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smallpox

 
Medical Encyclopedia: Smallpox
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Definition

Smallpox is an infection caused by the virus called variola, a member of the poxvirus family. Throughout all of history, smallpox has been a greatly feared disease, responsible for huge epidemics worldwide, and the cause of great suffering and massive 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 was strictly an infection of human beings. Animals and insects could neither be infected by smallpox, nor carry the virus in any form. Most infections were caused by contact with a person who had already developed the characteristic skin lesions (pox) of the disease, although a person who had a less severe infection (not symptomatic or diagnosable in the usual way) could unwittingly spreading the virus.

— Rosalyn Carson-DeWitt, MD


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Dictionary: small·pox   (smôl'pŏks') pronunciation
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n.
An acute, highly infectious, often fatal disease caused by a poxvirus and characterized by high fever and aches with subsequent widespread eruption of pimples that blister, produce pus, and form pockmarks. Also called variola.


Britannica Concise Encyclopedia: smallpox
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One of the world's most dreaded plagues before 1980, when it was declared eradicated. It was known in ancient China, India, and Egypt. It came to the Western Hemisphere with Europeans in the 16th century and devastated the native population, which lacked resistance. An infectious viral disease only of humans, it causes fever and then a rash of variable severity that blisters and dries up, leaving scars. It is not spread easily, but the virus can survive for long periods outside the body (e.g., in bedding). Edward Jenner developed a vaccine from cowpox. The World Health Organization's eradication project reduced smallpox deaths from two million in 1967 to zero in 1977 – 80. The virus now exists only in laboratories; in some countries it may be under development for purposes of biological warfare.

For more information on smallpox, visit Britannica.com.

Sci-Tech Encyclopedia: Smallpox
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An acute infectious viral disease characterized by severe systemic involvement and a single crop of skin lesions that proceeds through macular, papular, vesicular, and pustular stages. Smallpox is caused by variola virus, a brick-shaped, deoxyribonucleic acid-containing member of the Poxviridae family. Strains of variola virus are indistinguishable antigenically, but have differed in the clinical severity of the disease caused. Following a 13-year worldwide campaign coordinated by the World Health Organization (WHO), smallpox was declared eradicated by the World Health Assembly in May 1980. Smallpox is the first human disease to be eradicated.

Humans were the only reservoir and vector of smallpox. The disease was spread by transfer of the virus in respiratory droplets during face-to-face contact. Before vaccination, persons of all ages were susceptible. It was a winter-spring disease; there was a peak incidence in the drier spring months in the Southern Hemisphere and in the winter months in temperate climates. The spread of smallpox was relatively slow. The incubation period was an average of 10–12 days, with a range of 7–17 days. Fifteen to forty percent of susceptible persons in close contact with an infected individual developed the disease.

There were two main clinically distinct forms of smallpox, variola major and variola minor. Variola major, prominent in Asia and west Africa, was the more severe form, with widespread lesions and case fatality rates of 15–25% in unvaccinated persons, exceeding 40% in children under 1 year. From the early 1960s to 1977, variola minor was prevalent in South America and south and east Africa; manifestations were milder, with a case fatality rate of less than 1%.

There is no specific treatment for the diseases caused by poxviruses. Supportive care for smallpox often included the systemic use of penicillins to minimize secondary bacterial infection of the skin. When lesions occurred on the cornea, an antiviral agent (idoxuridine) was advised.

Edward Jenner, a British general medical practitioner who used cowpox to prevent smallpox in 1796, is credited with the discovery of smallpox vaccine (vaccinia virus). However, the global smallpox eradication program did not rely only on vaccination. Although the strategy for eradication first followed a mass vaccination approach, experience showed that intensive efforts to identify areas of epidemiologic importance, to detect outbreaks and cases, and to contain them would have the greatest effect on interrupting transmission. In 1978, WHO established an International Commission to confirm the absence of smallpox worldwide. The recommendations made by the commission included abandoning routine vaccination except for laboratory workers at special risk. See also Animal virus; Vaccination.

Encyclopedia of Public Health: Smallpox
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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 features—i.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.

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

— JOHN M. LAST


US History Encyclopedia: Smallpox
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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.

 
Columbia Encyclopedia: smallpox
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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 these 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, and WHO agreed to delay the destruction of virus stocks beyond 2002 to allow for the development of new vaccines. 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.

Bibliography

See E. A. Fenn, Pox Americana: The Great Smallpox Epidemic of 1775-1782 (2001), and J. B. Tucker, Scourge (2001).

Intelligence Encyclopedia: Smallpox
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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 12–14 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 10–12 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): 2127–137.

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).

Health Dictionary: smallpox
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An acute and infectious disease caused by a virus and now almost completely eradicated. Smallpox was characterized by high fever and large sores on the body that leave scars.

  • A surface with many blemishes is sometimes said to be “pockmarked” because it resembles the skin of a smallpox sufferer.
  • Smallpox is the first disease of humans to be completely eradicated by a worldwide campaign of inoculation.
  • Today, the smallpox virus exists only in laboratories.
  • The use of smallpox is a major concern in the area of bioterrorism.

    • Bioterrorism Dictionary: smallpox
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    The first infectious disease afflicting humans ever globally eradicated. Smallpox killed 300 million people in the 19th century. Human beings as a whole are extraordinarily susceptible to infection by smallpox right now, precisely because it has been eradicated. Within 48 hours, smallpox could travel from New York to Italy to Baghdad.

    Word Tutor: smallpox
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    pronunciation

    IN BRIEF: n. - A highly contagious viral disease characterized by fever and weakness and skin eruption with pustules that form scabs that slough off leaving scars.

    pronunciation After a 20-year study, Dr. Kempe recommends abolishing smallpox vaccination. — Dr. Charles Henry Kempe, Source: The Evening Bulletin, Philadelphia, May 7, 1965

    Wikipedia: Smallpox
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    "Variola" redirects here. For other uses, see Variola (disambiguation).
    Smallpox
    Classification and external resources

    Boy with smallpox
    ICD-10 B03.
    ICD-9 050
    DiseasesDB 12219
    MedlinePlus 001356
    eMedicine emerg/885
    MeSH D012899
    Variola virus (Smallpox)
    Virus classification
    Group: Group I (dsDNA)
    Family: Poxviridae
    Genus: Orthopoxvirus
    Species: Variola vera

    Smallpox is an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor.[1] The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning spotted, or varus, meaning "pimple". The term "smallpox" was first used in Europe in the 15th century to distinguish variola from the "great pox" (syphilis).[2]

    Smallpox localizes in small blood vessels of the skin and in the mouth and throat. In the skin, this results in a characteristic maculopapular rash, and later, raised fluid-filled blisters. V. major produces a more serious disease and has an overall mortality rate of 30–35%. V. minor causes a milder form of disease (also known as alastrim, cottonpox, milkpox, whitepox, and Cuban itch) which kills about 1% of its victims.[3][4] Long-term complications of V. major infection include characteristic scars, commonly on the face, which occur in 65–85% of survivors.[5] Blindness resulting from corneal ulceration and scarring, and limb deformities due to arthritis and osteomyelitis are less common complications, seen in about 2–5% of cases.

    Smallpox is believed to have emerged in human populations about 10,000 BC.[2] The disease killed an estimated 400,000 Europeans each year during the 18th century (including five monarchs), and was responsible for a third of all blindness.[3] Of all those infected, 20–60%—and over 80% of infected children—died from the disease.[6]

    During the 20th century, it is estimated that smallpox was responsible for 300–500 million deaths.[7][8][9] In the early 1950s an estimated 50 million cases of smallpox occurred in the world each year.[10] As recently as 1967, the World Health Organization (WHO) estimated that 15 million people contracted the disease and that two million died in that year.[10] After successful vaccination campaigns throughout the 19th and 20th centuries, the WHO certified the eradication of smallpox in December 1979.[10] To this day, smallpox is the only human infectious disease to have been completely eradicated.[11]

    Contents

    Cause

    Smallpox is caused by infection with variola virus, which belongs to the genus Orthopoxvirus, the family Poxviridae, and subfamily chordopoxvirinae. Variola is a large brick-shaped virus measuring approximately 302 to 350 nanometers by 244 to 270 nm,[12] with a single linear double stranded DNA genome 186 kilobase pairs (kbp) in size and containing a hairpin loop at each end.[13][14] The two classic varieties of smallpox are variola major and variola minor. The closest viral relative is molluscum contagiosum, which, like smallpox, infects only humans. However, unlike variola species, molluscum infection is benign.

    Four orthopoxviruses cause infection in humans: variola, vaccinia, cowpox, and monkeypox. Variola virus infects only humans in nature, although primates and other animals have been infected in a laboratory setting. Vaccinia, cowpox, and monkeypox viruses can infect both humans and other animals in nature.[15]

    The lifecycle of poxviruses is complicated by having multiple infectious forms, with differing mechanisms of cell entry. Poxviruses are unique among DNA viruses in that they replicate in the cytoplasm of the cell rather than in the nucleus. In order to replicate, poxviruses produce a variety of specialized proteins not produced by other DNA viruses, the most important of which is a viral-associated DNA-dependent RNA polymerase. Both enveloped and unenveloped virions are infectious. The viral envelope is made of modified Golgi membranes containing viral-specific polypeptides, including hemagglutinin.[13] Infection with either variola major or variola minor confers immunity against the other.[4]

    Evolution

    Smallpox appears to have evolved from an African rodent-borne variola-like virus.[16] The date of this evolution is uncertain at present and estimates vary between 16,000 and 68,000 years ago. The more severe form (variola major) originated in Asia between 400 and 1600 years ago. A second form –alastrim minor– found in West Africa and the Americas is thought to have evolved between 1,400 and 6,300 years ago. This clade gave rise to two subclades that diverged at least 800 years ago.

    Transmission

    Transmission of smallpox occurs through inhalation of airborne variola virus, usually droplets expressed from the oral, nasal, or pharyngeal mucosa of an infected person. It is transmitted from one person to another primarily through prolonged face-to-face contact with an infected person, usually within a distance of 6 feet, but can also be spread through direct contact with infected bodily fluids or contaminated objects (fomites) such as bedding or clothing. Rarely, smallpox has been spread by virus carried in the air in enclosed settings such as buildings, buses, and trains.[17] The virus can cross the placenta, but the incidence of congenital smallpox is relatively low.[4] Smallpox is not notably infectious in the prodromal period and viral shedding is usually delayed until the appearance of the rash, which is often accompanied by lesions in the mouth and pharynx. The virus can be transmitted throughout the course of the illness, but is most frequent during the first week of the rash, when most of the skin lesions are intact.[15] Infectivity wanes in 7 to 10 days when scabs form over the lesions, but the infected person is contagious until the last smallpox scab falls off.[18]

    Smallpox is highly contagious, but generally spreads more slowly and less widely than some other viral diseases, perhaps because transmission requires close contact and occurs after the onset of the rash. The overall rate of infection is also affected by the short duration of the infectious stage. In temperate areas, the number of smallpox infections were highest during the winter and spring. In tropical areas, seasonal variation was less evident and the disease was present throughout the year.[15] Age distribution of smallpox infections depends on acquired immunity. Vaccination immunity declines over time and is probably lost in all but the most recently vaccinated populations.[4] Smallpox is not known to be transmitted by insects or animals and there is no asymptomatic carrier state.[15]

    Signs and symptoms

    There are two clinical forms of smallpox. Variola major is the severe and most common form of smallpox, with a more extensive rash and higher fever. There are four types of variola major smallpox based on the Rao classification:[19] ordinary, modified, flat, and hemorrhagic. Historically, variola major has an overall fatality rate of about 30%; however, flat and hemorrhagic smallpox are usually fatal.[20] In addition, a form called variola sine eruptione (smallpox without rash) is seen generally in vaccinated persons. This form is marked by a fever that occurs after the usual incubation period and can be confirmed only by antibody studies or, rarely, by virus isolation.[15]

    Variola minor is a less common presentation of smallpox, and a much less severe disease, with historical death rates of 1% or less.[17] Subclinical (asymptomatic) infections with variola virus have also been noted, but are not believed to be common.[15]

    Child showing rash due to ordinary-type smallpox (variola major)

    The incubation period between contraction and the first obvious symptoms of the disease is around 12 days. Once inhaled, variola virus invades the oropharyngeal (mouth and throat) or the respiratory mucosa, migrates to regional lymph nodes, and begins to multiply. In the initial growth phase the virus seems to move from cell to cell, but around the 12th day, lysis of many infected cells occurs and the virus is found in the bloodstream in large numbers (this is called viremia), and a second wave of multiplication occurs in the spleen, bone marrow, and lymph nodes. The initial or prodromal symptoms are similar to other viral diseases such as influenza and the common cold: fever (at least 38.5 °C (101 °F)), muscle pain, malaise, headache, prostration, and as the digestive tract is commonly involved, nausea and vomiting and backache often occur. The prodrome, or preeruptive stage, usually lasts 2–4 days. By days 12–15 the first visible lesions—small reddish spots called enanthem—appear on mucous membranes of the mouth, tongue, palate, and throat, and temperature falls to near normal. These lesions rapidly enlarge and rupture, releasing large amounts of virus into the saliva.[4]

    Smallpox virus preferentially attacks skin cells, causing the characteristic pimples (called macules) associated with the disease. A rash develops on the skin 24 to 48 hours after lesions on the mucous membranes appear. Typically the macules first appear on the forehead, then rapidly spread to the whole face, proximal portions of extremities, the trunk, and lastly to distal portions of extremities. The process takes no more than 24 to 36 hours, after which no new lesions appear.[4] At this point Variola major infection can take several very different courses.

    Ordinary

    Ninety percent or more of smallpox cases among unvaccinated persons are of the ordinary type.[15] In this form of the disease, by the second day of the rash, the macules become raised papules. By the third or fourth day the papules fill with an opalescent fluid to become vesicles. This fluid becomes opaque and turbid within 24–48 hours, giving them the appearance of pustules; however, the so-called pustules are filled with tissue debris, not pus.[4]

    By the sixth or seventh day, all the skin lesions have become pustules. Between 7 and 10 days the pustules mature and reach their maximum size. The pustules are sharply raised, typically round, tense, and firm to the touch. The pustules are deeply embedded in the dermis, giving them the feel of a small bead in the skin. Fluid slowly leaks from the pustules, and by the end of the second week the pustules deflate, and start to dry up, forming crusts (or scabs). By day 16-20 scabs have formed over all the lesions, which have started to flake off, leaving de-pigmented scars.[21]

    Ordinary smallpox generally produces a discrete rash, in which the pustules stand out on the skin separately. The distribution of the rash is densest on the face; denser on the extremities than on the trunk; and on the extremities, denser on the distal parts than on the proximal. The palms of the hands and soles of the feet are involved in the majority of cases. In some cases, the blisters merge together into sheets, forming a confluent rash, which begin to detach the outer layers of skin from the underlying flesh. Patients with confluent smallpox often remain ill even after scabs have formed over all the lesions. In one case series, the case-fatality rate in confluent smallpox was 62%.[15]

    Modified

    Referring to the character of the eruption and the rapidity of its development, modified smallpox occurs mostly in previously vaccinated people. In this form the prodromal illness still occurs but may be less severe than in the ordinary type. There is usually no fever during evolution of the rash. The skin lesions tend to be fewer and evolve more quickly, are more superficial, and may not show the uniform characteristic of more typical smallpox.[21] Modified smallpox is rarely, if ever, fatal. This form of variola major is more easily confused with chickenpox.[15]

    This man is suffering from severe hemorrhagic-type smallpox.

    Malignant

    In Malignant-type smallpox (also called flat smallpox) the lesions remain almost flush with the skin at the time when raised vesicles form in ordinary-type smallpox. It is unknown why some people develop this type of disease. Historically, malignant smallpox accounted for 5%–10% of cases, and the majority (72%) were in children.[22] Malignant smallpox is accompanied by a severe prodromal phase that lasts 3–4 days, prolonged high fever, and severe symptoms of toxemia. The rash on the tongue and palate is usually extensive. The skin lesions mature very slowly and by the seventh or eighth day the lesions are flat and appear to be buried in the skin. Unlike ordinary-type smallpox, the vesicles contain very little fluid, are soft and velvety to the touch, and may contain hemorrhages. Malignant smallpox is nearly always fatal.[15]

    Hemorrhagic

    Hemorrhagic smallpox is a severe form of smallpox that is accompanied by extensive bleeding into the skin, mucous membranes, and gastrointestinal tract. This form developed in perhaps 2% of infections and occurred mostly in adults. In hemorrhagic smallpox the skin does not blister, but remains smooth. Instead, bleeding occurs under the skin, making the skin look charred and black, hence this form of the disease is also known as black pox.

    In the early, or fulminating form, hemorrhaging appears on the second or third day as sub-conjunctival bleeding turns the whites of the eyes deep red. Hemorrhagic smallpox also produces a dusky erythema, petechiae, and hemorrhages in the spleen, kidney, serosa, muscle, and, rarely, the epicardium, liver, testes, ovaries and bladder. Death often occurs suddenly between the fifth and seventh days of illness, when only a few insignificant skin lesions are present. A later form of the disease occurs in patients who survive for 8–10 days. The hemorrhages appear in the early eruptive period, and the rash is flat and does not progress beyond the vesicular stage.[15] Patients in the early stage of disease show a decrease in coagulation factors (e.g. platelets, prothrombin, and globulin) and an increase in circulating antithrombin. Patients in the late stage have significant thrombocytopenia; however, deficiency of coagulation factors is less severe. Some in the late stage also show increased antithrombin.[4] This form of smallpox occurs in anywhere from 3–25% of fatal cases depending on the virulence of the smallpox strain.[20] Hemorrhagic smallpox is usually fatal.[15]

    Diagnosis

    Smallpox virus pocks on the chorioallantoic membrane of a developing chick.
    Contrary to the rash in smallpox, the rash in chickenpox occurs mostly on the torso, spreading less to the limbs.

    The clinical definition of smallpox is an illness with acute onset of fever greater than 101°F (38.3°C) followed by a rash characterized by firm, deep seated vesicles or pustules in the same stage of development without other apparent cause. If a clinical case is observed, smallpox is confirmed using laboratory tests.

    Microscopically, poxviruses produce characteristic cytoplasmic inclusions, the most important of which are known as Guarnieri bodies, and are the sites of viral replication. Guarnieri bodies are readily identified in skin biopsies stained with hematoxylin and eosin, and appear as pink blobs. They are found in virtually all poxvirus infections but the absence of Guarnieri bodies cannot be used to rule out smallpox.[23] The diagnosis of an orthopoxvirus infection can also be made rapidly by electron microscopic examination of pustular fluid or scabs. However, all orthopoxviruses exhibit identical brick-shaped virions by electron microscopy.[4]

    Definitive laboratory identification of variola virus involves growing the virus on chorioallantoic membrane (part of a chicken embryo) and examining the resulting pock lesions under defined temperature conditions.[24] Strains may be characterized by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Serologic tests and enzyme linked immunosorbent assays (ELISA), which measure variola virus-specific immunoglobulin and antigen have also been developed to assist in the diagnosis of infection.[25]

    Chickenpox was commonly confused with smallpox in the immediate post-eradication era. Chickenpox and smallpox can be distinguished by several methods. Unlike smallpox, chickenpox does not usually affect the palms and soles. Additionally, chickenpox pustules are of varying size due to variations in the timing of pustule eruption: smallpox pustules are all very nearly the same size since the viral effect progresses more uniformly. A variety of laboratory methods are available for detecting chickenpox in evaluation of suspected smallpox cases.

    Prognosis

    The overall case-fatality rate for ordinary-type smallpox is about 30%, but varies by pock distribution: ordinary type-confluent is fatal about 50–75% of the time, ordinary-type semi-confluent about 25–50% of the time, in cases where the rash is discrete the case-fatality rate is less than 10%. The overall fatality rate for children younger than 1 year of age is 40%–50%. Hemorrhagic and flat types have the highest fatality rates. The fatality rate for flat-type is 90% or greater and nearly 100% is observed in cases of hemorrhagic smallpox. The case-fatality rate for variola minor is 1% or less.[21] There is no evidence of chronic or recurrent infection with variola virus.

    In fatal cases of ordinary smallpox, death usually occurs between the tenth and sixteenth days of the illness. The cause of death from smallpox is not clear, but the infection is now known to involve multiple organs. Circulating immune complexes, overwhelming viremia, or an uncontrolled immune response may be contributing factors.[15] In early hemorrhagic smallpox, death occurs suddenly about six days after the fever develops. Cause of death in hemorrhagic cases involved heart failure, sometimes accompanied by pulmonary edema. In late hemorrhagic cases, high and sustained viremia, severe platelet loss and poor immune response were often cited as causes of death.[22] In flat smallpox modes of death are similar to those in burns, with loss of fluid, protein and electrolytes beyond the capacity of the body to replace or acquire, and fulminating sepsis.

    Complications

    Complications of smallpox arise most commonly in the respiratory system and range from simple bronchitis to fatal pneumonia. Respiratory complications tend to develop on about the eighth day of the illness and can be either viral or bacterial in origin. Secondary bacterial infection of the skin is a relatively uncommon complication of smallpox. When this occurs, the fever usually remains elevated.[15]

    Other complications include encephalitis (1 in 500 patients), which is more common in adults and may cause temporary disability; permanent pitted scars, most notably on the face; and complications involving the eyes (2% of all cases). Pustules can form on the eyelid, conjunctiva, and cornea, leading to complications such as conjunctivitis, keratitis, corneal ulcer, iritis, iridocyclitis, and optic atrophy. Blindness results in approximately 35% to 40% of eyes affected with keratitis and corneal ulcer. Hemorrhagic smallpox can cause subconjunctival and retinal hemorrhages. In 2% to 5% of young children with smallpox, virions reach the joints and bone, causing osteomyelitis variolosa. Lesions are symmetrical, most common in the elbows, tibia, and fibula, and characteristically cause separation of an epiphysis and marked periosteal reactions. Swollen joints limit movement, and arthritis may lead to limb deformities, ankylosis, malformed bones, flail joints, and stubby fingers.[4]

    Treatment

    Smallpox vaccination within three days of exposure will prevent or significantly lessen the severity of smallpox symptoms in the vast majority of people. Vaccination four to seven days after exposure likely offers some protection from disease or may modify the severity of disease.[26] Other than vaccination, treatment of smallpox is primarily supportive, such as wound care and infection control, fluid therapy, and possible ventilator assistance. Flat and hemorrhagic types of smallpox are treated with the same therapies used to treat shock, such as fluid resuscitation. Patients with semi-confluent and confluent types of smallpox may have therapeutic issues similar to patients with extensive skin burns.

    No drug is currently approved for the treatment of smallpox. However, antiviral treatments have improved since the last large smallpox epidemics, and studies suggest that the antiviral drug cidofovir might be useful as a therapeutic agent. The drug must be administered intravenously, however, and may cause serious renal toxicity.[27]

    Prevention

    Main articles: Inoculation and Smallpox vaccine
    Vial containing variolation material (India)

    The earliest procedure used to prevent smallpox was inoculation (also known as variolation). Inoculation was allegedly first practiced in India as early as 1000 BC,[28] and involved either nasal insufflation of powdered smallpox scabs, or scratching material from a smallpox lesion into the skin. However, this idea has been challenged as few of the ancient Sanskrit medical texts of India described the process of inoculation.[29] Accounts of inoculation against smallpox in China can be found as early as the late 10th century, and the procedure was widely practiced by the 16th century, during the Ming Dynasty.[30] If successful, inoculation produced lasting immunity to smallpox. However, because the person was infected with variola virus, a severe infection could result, and the person could transmit smallpox to others. Variolation had a 0.5–2% mortality rate; considerably less than the 20–30% mortality rate of the disease itself.[15]

    In 1796 Edward Jenner, a doctor in Berkeley, Gloucestershire, rural England, discovered that immunity to smallpox could be produced by inoculating a person with material from a cowpox lesion. Cowpox is a poxvirus in the same family as variola. Jenner called the material used for inoculation vaccine, from the root word vacca, which is Latin for cow. The procedure was much safer than variolation, and did not involve a risk of smallpox transmission. Vaccination to prevent smallpox was soon practiced all over the world. During the 19th century, the cowpox virus used for smallpox vaccination was replaced by vaccinia virus. Vaccinia is in the same family as cowpox and variola but is genetically distinct from both. The origin of vaccinia virus and how it came to be in the vaccine are not known.[15]

    The current formulation of smallpox vaccine is a live virus preparation of infectious vaccinia virus. The vaccine is given using a bifurcated (two-pronged) needle that is dipped into the vaccine solution. The needle is used to prick the skin (usually the upper arm) a number of times in a few seconds. If successful, a red and itchy bump develops at the vaccine site in three or four days. In the first week, the bump becomes a large blister (called a “Jennerian vesicle”) which fills with pus, and begins to drain. During the second week, the blister begins to dry up and a scab forms. The scab falls off in the third week, leaving a small scar.

    Components of a modern smallpox vaccination kit including the diluent, a vial of Dryvax vaccinia vaccine, and a bifurcated needle.

    The antibodies induced by vaccinia vaccine are cross-protective for other orthopoxviruses (such as monkeypox, cowpox, and variola (smallpox) viruses). Neutralizing antibodies are detectable 10 days after first-time vaccination, and seven days after revaccination. Historically, the vaccine has been effective in preventing smallpox infection in 95% of those vaccinated.[26] Smallpox vaccination provides a high level of immunity for three to five years and decreasing immunity thereafter. If a person is vaccinated again later, immunity lasts even longer. Studies of smallpox cases in Europe in the 1950s and 1960s demonstrated that the fatality rate among persons vaccinated less than 10 years before exposure was 1.3%; it was 7% among those vaccinated 11 to 20 years prior, and 11% among those vaccinated 20 or more years prior to infection. By contrast, 52% of unvaccinated persons died.[31]

    There are side effects and risks associated with the smallpox vaccine. In the past, about 1,000 people for every 1 million people vaccinated for the first time experienced serious, but non-life-threatening, reactions including toxic or allergic reaction at the site of the vaccination (erythema multiforme), spread of the vaccinia virus to other parts of the body, and to other individuals. Potentially life-threatening reactions occurred in 14 to 500 people out of every 1 million people vaccinated for the first time. Based on past experience, it is estimated that 1 or 2 people in 1 million (0.000198%) who receive the vaccine may die as a result, most often the result of postvaccinial encephalitis or severe necrosis in the area of vaccination (called progressive vaccinia).[26]

    Given these risks, as smallpox became effectively eradicated and the number of naturally-occurring cases fell below the number of vaccine-induced illnesses and deaths, routine childhood vaccination was discontinued in the United States in 1972. Routine vaccination of healthcare workers was discontinued in 1976, and among military recruits in 1990. Military members deploying to the Middle East and Korea still receive the vaccination.[32] It is now primarily recommended for laboratory workers at risk for occupational exposure.[15] Mass smallpox vaccination was abandoned in most European countries in the early 1970s as well.[33]

    Eradication

    Vaccination during the Smallpox Eradication and Measles Control Program in Niger, February, 1969.

    Since Jenner demonstrated the effectiveness of cowpox to protect humans from smallpox in 1796, various attempts were made to eliminate smallpox on a regional scale. As early as 1803, the Spanish Crown organized a mission (the Balmis expedition) to transport the vaccine to the Spanish colonies in the Americas and the Philippines, and establish mass vaccination programs there.[34] By about 1817, a very solid state vaccination programme existed in the Dutch East Indies.[35] In British India a program was launched to propagate smallpox vaccination, through Indian vaccinators, under the supervision of European officials.[36] By 1832, the federal government of the United States established a smallpox vaccination program for Native Americans.[37] In 1842, the United Kingdom banned inoculation, later progressing to mandatory vaccination. The British government introduced compulsory smallpox vaccination by an Act of Parliament in 1853.[38] In the United States, from 1843 to 1855 first Massachusetts, and then other states required smallpox vaccination. Although some disliked these measures,[39] coordinated efforts against smallpox went on, and the disease continued to diminish in the wealthy countries. By 1897, smallpox had largely been eliminated from the United States.[40] In Northern Europe a number of countries had eliminated smallpox by 1900, and by 1914, the incidence in most industrialized countries had decreased to comparatively low levels. Vaccination continued in industrialized countries, until the mid to late 1970s as protection against reintroduction. Australia and New Zealand are two notable exceptions; neither experienced endemic smallpox and never vaccinated widely, relying instead on protection by distance and strict quarantines.[41]

    The first hemisphere-wide effort to eradicate smallpox was made in 1950 by the Pan American Health Organization.[42] The campaign was successful in eliminating smallpox from all American countries except Argentina, Brazil, Colombia, and Ecuador.[41] In 1958 Professor Viktor Zhdanov, Deputy Minister of Health for the USSR, called on the World Health Assembly to undertake a global initiative to eradicate smallpox. The proposal (Resolution WHA11.54) was accepted in 1959.[43] At this point, 2 million people were dying every year. Overall, however, progress towards eradication was disappointing, especially in Africa and in the Indian subcontinent. In 1967, the World Health Organization intensified the global smallpox eradication by contributing $2.4 million annually to the effort. An international team, the Smallpox Eradication unit, was formed under the leadership of an American, Donald Henderson.[44]

    To eradicate smallpox, each outbreak had to be stopped from spreading, by isolation of cases and vaccination of everyone who lived close by. This process is known as "ring vaccination". The key to this strategy was monitoring of cases in a community (known as surveillance) and containment. The initial problem the WHO team faced was inadequate reporting of smallpox cases, as many cases did not come to the attention of the authorities. The fact that humans are the only reservoir for smallpox infection, and that carriers did not exist, played a significant role in the eradication of smallpox. The WHO established a network of consultants who assisted countries in setting up surveillance and containment activities. Early on donations of vaccine were provided primarily by the Soviet Union and the United States, but by 1973, more than 80% of all vaccine was produced in developing countries.[41]

    This 1980 photograph, taken at the CDC, shows three former directors of the Global Smallpox Eradication Program as they read the news that smallpox had been globally eradicated.

    The last major European outbreak of smallpox was in 1972 in Yugoslavia, after a pilgrim from Kosovo returned from the Middle East, where he had contracted the virus. The epidemic infected 175 people, causing 35 deaths. Authorities declared martial law, enforced quarantine, and undertook widespread re-vaccination of the population, enlisting the help of the WHO. In two months, the outbreak was over.[45] Prior to this, there had been a smallpox outbreak in May–July 1963 in Stockholm, Sweden, brought from the Far East by a Swedish sailor; this had been dealt with by quarantine measures and vaccination of the local population.[46]

    By the end of 1975, smallpox persisted only in the Horn of Africa. Conditions were very difficult in Ethiopia and Somalia, where there were few roads. Civil war, famine, and refugees made the task even more difficult. An intensive surveillance and containment and vaccination program was undertaken in early and mid-1977. The last naturally occurring case of indigenous smallpox (Variola minor) was diagnosed in Ali Maow Maalin, a hospital cook in Merca, Somalia, on 26 October 1977.[15] The last naturally occurring case of the more deadly Variola major had been detected in October 1975 in a two-year-old Bangladeshi girl, Rahima Banu.[47]

    The global eradication of smallpox was certified, based on intense verification activities in countries, by a commission of eminent scientists on 9 December 1979 and subsequently endorsed by the World Health Assembly on 8 May 1980[10][48] as Resolution WHA33.3. The first two sentences of the resolution read: "Having considered the development and results of the global program on smallpox eradication initiated by WHO in 1958 and intensified since 1967 … Declares solemnly that the world and its peoples have won freedom from smallpox, which was a most devastating disease sweeping in epidemic form through many countries since earliest time, leaving death, blindness and disfigurement in its wake and which only a decade ago was rampant in Africa, Asia and South America."[49]

    Post-eradication

    The last cases of smallpox in the world occurred in an outbreak of two cases (one of which was fatal) in Birmingham, England in 1978. A medical photographer, Janet Parker, contracted the disease at the University of Birmingham Medical School and died on 11 September 1978,[49] after which the scientist responsible for smallpox research at the university, Professor Henry Bedson, committed suicide.[2] In light of this accident, all known stocks of smallpox were destroyed or transferred to one of two WHO reference laboratories; the Centers for Disease Control and Prevention (CDC) in the United States and the State Research Center of Virology and Biotechnology VECTOR in Koltsovo, Russia.[50] In 1986, the World Health Organization recommended destruction of the virus, and later set the date of destruction to be 30 December 1993. This was postponed to 30 June 1995.[51] In 2002 the policy of the WHO changed to be against its final destruction.[52] Destroying existing stocks would reduce the risk involved with ongoing smallpox research; the stocks are not needed to respond to a smallpox outbreak.[53] However, the stocks may be useful in developing new vaccines, antiviral drugs, and diagnostic tests.[54]

    In March 2004 smallpox scabs were found tucked inside an envelope in a book on Civil War medicine in Santa Fe, New Mexico.[55] The envelope was labeled as containing scabs from a vaccination and gave scientists at the Centers for Disease Control and Prevention an opportunity to study the history of smallpox vaccination in the US.

    Biological warfare

    The British considered using smallpox as a biological warfare agent during the French and Indian Wars (1754–63), against France and its Native American allies at the Siege of Fort Pitt.[56][57] On one occasion in June 1763, two blankets and a handkerchief that had been exposed to smallpox were given to representatives of the besieging Delawares with the aim of spreading the disease and ending the siege.[58] Historians do not agree on whether this effort to broadcast the disease was successful. It has also been alleged that smallpox was used as a weapon during the American Revolutionary War (1775–83).[59][60]

    During World War II, scientists from the United Kingdom, United States and Japan were involved in research into producing a biological weapon from smallpox.[61] Plans of large scale production were never carried through as they considered that the weapon would not be very effective due to the wide-scale availability of a vaccine.[59]

    In 1947 the Soviet Union established a smallpox weapons factory in the city of Zagorsk, 75 km to the northeast of Moscow.[62]. An outbreak of weaponized smallpox possibly occurred during testing at the factory in the 1970s. General Prof. Peter Burgasov, former Chief Sanitary Physician of the Soviet Army, and a senior researcher within the Soviet program of biological weapons described the incident:

    “On Vozrozhdeniya Island in the Aral Sea, the strongest recipes of smallpox were tested. Suddenly I was informed that there were mysterious cases of mortalities in Aralsk. A research ship of the Aral fleet came to within 15 km of the island (it was forbidden to come any closer than 40 km). The lab technician of this ship took samples of plankton twice a day from the top deck. The smallpox formulation—400 gr. of which was exploded on the island—”got her” and she became infected. After returning home to Aralsk, she infected several people including children. All of them died. I suspected the reason for this and called the Chief of General Staff of Ministry of Defense and requested to forbid the stop of the Alma-Ata—Moscow train in Aralsk. As a result, the epidemic around the country was prevented. I called Andropov, who at that time was Chief of KGB, and informed him of the exclusive recipe of smallpox obtained on Vozrazhdenie Island.”[63][64]

    Others contend that the first patient may have contracted the disease while visiting Uyaly or Komsomolsk, two cities where the boat docked.[65]

    Responding to international pressures, in 1991 the Soviet government allowed a joint US-British inspection team to tour four of its main weapons facilities at Biopreparat. The inspectors were met with evasion and denials from the Soviet scientists, and were eventually ordered out of the facility. In 1992 Soviet defector Ken Alibek confirmed that the Soviet bioweapons program at Zagorsk had produced a large stockpile—as much as twenty tons—of weaponized smallpox (possibly engineered to resist vaccines), along with refrigerated warheads to deliver it. It is not known whether these stockpiles still exist in Russia. In 1997, however, the Russian government announced that all of its remaining smallpox samples would be moved to the Vector Institute in Koltsovo.[66] With the breakup of the Soviet Union and unemployment of many of the weapons program's scientists, there is concern that smallpox and the expertise to weaponize it may have become available to other governments or terrorist groups who might wish to use virus as means of biological warfare.[67]

    History

    Main article: History of smallpox
    Drawing accompanying text in Book XII of the 16th-century Florentine Codex (compiled 1540–1585), showing Nahuas of conquest-era central Mexico suffering from smallpox.

    Smallpox likely diverged from an ancestral African rodent-borne variola-like virus between 16,000 and 68,000 years ago.[16] The precise origins of smallpox are unknown, and most early references to it are unreliable. Historical records from Asia describe evidence of smallpox-like disease in medical writings from ancient China (1122 B.C.) and India (as early as 1500 B.C.)[39] The earliest credible clinical evidence of smallpox is found in the Egyptian mummies of persons who died some 3000 years ago. It has been speculated that Egyptian traders brought smallpox to India during the 1st millennium BC, where it remained as an endemic human disease for at least 2000 years. Unmistakable descriptions of smallpox first appeared in the 4th century AD in China and the 7th century in India. Smallpox was likely introduced in China during the 1st century AD from the southwest, and in the 6th century was carried from China to Japan.[22]

    The arrival of smallpox in Europe and south-western Asia is less clear. Smallpox is not described in either the Old or New Testaments of the Bible, or in literature of the Greeks and Romans. Scholars agree it is very unlikely such a serious disease as variola major would have escaped a description by Hippocrates if it existed in the Mediterranean region.[68] While the Antonine Plague that swept through the Roman Empire in 165–180 AD may have been caused by smallpox,[69] other historians speculate that Arab armies first carried smallpox out of Africa to Southwestern Europe during the 7th and 8th centuries AD.[22] In the 9th century the Persian physician, Rhazes, provided one of the most definitive observations of smallpox and was the first to differentiate smallpox from measles and chickenpox in his Kitab fi al-jadari wa-al-hasbah (The Book of Smallpox and Measles).[70] During the Middle Ages, smallpox made periodic incursions into Europe but did not become established there until the population increased and population movement became more active during the time of the Crusades. By the 16th century smallpox was well established over most of Europe.[22] With its introduction in populated areas in India, China and Europe, smallpox affected mainly children, with periodic epidemics that killed up to 30% of those infected. The appearance of smallpox in Europe is of particular importance, as successive waves of European exploration and colonization served to spread the disease to other parts of the world. By the 16th century it had become an important cause of morbidity and mortality in the known world.[22]

    Smallpox sufferer: Illinois, 1912

    There are no credible descriptions of smallpox-like disease in the Americas before the westward exploration in the 15th century AD.[16] In 1507 smallpox was introduced into the Caribbean island of Hispaniola and to the mainland in 1520, when Spanish settlers from Hispaniola arriving in Mexico brought smallpox with them. Smallpox devastated the native Amerindian population and was an important factor in the conquest of the Aztecs and the Incas by the Spaniards.[22] Settlement of the east coast of North America in 1633 in Plymouth, Massachusetts was also accompanied by devastating outbreaks of smallpox among Native American populations, and subsequently among the native-born colonists.[71] Smallpox was introduced into Australia in 1789 and again in 1829 and caused devastation among the aborigines, but quickly died out on both occasions.[22]

    By the mid-18th century smallpox was a major endemic disease everywhere in the world except in Australia and in several small islands. In Europe smallpox was a leading cause of death in the 18th century, killing an estimated 400,000 Europeans each year, including five reigning European monarchs.[72] In Russia every 7th child born died from smallpox.[10] The widespread use of variolation in a few countries, notably Great Britain its North American colonies, and China, somewhat reduced the impact of smallpox among the wealthy classes during the latter part of the 18th century, but a real reduction in its incidence did not occur until vaccination became a common practice toward the end of the 19th century. Improved vaccines and the practice of re-vaccination led to a substantial reduction in cases in Europe and North America, but smallpox remained almost unchecked everywhere else in the world. In the United States and South Africa a much milder form of smallpox, variola minor, was recognized just before the close of the 19th century. By the mid-20th century variola minor occurred along with variola major, in varying proportions, in many parts of Africa. Patients with variola minor experience only a mild systemic illness, are often ambulant throughout the course of the disease, and are therefore able to more easily spread disease. Infection with v. minor induces immunity against the more deadly variola major form. Thus as v. minor spread all over the USA, into Canada, the South American countries and Great Britain it became the dominant form of smallpox, further reducing mortality rates.[22]

    Famous sufferers and survivors

    Famous historical figures who contracted smallpox include Ruqayyah bint Muhammad second daughter of prophet Muhammad and wife of third Islamic Caliph Uthman ibn Affan in the year 624, Lakota Chief Sitting Bull, Ramses V of Egypt,[48] the Kangxi Emperor (survived), Shunzhi Emperor and Tongzhi Emperor (refer to the official history) of China, Date Masamune of Japan (who lost an eye to the disease). Cuitláhuac, the 10th tlatoani (ruler) of the Aztec city of Tenochtitlan, died of smallpox in 1520, shortly after its introduction to the Americas, and the Incan emperor Huayna Capac died of it in 1527. More recent public figures include: Guru Har Krishan, 8th Guru of the Sikhs, in 1664, Peter II of Russia in 1730 (died),[73] and Maximilian III Joseph, Elector of Bavaria in 1777. Maharaja Ranjit Singh, the Lion of the Punjab, lost sight in his left eye due to an attack of smallpox during his childhood.[74][dubious – discuss]

    Prominent families throughout the world often had several people infected by and/or perish from the disease. For example, several relatives of Henry VIII survived the disease but were scarred by it. These include his sister Margaret, Queen of Scotland, his fourth wife, Anne of Cleves, and his two daughters: Mary I of England in 1527 and Elizabeth I of England in 1562 (as an adult she would often try to disguise the pockmarks with heavy makeup). His great-niece, Mary, Queen of Scots, contracted the disease as a child but had no visible scarring.

    In Europe, deaths from smallpox often changed dynastic succession. The only surviving son of Henry VIII, Edward VI, likely died from complications shortly after apparently recovering from the disease, thereby rendering his sire's infamous efforts to provide England with a male heir moot. (His immediate successors were all females.) Louis XV of France succeeded his great-grandfather Louis XIV through a series of deaths of smallpox or measles among those earlier in the succession line. He himself died of the disease in 1774. William III lost his mother to the disease when he was only ten years old in 1660, and named his uncle Charles as legal guardian: her death from smallpox would indirectly spark a chain of events that would eventually lead to the permanent ousting of the Stuart line from the British throne.

    In China, the Qing Dynasty had extensive protocols to protect Manchus from the Peking's endemic smallpox. Most notably, the Kangxi Emperor was promoted to the throne because he had survived the disease, ahead of older brothers who had not yet had it.

    Mozart and Beethoven contracted and survived the disease as children; both had visible pockmark scars on their faces.

    Both George Washington and Abraham Lincoln, Presidents of the United States, contracted and recovered from the disease. Lincoln was diagnosed with a mild form of the disease in late November 1863 having probably contracted it from his son Tad.[73] U.S. President Andrew Jackson and his older brother, Robert, contracted smallpox in his youth while imprisoned by the British during the American Revolutionary War. While Robert died from the disease, Andrew survived it and eventually served as the 7th President of the United States.

    Crime figure Lucky Luciano contracted the disease in 1907 at the age of ten, upon coming to New York from Sicily.

    Indian actress Geeta Bali died of smallpox in 1965.

    Turkish poet Aşık Veysel Şatıroğlu was blinded by smallpox at the age of seven.

    Hungarian poet Ferenc Kölcsey, who wrote the Hungarian anthem, lost his right eye to smallpox.

    See also

    References

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    Further reading

    • McNeill, William Hardy (1977). Plagues and peoples. Oxford: Basil Blackwell. ISBN 0-385-12122-9. 
    • Tucker, Jonathan B. (2001). Scourge: The Once and Future Threat of Smallpox. New York: Grove Press. ISBN 0-8021-3939-6. 
    • Lord Wharncliffe and W. Moy Thomas, editors. The Letters and Works of Lady Mary Wortley Montagu, vol. 1, London: Henry G. Bohn, 1861.

    External links

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    Translations: Smallpox
    Top
    Home > Library > Literature & Language > Translations

    Dansk (Danish)
    n. - kopper

    Nederlands (Dutch)
    pokken

    Français (French)
    n. - variole

    Deutsch (German)
    n. - Pocken

    Ελληνική (Greek)
    n. - (παθολ.) ευλογιά

    Italiano (Italian)
    vaiolo

    Português (Portuguese)
    n. - bexigas (f), varíola (f)

    Русский (Russian)
    оспа

    Español (Spanish)
    n. - viruela, viruelas

    Svenska (Swedish)
    n. - smittkoppor

    中文（简体）(Chinese (Simplified))
    天花

    中文（繁體）(Chinese (Traditional))
    n. - 天花

    한국어 (Korean)
    n. - 천연두

    日本語 (Japanese)
    n. - 天然痘, 疱瘡

    العربيه (Arabic)
    ‏(الاسم) ألجدري‏

    עברית (Hebrew)
    n. - ‮אבעבועות‬

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