Smallpox was once one of the most severe infectious diseases that was endemic throughout the world for most of the recorded history. It is caused by variola virus (a DNA virus and a member of the Poxviridae family), and characterized by three phases: incubation, prodrome and rash. This disease killed and disfigured innumerable millions of people globally.

The origin of smallpox

The historians believe that smallpox appeared around 10 000 B.C. during the first agricultural settlements in northeastern Africa. From there it spread to India by means of ancient Egyptian merchants. Furthermore, observations of typical skin rashes on Egyptian mummies dating from 1100 to 1580 B.C. give credence to theories that ancient Egypt was an early region with endemic smallpox.

Unambiguous descriptions of the disease were documented in 4th-century China, 7th-century India and Mediterranean region, as well as 10th-century southwestern Asia. It is estimated that smallpox was introduced to Europe between the 5th and 7th centuries, with frequent epidemics during the Middle Ages.

The disease was generally confined to the Eurasian landmass before the 15th century; however, European colonists introduced smallpox to the Americas between 15th and 18th century with devastating case-fatality rates that approached 90%. It is generally believed that this was instrumental in the fall of the empires of the Aztecs and the Incas.

By the end of 19th century a milder and less lethal form of smallpox (also known as variola minor) became apparent in the USA. Originally described as Amass (alastrim in South America), this variant of the virus eventually got recognized in Brazil during the 1970s, as well as in Ethiopia and Somalia during the 1970s.

Variolation and vaccination

The first protection against smallpox consisted in rubbing infectious material from patients with smallpox into the scratched skin of children. Lady Montagu brought this method (known as variolation) from Turkey to England in 1721. Albeit dangerous, it was adopted in Europe during the 18th century (mainly by aristocracy) after successful treatment of the two daughters of the Princess of Wales.

By the end of that century, variolation has been widely accepted throughout the world as an effective way to prevent smallpox. The pervasive use in Great Britain (and North American colonies) significantly reduced the impact of the virus in the upper classes, but not in the population as a whole.

Edward Jenner (1749-1823) was first to use cowpox in order to protect against smallpox in 1796. This virus caused only mild infections in humans, but induced an immune response which provided cross-protection against smallpox infection - the principle that underlies the development of all subsequent vaccines based on an attenuated organism.

Dissemination of the new technique, despite fierce opposition, was rapid throughout Europe and the United States. During more than 60 years the vaccination was carried out from “arm to arm” with a certain risk of transmission of syphilis; hence from 1864 onward the vaccine was primarily produced on cows to avoid this risk.

As smallpox vaccine was the first vaccine to be widely deployed in humans, it seems quite fitting that smallpox was the first human infectious disease to be eradicated by vaccination, which was a milestone achieved in 1979. Nevertheless, variola virus remains a risk as routine vaccination is no longer undertaken.