Smallpox was once a widespread global threat with a mortality rate reaching approximately 30% for the most severe strain. For centuries, it afflicted populations, leaving survivors scarred and frequently blind. The successful global vaccination campaign led by the World Health Organization culminated in the disease being declared eradicated in 1980, a monumental public health achievement. Although the virus no longer circulated in the human population, its physical existence was not entirely eliminated.
The Variola Virus in Storage
The Variola virus is now confined to two high-security, maximum containment facilities authorized by the World Health Organization. These official repositories are located at the Centers for Disease Control and Prevention (CDC) in Atlanta, United States, and the State Research Center of Virology and Biotechnology (VECTOR) in Koltsovo, Russia. The samples are maintained under stringent biosafety level 4 (BSL-4) conditions, with international inspections ensuring security and safety protocols are followed.
The continued retention of these samples is a subject of long-standing international debate among scientists and public health officials. Proponents for retaining the virus argue that it is necessary for developing advanced medical countermeasures, such as new antiviral drugs and safer vaccines. Opponents suggest that as long as the live virus exists, it presents an unacceptable risk of accidental release or deliberate misuse.
A smallpox resurgence would originate from one of two primary theoretical routes. The first is an accidental release, such as a laboratory error or security breach at one of the two authorized repositories. The second, more concerning route, is a deliberate act, such as bioterrorism, using undeclared or illicit samples that may exist outside the official repositories. Genetic sequencing technology also raises the possibility that the virus could be synthetically recreated by a state actor or sophisticated group.
Global Public Health Preparedness
The cessation of routine childhood vaccination shortly after 1980 means that most of the world’s population under the age of 40 to 50 lacks immunity. This lack of broad population-level protection creates a large susceptible demographic in the event of an outbreak. Currently, vaccination is generally limited to laboratory personnel who work with orthopoxviruses and select military personnel.
Global health authorities maintain substantial reserves of medical countermeasures specifically for a smallpox emergency. The United States Strategic National Stockpile, for example, holds a vaccine supply considered sufficient to vaccinate every person in the country if required. Globally, national stocks and a World Health Organization reserve contribute to a total estimated supply of several hundred million doses of smallpox vaccine.
These vaccine reserves consist of newer, safer generations of vaccines, such as ACAM2000 and JYNNEOS, which have fewer adverse side effects than the older vaccines used during the eradication campaign. Beyond vaccination, a significant development in preparedness is the availability of specific antiviral treatments. The drug tecovirimat, or TPOXX, was approved by the U.S. Food and Drug Administration for the treatment of smallpox.
Tecovirimat works by targeting a protein involved in the virus’s ability to exit infected cells, limiting the virus’s spread within the body. Another antiviral, brincidofovir, has also been approved and stockpiled. These treatments represent an important layer of defense that did not exist during the historical era of smallpox circulation.
Identifying and Containing an Outbreak
If a case of smallpox were identified, the immediate public health response would focus on rapid identification and strict containment to prevent widespread transmission. The initial symptoms of smallpox, including a high fever, severe backache, and malaise, typically precede the characteristic rash by two to four days. This severe prodromal illness is an important sign for clinicians.
The subsequent rash progresses systematically through specific stages:
- Macules (flat spots).
- Firm, raised papules.
- Fluid-filled vesicles.
- Pus-filled pustules before scabbing over.
A key diagnostic feature is that all lesions on any one part of the body are in the same stage of development, unlike chickenpox, where lesions appear in “crops” and can be seen in various stages simultaneously.
The smallpox rash is concentrated on the face and extremities, including the palms of the hands and soles of the feet, a distribution known as centrifugal. This contrasts with chickenpox, which typically has a more central concentration on the trunk. Once a case is confirmed, the primary strategy for containment is “ring vaccination.”
Ring vaccination involves identifying and vaccinating the infected person’s close contacts and their contacts, creating a protective barrier around the case. This targeted approach, which was successful during the final stages of the original eradication campaign, maximizes the use of vaccine supplies while minimizing the risks associated with mass vaccination. Confirmed and suspected cases would also be placed under strict isolation protocols in specialized facilities to stop the chain of transmission quickly.