Infection: Smallpox

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Infection: Smallpox

Causes and Symptoms
The Future
For more information


Smallpox is an infectious disease caused by the variola virus. Researchers think that it originated in rats or mice somewhere in Africa and was

transmitted to humans around 10,000 BCE. The disease presently affects only humans and cannot be acquired from any animal.

There are two types of smallpox, variola major and variola minor. Variola major is the more severe of the two, accounting for about 90 percent of cases; it has a mortality rate of 30–35 percent. Variola minor, sometimes nicknamed white pox, cotton pox, or Cuban itch, is a milder disease that kills less than 1 percent of those infected. Each type of smallpox makes a person who survives it immune to both forms of the disease.


Smallpox is one of the most destructive diseases known to humankind. It was first called smallpox in the fifteenth century to distinguish it from syphilis, which was then called the Great Pox. About 400,000 people died each year from smallpox in Europe alone for most of the eighteenth century. During the twentieth century between 300 and 500 million people around the world died from smallpox. The mortality rate rose as high as 60 percent in some countries, with 80 percent of infected children dying from the disease.

Smallpox was gradually eliminated following the development of an effective vaccine against it in 1796. Edward Jenner (1749–1826), an English doctor, had noticed that milkmaids rarely got smallpox and theorized that they were protected by exposure to cowpox, a disease similar to smallpox but much less deadly. Jenner tested his theory by inoculating an eight-year-old boy with pus taken from a milkmaid's cowpox blisters and showing that the boy was immune to smallpox. Jenner's early vaccine was refined and introduced in the developed countries during the nineteenth century. The term vaccination was derived from the French word for cow related to the original source of the immunization virus. By 1897, smallpox had been virtually eliminated in the United States; the last case of smallpox in North America was reported in 1949.

In the 1960s, the World Health Organization (WHO) led a worldwide effort to eradicate smallpox. A team of scientists led by Donald Henderson (1928–) was formed to vaccinate people in developing countries. The last case of naturally occurring smallpox was diagnosed in Somalia in 1977. In 1980 WHO declared that smallpox had been eradicated. As of 2008 two laboratories, one at the Centers for Disease Control and Prevention (CDC) and the other in Russia, maintained small stocks of the smallpox virus for research purposes.

The disease itself is characterized by a prodrome, or period of warning symptoms, characterized by high fever (101–104°F [38.3°C–40°C]) and flu-like symptoms that include severe headache and fatigue. The prodrome lasts between two and five days and is followed by red spots on the face and in the mouth, developing into open sores that spread the virus within the mouth and throat. About a day later, a rash spreads over the body that turns into papules (raised pimples) within three days. Unlike chickenpox, the skin lesions of smallpox are all in the same stage of development at the same time. The papules fill with a pus-colored fluid and may feel as if a hard, small, marble bead is present under the skin. The papules gradually form scabs that fall off the body, often leaving scar tissue behind. In fatal cases, death occurs between ten and sixteen days after the first symptoms.


Smallpox is equally likely to infect people of any race or age group and people of either sex during an epidemic. The chief difference is the mortality rate.

People who are at increased risk of dying from smallpox if they become infected include:

  • Pregnant women
  • Young children
  • Elderly adults
  • Anyone who has never been vaccinated against smallpox

Causes and Symptoms

The cause of smallpox is the variola virus, which usually enters the body through the mouth and respiratory tract. In most cases the virus is usually transmitted from person to person by close contact (within 6 feet [2 meters]); smallpox is not as easily transmitted as measles or influenza. The virus has an incubation period of seven to seventeen days before the prodrome occurs. Once in the person's mouth or throat, the smallpox virus multiplies rapidly in nearby lymph nodes and then enters the bloodstream. It is carried to the spleen, bone marrow, liver, and kidneys. People who have been infected with the virus can transmit it to others late during the prodrome; however, they are most contagious when the rash appears.

In addition to high fever and the characteristic rash, the symptoms of smallpox may include:

  • Severe headache
  • Fatigue
  • Muscle aches and pains
  • Severe back pain
  • Vomiting, diarrhea, or both
  • Delirium
  • In some cases, heavy bleeding in the internal organs

Patients who survive smallpox often have complications:

  • Permanent scars on the face. Called pock marks, these scars occur in about 80 percent of people who survive the disease. Queen Elizabeth I of England and the Russian dictator Josef Stalin were scarred by the disease; the queen wore heavy makeup in later life to try to hide her pock marks.
  • Eye infections. About 20 percent of survivors develop conjunctivitis; a few become permanently blind.
  • Infection of the bone. Between 2 and 20 percent of children who get smallpox develop an infection of the bone or bone marrow known as osteomyelitis.


The most important aspect of diagnosing smallpox is distinguishing it from chickenpox. This is particularly important since most doctors in

developed countries have never seen a case of smallpox. There are three major differences between chickenpox and smallpox:

  • The skin lesions of chickenpox occur mostly on the face and trunk rather than the face, arms and legs. They are also shallower and do not feel as if there is a hard object inside them.
  • Chickenpox lesions occur in waves or crops, so that the patient may have lesions at different stages of development at the same time. In smallpox, the lesions are all at the same stage of development at a given time.
  • Chickenpox is contagious before the infected person feels sick, whereas smallpox is not contagious until the symptoms appear.

Diagnosis is based on a combination of the patient's history—particularly a prodrome with fever two to four days before the rash appeared, and the appearance of the rash (lesions are hard to the touch, appear to be deep within the skin, and appeared first on the face, mouth, and forearms)—and a laboratory test. To test for the virus, the doctor will swab the patient's throat or take a smear from one of the skin lesions. The sample will be sent to a state health department laboratory for examination under an electron microscope or tested by a technique called polymerase chain reaction or PCR. Under a microscope, a cell infected with the smallpox virus will have pink clumps of the virus known as Guarnieri bodies, named for the Italian doctor who discovered them. PCR is a technique that identifies the virus's DNA.

Accurate diagnosis of a suspected case of smallpox is critical because it would be considered a major public health emergency. In the United States, the Centers for Disease Control and Prevention (CDC) and the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) must be consulted and public health officials notified.


There is no medication that can be given to cure smallpox; the goal of treatment is to keep the patient alive and isolated from others until he or she is no longer contagious. Once the patient has been taken to the hospital, the mainstays of treatment are supportive care and antibiotics to prevent bacterial infections from developing. Vaccination with smallpox vaccine can lessen the severity of the infection if given within four days of infection. However, since the incubation period of the disease is longer than four days, vaccination is primarily useful in protecting

health care workers and others who may have been in contact with the person.

The most important treatment measure is isolating the patient in order to prevent the disease from spreading further. The procedure that it usually followed is called ring vaccination. Everyone who has been in contact with the patient within the previous seventeen days, including hospital staff, is placed in quarantine and given smallpox vaccine. In addition, local, state, and federal health authorities are notified at once.


The prognosis for recovery from smallpox depends on the form of the disease and the patient's age and general health. Variola major has a death rate around 30 to 35 percent in unvaccinated people, although the rate rises to 60 percent in unvaccinated pregnant women. Variola minor has a mortality rate of about 1 percent. There are rare forms of variola major called hemorrhagic smallpox and malignant smallpox, both of which have fatality rates above 99 percent.


Smallpox can be prevented by vaccination. Although compulsory vacci-nation for the general population was discontinued in 1980 and for military personnel in 1989, vaccination against smallpox was reintroduced after the terrorist attacks of 9/11 for health care workers and members of the armed forces. Some public health officials are concerned about the possibility of a major smallpox epidemic in the event of a laboratory accident or act of bioterrorism, as the smallpox vaccine is thought to be effective for only ten years. In addition to the fact that most people in the United States have not been vaccinated since 1980, an estimated 42 percent of the population has never been vaccinated.

Apart from vaccination, the only preventive measures that are even partly effective are isolation and quarantine of persons thought to be infected with smallpox.

The Future

The major concern for the future regarding smallpox is the possibility of large-scale epidemics in the event of accidents or terrorist attacks. Smallpox would be a deadly biological weapon because only ten to one hundred particles of the virus are needed to infect a person. In 1978, the

year after the last reported case of naturally occurring smallpox, two people in England died of smallpox through a laboratory accident. As a result of the accident, all known stocks of the smallpox virus were either destroyed or sent to two laboratories, one at the CDC and the other in Russia. The remaining supplies of the virus were originally scheduled to be destroyed in 1995, but the WHO decided in 2002 to preserve the virus for development of new vaccines, diagnostic tests, and drugs that might be effective in treating smallpox.

SEE ALSO Anthrax; Chickenpox; Conjunctivitis; Plague


Bioterrorism : The use of disease agents to frighten or attack civilians.

Delirium : A suddenly developing mental disturbance characterized by confused thinking, difficulty focusing attention, and disorientation.

Eradication : The complete elimination of a disease.

Lesion : A general term for any skin injury.

Papule : A small cone-shaped pimple or elevation of the skin.

Prodrome : A group of warning signs or symptoms that appear before the onset of a disease.

Quarantine : The practice of isolating people with a contagious disease for a period of time to prevent the spread of the disease.

For more information


Krasner, Robert I. Twentieth-Century Microbe Hunters. Sudbury, MA: Jones and Bartlett Publishers, 2008. Chapter 6 is about Dr. Donald Henderson and the eradication of smallpox.

Sherman, Irwin W. Twelve Diseases That Changed Our World. Washington, DC: ASM Press, 2007. Syphilis is the subject of Chapter 4, “Smallpox: The Speckled Monster.”

Straus, Eugene, and Alex Straus. Medical Marvels: The 100 Greatest Advances inMedicine. Amherst, NY: Prometheus Books, 2006.


Barquet, Nicolau, and Pere Domingo. “Smallpox: The Triumph over the Most Terrible of the Ministers of Death.”Annals of Internal Medicine 127 (October 15, 1997): 635–642. Available online at (accessed September 11, 2008). This is an article about the history of smallpox epidemics, Jenner's development of his vaccine, and the gradual eradication of the disease.

Preston, Richard. “A Reporter at Large: The Demon in the Freezer.” NewYorker, July 12, 1999, 44–61. Available online at (accessed September 12, 2008). This is an article about the potential use of smallpox as an agent of bioterrorism.


Centers for Disease Control and Prevention (CDC). Smallpox Home Page. Available online at (accessed September 11, 2008).

Mayo Clinic. Smallpox. Available online at (accessed September 11, 2008).

National Institute of Allergy and Infectious Diseases (NIAID). Smallpox. Available online at (accessed September 11, 2008).

NOVA Online. Agents of Bioterror: Smallpox. Available online at (accessed September 12, 2008).

TeensHealth. Smallpox. Available online at (accessed September 11, 2008).