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Brenda L. Tesini

, MD, University of Rochester School of Medicine and Dentistry

Last full review/revision Oct 2019| Content last modified Oct 2019
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Smallpox is a highly contagious, very deadly disease caused by the variola virus. The disease is now considered eliminated.

  • There have been no cases of smallpox since 1977.

  • People can acquire the infection by breathing air exhaled or coughed out by an infected person.

  • People have a fever, headache, backache, and rash, sometimes with severe abdominal pain, and they feel very ill.

  • The diagnosis is confirmed when the virus is identified in a sample taken from the rash.

  • Vaccination within the first few days of exposure can prevent the disease or limit its severity.

  • Treatment involves fluids, relief of symptoms, and treatments to maintain blood pressure and help with breathing.

The smallpox virus can exist only in people—not in animals.

There are two main forms:

  • The severe form (variola major) is the most common and is the one of concern.

  • The other form (variola minor) is much less common and much less severe.

Throughout history, smallpox has killed millions of people. Over 200 years ago, a vaccine against smallpox (the first vaccine ever) was developed. The vaccine proved very effective and was given to people throughout the world. The last case of smallpox was reported in 1977. In 1980, the World Health Organization (WHO) declared the disease eliminated and recommended stopping vaccination.

Samples of the virus are kept in two high-security laboratories (one in the United States and one in Russia).

Because the vaccine’s protective effects gradually wear off, nearly all people—even those previously vaccinated—are believed to be susceptible to smallpox to various degrees. This lack of protection is a concern only because samples of the virus have been stored, and some people worry that terrorist groups could obtain the virus and release it into the population. The resulting epidemic would be devastating.

The smallpox virus spreads directly from person to person and is acquired by breathing air contaminated with droplets of moisture breathed or coughed out by an infected person. Contact with clothing or bed linens used by an infected person can also spread the disease. Smallpox usually spreads to people who have close personal contact with an infected person. Rarely, smallpox spreads through the air in an closed environment, such as a building, where someone has smallpox. A large outbreak in a school or workplace would be uncommon.

The virus survives no more than 2 days in the environment— less if temperature and humidity are high.

Did You Know...

  • Nearly all people, even people who were previously vaccinated, are now believed to be susceptible to smallpox.


Variola major

Symptoms of the severe form usually begin 7 to 17 days after infection. Infected people develop fever, headache, and backache and feel extremely ill. They may have severe abdominal pain and become delirious.

After 2 or 3 days, a rash of flat, red spots develops in the mouth and on the face. Shortly thereafter, it spreads to the trunk and legs, then the hands and feet. People are contagious only after the rash has started and are most contagious for the first 7 to 10 days after the rash appears. After 1 or 2 days, the spots turn into blisters, which fill with pus (forming pustules). After 8 or 9 days, the pustules become crusted.

The lungs, brain, and/or bone may become infected.

About 30% of people with smallpox die, usually in the second week of the disease. Some of the survivors are left with large, disfiguring scars.

In a few people with the severe form, the initial symptoms develop more quickly and are more intense. One rare type, called hemorrhagic smallpox, causes bleeding. After a few days, bleeding occurs in the skin, mucous membranes, and gastrointestinal tract. Almost all people with hemorrhagic smallpox die in 5 or 6 days.

Variola minor

In the less severe form, symptoms are similar but much less severe. The rash is much less extensive, and fewer than 1% of people die.


  • Tests for smallpox DNA in a sample of fluid from the blisters

A doctor suspects smallpox when people have the disease’s characteristic spots—particularly when there is an outbreak of the disease.

The diagnosis of smallpox can be confirmed by identifying the smallpox virus in a sample that is taken from the blisters or pustules and is tested for the genetic material (DNA) of smallpox.

A sample can also be examined under a microscope or sent to a laboratory for the virus to be grown (cultured) and analyzed.


Prevention is the best response to the threat of smallpox. Prevention involves

  • Vaccination

  • Isolation

The smallpox vaccine is not made from the smallpox virus. Instead, the vaccine contains live vaccinia virus, which is related to the viruses that cause monkeypox and smallpox. Vaccination with vaccinia virus causes a mild infection and protects people against smallpox.

Vaccination works best when given before exposure. However, even after exposure, vaccination can help prevent the disease or limit its severity. Vaccination can be helpful up to 4 days after exposure, but it is more effective the sooner it is given.

If vaccination is successful, a blister develops at the vaccination site within about 7 days. If it does not appear, the person is vaccinated again. The area around the blister may become red. Many people also have a fever and muscle aches and feel generally unwell the week after they are vaccinated.

Vaccination is dangerous for some people, especially those with a weakened immune system (such as those who have AIDS or who take drugs that suppress the immune system). Rarely, even some healthy people have adverse reactions to smallpox vaccination. Adverse reactions are less common among previously vaccinated people than among those who have never received the vaccine:

  • About 1 in every 10,000 previously unvaccinated healthy people have serious complications, and 1 in every million die.

  • One in every 4 million previously vaccinated healthy people die from the vaccine.

Newer drugs, such as vaccinia immune globulin and an antiviral drug, cidofovir, may help treat adverse reactions and lower the risk of death. However, because of the risks, vaccination is recommended only for people at high risk of exposure, mainly certain military personnel and laboratory technicians and health care workers who give or handle the vaccine and related materials.

People with symptoms suggesting smallpox need to be isolated to prevent spread of the infection. Contacts of these people need not be isolated because they cannot spread the infection unless they become sick and develop a rash. However, contacts are watched closely and isolated at the first sign of infection.


  • Supportive measures

  • Possibly, antiviral drugs

Treatment of smallpox is supportive. It includes fluids, symptom relief, assistance with breathing (for example, with a face mask to supply oxygen), and treatments to maintain blood pressure.

Antiviral drugs have not been tested in smallpox because they did not exist when the disease was present. However, if smallpox were to return, doctors think that cidofovir and several experimental drugs might be helpful.

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