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23 / 02 / 2018
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Smallpox (variola)


Viral Illnesses

Smallpox is a relatively old disease. Smallpox (variola) is a contagious, disfiguring and often deadly disease caused by the variola virus. Smallpox infection was eliminated from the world in 1977.

Naturally occurring smallpox was finally eradicated worldwide in the 1970s - the result of a concerted immunization campaign. But the virus didn't disappear entirely. Stocks of smallpox virus, set aside for research purposes, are officially stored in two high-security World Health Organization (WHO) labs - one in the United States and one in Siberia. This has lead to concerns that smallpox might be used as an agent in biological warfare.

Most often, the virus is transmitted through particles that are released into the air when an infected person coughs, sneezes or simply talks. But it can also spread through direct contact such as kissing or through contaminated bed linen and clothing. Inhaling a single virus particle may be enough to cause infection. Smallpox has the potential to spread rapidly - an epidemic could conceivably start with one infected individual. Once symptoms develop, there's no effective treatment for smallpox and no known cure, but a vaccine is available that can protect against the disease.

Signs and symptoms

The first symptoms of smallpox usually appear 12 to 14 days after you're infected. During the incubation period of seven to 17 days, you look and feel healthy and can't infect others.

Following the incubation period, a sudden onset of flu-like signs and symptoms occurs. These include:

A few days later, the characteristic smallpox rash appears as flat, red spots (lesions). Within a day or two, these lesions become filled with clear fluid (vesicles) and then with pus (pustules). The rash appears first on your face, hands and forearms and later on the trunk. It's usually most noticeable on the palms of your hands and the soles of your feet. Lesions also develop in the mucous membranes of your nose and mouth. The way the lesions are distributed is a hallmark of smallpox and a primary way of diagnosing the disease.

When the pustules erupt, the skin doesn't break, but actually separates from its underlying layers. The pain can be excruciating. Scabs begin to form eight to nine days later and eventually fall off, leaving deep, pitted scars. All lesions in a given area progress at the same rate through these stages. People who don't recover usually die during the second week of illness.

Smallpox vs. chickenpox
In the past, smallpox was sometimes confused with chickenpox - a childhood infection that's seldom deadly. Yet chickenpox differs from smallpox in several important ways:

  • Severity and location of lesions. Chickenpox lesions are much more superficial than are those of smallpox and occur primarily on the trunk, rather than on the face, arms and hands.

  • Types of lesions. You'll often see a combination of scabs, vesicles and pustules in someone with chickenpox. In smallpox, on the other hand, all of the lesions in a given area are at the same stage.

  • Timing of transmission. A person infected with chickenpox can unknowingly transmit the virus to others before symptoms ever develop. But smallpox becomes infectious only when symptoms appear and remains contagious until scabs fall from the pustules. According to the WHO, smallpox is most contagious after the fever starts and during the first week of the rash. You're less likely to become infected if you're exposed to someone in the later stages of the disease.


The variola virus causes smallpox. Under high magnification, variola particles look like rectangles with a deeply patterned surface. They're sometimes referred to as bricks. Each brick is composed of at least a hundred different proteins. Although extraordinarily large for a virus, 3 million smallpox bricks lined end to end would be no larger than the period at the end of a sentence.

Once you're infected, the virus immediately begins replicating inside your cells - first in the lymph nodes and then in your spleen and bone marrow. Eventually, the virus settles in the blood vessels in your skin and the mucous membranes of your nose and throat. When the lesions in your mouth slough off, they release large amounts of the virus into your saliva. This is when you're most likely to transmit the disease to others.

How smallpox spreads
Smallpox usually requires face-to-face contact to spread. It's most often transmitted in air droplets when an infected person coughs, sneezes or talks. But airborne particles can also spread through the ventilation system in a building, infecting people in other rooms or floors. In addition, smallpox can spread through contact with contaminated clothing and bedding, although the risk of infection from these sources is much lower.

Smallpox outbreaks typically occur in two-week intervals. Initially, just a few people get sick. Fourteen days later, a larger number of people develop the disease, and in another two weeks, even more cases appear. This pattern reflects the incubation period of the virus as well as its exponential spread.

Types of smallpox
Two main forms of smallpox exist - variola major and minor. Variola minor is a milder form of the disease and causes a less serious illness. It's fatal in less than 1 percent of people who contract it. Variola major, on the other hand, kills one-third of the people it infects.

Smallpox also occurs in two rare forms:

  • Hemorrhagic smallpox. This form is characterized by a red, pinpoint rash and bleeding (hemorrhages) in the skin and mucous membranes. In some cases, hemorrhagic smallpox may destroy the entire skin surface and all mucous membranes. Hemorrhagic smallpox is almost always fatal within five to seven days.

  • Malignant smallpox. This form is also often fatal. The early symptoms are similar to other forms of the disease, but the lesions are velvety and never become filled with pus. Eventually, the skin takes on a rubbery appearance. Bleeding in the skin and intestinal tract also may occur.

Screening and diagnosis

Trained health workers can diagnose smallpox without the need for laboratory tests. The World Health Organization provides training materials to help health staff recognize smallpox and distinguish it from chickenpox. Still, an initial case of smallpox is likely to be confirmed by laboratory testing.

Even a single confirmed case of smallpox would be considered an international health emergency to be reported immediately to local health authorities and national officials.


Historically, variola major is fatal in about 30 percent of people who contract it. Almost no one survives the hemorrhagic and malignant forms of the disease. People who recover from smallpox usually have severe scars, especially on their face, arms and legs. In many cases, smallpox may lead to blindness.


No cure for smallpox currently exists. There's some evidence that cidofovir - an antiviral medication normally used to treat an infection known as cytomegalovirus (CMV) - might prevent smallpox if it's administered within a day or two of exposure. The smallpox vaccine itself can prevent or lessen the severity of the disease if given within four days of infection. But neither of these is useful once signs and symptoms develop, and both can have serious side effects. For now, the best that doctors can offer people with symptomatic smallpox is supportive therapy and antibiotics to prevent secondary infections.

Apart from immediate vaccination, isolation is the only way to manage the disease. Unfortunately, isolation can only contain the spread of the virus, not eradicate it.

In most cases, people with confirmed cases of smallpox would be treated in separate hospitals, in other special facilities or at home. Those admitted to regular hospitals are likely to be confined to negative-pressure rooms - the pressure outside the room is greater than the pressure inside - that have highly sophisticated air filtration systems. Strict precautions would be taken with bed linen and clothing. Even so, the risk is so high that all hospital employees as well as most other patients would probably be vaccinated against the disease.


Smallpox is one of the most devastating of human diseases. In its 12,000-year history, it has probably killed more people than any other illness - including the plague. Yet no naturally occurring smallpox cases have been reported for nearly 25 years. The story of smallpox prevention - and its eventual eradication through immunization - is a long and compelling one.

Smallpox vaccine
For centuries, it was known that people who survived smallpox became immune to it. For that reason, nearly every culture tried to induce immunity in healthy individuals. The Chinese used tubes to insert powdered smallpox scabs into their nostrils. In Turkey, pus from lesions was scratched into the skin.

Eventually these methods - collectively known as variolation - reached Europe and the New World. There, as elsewhere, variolation had varying degrees of success. Some people became immune, but others contracted the disease and died or became the source of a new epidemic. Still, by the early 1700s, "do-it-yourself" smallpox inoculation had become widespread.

In 1788, the scientist Edward Jenner inoculated a healthy, 8-year-old boy with cowpox - a disease caused by a virus that closely resembles variola. Cowpox's natural hosts are small mammals such as wood mice, but the virus can spread to other animals, especially cattle, and lesions on the udders and teats of cows can infect people who milk them. Although rare today, cowpox was widespread in 18th-century Europe, where it was common knowledge that milkmaids who had been infected with cowpox - which is generally mild - were then immune to the far more deadly disease, smallpox.

Jenner's experiment was a success. His patient failed to contract smallpox, even when deliberately exposed to variola. By 1800, cowpox vaccinations (the word vaccine is from the Latin vacca, for "cow") were commonplace, primarily because they caused fewer side effects and deaths than variolation with smallpox itself.

Smallpox vaccine that was used until vaccinations were stopped contained live vaccinia virus - a virus similar to cowpox and closely related to variola. Before 1972, most young children were vaccinated against smallpox, as were military recruits and many people traveling out of the country.

In 1967, the World Health Organization launched a global immunization campaign to eradicate smallpox. At that time, 2 million to 3 million people died of smallpox every year. The WHO efforts were remarkably effective, and the last naturally occurring case of smallpox was reported in 1977. In 1980, smallpox vaccinations were discontinued worldwide.

The vaccine today
Currently has enough smallpox vaccine to vaccinate.

Evidence from the vaccination of some military personnel and health care professionals also suggests that the smallpox vaccine may cause inflammation of the heart (myocarditis), inflammation of the membrane covering the heart (pericarditis), or a combination of these two conditions (myopericarditis).

Who should not receive the vaccinia vaccination
You should not receive the smallpox vaccine if you:

  • Have eczema, a history of eczema or other chronic skin conditions, or share a household with someone with eczema, a history of eczema or skin conditions such as impetigo.

  • Are pregnant. The vaccinia vaccine is not known to cause birth defects, but in rare cases it may cause infection of the fetus, leading to stillbirth or death soon after delivery.

  • Have a disease or are undergoing treatment that suppresses your immune system. This includes people with cancer, organ transplants, and those undergoing radiation therapy or treatment with drugs that suppress the immune system.

  • Have AIDS or are HIV-positive. The human immunodeficiency virus (HIV) wasn't identified before the end of routine smallpox vaccination, so it's not known what effect vaccinia might have on people with the disease. Currently, the CDC recommends that HIV-positive people not receive the vaccine.

  • Are allergic to any of the ingredients in the vaccine, including the antibiotics polymyxin B sulfate, streptomycin sulfate, chlortetracycline hydrochloride and neomycin sulfate. Vaccinia vaccine does not contain penicillin.

  • Have underlying heart disease, or have three or more known risk factors for heart disease, including high blood pressure, diabetes, high cholesterol, smoking or a parent or sibling with heart disease.

If you were vaccinated before 1972
About 40 percent of Americans have never been vaccinated against smallpox. Others received the vaccine 25 years ago or more. It's not known how long immunity lasts, although it's likely the vaccine is most effective for about five to 10 years. Partial immunity may last much longer. In addition, people who are revaccinated appear to have increased immunity.

AMA Urges Caution On Mass Smallpox Vaccination

The AMA voted December 4 to take a cautious approach to any national smallpox vaccination program, urging the federal government to wait for good science before ordering vaccinations for all Americans.

The smallpox vaccine is associated with a number of side effects and vaccinating every American could result in as many as 300 deaths.

The Florida delegation backed the resolution that asked the AMA to "provide federal authority and funding for direct conversion of all available and appropriate vaccine facilities to create doses sufficient to appropriately vaccinate the entire population of the United States for smallpox."

Smallpox vaccination plans have gathered momentum because the viral infection could be used as a potent bioterrorism weapon. Health and Human Services Secretary Tommy Thompson announced plans to buy as many as 300 million doses of smallpox vaccine.

Instead of endorsing universal smallpox vaccination, the AMA House approved a resolution that asks for more study of "risks and benefits of pre-exposure vaccination of the US population," while plans for mass vaccination continue.

The American Medical Association's (AMA) House of Delegates December 4, 2001 San Francisco, CA

Smallpox Vaccine Provides Long-term Immunity

The researchers evaluated how immune system cells responded when participants were exposed to vaccinia, a virus related to the smallpox virus used in vaccines to trigger immunity to smallpox.

What were the results of vaccinia exposure?

Exposure to vaccinia produced a robust response in people who had been vaccinated in recent years. The response was still considerable in people who had been vaccinated 6 to 35 years before. People who had been vaccinated more than 35 years ago still had a considerable immune response.

When was the smallpox vaccine used?

The smallpox vaccine was required for school entry in the U.S. prior to 1972. About 60 percent of the US population is vaccinated. The eradication of smallpox was officially declared in 1980, and according to the World Health Organization, national vaccination programs stopped in all countries by the early 1980s.

What are the symptoms of smallpox?

The initial signs of smallpox infection include headache, vomiting and fever. Then pus-filled lesions form on the head and face, and may also appear on other parts of the body.

What treatments exist for smallpox?

There is no treatment for the disease, which is fatal 20 percent to 40 percent of the time in unvaccinated people. However, if an individual has been exposed to the virus and is vaccinated within the next 4 days, the vaccine can reduce symptoms or prevent the disease.

Does smallpox still exist?

Officially, smallpox exists in only two laboratories -- one in the US and the other in Russia. However, there are some concerns that other organizations may have samples of the deadly virus.

The New England Journal of Medicine August 29, 2002;347:689-690

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