Smallpox was an infectious disease caused by variola virus (often called smallpox virus) which belongs to the genus Orthopoxvirus.[7][11] The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) certified the global eradication of the disease in 1980,[10] making it the only human disease to be eradicated.[12]

Other namesvariola,[1] variola vera,[2] pox,[3] red plague[4]
A child with smallpox in Bangladesh in 1973. The bumps filled with thick fluid and a depression or dimple in the center are characteristic.
SpecialtyInfectious disease
ComplicationsScarring of the skin, blindness[6]
Usual onset1 to 3 weeks following exposure[5]
DurationAbout 4 weeks[5]
Causesvariola major virus, variola minor virus (spread between people)[6][7]
Diagnostic methodBased on symptoms and confirmed by PCR[8]
Differential diagnosisChickenpox, impetigo, molluscum contagiosum, monkeypox[8]
PreventionSmallpox vaccine[9]
TreatmentSupportive care[10]
Prognosis30% risk of death[5]
FrequencyEradicated (last wild case in 1977)

The initial symptoms of the disease included fever and vomiting.[5] This was followed by formation of ulcers in the mouth and a skin rash.[5] Over a number of days, the skin rash turned into the characteristic fluid-filled blisters with a dent in the center.[5] The bumps then scabbed over and fell off, leaving scars.[5] The disease was spread between people or via contaminated objects.[6][13] Prevention was achieved mainly through the smallpox vaccine.[9] Once the disease had developed, certain antiviral medications could potentially have helped, but such medications did not become available until after the disease was eradicated.[9] The risk of death was about 30%, with higher rates among babies.[6][14] Often, those who survived had extensive scarring of their skin, and some were left blind.[6]

The earliest evidence of the disease dates to around 1500 BC in Egyptian mummies.[15][16] The disease historically occurred in outbreaks.[10] In 18th-century Europe, it is estimated that 400,000 people died from the disease per year, and that one-third of all cases of blindness were due to smallpox.[10][17] Smallpox is estimated to have killed up to 300 million people in the 20th century[18][19] and around 500 million people in the last 100 years of its existence.[20] Earlier deaths included six European monarchs.[10][17] As recently as 1967, 15 million cases occurred a year.[10]

Inoculation for smallpox appears to have started in China around the 1500s.[21][22] Europe adopted this practice from Asia in the first half of the 18th century.[23] In 1796, Edward Jenner introduced the modern smallpox vaccine.[24][25] In 1967, the WHO intensified efforts to eliminate the disease.[10] Smallpox is one of two infectious diseases to have been eradicated, the other being rinderpest in 2011.[26][27] The term "smallpox" was first used in England in the 16th century to distinguish the disease from syphilis, which was then known as the "great pox".[28][29] Other historical names for the disease include pox, speckled monster, and red plague.[3][4][29]

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