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acute, highly contagious disease causing a high fever and successive stages of severe skin eruptions. Occurring worldwide in epidemics, it killed up to 40% of those who contracted it and accounted for more deaths over time than any other infectious disease. Spreading to the New World with European colonization, it killed huge numbers of indigenous peoples, who had no immunity, greatly contributing to the annihilation of native cultures. It is unclear how ancient smallpox is. The disease had been believed to date from the time of ancient Egypt or before, on the basis of pockmarks found on ancient mummies, but a genetic study published in 2016 suggested that that the smallpox virus, or at least the form of it that produces deadly epidemic disease, may only date to the 16th cent.

Smallpox is caused by a virus that may be airborne or spread by direct contact. After an incubation period of about two weeks, fever, aching, and prostration occur, lasting two or three days. An eruption then appears and spreads over the entire body; the lesions become blisterlike and pustular within a week. The lesions then open and crust over, causing itching and pain. When the crusts fall off, usually in another one or two weeks, the extent of permanent damage to the skin (pockmarks) becomes evident. There is no specific treatment for smallpox; an antibiotic may be administered to prevent secondary bacterial infection.

A crude vaccinationvaccination,
means of producing immunity against pathogens, such as viruses and bacteria, by the introduction of live, killed, or altered antigens that stimulate the body to produce antibodies against more dangerous forms.
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 method began with Emanuel Timoni, a Greek physician, in the early 18th cent. Edward JennerJenner, Edward,
1749–1823, English physician; pupil of John Hunter. His invaluable experiments beginning in 1796 with the vaccination of eight-year-old James Phipps proved that cowpox provided immunity against smallpox.
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 modified the procedure (1796) by using the related cowpox virus to confer immunity. By 1977, vaccination programs, such as those by the World Health Organization (WHO), had eliminated the disease worldwide.

After 1980, when WHO officially declared smallpox eradicated as a disease, scientists retained some samples of the virus in laboratories for study. They mapped the genetic sequence of three strains of smallpox, and the destruction of the remaining samples of the live virus was scheduled and postponed several times. Owing to fears of a new natural outbreak or of the potential use of smallpox as a terrorist weapon against populations no longer vaccinated, research with the virus continued. The last declared samples of live virus are now stored by the U.S. and Russian governments under strict security, but it is believed that some nations may have secret stores of the virus that they could use as biological weapons.

Responding to such concerns, WHO postponed the scheduled 1999 destruction of all remaining stocks of the smallpox virus until 2002. The 2001 bioterror attacks in the United States with anthraxanthrax
, acute infectious disease of animals that can be secondarily transmitted to humans. It is caused by a bacterium (Bacillus anthracis) that primarily affects sheep, horses, hogs, cattle, and goats and is almost always fatal in animals.
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 led the United States and other nations to stockpile doses of smallpox vaccine out of concern that the smallpox virus might be used by terrorists. WHO agreed to delay the destruction of virus stocks beyond 2002 to allow for the development of new vaccines, and since then no plan for destruction has been agreed upon. In 2002, because of bioterrorism concerns, the G. W. Bush administration decided to vaccinate frontline military personnel and health-care and emergency workers against smallpox.


See E. A. Fenn, Pox Americana: The Great Smallpox Epidemic of 1775–1782 (2001); J. B. Tucker, Scourge (2001); M. Willrich, Pox: An American History (2011).


An acute infectious viral disease characterized by severe systemic involvement and a single crop of skin lesions that proceeds through macular, papular, vesicular, and pustular stages. Smallpox is caused by variola virus, a brick-shaped, deoxyribonucleic acid-containing member of the Poxviridae family. Strains of variola virus are indistinguishable antigenically, but have differed in the clinical severity of the disease caused. Following a 13-year worldwide campaign coordinated by the World Health Organization (WHO), smallpox was declared eradicated by the World Health Assembly in May 1980. Smallpox is the first human disease to be eradicated.

Humans were the only reservoir and vector of smallpox. The disease was spread by transfer of the virus in respiratory droplets during face-to-face contact. Before vaccination, persons of all ages were susceptible. It was a winter-spring disease; there was a peak incidence in the drier spring months in the Southern Hemisphere and in the winter months in temperate climates. The spread of smallpox was relatively slow. The incubation period was an average of 10–12 days, with a range of 7–17 days. Fifteen to forty percent of susceptible persons in close contact with an infected individual developed the disease.

There were two main clinically distinct forms of smallpox, variola major and variola minor. Variola major, prominent in Asia and west Africa, was the more severe form, with widespread lesions and case fatality rates of 15–25% in unvaccinated persons, exceeding 40% in children under 1 year. From the early 1960s to 1977, variola minor was prevalent in South America and south and east Africa; manifestations were milder, with a case fatality rate of less than 1%.

There is no specific treatment for the diseases caused by poxviruses. Supportive care for smallpox often included the systemic use of penicillins to minimize secondary bacterial infection of the skin. When lesions occurred on the cornea, an antiviral agent (idoxuridine) was advised.

Edward Jenner, a British general medical practitioner who used cowpox to prevent smallpox in 1796, is credited with the discovery of smallpox vaccine (vaccinia virus). However, the global smallpox eradication program did not rely only on vaccination. Although the strategy for eradication first followed a mass vaccination approach, experience showed that intensive efforts to identify areas of epidemiologic importance, to detect outbreaks and cases, and to contain them would have the greatest effect on interrupting transmission. In 1978, WHO established an International Commission to confirm the absence of smallpox worldwide. The recommendations made by the commission included abandoning routine vaccination except for laboratory workers at special risk. See Animal virus, Vaccination


An acute, infectious, viral disease characterized by severe systemic involvement and a single crop of skin lesions which proceeds through macular, papular, vesicular, and pustular stages. Also known as variola.


an acute highly contagious viral disease characterized by high fever, severe prostration, and a pinkish rash changing in form from papules to pustules, which dry up and form scabs that are cast off, leaving pitted depressions