The history of smallpox holds a unique place in human health and medicine. One of the deadliest diseases known to humans, smallpox is also the only human disease to have been eradicated by vaccination.

Symptoms and Causative Agent

Symptoms of a typical smallpox infection began with a fever and lethargy about two weeks after exposure to the Variola major virus. Headache, sore throat, and vomiting were common as well. In a few days, a raised rash appeared on the face and body, and sores formed inside the mouth, throat, and nose. Fluid-filled pustules would develop and expand, in some cases joining together and covering large areas of skin. In about the third week of illness, scabs formed and separated from the skin.

The virus Variola minor caused a similar, though much less severe, form of smallpox.


Smallpox was spread by close contact with the sores or respiratory droplets of an infected person. Contaminated bedding or clothing could also spread the disease. A patient remained infectious until the last scab separated from the skin.

Complications and Mortality

About 30% of smallpox cases of the variola major type ended in death, typically in the second week of infection. Most survivors had some degree of permanent scarring, which could be extensive. Other deformities could result, such as loss of lip, nose, and ear tissue. Blindness could occur as a result of corneal scarring. Variola minor was less severe and caused fewer of those infected to die.

Some estimates indicate that 20th century worldwide deaths from smallpox numbered more than 300 million.

Available Vaccines and Vaccination Campaigns

People have been using smallpox vaccine since Edward Jenner first tested his idea that inoculation with matter from a cowpox sore would protect a person from smallpox. Jenner’s work eventually led to widespread production and commercialization of smallpox vaccine.

Successful use of smallpox vaccine led to the gradual reduction of smallpox cases. The last U.S. wild smallpox case occurred in 1949. After intensive vaccination campaigns in the 1960s and 1970s, the last case of wild smallpox in the world occurred in 1977.

U.S. Vaccination Recommendations

Routine vaccination against smallpox ended in the United States in the early 1970s as its incidence lessened.

Certain U.S. military personnel and some civilian workers receive the smallpox vaccine due to the threat of bioterrorism. The U.S. military uses a smallpox vaccine called ACAM2000, produced by Sanofi Pasteur. The virus in ACAM2000 is produced not on the flanks of cows, as with previous generations of vaccine, but in lab cultures of African green monkey cells.


Centers for Disease Control and Prevention. Emergency Preparedness and Response. Smallpox. Accessed 2/9/2016.

Center for Infectious Disease Research & Policy. U.S. Military Switching to New Smallpox Vaccine. Accessed 2/9/2016.

Last update 9 Feb 2016

Timeline Entry: 1770

Protection by Cowpox Infection

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Timeline Entry: 10/16/1975

Last Wild Case of Variola Major

The last wild human case of variola major (Rahima Banu in Bangladesh) occurred in the village of Kuralia, Bhola Island, Barisal district, Bangladesh.

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Timeline Entry: 10/26/1977

Last Wild Case of Variola Minor

Ali Maow Maalin, a cook in Merca, Somalia, who worked in a hospital but never been vaccinated himself, contracted the last case of naturally occurring smallpox (variola minor). He made a full recovery. He became an advocate for polio vaccination and worked as a vaccinator in Somalia. He died July 22, 2013, at age 59 of malaria.

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Assessment Questions

Smallpox is the only human disease to have been __________ by vaccination.

  • reduced
  • eradicated
  • cured
  • made more deadly

About __________ of people infected with smallpox would die from it.

  • 1%
  • 10%
  • 30%
  • 50%

True or false? Smallpox vaccination is recommended for all children.

  • True
  • False
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