What Is Smallpox?

  • Shajrat Mir, Master's Degree, Biotechnology Engineering, International Islamic University Malaysia
  • Katheeja Imani, MRes Biochemistry, University of Nottingham, UK


Smallpox is an extremely contagious infectious disease that is estimated to have taken the lives of more than 300 million people since 1900, meaning that it was one of the most devastating diseases ever seen on planet Earth. Around 30% of those infected died. Due to the enormous success of widespread vaccination, the WHO certified the global eradication of smallpox in 1980. It remains to be the only infectious disease for which worldwide eradication has been achieved.1

There are currently no cases of naturally occurring smallpox anywhere in the world, the only live smallpox virus that exists is located in laboratories in America and Russia. These virus samples have been kept because the stored samples can help to develop treatments for other poxviruses and in the unlikely case of the smallpox virus being used in biological warfare, the samples could be used to develop treatment.

Causes of smallpox

The origins of smallpox remain unknown. Evidence of the disease found on Egyptian mummies suggests that it has existed for at least 3000 years. Although it is unknown where the disease first came from, the cause of it is known. 

Smallpox is caused by the variola virus, the largest of the human pathogen. Variola is a member of the orthopoxvirus family.1  

Smallpox is spread through contact with infected people, particularly prolonged face-to-face contact with somebody who was infected if they sneeze or cough, etc. The virus was also spread through materials that had virus particles on them; these could have been clothes that had been worn by a patient. It could also spread through the air in closed buildings, but this is rare. 

Signs and symptoms of smallpox

The symptoms that a person with smallpox usually experiences are fatigue, back pain, high temperature, and sometimes abdominal pain and vomiting.

As smallpox progresses, the patient would go through several stages. They are:

Incubation period

Initially, the incubation period of the disease lasts around 10-14 days, when the individual gets infected with the virus but is asymptomatic and not contagious. 

The early stages

The person might present with general flu-like symptoms, including a high temperature and body aches for roughly 2-4 days and might be contagious at this point. 

Rash appears

This is the stage where the patient is the most contagious. Starting on the tongue and around the mouth, patients develop small red spots that then open up, spreading large amounts of the variola virus into the mouth and throat. The patient’s temperature remains high and the rash spreads to other areas of the body within 24 hours. Once this rash is fully developed, the patient starts to feel better as their high temperature is often reduced at this stage. At approximately day 4, the rash becomes sores filled with thick fluid, and the patient’s temperature may rise again until the sores are scabbed over. 

Rash becomes pustules

The person continues to be contagious at this stage. The rash becomes lumps under the skin, which later starts to develop into scabs. 

Scabs fall off

The patient is still contagious at this stage. The scabs fall off the pustules, leaving behind marks on the skin. Permanent scarring was seen in some patients who recovered from smallpox. It is around 3-4 weeks after the onset of the rash that all of the scabs will have fallen off, and the patient is no longer contagious. 

Management and treatment for smallpox

One of the early methods used to control smallpox is a process called variolation, whereby individuals who are not infected with smallpox are intentionally exposed to pus from smallpox sores by scratching the liquid into their arm or inhalation. This would result in the person being infected with the virus but they were not as unwell as they would have been had they caught the infectious disease from another infected patient.1 Edward Jenner was an English doctor who observed that milkmaids who had been infected with cowpox did not develop smallpox. He hypothesized that this exposure to the cowpox virus was protecting them. Through the process of variolation, Jenner exposed people to cowpox and found that he was correct; they were indeed protected from smallpox. This was the first successful vaccine to be developed. 

Nowadays, smallpox vaccination is a live vaccine made from vaccinia, which is a less harmful poxvirus, and is stockpiled. The vaccine does not contain the smallpox virus and so cannot infect people with it but is effective at preventing it. New antiviral treatments have been approved for use to treat smallpox should an outbreak occur. These medications have not been tested on humans with smallpox but have been tested on healthy humans with little side effects. These drugs are tecovirimat and brincidofovir. 


How is smallpox diagnosed?

Smallpox is usually diagnosed by assessing the patient’s symptoms. A definite diagnosis could be achieved by testing the blood for variola or by checking for smallpox lesions.

How can I prevent smallpox? 

As smallpox is now a globally eradicated disease, you do not need to worry about catching it. However, should an outbreak ever occur, vaccination is the best way to prevent the disease. The smallpox vaccine provides protection, and even if you have already been infected with the virus, you may not get as unwell as an unvaccinated person. However, if the smallpox rash has already developed then vaccination will not be effective.

Who is at risk of smallpox?

Currently, there is no risk of catching smallpox because the only samples of live virus that exist are locked away in a laboratory. Of course, there is a tiny risk to those working in the laboratory, but there are strict safety protocols in place to ensure that the samples are held at the highest level of security within secure facilities. There is also a risk of the variola virus being used in bioterrorism and biological warfare, but there are bioterrorism response plans in place should an event like this occur. This is a concern amongst some infectious disease experts because most people are no longer readily vaccinated against smallpox as it has been eradicated for a significant period of time. On the other hand, if an outbreak were to occur, public health professionals would be able to use smallpox vaccines and other disease control methods such as isolating those infected.  

How common is smallpox?

Smallpox is now eradicated and so there are no known cases of the disease.

When should I see a doctor?

If you have any symptoms of smallpox, you should see your doctor right away. It's highly unlikely that the symptoms would be caused by contracting a smallpox infection, but other viruses might have similar symptoms, so it’s important to contact a medical professional if you are worried or if the symptoms do not dissipate within a few days. 


Smallpox was one of the most devastating infectious diseases ever seen on the planet. Thanks to a huge vaccination project, the World Health Organisation confirmed that smallpox is now an eradicated disease and so the risk to the human population is very low. There are small stockpiles of the disease located in laboratories, and this is controversial because some scientists fear that it could fall into the wrong hands and be used for bioterrorism or biological warfare. Smallpox can easily spread by face-to-face contact with somebody already infected with the virus; the symptoms include high fever and skin pustules. Edward Jenner first used pus from cowpox lesions to innoculate people against smallpox, now there is a vaccine widely available should it be needed in the future. 


  1. Simonsen KA, Snowden J. Smallpox. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Nov 14]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK470418/ 
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Jessica Gibson

Bachelor of Science- BSc(Hons)- Health Sciences- The Open University

Jessica is a Health Sciences graduate with a passion for both Science and English and is delighted to have found a way to combine the two. She is a motivated and enthusiastic writer determined to make scientific information more widely accessible.
Jessica is especially interested in infectious diseases, neurodegenerative diseases, the impact of trauma on physical health, health equity and the health of children residing in developing nations.

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