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Smallpox is a highly infectious disease caused by the variola virus. Two distinct variola viruses (major and minor) exist, and each manifests different clinical characteristics and host mortality. The most common form of smallpox described in the literature was due to variola major, which resulted in severe, disfiguring disease and carried a 30% mortality rate. The mildest form of smallpox was due to variola minor (also known as alastrim), which presented similarly to variola major but with less toxicity and had more superficial lesions that resulted in a faster healing time and lower mortality (1%). The diagnosis of variola minor was based on the assessment of an outbreak and its severity. If there were few deaths (1%), then the disease was determined to be variola minor.

The variola virus, an Orthopoxvirus from the family Poxviridae, is a large and complex DNA virus. Variola is genetically homologous to other similar viruses such as vaccinia or those that cause monkeypox, camelpox, and cowpox. For those that receive smallpox vaccine, the high degree of genetic similarity results in protection not only against smallpox, but also monkeypox, camelpox, and cowpox.


Smallpox is spread by droplet, aerosol, direct person-to-person contact, or direct contact with contaminated fomites. It had a seasonal distribution, with the highest rates occurring in the late winter and early spring. Variola virus enters through the respiratory tract, seeds the mucous membranes, and is transported to the regional lymph nodes where it replicates and enters the lymphatics and blood. The virus is very stable and can survive for long periods (years) in scabs.

Smallpox is one of the oldest recorded infections, with its earliest descriptions dating back to 10,000 BC in Asia and India and the earliest credible evidence being found in Egyptian mummies from over 3000 years ago. The global elimination of smallpox by vaccination remains a major historical and medical milestone, and the last recorded case of smallpox in the world occurred in 1978. Several important factors were crucial in the success of this eradication program: there is no latent or persistent human infection; it is an easily recognizable and diagnosable disease; and vaccination is cost-effective, stable, and easily administered, as well as highly effective against all strains of the virus.


The symptoms of smallpox include high fever, malaise, pain (typically in the back, abdomen, and head), and prostration. Approximately 24 hours before onset of rash, an enanthem occurs on the oral mucosa. In contrast to the similar-appearing varicella (chickenpox), the rash begins on the face, is centrifugal in distribution, and is often present on the palms and soles. Rash progresses from macules to papules and pustules, some of which may become umbilicated. Rash lesions are all in the same stage of development, in contrast to varicella in which macules, papules, and pustules coexist in one area of ...

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