Smallpox was an infectious disease caused by one of two virus variants, Variola major and Variola minor.[7] The agent of variola virus (VARV) belongs to the genus Orthopoxvirus.[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] The risk of death after contracting the disease was about 30%, with higher rates among babies.[6][12] Often those who survived had extensive scarring of their skin, and some were left blind.[6]

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, Variola minor (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 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 medication may have helped.[9]

The origin of smallpox is unknown;[14] however, the earliest evidence of the disease dates to the 3rd century BCE in Egyptian mummies.[14] 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][15] Smallpox is estimated to have killed up to 300 million people in the 20th century[16][17] and around 500 million people in the last 100 years of its existence.[18] Earlier deaths included six monarchs.[10][15] As recently as 1967, 15 million cases occurred a year.[10]

Inoculation for smallpox appears to have started in China around the 1500s.[19][20] Europe adopted this practice from Asia in the first half of the 18th century.[21] In 1796 Edward Jenner introduced the modern smallpox vaccine.[22][23] 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.[24][25] The term "smallpox" was first used in Britain in the early 16th century to distinguish the disease from syphilis, which was then known as the "great pox".[26][27] Other historical names for the disease include pox, speckled monster, and red plague.[3][4][27]