Smallpox and Other Orthopoxvirus Diseases

Abstract

Smallpox was a severe disease causing substantial mortality among populations over several thousand years. It is caused by an orthopoxvirus, the variola (= smallpox) virus. Smallpox is a febrile disease with a maculo-, papulo-, vesicular and finally pustular rash, the typical pox lesions, numerous complications and a fatality rate of approximately 30%. Material from smallpox patients was used to inoculate healthy subjects (“variolation”) in medieval China, possibly offering some protection, but it was associated with high risk of complications and death. In 1796, the English physician Edward Jenner discovered that material from cowpox lesions inoculated into healthy subjects protected against smallpox in a comparatively safe way. This discovery was the invention of vaccination. Vaccination campaigns in the 19th and 20th century controlled smallpox, and following a global WHO-coordinated eradication campaign, it was finally declared eradicated by 1980. Other orthopoxviruses, such as the monkeypox virus, are still causing human disease in some geographies and may be emerging due to waning population immunity and population growth in previously rural or forested areas. Two antiviral compounds have been licensed for specific treatment. Various vaccines based on Jenner’s invention, using scarification with replicating live vaccinia strains, are still available globally for outbreaks. In the Western world, two smallpox vaccines are licensed and stockpiled today for emergency use: ACAM2000, a cell culture GMP-produced vaccinia strain; and a non-replicating, “Modified Vaccinia Ankara” (MVA) vaccine, GMP-produced on chicken embryo fibroblasts.