Natural history of smallpox We briefly review relevant features of the natural history and epidemiology of smallpox [17, [25] [26] [27] 8, 28] . Following infection by the variola virus, individuals exhibited an incubation period of approximately 7-19 days with 10-14 being most typical. Sudden onset of fever and malaise, often with accompanying headache and backache, began the initial (or pre-eruptive) phase of smallpox. After 2-3 (or perhaps 4) days, individuals with the most common form, ordinary type smallpox, developed the characteristic focal rash, preceded in many cases by oropharyngeal lesions. In fatal cases of ordinary smallpox, death often occurred between the tenth and sixteenth day of symptoms; among survivors, most scabs had separated by day 22-27 of illness [26] .