Smallpox man dared to count his children as his own until they had had the disease. - Comte de la Condamine

Smallpox is a serious, contagious, and sometimes fatal infectious disease caused by the variola virus. Smallpox is an ancient disease and one of the deadliest diseases known to humans.

Smallpox outbreaks have occurred from time to time for thousands of years, but the disease is now eradicated after a successful worldwide vaccination program. Smallpox is the only human disease to have been eradicated by vaccination. The last case of smallpox in the United States was in 1949. The last naturally occurring case in the world was in Somalia in 1977. After the disease was eliminated from the world, routine vaccination against smallpox among the general public was stopped because it was no longer necessary for prevention.


There are two clinical forms of smallpox. Variola major and Variola minor.

  • Variola minor is a less common presentation of smallpox, and a much less severe disease, with death rates historically of 1% or less.

  • Variola major is the severe and most common form of smallpox, with a more extensive rash and higher fever. There are four types of variola major smallpox:

    • Ordinary - The most frequent type, accounting for 90% or more of cases. The overall case-fatality rate for ordinary-type smallpox is about 30%.

    • Modified - Mild and occurring in previously vaccinated persons.

    • Flat - Rare and very severe. The fatality rate for flat-type is 90% or greater.

    • Hemorrhagic - Rare and very severe. The fatality rate is nearly 100% in observed cases of hemorrhagic smallpox.

There is no evidence of chronic or recurrent infection with variola virus.


Generally, direct and fairly prolonged face-to-face contact is required to spread smallpox from one person to another. Smallpox also can be spread through direct contact with infected bodily fluids or contaminated objects such as bedding or clothing. Rarely, smallpox has been spread by virus carried in the air in enclosed settings such as buildings, buses, and trains. Humans are the only natural hosts of variola. Smallpox is not known to be transmitted by insects or animals.


There is no proven treatment for smallpox. Patients with smallpox may be helped by intravenous fluids, medicine to control fever or pain, antibiotics for any secondary bacterial infections that may occur, and possible ventilator assistance. All in primarily a supportive role.

Scientists are currently researching new treatments. No drug is currently approved for the treatment of smallpox. However, antiviral treatments have improved since the last large smallpox epidemics, and studies suggest that the antiviral drug cidofovir might be useful as a therapeutic agent. The drug must be administered intravenously, however, and may cause serious kidney toxicity.


Once inhaled, variola major virus invades the mouth and throat or the respiratory lining, migrates to regional lymph nodes, and begins to multiply. In the initial growth phase the virus seems to move from cell to cell, but around the 12th day, breaking down of many infected cells occurs and the virus is found in the bloodstream in large numbers (this is called viremia), and a second wave of multiplication occurs in the spleen, bone marrow, and lymph nodes.

Signs and Symptoms
Incubation Period(Duration: 7 to 17 days)Not contagious Exposure to the virus is followed by an incubation period during which people do not have any symptoms and may feel fine. This incubation period averages about 12 to 14 days but can range from 7 to 17 days. During this time, people are not contagious.
Initial Symptoms (Prodrome)
(Duration: 2 to 4 days)
Sometimes contagious*
The first symptoms of smallpox include fever, malaise, head and body aches, and sometimes vomiting. The fever is usually high, in the range of 101 to 104 degrees Fahrenheit. At this time, people are usually too sick to carry on their normal activities. This is called the prodrome phase and may last for 2 to 4 days.
Early Rash
(Duration: about 4 days)
Most contagious
A rash emerges first as small red spots on the tongue and in the mouth.
These spots develop into sores that break open and spread large amounts of the virus into the mouth and throat. At this time, the person becomes most contagious.
Around the time the sores in the mouth break down, a rash appears on the skin, starting on the face and spreading to the arms and legs and then to the hands and feet. Usually the rash spreads to all parts of the body within 24 hours. As the rash appears, the fever usually falls and the person may start to feel better.
By the third day of the rash, the rash becomes raised bumps.
By the fourth day, the bumps fill with a thick, opaque fluid and often have a depression in the center that looks like a bellybutton. (This is a major distinguishing characteristic of smallpox.)
Fever often will rise again at this time and remain high until scabs form over the bumps.
Pustular Rash
(Duration: about 5 days)
The bumps become pustules - sharply raised, usually round and firm to the touch as if there's a small round object under the skin. People often say the bumps feel like BB pellets embedded in the skin.
Pustules and Scabs
(Duration: about 5 days)
The pustules begin to form a crust and then scab.
By the end of the second week after the rash appears, most of the sores have scabbed over.
Resolving Scabs
(Duration: about 6 days)
The scabs begin to fall off, leaving marks on the skin that eventually become pitted scars. Most scabs will have fallen off three weeks after the rash appears.
The person is contagious to others until all of the scabs have fallen off.
Scabs resolved
Not contagious
Scabs have fallen off. Person is no longer contagious.

* Smallpox may be contagious during the prodrome phase, but is most infectious during the first 7 to 10 days following rash onset.


Smallpox vaccination within three days of exposure will prevent or significantly lessen the severity of smallpox symptoms in the vast majority of people. Vaccination four to seven days after exposure can offer some protection from disease or may modify the severity of disease.

Anyone who has been vaccinated against smallpox (in most countries, this means anyone aged 25-30 or over) will have some level of protection. The vaccination may not still be fully effective, but it is likely to protect you from the worst effects of the disease. However, if you were directly exposed to the virus which causes smallpox, a repeat vaccination would be recommended.

Currently, the smallpox vaccine is not widely available to the general public. However, there is enough smallpox vaccine to vaccinate every person in the United States in the event of a smallpox emergency.


Today, the smallpox virus is kept in two approved labs in the U.S. and Russia. However, credible concern exists that the virus was made into a weapon by some countries and that terrorists may have obtained it. Smallpox is a serious, even deadly, disease. CDC calls it a "Category A" agent. Category A agents are believed to present the greatest potential threat for harming public health.