Fast Facts
- Variola virus is what causes smallpox.
- Smallpox was declared eradicated in 1980 by the World Health Organization, with no known cases of naturally occurring smallpox since 1977. The last outbreak of smallpox in the U.S. occurred in 1949.
- While there is no known immediate, direct threat of a biological attack using smallpox (i.e., an intentional release of Variola virus), concerns over the possible use of Variola virus in a biological attack have led to increased preparedness efforts.
- Transmission: Smallpox can be transmitted or spread from person-to-person via inhalation of virus-containing airborne droplets of saliva from an infected person. Transmission can also occur via contact with material from the smallpox pustules or crusted scabs, or through materials such as bedding or clothing that has been in contact with the pustules or scabs.
- Prevention: Smallpox can be prevented by vaccination with smallpox vaccine. The vaccine does not contain the smallpox virus and cannot give you smallpox.
- Treatment: Treatment of patients with smallpox generally involves supportive care. TPOXX (tecovirimat) and Tembexa (brincidofovir) are approved for the treatment of smallpox.
FDA’s role
The FDA plays a critical role in protecting the United States from chemical, biological, radiological, nuclear (CBRN), and emerging infectious disease threats.
The FDA’s roles in smallpox preparedness and response include:
- Facilitating the development and availability of medical countermeasures (MCMs) that can be used to diagnose, prevent, or treat smallpox.
- Working with medical product sponsors to clarify regulatory and data requirements necessary to rapidly advance development of MCMs essential to supporting response efforts.
- Protecting the safety of the nation’s blood supply and human cells, tissues, and cellular/tissue-based products for transplantation.
- Enabling access to investigational MCMs—when necessary—through an appropriate regulatory mechanism such as under an Emergency Use Authorization (EUA) or under expanded access when the clinical circumstances warrant.
- Protecting consumers against fraudulent products – Unfortunately, during emergency situations, fraudulent products claiming to prevent, treat or cure conditions associated with the emergency almost always appear for sale. The FDA monitors for fraudulent products and false product claims related to CBRN and emerging infectious disease threats and takes appropriate action to protect consumers.
Medical countermeasures
Vaccines
Vaccination against smallpox before contact with the Variola virus can protect you from getting sick. Vaccination within 7 days of being exposed to Variola virus may provide protection from disease and, if you still get smallpox, may reduce the severity of disease. Currently, smallpox vaccine is not available to the general public because smallpox has been eradicated, and the virus no longer exists in nature.
The Strategic National Stockpile (SNS) currently contains three smallpox vaccines:
- ACAM2000 (Smallpox [Vaccinia] Vaccine, Live) is a replication-competent vaccinia virus vaccine, indicated for active immunization against smallpox disease in persons determined to be at high risk for smallpox infection.
- Jynneos Smallpox and Monkeypox Vaccine, Live, Non-Replicating was approved on September 24, 2019, for the prevention of smallpox and monkeypox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection. This is the only currently FDA-approved vaccine for the prevention of monkeypox disease. Jynneos will be available for those determined to be at high risk of either smallpox or monkeypox infection.
- Aventis Pasteur Smallpox Vaccine (APSV) is an investigational, replication-competent vaccinia virus vaccine. In a smallpox emergency, APSV could potentially be made available under an IND or EUA for use in circumstances where approved vaccines are depleted or not readily available.
Replication-competent vaccinia virus vaccines are generally safe and effective, but some people do experience side effects and adverse reactions. Severe adverse reactions are more common in people who are being vaccinated for the first time and among young children (≤5 years of age). Vaccinia Immune Globulin Intravenous (Human) (VIGIV) is indicated for the treatment and/or modification of certain conditions that are complications resulting from smallpox vaccination with replication-competent vaccinia virus vaccines.
Therapeutics
There are two FDA-approved drugs for the treatment of smallpox.
- TPOXX (tecovirimat) is indicated for the treatment of smallpox. TPOXX was the first approved smallpox therapeutic in the United States, approved July 13, 2018. On May 18, 2022, the FDA approved an intravenous (IV) formulation of TPOXX to treat smallpox. The IV formulation (PDF, 565 KB) is an option for those who are unable to swallow the oral capsule.
- Tembexa (brincidofovir) – The FDA approved Tembexa to treat smallpox on June 4, 2021.
The Strategic National Stockpile (SNS) currently contains three smallpox therapeutics:
- TPOXX (tecovirimat) is indicated for the treatment of smallpox.
- Cidofovir is an investigational therapeutic for the treatment of smallpox. Cidofovir has not been tested in people with smallpox, and thus it is not known whether a person with smallpox would benefit from treatment with Cidofovir. In a smallpox emergency, Cidofovir could potentially be made available under an IND or EUA for the treatment of smallpox if the circumstances warrant.
- Tembexa (brincidofovir) is indicated for the treatment of smallpox.
Diagnostics
Diagnosis of initial cases of smallpox in a smallpox emergency would likely be based on clinical diagnosis confirmed by follow-up laboratory testing. Laboratory diagnostic testing for Variola virus would occur in a CDC Laboratory Response Network (LRN) laboratory using specialized diagnostic tests and protocols for Variola virus.
Consumer protection
Unfortunately, during outbreak situations, fraudulent products claiming to prevent, treat or cure a disease almost always appear. The FDA monitors for fraudulent products and false product claims related to smallpox and takes appropriate action to protect consumers.
