Smallpox

Unique identifier / Notation

BI0235

Synonyms

Variola variola vera pox red plague

Smallpox is an acute contagious disease caused by the variola virus. Before its eradication, smallpox was one of the world’s most devastating diseases known and was fatal in up to 30% of cases (WHO, no date a).

Primary reference(s)

WHO, no date a. Smallpox. World Health Organization (WHO). Accessed 27 May 2025.

Annotations

Additional scientific description

Smallpox is an acute contagious disease caused by the variola virus, a member of the orthopoxvirus family. It was one of the most devastating diseases known to humanity and caused millions of deaths before it was eradicated. It is believed to have existed for at least 3000 years (WHO, no date a).

The smallpox vaccine, created by Edward Jenner in 1796, was the first successful vaccine to be developed. He observed that milkmaids who previously had caught cowpox did not catch smallpox and showed that a similar inoculation could be used to prevent smallpox in other people (WHO, no date a).

The World Health Organization launched an intensified plan to eradicate smallpox in 1967. Widespread immunization and surveillance were conducted around the world for several years. The last known natural case was in Somalia in 1977. In 1980 WHO declared smallpox eradicated - the only infectious disease to achieve this distinction. This remains among the most notable and profound public health successes in history (WHO, no date a).

Early symptoms of smallpox include high fever, fatigue, severe back pain, and less often, abdominal pain and vomiting. Two to three days later the virus produces a characteristic rash with bumps full of a clear liquid, which later fill with pus and finally develop a crust that dries and falls off. The rash begins on the face and hands, then spreads to the rest of the body. Lesions develop in the mucous membranes of the nose and mouth and ulcerate soon after formation (WHO, no date a).

The World Health Organization (WHO) has published guidance on case classification and surveillance standards (WHO, no date a).

Metrics and numeric limits

Not applicable.

Key relevant UN convention / multilateral treaty

Convention on the prohibition of the development, production and stockpiling of bacteriological (biological) and toxin weapons and on their destruction: Article I (UNODA, 1972).

International Health Regulations (2005), 3rd ed. (WHO, 2016).

Drivers

Vaccination campaigns and surveillance and prevention measures were undertaken to contain epidemic hotspots and to better inform affected populations. Smallpox was officially declared eradicated in 1980 and is the first disease to have been fought on a global scale (WHO, 2010).

Impacts

Smallpox was fatal in up to 30% of cases (WHO, 2010). Even a single confirmed case of smallpox today would be considered an emergency (CDC, 2024).

Multi-hazard context

Thanks to a successful worldwide vaccination effort in the 20th century, smallpox has been eradicated. No smallpox case has been identified since 1977. Even a single confirmed case of smallpox today would be considered an emergency (CDC, 2024a; 2024b).

However, it is possible that variola virus could be used in a biological attack (an intentional release of viruses, bacteria, or other germs that can sicken or kill people, livestock, or crops). Public health authorities prepare for a possible but unlikely biological attack that uses smallpox as a weapon. Public health authorities are concerned about smallpox because it is a serious—even deadly—disease. Today, there are only two labs in the world that are approved to have the smallpox virus for research: the Centers for Disease Control and Prevention (CDC) in the United States and the Russian State Centre for Research on Virology and Biotechnology in the Russian Federation. There is credible concern that in the past some countries made the virus into weapons, which may have fallen into the hands of terrorists or other people with criminal intentions (CDC, no date). Post-eradication, there are concerns about accidental or deliberate release or reconstruction of variola virus that could be deployed as a biological weapon (UNODA, 1972).

Risk Management

Vaccination against smallpox can be used very effectively to prevent infection and disease (WHO, no date a). A global smallpox vaccine stockpile is maintained by the WHO to complement stocks held by a number of countries (WHO, 2017).

Preparedness for smallpox also entails education of health personnel in the differential diagnosis of smallpox, strengthening laboratory capacities for diagnostics, expansion of expertise in the area of laboratory biosafety and biosecurity, and strengthening of national-level biosafety regulations in all countries (WHO, no date a).

The WHO Smallpox Secretariat based in WHO Headquarters coordinates all smallpox eradication-related and post-eradication activities. These include overseeing permitted research with live variola virus for the development of countermeasures such as vaccines and antivirals. Since the eradication era, safer vaccines and specific treatments have been developed for smallpox and related diseases such as Mpox. The Secretariat is also responsible for emergency preparedness and manages a smallpox vaccine emergency stockpile in the unlikely event that the disease re-emerges. The Secretariat manages the biosafety and biosecurity measures of the authorized variola virus repositories as mandated by the World Health Assembly and ensures annual reporting to WHO Governing Bodies. The Smallpox Secretariat supports WHO Archives in preserving the global history of smallpox and documenting the lessons learned from the successful eradication of smallpox (WHO, no date a).

Monitoring

WHO supports countries to conduct all-hazards strategic risk assessment in the contexts of health emergencies and disasters, which results in the development of a country risk profile. Empowered with the country risk profile, inclusive of a seasonal risk calendar, countries can anticipate potential emergencies before they occur to trigger early alerts and inform early actions (WHO, 2021).

WHO's Early Warning, Alert and Response System (EWARS) has been designed to improve disease outbreak detection in emergency settings, such as in countries in conflict or following a natural disaster. It is a simple and cost-effective way to rapidly set up a disease surveillance system. EWARS is deployed during an emergency as an adjunct to the national disease surveillance system. WHO works with Ministries of Health and health sector partners to train local health workers to use the system. After the emergency, EWARS should re-integrate back into the national system (WHO, no date b).