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Smallpox is an acute infectious disease unique to humans, caused by either of two virus variants named Variola major and Variola minor. Also known by the Latin names Variola or Variola vera; a derivative of the Latin varius, meaning spotted, or varus, meaning "pimple". The term "smallpox" was first used in Europe in the 15th century to distinguish variola from the great pox (syphilis).

Smallpox localizes in small blood vessels of the skin and in the mouth and throat. In the skin, this results in the characteristic maculopapular rash, which evolves into raised vesicles, then into fluid-filled pustules. V. major produces a more serious disease and has an overall mortality rate of 30–35%. V. minor (also known as alastrim, cottonpox, milkpox, whitepox, and Cuban itch) causes a milder form of disease which kills ~1% of its victims.

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