Smallpox was an infectious disease unique to humans, 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 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 produces a more serious disease and has an overall mortality rate of 30–35%. V. minor causes a milder form of disease (also known as alastrim, cottonpox, milkpox, whitepox, and Cuban itch) which kills about 1% of its victims. Long-term complications of V. major infection include 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 are less common complications, seen in about 2–5% of cases.
Smallpox is believed to have emerged in human populations about 10,000 BC. The earliest physical evidence of it is probably the pustular rash on the mummified body of Pharaoh Ramses V of Egypt. The disease killed an estimated 400,000 Europeans annually during the closing years of the 18th century (including five reigning monarchs), and was responsible for a third of all blindness. Of all those infected, 20–60%—and over 80% of infected children—died from the disease. Smallpox was responsible for an estimated 300–500 million deaths during the 20th century. As recently as 1967, the World Health Organization (WHO) estimated that 15 million people contracted the disease and that two million died in that year.