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Smallpox: Definition, Symptoms, and Causes

Smallpox is a deadly infectious disease caused by a virus. It hasn’t caused an infection in the wild since the 1970s. No one has had smallpox in the United States since 1949. The last death from smallpox was in the United Kingdom in 1978.

Though you’re not likely to encounter smallpox in the wild, it still exists in two labs. These two labs are the Centers for Disease Control and Prevention (CDC) in the United States and the Vector Institute in Russia. These samples are kept to test drugs and conduct other experiments.

The virus is deadly and highly contagious.

This article will discuss the different types of smallpox and its related viruses. It will cover the symptoms, causes, diagnosis, and treatment for smallpox historically and what how they might change if the virus were to cause a new outbreak. We’ll also discuss the outlook for smallpox infection.

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Types of Smallpox

The type of smallpox virus that causes a deadly human disease is the variola virus. It occurs as two closely related virus strains:

  • Variola major is the most severe form. It causes an extensive rash and a high fever. 
  • Variola minor is a milder form that is far less severe and dangerous. 

Variola major has four forms:

  • Ordinary smallpox is the most frequent, making up 85% of cases.
  • Modified variola major is mild and occurs in vaccinated persons. There are fewer lesions, and they heal faster.
  • Flat or malignant-type smallpox causes a rash that shows up slowly, merges, and remains flat and soft or “velvety” to the touch. It’s rare and more deadly.
  • Hemorrhagic smallpox causes reddened skin, burst blood vessels, and bleeding from the gums and sores. 

The flat and hemorrhagic types are more deadly than others but less common. 

One of the first ways humans tried to control smallpox infection was by variolation. This involved taking scabs from people with smallpox and scraping them into an open cut on the skin of people who didn’t have smallpox or having them inhale this scab material through their noses. These people would get milder smallpox, and their immunity would protect them from severe smallpox.

The first smallpox vaccine used the cowpox virus in the same way that variolation had used scabs from people with smallpox. By inoculating a person with the milder cowpox virus, they developed immunity that kept them safe from smallpox.

Modern vaccines are made with the vaccinia virus, which replaced cowpox sometime in the 1800s.

Other viruses in the same family as smallpox exist and infect animals and humans. These Orthopoxviruses often look like smallpox and cause similar symptoms. They can cause severe disease. These include:

  • Cowpox: This virus can be contracted by both cows and humans. Humans can acquire it from cattle, but it is not transmitted from human to human.
  • Vaccinia: This virus can also be contracted by cattle. It is the live virus used in the smallpox vaccine.
  • Mpox (formerly known as monkeypox): This virus can spread from human to human through direct contact with the lesions and scabs. It caused a worldwide outbreak in 2022.
  • Camelpox: This virus can be contracted by camels and can also cross over to humans.
  • Buffalopox: This virus is closely related to vaccinia. Outbreaks are seen in India in cattle, buffaloes, and humans.

Smallpox Symptoms

Smallpox infection takes seven to 19 days to take hold and show symptoms. At this point, the person who has contracted the virus isn’t contagious.

It feels like the flu for the first two to four days. Symptoms of smallpox may include:

  • High fever
  • Fatigue
  • A bad headache​
  • A backache
  • Vomiting (sometimes)

A few days after becoming symptomatic, a person with smallpox develops a rash. The sores feel like firm round nubs in the skin that form red bumps. They first show up inside the mouth, throat, and tongue.

When the sores in the mouth break down, the rash appears on the skin of the face and around the eyes, spreading them to the forearm, then to the belly and legs. Sometimes, these sores appear on the palms of the hands and feet. This process takes about a day. The fever starts to break, and the person begins to feel better.

The sores become bubbles of clear fluid, eventually filling with pus. The fever may come back at this point. The sores eventually crust over, usually three weeks after they show up. When all the scabs fall off, the person can no longer transmit the virus.

Complications of smallpox infections include:

  • Permanent scars, including pockmarks and scarring
  • Disfigured nose or face
  • Eye infections or other complications
  • Blindness 
  • Inflammation of the brain
  • Inflammation of the bones
  • Pregnancy loss
  • Infertility in people with testes


A virus causes smallpox. This virus lives only in humans and doesn’t exist in the wild anymore, so there are no more cases of smallpox. The virus only exists as samples in labs.

The virus spreads during the rash phase by coming into contact with liquid from the sores. Saliva droplets also hold the virus from sores in the mouth and throat. These droplets can spread the virus as a person talks or breathes.

If these droplets are tiny enough, they may spread the virus through the air in enclosed settings.


Healthcare professionals diagnose smallpox with a physical exam and medical history. They’ll ask about your symptoms and may perform blood tests to look for the virus that causes it.


There is no specific treatment for smallpox because no treatment has been tested in humans with smallpox since it was eradicated.

Antiviral drugs that may treat smallpox in an emergency include:

Two vaccines have been created and stockpiled in the case of a smallpox outbreak. These vaccines can stop people from getting sick and make the disease less severe if given within a week of contact with the virus.

Medical care was very different before smallpox was eradicated. Treatment for smallpox often only involved supportive care. 


You can survive smallpox. When the virus was circulating, about 30% of those with variola major died. Only about 1% of those with variola minor died. Severe forms of the disease are more deadly and would have a lower survival rate.

If an outbreak of smallpox were to happen today, modern medicine and antiviral drugs would likely improve these numbers. People are no longer routinely vaccinated for smallpox, but the U.S. stockpile of smallpox vaccine is sufficient to vaccinate everyone in the United States in case of an outbreak.


Smallpox is a deadly infectious disease caused by a virus. It hasn’t caused an infection since the 1970s. It no longer exists in the wild, but scientists keep samples of the virus in two labs. Several related pox viruses exist in nature.

Smallpox can appear in different ways, but typically a person gets a high fever and feels a flu-like illness. They develop sores in their mouth first, then their face, limbs, and abdomen.

The virus is transmitted through contact with fluid from the sores. A person may breathe out droplets of saliva containing the virus from sores in the mouth. It can also transfer to surfaces from sores on the body. Historically, smallpox killed about one-third of the people who contracted the virus that causes it.

Three current antiviral drugs may help treat people who contract smallpox during an outbreak. There is also a stockpile of smallpox vaccines. Vaccination may protect people if given soon after exposure to the virus.

By Jennifer Welsh

Jennifer Welsh is a Connecticut-based science writer and editor with over ten years of experience under her belt. She’s previously worked and written for WIRED Science, The Scientist, Discover Magazine, LiveScience, and Business Insider. 


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