Entry last updated: 10/13/2005
- Understanding the Disease
- Available Vaccines
- History of the Vaccine
- Who Should and Should Not Receive the Vaccine
- Dose Schedule
- Effectiveness of the Vaccine
- Known Side Effects
- Related Issues
- Key References and Sources of Additional Information
Understanding the Disease
Most people in the U.S.—indeed in the world—have not considered smallpox a health threat for several decades. Smallpox hasn't occurred in the U.S. since 1949, and routine vaccination against it ended here in 1972. When the World Health Organization (WHO) certified that smallpox had been eradicated from the planet in 1980, this was the first time in history that medical scientists and public health workers had completely purged the world of a devastating infectious disease.
Though the disease was eradicated over 20 years ago, several samples of the live virus were preserved, mainly for research purposes. Today the only verified repositories of the virus are held in secure laboratories at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the State Center for Research on Virology and Biotechnology in Koltsovo, Russia. However, it is believed that clandestine stocks of smallpox exist in 10 or more other countries.
Due to the events of September 11, 2001, and the subsequent spread of anthrax in October, public health officials regard the use of biological weapons by terrorists as a real possibility. The Congressional testimony of former Soviet scientist, Kenneth Alibek, supports this view. Alibek said that as recently as the early 1990s, dozens of tons of smallpox were being stockpiled in the former Soviet Union annually for use as weapons. He also reported that some of the more than 60,000 people involved in biological weapons research for the former Soviet government may be employed by governments wishing to develop biological weapons. Read Alibek’s testimony before Congress at www.house.gov/jec/hearings/intell/alibek.htm. Most recently, a CIA intelligence review concluded that Iraq, France, North Korea, and Russia have covert stocks of smallpox virus, although the French government has denied the allegation.
Of all the disease-causing agents that might be used as weapons, smallpox has the potential to cause the greatest harm, since, prior to its eradication, it was considered the most devastating of all infectious diseases.
Smallpox is caused by the variola virus, which can be spread from person to person via respiratory droplets produced in the nose, mouth, and throat of someone who is infected and has begun to show signs of illness. After a person has been exposed to the virus, there is an incubation period of between 7 and 17 days prior to the onset of symptoms, which include high fever, severe headache and backache, and often vomiting and tremors. Two to five days later, the characteristic smallpox rash develops. It begins as flat, round lesions, primarily on the face and forearms, and evolves into deep, pus-filled blisters that may cover the entire body, including the palms and soles of the feet. Some patients have a fever throughout the course of the rash (two to four weeks), and often the blisters cause significant pain. In the last stage of the rash scabs form and fall off, leaving pitted scars. Some smallpox survivors are blind as a result of deep scarring in the eye area. Smallpox during pregnancy often results in miscarriage or stillbirth.
In the first two to three days of the rash, smallpox can be confused with chickenpox (varicella). However, chickenpox lesions generally develop in crops over a period of several days and are much more superficial than smallpox lesions. Chickenpox lesions in one area may be in different stages of development (macule, papule, and pustule). In contrast, smallpox lesions in any area are all at the same stage in development and, in addition, smallpox lesions may have a small dimple in their center. Chickenpox lesions generally occur on the torso, while the smallpox rash is most prominent on the face and extremities. Also, chickenpox lesions occur much less frequently on the palms or soles of the feet.
A timeline of disease development is available at the CDC smallpox website, www.cdc.gov/smallpox.
The smallpox patient is most contagious during the first week of the rash, when the virus is most abundant in the saliva. But the disease remains transmissible to others until all the scabs have fallen off.
Historically, the two most prevalent forms of smallpox were variola major, which caused severe illness and killed about 30% of unvaccinated persons, and variola minor, which caused a much milder form of illness and had about a 1% death rate. Two less common forms of the disease were even more deadly. Malignant smallpox, noted by its abrupt onset and by its flat, velvety lesions that never became pustular, caused death in more than 96% of people affected. Hemorrhagic-type smallpox caused bleeding into the skin and other body parts and was almost always fatal within less than a week of the appearance of a rash. Pregnant women were highly susceptible to hemorrhagic-type smallpox.
Currently the U.S. has stockpiles of several vaccines used in the past. The stockpile includes approximately 15 million doses of Dryvax®, a calf lymph-derived vaccine produced by Wyeth, which was recently re-tested and shown to be effective. Other tests on this vaccine have demonstrated that it can be expanded up to five-fold in the event of an emergency to vaccinate as many as 75 million people.
In addition, in March 2002 Aventis Pasteur announced the availability of approximately 85 million doses of its smallpox vaccine, also derived from calf lymph, which had been stored since 1972, and donated these to the government.
The government has also contracted with Acambis, a company in England, to manufacture 200 million doses of a new smallpox vaccine made with modern production techniques in tissue culture. It’s currently being tested and will likely be licensed by the FDA in 2005. A new and probably safer smallpox vaccine is under development by the National Institutes of Health.
While these stockpiles have been developed to ensure an adequate supply of vaccine to protect all Americans in case of a bioterror attack, the smallpox vaccine is not routinely available in the U.S.
History of the Vaccine
An English physician named Edward Jenner observed that many milkmaids who contracted cowpox, a disease in cows that causes only mild illness in humans, either did not contract smallpox or had milder disease and lower mortality. In 1796, he experimented by taking the fluid from a cowpox blister on a milkmaid’s hand and administering it to a young boy through incisions on his arm. Jenner discovered that exposing the boy to the cowpox virus protected him from smallpox. This experiment was the first scientific attempt to control an infectious disease through vaccination. In fact, the word vaccine comes from the Latin word for cow, vacca. The smallpox vaccine later developed and administered today in very limited circumstances uses the vaccinia virus (a virus closely related to cowpox) to induce an immune response, and does not contain smallpox virus.
Smallpox vaccine became the first mandatory vaccine in the United States in 1809 when Massachusetts required the entire state population to be vaccinated against the disease. Before 1972, smallpox vaccine was recommended for all children in the U.S. at one year of age, military recruits, and international travelers. U.S. physicians stopped routinely administering the vaccine in 1972 because of the global control of the disease, and because the risk of serious adverse events, including death, from the vaccine was considered to be greater than the risk of the disease in the U.S. The last case of naturally occurring smallpox was diagnosed in Somalia in 1977, and the World Health Organization declared smallpox disease eradicated from the planet in 1980.
Who Should and Should Not Receive this Vaccine
Who should receive the vaccine?
The smallpox vaccine is not currently recommended for or available to the general public in the U.S. The smallpox vaccine is now available under limited circumstances, for example:
- Department of Defense military and civilian personnel and State Department personnel who work in high threat areas
- Healthcare providers and “first responders” who volunteer for smallpox response teams
- For laboratory workers and others at risk for exposure to the smallpox virus, or closely related viruses
- Participants in smallpox vaccine clinical trials
Recommendations for what to do in an epidemic of smallpox or a bioterrorist act with smallpox might change quickly; the most up-to-date information is provided by the CDC. In the event of exposure to smallpox virus the risk of serious complications from the vaccine among those exposed to the disease would be less than the risk of the disease, even for those listed below for whom the vaccine is generally contraindicated. Vaccination within four days of a first exposure offers some protection against infection, and those vaccinated who do become infected are apt to have much less severe disease.
Who should not receive the vaccine?
When the vaccine was routiney administered in the U.S., it was not given to:
- Children under one year of age
- People with eczema, atopic dermatitis, a history of eczema, another unresolved skin condition (including burns), or a household contact with eczema or a history of eczema
- People with weakened immune system (such as those undergoing chemotherapy or who have received organ transplants), or a household contact with a weakened immune system
- People with HIV-infection (Although HIV and AIDS were unknown at the time that smallpox vaccination was given routinely to U.S. civilians, military personnel continued to be vaccinated until 1990. In at least one instance, a military recruit with HIV had a severe adverse reaction to vaccinia vaccine.)
- Pregnant women
- Those who had a serious adverse reaction to a previous dose of the vaccine or its ingredients
Smallpox vaccine is administered by making 15 punctures in the skin with a special needle. When the vaccine was routinely administered, revaccination was recommended at least every 10 years. About a week after a person receives the vaccine, the inoculation site should be examined by a healthcare professional to determine if the recipient has had a successful inoculation site reaction (described as a “take”), a reaction severe enough to indicate that the person developed an immune response.
Effectiveness of the Vaccine
More than 95% of vaccine recipients are protected against smallpox for three years after the first dose, though some immunity may last as long as 10 years. Revaccination several years after the first dose increases immunity anywhere from 10 years to 30 years.
Known Side Effects
Although smallpox vaccine is considered a safe vaccine, it does have potential side effects.
When the vaccine was routinely administered in the U.S., the most common side effects included swollen and tender lymph nodes that lasted for two to four weeks after the vaccination site healed. Fever was common, and approximately 70% of those immunized experienced a day or more with temperatures over 100 degrees F, and 15% to 20% had fevers over 102 degrees F. As many as 30% of adults immunized experienced symptoms severe enough to cause them to miss at least one day of work. Rashes without fever can sometimes occur and generally clear without treatment.
The vaccine, in rare cases, can cause serious adverse reactions, including death. Serious reactions after the first dose of smallpox vaccine can include severe vaccinia infection in the skin of people with eczema or atopic dermatitis (less than one per 10,000 immunized). Occasionally, vaccinia necrosum, which begins with death of the tissue around the inoculation site, occurred in seriously immunocompromised people; this often-fatal reaction was rare in the past, affecting less than 1 per 10,000 immunized. Inflammation of the brain (less than 1 per 10,000 immunized) is another serious reaction, and mainly affected children less than one year of age when the vaccine was administered to this group. Rates of these side effects after a second dose of smallpox vaccine are lower.
Recently immunized people may pass the vaccinia virus to a susceptible person (about 27 infections per 10,000 immunized) or other parts of the body if the vaccine site is touched. Almost half of these contact infections were seen in children five years or younger. Washing hands thoroughly with soap and water or disinfectants after contact with the inoculation site can help prevent spread of the virus. The site also can be loosely dressed with gauze held in place by a semipermeable dressing, but should not be tightly bandaged. Bandages, scabs, or anything that has touched the inoculation site should be sealed in a plastic bag and safely discarded, or incinerated. Items that aren’t disposable can be washed with hot water and bleach.
In 2005, the FDA implemented a new "black box" warning for Wyeth's smallpox vaccine Dryvax, alerting physicians and consumers to the increased risk of cardiac problems that some people experience after immunization. The warning points to an increased risk of adult recipients of the smallpox vaccine developing myopericarditis, or heart inflammation
A summary of side effects from the smallpox vaccine, their frequency and management is available at the CDC’s smallpox website, http://www.bt.cdc.gov/agent/smallpox/index.asp.
The global eradication of smallpox is widely considered one of the greatest achievements of modern medicine. In 1967 there were an estimated 10 million to 15 million smallpox cases in 31 countries. By 1980 there were zero cases. The eradication campaign was based on two key strategies: (1) mass vaccination and (2) the detection and containment of all cases of smallpox. This approach was possible in part because there were no animal reservoirs of smallpox. Without continuous opportunity for human-to-human spread, smallpox could not survive.
The U.S. was scheduled to destroy its remaining supply of live smallpox virus in 1996, so that no one could spread the disease accidentally or intentionally. U.S. officials then decided to keep vials containing the virus so that scientists could use it to produce a safer smallpox vaccine, in case the virus ever escaped from the secured labs or was used as a bioweapon. Smallpox vaccine may also be of value in developing antiviral drugs to treat smallpox. Several deadlines for smallpox virus destruction have been set; however, officials have decided each time to keep the supply. Owing to the post-September 11 threat of terrorist attacks, the most recent destruction date, December 31, 2002, was abandoned and no new destruction date has been set.
Because of the fear of bioterrorist attacks, in the fall of 2001 the U.S. Department of Health and Human Services created an Office of Public Health Preparedness to coordinate the national public health response. In addition, the CDC updated its Interim Smallpox Response Plan and Guidelines, which can be read at www.bt.cdc.gov/agent/smallpox/index.asp
Researchers now are concentrating on developing and testing drugs against smallpox; developing a new vaccine with fewer side effects, which is particularly important for people with compromised immune systems; and researching the smallpox genetic code.
Key References and Sources of Additional Information
- American Academy of Pediatrics (AAP), Committee on Infectious Diseases. (2003). Red Book: Report of the Committee on Infectious Diseases (LK Pickering, Ed.) (26th ed.). Elk Grove Village, IL: Author.
- AAP. (2001). Children, terrorism, and disasters [Web page].
- Barquet N and Domingo P. (1997). Smallpox: The triumph over the most terrible of the ministers of death. Annals of Internal Medicine, 127(8 Pt 1), 635-642.
- Centers for Disease Control and Prevention (CDC), Public Health Emergency Preparedness and Response. (2004). Smallpox [Web page].
- CDC. (2003). Smallpox Pre-Vaccination Information Packet.
- National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases. (2002). The Jordan Report 2002: Accelerated development of vaccines. Bethesda, MD: Author.
- Letai A G, Snyder KM, Fett JD, et al (2002). Smallpox and smallpox vaccination. New England Journal of Medicine 347:691-692.
- Parents of Kids with Infectious Diseases. (2001). In the event of bioterrorism: Protecting families from deadly diseases [Web page].
- White PJ and Shackelford PG (1983). Edward Jenner, MD, and the scourge that was. American Journal of Diseases of Children, 137(9), 864-869.
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Including available vaccines, history of the vaccine, who should and should not receive it, dose schedules, effectiveness, known side effects, and related issues.