May 25, 2022

Smallpox was an infectious disease caused by two variants of the Variola virus, Variola maior and Variola minor. The disease is also known by the Latin terms variola or variola vera (from the late Latin variŏla, derived from varius, meaning vario, spotted), while the English term smallpox was coined in the United Kingdom in the 15th century to distinguish it from syphilis, called great pox. The smallpox virus is localized in the small circulation of the skin, oral cavity and pharynx. On the skin it manifests itself with a maculo-papular rash and, subsequently, with raised vesicles filled with fluid. Variola maior causes more relevant clinical manifestations and is characterized by a lethality of 30-35%. Long-term complications include characteristic scarring, especially on the face, in 65–85% of those who manage to survive; moreover, blindness, as a consequence of corneal ulcers and subsequent scarring, and deformity of the limbs, due to episodes of arthritis and osteomyelitis, can also occur, albeit with a lower prevalence estimated in 2-5% of cases. Variola minor causes a milder form of the disease, also known as alastrim, which can lead to death in 1% of cases. Smallpox is believed to have emerged in the human population around the 2nd millennium BC. and the earliest physical evidence can be traced back to the pustular rash found on the mummy of Pharaoh Ramses V. It is estimated that the disease killed around 400,000 Europeans each year during the 18th century and was responsible for one third of all cases of blindness. Of all infected people, about 20-60% of adults and 80% of children died. Smallpox is believed to have been the cause of 300-500 million deaths during the 20th century. In 1967 alone, according to data from the World Health Organization, fifteen million people contracted the disease and of these two million died. After a massive vaccination campaign carried out since the 19th century and conducted with a massive joint effort between 1958 and 1977, WHO declared the disease eradicated in 1979, after the last case of naturally occurring smallpox caused by Variola minor was diagnosed in Somalia on October 26, 1977. It was the only disease eradicated in human history until 2011, when rinderpest suffered the same fate.


Smallpox is caused by Variola virus infection which belongs to the Orthopoxvirus genus of the Poxviridae family. The virus is large, brick-shaped and measures approximately 302-350 nm by 244-270 nm with a single linear double-stranded DNA and 186 kbp genome characterized by a stem-loop terminator at each end. It exists in two forms: Variola maior and Variola minor. The four orthopoxviruses that can cause infections in humans are, in addition to the Variola virus, the Vaccinia virus, the cowpox virus and the monkeypox virus. Variola virus naturally infects humans only, although primates and other animals have been infected in the laboratory. Understanding the life cycle of poxviruses is complicated by the fact that there are numerous infectious forms with different mechanisms of access to the cell. The virus replicates in the cell's cytoplasm, unlike other DNA viruses which normally replicate in the nucleus. It also produces numerous specific proteins, the most important of which is a DNA-dependent RNA polymerase. Both enveloped and non-enveloped virions are infectious; this is synthesized at the level of the Golgi apparatus of the cell and includes several specific viral polypeptides, including a hemagglutinin. Infection with one of the two Variola viruses confers immunity towards the other.

Transmission mode

The virus is transmitted by air, through the inhalation of contained droplets