Prevention and Treatment

There are vaccines to protect people from smallpox. Currently, smallpox vaccines are not recommended for the general public because smallpox has been eradicated. If there were a smallpox outbreak, health officials would use smallpox vaccines to control it. While some antiviral drugs may help treat smallpox disease, there is no treatment for smallpox that has been tested in people who are sick with the disease and proven effective.

Smallpox Vaccines

Smallpox can be prevented by smallpox vaccines, also called vaccinia virus vaccines. The vaccines are made from a virus called vaccinia, which is a poxvirus similar to smallpox, but less harmful. There are two licensed smallpox vaccines in the United States and one investigational vaccine that may be used in a smallpox emergency.

The replication-competent smallpox vaccines (ACAM2000 and APSV) can protect people from getting sick or make the disease less severe if they receive the vaccine either before or within a week of coming in contact with smallpox virus. If you get the vaccine:

• Before contact with the virus, the vaccine can protect you from getting sick.
• Within 3 days of being exposed to the virus, the vaccine might protect you from getting the disease. If you still get the disease, you might get much less sick than an unvaccinated person would.
• Within 4 to 7 days of being exposed to the virus, the vaccine likely gives you some protection from the disease. If you still get the disease, you might not get as sick as an unvaccinated person would.

Once you have developed the smallpox rash, the vaccine will not protect you.

Currently, smallpox vaccines are not available to the general public because smallpox has been eradicated, and the virus no longer exists in nature. However, there is enough smallpox vaccine to vaccinate every person in the United States if a smallpox outbreak were to occur.

For more details about the vaccine, see Smallpox Vaccine Basics.

Antiviral Drugs

• In July 2018, the FDA approved tecovirimat (TPOXX) for treatment of smallpox. In laboratory tests, tecovirimat has been shown to stop the growth of the virus that causes smallpox and to be effective in treating animals that had diseases similar to smallpox. Tecovirimat has not been tested in people who are sick with smallpox, but it has been given to healthy people. Test results in healthy people showed that it is safe and causes only minor side effects. In addition to treating smallpox disease, tecovirimat could also be used under an investigational new drug (IND) protocol to treat adverse reactions from vaccinia virus vaccination.
• In June 2021, the FDA approved brincidofovir (TEMBEXA) for treatment of smallpox. In laboratory tests, brincidofovir has been shown to stop the growth of the virus that causes smallpox and to be effective in treating animals that had diseases similar to smallpox. Brincidofovir has not been tested in people who are sick with smallpox, but it has been given to healthy people and people with other viral infections. Test results in people who received brincidofovir for bone marrow transplants showed the most common side effects were diarrhea, nausea, vomiting, and abdominal pain.
• In laboratory tests, cidofovir has also been shown to stop the growth of the virus that causes smallpox and to be effective in treating animals that had diseases similar to smallpox. Cidofovir has not been tested in people who are sick with smallpox, but has been tested in healthy people and in those with other viral illnesses. Cidofovir is not FDA-approved for the treatment of any orthopoxvirus infections, including smallpox or mpox, but is commercially available. Clinicians could choose to use cidofovir to treat patients with orthopoxvirus infection based on individual risk-benefit assessment under practice of medicine.

Because these drugs were not tested in people sick with smallpox, it is not known if a person with smallpox would benefit from treatment with them. However, their use may be considered if there is ever a smallpox outbreak.

Tecovirimat and brincidofovir are currently stockpiled by the Assistant Secretary for Preparedness and Response (ASPR) Strategic National Stockpile, which has medicine and medical supplies to protect the American public if there is a public health emergency, including one involving smallpox.