The origin of smallpox is unknown. The earliest evidence of the disease dates to the 3rd century BCE in Egyptian mummies. The disease historically occurred in outbreaks. In 18th-century Europe, it is estimated 400,000 people per year died from the disease, and one-third of the cases resulted in blindness. These deaths included those of four reigning monarchs and a queen consort. Smallpox is estimated to have killed up to 300 million people in the 20th century and around 500 million people in the last 100 years of its existence. As recently as 1967, 15 million cases occurred a year.
Edward Jenner discovered in 1798 that vaccination could prevent smallpox. In 1967, the WHO intensified efforts to eliminate the disease. Smallpox is one of two infectious diseases to have been eradicated, the other being rinderpest in 2011. The term "smallpox" was first used in Britain in the 15th century to distinguish the disease from syphilis, which was then known as the "great pox". Other historical names for the disease include pox, speckled monster, and red plague.
There were two clinical forms of smallpox. Variola major was the severe and most common form, with a more extensive rash and higher fever. Variola minor was a less common presentation, and a much less severe disease, with historical death rates of one percent or less. Subclinical (asymptomatic) infections with Variola virus were noted but were not common. In addition, a form called variola sine eruptione (smallpox without rash) was seen generally in vaccinated persons. This form was marked by a fever that occurred after the usual incubation period and could be confirmed only by antibody studies or, rarely, by virus isolation.