Smallpox

Smallpox is an infectious disease caused by the variola virus, which belongs to the genus Orthopoxvirus within the family Poxviridae.^[1][3][4] It is an acute contagious illness that affected humans for thousands of years before being declared eradicated.^[2][3]

The initial symptoms of smallpox included high fever, fatigue, severe back pain, and sometimes vomiting or abdominal pain.^[1][2][3] Two to three days after fever onset, a characteristic rash developed, beginning on the face and hands and then spreading to the trunk and limbs, while lesions also appeared and ulcerated on the mucous membranes of the nose and mouth.^[1][2][3] The skin spots progressed from macules to fluid-filled vesicles with a central depression, then to pustules, and finally formed crusts that dried and fell off, often leaving permanent scars; blindness was a recognized sequela in some survivors.^[1][2][3] The overall case fatality rate was about 30%, with higher rates among infants, and a rare hemorrhagic form—variola nigra or "black pox"—was typically fatal.^[1][2]

Smallpox was an ancient infectious disease that persisted for millennia, historically manifesting in widespread outbreaks across the globe. Following its introduction to the Americas during the Columbian Exchange, it caused catastrophic mortality among Indigenous populations. During the 18th century, the disease alone was responsible for an estimated 400,000 deaths annually in Europe and accounted for approximately one-third of all blindness cases in the region . Despite being highly contagious, smallpox generally spread more slowly than other viral pathogens because transmission typically required prolonged face-to-face contact and usually occurred only after the onset of the characteristic rash . Epidemiological patterns exhibited seasonal variation, with infection rates peaking during winter and spring in temperate zones, while tropical regions experienced relatively consistent year-round transmission . The demographic profile of infections was heavily influenced by population-level acquired immunity; as vaccine-derived protection waned—typically within three decades—susceptibility increased across broader age groups . The overall case fatality rate hovered around 30%, with elevated mortality observed in infants, and survivors frequently suffered from permanent disfigurement or vision loss . Through a coordinated global vaccination initiative led by the World Health Organization, natural transmission was interrupted, culminating in the last documented indigenous case in Somalia in October 1977 and official certification of global eradication in 1980 . A subsequent isolated incident involving a laboratory accident in Birmingham, England, in 1978 resulted in a minor outbreak and one fatality, but no further natural cases have occurred since ^[2].

Smallpox was transmitted from person to person primarily through prolonged face-to-face contact with an infected symptomatic individual, via infective droplets.^[1][3] Transmission occasionally occurred through contaminated objects such as clothing or bedding.^[1][3] The incubation period was 7–17 days, and infected individuals generally became infectious only after the onset of fever and remained contagious until the last scabs fell off.^[3]

Smallpox was prevented primarily through vaccination, with the modern vaccine originating from Edward Jenner's 1796 demonstration that inoculation with cowpox material protected against smallpox.^[1][3] A worldwide immunization program coordinated by the World Health Organization from 1967 onward, combined with case identification and surveillance, led to the interruption of smallpox transmission.^[1][2][3] Vaccination within three days of exposure could prevent or substantially modify the disease, and vaccination four to seven days after exposure could still offer some protection.^[1]

1. 1Wikipedia contributors. Smallpox - Wikipedia [Internet]. Wikipedia. cited 3 Sept 2026.Available from: https://en.wikipedia.org/wiki/Smallpox
2. 2World Health Organization. Smallpox [Internet]. cited 3 Sept 2026.Available from: https://www.who.int/news-room/questions-and-answers/item/smallpox
3. 3World Health Organization. Smallpox [Internet]. cited 3 Sept 2026.Available from: https://www.who.int/health-topics/smallpox
4. 4Nucera 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/