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Last updated: 8/21/2024
Years published: 2001, 2004, 2009, 2024
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders, for assistance in the preparation of this report.
Smallpox is a highly infectious disease caused by the variola virus. It is characterized by symptoms such as fever, a general feeling of unwellness (malaise), headaches and back pain, followed by the development of a rash and raised lesions (pocks) within two to three days. The virus had two primary strains: variola major and variola minor.
In 1980, the World Health Assembly declared smallpox eliminated (eradicated), and no cases of naturally occurring smallpox have happened since, however, concerns about its potential use as a bioterrorism weapon have resurfaced in recent years.
Smallpox is a serious disease that progresses through distinct stages, from initial symptoms to rash development, and finally to scabbing and recovery.
Incubation period (7-17 days):
After being exposed to the smallpox virus, symptoms typically begin to appear after an incubation period of about 12 days, though it can range from 7 to 17 days. During this period, the virus is in your body, but you won’t show any symptoms and won’t feel sick. People are not contagious at this stage.
Initial symptoms (2-4 Days) (appear after the incubation period):
The first signs of smallpox usually include a high fever, severe headaches, back pain and malaise. Some people may also experience vomiting, severe abdominal pain and delirium. At this point, most people feel too sick to carry on with their normal activities. During this stage, people may become contagious, but the risk is higher in the stages that follow.
Early rash (about 4 days):
Two to three days after the initial symptoms begin, a rash appears, first as small red spots on the tongue and in the mouth. These spots quickly turn into sores that break open, releasing large amounts of the virus into the mouth and throat. This marks the beginning of the most contagious stage.
The rash then spreads to the skin, starting on the face and quickly moving to the arms, legs, hands, feet and eventually the entire body within 24 hours. As the rash spreads, the fever may decrease, and you might start feeling a little better. By the fourth day of the rash, the sores fill with a thick, opaque fluid, often with a dent in the center, and the fever may spike again.
Pustular rash (about 10 days):
Around the sixth day of the rash, the sores become pustules—round, firm bumps that feel like peas under the skin. This stage lasts about 10 days, during which people remain highly contagious. After about 5 days, the pustules begin to crust over and form scabs.
Scabs and recovery (about 2 weeks):
By the end of the second week after the rash first appeared, most of the sores will have scabbed over. Over the next week or so, these scabs start to fall off, leaving marks or scars on the skin. This stage lasts about 6 days.
People are still contagious until all the scabs have fallen off, which usually happens about three weeks after the rash appears. After four weeks, once all the scabs have fallen off, people are no longer contagious.
Smallpox comes in two strains according to the severity of the disease:
Smallpox can lead to serious, life-threatening complications including:
Smallpox is caused by the variola virus and spreads primarily through person-to-person contact via inhalation of respiratory droplets expelled by an infected individual. The virus can also spread through direct contact with contaminated materials, such as clothing or bedding. Individuals are most contagious during the first week of illness.
Smallpox existed for thousands of years until the World Health Assembly declared it eradicated in May of 1980. The last known case of smallpox occurred in Somalia in 1977.
The only known stores of the smallpox virus are in two locations: the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, GA and Russian Federation government laboratories near Moscow. However, government officials fear that secret stores may be maintained elsewhere and may be released deliberately as an act of warfare (bioterrorism).
Individuals with weakened immune systems such as those with leukemia, lymphoma or AIDS would be more susceptible to smallpox infection if the disease was reintroduced into society.
Smallpox is eradicated and therefore doctors nowadays do not have experience with it. Even one case of smallpox would be a public health emergency. When the disease still existed, doctors used the appearance of the rash and pattern of symptoms to make a diagnosis of smallpox. Diagnosis could be confirmed by finding viral DNA or antibodies to smallpox in blood or skin tissue samples. The Centers for Disease Control and Prevention uses special labs to test tissue samples for smallpox. This test can tell for sure if a person has the virus.
The World Health Organization has training materials to help medical care providers recognize smallpox and avoid common diagnostic errors: Smallpox recognition card
The algorithm, “Evaluating Patients for Smallpox: Acute, Generalized Vesicular or Pustular Rash Illness Protocol” provides a standard method for evaluating patients with acute, severe vesicular or pustular rash illness by giving clinical clues for differentiating smallpox from varicella and other rash illnesses.
Before 1972, smallpox vaccinations were routinely administered to children in the United States. However, the immunity provided by this vaccine typically lasts only 10 to 15 years, meaning that people who were vaccinated as children may no longer be protected. Although smallpox was eradicated and the virus no longer exists in nature, vaccines remain a critical tool in case of an outbreak.
Smallpox vaccines, known as vaccinia virus vaccines, are made from the vaccinia virus, a poxvirus similar to but less harmful than the smallpox virus. The two licensed smallpox vaccines in the U.S. are ACAM2000 and APSV, both replication-competent vaccines that can protect against smallpox if administered before exposure or within a week of contact with the virus.
Once smallpox symptoms, particularly the rash, have developed, the vaccine is no longer effective. While smallpox vaccines are not available to the public, there is enough vaccine stockpiled to vaccinate everyone in the United States in the event of an outbreak. The U.S. has maintained an emergency supply of the vaccine, and in 2000-2001, the CDC worked with pharmaceutical companies to produce more vaccines in case of a bioterrorism threat.
In rare cases, the smallpox vaccine can cause severe reactions. These can be treated with a specialty antibody called vaccinia immune globulin intravenous (human) or VIGIV. This treatment was approved by the U.S. Food and Drug Administration (FDA) in 2005.
Although there is no treatment for smallpox that has been proven effective in people who are sick with the disease, several antiviral drugs have shown promise in laboratory and animal studies. These include:
Because these drugs have not been tested in people sick with smallpox, it is unclear how effective they would be in treating the disease. However, they are considered potential options in the event of a smallpox outbreak. The U.S. government’s Strategic National Stockpile includes tecovirimat and brincidofovir to ensure preparedness for a public health emergency involving smallpox.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, in the main, contact: www.centerwatch.com
For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
INTERNET
Smallpox. Centers for Disease Control and Prevention. July 12, 2017. https://www.cdc.gov/smallpox/index.html Accessed Aug 20, 2024.
Smallpox Prevention and Treatment. Centers for Disease Control and Prevention. April 8, 2024. https://www.cdc.gov/smallpox/prevention-treatment/index.html Accessed Aug 20, 2024.
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