Smallpox is a highly contagious, virulent, and often fatal
disease caused by variola virus, a large orthopoxvirus of
the family Poxviridae, subfamily Chordopoxvirinae. Four species
of the genus Orthopoxvirus cause infection in humans: vaccinia
virus, cowpox virus, monkeypox virus, and variola virus. Vaccinia
virus is a laboratory virus and used to vaccinate humans against
smallpox. Cowpox virus is a virus of rodents that is transmitted
to humans by cows or cats. Monkeypox is clinically indistinguishable
from smallpox but has a lower mortality rate. The two classic
varieties of smallpox are variola major and variola minor.
Variola major was endemic in India for at least 2000 years
and spread to China, Japan, Africa, and the Americas. Beginning
in the 20th century, the less virulent form of smallpox, variola
minor, spread from South Africa to Florida and the Americas,
and then to Europe. A world-wide eradication program began
in 1956. The case fatality rate of smallpox in unvaccinated
patients was 30% or more for variola major and 1% or less
for variola minor; significant morbidity was much higher.
Routine vaccinations against smallpox were discontinued in
the United States in 1972.