Since Jenner demonstrated the effectiveness of cowpox to protect humans from smallpox in 1796, various attempts were made to eliminate smallpox on a regional scale. As early as 1803, the Spanish Crown organized a mission (the Balmis expedition) to transport the vaccine to the Spanish colonies in the Americas and the Philippines, and establish mass vaccination programs there. By about 1817, a very solid state vaccination programme existed in the Dutch East Indies.
In British India a program was launched to propagate smallpox vaccination, through Indian vaccinators, under the supervision of European officials. By 1832, the federal government of the United States established a smallpox vaccination program for Native Americans. In 1842, the United Kingdom banned inoculation, later progressing to mandatory vaccination. The British government introduced compulsory smallpox vaccination by an Act of Parliament in 1853. In the United States, from 1843 to 1855 first Massachusetts, and then other states required smallpox vaccination.
Although some disliked these measures, In Northern Europe a number of countries had eliminated smallpox by 1900, and by 1914, the incidence in most industrialized countries had decreased to comparatively low levels. Vaccination continued in industrialized countries, until the mid to late 1970s as protection against reintroduction. Australia and New Zealand are two notable exceptions; neither experienced endemic smallpox and never vaccinated widely, relying instead on protection by distance and strict quarantines.
The first hemisphere-wide effort to eradicate smallpox was made in 1950 by the Pan American Health Organization. The campaign was successful in eliminating smallpox from all American countries except Argentina, Brazil, Colombia, and Ecuador. At this point, 2 million people were dying every year. Overall, however, progress towards eradication was disappointing, especially in Africa and in the Indian subcontinent. In 1967, the World Health Organization intensified the global smallpox eradication by contributing $2.4 million annually to the effort. An international team, the Smallpox Eradication unit, was formed under the leadership of an American, Donald Henderson.
To eradicate smallpox, each outbreak had to be stopped from spreading, by isolation of cases and vaccination of everyone who lived close by. This process is known as "ring vaccination". The key to this strategy was monitoring of cases in a community (known as surveillance) and containment. The initial problem the WHO team faced was inadequate reporting of smallpox cases, as many cases did not come to the attention of the authorities. The fact that humans are the only reservoir for smallpox infection, and that carriers did not exist, played a significant role in the eradication of smallpox. The WHO established a network of consultants who assisted countries in setting up surveillance and containment activities. Early on donations of vaccine were provided primarily by the Soviet Union and the United States, but by 1973, more than 80% of all vaccine was produced in developing countries. Prior to this, there had been a smallpox outbreak in May–July 1963 in Stockholm, Sweden, brought from the Far East by a Swedish sailor; this had been dealt with by quarantine measures and vaccination of the local population.
By the end of 1975, smallpox persisted only in the Horn of Africa. Conditions were very difficult in Ethiopia and Somalia, where there were few roads. Civil war, famine, and refugees made the task even more difficult. An intensive surveillance and containment and vaccination program was undertaken in early and mid-1977. The last naturally occurring case of indigenous smallpox (''Variola minor'') was diagnosed in Ali Maow Maalin, a hospital cook in Merca, Somalia, on 26 October 1977.
The global eradication of smallpox was certified, based on intense verification activities in countries, by a commission of eminent scientists on 9 December 1979 and subsequently endorsed by the World Health Assembly on 8 May 1980 as Resolution WHA33.3. The first two sentences of the resolution read: "Having considered the development and results of the global program on smallpox eradication initiated by WHO in 1958 and intensified since 1967 … Declares solemnly that the world and its peoples have won freedom from smallpox, which was a most devastating disease sweeping in epidemic form through many countries since earliest time, leaving death, blindness and disfigurement in its wake and which only a decade ago was rampant in Africa, Asia and South America."
The last cases of smallpox in the world occurred in an outbreak of two cases (one of which was fatal) in Birmingham, England in 1978. A medical photographer, Janet Parker, contracted the disease at the University of Birmingham Medical School and died on 11 September 1978, In 1986, the World Health Organization recommended destruction of the virus, and later set the date of destruction to be 30 December 1993. This was postponed to 30 June 1995. In 2002 the policy of the WHO changed to be against its final destruction. Destroying existing stocks would reduce the risk involved with ongoing smallpox research; the stocks are not needed to respond to a smallpox outbreak. However, the stocks may be useful in developing new vaccines, antiviral drugs, and diagnostic tests.
In March 2004 smallpox scabs were found tucked inside an envelope in a book on Civil War medicine in Santa Fe, New Mexico. The envelope was labeled as containing scabs from a vaccination and gave scientists at the Centers for Disease Control and Prevention an opportunity to study the history of smallpox vaccination in the US.
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