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Smallpox is an infection caused by the variola virus, a member of the poxvirus family. Throughout history, smallpox has been a greatly feared disease because it was responsible for huge epidemics worldwide that resulted in large numbers of deaths. In 1980, the World Health Organization (WHO) announced that an extensive program of vaccination against the disease had resulted in the complete eradication of the virus, with the exception of samples of stored virus in two laboratories.


Smallpox is strictly an infection of human beings. Animals and insects can neither be infected by smallpox, nor carry the virus in any form. Most infections are caused by contact with a person who has already developed the characteristic skin lesions (pox) of the disease, although a person who has a less severe infection (not symptomatic or diagnosable in the usual way) can unwittingly spread the virus.

Causes and symptoms

Smallpox is a relatively contagious disease, which accounts for its ability to cause massive epidemics. The variola virus is acquired from direct contact with individuals infected with the disease, from contaminated air droplets, and even from objects used by another smallpox victim (books, blankets, utensils, etc.). The respiratory tract is the usual entry point for the variola virus into a human being.
After the virus enters the body, there is a 12-14 day incubation period during which the virus multiplies, although no symptoms are recognizable. After the incubation period, symptoms appear abruptly and include fever, chills, and muscle aches. Two to three days later, a bumpy rash begins appearing first on the face and forearms. The rash progresses, ultimately reaching the chest, abdomen, and back. Seven to ten days after the rash appears, the patient is most infectious. The individual bumps (papules) fill with clear fluid and eventually become pus-filled over the course of 10-12 days. These pox eventually scab over, each leaving a permanently scarred pock or pit when the scab drops off.
Initially, the smallpox symptoms and rash appear similar to chickenpox. However, unlike chickenpox, smallpox lesions develop at the same rate so that they are all visible in the same stage. Another major difference is that smallpox occurs primarily on the face and entremities, whereas chickenpox tends to be concentrate on the face and trunk area.
Complications such as bacterial infection of the open skin lesions, pneumonia, or bone infections are the major causes of death from smallpox. A very severe and quickly fatal form called "sledgehammer smallpox," occurs in 5-10% of patients and results in massive, uncontrollable bleeding (hemorrhage) from the skin lesions, as well as from the mouth, nose, and other areas of the body. This form is very infectious and usually fatal five to seven days after onset.
Fear of smallpox comes from both the epidemic nature of the disease, as well as from the fact that no therapies have ever been discovered to either treat the symptoms of smallpox, or shorten the course of the disease.


In modern times, a diagnosis of smallpox is made using an electron microscope to identify virus in fluid from the papules, urine, or in the patient's blood prior to the appearance of the papular rash.


No treatments have been developed to halt the progression of the disease. Treatment for smallpox is only supportive, meaning that it is aimed at keeping a patient as comfortable as possible. Antibiotics are sometimes administered to prevent secondary bacterial infections.


Approximately one in three patients die from smallpox, with the more severe, hemorrhagic form nearly 100% fatal. Patients who survive smallpox infection nearly always have multiple areas of scarring where each pock has been.


From about the tenth century in China, India, and the Americas, it is noted that individuals who had even a mild case of smallpox could not be infected again. Fascinating accounts appear in writings from all over the world of ways in which people tried to prevent smallpox. Material from people mildly ill with smallpox (fluid or pus from the papules, scabs over the pox) was scratched into the skin of people who had never had the illness, in an attempt to produce a mild reaction and its accompanying protective effect. These efforts often resulted in full-fledged smallpox, and probably served only to help effectively spread the infection throughout a community. In fact, such crude smallpox "vaccinations" were against the law in Colonial America.
In 1798, Edward Jenner published a paper in which he discussed his important observation that milkmaids who contracted a mild infection of the hands (called cowpox, and caused by a relative of the variola virus) appeared to be immune to smallpox. Jenner created an immunization against smallpox using the pus found in the lesions of cowpox infection. Jenner's paper led to much work in the area of vaccinations, and ultimately resulted in the creation of a very effective vaccination against smallpox that utilized the vaccinia virus, another close relative of variola. Indeed, the term vaccination is derived from vacce, Latin for cow and related to the cowpox link. Later, the term was applied to other vaccinations.
In 1967, WHO began its attempt to eradicate the smallpox virus worldwide. The methods used in the program were simple:
  • Careful surveillance for all smallpox infections worldwide, to allow for quick diagnosis and immediate quarantine of patients.
  • Immediate vaccination of all contacts diagnosed with infection, in order to interrupt the virus' usual pattern of infection.
The WHO's program was extremely successful, and the virus was declared eradicated worldwide in May 1980.

Future concerns

Today, two laboratories (the Centers for Disease Control and Prevention in Atlanta, Georgia, and the Russian State Centre for Research on Virology and Biotechnology in Koltsovo, Novosibirsk Region) officially retain samples of the smallpox virus. These samples, as well as stockpiles of the smallpox vaccine, are stored because some level of concern exists that another poxvirus could undergo genetic changes (mutate) and cause human infection. There is also the remote chance that smallpox virus could somehow escape from the laboratories where it is stored. For these reasons, surveillance continues of various animal groups that continue to be infected with viruses related to the variola virus, and large quantities of vaccine are stored in different countries around the world, so that response to any future threat by the smallpox virus could be prompt.
Of greatest concern is the potential use of smallpox as a biological weapon. Since 1980, when the WHO announced smallpox had been eradicated, essentially no one has been vaccinated against the disease. Those individuals vaccinated prior to 1980 are believed to be susceptible as well because immunity only lasts 15-20 years. These circumstances coupled with the nature of smallpox to spread quickly from person to person could lead to devastating consequences.
The United States and Russia are the only two countries to officially house remaining samples of the virus. However, it is believed that other countries, such as Iraq, may have obtained samples of the smallpox virus during the Cold War through their association with Russia. It is also possible that scientists with access to the virus may have sold their services and knowledge to other governments.
On June 22-23, 2001, four U.S. organizations (CSIS—Center for Strategic and International Studies, Johns Hopkins Center for Civilian Biodefense Studies, ANSER—Analytic Services Inc., and MIPT—Memorial Institute for the Prevention of Terrorism) presented a fictitious scenario of the United States' response to a deliberate introduction of smallpox titled Dark Winter. This exercise demonstrated that if such an event were to occur, the United States would be ill prepared on several fronts. The primary concern is an inadequate supply of vaccine, which is essential to preventing disease development in exposed persons. Between 1997 and 2001, two companies were contracted to produce additional smallpox vaccines for both military and civilian use. Through these contracts, an additional 40 million doses would be made available for civilian use by 2005. In the meantime, studies are underway to determine if the existing vaccines can be diluted in order to increase the number of doses available for immediate use. Results from a very small group of volunteers tested in 2000 found that at one-tenth strength, the existing smallpox vaccines are approximately 70% effective. In late 2001, a new study began evaluating the effectiveness of the vaccine at one-fifth strength.

Key terms

Epidemic — A situation in which a particular infection is experienced by a very large percentage of the people in a given community within a given time frame.
Eradicate — To completely do away with something, eliminate it, end its existence.
Hemorrhage — Bleeding that is massive, uncontrollable, and often life-threatening.
Lesion — The tissue disruption or the loss of function caused by a particular disease process.
Papules — Firm bumps on the skin.
Pox — A pus-filled bump on the skin.
Vaccine — A preparation using a non-infectious element or relative of a particular virus or bacteria, and administered with the intention of halting the progress of an infection, or completely preventing it.
In the event that smallpox is reintroduced into the current population, it will be imperative that doctors immediately recognize the symptoms and isolate the individual to prevent further spread of the disease. Prompt vaccination of any persons who had contact with the patient is also necessary to prevent additional cases of smallpox from developing. Controlling and containing spread of this disease is critical for prevention of a world-wide epidemic that would have a devastating impact on current populations.



Broad, William J. "U.S. Acts to Make Vaccines and Drugs Against Smallpox." The New York Times October 9, 2001: D1-2.
Miller, Judith, and Sheryl Gay Stolberg. "Sept. 11 Attaks Led to Push for More Smallpox Vaccine." The New York Times October 22, 2001: A1.


Hamre, John, Randy Larsen, Mark DeMier, General Dennis Reimer, and Tara O'Toole. "Dark Winter." ANSER Analytic Services Inc. [cited October 25, 2001]. 〈〉.
Henderson, D. A. "Smallpox: Clinical and Epidemiologic Features." In: Emerging Infectious Diseases 15, no. 4 (July-August 1999) [Online Journal]. [cited October 25, 2001].
Rotz, Lisa D., Debra A. Dotson, Inger K. Damon, and John A. Becher. "Vaccinia (Smallpox) Vaccine Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001." In: Morbidity and Mortality Weekly Report 50, rr 10 (June 22, 2001): 1-25. [cited October 25, 2001].


a highly contagious, often fatal disease caused by a poxvirus; its most noticeable symptom is the appearance of blisters and pustules on the skin. It formerly occurred in epidemics that killed millions but has now been eradicated throughout the world as a result of a global eradication program by the World Health Organization. Called also variola.

There are now concerns that the smallpox virus could be reintroduced for the purpose of bioterrorism. Because of this, the Centers for Disease Control and Prevention (CDC) has revised and updated its guidelines to help health care providers and public health officials respond to such an event. Information is available on the CDC website:


An acute eruptive contagious disease caused by a poxvirus (Orthopoxvirus, a member of the family Poxviridae) and marked at the onset by chills, high fever, backache, and headache. In 2-5 days these constitutional symptoms subside and an eruption appears as papules, which become umbilicated vesicles, develop into pustules, dry, and form scabs that, on falling off, leave a permanent marking of the skin (pock marks). The average incubation period is 8-14 days. As a result of increasingly aggressive vaccination programs carried out over a period of about 200 years, smallpox is now extinct.
Synonym(s): variola major, variola
[E. small pocks, or pustules]

Smallpox was a universally dreaded scourge for more than 3 millennia, with case fatality rates sometimes exceeding 20%. In many ways a unique disease, it had no nonhuman reservoir species and no asymptomatic human carriers. First subjected to some control by variolation in the 10th century in India and China, it was gradually suppressed in the industrialized world after Edward Jenners 1776 landmark demonstration that infection with the harmless cowpox (vaccinia) virus renders humans immune to the smallpox virus. The last case diagnosed in the U.S. occurred in 1949. A global eradication program was initiated by the World Health Organization in 1966, and the last naturally occurring case of the disease was reported in Somalia in 1977. Routine vaccination against smallpox, discontinued in the 1970s, has been resumed for military and health care personnel and others who would be at high risk if smallpox virus should be used as a weapon of biologic warfare or bioterrorism.


/small·pox/ (smawl´poks) variola; an acute, highly contagious, often fatal infectious disease, now eradicated worldwide by vaccination programs, caused by an orthopoxvirus and marked by fever and distinctive progressive skin eruptions.


An acute, highly infectious, often fatal disease caused by a poxvirus and characterized by high fever and aches with subsequent widespread eruption of pimples that blister, produce pus, and form pockmarks. Smallpox was eradicated worldwide by 1979 as a result of numerous vaccination campaigns and exists only as a laboratory specimen. Also called variola.


Etymology: AS, smael + pocc
a highly contagious and sometimes fatal viral disease characterized by fever, prostration, and a vesicular, pustular rash. It is caused by one of two species of poxvirus, variola minor (alastrim) or variola major, the latter being the severe and most common form. Because human beings are the only reservoir for the virus, worldwide vaccination with vaccinia, a related poxvirus, has been effective in eradicating smallpox; the last case of smallpox in the U.S. was in 1949, and the last recorded case in the world was in Somalia in 1977. The only known remaining sources of the virus are stored frozen at the U.S. Centers for Disease Control and Prevention. Smallpox is a potential agent for bioterrorism. Also called variola, variola major.
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Variola Virology A DNA virus, genus Orthopoxvirus, transmissible by aerosol and implanted on the oropharyngeal or respiratory mucosa Clinical After a 2-wk incubation, high fever, malaise, prostration, headache, backache, abdominal pain, delirium, oral and upper body rash, that became vesicular then pustular. See Maalin.


An acute eruptive contagious disease caused by a poxvirus (variola); characterized by chills, fever, and an eruption of papules that become umbilicated vesicles, develop into pustules, dry, and then form scabs that, when they fall off, leave permanent indentations on the skin (pockmarks). The World Health Organization initiated a global vaccination effort in 1967; no cases other than laboratory infection have been reported in the human population since 1975. Although only two legal stores of smallpox are held (one in the United States and one in Russia), evidence exists that other nations possess the virus, possibly even in biowarfare arsenals.
[E. small pocks, or pustules]


(smawl'poks) [AS. smael, tiny, + poc, pustule]
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SMALLPOX: Centripetal distribution.
An acute, highly contagious, and frequently fatal viral illness caused by the variola virus. Synonym: variola See: illustration; smallpox vaccine


Influenza-like symptoms, esp. high fever, chills, headache, backache, and prostration, are commonly the first sign of infection. These symptoms constitute the pre-eruptive stage of smallpox, i.e., the stage that precedes the appearance of the rash. The pre-eruptive phase lasts about 72 hours and is followed by a maculopapular rash that changes over the next couple of weeks to papules, small blisters, pustules, and then scabs. This eruptive phase of the illness usually begins on the mouth, face, and arms and then spreads to other body parts, such as the back and chest.


The disease typically begins 12–14 days after exposure to the virus.

Patient care

Patients diagnosed with smallpox require airborne precautions with special ventilation and engineering requirements. The patient must be placed in a monitored negative-air-pressure room that allows 6 to 12 air changes per hour. The room door must remain closed except for entering and exiting. Anyone entering must wear adequate droplet protection. Contact precautions require wearing clean gloves and gown during all patient contact; these barriers must be removed before leaving the room. All contaminated instruments, surfaces, excretions, fluid, or other materials require decontamination with chemicals or heat or incineration. Clothing and bedding should be washed in hot water with hypochlorite bleach or may be incinerated. If the patient dies, droplet and contact precautions should be used throughout postmortem care, treating body bags with hypochlorite bleach. Eating and drinking may be difficult because of painful lesions in the mouth and oropharynx. This discomfort may be alleviated with frequent oral hygiene and a prescribed mouth rinse. Pain is assessed and managed with prescribed analgesic drugs. Intravenous fluids are prescribed as required to prevent dehydration and antipyretic drugs to control high fever. Skin lesions are kept clean and dry. Antipruritics usually are required during the pustular stage. Secondarily infected lesions may need antibiotic therapy. The patient, family, and significant others may need assistance in coping with the psychosocial implications of smallpox, including disfigurement, fear of contagion, fear of death, and grief. Whenever possible, smallpox victims who die should be cremated. Variola virus, which no longer exists in the wild, has been preserved in laboratories and has been considered a bioterrorism threat. Although smallpox vaccination is not required, it has been offered to the military, health department, first responders and key health care workers because of this threat.


A severe, highly infectious virus disease that was eradicated in 1980. Smallpox was spread mainly by droplet infection and caused fever, headache, muscle aches and a severe blistering rash that left deep pitted scars. The mortality was sometimes as high as 20%. Stocks of the virus still exist and this has raised fear of military or terrorist use as a weapon. Of nearly half a million American service personnel vaccinated against smallpox between December 2002 and May 2003 there was one case of encephalitis and 37 cases of myopericarditis. Ironically, knowledge of smallpox and its management is now more detailed that ever it was when the disease was epidemic.


a contagious viral disease of humans characterized by pustules on the skin and scar formation. Smallpox was the first disease to be controlled by vaccination (see JENNER and world-wide immunization programmes organized by the World Health Organization are believed to have virtually wiped out the disease. Unfortunately, with the disappearance of the disease it is likely that the general susceptibility levels will rise in human populations, making wide-scale epidemics a real possibility should the disease return. It is a potential agent of BIOLOGICAL WARFARE.


An acute eruptive contagious disease caused by a poxvirus (variola); characterized by chills, fever, and an eruption of papules.
[E. small pocks, or pustules]


n See variola.


see variola.