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Smallpox - Causes, Symptoms, Diagnosis, and Treatment

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Smallpox is a highly contagious and deadly infection caused by the variola virus. Read the article below to learn more about smallpox.

Medically reviewed by

Dr. Arpit Varshney

Published At January 2, 2023
Reviewed AtFebruary 13, 2023


Although the origin of smallpox is unknown, it is believed to have existed for at least 3000 years. It was one of the most devastating, contagious, and deadly infections that caused millions of deaths. Some experts say smallpox alone was responsible for 300 million deaths in the 20th century. As a result, the world health organization (WHO) launched widespread immunization and surveillance worldwide to eradicate smallpox. The latest known natural case of smallpox was in Somalia in 1977. And finally, in 1980, WHO declared smallpox eradicated, making it the only human disease to be eradicated.

What Is Smallpox?

Smallpox was a deadly and contagious disease before it got eradicated. Although many who had the disease recovered, one out of three who got infected, died. Many recovered had permanent scarring on the back and face; some were left blind. The condition is caused by the Variola virus and has a distinctive progressive rash.

What Causes Smallpox?

Smallpox is caused by one of the variola virus variants - Variola major and Variola minor. The virus belongs to the genus orthopoxvirus, and humans are the only known carriers of the disease. The origin is apparent, but the earliest evidence of the disease was in the 3rd century BCE in Egyptian mummies.

What Are the Symptoms of Smallpox?

The signs and symptoms of smallpox differ at each stage of its progression.

  • Incubation Period: The incubation period refers to the time between exposure to the causative organism till the first symptom. The incubation period for smallpox infection is seven to 17 days, and they are not contagious during this period.

  • Initial Symptoms: The initial symptoms last for two to four days. During this phase, smallpox can be contagious. Symptoms during the initial phase include:

    • High fever (at least 103 degrees Fahrenheit).

    • Headache.

    • Bodyache

    • Severe backache.

    • Vomiting.

    • Severe fatigue.

  • Early Rash: This is the most contagious stage and lasts four days. It starts as red spots on the tongue and in the mouth. These change into sores and rupture, releasing large amounts of the virus into the mouth and throat of the person.

Once the sores in the mouth rupture, sores start appearing on the skin, starting from the face, then the arms and legs, and then to the hands and feet. It usually spreads throughout the body within 24 hours. As the rashes on the skin start appearing, the fever declines, and the person feels better.

The skin sores start to fill with thick opaque fluid with a dent in the center by the fourth day. The fever may rise again at this stage and stay high until the scabs are formed over the bumps.

  • Pustular Rashes and Scabs: This stage is characterized by the sores turning into pustules. This stage lasts for ten days. The pustules or pimples begin to crust and form scabs within five days. Most of the sores will have scabs within two weeks after the rash appears. The virus is contagious at this stage.

  • Scabs Fall Off: The scabs start falling off, leaving marks on the skin, and within three weeks after the rash, most of the scabs would have fallen off. The virus is contagious only till this stage.

  • No Scabs: Once all the scabs have fallen off, the virus is no longer contagious. All the scabs fall off within four weeks from the rash.

How Is Smallpox Spread?

Before the disease was eradicated, smallpox spread from person to person through direct, prolonged face-to-face contact. When an infected person coughed or sneezed, the virus spread through droplets to other people. Smallpox was contagious from when the first sore appeared in a person’s mouth or throat and remained contagious until the last scab fell off.

The scabs on the body and the fluid within the sores contain the variola virus. The smallpox viruses spread through surfaces that were contaminated by the fluid. Hence, people who cared for the infected were at risk of the disease and had to wear gloves and protective wear. The virus could also circulate in the air and spread through the ventilation system in a building.

Smallpox could also be used as a bioterrorism weapon; a sudden, deliberate release of the disease is a remote threat. Only humans could spread smallpox; there has not been single evidence of smallpox transmitted through animals or insects.

What Is the Difference Between Smallpox and Chickenpox?

Although smallpox and chickenpox have similar symptoms of rash and fever, they are different. Chickenpox is caused by the Varicella zoster and is a mild illness compared to smallpox. Chickenpox sores appear on different body parts at different times and look like blisters. The lesions change rapidly, forming scabs within 24 hours. The smallpox sore appears all at once at different parts of the body, and all the lesions look the same.

Moreover, smallpox has been eradicated globally with the vaccine, but chickenpox is still around the corner.

What Are the Complications of Smallpox?

Most people infected by the smallpox virus recovered. However, it has been a life-threatening and deadly disorder. WHO estimates that smallpox is fatal in up to 30 % of cases.

The severe forms of smallpox were seen in people with impaired immunity and pregnant women. The people who recovered from smallpox usually had severe scars on the face and extremities; some were blind.

What Is the Treatment for Smallpox?

Smallpox treatment in the past focused on relieving the symptoms and preventing the spread of the disease. So the patients were isolated until all the scabs fell off. However, in recent years, researchers have developed antiviral drugs against smallpox. But since the condition has been eradicated, the tests on human subjects were impossible. Hence the effectiveness of the medication is still unknown.

How To Prevent Smallpox?

The smallpox vaccines, also called the vaccinia virus vaccines, help prevent smallpox. There are two licensed vaccines and one investigational vaccine for emergency outbreaks in the United States. ACAM2000 and Aventis Pasteur smallpox vaccine, the replication-competent smallpox vaccine, can lessen the severity of the disease or prevent getting the disease. If the person gets the vaccine before exposure to the virus, it can help prevent the disease. If the person gets the vaccine within three to seven days of being exposed to it, the vaccine may either prevent the disease or lessen its severity. However, the vaccine cannot prevent the disease after the rash appears. Since the disease has been eradicated, smallpox vaccines are unavailable to the general public.


Smallpox was a highly contagious and deadly disorder. Although many survived the disease, they had extensive scars on their faces and extremities. However, the disease was eradicated decades ago, and there is no more fear of contracting it again. Unless a bioterrorist attack using smallpox occurs. The centers for disease control and prevention (CDC) and other health departments have been preparing for any emergency. Smallpox vaccines to the rescue are available in enough stock to face such situations.

Dr. Arpit Varshney
Dr. Arpit Varshney

General Medicine


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