Smallpox was a systemic disease, officially eradicated since 1979 (WHO), caused by infection with the Variola major virus, whose only reservoir was infected humans.
The infection was usually transmitted via inhalation of droplets. After an average incubation period of 12 days, a high fever accompanied by non-specific general symptoms abruptly appeared. The fever then receded and a characteristic skin eruption appeared. Subsequently the fever rose again, and serious complications generally developed (pulmonary, cardio-circulatory, neurological, etc.), resulting in death in up to 50% of cases. Survivors who overcame this phase would see the rash resolving, leaving permanent scars. No effective therapy was available. The disease was preventable by an effective live-attenuated vaccine, whose large scale use lead to its eradication.