Smallpox

Smallpox begins with a prodromal phase of high fever, malaise, headache, and severe back pain, lasting 2–4 days. The characteristic rash then appears, starting on the face and extremities, and progresses through macular, papular, vesicular, and pustular stages. The pustules are deeply embedded in the dermis, giving a characteristic 'shotty' feel, and they crust and leave pitted scars. Diagnosis is primarily clinical, but laboratory confirmation uses polymerase chain reaction (PCR) and electron microscopy, with variola virus being a Biosafety Level 4 pathogen. Differential diagnosis includes chickenpox, monkeypox, and drug eruptions.

Smallpox has afflicted humanity for millennia, with evidence of the disease in ancient Egyptian mummies. Edward Jenner's 1796 demonstration of cowpox vaccination laid the foundation for eradication. The global eradication campaign, led by the WHO from 1967, used ring vaccination and surveillance-containment strategies. The last natural case was in Somalia in 1977, and in 1980 the World Health Assembly declared the world free of smallpox. This success is attributed to the virus's lack of animal reservoir, effective vaccine, and visible rash aiding detection.

Variola virus is a large, brick-shaped DNA virus with a linear double-stranded genome of about 186,000 base pairs. It exists in two forms: variola major (more virulent) and variola minor (less severe). The virus enters via the respiratory tract, replicates in the upper respiratory mucosa, and spreads to regional lymph nodes, then to the bloodstream (primary viremia), and finally to the skin and internal organs. The immune response involves both humoral and cell-mediated immunity, but the virus encodes proteins that subvert host defenses, including complement inhibitors and cytokine-binding proteins.

Beyond the well-known history, smallpox has several lesser-known facets. The variola virus has been used as a biological weapon, notably by the British in the French and Indian War, and by the Soviet Union in its bioweapons program. The only known remaining stocks are held in two WHO collaborating centers: the CDC in Atlanta and the State Research Center of Virology and Biotechnology (VECTOR) in Russia. The eradication campaign faced challenges in countries like Ethiopia and Somalia, where nomadic populations made surveillance difficult. Additionally, the vaccine, derived from vaccinia virus, has been used as a vector for other vaccines and cancer immunotherapy. The last known case of smallpox was a laboratory accident in Birmingham, England, in 1978, which led to the death of a medical photographer and the suicide of the responsible scientist.

Variola virus

The virus that causes smallpox; a member of the Orthopoxvirus genus.

Eradication

The permanent reduction to zero of the worldwide incidence of infection caused by a specific agent.

Ring vaccination

A strategy of vaccinating all people in close contact with a confirmed case, and those contacts' contacts.

Vaccinia virus

A virus used in the smallpox vaccine, distinct from variola but sharing antigens.

Biosafety Level 4

The highest level of biological containment, required for work with dangerous pathogens like variola.