Symptoms and Signs of Smallpox

Medical Author: John P. Cunha, DO, FACOEP
Medically Reviewed on 9/26/2022

Doctor's Notes on Smallpox

Smallpox (also called variola) is a viral illness caused by a poxvirus transmitted from person to person that causes high fever and characteristic rash. About one-third of those infected may die. Due to the success of an intense global public health initiative, smallpox is the only disease that has been completely eradicated worldwide, but it remains a potentially devastating biological weapon.

Symptoms of smallpox infection can take one week to 17 days to appear and may include

  • fever,
  • chills,
  • vomiting,
  • body aches,
  • headache,
  • felling unwell (malaise),
  • muscle aches,
  • backache, and
  • confusion.

About 48-72 hours after the initial smallpox symptoms, a characteristic rash appears and turns into virus-filled sores, which later scab over. These sores may easily be mistaken for chickenpox. Just after the rash appears, the virus is highly contagious. When the scabs heal and fall off a depression or light-skinned scar remains.

What Is the Treatment for Smallpox?

There is no specific treatment for smallpox. If a smallpox outbreak were to occur, public health officials would use the smallpox vaccine to control it. 

Some antiviral drugs may help treat smallpox but there is no smallpox treatment that has been tested in people who are sick with the disease and that has proven effective.

Antiviral medications that might be used to treat smallpox include: 

  • Tecovirimat (TPOXX) 
    • Food and Drug Administration (FDA) approved for treatment of smallpox in case of an outbreak
    • Has been shown effective in lab tests and animal tests
    • Has been used successfully in the recent monkeypox outbreak
  • Cidofovir and brincidofovir
    • Not FDA approved to treat the variola virus that causes smallpox but might be used for isolated cases or during an outbreak under an appropriate regulatory mechanism (such as an investigational new drug [IND] protocol or Emergency Use Authorization [EUA])
    • Have been shown to stop the growth of the variola virus in lab tests and are effective in treating animals with similar diseases to smallpox

These drugs have not been tested in people sick with smallpox, so it is unknown if a person with smallpox would benefit from treatment with them.

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Kasper, D.L., et al., eds. Harrison's Principles of Internal Medicine, 19th Ed. United States: McGraw-Hill Education, 2015.