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Synonyms of Smallpox

Disorder Subdivisions

General Discussion

Smallpox is an infectious disease caused by the variola virus. It is characterized by fever, a general feeling of ill health (malaise), headaches and back pain. These initial symptoms are followed by a rash and small, raised bumps or lesions (pocks) within two or three days. Smallpox was a highly contagious disease, but was declared eradicated in 1980. However, recently smallpox has become of interest because of the possibility of its use as a weapon of warfare or of terrorism. There were two strains of smallpox, variola major and variola minor.


Symptoms of smallpox appear after an incubation period of approximately 12 days (7-17 days). Initial symptoms are a high fever, a general feeling of ill health (malaise), headaches, and back pain often resulting in affected individuals becoming bedridden. In some cases, severe abdominal pain and delirium may also be present.

Approximately two to three days after the onset of the disease, a characteristic rash forms on the mucous membranes (mucosa) of the mouth and throat (pharynx) as well as on the face and arms. The rash often spreads to affect the legs and trunk. Within one or two days, small, red bumps or lesions form (papules). These lesions become pus-filled (pustules) sometimes breaking open and resulting in bloody, oozing sores. Eventually, the pustules begin to crust and then scab. In three to four weeks, the scabs fall off, usually leaving scars or pox marks.

There were two strains of smallpox. Variola major was more severe and had a fatality rate of approximately 30 percent; variola minor was less severe and had a fatality rate of less than 1 percent.

Life-threatening complications that may be associated with smallpox include blood loss, the presence of toxins in the blood (toxcemia), cardiovascular problems, and/or secondary bacterial infections.


Smallpox is caused by infection with the variola virus. The disease is spread through person to person contact, most often from inhalation of droplet nuclei expelled through the back of the throat (oropharynx) of an infected person. Droplet nuclei are small particles containing virus-infected respiratory secretions that are pushed out into the air by coughing or sneezing. These airborne particles may then be inhaled by another person. Individuals with smallpox are most infectious during the first week of illness.

Smallpox may also be spread through direct contact with an infected person or through contact with contaminated material such as clothing, blankets or bed linen.

Affected Populations

Smallpox existed for thousands of years until the World Health Organization declared it extinct in May of 1980. The last known case of smallpox occurred in Somalia in 1977.

The only known stores of the smallpox virus are in two locations: the Centers for Disease Control and Prevention (CDC) in Atlanta and Russian government laboratories near Moscow. However, government officials fear that secret stores may be maintained elsewhere and may be released deliberately as an act of warfare (bioterrorism).

Individuals with weakened immune systems such as those with leukemia, lymphoma or AIDS would be more susceptible to smallpox infection if the disease was reintroduced into society.

Related Disorders

Symptoms of the following disorders can be similar to those of smallpox. Comparisons may be useful for a differential diagnosis:

Monkeypox is a rare infectious disease caused by a virus that is related to the virus that causes smallpox. Individuals with monkeypox develop a rash that is similar to one associated with smallpox. Most cases of monkeypox occur in remote villages in Africa where there is close contact with infected animals. The vaccine developed to treat smallpox also protects against monkeypox.

Varicella-zoster is an infectious disease caused by a common virus known as herpes virus. During childhood, infection with the varicella virus causes chickenpox . The varicella virus remains viable in body nerve cells for the rest of that individual's life. From time to time, the latent virus leaves its nerve cell home and travels down nerve rootlets to the skin, where it produces the typical rash and pain of the syndrome known as shingles. First infection with the varicella virus always causes chickenpox, even in adults who never had the infection as children. Chickenpox is a highly contagious disease characterized by an itchy skin rash and fever. Chickenpox usually begins with mild constitutional symptoms such as a mild headache, moderate fever and discomfort followed by an eruption appearing in itchy groups of flat or elevated spots and blisters, which form crusts. Shingles is a painful localized recurrence of the skin rash during adulthood. The rash consists of small, red spots that become inflamed and develop into small fluid-filled bumps or lesions. These lesions then become pus-filled before crusting and healing. Fever and muscle aches may precede the development of the rash. Before smallpox's eradication in 1980, mild cases may have been confused with varicella-zoster infection. (For more information on this disorder, choose varicella-zoster as your search term in the Rare Disease Database.)

Standard Therapies

In the United States before 1972, children received routine smallpox vaccinations. However, the duration of immunity granted by the vaccination may be only 10 to 15 years, so those who received the vaccine in childhood may no longer be immune to the disease.

According to the Centers for Disease Control and Prevention (CDC), the smallpox vaccine can lessen the severity or prevent illness in individuals who are exposed to the smallpox virus if administered within four days after exposure.

The smallpox vaccine contains another virus, vaccina, made from the cowpox virus. The United States currently has an emergency supply of the vaccine in storage at the CDC. During 2000 and 2001, the CDC contracted with pharmaceutical companies to manufacture more of the smallpox vaccine for use if smallpox is employed as a terrorism weapon.

In rare cases, the administration of smallpox vaccine results in a severe reaction. Such reaction may be treated by a specialty antibody prepared from human plasma that has been approved by the FDA (February 2005). This vaccine, vaccinia immune globulin intravenous (human) is also known by the trade name VIGIV and is manufactured and marketed by:

DynPort Vaccine Company LLC.
64 Thomas Johnson Drive
Frederick, Maryland 21702.

There is no specific treatment for individuals infected by smallpox. Treatment is supportive and directed at specific symptoms present in each individual. Supportive therapy may include antibiotics for secondary bacterial infections and/or medications for pain or fever.

In 2002, the U.S. Food and Drug Administration (FDA) granted orphan status to the drug poly-ICLC (Hiltonol), to be used as an adjuvant to smallpox vaccination. Hiltonol is manufactured by Oncovir, Inc., a Washington, DC, pharmaceutical corporation. Additional information on this experimental product may be found at www.oncovir.com.

Vaxgen, Inc., in partnership with the Chemo-Sero Research Institute in Japan, is developing a smallpox vaccine, LC16m8, that has been licensed for use in Japan for several years. Their goal is to develop a vaccine that is safer than Dryvax, but equally effective.

Investigational Therapies

Research is underway to develop new antiviral drugs for the treatment of infectious diseases such as smallpox.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

Smallpox Resources



Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996: 1765-68.

Fields BN, et al. Fields Virology, 2nd ed. New York, NY: Raven Press; 1990:2113-33.

Mandell GL, et al. eds. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 4th ed. New York, NY: Churchill Livingstone Inc; 1995:1328-29.

Henderson DA, et al. Smallpox as a biological weapon. Medical and public health management. JAMA. 1999;281:2127-37.

Georges AJ, et al. Biohazards due to Orthopoxvirus: should we re-vaccinate against smallpox? Med Top (Mars). 1999;59:483-87.

Report last updated: 2009/04/07 00:00:00 GMT+0