include edema extending from the local site to the elbow or forearm, and a small, painless nodule that may persist for weeks. People who have recovered from a cutaneous infection with anthrax may have very severe local reactions. Systemic reactions are characterized by mild myalgia (muscle pain,) headache, and mild-to-moderate malaise (fatigue) that lasts for 1 to 2 days. There are no long-term sequelae of local or systemic reactions.
1. Inglesby, TV et al, Anthrax as a Biological Weapon, JAMA, May 12, 1999-Vol 281, No. 18.
2. Friedlander AM, Welkos SL, Pitt MLM, et al. Postexposure prophylaxis against experimental inhalation anthrax. J Infect Dis. 1993;167(5):1239–1243.
3. Ivins BI, Ezzell JW Jr, Jemski J, Hedlund KW, Ristroph JD, Leppla SH. Immunization studies with attenuated strains of Bacillus anthracis. Infect Immun. 1986;52:454–458.
4. Ivins BE, Welkos SL. Recent advances in the development of an improved, human anthrax vaccine. Eur J Epidemiol. 1988;4:12–19.
5. Little SF, Knudson GB. Comparative efficacy of Bacillus anthracis live spore vaccine and protective antigen vaccine against anthrax in the guinea pig. Infect Immun. 1986;52:509–512.
6. Turnbull PCB, Broster MG, Carman JA, Manchee RJ, Melling J. Development of antibodies to protective antigen and lethal factor components of anthrax toxin in humans and guinea pigs and their relevance to protective immunity. Infect Immun. 1986;52:356–363.
7. Ivins BE, Welkos SL. Cloning and expression of the Bacillus anthracis protective antigen gene in Bacillus subtilis. Infect Immun. 1986;54:537–542.
9. Buchanan TM, Feeley JC, Hayes PS, Brachman PS. Anthrax indirect microhemagglutination test. J Immunol. 1971;107:1631–1636.
10. Lincoln RE, Fish DC. Anthrax toxin. In: Montie TC, Kadis S, Ajl SJ, eds. Microbial Toxins. Vol 3. New York, NY: Academic Press; 1970: 361–414.
11. Hambleton P, Carman JA, Melling J. Anthrax: The disease in relation to vaccines. Vaccine. 1984;2:125–132.
12. Wright GG, Green TW, Kanode RG Jr. Studies on immunity in anthrax, V: Immunizing activity of alum-precipitated protective antigen. J Immunol. 1954;73:387–391.
(The preceding material was derived from the Virtual Naval Hospital web site, www.vnh.org)