How Smallpox Is Treated

When smallpox was still a naturally occurring medical disease, treatment was often supportive. Patients were made as comfortable as possible and the disease was left to take its course. There were no useful antiviral medication options. Post-exposure vaccination was the only viable treatment option that doctors could try, and it relied upon the patient recognizing that he or she was exposed (or that healthcare officials tracked down those who had any contact with newly diagnosed patients).

Since the World Health Organization (WHO) announced that smallpox was eradicated in 1980, researchers have only had animal analogs to test treatment options.

Development of antiviral medications to treat variola is now based solely on the zoonotic versions of orthopoxvirus.

Post-Exposure Vaccination

Giving a patient the smallpox vaccine after the patient has already been exposed was the main treatment of choice if it was thought that there would be time for the vaccine to work. The treatment was not an option if the patient already had developing lesions. However, there had been a decrease in severity of smallpox and in some cases, it was likely that smallpox never developed as a result of post-exposure vaccination.

Unfortunately, the data obtained during the years when healthcare officials were actively eradicating the disease are not necessarily accurate to a modern outbreak.

Contemporary patients in many parts of the world are immunocompromised due to HIV and aggressive modern medical treatments.

The vaccine used during the eradication years was the first generation and today's version might be more or less effective. Likewise, side effects of the vaccine might be different and will certainly have different frequencies of common effects.

Antiviral Medications

Because there have been no more cases of actual smallpox occurring in humans since 1977, there's no way to test new antiviral medications on a human infected with the variola virus. Instead, researchers use humans infected with other orthopoxviruses or on primates infected with live variola virus. There are two potential new antiviral drugs being developed and one is already being stockpiled in the event of a smallpox outbreak.

Without human testing with actual variola virus, there is no way to know for sure how these medications will behave or if they will be effective.

Animal testing shows that administration of an antiviral medication after lesions appear—that's the expected clinical sign that tells doctors that a patient has smallpox—does shorten the illness in a statistically significant way. However, antiviral medications are not a panacea and even if the drugs are effective for smallpox in humans, dosing might be way off in the initial cases.


Since treatment for smallpox is limited to only vaccination and a couple of untested antiviral medications, prevention becomes the best treatment option.

Smallpox Causes and Risk Factors

The current stockpiles of live variola virus are kept only in two labs worldwide: the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the VECTOR Institute in Russia.

These live virus specimens are kept for research purposes in order to help identify potential drugs and other treatment options.

The two biggest threats to create a smallpox outbreak are either release of the live variola virus (accidentally or intentionally) or a mutation of another orthopoxvirus, most likely the virus that causes mpox (formerly known as monkeypox), to affect humans in a similar way as the smallpox disease.

Frequently Asked Questions

  • Are smallpox and chickenpox related diseases?

    No. Chickenpox is caused by a herpes virus while smallpox is caused by a variola (pox) virus. For infants and those with compromised immune systems, chickenpox may cause complications, but usually its symptoms are mild. Smallpox, on the other hand, was deadly, killing about 30% of those who contracted it.

  • How do you treat smallpox?

    It has not been necessary to treat smallpox since the disease was eradicated in 1980. However, antiviral drugs have been approved by the FDA to treat smallpox and would be available in case the disease was ever active again.

  • If I was vaccinated for smallpox am I immune to the disease?

    Not necessarily. Immunity from the vaccine may only last 10 to 15 years, so people who received the vaccine as children might be susceptible if they’re exposed to smallpox. But since the disease is eradicated, there’s currently no risk of infection.

6 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Meseda CA, Weir JP. Third-generation smallpox vaccines: challenges in the absence of clinical smallpox. Future Microbiol. 2010;5(9):1367-82. doi:10.2217/fmb.10.98

  2. World Health Organization. Smallpox vaccines.

  3. Keckler MS, Reynolds MG, Damon IK, Karem KL. The effects of post-exposure smallpox vaccination on clinical disease presentation: addressing the data gaps between historical epidemiology and modern surrogate model data. Vaccine. 2013;31(45):5192-201. doi:10.1016/j.vaccine.2013.08.039

  4. Petersen E, Abubakar I, Ihekweazu C, et al. Monkeypox - Enhancing public health preparedness for an emerging lethal human zoonotic epidemic threat in the wake of the smallpox post-eradication era. Int J Infect Dis. 2019;78:78-84. doi:10.1016/j.ijid.2018.11.008

  5. National Organization for Rare Disorders. Smallpox.

  6. Center for Disease Control and Prevention. Smallpox: Treatment.

Additional Reading
Rod Brouhard, EMT-P

By Rod Brouhard, EMT-P
Rod Brouhard is an emergency medical technician paramedic (EMT-P), journalist, educator, and advocate for emergency medical service providers and patients.