Smallpox was a severe infectious disease that affected humans for thousands of years before its eradication in the late 20th century. The symptoms included a distinctive rash, pustules, and fever.

Many people with smallpox recovered, but the mortality rate was high. About 30% of smallpox cases were fatal. In addition, the disease often left survivors with large areas of scarring and, sometimes, blindness.

Smallpox no longer affects humans because a smallpox vaccine became available. The smallpox vaccine was the first successful vaccine that doctors ever developed, and it represented a significant advancement for modern medicine.

In this article, we look at what smallpox was and who it affected. We also look at the symptoms and treatment of smallpox and explain whether it could come back.

An old photo of children with one sleeve rolled up as they wait to get a smallpox vaccine.Share on Pinterest
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Smallpox was a serious contagious disease that affected humans until the late 20th century. Experts do not know where it originated, but — based on the presence of smallpox-like rashes on some ancient Egyptian mummies — they estimate that it existed for about 3,000 years.

The variola virus caused smallpox. This virus is a member of the orthopoxvirus family, which also includes cowpox and monkeypox. Historians believe that the first written description of smallpox comes from 4th century China.

Human activities allowed the variola virus to spread to different countries and regions over the centuries. Trade gave it the opportunity to spread to Korea and Japan by the 6th century, while the growth of empires meant that it spread through the Middle East, North Africa, Spain, and Portugal.

The wars known as the Crusades brought smallpox to northern Europe in the 11th century. Colonialism and the slave trade then transported smallpox from Portugal to western Africa, and then across the Atlantic to the Caribbean, North America, and South America. Here, it decimated the populations of Indigenous peoples.

Smallpox was an epidemic, which means that it was a disease that spread quickly over a large geographical area. It was one of the most devastating diseases known to humans.

Smallpox is the only infectious disease that humans have managed to eradicate. A couple of secure laboratories do still have samples of variola virus, but these are the only known surviving samples. There is no variola virus in circulation among humans.

People were able to eradicate smallpox due to the creation of the world’s first successful vaccine.

At the end of the 18th century, a British doctor called Edward Jenner observed that milkmaids who had already had cowpox did not get smallpox. From this, he deduced that getting cowpox — which occurs due to a milder type of orthopoxvirus — could protect people against the more severe disease.

He created the first vaccine in 1796, but it took a long time for people to begin using it. Many were afraid of the vaccine and did not trust that it was safe. However, over time, scientists improved the vaccine, and people became more familiar with this prevention method.

In 1900, scientists started using an orthopoxvirus known as vaccinia as the viral agent in this method of inoculation, rather than cowpox. In 1959, the World Health Organization (WHO) launched a plan to eradicate the disease by conducting mass immunizations around the world.

The last naturally occurring case of smallpox occurred in 1977, and the WHO declared the disease eradicated in 1980.

Smallpox affected people from many continents across the world and many different backgrounds. However, smallpox was especially devastating for some populations.

When Europeans arrived in the Americas, they exposed Indigenous people to diseases to which they had no immunity. This meant that illnesses such as influenza, measles, and smallpox had a severe effect on them. Smallpox, in particular, became one of the diseases that Native American people feared most.

While smallpox killed 20–50% of Europeans, it destroyed entire communities of Native American people. In many cases, this was accidental. But in others, colonists used smallpox as an early form of biological warfare.

During 1763–1764, British officers intentionally used smallpox as a weapon to weaken or kill Native American people. There are recorded instances of officers encouraging its spread by handing out blankets or handkerchiefs carrying the variola virus.

Long after the development of the smallpox vaccine, the disease continued to affect some populations more severely than others. While smallpox steadily declined in North America and Europe, with the last cases taking place in the early 1950s, the disease continued to thrive in South America, Asia, and Africa.

Several factors contributed to this, including a lack of:

  • funding
  • commitment from governments
  • vaccine donations to less wealthy countries

The WHO’s global eradication program began in 1959 but was unable to achieve its aim for nearly 20 years because of these factors. Advancements in storing and delivering the vaccine also played a role.

By the late 20th century, the estimated death toll of smallpox worldwide was more than 300 million.

Smallpox symptoms went through several stages over the course of the illness. The initial symptoms included:

  • sore throat
  • headaches
  • high fever
  • weakness or fatigue
  • backache
  • vomiting
  • severe abdominal pain
  • chills
  • lack of appetite

The initial symptoms would last about 4 days. Then, the eruptive phase would begin. This involved a rash that began in the throat before spreading to the face and other parts of the body. The rash consisted of lesions that would grow and develop into deep, round pustules.

These pustules would crust and form scabs before falling off after about 14 days. Often, they would leave scars in people who survived.

Other potential complications of smallpox included:

  • encephalitis
  • osteomyelitis
  • miscarriage or stillbirth
  • infertility in males
  • blindness

There was no treatment for smallpox before the creation of vaccines. Doctors gave people supportive care to help them manage the symptoms, but that was all they could do.

Smallpox vaccines prevented people from getting smallpox, but they were not a cure for existing cases. Only with widespread immunization did the disease begin to die out around the world.

Since smallpox’s eradication, vaccination against the disease has become unnecessary, as it is no longer in circulation. However, those who work in certain laboratories and some military personnel may still receive it as a precaution.

Researchers also continue to work on developing treatments for smallpox, even though there is a vaccine. In 2018, the United States approved tecovirimat (Tpoxx) as the first antiviral treatment for smallpox. Safety trials for this drug are ongoing.

It is possible, though highly unlikely, that smallpox could come back. It is possible because some samples of it do still exist in two secure laboratories. The WHO Collaborating Centers on Smallpox and Other Poxvirus Infections at the CDC holds some, and so does the Russian State Research Center of Virology and Biotechnology.

Concerns about bioterrorism have led to an increased interest in using samples of smallpox to understand and develop treatments for orthopoxviruses. Experts do not consider a smallpox attack likely, but public health authorities are prepared for this scenario should it occur.

Smallpox was a severe infectious disease resulting from the variola virus. Historians believe that it existed for about 3,000 years. It had a high mortality rate, killing 3 in every 10 people who got it.

The symptoms of smallpox included head and body aches, fever, vomiting, and a rash that turned into pustules and scabs. There was no treatment, but the development of the first vaccine meant that people could prevent it.

The last recorded case of a person getting smallpox naturally was in 1977, in Somalia. The WHO declared the disease eradicated in 1980, after many years of efforts to vaccinate the global population. Scientists are still trying to develop drugs that target the variola virus, should humans ever need them.