Smallpox was a highly contagious viral disease that caused widespread death and disfigurement for centuries. The infection is caused by the Variola virus, a large, double-stranded DNA virus belonging to the Orthopoxvirus genus. Before its eradication, the disease had a mortality rate of approximately 30 percent, killing hundreds of millions of people in the 20th century alone. The Variola virus exclusively infects humans, meaning there was no animal reservoir to sustain its presence in nature.
The Distinctive Stages of the Smallpox Rash
The visual hallmark of smallpox was a severe rash that progressed through distinct, predictable stages. The process began after a prodromal phase of high fever, headache, and severe backache. Small, reddish spots called macules first appeared, typically on the mucous membranes of the mouth and throat. Within 24 to 48 hours, the characteristic skin rash emerged, starting on the face and forearms before spreading outward to the extremities and trunk in a centrifugal pattern.
The initial macules quickly developed into raised, firm bumps known as papules, which felt like shot under the skin. Over the next one to two days, these papules became vesicles, which were round, tense, and filled with clear fluid. A distinguishing trait of the smallpox rash was that all lesions in a specific area of the body, such as the face, were at the same stage of development, unlike the asynchronous “cropping” seen in chickenpox.
As the disease progressed, the fluid within the vesicles became cloudy and opaque, transitioning them into deep-seated pustules by approximately the seventh to tenth day of the rash. These pustules were firm to the touch and often featured a central depression or umbilication. The image of the dense, widespread pustular rash is most commonly associated with historical smallpox photography.
Finally, over the second week, the pustules began to dry out, collapsing to form thick, dark crusts or scabs. These scabs eventually detached, typically by the third or fourth week after the rash began, leaving behind pitted, depigmented scars known as pockmarks, especially on the face. The concentration of lesions on the face and the centrifugal distribution were clinical indicators used during the eradication campaign.
Global Eradication Through Vaccination
The effort to eliminate smallpox began centuries ago, culminating in one of public health’s greatest achievements. The foundation was laid in 1796 by English physician Edward Jenner, who observed that people infected with the mild cowpox virus were protected from smallpox. Jenner used material from a cowpox lesion to inoculate a young boy, successfully demonstrating that this process, which he termed vaccination, conferred immunity.
While the concept was established early, a coordinated global effort did not begin until the World Health Organization (WHO) launched its Intensified Eradication Programme (IEP) in 1967. This campaign was made possible by logistical and scientific innovations that streamlined vaccine delivery in remote areas. One innovation was the development of a freeze-dried, heat-stable vaccine. This vaccine maintained its potency in tropical climates without constant refrigeration, overcoming a significant barrier to global deployment.
Another advancement was the bifurcated needle, a small, two-pronged instrument that greatly simplified the vaccination process. This needle required only one-fourth the amount of vaccine compared to previous methods. It allowed for quick, effective administration by non-specialized personnel, becoming the primary tool used during the final years of the IEP. The primary strategy employed was “ring vaccination,” where newly identified cases were isolated and all close contacts were quickly vaccinated to create a protective barrier of immunity.
This combination of active case-finding, surveillance, and targeted vaccination successfully contained outbreaks and halted transmission chains. The last naturally occurring case of smallpox was recorded in Somalia in 1977. Following years of intensive surveillance, the World Health Assembly officially declared smallpox eradicated globally in May 1980, marking the first and only time a human infectious disease has been intentionally eliminated from the planet.
Why Smallpox Remains a Current Concern
Despite its eradication in the wild, the Variola virus still exists in secure, controlled laboratory environments. Following global elimination, the WHO mandated that all known stocks of the virus be either destroyed or consolidated into two official repositories. These remaining stockpiles are held under high-security conditions at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and at the State Research Centre of Virology and Biotechnology (Vector) in Koltsova, Russia.
The continued existence of these samples is the subject of an ongoing, decades-long debate within the international scientific and public health communities. Advocates for their retention argue the live virus is necessary for developing next-generation countermeasures, including improved antiviral drugs and safer vaccines. They contend that the unique properties of the Variola virus must be studied to ensure the world is prepared for any re-emergence.
Conversely, those who favor destruction cite the unacceptable risk posed by accidental release or intentional misuse. They argue that as long as the virus exists, there is a possibility it could escape containment or be weaponized by a rogue state or terrorist organization. The World Health Assembly has repeatedly postponed the final decision on destruction, maintaining the stocks for research under strict WHO oversight while the debate continues.
The cessation of routine childhood smallpox vaccination means that the global population under the age of 40 has little to no immunity to orthopoxviruses. This lack of population immunity amplifies the risk associated with the remaining stockpiles and any potential future outbreak. The concern about the virus’s potential use as a biological weapon ensures that preparedness for a smallpox scenario remains a consideration for global security agencies.