MSD Manual

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Brenda L. Tesini

, MD, University of Rochester School of Medicine and Dentistry

Reviewed/Revised Apr 2023
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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 Prevention 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... read more Prevention (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 Biological Weapons Biological warfare is the use of microbiological agents as weapons. Such use is contrary to international law and has rarely taken place during formal warfare in modern history, despite the... read more 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.

Symptoms of 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.

Diagnosis of Smallpox

  • 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 of Smallpox

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

  • Vaccination

  • Isolation

  • ACAM2000 is a live vaccinia virus that reproduces in the person who receives it. Vaccination with vaccinia virus causes a mild infection and protects people against smallpox.

  • JYNNEOS is a live but weakened (attenuated) vaccinia virus that does not reproduce in the person who receives it. It is approved for prevention of both smallpox and mpox.

ACAM2000 vaccine is given with a special type of needle dipped in reconstituted vaccine. The needle is rapidly jabbed 15 times in an area about 5 mm in diameter and with sufficient force to draw a trace of blood. If vaccination is successful, a blister develops at the vaccination site within about 7 days. The vaccine site is covered with a dressing to prevent spread of the vaccine virus to other body sites or to close contacts. Fever, muscle aches, and a general ill feeling are common the week after vaccination. Vaccination with ACAM2000 can be helpful up to 7 days after exposure to smallpox, but it is more effective the sooner it is given.

Vaccination with ACAM2000 is dangerous and not recommended for some people, especially those with the following risk factors:

  • Weakened immune system (such as those who have AIDS or who take medications that suppress the immune system)

  • Skin disorders (particularly atopic dermatitis [eczema])

  • Eye inflammation

  • Heart condition

  • Age under 1 year

  • Pregnancy

Rarely, even some healthy people have adverse reactions to this 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.

If people have a very severe reaction to the vaccine, doctors may try giving antiviral drugs such as tecovirimat, cidofovir, or brincidofovir.

JYNNEOS is administered as 2 injections 4 weeks apart. It is approved for people 18 years of age and older and may have a particular role in vaccinating people for whom ACAM2000 may be dangerous, such as those with a weak immune system or atopic dermatitis Atopic Dermatitis (Eczema) Atopic dermatitis (commonly referred to as eczema) is chronic, itchy inflammation of the upper layers of the skin that often develops in people who have hay fever or asthma and in people who... read more Atopic Dermatitis (Eczema) .

Vaccination for smallpox 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.

Treatment of Smallpox

  • 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 tecovirimat, cidofovir, or brincidofovir might be helpful. Tecovirimat and cidofovir are currently part of the Strategic National Stockpile, the nation’s largest supply of potentially life-saving drugs for use in a public health emergency (see CDC: Smallpox Prevention and Treatment).

More Information

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

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