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Smallpox

Smallpox

Definition

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.

Description

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.

Diagnosis

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.

Treatment

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.

Prognosis

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.

Prevention

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 (CSISCenter for Strategic and International Studies, Johns Hopkins Center for Civilian Biodefense Studies, ANSERAnalytic Services Inc., and MIPTMemorial 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.

Resources

PERIODICALS

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.

OTHER

Hamre, John, Randy Larsen, Mark DeMier, General Dennis Reimer, and Tara O'Toole. "Dark Winter." ANSER Analytic Services Inc. [cited October 25, 2001]. http://www.aha.org/Emergency/Readiness/FieldLessons.asp.

Henderson, D. A. "Smallpox: Clinical and Epidemiologic Features." In: Emerging Infectious Diseases 15, no. 4 (July-August 1999) [Online Journal]. [cited October 25, 2001]. http://www.cdc.gov/ncidod/EID/vol5no4/henderson.htm.

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]. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5010a1.htm.

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Smallpox

SMALLPOX

SMALLPOX. For most of recorded history, smallpox killed half of all children who died before age five. On 9 December 1979, the World Health Organization (WHO) certified that smallpox had been eradicated globally after a thirteen-year effort. Supposedly, only two remaining stocks of smallpox virus remained, for research purposes, at the Centers for Disease Control and Prevention in Atlanta and at the Ivanovsky Institute of Virology in Moscow. However, subsequent revelations about the Soviet biological warfare program, secretly advanced during the 1980s under Mikhail Gorbachev as a hedge against nuclear weapons reductions, raised the specter of smallpox's return as a means of terrorism and mass destruction.

Early History

Smallpox may have begun as a monkey or a camel pox virus that mutated to infect humans and then evolved into two species: Variola major, the great killer, and Variola minor, with a mortality of less than one percent. In the worst cases, the disease often began with a sneeze or cough beginning twelve to fourteen days after exposure. After an incubation period of twelve days, a high fever, a headache, and muscle pain appeared. From two to five days later a rash appeared, which turned into pustules. By the eighth or ninth day after onset, the pustules dried and crusted before falling off. For about 30 percent of those infected, death occurred, usually in seven to ten days after symptoms first appeared. Dust from the scabs, lingering in and around the sick bed, infected others who encountered it and were susceptible.

The oldest evidence of the disease dates from the mummified body of the Egyptian pharaoh Ramses V (d. 1156 b.c.), although smallpox surely existed for centuries before, from the time when enough people lived in close enough proximity to sustain its spread. The disease only passed from person to person. Human migrations, commerce, and wars spread epidemics, but it was the European colonization of the Americas, southern Africa, and Australia that destroyed the nonresistant native populations between the sixteenth and nineteenth centuries.

Perhaps more than any other single factor, smallpox accounted for the collapse of the Amerindian populations facing European expansion. As Governor John Winthrop of Massachusetts Bay wrote in 1634, "For the natives, they are neere all dead of the small Poxe, so the Lord hathe cleared our title to what we possess." Most of the Amerindian epidemics over the next 250 years probably arose from casual causes, but in 1763 Sir Jeffery Amherst, commanding British military forces in North America, proposed an intentional infection to quell Pontiac's Rebellion. Over time, from the Atlantic to the Pacific, and the Great Lakes to the Gulf, smallpox decimated the tribes, until those finally confined to reservations either acquired immunity and survived or perished like their ancestors.

Ancient observers in China and India knew that afflicted people who survived very rarely became infected again. With that, practices of variolation arose: the Chinese developed insufflation, where a person breathed scab particles; inoculation, or the insertion of a minute amount of virus-carrying pus under the skin, originated in India. Although variolations involved the Variola major virus, and probably caused epidemics from time to time, mortality was slight enough (usually less than 2 percent) to win proponents widely, in both East and West. Zabdiel Boylston's inoculation of 244 people in Boston, during a smallpox


outbreak in 1721, was an early and well-documented success in British America.

Modern Eradication Efforts and Dangers

Three-quarters of a century after Boylston, Edward Jenner—an English variolator—realized the merit of a folk belief that farmers and milkmaids who had encountered a mild pox virus of cattle seldom contracted smallpox. He conducted experiments proving the point, and published his findings in 1798 as An Inquiry into the Cause and Effects of the Variolae Vaccinae. "Vaccination" and "vaccine" came from the Latin word for cow.

Whether or not Jenner had actually used cowpox virus or, as later authorities claimed, had accidentally applied an attenuated Variola, researchers discovered in 1939 that an altogether distinct virus, vaccinia, had mysteriously become the artificial immunizing agent against smallpox. By then, however, the combined effects of vaccination and widespread epidemics of Variola minor had knocked down smallpox incidence and mortality to very low levels. No smallpox deaths occurred in the United States from 1930 to 1943. Nearly fourteen hundred cases, with forty-five deaths, occurred between 1944 and 1949, but the United States remained smallpox-free after 1950.

In 1966, the World Health Organization began a global smallpox eradication project under the leadership of Donald A. Henderson of the U.S. Public Health Service. At the time, between ten million and fifteen million people outside Europe and North America contracted the disease annually. The campaign's strategy was not to vaccinate entire national populations, but to find every case of actual disease and vaccinate everyone in that immediate vicinity. Some 150,000 WHO workers gradually isolated "islands" of the disease and eliminated them. The last case from South America occurred in 1972, the last in Asia appeared in 1975, and the last in Africa happened in 1977. Ali Maow Maalin, a Somali, found on 26 October 1977, was the final person to have naturally occurring smallpox. A laboratory accident in 1978 killed two more people in England, but no further cases were reported. WHO's announcement in 1979 that global eradication had been achieved came as medicine's single greatest achievement—total victory over a human disease.

A dozen years passed between the proclaimed "end" of smallpox and serious reservations about that claim. In 1992, the former deputy chief of the Soviet Union's biological weapons program defected to the West and made startling assertions. Kanatjan Alibekov (later anglicized to Ken Alibek) told American defense officials that during the 1980s a massive stockpile of plague agents, including an annual reserve of twenty tons of liquid smallpox, had been produced and maintained, mainly at a Soviet laboratory in Koltsovo, Siberia. Moreover, by 1990 production facilities existed to manufacture up to one hundred tons of smallpox a year. Investigations after the Soviet Union's collapse were unable fully to confirm or deny Alibekov's details, or the possibility that former Soviet biological warfare scientists found subsequent secret work in several Middle Eastern countries. Yet because of the risk of smallpox's return via terrorism or biological warfare, the U.S. Centers for Disease Control and Prevention in 2001 awarded a contract to Wythe Laboratories, Inc., in Marietta, Pennsylvania to create forty million doses of vaccinia as an annual national vaccine reserve. Meanwhile, at the beginning of the twenty-first century the U.S. population remains about as immunologically vulnerable to smallpox as the Amerindians were in the seventeenth century.

BIBLIOGRAPHY

Alibek, Ken. Biohazard: The Chilling True Story of the Largest Covert Biological Weapons Program in the World. New York: Random House, 1999.

Crosby, Alfred. "Smallpox." In the Cambridge World History of Human Disease. Edited by Kenneth F. Kiple. Cambridge, U.K.: Cambridge University Press, 1994.

Fender, Frank, et al. Smallpox and Its Eradication. Geneva, Switzerland: World Health Organization, 1988.

Tucker, Jonathan B. Scourge: The Once and Future Threat of Smallpox. New York: Atlantic Monthly Press, 2001.

G. TerrySharrer

See alsoCenters for Disease Control ; Public Health .

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Smallpox and Revolution

Smallpox and Revolution

Sources

Dreaded Disease. Before the nineteenth century smallpox swept eastern North America in recurrent epidemics. Unlike malaria or yellow fever, which kept mostly to the southern half of the eastern seaboard, smallpox could break out anywhere. For any early American its appearance in his or her neighborhood was an ever-present possibility, and there was even an atmosphere of inevitability about its arrival, much as there is about the flu today. It is the opinion of some very observent men, according to a contemporary, that there are few persons but what have the Small-pox at some period of their lives. It was a killer and was feared not only because it could spread like wildfire but also because it was an ugly, disfiguring disease. One writer concluded there is no disease so universal, and at the same time so mortal.

Characteristics. The onset of smallpox was signaled by fatigue, high fever, and aching. Since these could be

A DIFFICULT DECISION

People who had never had smallpox tended to avoid inoculating themselves and their children until a crisis appeared. After all, the procedure involved deliberate exposure to the disease, with the certainty of a period of sickness and the possibility of death. When smallpox struck a community, people were forced to make painful choices. Contracting the disease in the natural way was terrible even to contemplate, but the uncertainty of inoculation could be even more frightening. Sally Fisher of Philadelphia was Very anxious, about my little Boy what to do for the best, whether to Inoculate him or not. She decided in favor of the procedure. Her son survived, and when smallpox revisited the city two years later, she had her daughter inoculated also. Women often had to make these choices in the absence of their husbands. Lucy Knox, whose husband Henry was a general in the American army, placed herself and their baby daughter in a Boston smallpox hospital to receive the treatment. Henry approved of the decision but confessed my heart palpitates at the thoughtof my Lucy being in the least danger, May God preserve and carry you and our dear babe safe through it. Abigail Adams likewise made the decision without her Congressman husband John, but as she left the inoculation hospital in Boston, she was able to report that all my treasure of children have passed thro one of the most terrible Diseases to which human nature is subject, and not one of us is wanting. Those who were reluctant to choose inoculation, however, ran a great risk. Even Benjamin Franklin hesitated, and it cost him dearly: his four-year-old son died in 1736, by the Small Pox taken in the common way. Many years later he confessed in his Autobiography (1868): I long regretted bitterly and still regret that I had not given it to him by Inoculation. This I mention for the Sake of parents, who omit that Operation on the Supposition that they should never forgive themselves if a child died under it; my Example showing that the Regret may be the same either way, and that therefore the safer should be chosen.

Sources: Mary Beth Norton, Libertys Daughters: The Revolutionary Experience of American Women, 1750-1800 (Ithaca, N.Y.: Cornell University Press, 1996);

Benjamin Franklin, The Autobiography of Benjamin Franklin, edited by Leonard W. Labaree, Ralph L. Ketcham, and others (New Haven: Yale University Press, 1964).

symptoms of any number of ailments, the victim could easily spread the illness before breaking out with the definitive pock marks. These were blisters, often large, which filled with pus as the sickness progressed. If the sufferer survived, the eruptions eventually subsided but left permanent scars. George Washington contracted smallpox as a young man, and although his eruptions were not severe, his face bore the scars to the end of his life. A communitys first and best defense was to quarantine the afflicted person and anyone who had had recent contact with him. Even so, sometimes the disease was too widespread to contain, and it became epidemic, especially in urban centers such as Philadelphia or New York. When that occurred, the mortality rate could be high. Cotton Mather, a Boston minister, compiled statistics during the 1720-1721 outbreak there, noting that 15 percent of uninoculated smallpox victims had died of the disease.

Debatable Safeguard. Fortunately those who contracted smallpox and survived never had to go through the ordeal again: they were now immune. In addition some victims seemed to have much milder cases and yet were also immune thereafter. A procedure originating in the Orient slowly made its way into Europe and America that seemed to promise relief. If a small incision was made in the skin of a healthy person, and the wound was dabbed with the pus, or matter, from a smallpox victim, the healthy person then contracted a mild form of the disease and was thereafter immune. The procedure still carried riskaccording to Mathers study, 3 percent of those thus inoculated died anywaybut the odds of escaping death and disfigurement improved dramatically. Many opposed inoculation, however, as untrustworthy and too dangerous, believing that it actually spread the disease. In 1774 concerned citizens in Philadelphia formed a Society for Inoculating the Poor, which unfortunately foundered during the Revolution, but this was an exceptionally foresighted effort. Resistance to the procedure was still high a year later, when the Revolutionary War began; several colonies passed laws forbidding its practice within their borders.

Epidemic. Armies and cities under siege were ideal breeding grounds for diseases of all sorts. In 1776 New England was struck with a smallpox epidemic directly related to the Revolutionary War. British troops had just evacuated Boston after a ten-month siege, leaving an outbreak of smallpox behind them (Americans accused them of deliberately spreading the disease). At nearly the same time some New England soldiers returning from the failed Canada expedition brought smallpox back with them: of the eight thousand men who marched to Canada, two thousand fell ill with the disease. George Washington knew from firsthand experience what smallpox could do. Fearing an outbreak that would cripple his main army, he ordered a general inoculation for his troops and made the procedure available to civilians as well. The experiment-by-necessity was a resounding success; physician Benjamin Gale compiled statistics from Boston to show that only one person out of one hundred inoculated dieda great improvement over Mathers 3 percent a half century before. One might think that the benefits of inoculation could no longer be doubted, but that would be to underestimate conservative resistance to the procedure. New York still outlawed the practice, so Washington was forced to suspend inoculation while his army operated there and even to threaten punishment for any soldier or officer undergoing the procedure. As a result smallpox outbreaks continued throughout the war.

Sources

Harold L. Peterson, The Book of the Continental Soldier (Harrisburg, Pa.: Stackpole, 1968);

Ola Elizabeth Winslow, A Destroying Angel: The Conquest of Smallpox in Colonial Boston (Boston: Houghton Mifflin, 1974).

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Smallpox

Smallpox

Smallpox is an infection caused by the variola virus, a member of the poxvirus family. The disease is highly infectious. Passage from person to person via contaminated aerosolized droplets (from sneezing, for example) occurs easily, and so the spread of smallpox through a population can occur quickly. Like most viruses and other microorganisms, the variola virus can be transported from one location to another without difficulty, thus making smallpox a potentially attractive choice for biological warfare and a serious threat as a weapon of bioterrorists.

Smallpox is a highly contagious disease. The virus can spread by direct contact with those who are infected, in contaminated air droplets, and even by touching objects such as books and blankets that have been previously used by someone who has smallpox.

When infected with the virus, there is a 1214 day symptom-free period, during which the virus is multiplying in the body. There is then a sudden onset of symptoms. The symptoms include fever and chills, muscle aches, and a flat, reddish-purple rash on the chest, abdomen, and back. These symptoms last about three days, after which the rash fades and the fever drops. A day or two later, the fever returns, along with a bumpy rash starting on the feet, hands, and face. This rash progresses from the feet along the legs, from the hands along the arms, and from the face down the neck, ultimately reaching and including the chest, abdomen, and back. The individual bumps, or papules, fill with clear fluid, and, over the course of 1012 days, became pus-filled. The pox eventually scabs over, and when the scab falls off it leaves behind a pock-mark or pit, which remains as a permanent scar on the skin of the victim.

Smallpox can be lethal, usually due to bacterial infection of the open skin lesions, pneumonia, or bone infections. A severe and quickly fatal form of smallpox is known as "sledgehammer smallpox." This form of smallpox is characterized by bleeding from the skin lesions, as well as from the mouth, nose, and other areas of the body.

Smallpox has been present for thousands of years. For example, studies of the mummy of Pharaoh Ramses V, who died in 1157 b.c., revealed symptoms of smallpox infection.

Large smallpox epidemics have occurred throughout recorded history. Attempts to protect against smallpox infection began centuries ago, even thought the microbiological nature of the disease was then unknown. In the tenth century, accounts from China, India, and the Americas describe how individuals who had even a mild case of smallpox could not be infected again. Fluid or pus from the skin lesions was scratched into the skin of those who had never had the illness, in an attempt to produce a mild reaction and its accompanying protective effect. Unfortunately, these efforts sometimes resulted in full-fledged smallpox, and helped spread the infection. Such crude vaccinations against smallpox were outlawed in Colonial America.

In 1798, Edward Jenner published his observation that milkmaids who contracted cowpox infection caused by vaccinia virus (a relative of variola) were immune to smallpox. He used infected material from the cowpox lesions to prepare an injection that helped protect the humans. Although Jenner's development of immunization was harshly criticized at first, the work paved the way for the development of vaccines.

Until the development of a smallpox vaccine, no treatment for smallpox was known, nor could anything shorten the course of the disease. Until its eradication, smallpox was diagnosed most clearly from the patients' symptoms. Electron microscopic studies could identify the variola virus in fluid isolated from disease papules, from infected urine, or from the blood prior to the appearance of the papular rash.

In the 1960s, the World Health organization (WHO) began a campaign to treat people infected with smallpox and vaccinate those who might be exposed to the infection. The WHO program was extremely successful, and the virus was declared eradicated worldwide in May of 1980. Stored stocks of the virus were maintained in two laboratories. One is housed at the Centers for Disease Control and Prevention in Atlanta, Georgia. The other smallpox stock is maintained in Russia.

These stocks were slated to be destroyed in the late 1990s however, U.S. President William J. Clinton halted plans for destruction of the American stocks. Concern that another poxvirus could mutate (undergo genetic changes) and cause human infection, along with the possible use of smallpox as a bioterrorist weapon or as a weapon of stateanctioned war, has made preservation of the smallpox stock for vaccine development purposes important. As of early 2003, the stocks remain undisturbed.

FURTHER READING:

BOOKS:

Hopkins, D. R. The Greatest Killer: Smallpox in History. Chicago: University of Chicago Press, 2002.

Preston, R. The Demon in the Freezer. New York: Random House, 2002.

PERIODICALS:

Henderson, D. A., T. V. Inglesby, J. G. Bartlett, et al. "Smallpox as a Biological Weapon: Medical and Public Health Management." Journal of the American Medical Association no. 281 (1999): 2127137.

ELECTRONIC:

Centers for Diseases Control and Prevention. "Smallpox." Public Health Emergency Preparedness and Response. November 26, 2002. <http://www.bt.cdc.gov/agent/smallpox/index.asp> (27 November 2002).

SEE ALSO

Biocontainment Laboratories
Biological Weapons, Genetic Identification
Bioterrorism

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Smallpox

Smallpox

Smallpox is an infection caused by the variola virus , a member of the poxvirus family. Throughout history, smallpox has caused huge epidemics resulting in great suffering and enormous death tolls worldwide. In 1980, the World Health Organization (WHO ) announced that a massive program of vaccination against the disease had resulted in the complete eradication of the virus (with the exception of stored virus stocks in two laboratories).

Smallpox is an extraordinarily contagious disease. The virus can spread by contact with victims, as well as in contaminated air droplets and even on the surfaces of objects used by other smallpox victims (books, blankets, etc.). After acquisition of the virus, there is a 1214 day incubation period, during which the virus multiplies, but no symptoms appear. The onset of symptoms occurs suddenly and includes fever and chills, muscle aches, and a flat, reddish-purple rash on the chest, abdomen, and back. These symptoms last about three days, after which the rash fades and the fever drops. A day or two later, the fever returns, along with a bumpy rash starting on the feet, hands, and face. This rash progresses from the feet along the legs, from the hands along the arms, and from the face down the neck, ultimately reaching and including the chest, abdomen, and back. The individual bumps, or papules, fill with clear fluid, and, over the course of 1012 days, became pus-filled. The pox eventually scabs over, and when the scab falls off it leaves behind a pock-mark or pit, which remains as a permanent scar on the skin of the victim.

Death from smallpox usually follows complications such as bacterial infection of the open skin lesions, pneumonia , or bone infections. A very severe and quickly fatal form of smallpox was "sledgehammer smallpox," and resulted in hemorrhage from the skin lesions, as well as from the mouth, nose, and other areas of the body. No treatment was ever discovered for smallpox nor could anything shorten the course of the disease. Up until its eradication, smallpox was diagnosed most clearly from the patients' symptoms. Electron microscopic studies could identify the variola virus in fluid isolated from disease papules, from infected urine, or from the blood prior to the appearance of the papular rash.

Smallpox is an ancient disease. There is evidence that a major epidemic occurred towards the end of the eighteenth Egyptian dynasty. Studies of the mummy of Pharaoh Ramses V (d. 1157 b.c. ) indicate that he may have died of smallpox. Several historical accounts, some dating to the sixth century, describe how different peoples attempted to vaccinate against smallpox. In China, India, and the Americas, from about the tenth century, it was noted that individuals who had even a mild case of smallpox could not be infected again. Material from people ill with smallpox (e.g., fluid or pus from the papules) was scratched into the skin of those 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 sometimes served only to effectively spread the infection throughout the community. In Colonial America, such crude vaccinations against smallpox were outlawed because of the dangers.

In 1798, Edward Jenner (17491823) published a paper in which he discussed an important observation that milkmaids who contracted a mild infection of the hands (caused by vaccinia virus, a relative of variola) appeared to be immune to smallpox. He created an immunization against smallpox that used the pus material found in the lesions of cowpox infection. Jenner's paper, although severely criticized at first, later led to much work in the area of vaccinations. Vaccination using Jenner's method proved instrumental in decreasing the number of smallpox deaths.

Smallpox is dangerous only to human beings. Animals and insects can neither be infected by smallpox, nor carry the virus in any form. Humans also cannot carry the virus unless they are symptomatic. These important facts entered into the decision by the WHO to attempt worldwide eradication of the smallpox virus. The methods used in the WHO eradication program were simple and included the careful surveillance of all smallpox infections worldwide to allow for quick diagnosis and immediate quarantine of patients. It also included the immediate vaccination of all contacts of any patient diagnosed with smallpox infection. The WHO program was extremely successful, and the virus was declared eradicated worldwide in May of 1980. Two laboratories (in Atlanta, Georgia and in Koltsovo, Russia) retain samples of the smallpox virus, because some level of concern exists that another poxvirus could mutate (undergo genetic changes) and cause human infection. Other areas of concern include the possibility of smallpox virus being utilized in a situation of biological warfare , or the remote chance that the smallpox virus could somehow escape from the laboratories where it is being stored. For these reasons, large quantities of vaccine are stored in different countries around the world, so that response to any future threat by the smallpox virus can be prompt.

See also Smallpox, eradication, storage, and potential use as a bacteriological weapon; Vaccine

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Smallpox

Smallpox

Knowledge of the behavior of disease-causing (pathogenic) bacteria and viruses is especially vital when a forensic investigation is concerned with the possibility of an infection that is a serious threat to health and is easily spread from person to person. A prime example is smallpox.

Smallpox is an infection caused by the variola virus , a member of the poxvirus family. The disease is highly infectious. Passage from person to person via contaminated aerosolized droplets (from sneezing, for example) and even by touching objects such as books and blankets that have been previously used by someone who has smallpox occurs easily, and so the spread of smallpox through a population can occur quickly. Like most viruses and other microorganisms, the variola virus can be transported from one location to another without difficulty.

When infected with the virus, there is a twelve to fourteen day symptom-free period, during which the virus is multiplying in the body. There is then a sudden onset of symptoms. The symptoms include fever and chills, muscle aches, and a flat, reddish-purple rash on the chest, abdomen, and back. These symptoms last about three days, after which the rash fades and the fever drops. A day or two later, the fever returns, along with a bumpy rash starting on the feet, hands, and face. This rash progresses from the feet along the legs, from the hands along the arms, and from the face down the neck, ultimately reaching and including the chest, abdomen, and back. The individual bumps, or papules, fill with clear fluid, and, over the course of ten to twelve days, became pus-filled. The pox eventually scabs over, and when the scab falls off it leaves behind a pock-mark or pit, which remains as a permanent scar on the skin of the victim.

Smallpox can be lethal, usually due to bacterial infection of the open skin lesions, pneumonia, or bone infections. A severe and quickly fatal form of smallpox is known as "sledgehammer smallpox." This form of smallpox is characterized by bleeding from the skin lesions, as well as from the mouth, nose, and other areas of the body.

Smallpox has been present for thousands of years. For example, studies of the mummy of Pharaoh Ramses V, who died in 1157 b.c., revealed symptoms of smallpox infection.

Large smallpox epidemics have occurred throughout recorded history. Attempts to protect against smallpox infection began centuries ago, even thought the microbiological nature of the disease was then unknown. In the tenth century, accounts from China and India describe how individuals who had even a mild case of smallpox could not be infected again. Fluid or pus from the skin lesions was scratched into the skin of those who had never had the illness, in an attempt to produce a mild reaction and its accompanying protective effect. Unfortunately, these efforts sometimes resulted in full-fledged smallpox, and helped spread the infection. Such crude vaccinations against smallpox were outlawed in Colonial America.

In 1798, Edward Jenner published his observation that milkmaids who contracted cowpox infection caused by vaccinia virus (a relative of variola) were immune to smallpox. He used infected material from the cowpox lesions to prepare an injection that helped protect the humans. Although Jenner's development of immunization was harshly criticized at first, the work paved the way to the development of vaccines .

Until the development of a smallpox vaccine, no treatment for smallpox was known, nor could anything shorten the course of the disease. Until its eradication, smallpox was diagnosed most clearly from the patients' symptoms. Electron microscopic studies could identify the variola virus in fluid isolated from disease papules, from infected urine, or from the blood prior to the appearance of the papular rash.

In the 1960s, the World Health Organization (WHO) began a campaign to treat people infected with smallpox and vaccinate those who might be exposed to the infection. The WHO program was extremely successful, and the virus was declared eradicated worldwide in May of 1980. Stored stocks of the virus were maintained in two laboratories. One is housed at the Centers for Disease Control and Prevention in Atlanta, Georgia. The other smallpox stock is maintained in Russia.

These stocks were slated to be destroyed in the late 1990s, however, President Bill Clinton halted plans for destruction of the American stocks. Concern that another poxvirus could mutate (undergo genetic changes) and cause human infection has made preservation of the smallpox stock for vaccine development purposes important. As of 2005, the stocks remain undisturbed.

see also Bioterrorism; Pathogens; Vaccines; Variola virus.

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Smallpox

SMALLPOX

Epidemic smallpox was one of the deadliest scourges ever to afflict humankind. It killed ancient Egyptian Pharoahs, villagers in teeming Asian villages, aristocrats in Paris and St. Petersburgh, and children in colonial New England. It contributed substantially to the collapse of the Aztec empire in Mexico, where it was introduced by the Spanish conquistadors. It was an ever-present threat, always lurking, occasionally breaking out in large epidemics. Smallpox occurred in two forms, variola major and variola minor. Variola major was the fulminant, often epidemic, variety, with a mortality rate of 40 percent or more and severe complications among survivors. Variola minor was more mild, with a mortality rate of less than 5 percent.

About 1,000 years ago, Chinese physicians discovered that susceptible persons inoculated with secretions from a smallpox scab generally had only a mild attack, and thereafter were immune. This procedure, called variolation, reached Constantinople about 1700, and was reported in a letter by Lady Mary Wortley Montagu, wife of the British plenipotentiary, to a friend in England in 1717. In 1798, Edward Jenner, a Gloucestershire doctor, vaccinated a boy with secretions from a cowpox blister, and soon reported successful vaccination of over twenty others. This was the prelude to the twentieth-century eradication of smallpox in a worldwide vaccination campaign coordinated by the World Health Organization. The last naturally occurring case was a girl in Somalia in 1977 (two further laboratory cases occurred in England in 1978).

Smallpox was an acute illness with high fever, a widespread skin rash with blebs and blisters, generalized prostration, collapse, and, commonly, death. Survivors often carried disfiguring scars for the rest of their lives, and were usually blind if lesions affected their eyes. The cause was a brickshaped virus in the orthopox virus family. Humans were its only natural host. The virus survives now only in tissue cultures in two or three high-security microbiology research institutes. Total eradication was made possible by unique epidemiological featuresi.e., there is no nonhuman host and vaccination was rapidly efficacious, so those who had been exposed to a case were protected from infection if they were immediately vaccinated. This was the basis for the containment strategy that was ultimately the key to global eradication.

Smallpox has been identified as a potential biological weapon. It would wreak havoc in an unvaccinated population, and it would be difficult for a vulnerable nation to mount an effective vaccination campaign in time to prevent national devastation. However, attackers who used smallpox as a weapon would have to ensure that they were all vaccinated, and it would be difficult to conceal a vaccination program against smallpox from the world.

John M. Last

(see also: Communicable Disease Control; Epidemics; Immunizations; Jenner, Edward; Montagu, Lady Mary Wortley )

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smallpox

smallpox, acute, highly contagious disease causing a high fever and successive stages of severe skin eruptions. The disease dates from the time of ancient Egypt or before. It has occurred worldwide in epidemics throughout history, killing up to 40% of those who contracted it and accounting for more deaths over time than any other infectious disease. Spreading to the New World with European colonization, it killed huge numbers of the indigenous people, who had no immunity, greatly contributing to the annihilation of native cultures.

Smallpox is caused by a virus that may be airborne or spread by direct contact. After an incubation period of about two weeks, fever, aching, and prostration occur, lasting two or three days. An eruption then appears and spreads over the entire body; the lesions become blisterlike and pustular within a week. The lesions then open and crust over, causing itching and pain. When the crusts fall off, usually in another one or two weeks, the extent of permanent damage to the skin (pockmarks) becomes evident. There is no specific treatment for smallpox; an antibiotic may be administered to prevent secondary bacterial infection.

A crude vaccination method began with Emanuel Timoni, a Greek physician, in the early 18th cent. Edward Jenner modified the procedure (1796) by using the related cowpox virus to confer immunity. By 1977, vaccination programs, such as those by the World Health Organization (WHO), had eliminated the disease worldwide.

After 1980, when WHO officially declared smallpox eradicated as a disease, scientists retained some samples of the virus in laboratories for study. They mapped the genetic sequence of three strains of smallpox, and the destruction of the remaining samples of the live virus was scheduled and postponed several times. Owing to fears of a new natural outbreak or of the potential use of smallpox as a terrorist weapon against populations no longer vaccinated, research with the virus continued. The last declared samples of live virus are now stored by the U.S. and Russian governments under strict security, but it is believed that some nations may have secret stores of the virus that they could use as biological weapons.

Responding to such concerns, WHO postponed the scheduled 1999 destruction of all remaining stocks of the smallpox virus until 2002. The 2001 bioterror attacks in the United States with anthrax led the United States and other nations to stockpile doses of smallpox vaccine out of concern that the smallpox virus might be used by terrorists. WHO agreed to delay the destruction of virus stocks beyond 2002 to allow for the development of new vaccines, and since then no plan for destruction has been agreed upon. In 2002, because of bioterrorism concerns, the G. W. Bush administration decided to vaccinate frontline military personnel and health-care and emergency workers against smallpox.

See E. A. Fenn, Pox Americana: The Great Smallpox Epidemic of 1775–1782 (2001); J. B. Tucker, Scourge (2001); M. Willrich, Pox: An American History (2011).

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Smallpox

SMALLPOX

DEFINITION


Smallpox is an infection caused by the virus called variola (pronounced vuh-RY-uh-luh). Throughout history, smallpox has been a greatly feared disease. It has been responsible for huge epidemics worldwide. The disease has caused great suffering and many deaths. Smallpox is now thought to have been eliminated from the Earth. In 1980 the World Health Organization (WHO) announced that the disease had been wiped out by a bold program of vaccination.

DESCRIPTION


The smallpox virus infected humans only. It did not infect other animals or insects. Neither could animals or insects transmit the virus from one human to another. The disease could be transmitted only by contact between humans. Sometimes a person came into contact with someone with skin lesions caused by the disease. Skin lesions are wounds produced by the virus. They were known as pox. A person also could catch the virus even if the infected person had no lesions.

CAUSES


Smallpox was a relatively contagious disease. The virus could be transferred from one person to another in a number of ways. A person could catch the virus by touching the lesions of an infected person. The virus could also be transferred in droplets of moisture produced during coughing or sneezing. And a person could get the virus from books, blankets, utensils, or other objects used by someone with the disease.

The virus usually entered the body through the respiratory (breathing) tract. It then passed through an incubation period of twelve to fourteen days. An incubation period is the time that passes after a person is infected before symptoms appear. During this time, the virus was multiplying within the body and moving through the bloodstream.

SYMPTOMS


The first symptoms of smallpox were fever and chills, muscle aches, and a flat, reddish-purple rash on the chest, abdomen, and back. These symptoms lasted for about three days. Then the rash faded and the fever dropped.

A day or two later, the fever would return. A bumpy rash would begin to appear on the feet, hands, and face. The rash then spread to the chest, abdomen, and back. The individual bumps in the rash filled with clear fluid. They eventually became filled with pus over a period of ten to twelve days. The bumps (pox) would eventually form scabs. When the scabs fell off, a small pit was left on the skin. People who survived a smallpox infection were often terribly scarred in this way.

Death from smallpox was usually caused by complications. For example, bacteria could easily get into the open skin lesions. Pneumonia, bone infections, or other diseases would result.

An especially severe form of smallpox was called sledgehammer smallpox. The name came from the fact that the infection struck very quickly and with great force. It caused massive, uncontrolled bleeding from the skin lesions, the mouth, nose, and other areas of the body. A person could die very quickly from sledgehammer smallpox.

Throughout history, people have been terrified by smallpox. One reason for their concern was the ease with which the disease spread through whole communities. The other reasons for worry was that no cure for the disease was ever found.

Smallpox: Words to Know

Epidemic:
An outbreak of a disease that spreads over a wide area in a relatively short period of time.
Lesion:
A change in the structure or appearance of a part of the body as the result of an injury or infection.
Vaccine:
A substance that causes the body's immune system to build up resistance to a particular disease.
Variola:
The virus that causes small pox. The only two small samples of variola that remain on Earth are being stored in two separate research laboratories.

DIAGNOSIS


At one time, most doctors could diagnose smallpox simply by examining a patient. The skin lesions had a very characteristic appearance. Doctors also knew what to look for when there was a smallpox epidemic in an area. In modern times, diagnosis could also be made by a blood test. A sample of the patient's blood could be examined under an electron microscope. An electron microscope is a very powerful type of microscope. The variola virus can actually be seen in the blood with this type of microscope.

TREATMENT


No cure for smallpox was ever found. The best that could be done was to keep a patient comfortable and wait for the disease to die off on its own.

PROGNOSIS


Death from smallpox ranged as high as 35 percent of those who were infected. In the case of sledgehammer smallpox, the death rate was nearly 100 percent. Patients who recovered from the disease almost always had severe scarring from skin lesions.

THE END OF THE SMALLPOX VIRUS?

Smallpox has been eliminated as a human disease. But the virus has not. Two samples remain in scientific laboratories. They have been kept for the purpose of research. Has the time now come to destroy these last two samples of variola virus also?

The World Health Organization (WHO) thinks so. WHO is an international agency that deals with health problems throughout the world. It recommended in March 1986, December 1990, and September 1994 that the virus samples in Atlanta and Moscow be destroyed. The organization was worried that the virus might fall into the hands of terrorists. It could be used to reintroduce the world's most terrible infectious disease to human populations. That risk is too great, WHO believes.

Other scientists disagree. We should not intentionally eliminate any organism, they say, even one as terrible as variola. Besides, we can learn about other viruses by continuing to study the smallpox virus.

In the summer of 1999 the World Health Organization decided to delay destruction of the remaining samples of the smallpox virus until 2003.

PREVENTION


A person who has had smallpox can never have the disease again. This fact was known as far back in history as the tenth century. Medical workers in China, India, and the Americas made use of this information. They often tried to protect people from smallpox with a simple form of vaccination. First, they removed the liquid material from the rash of a person infected with smallpox. Then, they would make small scratches in the arm of the person to be vaccinated and place the liquid material from the infected person into the scratch.

This method had mixed results. Under the best circumstances, people who received this treatment developed a mild case of smallpox. They were then protected against the disease for the rest of their lives. However, the vaccinated person sometimes developed a full-blown case of smallpox. Instead of receiving protection from the disease, they would become ill from it.

In 1798 the English scientist Edward Jenner developed a variation on this procedure. He noticed that milkmaids sometimes caught a mild form of smallpox called cowpox. Cowpox was caused by a virus similar to, but less damaging than, the variola virus. Jenner used fluid from cowpox lesions to vaccinate people against smallpox. The cowpox fluid was much more likely to cause mild symptoms of the disease. But it still provided a person with protection against smallpox.

By the twentieth century a very effective smallpox vaccine was available. A vaccine (pronounced vak-SEEN) is a substance that causes the body's immune

system to build up resistance to a particular disease. Most young children in developed nations were routinely vaccinated against the disease and smallpox began to die out in some parts of the world. But it was still common in developing nations.

In 1967 WHO began a campaign to eliminate the variola virus completely. The organization watched carefully for outbreaks of smallpox throughout the world. When those outbreaks occurred, WHO workers were sent to the area where an epidemic was beginning. Everyone in the area was then vaccinated against the disease.

The program eventually worked. By 1980 WHO was able to announce that the disease no longer existed anywhere in the world. Today, samples of the variola virus exist in two research laboratories, one in Atlanta, Georgia, and one in Moscow, Russia. These samples are being saved for research purpose only. Some people worry that a relative of the variola virus may develop that can cause a smallpox-like infection. The variola samples might then be useful in developing a vaccine against the new infection.

FOR MORE INFORMATION


Books

Giblin, James Cross. When Plague Strikes: The Black Death, Smallpox, AIDS. New York: HarperCollins Children's Books, 1995.

Lyons, Albert A., and R. Joseph Petrucelli, II. Medicine: An Illustrated History. New York: Harry N. Abrams, 1987.

Stoffman, Phyllis. The Family Guide to Preventing and Treating 100 Infectious Diseases. New York: John Wiley and Sons, 1995.

Periodicals

Siebert, Charles. "Smallpox is Dead: Long Live Smallpox." New York Times Magazine (August 21, 1994): pp. 30+.

Wagner, Betsy. "Smallpox is Now a Hostage in the Lab." Washington Post (January 4, 1997): pp. WH8+.

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Smallpox

Smallpox

What Is Smallpox?

How Common Is the Disease?

Is It Contagious?

Signs and Symptoms

How Do Doctors Make the Diagnosis?

What Is the Treatment for Smallpox?

What to Expect

How Can Smallpox Be Prevented?

Resources

Smallpox is a contagious and often fatal infection caused by the variola (ver-e-O-luh) virus.

KEYWORDS

for searching the Internet and other reference sources

Biological weapon

Edward Jenner

Vaccinia vaccine

Variola major

Variola minor

Vesicles

What Is Smallpox?

What do Queen Mary II of England, King Louis XV of France, and Czar Peter II of Russia have in common? Other than being royalty, they all died from smallpox, one of the deadliest diseases in history. This devastating illness first surfaced thousands of years ago, and many believe smallpox killed more people than all other diseases combined before it was wiped out in the late 1970s. The variola (from the Latin word varus, meaning spotted) virus causes two types of smallpox: variola major and variola minor. Variola major (the type discussed in this chapter) is extremely serious and can be fatal in up to 30 percent of cases. The milder variola minor is fatal in less than 1 percent of patients.

How Common Is the Disease?

Thanks to the vaccine* developed by Edward Jenner in 1796 and the World Health Organizations (WHO) intensified immunization program begun in 1967, smallpox is no longer found in the world; the last naturally occurring case was reported in Somalia in Africa in 1977. Before this successful eradication program, the illness affected millions of people of all ages every year. Those who survived the severe period of infection often were left scarred or blinded.

*vaccine
(vak-SEEN) is a preparation of killed or weakened germs, or a part of a germ or product it produces, given to prevent or lessen the severity of the disease that can result if a person is exposed to the germ itself. Use of vaccines for this purpose is called immunization.

Is It Contagious?

Smallpox is so contagious that just one infected person can launch an epidemic*. As soon as the first symptoms of the disease appear, an infected person can spread the virus by coughing, sneezing, or even talking. This expels tiny virus-packed drops of moisture into the air. When a healthy person breathes in these drops, the virus finds a new home. Less often, touching patients sores or even just their bed linens or clothes can spread the infection. Smallpox is typically most contagious during the first week of illness. Outbreaks of the disease in a community have tended to occur at 2- to 3-week intervals.

*epidemic
(eh-pih-DEH-mik) is an outbreak of disease, especially infectious disease, in which the number of cases suddenly becomes far greater than usual. Usually epidemics are outbreaks of diseases in specific regions, whereas worldwide epidemics are called pandemics.

Signs and Symptoms

Once the virus enters the body, it quickly reproduces and takes over healthy cells. An infected person usually is not even aware of the viral intruders for at least a week. Then the first wave of smallpox symptoms appears, often resembling those of a cold or the flu: fever, extreme tiredness, headache, backache, and occasionally, nausea (NAW-zee-uh) and vomiting. These symptoms can last up to a week. About 2 to 3 days after the onset of symptoms, a rash of red blisters or lesions* appears suddenly on the face, arms, and palms. Within a few days, the lesions fill with fluid and pus* and spread to other parts of the body, including the inside of the nose and mouth. The sores can expand and break open, causing pain. Eventually, scabs form and later fall off. During its early stages, smallpox can be confused with chicken pox, which is caused by a different virus (varicella zoster, var-uh-SEH-luh ZOS-ter). Chicken pox produces a much milder rash that usually develops on the body and is less prominent on the face, arms, and hands.

*lesions
(LEE-zhuns) is a general term referring to sores or damaged or irregular areas of tissue.
*pus
is a thick, creamy fluid, usually yellow or greenish in color, that forms at the site of an infection. Pus contains infection-fighting white cells and other substances.

How Do Doctors Make the Diagnosis?

Because smallpox was wiped out in the last quarter of the twentieth century, very few doctors practicing today have ever seen a case. With the heightened awareness of the possibility that smallpox could be used as a weapon in biological warfare*, doctors are being trained to recognize the disease. To make a diagnosis of smallpox, tests would be done on blood and fluid from a patients lesions to identify the virus. To prevent a widespread outbreak, the patient most likely would be isolated, and those in close contact with the person would be vaccinated. If just one case of smallpox were diagnosed today, it could cause a public health emergency.

*biological warfare
is a method of waging war by using harmful microorganisms to purposely spread disease to many people.

What Is the Treatment for Smallpox?

There is no known cure for smallpox. Receiving the smallpox vaccine within 4 days of being exposed to someone who has the disease may prevent infection or lessen symptoms. Scientists are looking for new medicines as possible treatments for the disease. Public health agencies recommend

Birth Of A Vaccine

Edward Jenner often is called the father of modern immunology* because of his major contribution to ending smallpox. As an English country doctor, Jenner was fascinated that milkmaids exposed to cowpox (a disease that affects cows and is caused by a virus similar to variola) did not contract smallpox. He developed a vaccine containing live cowpox virus and injected it into an 8-year-old boy. The boy did not contract smallpox, and vaccinations for the disease quickly became standard. Following Jenners discovery, fatalities from smallpox dropped significantly. Jenner believed that his vaccine provided lifelong immunity to the disease. It is now thought, however, that the vaccine may not protect people for more than 10 years.

*immunology
(ih-myoo-NOL-uh-jee) is the science of the system of the body composed of specialized cells and the substances they produce that help protect the body against disease-causing germs.

that patients who have symptoms of smallpox be isolated immediatelyeither in a special unit of a hospital or at homeso that the infection will not spread to others. Health care workers are advised to take careful precautions when treating these patients. In the absence of a cure, treatment focuses on easing symptoms and preventing further infections. Patients may receive intravenous fluids (fluids injected directly into a vein), pain relievers, and antibiotics (to combat bacterial infections that can develop in the open sores) while the disease runs its course.

What to Expect

Smallpox infection can last from 3 to 4 weeks or until the last scabs fall off. The lesions often leave behind deep, pitted scars. When smallpox is fatal, patients usually die during the second week of illness. Smallpox can lead to serious complications, including these:

  • hemorrhagic (heh-muh-RAH-jik) smallpox (which is associated with bleeding in the skin and body membranes)
  • malignant smallpox (in which the sores are flat and close together)
  • blindness
  • bacterial infections
  • pneumonia*
  • encephalitis*
*pneumonia
(nu-MO-nyah) is inflammation of the lung.
*encephalitis
(en-seh-fuh-LYE-tis) is an inflammation of the brain, usually caused by a viral infection.

How Can Smallpox Be Prevented?

Widespread vaccination in the United States for smallpox ended in 1972. In 1980 WHO declared the disease eradicated. It is unknown how long vaccine-generated immunity* lasts. Experts believe that it prevents infection for at least 10 years, but scientists think that few people in the world today are still immune to smallpox.

*immunity
(ih-MYOON-uh-tee) is the condition of being protected against an infectious disease. Immunity often develops after a germ is introduced to the body. One type of immunity occurs when the body makes special protein molecules called antibodies to fight the disease-causing germ. The next time that germ enters the body, the antibodies quickly attack it, usually preventing the germ from causing disease.

Today there are two official facilities that store samples of the virus: the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the Russian State Research Center of Virology and Biotechnology in Koltsovo. In the unlikely event that bioterrrorists were to get access to any of these stored samples, it is possible that they might use the virus to launch a biological attack. If this were to happen, vaccines would be in high demand. To prepare for such a potential emergency, mass production of the vaccine is under way in the United States.

Owing to possible side effects of the smallpox vaccine, the CDC suggests that it be given only to those at greatest risk of being exposed to the virus, including military personnel and first responders, for example, medical care providers, law enforcement personnel, and laboratory workers. About one in a million people who are vaccinated die from the effects of the vaccine, and a small percentage experience scarring or serious infections.

See also

Bioterrorism

Encephalitis

Pneumonia

Public Health

Varicella (Chicken Pox) and Herpes Zoster (Shingles)

Resources

Organizations

Center for Civilian Biodefense Strategies, Johns Hopkins University, 111 Market Place, Suite 830, Baltimore, MD 21202. The Center for Civilian Biodefense Strategies has fact sheets on smallpox and its place in bioterrorism.

Telephone 410-223-1667 http://www.hopkins-biodefense.org

U.S. Centers for Disease Control and Prevention (CDC), 1600 Clifton Road, Atlanta, GA 30333. The CDC provides fact sheets and vaccine information on smallpox.

Telephone 800-311-3435 http://www.cdc.gov

World Health Organization (WHO), Avenue Appia 20, 1211 Geneva 27, Switzerland. The WHO website has links to fact sheets and information on the prevention and control of smallpox.

Telephone 011-41-22-791-2111 http://www.who.int

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smallpox

smallpox (smawl-poks) n. an acute infectious virus disease causing high fever and a rash that scars the skin. The rash consists of red spots (macules) that appear on the face, spread to the trunk and extremities, and gradually develop into pustules. Most patients recover but serious complications, such as nephritis or pneumonia, may develop. Treatment with thiosemicarbazone is effective. Immunization against smallpox has now totally eradicated the disease. Medical name: variola. See also alastrim, cowpox.

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smallpox

smallpox Formerly a highly contagious viral disease characterized by fever, vomiting, and skin eruptions. It remained endemic in many countries until the World Health Organization (WHO) campaign, launched in the late 1960s; global eradication was achieved by the early 1980s.

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smallpox

small·pox / ˈsmôlˌpäks/ • n. an acute contagious viral disease, with fever and pustules usually leaving permanent scars. It was effectively eradicated through vaccination by 1979. Also called variola.

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smallpox

smallpoxbox, cox, detox, fox, Foxe, Knox, lox, outfox, ox, phlox, pox, Stocks •matchbox •bandbox, sandbox •hatbox • haybox • mailbox • brainbox •paintbox • squeezebox • pillbox •icebox • strongbox • horsebox •saltbox • soundbox • soapbox •shadow-box • shoebox • jukebox •toolbox • snuffbox • gearbox • firebox •tinderbox • thunderbox • pillar box •pepperbox • chatterbox • letter box •workbox • paradox • heterodox •orthodox • dementia praecox •Wilcox • backblocks • dreadlocks •Goldilocks • Magnox • equinox •chickenpox • smallpox • cowpox •aurochs • xerox • volvox •Faux, Fawkes •Boaks, coax, hoax, Oaks, stokes •yoicks •Fuchs, gadzooks, Jukes •Brooks, Crookes

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Smallpox

Smallpox

Symptoms and progression of the disease

Diagnosis

Discovery of smallpox vaccine

Global eradication of smallpox virus

Resources

Smallpox is an infection caused by the variola virus, a member of the poxvirus family. Throughout world history, smallpox has caused epidemics resulting in suffering and death. In 1980, the World Health Organization (WHO) announced that a massive program of vaccination against the disease had resulted in the complete eradication of the virus (with the exception of the known stored virus in two laboratories).

Symptoms and progression of the disease

Smallpox is a highly contagious disease. The virus spread from contact with victims, as well as from contaminated air droplets and even from objects used by other smallpox victims (books, blankets, etc.).

After acquisition of the virus, there is a 12-14 day incubation period, during which the virus multiplied, but no symptoms appeared. The onset of symptoms occurs suddenly and includes fever and chills, muscle aches, and a flat, reddish-purple rash on the chest, abdomen, and back. These symptoms last about three days, after which the rash fades and the fever drops. A day or two later, the fever returns, along with a bumpy rash starting on the feet, hands, and face. This rash progresses from the feet along the legs, from the hands along the arms, and from the face down the neck, ultimately reaching and including the chest,

abdomen and back. The individual bumps, or papules, fill with clear fluid, and, over the course of 10-12 days, becomes pus-filled. The pox eventually scab over, and when the scab falls off, left behind is a pock or pit which remained as a permanent scar.

Death from smallpox usually follows complications such as bacterial infection of the open skin lesions, pneumonia, or bone infections. A very severe and quickly fatal form of smallpox called sledgehammer smallpox resulted in hemorrhage from the skin lesions, as well as from the mouth, nose, and other areas of the body.

Diagnosis

Diagnosis, up until the eradication of smallpox, consisted of using an electronmicroscope to identify the virus in fluid from the papules, in the urine, or in the blood prior to the appearance of the papular rash.

Discovery of smallpox vaccine

Fascinating accounts have been written describing ways in which different peoples tried to vaccinate themselves against smallpox. In China, India, and the Americas, from about the tenth century, it was noted that individuals who had had even a mild case of smallpox could not be infected again. Material from people ill with smallpox (fluid or pus from the papules, the scabs) 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 the community. In fact, such crude vaccinations against smallpox 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 variola) appeared to be immune to smallpox. He created an immunization against smallpox that used the infected material found in the lesions of cowpox infection. Jenners paper led to much work in the area of vaccinations and ultimately resulted in the creation of an effective smallpox vaccine, which utilizes the vaccinia virusanother close relative of variola.

Global eradication of smallpox virus

Smallpox is dangerous only to human beings. Animals and insects can neither be infected by smallpox, nor carry the virus in any form. Humans cannot carry the virus, unless they are symptomatic. These important facts entered into the 1967 decision by the WHO to attempt worldwide eradication of the smallpox virus.

The methods used in WHOs eradication program were straightforward: 1) careful surveillance for all smallpox infections worldwide to allow for quick diagnosis and immediate quarantine of patients; 2) immediate vaccination of all contacts of any patient diagnosed with smallpox infection to interrupt the virus usual pattern of contagion.

The WHOs program was extremely successful, and after the last naturally occurring case of smallpox was resolved in Somalia in 1977, the virus was declared eradicated worldwide in May 1980. Two laboratories (in Atlanta, Georgia, and in Moscow, Russia) retain samples of the smallpox virus. Remaining concerns include the possibility of smallpox virus being utilized in a situation of biological warfare, or the remote

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, ending its existence.

Hemorrhage Severe, massive bleeding which is difficult to control.

Lesion The tissue disruption or the loss of function caused by a particular disease process.

Papules Firm bumps on the skin.

chance that smallpox virus could somehow escape from the laboratories which are storing it. For these reasons, large quantities of vaccine are stored in different countries around the world. In the U.S., researchers, members of the military, key health personnel, and first responders in the community are vaccinated so that response to any future threat by the smallpox virus can be prompt.

Resources

BOOKS

Cormican, M.G. and M.A. Pfaller. Molecular Pathology of Infectious Diseases, in Clinical Diagnosis and Management by Laboratory Methods. 20th ed. Philadelphia: W. B. Saunders, 2001.

Finn, Elizabeth A. Pox Americana: Great Smallpox Epidemic of 1775-82. New York: Hill & Wang, 2001.

Jenner, Edward, and Herve Bazin. Andrew Morgan, and Glenise Morgan, trans. The Eradication of Small Pox: Edward Jenner and the First and Only Eradication of a Human Infectious Disease. San Diego: Academic Press, 2000.

Kobayashi, G., Patrick R. Murray, Ken Rosenthal, and Michael Pfaller. Medical Microbiology. St. Louis, MO: Mosby, 2003.

Richman, D.D., and R.J. Whitley. Clinical Virology. 2nd ed. Washington: American Society for Microbiology, 2002.

Tucker, Jonathan B. The Once and Future Threat of Smallpox. New York: Atlantic Monthly Press, 2001.

PERIODICALS

Jezek, Z. 20 Years Without Smallpox. Epidemiology, Microbiology, and Imunology 49, no. 3 (2000): 95-102

Levin, N. A., and B. B. Wilson. Cowpox Infection, Human. eMedicine Journal no. 2 (December 2001): 1-8.

Robert, J. The Public And The Smallpox Threat. New England Journal Of Medicine 348 no.5 (2003): 426-432.

OTHER

Centers for Disease Control and Prevention. Smallpox Disease Overview. <http://www.bt.cdc.gov/agent/smallpox/overview/disease-facts.asp> (accessed on November 26, 2006).

Rosalyn Carson-DeWitt

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Smallpox

Smallpox

Introduction

Disease History, Characteristics, and Transmission

Scope and Distribution

Treatment and Prevention

Impacts and Issues

Primary Source Connection

BIBLIOGRAPHY

Introduction

Smallpox is a infectious disease caused by a virus. It was eradicated by 1980 thanks to a global vaccination program, but stocks of variola virus are still held by at least two governments, those of the United States and the Russian Federation. The smallpox virus, also called the variola virus or simply variola, is most often spread by ingestion of virus particles in saliva, either by direct contact or through inhaling droplets dispersed in the air by coughing. When ingested, the smallpox virus first infects the tissues of the throat and nasal cavities, followed by the blood and lymph nodes. About 12 days after infection, a variety of flulike symptoms appear, including fever. Pustules (pus-filled lumps) develop on the skin and are painful at first, then itchy. The more deadly of variola's two varieties, Variola major, kills about 30% of the people that it infects. Sixty-five percent to 80% of those that do survive the disease are disfigured by pitted scars (pockmarks). Some survivors are also blinded by scarring of the retina. Before a vaccine was developed, smallpox was one of the most common causes of blindness worldwide.

Disease History, Characteristics, and Transmission

History

The evolutionary origin of the variola (smallpox) virus, a member of the genus Orthopoxvirus, family Poxviridae, is still obscure. It probably began as a virus in rodents and first infected humans in Africa about 12,000 years ago. The oldest historical reference is in a Chinese document dating to the fourth century. The name “variola,” from the Latin for “spotted,” dates to the sixth century. The term “smallpox” dates to the 1400s, when it was used to distinguish smallpox from syphilis (the “great pox”).

North and South America were free of smallpox until European explorers arrived in the late 1400s. The disease soon spread to the Native American population, which had a much higher mortality rate than the Old World population, probably because there had been no history of natural selection for resistance to the disease. Some historians estimate that 90% of the population of the New World was killed by smallpox. For example, the Aztec population in South America fell from 25 million in 1519 to only 3 million in 1569. Smallpox was not originally spread deliberately by the Europeans, although in the French and Indian wars of the mid-1700s British military forces gave smallpox-infected blankets to Indians who were cooperating with the French—one of the earliest recorded efforts at biological warfare.

In 1796, English physician Edward Jenner (1749– 1823) showed that inoculating a person with pus from a cowpox lesion could prevent smallpox. Inoculation had been discovered before—the earliest known use of smallpox inoculation dates to about 1000 BC, in India—but the idea of inoculation with the harmless cowpox virus had not yet been put forward in Europe by somebody with the professional and class standing to establish it as a known medical fact.

At the time of Jenner's work, smallpox was killing about 400,000 people a year in Europe and millions worldwide. The practice of variolation had already been used to fight smallpox for some decades in Europe and for centuries in Asia. Variolation (named after the disease, variola—the existence of viruses was not yet understood) involved infecting a healthy person with smallpox from a mild case of the disease, either by inserting smallpox-scab material into the nostrils or by rubbing it onto a scratch on the skin. People inoculated in this way were far less likely to die from the more severe form of smallpox than were un-inoculated people. However, there was still a significant death rate from smallpox contracted through variolation (1–2%). Jenner's method of inoculation with cowpox virus was much safer. Although his views were not accepted for a few years, they did catch on. Over 100,000 inhabitants of Britain had been vaccinated with cowpox by 1800 and the British Parliament passed the Vaccination Act in 1840 to make vaccination of infants mandatory and to outlaw variolation. Mandatory smallpox vaccination of children soon became the standard in industrialized countries.

So successful was vaccination that the disease was eradicated from prosperous countries. The last case of smallpox in the United States occurred in 1949. At that time, smallpox was still infecting about 50 million people every year worldwide, about 30% of whom died. Thanks to vaccination, the number of infections dropped to about 15 million per year by 1967. In that year, the World Health Organization (WHO) of the United Nations started a program—the WHO Intensified Smallpox Eradication Program—to eliminate smallpox completely. In 1972, the United States began phasing out mandatory vaccination of schoolchildren. In 1977, the last natural case of smallpox on Earth was seen in Somalia, and in 1980, WHO declared that the eradication campaign had been a success. Smallpox had become the first (and, as of 2007, still the only) major infectious disease to be completely eradicated by human effort.

Characteristics

Smallpox occurs in two forms, variola major and variola minor. Both forms cause similar symptoms, but variola minor is fatal only about 1–2% of the time, compared to 30% or higher for variola major. These two varieties of variola have been recognized for centuries, even before the viral nature of the disease was understood. The two varieties of virus are similar enough that immunity to one confers immunity to the other. Variolation with scabs or pus from mild smallpox cases—an ancient method of immunizing people against smallpox—usually involved infected people with variola minor, granting them immunity from variola major with a fairly low risk of death from the treatment.

The variola virus is most often caught by inhalation of saliva droplets coughed out by a person who already has the disease. Virus particles lodge in the nasal cavities or throat and infect those tissues first, then grow in the lymph nodes nearest the site of infection. (Lymph nodes are small, bean-shaped organs that filter lymph, a clear fluid that is drained from tissues through the system of lymphatic vessels and then returned to the blood.) The patient has no symptoms during this phase of the disease. After three or four days, virus particles spread through the bloodstream to the bone marrow, spleen, and other parts of the lymphatic system, where they multiply. The smallpox virus, like all viruses, multiplies by tricking body cells into manufacturing more virus particles, using genetic material supplied by the virus itself. More smallpox virus particles appear in the blood 8–10 days after infection. During these initial phases— termed the incubation period—the patient feels healthy and cannot infect other persons. About 12–14 days after infection (with a range of 7–17 days), the incubation period ends and the next phase of the illness—termed the prodrome, prodromal stage, or preeruptive stage— begins suddenly. In this stage, symptoms appear, but do not yet include the skin eruptions or lesions that make the patient capable of spreading the infection. Prodromal symptoms may include fever and last 2–4 days. After the prodromal stage, the disease can next show four distinct courses or clinical presentations. These are termed ordinary smallpox, modified smallpox, flat smallpox, and hemorrhagic smallpox.

Ordinary Smallpox Ordinary smallpox accounts for about 90% of cases. After the prodromal stage, the fever may drop and the patient feels less sick. The smallpox rash then appears as small red spots (lesions) on the tongue, on the inside of the mouth, and at the back of the throat (on the pharynx). The mouth-and-throat lesions grow, releasing billions of virus particles into the saliva that may then be transmitted to other people. The lesions in the throat trigger coughing, which tends to spread the disease. About 24 hours after the appearance of the mouth-and-throat rash, a rash appears on the skin, first on the face and limbs and then on the trunk. The rashes become lumpier and fill with fluid. In about a week the lumps, now filled with pus and called pustules, have become round, raised, and hard to the touch, like beads under the skin. Generally, the more severe the rash, the greater the chance that the patient will die. In another week the fluid in the pustules has been absorbed and a crust or scab begins to form over them. Finally, a week later, the crusts fall off, leaving bleached skin and indented scars. At this point the patient has ceased to be infectious.

Modified Smallpox Modified smallpox is a milder form of the disease that sometimes occurs in persons who have been vaccinated. The fever does not return after the prodromal phase and the rash appears more quickly but produces fewer and smaller lesions. This form of the disease is almost never fatal.

Flat Smallpox In flat smallpox, the raised lesions or pustules of ordinary smallpox do not develop on the skin. This form of the disease has been observed in a study in India to occur about 5–10% of the time, usually in children. The prodromic stage is more severe in flat smallpox, and so is the rash on the tongue and at the back of the throat. The skin lesions appear slowly and are flatter than in ordinary smallpox. This form of the disease is usually fatal.

Hemorrhagic Smallpox Hemorrhagic smallpox occurs about 2% of the time in India. It is called “hemorrhagic” because to hemorrhage means to bleed; patients with this form of smallpox begin to bleed—sometimes only a few days into the course of the disease—in the eyes, gums, mouth, and skin lesions. Death usually occurs about a week after the onset of symptoms, before the skin rash has had a chance to develop much.

Transmission

Variola virus is quite virulent, that is, easy to spread from one person to another. Only a small number of virus particles need be taken into the body to cause the disease. Virus concentrations in the saliva and mucus are highest during the first week of symptomatic illness (after the prodromic stage), and it is during this time that the patient is most infectious. However, the patient remains infectious until all crusts have separated from the healing pustules on the skin. Virus particles can be transmitted through the air or by direct contact with the patient or materials they have touched. They do not enter through the skin, but may be transferred to the mucous membranes of the mouth, eyes, or nose by hand contact.

Scope and Distribution

Smallpox infection no longer occurs naturally. As of 2007, the only stocks of the virus known to exist are held by the governments of Russia and the United States.

Treatment and Prevention

Since smallpox is caused by a virus, it cannot be treated using antibiotics (which kill only bacteria). Nor, as of 2006, had any antiviral drug had been approved by the U.S. Food and Drug Administration for the treatment of smallpox. The Centers for Disease Control and Prevention suggested that the antiviral drug cidofovir might be used for smallpox under the supervision of an infectious diseases specialist, but warns that the drug can injure the kidneys. The usual treatment is strictly supportive: the patient is kept clean, sheltered, and hydrated, while their own immune system fights the infection.

The main method of preventing transmission of smallpox is to avoid having other people ingest the virus. To this end, all persons having contact with a smallpox patient should wear fitted breathing masks and disposable gloves, gowns, and shoes. Breathing masks prevent the inhalation of virus particles.

Where high-technology medical settings are available, a smallpox patient should be isolated in a room with negative pressure, that is, one where the air-circulation system draws air into the room and filters it before pumping it out rather than allowing it to escape. This is because smallpox transmission can be caused by virus particles conveyed in tiny, airborne particles. Air that has contacted a smallpox patient must be assumed to be potentially carrying the disease.

WORDS TO KNOW

ERADICATION: The process of destroying or eliminating a microorganism or disease.

PRODROME: A prodrome of a disease is a symptom indicating the disease's onset; it may also be called a prodroma. For example, painful swallowing is often a prodrome of infection with a cold virus.

VARIOLATION: Variolation was the pre-modern practice of deliberately infecting a person with smallpox in order to make them immune to a more serious form of the disease. It was dangerous, but did confer immunity on survivors.

The primary method of preventing smallpox infection is the smallpox vaccine. It is not made using smallpox virus, but a live vaccinia virus strain. The standard vaccine available today was developed in the early 1980s and is supplied as a freeze-dried powder in 100-dose units. The dry vaccine mixture contains several antibiotics and is mixed with a special liquid consisting of water, glycerin, and phenol as a preservative. The vaccine is guaranteed to confer immunity for at least 10 years, but there is evidence that it may confer immunity for far longer. About 15 million doses of this vaccine are stockpiled in the United States as of 2007; this number could be increased in an emergency by diluting the vaccine to increase its volume by a factor as great as 5.

Smallpox vaccine causes a number of medical complications, but death is rare. It should not be taken by pregnant women, because the vaccinia virus can cause fetal vaccinia, an infection of the fetus with the vaccinia virus. This usually causes stillbirth or death of the child soon after birth.

Impacts and Issues

The eradication of smallpox was one of the major public health success stories of the twentieth century. This effort demonstrated that international cooperation on important health issues could be achieved. Moreover, it also demonstrated that it is possible to eradicate an infectious disease with an effective vaccination program, and that vaccination is a useful preventative method in the fight against infectious diseases. Smallpox stocks still exist, however, and if released into the environment, could cause an epidemic in an unvaccinated population. As of 2007, a large but unknown percentage of Americans were not immune to smallpox. This uncertainty arises because nobody is sure how much immunity is still conferred by immunizations received before 1972.

SMALLPOX: AN ANCIENT DISEASE

As a disease, smallpox has an ancient history. Studies of the mummy of Pharaoh Ramses V, who died in 1157 BC, revealed symptoms of smallpox infection.

Smallpox has long been considered as a biological weapon of war or terror. In the mid–1700s, British army commanders in what is now Canada gave smallpox-infested blankets to Indians who were collaborating with the French (the enemies of the British at that time). Systematic bioweapons research by the U.S., Japan, the Soviet Union, and other countries began during World War II but concentrated on bacteria (e.g., anthrax) rather than viruses for some years. In the 1950s, American bioweapon developers, concerned that the Soviet Union might be developing smallpox and other viruses as well, began studying techniques for producing freezedried smallpox powder that could be efficiently spread over a wide area. In the mid-1960s, Army planners approached the U.S. bioweapons labs at Fort Detrick, Maryland, to see whether biological weapons could be used to attack military traffic between North and South Vietnam. Smallpox was considered the best candidate, but the idea was abandoned because U.S. use of biological warfare might be exposed, North Vietnam might retaliate in kind, and the disease might spread to friendly forces. At about this time, Soviet agents secretly sampled highly virulent smallpox strains in India for use in the large Soviet bioweapons program. In 1969, President Richard Nixon abolished the U.S. biological warfare program and supported an international ban on biological weapons. This was formalized as the 1972 Biological and Toxic Weapons Convention Treaty, which was eventually signed by the Soviet Union and most of the rest of the countries of the world.

After biological attacks using anthrax occurred in the United States in 2001, the issue of smallpox as a potential agent of biological terror again surfaced. In the United States, researchers, members of the military, key health personnel, and first responders in the community were vaccinated against smallpox so that response to any future threat by the smallpox virus can be prompt. Large reserves of smallpox vaccine are maintained by many countries in the developed world and the World Health Organization.

Today, the smallpox virus is only known to exist in two secure repositories, both authorized by WHO: one is at the Centers for Disease Control and Prevention in the United States and the other is at the State Research Center of Virology and Biotechnology of the Russian Federation in Siberia. Debate continues on whether the last remaining stocks of smallpox virus should be used for research or destroyed.

Primary Source Connection

Disease outbreaks are reported by World Health Organization (WHO, Epidemic and Pandemic Alert and Response (EPR), Disease Outbreak News.

WHO maintains the EPR as a “major pillar of global health security aimed at the detection, verification and containment of epidemics. In the event of the intentional release of a biological agent these activities would be vital to effective international containment efforts.”

As the bulletin below indicates, the system is also used to clarify information and allay fear concerning infectious agents that could be used as biological weapons.

ACCIDENTAL EXPOSURE TO SMALLPOX VACCINE IN THE RUSSIAN FEDERATION

20 JUNE 2000

DISEASE OUTBREAK REPORTED

The recent report of illness amongst 8 young children in Vladivostock who had played with discarded ampoules of smallpox vaccine has now been confirmed by the Ministry of Health of the Russian Federation. Laboratory confirmation of the illness in the children is being sought. The report has evoked much public concern. In some of the reports, there were misconceptions about the components of the vaccine used to prevent smallpox, and about why any country might still be retaining stocks of smallpox vaccine. This note aims to clarify these issues.

  1. Smallpox vaccine is not made from smallpox virus. The vaccine which was used for centuries to vaccinate against smallpox was not made from smallpox, but from vaccinia virus. Vaccinia is a different virus from the virus which causes smallpox. However, it is a member of the same family of viruses to which the smallpox virus belongs. The smallpox virus is also known as variola virus. Mass vaccinations with smallpox vaccine made from vaccinia virus led to the eradication of smallpox announced by WHO in 1980. People vaccinated with smallpox vaccine (vaccinia) develop reactions to it which range from mild and transient to severe, and very rarely, fatal.
  2. Two countries still keep smallpox virus (variola) stocks. Although smallpox disease has been eradicated, two laboratories still hold stocks of smallpox virus (variola). These are the WHO Collaborating Centres in Atlanta, USA and Koltsovo, Russian Federation.
  3. Many countries still hold smallpox vaccine (vaccinia) stocks. WHO recommends that countries which still have stocks of smallpox vaccine (vaccinia) maintain these stocks. This recommendation has been made for two reasons. Firstly, small amounts of vaccine are still needed to vaccinate laboratory personnel handling vaccinia virus and other members of this virus family. Some of these viruses are found in nature and cause illness among animals, and some are used in research to make new, safer vaccines against a variety of infectious diseases. Secondly, smallpox vaccine (vaccinia) will also be needed in case of a deliberate or accidental release of smallpox virus (variola), which is a very unlikely event but currently of great concern to some countries. For further information on this topic, see the summary of the recent meeting of the WHO Advisory Committee on Variola Virus Research, published in the Weekly Epidemiological Record.
  4. Disposal of biological materials and pharmaceuticals. All biological materials and pharmaceuticals such as vaccines, drugs and diagnostic specimens should be disposed of safely. Some may require inactivation before disposal. This can be accomplished by autoclaving or incineration.

World Health Organization

WORLD HEALTH ORGANIZATION, EPIDEMIC AND PANDEMIC ALERT AND RESPONSE (EPR), DISEASE OUTBREAK NEWS “ACCIDENTAL EXPOSURE TO SMALLPOX VACCINE IN THE RUSSIAN FEDERATION: 20 JUNE, 2000.” <HTTP://WWW.WHO.INT/CSR/DON/2000_06_20E/EN/INDEX.HTML> (ACCESSED APRIL 12, 2007)

See AlsoSmallpox Eradication and Storage; Viral Disease; World Health Organization (WHO).

BIBLIOGRAPHY

Books

Ian, Glynn, and Jennifer Glynn. Life and Death of Smallpox. London: Profile Books, 2005.

Miller, Judith, et al. Germs: Biological Weapons and America's Secret War. New York: Simon & Schuster, 2002.

Rodriguez, Ana Maria. Edward Jenner: Conqueror of Smallpox. Springfield, NJ: Enslow, 2006.

Periodicals

Cohen, Jon. “Leaks Produce a Torrent of Denials.” Science 298 (2002): 1313–1314.

Esposito, Joseph J., et al. “Genome Sequence Diversity and Clues to the Evolution of Variola (Smallpox) Virus.” Science 313 (2006): 807–812.

Koopman, Jim. “Controlling Smallpox.” Science 298 (2002): 1342–1344.

Web Sites

Centers for Disease Control and Prevention. “Emergency Preparedness and Response: Smallpox.” <http://www.bt.cdc.gov/agent/smallpox/> (accessed February 21, 2007).

Journal of Young Investigators. “Smallpox: Historical Review of a Potential Bioterrorist Tool.” September 2002. <http://www.jyi.org/volumes/volume6/issue3/features/bourzac.html> (accessed February 21, 2007).

World Health. “Smallpox.” <http://www.who.int/mediacentre/factsheets/smallpox/en/> (accessed February 20, 2007).

Larry Gilman

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Smallpox

Smallpox

Smallpox is an infection caused by the variola virus , a member of the poxvirus family. Throughout history, smallpox has caused huge epidemics resulting in great suffering and enormous death tolls worldwide. In 1980, the World Health Organization (WHO) announced that a massive program of vaccination against the disease had resulted in the complete eradication of the virus (with the exception of stored virus in two laboratories).


Symptoms and progression of the disease

Smallpox was an extraordinarily contagious disease. The virus spread from contact with victims, as well as from contaminated air droplets and even from objects used by other smallpox victims (books, blankets, etc.).

After acquisition of the virus, there was a 12-14 day incubation period, during which the virus multiplied, but no symptoms appeared. The onset of symptoms occurred suddenly and included fever and chills, muscle aches, and a flat, reddish-purple rash on the chest, abdomen, and back. These symptoms lasted about three days, after which the rash faded and the fever dropped. A day or two later, the fever would return, along with a bumpy rash starting on the feet, hands, and face. This rash progressed from the feet along the legs, from the hands along the arms, and from the face down the neck, ultimately reaching and including the chest, abdomen and back. The individual bumps, or papules, filled with clear fluid, and, over the course of 10-12 days, became pus-filled. The pox would eventually scab over, and when the scab fell off, left behind was a pock or pit which remained as a permanent scar.

Death from smallpox usually followed complications such as bacterial infection of the open skin lesions, pneumonia , or bone infections. A very severe and quickly fatal form of smallpox was called "sledgehammer smallpox," and resulted in hemorrhage from the skin lesions, as well as from the mouth, nose, and other areas of the body.

No treatment was ever discovered to treat the symptoms of smallpox, or to shorten the course of the disease.


Diagnosis

Diagnosis , up until the eradication of smallpox, consisted of using an electron microscope to identify the virus in fluid from the papules, in the patient's urine, or in the blood prior to the appearance of the papular rash.


The discovery of the vaccine

Fascinating accounts have been written describing ways in which different peoples tried to vaccinate themselves against smallpox. In China, India, and the Americas, from about the tenth century, it was noted that individuals
who had had even a mild case of smallpox could not be infected again. Material from people ill with smallpox (fluid or pus from the papules, the scabs) 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 the community. In fact, such crude vaccinations against smallpox 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 variola) appeared to be immune to smallpox. He created an immunization against smallpox that used the pussy material 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 smallpox vaccine , which utilizes the vaccinia virus-another close relative of variola.

Global eradication of smallpox virus

Smallpox is dangerous only to human beings. Animals and insects can neither be infected by smallpox, nor carry the virus in any form. Humans cannot carry the virus, unless they are symptomatic. These important facts entered into the 1967 decision by the WHO to attempt worldwide eradication of the smallpox virus.

The methods used in WHO's eradication program were simple: 1) careful surveillance for all smallpox infections worldwide to allow for quick diagnosis and immediate quarantine of patients; 2) immediate vaccination of all contacts of any patient diagnosed with smallpox infection to interrupt the virus' usual pattern of contagion.

The WHO's program was extremely successful, and the virus was declared eradicated worldwide in May of 1980. Two laboratories (in Atlanta, Georgia, and in Moscow, Russia) retain samples of the smallpox virus, because some level of concern exists that another poxvirus could mutate (undergo genetic changes) and cause human infection. Other areas of concern include the possibility of smallpox virus being utilized in a situation of biological warfare , or the remote chance that smallpox virus could somehow escape from the laboratories which are storing it. For these reasons, large quantities of vaccine are stored in different countries around the world, so that response to any future threat by the smallpox virus can be prompt.


Resources

books

Cormican, M.G., and M.A. Pfaller. "Molecular Pathology of Infectious Diseases," in Clinical Diagnosis and Management by Laboratory Methods. 20th ed. Philadelphia: W. B. Saunders, 2001.

Finn, Elizabeth A. Pox Americana: Great Smallpox Epidemic of 1775-82. New York: Hill & Wang, 2001

Flint, S.J., et al. Principles of Virology: Molecular Biology, Pathogenesis, and Control Washington: American Society for Microbiology, 1999.

Isselbacher, Kurt J., et al. Harrison's Principles of Internal Medicine. New York: McGraw Hill, 1994.

Jenner, Edward, and Herve Bazin. Andrew Morgan, and Glenise Morgan, trans. The Eradication of Small Pox: Edward Jenner and the First and Only Eradication of a Human Infectious Disease. San Diego: Academic Press, 2000.

Kobayashi, G., Patrick R. Murray, Ken Rosenthal, and Michael Pfaller. Medical Microbiology. St. Louis, MO: Mosby, 2003.

Lyons, Albert S., and R. Joseph Petrucelli, II. Medicine: An Illustrated History. New York: Harry N. Abrams, Inc., 1987.

Mandell, Douglas, et al. Principles and Practice of Infectious Diseases. New York: Churchill Livingstone, 1995.

Richman, D.D., and R.J. Whitley. Clinical Virology. 2nd ed. Washington: American Society for Microbiology, 2002.

Tucker, Jonathan B. The Once and Future Threat of Smallpox. New York: Atlantic Monthly Press, 2001.

periodicals

Jezek, Z. "20 Years Without Smallpox." Epidemiology, Microbiology, and Imunology 49, no. 3 (2000): 95-102

Levin, N. A., and B. B. Wilson. "Cowpox Infection, Human." eMedicine Journal no. 2 (December 2001): 1-8.

Robert, J. "The Public And The Smallpox Threat." New England Journal Of Medicine 348 no.5 (2003): 426-432.


Rosalyn Carson-DeWitt

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, ending its existence.

Hemorrhage

—Very severe, massive bleeding which is difficult to control.

Lesion

—The tissue disruption or the loss of function caused by a particular disease process.

Papules

—Firm bumps on the skin.

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Smallpox

SMALLPOX

Smallpox is a highly infectious disease whose normal mode of transmission is through inhalation. Case mortality can be as high as 30 percent, and the disease is also feared for the permanent scarring it leaves. It was introduced to the Americas by Spanish explorers. Credited with the extinction of the indigenous Amerindian populations of the Caribbean islands by 1519, smallpox also contributed to the conquest of Mexico and Peru. In the 1760s Sir Jeffrey Amherst ordered the deliberate spread of the disease among Native Americans participating in Pontiac's War in western Pennsylvania.

The British also inadvertently brought smallpox to the territory of what would become the United States. As early as 1633, William Bradford noticed severe cases among Indians living near the Plymouth colony. The spread-out population of the English colonies—with regular replenishment of new smallpox cases disembarking from transatlantic voyages—meant that smallpox was sporadic but also more dangerous to nonimmune populations. Throughout the eighteenth century, natural outbreaks continued to afflict Indian populations. In 1763, for example, a group of Indian converts to Christianity who lived in Philadelphia lost one-third of their members to the disease.

Many Old-World cultures developed the practice of deliberately inoculating smallpox in order to confer lifetime immunity. Around the same time that this procedure was brought to England, the Puritan clergyman Cotton Mather independently learned of it from his slave, Onesimus. With the assistance of the physician Zabdiel Boylston, Mather began inoculating in Boston during an epidemic in 1721. During a 1731 epidemic in Philadelphia, Benjamin Franklin hailed inoculation, and over the course of the following decades, the practice became more popular in the Philadelphia region than elsewhere in the colonies.

Inoculation was a dangerous procedure since it bore the risk both of killing the inoculated person and of spreading the disease. As a consequence the procedure was generally restricted to more substantial members of the community, who could be more easily isolated and better cared for. In 1774 Philadelphians established a Society for the Inoculation of the Poor, whose work was soon suspended because nonimmune delegates to the Continental Congress (mainly from the South) were concerned about infection. During the War of Independence, George Washington had himself and his troops inoculated, in part because the British were rumored to be deliberately spreading smallpox. The fact that an eminent Virginian encouraged the practice may have led to inoculation becoming official policy of the Continental Congress.

In 1798 Edward Jenner published his Inquiries, detailing how inoculation with the relatively mild cowpox (or vaccinia) would immunize the patient against smallpox. Inoculation with smallpox now became known as "variolation" (variola being the Latin name for smallpox), and was gradually replaced by vaccination. Vaccination was introduced to the new Republic in 1800 by Benjamin Waterhouse of the Harvard Medical School, and President Thomas Jefferson immediately became an advocate of the new procedure. In 1802 Valentine Seaman of New York organized a system to provide free vaccination to the poor.

During his administration, James Madison encouraged the distribution of smallpox vaccine, and public health statutes from the colonial period into the early nineteenth century were concerned primarily with isolating smallpox patients among immigrants. In Pennsylvania, for example, it was only in 1824—when variolation was outlawed—that smallpox became a reportable disease and the isolation hospital within the city began receiving smallpox patients.

Although it had its opponents, vaccination gained general acceptance rapidly, and smallpox incidence in the United States declined significantly during the first three decades of the nineteenth century. Unfortunately this led to complacency, and after 1830 the United States experienced a number of devastating epidemics.

See alsoDeath and Dying; Epidemics; Health and Disease; Medicine .

bibliography

Fenn, Elizabeth Anne. Pox Americana: The Great Smallpox Epidemic of 1775–82. New York: Hill and Wang, 2001.

Stearn, E. Wagner, and Allen E. Stearn. The Effect of Smallpox on the Destiny of the Amerindian. Boston: Bruce Humphries, 1945.

Wolman, Roslyn Stone. "A Tale of Two Colonial Cities: Inoculation against Smallpox in Philadelphia and in Boston." Transactions and Studies of the College of Physicians of Philadelphia 45, no. 6 (1978): 338–347.

Edward T. Morman

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Smallpox

SMALLPOX

inoculation and vaccination
opposition to vaccination
bibliography

Smallpox is an acute infectious disease caused by the variola virus. It appears in many forms, some which are very mild and others that are usually fatal. Although the disease has been eradicated since 1977, during the eighteenth century, smallpox became one of Europe's most feared diseases, usually appearing in cycles of between five to seven years. Symptoms include headache, high fever, and vomiting; after the fever subsides, red spots appear that become filled with pus. Scabs formed by the drying out of the pustules fall off between one and three weeks later, leaving permanent scars. Some survivors were left blind by the disease and nearly all were disfigured to some degree.

It is hard to say whether deaths from smallpox actually increased or merely became more visible following the retreat of plague from western Europe. Yet there is some evidence to suggest that epidemics—like those that ravaged Europe in the 1750s—became more common as commercial and agricultural revolutions united hitherto remote populations.

inoculation and vaccination

More attention began to be paid to the best means of treating and preventing the disease. Early in the century, the practice of inoculation—the use of the dried crusts of smallpox pustules to induce a mild form of the disease—was introduced into Europe from the Middle East. The practice could confer lifelong immunity but it was risky and many of those inoculated died, either from smallpox or some other infection introduced by the inoculator's lancet.

The appeal of inoculation was understandably limited. Most enthusiasm was shown by the aristocracy, which dreaded scarring from smallpox as something that adversely affected marriage prospects and, hence, the continuation of their dynasties. Outside the royal courts the practice thrived only where it was actively promoted by private individuals, such as improving landlords and philanthropic doctors. Inoculation was never embraced by the state and there is little evidence that it contributed materially to the stabilization of mortality that occurred in many European countries during the eighteenth century.

The advent of vaccination, by contrast, made an enormous difference. Pioneered by an English doctor, Edward Jenner (1749–1823), vaccination was based on the observation that milkmaids who contracted cowpox in the course of their work were seldom afflicted by the more serious disease, smallpox. In 1796 Jenner designed an experiment to test this, inoculating a local boy with cowpox and then with smallpox; he found that no symptoms of smallpox appeared. Further experiments confirmed these findings, and Jenner's new technique of "vaccination" was rapidly accepted by many medical practitioners and statesmen, including the French emperor Napoleon I and Thomas Jefferson. Indeed, many European states were quick to promote vaccination as a way of preventing costly and unnecessary deaths, and it soon became compulsory among key groups such as soldiers and sailors. Within a decade or so after Jenner's discovery, some local authorities in Britain were demanding vaccination before administering poor relief, while states such as Bavaria made it compulsory for those entering apprenticeships.

Thereafter, compulsory vaccination spread to other sections of the population, but with some national differences. One might expect authoritarian states to have proceeded more rapidly than others, but this was not always the case. Britain, which was famed for its liberalism, was quicker to introduce vaccination than was autocratic Prussia, for instance. In 1840 Britain was the first country to ban inoculation, and in 1853 it passed an act making vaccination compulsory within three months of birth. Prussia felt no need to follow suit at that time because its provisions for voluntary vaccination were so extensive.

opposition to vaccination

Yet vaccination had numerous detractors. Its supporters found it difficult to explain the fact that some of those who had been vaccinated were still susceptible to smallpox. Such cases were comparatively few but they were sufficient to raise doubts about the efficacy of the operation among the public; at least until the introduction of revaccination later in the century. Infection was another serious problem. Multiple incisions were made with lancets and lymph from a previously vaccinated child was rubbed into them. This arm-to-arm method carried with it the risk of infection with diseases like erysipelas—a problem that was overcome in the 1880s and 1890s with the widespread use of lymph harvested from cows and the addition of glycerine, which killed many bacterial infections.

As vaccination was promoted more aggressively by the state, rumors abounded that governments were seeking to poison the lower classes or to "brand" them like cattle. There were also protests against the fines imposed on those who refused to bring children for vaccination. Nor was opposition confined to the working class. Concerns were expressed generally about compulsory vaccination as an infringement of civil liberties, while in some countries, especially Germany, advocates of holistic medicine argued that vaccination was unnecessary and unnatural, as it violated the integrity of the human body.

Opposition to vaccination grew in the face of more concerted efforts to prevent the disease, in the wake of the dreadful epidemic that afflicted Europe in the early 1870s. The epidemic appears to have begun in France immediately before the war with Prussia, and it spread via French prisoners of war to Prussian civilians. Claiming the lives of around half a million people, the epidemic spurred newly unified Germany to introduce compulsory vaccination and revaccination in 1874. The act provoked considerable resistance, and petitions amounting to over thirty thousand signatures were sent to the Reichstag. Many in France also wished to move toward compulsion, especially in view of the fact that the Prussian army (in which vaccination had been compulsory since 1834) suffered fewer than three hundred deaths from smallpox by comparison with over twenty-three thousand among French troops. Yet political conditions in the new Third Republic prevented the passage of such legislation until 1902.

Despite widespread resistance to compulsion, anti-vaccinationists won few victories. Only in Britain did they enjoy some success and then because their demands were moderate—the introduction of opt-outs for those who refused vaccination on grounds of conscience. Most European countries experienced a marked decline in smallpox mortality between 1880 and 1914. The disease continued to be a major cause of death only in Russia, Spain, Italy, and Portugal, which had poorly developed systems of vaccination. Other countries experienced falls in mortality consistent with the dates at which legislation was enacted and the rigor with which it was enforced. For example, in 1910 Russia suffered 400,000 recorded deaths from smallpox and Spain 37,000, whereas France had 11,000 and Germany only 386. The disruption caused by World War I inevitably led to an increase in smallpox deaths throughout Europe, with the worst epidemics occurring in countries such as Russia and Italy. Many central and western European countries also experienced epidemics but they were able to prevent the widespread devastation that had followed the war between France and Prussia in 1870. In these countries, smallpox was increasingly perceived as an alien disease, associated either with immigrants from eastern Europe, or with "reservoirs" of infection in Europe's Asian and African colonies.

See alsoJenner, Edward; Public Health; Science and Technology.

bibliography

Baldwin, Peter. Contagion and the State in Europe, 1830– 1930. Cambridge, U.K., 1999.

Cliff, A. D., and Matthew R. Smallman-Raynor. War Epidemics: An Historical Geography of Infectious Diseases in Military Conflict and Civil Strife, 1850–2000. Oxford, U.K., 2004.

Harrison, Mark. Disease and the Modern World: 1500 to the Present Day. Cambridge, U.K., 2004.

Hopkins, Donald R. The Greatest Killer: Smallpox in History. Chicago, 2002.

Porter, D., and R. Porter. "The Politics of Prevention: Anti-Vaccinationism and Public Health in Nineteenth-Century England." Medical History 32 (1988): 231–252.

Razzell, Peter. The Conquest of Smallpox: The Impact of Inoculation on Smallpox Mortality in Eighteenth Century Britain. Sussex, U.K., 1977.

Mark Harrison

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