Smallpox, caused by the variola virus, was an ancient and devastating disease that afflicted humanity for thousands of years, leading to widespread suffering and death. This highly contagious illness left survivors with permanent scars and, in many cases, blindness. Smallpox is unique in medical history as the only human disease to have been completely eradicated worldwide.
The Eradication of Smallpox
The global effort to eradicate smallpox was a monumental undertaking, spearheaded by the World Health Organization (WHO) through its Intensified Smallpox Eradication Programme launched in 1967. Before 1967, mass vaccination campaigns were the primary strategy, but they proved less effective. This led to a shift towards a more targeted approach: surveillance and containment.
This strategy involved actively searching for new cases, isolating infected individuals, and vaccinating everyone in the immediate vicinity of an outbreak, a method known as “ring vaccination.” Public health workers went door-to-door, offering rewards for reporting cases and monitoring exposed individuals and their contacts. This systematic approach, combined with a stable and effective vaccine, proved highly successful.
The last naturally occurring case of smallpox was reported in Somalia in 1977. In May 1980, the World Health Assembly officially declared smallpox eradicated globally.
Factors Contributing to Resurgence Concerns
Despite its eradication, concerns about smallpox reappearing persist. A primary concern is the continued existence of variola virus stocks in highly secure laboratories. The World Health Organization has designated two repositories: the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the State Research Center of Virology and Biotechnology (VECTOR) in Koltsovo, Russia.
These facilities operate under maximum containment (Biological Safety Level 4, BSL-4), with regular WHO inspections. While these labs are intended for research on new antiviral drugs, safer vaccines, and improved diagnostic tests, the possibility of accidental release or deliberate misuse remains a worry. Instances of unaccounted-for vials have occurred, such as the discovery of variola samples in an unused storage room at a U.S. Food and Drug Administration (FDA) laboratory in 2014. These were subsequently secured and tested.
Another concern is declining global immunity, as routine vaccination ceased in most countries after eradication in the 1970s and 1980s. This means a large portion of the global population has no protection against the virus.
Consequences of a Smallpox Outbreak
Should smallpox re-emerge, the consequences could be severe, as much of the world’s population lacks immunity. Smallpox, caused by the variola virus, spreads readily from person to person through infected aerosols and droplets, particularly during face-to-face contact. Transmission can also occur, with lower risk, through contaminated items like clothing or bedding.
The illness begins with influenza-like symptoms, including high fever, body aches, and prostration, followed by a characteristic rash that progresses from spots to pustules. Historically, the variola major form had a mortality rate of about 30% in unvaccinated individuals. Rarer forms like hemorrhagic or flat smallpox were almost always fatal, with mortality rates between 94% and 100%.
Survivors often suffered from deep, pitted scars, especially on the face. About 5-9% developed ocular complications leading to blindness. The virus’s highly contagious nature, combined with a largely susceptible global population, could lead to rapid international spread and overwhelm healthcare systems.
Global Strategies Against Re-emergence
To counter the threat of smallpox re-emergence, global strategies ensure preparedness and rapid response. Several countries maintain emergency stockpiles of smallpox vaccines, such as ACAM2000 and Jynneos. ACAM2000 is a replicating vaccine, while Jynneos is a non-replicating alternative approved for both smallpox and monkeypox.
Research continues into new antiviral treatments, with drugs like tecovirimat (TPOXX) and brincidofovir (TEMBEXA) approved for smallpox treatment. Their effectiveness in humans has not been directly tested against the variola virus. International surveillance mechanisms detect suspicious cases, with rapid detection and diagnosis being paramount for containment.
In an outbreak, a primary response would involve targeted vaccination, similar to the ring vaccination strategy used during eradication, along with isolating cases to break the chain of transmission.