THE DISEASE — History − Smallpox was a world-wide infectious disease, affecting only humans, until it was eradicated in 1977 by intensive case finding and vaccination. The last case in the US occurred in 1949. Smallpox vaccination in the US was discontinued in civili

Epidemiology − Smallpox is transmitted by inhalation of the causative variola virus (an orthopoxvirus) in droplets or aerosols from the respiratory tract, or by contact with skin le- sions of infected patients or their bedding or clothing. The incubation period is 7 to 17 days, with an average of 12 days. The disease begins with fever and prostration for 2 to 4 days, fol- lowed by the rash, which lasts for weeks with slow evolution from papules to vesicles, then pustules and finally scabs, all at the same stage in any one area. Disease transmission may occur late in the prodrome but mainly occurs during the rash, and diminishes as the lesions scab. Transmission is most common in families; about 50% of unvaccinated family members become infected. In the past the mortality rate of smallpox was 20%-30% in unvaccinated po- pulations; many survivors were left with severe scarring, and some with blindness from ocu- lar involvement. Natural infection confers lifelong immunity. SMALLPOX VACCINE — Formulations − Smallpox vaccine is a suspension of live vac- cinia virus, a virus that apparently evolved from serial passage of cowpox. The vaccine to be used in the first and second phases of vaccination (Dryvax − Wyeth) is a lyophilized prepara- tion derived from the lymph of calves that had been inoculated with vaccinia virus. According to the CDC, Dryvax is already available in adequate amounts for Phases I and II. It contains small amounts of polymyxin B, dihydrostreptomycin, chlortetracycline and neomycin to prevent bacterial contamination. A similar calf-derived vaccine produced by Aventis-Pasteur years ago is also available as a reserve supply. A third vaccine produced by Acambis-Baxter using the same strain of vaccinia virus as in Dryvax, but grown in monkey kidney and human fibroblast cells, is expected to be available in sufficient amounts to vaccinate the entire US po- pulation in 2004.