Variole

Smallpox was an infectious disease produced by the variola virus, an Orthopoxvirus, characterized by fever and a progressive skin rash that evolved into fluid-filled lesions ^[1][3]. The illness was historically endemic for millennia and was declared eradicated by the World Health Organization in 1980 ^[1][2][3].

Initial manifestations included fever, fatigue, and often vomiting or back pain, followed by oral ulcers and a characteristic rash beginning on the face and limbs ^[1][3]. The rash progressed over days into clear-fluid blisters that became pus-filled, crusted, and left scars upon healing ^[1][2][3]. A severe hemorrhagic form with extensive internal and skin bleeding occurred in a small minority of infections and was generally fatal ^[1].

Smallpox was an ancient disease with evidence dating to around 1500 BCE and caused substantial mortality, including an estimated 400,000 deaths per year in 18th-century Europe ^[1][2]. It occurred in recurrent outbreaks, was introduced to the Americas with major Indigenous mortality, and was endemic worldwide until eradication ^[1][2]. In temperate zones, infections peaked in winter and spring, whereas tropical areas showed less seasonality ^[1].

The virus passed between people mainly through prolonged face-to-face contact with an infectious individual via respiratory droplets, and rarely through contaminated objects or textiles ^[1][3]. Transmission generally required close contact and began after rash onset, with the infectious period limited to the symptomatic phase ^[1][3]. Seasonal and age-related patterns were shaped by close-contact requirements and waning vaccine-derived immunity ^[1].

Prevention relied principally on smallpox vaccination, with immunization within days of exposure reducing or markedly lessening illness severity ^[1][3]. A global vaccination campaign led by the World Health Organization achieved eradication through widespread immunization paired with active case surveillance ^[2][3]. Post-eradication, the variola virus is retained only as a recognized biological threat, and approved vaccines remain available for specific high-risk indications ^[4].

1. 1 Wikipedia contributors. Smallpox - Wikipedia [Internet]. Wikipedia. cited 23 Oct 2026. Available from: https://en.wikipedia.org/wiki/Smallpox
2. 2 World Health Organization. Smallpox [Internet]. cited 3 Sept 2026. Available from: https://www.who.int/news-room/questions-and-answers/item/smallpox
3. 3 World Health Organization. Smallpox [Internet]. cited 3 Sept 2026. Available from: https://www.who.int/health-topics/smallpox
4. 4 Nucera F et al. Poxviridae Pneumonia. Adv Exp Med Biol. 2024. PMID: 38801579. doi: 10.1007/978-3-031-57165-7_12. PubMed: https://pubmed.ncbi.nlm.nih.gov/38801579/
5. 5 Bunge EM et al. The changing epidemiology of human monkeypox-A potential threat? A systematic review. PLoS Negl Trop Dis. 2022 Feb. PMID: 35148313. doi: 10.1371/journal.pntd.0010141. PubMed: https://pubmed.ncbi.nlm.nih.gov/35148313/