Smallpox, which is believed to have originated over 3,000 years ago in India or Egypt, is one of the most devastating diseases known to mankind. Smallpox killed Queen Mary II of England, Emperor Joseph I of Austria, King Luis I of Spain, Tsar Peter II of Russia, Queen Ulrika Elenora of Sweden and King Louis XV of France.

The causative agent, Variola virus is a member of the genus Orthopoxvirus, subfamily Chordopoxvirinae of family Poxviridae. Other members of the genus include cowpox, camelpox, and monkeypox, the last one has caused the most serious recent human poxvirus infections.

The Variola virus measures 260 by 150 nanometers and contains a molecule of double-stranded DNA, coding for some 200 different proteins. It is one of the largest viral genomes known and this large size of the genome makes it especially difficult to create a synthetic copy of the virus.

 There are two forms of smallpox virus out of which Variolamajor causes the severe and most common form of smallpox, with a more extensive rash and higher fever. There are four strains of Variola major, namely, ordinary type that accounts for 90% or more of cases; modified type which is mild and occurs in previously vaccinated persons; flat type and haemorrhagic type, the last two of which are rare but very severe and fatal. Historically, Variola major has an overall fatality rate of about 30%. Variola minor causes a less common form of smallpox that is much less severe disease, with death rates of less than 1%.

The smallpox disease has now been eradicated after a successful worldwide vaccination program. 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.


Smallpox can be spread through direct contact with infected body fluids or contaminated objects such as bedding or clothing. Exposure to the virus is followed by an incubation period during which people do not have any symptoms and may feel fine. This averages about 12 to 14 days but can range from 7 to 17 days. During this time, people are not 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. Rashes emerge first as small red spots on the tongue and mouth. Later, red spots change into sores that break open and spread large amounts of virus into the mouth and throat. At this time, the person becomes most contagious. Then rashes appear on the skin, starting on the face and then spreading to the arms and legs and then to the hands and feet. Usually the rashes spread to all parts of the body within 24 hours. As the rashes appear, fever usually falls and the person may start to feel better. By the third day, the rashes become raised into bumps. By the fourth day, the bumps fill with a thick, opaque fluid and often have a button-like depression in the center. Fever often will rise again at this time and remain high until scabs form over the bumps. The bumps become pustules which are sharply raised, usually round and firm to the touch. The pustules begin to form a crust and then turn into scabs.

By the end of the second week after the rashes appear, most of the sores are scabbed over. Then the scabs begin to fall off, leaving marks on the skin that eventually turns into pitted scars. Most scabs fall off by the fourth week after the rashes appear. The disease is contagious to others until all of the scabs have fallen off.

There is no animal reservoir of the disease and insects do not play any role in transmission.

In the past, smallpox was sometimes confused with chickenpox, a worldwide infection of children that is seldom lethal. Chickenpox can be distinguished from smallpox by its much more superficial lesions, their appearance more on the trunk than on face and extremities, and by the development of successive crops of lesions in the same area.


The disease, for which no effective treatment is known, killed as many as 30% of infected persons. Between 65–80% of the survivors were left with deep pitted scars or pockmarks, most of which are prominent on the face.

Edward Jenner (1798) demonstrated that inoculation with cowpox could protect against smallpox, which brought the first hope that the disease could be controlled.

Through the success of global eradication campaign smallpox was finally restricted back to Africa and then to a single last natural case that occurred in Somalia in 1977. A fatal laboratory-acquired case occurred in the United Kingdom in 1978. The global eradication of smallpox was certified, based on intense verification activities in several countries by a commission of eminent scientists in December 1979 and subsequently endorsed by the World Health Assembly in 1980. The vaccination administered up to 4 days after exposure to the virus and before the rashes appear, provides protective immunity and prevents severity of the disease.

 No effective treatment, other than the management of symptoms, is currently available. A number of compounds are under investigation as chemotherapic agents. One of these, Cidofovir, has produced promising results in laboratory studies.

Due to the success of an intense worldwide public health campaign, no naturally occurring case of this deadly disease has occurred since October 26, 1977, when an unvaccinated hospital cook in Somalia became the last person to have naturally contracted the smallpox virus.

The World Health Organization (WHO) officially declared smallpox eradicated in 1980.


In 1796, Edward Jenner tested his theory of disease protection by inoculating a young boy with material obtained from a milkmaid who was infected with the milder cowpox virus. The success of that experiment led to the development of a vaccine ( name from vacca, the Latin word for cow) against smallpox.

Smallpox vaccine contains live Vaccinia virus of the orthopoxvirus family and closely related to Variola virus, the agent that causes smallpox. Immunity resulting from immunization with Vaccinia virus protects against smallpox. Vaccination usually prevents smallpox infection for at least ten years.

Most existing vaccine stocks and the vaccine used in the WHO eradication campaign consist of pulp scraped from Vaccinia-infected animal skin, mainly calf or sheep, with phenol added to a concentration sufficient to kill bacteria but not so high as to inactivate the Vaccinia virus. The vaccine is then freeze dried and sealed in ampules for later re-suspension in sterile buffer and subsequent intradermal inoculation by multiple puncture with a bifurcated needle.


 Only two laboratories in the world are known to house smallpox virus, namely, the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the State Research Center of Virology and Biotechnology in Koltsovo, Russia. The seed virus (Vaccinia virus strain Lister Elstree) used for producing vaccine is being held for WHO by the WHO Collaborating Centre for Smallpox Vaccine in Bilthoven, the Netherlands.