Any assessment of the scientific needs for variola virus must include some grasp of the ravages of smallpox and the terrible suffering caused by the disease.
The incubation period of smallpox, which can be as short as 7 days or as long as 19 days, is a period of intense activity in terms of viral replication and spread within the body despite the absence of clinical symptoms. The incubation period ends when the patient becomes feverish and ill. The onset of fever is sudden, the patient's temperature usually rising to between 38.5°C and 40.5°C. Other symptoms include severe headache and backache. Vomiting occurs in about half and diarrhea in about 10 percent of cases. The patient frequently exhibits general lethargy and malaise. By the second or third day the temperature falls, and the patient feels somewhat better. At this time the smallpox rash begins to appear.
The lesions typically begin as minute red spots on the tongue and palate. Over a period of 24–48 hours, a macular rash appears on the face, then spreads to the trunk and extremities. The lesions progress over a 2-week period to vesicles, pustules, and crusts (scabs). A hemorrhagic and rapidly fatal form of the disease occurs in a minority of patients, Secondary infection of lesions can lead to osteomyelitis and septic arthritis, resulting in bone shortening, flail joints, and gross bone deformities. Scarred lesions or pockmarks remain with those who have survived the disease.