Smallpox was an infectious disease caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, derived from varius ("spotted") or varus ("pimple"). The disease was originally known in English as the "pox" or "red plague"; the term "smallpox" was first used in Britain in the 15th century to distinguish variola from the "great pox" (syphilis). The last naturally occurring case of smallpox (Variola minor) was diagnosed on 26 October 1977.
Smallpox was localized in small blood vessels of the skin and in the mouth and throat. In the skin it resulted in a characteristic maculopapular rash and, later, raised fluid-filled blisters. V. major produced a more serious disease and had an overall mortality rate of 30–35%. V. minor caused a milder form of disease (also known as alastrim, cottonpox, milkpox, whitepox, and Cuban itch) which killed about 1% of its victims. Long-term complications of V. major infection included characteristic scars, commonly on the face, which occur in 65–85% of survivors. Blindness resulting from corneal ulceration and scarring, and limb deformities due to arthritis and osteomyelitis were less common complications, seen in about 2–5% of cases.
Except as a bioweapon smallpox was extinct in the home timeline. However, smallpox was a threat in several low-tech alternates. Crosstime Traffic employees were required to keep their immunizations up to date before traveling.
Unit 731 had experimented with smallpox along with other infectious diseases. A detachment from Unit 113 based on Midway used this in their raids on Hawaii leaving spore on Midway to potentially infect the Americans who succeeded in taking the island back from the Japanese. One marine did become infected and died from smallpox despite his inoculations.