The committee examined information on the human studies and extensive field trials conducted in the Soviet republics from the 1940s to the 1970s (described in Shlyakhov and Rubinstein, 1994a). These Soviet studies used the live spore anthrax vaccine, which differs substantially from the protective antigen anthrax vaccines used in the United States and the United Kingdom, in terms of composition, reactogenicity, and potential residual virulence. Moreover, the Soviet studies performed neither passive nor active long-term monitoring. For these reasons, the committee did not include the live spore vaccine studies in its analysis.
The committee notes a recent literature review on anthrax vaccine studies (Demicheli et al., 1998) conducted according to Cochrane Collaboration guidelines for systematic reviews of health care interventions. Only the Brachman study (described below) met the Cochrane criteria for prospective randomized or quasi-randomized studies of a protective antigen vaccine.5
During the development of the anthrax vaccine, several early studies examined adverse reactions in humans but did not provide detailed information on the nature of the monitoring for adverse effects. These studies used early versions of the culture filtrate (protective antigen) vaccine. Wright and colleagues (1954) described the reactions of 660 persons at Camp Detrick who received a total of 1,936 injections. They found that 0.7 percent of vaccinated subjects reported systemic reactions—typically consisting of mild muscle aches, headaches, and mild-to-moderate malaise lasting 1 to 2 days. Significant local reactions—typically swelling (5–10 cm in diameter) and local pruritus (itching)—occurred in 2.4 percent of the subjects. The incidence of local reactions increased with the number of injections.
In another study at Fort Detrick (Puziss and Wright, 1963), 0.5-ml injections of protective antigen led to similar results. The study reported low rates of erythema, edema, or pruritus at the site of injection (no details were provided) and no systemic reactions.
Darlow and colleagues in Great Britain (1956) reported on the administration of 1,057 injections of the anthrax vaccine to 373 individuals (369 persons received two or more injections) over a period of 4 years. Most of the reactions were mild and brief (local tenderness and swelling). There was an increase in the number of persons experiencing pain after the second dose, and local reactions
The one live spore vaccine study that met the Cochrane criteria was a field trial conducted by Burgasov and colleagues. In this study, 107,285 individuals received the live spore anthrax vaccination and 49,974 individuals served as controls. The review by Demicheli and colleagues (1998) does not report any information from the Burgasov study regarding adverse effects of the vaccine.