Smallpox: Wikis

  
  
  

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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 per year during the closing years of the 18th century (including five monarchs),[6] and was responsible for a third of all blindness.[3][7] Of all those infected, 20–60%—and over 80% of infected children—died from the disease.[8]

During the 20th century, it is estimated that smallpox was responsible for 300–500 million deaths.[9][10][11] In the early 1950s an estimated 50 million cases of smallpox occurred in the world each year.[12] 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.[12] After successful vaccination campaigns throughout the 19th and 20th centuries, the WHO certified the eradication of smallpox in December 1979.[12] To this day, smallpox is the only human infectious disease to have been eradicated.[13]

Contents

Cause

This transmission electron micrograph depicts a number of smallpox virions. The “dumbbell-shaped” structure inside the virion is the viral core, which contains the viral DNA; Mag. = ~370,000x.

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,[14] with a single linear double stranded DNA genome 186 kilobase pairs (kbp) in size and containing a hairpin loop at each end.[15][16] 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.[17]

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.[15] Infection with either variola major or variola minor confers immunity against the other.[4]

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.[18] 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.[17] 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.[19]

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.[17] 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.[17]

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:[20] ordinary, modified, flat, and hemorrhagic. Historically, variola major has an overall fatality rate of about 30%; however, flat and hemorrhagic smallpox are usually fatal.[21] 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.[17]

Variola minor is a less common presentation of smallpox, and a much less severe disease, with historical death rates of 1% or less.[18] Subclinical (asymptomatic) infections with variola virus have also been noted, but are not believed to be common.[17]

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.[17] 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.[22]

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%.[17]

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.[22] Modified smallpox is rarely, if ever, fatal. This form of variola major is more easily confused with chickenpox.[17]

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.[23] 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.[17]

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.[17] 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.[21] Hemorrhagic smallpox is usually fatal.[17]

Diagnosis

Smallpox virus pocks on the chorioallantoic membrane of a developing chick.
In contrast 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.[24] 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.[25] 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.[26]

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.[22] 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.[17] 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.[23] 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.[17]

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.[27] 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.[28]

Prevention

Vial containing variolation material (India)

The earliest procedure used to prevent smallpox was inoculation (also known as variolation). Inoculation was possibly practiced in India as early as 1000 BC,[29] 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.[30] 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.[31] 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.[17]

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.[17]

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.[27] 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.[32]

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).[27]

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.[33] It is now primarily recommended for laboratory workers at risk for occupational exposure.[17] Mass smallpox vaccination was abandoned in most European countries in the early 1970s as well.[34]

History

Viral evolution

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.[35] 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. Alastrim minor, a second form 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.

Human history

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.)[36] 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.[23] At least seven religious deities have been specifically dedicated to smallpox, such as the god Sopona in the Yoruba religion. In India, the Hindu goddess of smallpox, Sitala Mata, was worshiped in temples throughout the country.[37]

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.[38] While the Antonine Plague that swept through the Roman Empire in 165–180 AD may have been caused by smallpox,[39] other historians speculate that Arab armies first carried smallpox out of Africa to Southwestern Europe during the 7th and 8th centuries AD.[23] The epidemic of 735-737 is believed to had killed as many as one-third of the population of Japan.[40] 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).[41] 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.[23] 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.[23]

Smallpox sufferer in the United States, 1912

There are no credible descriptions of smallpox-like disease in the Americas before the westward exploration in the 15th century AD.[35] 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.[23] 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.[42] Smallpox was introduced into Australia in 1789 and again in 1829 and caused devastation among the aborigines, but quickly died out on both occasions.[23]

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.[43] In Russia every 7th child born died from smallpox.[12] 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.[23]

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.[44] The US Congress passed the Vaccine Act of 1813 to ensure that safe smallpox vaccine would be available to the American public. By about 1817, a very solid state vaccination program existed in the Dutch East Indies.[45] In British India a program was launched to propagate smallpox vaccination, through Indian vaccinators, under the supervision of European officials.[46] By 1832, the federal government of the United States established a smallpox vaccination program for Native Americans.[47] 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.[48] In the United States, from 1843 to 1855 first Massachusetts, and then other states required smallpox vaccination. Although some disliked these measures,[36] 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.[49] 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.[50]

The first hemisphere-wide effort to eradicate smallpox was made in 1950 by the Pan American Health Organization.[51] The campaign was successful in eliminating smallpox from all American countries except Argentina, Brazil, Colombia, and Ecuador.[50] 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.[52] At this point, 2 million people were dying from smallpox every year. Overall, however, the 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.[53]

Two-year old Rahima Banu of Bangladesh was the last person infected with naturally occurring Variola major, in 1975

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.[50]

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.[54] 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.[55]

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.[17] 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.[56]

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[12][57] 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."[58]

Post-eradication

Three former directors of the Global Smallpox Eradication Program read the news that smallpox had been globally eradicated, 1980

The last cases of smallpox in the world occurred in an outbreak of two cases (one of which was fatal) in Birmingham, UK in 1978. A medical photographer, Janet Parker, contracted the disease at the University of Birmingham Medical School and died on 11 September 1978,[58] 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.[59] 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.[60] In 2002 the policy of the WHO changed to be against its final destruction.[61] Destroying existing stocks would reduce the risk involved with ongoing smallpox research; the stocks are not needed to respond to a smallpox outbreak.[62] However, the stocks may be useful in developing new vaccines, antiviral drugs, and diagnostic tests.[63]

In March 2004 smallpox scabs were found tucked inside an envelope in a book on Civil War medicine in Santa Fe, New Mexico.[64] 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.[65][66] 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.[67] 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).[68][69]

During World War II, scientists from the United Kingdom, United States and Japan were involved in research into producing a biological weapon from smallpox.[70] 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.[68]

In 1947 the Soviet Union established a smallpox weapons factory in the city of Zagorsk, 75 km to the northeast of Moscow.[71]. 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.”[72][73]

Others contend that the first patient may have contracted the disease while visiting Uyaly or Komsomolsk, two cities where the boat docked.[74]

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.[75] 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.[76]

Famous sufferers and survivors

Famous historical figures who contracted smallpox include Lakota Chief Sitting Bull, Ramses V of Egypt,[57] 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, George Washington, Peter II of Russia in 1730 (died),[77] 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.[78]

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, 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.[citation needed]

U.S. Presidents George Washington, Andrew Jackson, and Abraham Lincoln all contracted and recovered from the disease. Washington became infected with smallpox on a visit to the Barbados in 1751.[79] Jackson developed the illness after being taken prisoner by the British during the American Revolution, and though he recovered, his brother Robert did not.[79] Lincoln contracted the disease during his Presidency, possibly from his son Tad, and was quarantined shortly after giving the Gettysburg address in 1863.[79]

Famous theologian Jonathan Edwards died of smallpox in 1758 following an inoculation.

U.S.S.R. leader Stalin fell ill with smallpox at the age of seven. His face was badly scarred by the disease. He later had photographs retouched to make his pockmarks less apparent.[80]

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

Indian actress Geeta Bali died of smallpox in 1965.[citation needed]

Turkish poet Aşık Veysel Şatıroğlu was blinded by smallpox at the age of seven.[citation needed]

Hungarian poet Ferenc Kölcsey, who wrote the Hungarian anthem, lost his right eye to smallpox.[81]

See also

References

  1. ^ Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 525–8. ISBN 0838585299. 
  2. ^ a b c Barquet N, Domingo P (15 October 1997). "Smallpox: the triumph over the most terrible of the ministers of death". Ann. Intern. Med. 127 (8 Pt 1): 635–42. doi:10.1059/0003-4819-127-8_Part_1-199710150-00010 (inactive 2010-03-07). PMID 9341063. http://www.annals.org/cgi/content/full/127/8_Part_1/635. 
  3. ^ a b Behbehani AM (1 December 1983). "The smallpox story: life and death of an old disease". Microbiol Rev 47 (4): 455–509. PMID 6319980. PMC 281588. http://mmbr.asm.org/cgi/pmidlookup?view=long&pmid=6319980. 
  4. ^ a b c d e f g h i j "Smallpox". Armed Forces Institute of Pathology: Department of Infectious and Parasitic Diseases. http://web.archive.org/web/20071009141639/http://www.afip.org/Departments/infectious/sp/text/1_1.htm. Retrieved 2008-10-28. 
  5. ^ Jezek Z, Hardjotanojo W, Rangaraj AG (1981). "Facial scarring after varicella. A comparison with variola major and variola minor". Am. J. Epidemiol. 114 (6): 798–803. PMID 7315828. 
  6. ^ "Epidemics and pandemics: their impacts on human history". J. N. Hays (2005). p.151. ISBN 1851096582
  7. ^ "Smallpox and Vaccinia". National Center for Biotechnology Information.
  8. ^ Riedel S (2005). "Edward Jenner and the history of smallpox and vaccination". Proc (Bayl Univ Med Cent) 18 (1): 21–5. PMID 16200144. 
  9. ^ Koplow, David A. (2003). Smallpox: the fight to eradicate a global scourge. Berkeley: University of California Press. ISBN 0-520-24220-3. http://books.google.com/books/ucpress?vid=ISBN9780520242203. 
  10. ^ "UC Davis Magazine, Summer 2006: Epidemics on the Horizon". http://ucdavismagazine.ucdavis.edu/issues/su06/feature_1b.html. Retrieved 2008-01-03. 
  11. ^ How Poxviruses Such As Smallpox Evade The Immune System, ScienceDaily, February 1, 2008
  12. ^ a b c d e "Smallpox". WHO Factsheet. http://www.who.int/mediacentre/factsheets/smallpox/en/. Retrieved 2007-09-22. 
  13. ^ Kanda, N (2001). "(Book Review) The Eradication of Smallpox: Edward Jenner and The First and Only Eradication of a Human Infectious Disease". Nature Medicine 7 (1): 15–6. doi:10.1038/83283. PMID 83283. http://www.nature.com/nm/journal/v7/n1/full/nm0101_15b.html. 
  14. ^ Dubochet J, Adrian M, Richter K, Garces J, Wittek R (1994). "Structure of intracellular mature vaccinia virus observed by cryoelectron microscopy". J. Virol. 68 (3): 1935–41. PMID 8107253. 
  15. ^ a b Moss B (2006). "Poxviridae: the viruses and their replication". in Fields BN, Knipe DM, Howley PM, et al. (eds). Fields Virology. Vol 2 (5th ed.). Philadelphia, PA: Lippincott-Raven. pp. 2905–46. ISBN 0781760607. 
  16. ^ Damon I (2006). "Poxviruses". in Fields BN, Knipe DM, Howley PM, et al. (eds). Fields Virology. Vol 2 (5th ed.). Philadelphia, PA: Lippincott-Raven. pp. 2947–76. ISBN 0781760607. 
  17. ^ a b c d e f g h i j k l m n o p q r Atkinson W, Hamborsky J, McIntyre L, Wolfe S (eds.) (2005). "Smallpox" (PDF). Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book) (9th ed.). Washington DC: Public Health Foundation. pp. 281–306. http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/smallpox.pdf. 
  18. ^ a b "CDC Smallpox". Smallpox Overview. http://www.bt.cdc.gov/agent/smallpox/overview/disease-facts.asp. Retrieved 2007-12-26. 
  19. ^ Henderson DA, Inglesby TV, Bartlett JG, et al. (1999). "Smallpox as a biological weapon: medical and public health management. Working Group on Civilian Biodefense". JAMA 281 (22): 2127–37. doi:10.1001/jama.281.22.2127. PMID 10367824. 
  20. ^ Rao, A. R. (1972). Smallpox. Bombay: Kothari Book Depot. OCLC 723806
  21. ^ a b Hogan CJ, Harchelroad F. "CBRNE - Smallpox". eMedicine. http://www.emedicine.com/emerg/topic885.htm. Retrieved 2006-09-23. 
  22. ^ a b c "Smallpox Disease and Its Clinical Management" (pdf). From the training course titled "Smallpox: Disease, Prevention, and Intervention" (www.bt.cdc.gov/agent/smallpox/training/overview). http://emergency.cdc.gov/agent/smallpox/training/overview/pdf/diseasemgmt.pdf. Retrieved 2007-12-26. 
  23. ^ a b c d e f g h i Fenner, Frank (1988) (PDF). Smallpox and Its Eradication (History of International Public Health, No. 6). Geneva: World Health Organization. ISBN 92-4-156110-6. http://whqlibdoc.who.int/smallpox/9241561106.pdf. 
  24. ^ Riedel S (January 2005). "Smallpox and biological warfare: a disease revisited". Proc (Bayl Univ Med Cent) 18 (1): 13–20. PMID 16200143. 
  25. ^ "Smallpox: Current, comprehensive information on pathogenesis, microbiology, epidemiology, diagnosis, treatment, and prophylaxis". Center for Infectious Disease Research & Policy. http://www.cidrap.umn.edu/cidrap/content/bt/smallpox/biofacts/smllpx-summary.html#_Criteria_for_Determining. Retrieved 2007-12-27. 
  26. ^ LeDuc JW, Jahrling PB (2001). "Strengthening national preparedness for smallpox: an update". Emerging Infect. Dis. 7 (1): 155–7. doi:10.3201/eid0701.010125. PMID 11266310. PMC 2631676. http://www.cdc.gov/ncidod/eid/vol7no1/leduc.htm. 
  27. ^ a b c "Vaccine Overview" (PDF). Smallpox Fact Sheet. http://www.bt.cdc.gov/agent/smallpox/vaccination/pdf/vaccine-overview.pdf. Retrieved 2008-01-02. 
  28. ^ Bray M, Roy CJ (2004). "Antiviral prophylaxis of smallpox". J. Antimicrob. Chemother. 54 (1): 1–5. doi:10.1093/jac/dkh286. PMID 15163655. http://jac.oxfordjournals.org/cgi/content/full/54/1/1. 
  29. ^ Bourzac K (2002). "Smallpox: Historical Review of a Potential Bioterrorist Tool". Journal of Young Investigators 6 (3). http://www.jyi.org/volumes/volume6/issue3/features/bourzac.html. 
  30. ^ Wujastyk, Dominik. (1995). "Medicine in India," in Oriental Medicine: An Illustrated Guide to the Asian Arts of Healing, 19–38. Edited by Serindia Publications. London: Serindia Publications. ISBN 0906026369. p. 29.
  31. ^ Temple, Robert. (1986). The Genius of China: 3,000 Years of Science, Discovery, and Invention. With a forward by Joseph Needham. New York: Simon and Schuster, Inc. ISBN 0671620282. p. 135–7.
  32. ^ Mack TM (1972). "Smallpox in Europe, 1950–1971". J. Infect. Dis. 125 (2): 161–9. PMID 5007552. 
  33. ^ Questions and Answers - DoD Smallpox Vaccination Program (SVP)
  34. ^ Pütz MM, Alberini I, Midgley CM, Manini I, Montomoli E, Smith GL (2005). "Prevalence of antibodies to Vaccinia virus after smallpox vaccination in Italy". J. Gen. Virol. 86 (Pt 11): 2955–60. doi:10.1099/vir.0.81265-0. PMID 16227216. http://vir.sgmjournals.org/cgi/content/full/86/11/2955. 
  35. ^ a b Li Y, Carroll DS, Gardner SN, Walsh MC, Vitalis EA, Damon IK (October 2007). "On the origin of smallpox: correlating variola phylogenics with historical smallpox records". Proc. Natl. Acad. Sci. U.S.A. 104 (40): 15787–92. doi:10.1073/pnas.0609268104. PMID 17901212. 
  36. ^ a b Hopkins DR (2002). The Greatest Killer: Smallpox in history. University of Chicago Press. ISBN 0-226-35168-8.  Originally published as Princes and Peasants: Smallpox in History (1983), ISBN 0-226-35177-7
  37. ^ Henderson, D. A.; Preston, Richard (23 June 2009). Smallpox- the Death of a Disease: The Inside Story of Eradicating a Worldwide Killer (1st ed.). Prometheus Books. p. 32. ISBN 1591027225. http://www.amazon.com/o/ASIN/1591027225/sciencefriday/#reader_1591027225. 
  38. ^ Dixon, C. W. (1962). Smallpox. London: Churchill. .
  39. ^ Past pandemics that ravaged Europe, BBC News, November 7, 2005
  40. ^ "Epidemics and pandemics: their impacts on human history". J. N. Hays (2005). p.31. ISBN 1851096582
  41. ^ Harminder S. Dua, Ahmad Muneer Otri, Arun D. Singh (2008). "Abu Bakr Razi". British Journal of Ophthalmology (BMJ Group) 92: 1324. 
  42. ^ Koplow, David A. (2003). "Smallpox The Fight to Eradicate a Global Scourge". University of California Press. http://www.ucpress.edu/books/pages/9968/9968.ch01.html. Retrieved 2009-02-22. 
  43. ^ Smallpox and Vaccinia
  44. ^ Dr. Francisco de Balmis and his Mission of Mercy, Society of Philippine Heath History
  45. ^ Against all odds: vanquishing smallpox in far-flung Japan
  46. ^ Smallpox History - Other histories of smallpox in South Asia
  47. ^ Lewis Cass and the Politics of Disease: The Indian Vaccination Act of 1832
  48. ^ Bodily Matters: The Anti-Vaccination Movement in England, 1853–1907
  49. ^ C.V. Chapin. Variation in type of infectious disease as shown by the history of smallpox in the United States 1895–1912. Infect Dis 1913. 13: 171–196.
  50. ^ a b c Orenstein, Walter A.; Plotkin, Stanley A. (1999). Vaccines. Philadelphia: W.B. Saunders Co. pp. e-book. ISBN 0-7216-7443-7. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=smallpox&rid=vacc.section.45#47. 
  51. ^ Rodrigues BA (1975). "Smallpox eradication in the Americas". Bull Pan Am Health Organ 9 (1): 53–68. PMID 167890. 
  52. ^ Fenner, Frank (1988). "Development of the Global Smallpox Eradication Programme". Smallpox and Its Eradication (History of International Public Health, No. 6). Geneva: World Health Organization. pp. 366–418. ISBN 92-4-156110-6. http://whqlibdoc.who.int/smallpox/9241561106_chp9.pdf. 
  53. ^ Fenner, Frank (1988). "The Intensified Smallpox Eradication Programme" (PDF). Smallpox and Its Eradication (History of International Public Health, No. 6). Geneva: World Health Organization. pp. 422–538. ISBN 92-4-156110-6. http://whqlibdoc.who.int/smallpox/9241561106.pdf. 
  54. ^ "BBC - History - Smallpox: Eradicating the Scourge". http://www.bbc.co.uk/history/british/empire_seapower/smallpox_03.shtml. Retrieved 2008-11-24. 
  55. ^ Centers for Disease Control and Prevention (CDC) (1996). "International Notes—Quarantine Measures Smallpox—Stockholm, Sweden, 1963". MMWR 45 (25): 538–45. PMID 9132571. http://www.cdc.gov/MMWR/preview/mmwrhtml/00042757.htm. 
  56. ^ Preston, Richard (12 July 1999). "A reporter at large: Demon in the Freezer". The New Yorker. http://cryptome.org/smallpox-wmd.htm. Retrieved 2008-01-03. 
  57. ^ a b Fenner, Frank (2006). Nature, Nurture and Chance: The Lives of Frank and Charles Fenner. Canberra, ACT 0200: Australian National University Press. ISBN 1-920942-62-9. 
  58. ^ a b Pennington H (2003). "Smallpox and bioterrorism". Bull. World Health Organ. 81 (10): 762–7. PMID 14758439. PMC 2572332. http://www.scielosp.org/scielo.php?script=sci_arttext&pid=S0042-96862003001000014&lng=en&nrm=iso&tlng=en. 
  59. ^ Connor, Steve (2002-01-03). "How terrorism prevented smallpox being wiped off the face of the planet for ever". The Independent. http://www.independent.co.uk/news/science/how-terrorism-prevented-smallpox-being-wiped-off-the-face-of-the-planet-for-ever-672121.html. Retrieved 2008-10-03. 
  60. ^ Altman, Lawrence (1996-01-25). "Final Stock of the Smallpox Virus Now Nearer to Extinction in Labs". New York Times. http://query.nytimes.com/gst/fullpage.html?res=9800EED61639F936A15752C0A960958260&sec=&spon=&pagewanted=print. Retrieved 2007-11-23. 
  61. ^ MacKenzie, Debora (2002-01-26). "Stay of execution". New Scientist. http://www.newscientist.com/article/mg17323271.300-stay-of-execution.html. Retrieved 2007-11-23. 
  62. ^ Hammond, Edward (2007). "Should the US and Russia destroy their stocks of smallpox virus?". BMJ 334 (7597): 774. doi:10.1136/bmj.39155.695255.94. PMID 17431261. http://www.bmj.com/cgi/content/full/334/7597/774. 
  63. ^ Agwunobi, John O. (2007). "Should the US and Russia destroy their stocks of smallpox virus?". BMJ 334 (7597): 775. doi:10.1136/bmj.39156.490799.BE. PMID 17431262. http://www.bmj.com/cgi/content/full/334/7597/775. 
  64. ^ "Century-old smallpox scabs in N.M. envelope". USA Today: Health and Behavior. http://www.usatoday.com/news/health/2003-12-26-smallpox-in-envelope_x.htm. Retrieved 2006-09-23. 
  65. ^ Peckham, Indian Uprising, 226; Anderson, Crucible of War, 542, 809n.
  66. ^ Anderson, Crucible of War, 809n; Grenier, First Way of War, 144; Nester, Haughty Conquerors", 114–15.
  67. ^ Anderson, Crucible of War, 541–42; Jennings, Empire of Fortune, 447n26.
  68. ^ a b "BBC - History - Silent Weapon: Smallpox and Biological Warfare". http://www.bbc.co.uk/history/worldwars/coldwar/pox_weapon_01.shtml. Retrieved 2008-01-02. 
  69. ^ Elizabeth A. Fenn. "Biological Warfare in Eighteenth-Century North America: Beyond Jeffery Amherst," The Journal of American History, Vol. 86, No. 4 (Mar., 2000), pp. 1552–1580
  70. ^ "USAMRIID’s Medical Management of Biological Casualties Handbook" (PDF). http://usamriid.detrick.army.mil/education/bluebookpdf/USAMRIID%20Blue%20Book%205th%20Edition.pdf. Retrieved 2008-01-02. 
  71. ^ Alibek K, Handelman S (1999). Biohazard: The Chilling True Story of the Largest Covert Biological Weapons Program in the World—Told from Inside by the Man Who Ran It. New York: Delta. ISBN 0-385-33496-6. 
  72. ^ Shoham D, Wolfson Z (2004). "The Russian biological weapons program: vanished or disappeared?" ( – Scholar search). Crit. Rev. Microbiol. 30 (4): 241–61. doi:10.1080/10408410490468812. PMID 15646399. http://www.ingentaconnect.com/content/tandf/bmcb/2004/00000030/00000004/art00002. 
  73. ^ "Smallpox - not a bad weapon" (in Russian). Interview with General Burgasov. Moscow News. http://mn.ru/issue.php?2001-46-48. Retrieved 2007-06-18. 
  74. ^ Enserink M (2002). "Biowarfare. Did bioweapons test cause a deadly smallpox outbreak?". Science 296 (5576): 2116–7. doi:10.1126/science.296.5576.2116. PMID 12077372. 
  75. ^ Preston, Richard. The Demon in the Freezer. Fawcett. pp. 105–115. ISBN 0-345-46663-2. 
  76. ^ History and Epidemiology of Global Smallpox Eradication From the training course titled "Smallpox: Disease, Prevention, and Intervention". The CDC and the World Health Organization. Slide 16-17.
  77. ^ "President Abraham Lincoln: Health & Medical History". 2007-03-24. http://www.doctorzebra.com/prez/g16.htm#25. Retrieved 2007-06-18. 
  78. ^ Prakash, Om (2001). Encyclopaedic History of Indian Freedom Movement. Anmol Publications PVT. LTD. p. 85. ISBN 8126109386, ISBN 9788126109388. 
  79. ^ a b c Oldstone, Michael (2010). Viruses, Plagues, and History. Oxford University Press. p. 65-71. ISBN 0195327314, ISBN 9780195327311. 
  80. ^ Montefiore, Young Stalin, p. 61
  81. ^ Szinnyei József: Magyar írók élete és munkái, Arcanum, Budapest, 2000, ISBN 9638602996

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


Simple English

File:Child with Smallpox
Child with smallpox, Bangladesh, 1973. Photo from the Centers for Disease Control and Prevention

Smallpox is a very bad disease with a high mortality rate. It is caused by a virus. There are two different kinds of viruses that cause the disease. They are called Variola major and Variola minor. Some people also call smallpox Variola, named after the viruses' scientific name.

Only people can get this disease. Variola major kills between 20% and 40% of those who get it. Variola minor kills only about 1%. Many people who survive become blind because of the damage the virus does to the eyes.

During the first half of the 20th century, between 300 million and 500 million people died of this disease. Even in 1967, about 15 million people caught the disease, and about two million people died of it, according to the World Health Organization (WHO).

The first cure for smallpox used the results of cowpox infections. A vaccine was developed and used to stop people getting smallpox. This vaccine, called vaccina, was the first vaccine ever made, and the word "vaccine" came from "vaccina". A vaccine is the real word for that "shot" we all have to get from time to time. In 1979, the WHO said the disease no longer existed, and no one would ever get sick from it again. However, live copies of smallpox are kept in different maximum-security laboratories around the world.

Some believe that smallpox could be used as an agent for purposely infecting enemies in a war. Today, most people no longer receive a smallpox shot; but a few very, very old people still need it.

If somebody has got smallpox, their entire body would be covered in bumps infiltrated by blood that are far worse than the chicken pox.

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