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| Smallpox | |
|---|---|
| Classification and external resources | |
Child infected with smallpox. Bangladesh, 1973. In ordinary type
smallpox the bumps are filled with a thick, opaque fluid and often have a
depression or dimple in the center. This is a major distinguishing
characteristic of smallpox.
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| ICD-10 | B03 |
| ICD-9 | 050 |
| DiseasesDB | 12219 |
| MedlinePlus | 001356 |
| eMedicine | emerg/885 |
| MeSH | D012899 |
Smallpox localized in small blood vessels of the skin and in the mouth and throat. In the skin it resulted 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.[6][7] Long-term complications of V. major infection include characteristic scars, commonly on the face, which occur in 65–85% of survivors.[8] 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.[4] The earliest physical evidence of it is probably the pustular rash on the mummified body of Pharaoh Ramses V of Egypt.[9] The disease killed an estimated 400,000 Europeans annually during the closing years of the 18th century (including five reigning monarchs),[10] and was responsible for a third of all blindness.[6][11] Of all those infected, 20–60%—and over 80% of infected children—died from the disease.[12] Smallpox was responsible for an estimated 300–500 million deaths during the 20th century.[13][14][15] 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.[5]
After vaccination campaigns throughout the 19th and 20th centuries, the WHO certified the eradication of smallpox in 1979.[5] Smallpox is one of two infectious diseases to have been eradicated, the other being rinderpest, which was declared eradicated in 2011.[16][17][18]
Contents
Classification
There were two clinical forms of smallpox. Variola major was the severe and most common form, with a more extensive rash and higher fever. Variola minor was a less common presentation, and a much less severe disease, with historical death rates of 1% or less.[19] Subclinical (asymptomatic) infections with variola virus were noted but were not common.[20] In addition, a form called variola sine eruptione (smallpox without rash) was seen generally in vaccinated persons. This form was marked by a fever that occurred after the usual incubation period and could be confirmed only by antibody studies or, rarely, by virus isolation.[20]Signs and symptoms
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.[7] At this point variola major infection can take several very different courses, resulting in four types of smallpox disease based on the Rao classification:[21] ordinary, modified, malignant (or flat), and hemorrhagic. Historically, smallpox has an overall fatality rate of about 30%; however, the malignant and hemorrhagic forms are usually fatal.[22]
Ordinary
Ninety percent or more of smallpox cases among unvaccinated persons are of the ordinary type.[20] 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.[7]By the sixth or seventh day, all the skin lesions have become pustules. Between seven and ten 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 depigmented scars.[23]
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. Sometimes, the blisters merge 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%.[20]
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.[23] Modified smallpox is rarely, if ever, fatal. This form of variola major is more easily confused with chickenpox.[20]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 the ordinary type. It is unknown why some people develop this type. Historically, it accounted for 5%–10% of cases, and the majority (72%) were children.[24] 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 extensive. Skin lesions mature slowly and by the seventh or eighth day they are flat and appear to be buried in the skin. Unlike ordinary-type smallpox, the vesicles contain little fluid, are soft and velvety to the touch, and may contain hemorrhages. Malignant smallpox is nearly always fatal.[20]Hemorrhagic
Hemorrhagic smallpox is a severe form that is accompanied by extensive bleeding into the skin, mucous membranes, and gastrointestinal tract. This form develops in approximately 2% of infections and occurred mostly in adults.[20] In hemorrhagic smallpox the skin does not blister, but remains smooth. Instead, bleeding occurs under the skin, making it look charred and black,[20] hence this form of the disease is also known as black pox.[25]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.[20] 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.[7] This form of smallpox occurs in anywhere from 3 to 25% of fatal cases depending on the virulence of the smallpox strain.[22] Hemorrhagic smallpox is usually fatal.[20]
Cause
| Variola virus (Smallpox) | |
|---|---|
 |
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| 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 | |
| Virus classification | |
| Group: | Group I (dsDNA) |
| Order: | Unassigned |
| Family: | Poxviridae |
| Subfamily: | Chordopoxvirinae |
| Genus: | Orthopoxvirus |
| Type species | |
| Vaccinia virus | |
| Species | |
|
Variola virus |
|
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.[20]
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.[27] Infection with either variola major or variola minor confers immunity against the other.[7]
Transmission
Transmission 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 (1.8 m), 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.[19] The virus can cross the placenta, but the incidence of congenital smallpox is relatively low.[7] 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.[20] 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.[29]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.[20] 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.[7] Smallpox is not known to be transmitted by insects or animals and there is no asymptomatic carrier state.[20]
Diagnosis
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.[20] 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.[30] 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.[7]
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.[31] 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.[32]
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.[20]
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Smallpox virus lesions on the chorioallantoic membrane of a developing chick.
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In contrast to the rash in smallpox, the rash in chickenpox occurs mostly on the torso, spreading less to the limbs.
Prevention
Main article: Smallpox vaccine
Lady Mary Wortley Montagu observed smallpox inoculation during her stay in the Ottoman Empire, writing detailed accounts of the practice in her letters, and enthusiastically promoted the procedure in England upon her return in 1718.[36] In 1721, Cotton Mather and colleagues provoked controversy in Boston by inoculating hundreds. 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.[20]
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.[38] 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.[39]
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, and was abandoned in most European countries in the early 1970s.[5][40] Routine vaccination of health care workers was discontinued in the U.S. in 1976, and among military recruits in 1990 (although military personnel deploying to the Middle East and Korea still receive the vaccination.[41]) By 1986, routine vaccination had ceased in all countries.[5] It is now primarily recommended for laboratory workers at risk for occupational exposure.[20]
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 can offer some protection from disease or may modify the severity of disease.[38] 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. People with semi-confluent and confluent types of smallpox may have therapeutic issues similar to patients with extensive skin burns.[42]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 kidney toxicity.[43]
Prognosis
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.[20] 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.[24] 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.[42]
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.[20]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.[7]
History
Main article: History of smallpox
Viral evolution
The date of the appearance of smallpox is not settled. It most likely evolved from a rodent virus between 68,000 and 16,000 years ago.[44][45] The wide range of dates is due to the different records used to calibrate the molecular clock. One clade was the variola major strains (the more clinically severe form of smallpox) which spread from Asia between 400 and 1,600 years ago. A second clade included both alastrim minor (a phenotypically mild smallpox) described from the American continents and isolates from West Africa which diverged from an ancestral strain between 1,400 and 6,300 years before present. This clade further diverged into two subclades at least 800 years ago.A second estimate has placed the separation of variola from Taterapox at 3000–4000 years ago.[46] This is consistent with archaeological and historical evidence regarding the appearance of smallpox as a human disease which suggests a relatively recent origin. However if the mutation rate is assumed to be similar to that of the herpesviruses the divergence date between variola from Taterapox has been estimated to be 50,000 years ago.[46] While this is consistent with the other published estimates it suggests that the archaeological and historical evidence is very incomplete. Better estimates of mutation rates in these viruses are needed.
It seems to have emerged in its endemic form in India 2500–3000 years ago.[47]
Other history
The earliest credible clinical evidence of smallpox is found in the smallpox-like disease in medical writings from ancient India (as early as 1500 BC),[48] Egyptian mummy of Ramses V who died more than 3000 years ago (1145 BC).[9] and China (1122 BC).[49] 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. Smallpox was probably introduced into China during the 1st century AD from the southwest, and in the 6th century was carried from China to Japan.[24] In Japan, the epidemic of 735–737 is believed to have killed as much as one-third of the population.[10][50] 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.[51]
Eradication
See also: Smallpox vaccine
The English physician Edward Jenner
demonstrated the effectiveness of cowpox to protect humans from
smallpox in 1796, after which 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.[60] The U.S. 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.[61] In British India
a program was launched to propagate smallpox vaccination, through
Indian vaccinators, under the supervision of European officials.[62]
Nevertheless, British vaccination efforts in India, and in Burma in
particular, were hampered by stubborn indigenous preference for
inoculation and distrust of vaccination, despite tough legislation,
improvements in the local efficacy of the vaccine and vaccine
preservative, and education efforts.[63] By 1832, the federal government of the United States established a smallpox vaccination program for Native Americans.[64] 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.[65]
In the United States, from 1843 to 1855 first Massachusetts, and then
other states required smallpox vaccination. Although some disliked these
measures,[49]
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.[66]
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.[67]
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.[73] 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.[74]
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 these countries in early and mid-1977, under the direction of Australian microbiologist Frank Fenner. As the campaign neared its goal, Fenner and his team played an important role in verifying eradication.[75] 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.[20] 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.[25]
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.[5][76] 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."
—World Health Organization, Resolution WHA33.3[77]
Post-eradication
In 1986, the World Health Organization first recommended destruction of the virus, and later set the date of destruction to be 30 December 1993. This was postponed to 30 June 1999.[79] Due to resistance from the U.S. and Russia, in 2002 the World Health Assembly agreed to permit the temporary retention of the virus stocks for specific research purposes.[80] Destroying existing stocks would reduce the risk involved with ongoing smallpox research; the stocks are not needed to respond to a smallpox outbreak.[81] Some scientists have argued that the stocks may be useful in developing new vaccines, antiviral drugs, and diagnostic tests;[82] however, a 2010 review by a team of public health experts appointed by the World Health Organization concluded that no essential public health purpose is served by the U.S. and Russia continuing to retain virus stocks.[83] The latter view is frequently supported in the scientific community, particularly among veterans of the WHO Smallpox Eradication Program.[84]
In March 2004 smallpox scabs were found tucked inside an envelope in a book on Civil War medicine in Santa Fe, New Mexico.[85] 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 U.S.
Society and culture
Biological warfare
The British considered using smallpox as a biological warfare agent at the Siege of Fort Pitt during the French and Indian Wars (1754–63) against France and its Native American allies.[86][87] Although it is not clear whether the actual use of smallpox had official sanction, on June 24, 1763, William Trent, a local trader, wrote, "Out of our regard for them [sc. representatives of the besieging Delawares], we gave them two Blankets and an Handkerchief out of the Small Pox Hospital. I hope it will have the desired effect."[88][89] 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).[90][91]Subsequently, according to an article in Journal of Australian Studies, in 1789, British marines used smallpox against indigenous tribes in New South Wales.[92] This occasion was also discussed earlier in Bulletin of the History of Medicine[93] and by David Day in his book Claiming a Continent A New History of Australia.[94]
During World War II, scientists from the United Kingdom, United States and Japan (Unit 731 of the imperial Japanese army) were involved in research into producing a biological weapon from smallpox.[95] 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.[96]
In 1947 the Soviet Union established a smallpox weapons factory in the city of Zagorsk, 75 km to the northeast of Moscow.[97] An outbreak of weaponized smallpox occurred during testing at a facility on an island in the Aral Sea in 1971. 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.[98][99]Others contend that the first patient may have contracted the disease while visiting Uyaly or Komsomolsk-on-Ustyurt, two cities where the boat docked.[100][101]
Responding to international pressures, in 1991 the Soviet government allowed a joint U.S.-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.[102] In 1992 Soviet defector Ken Alibek alleged 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, Alibek further alleged), along with refrigerated warheads to deliver it. Alibek's stories about the former Soviet program's smallpox activities have never been independently verified.
In 1997, the Russian government announced that all of its remaining smallpox samples would be moved to the Vector Institute in Koltsovo.[102] With the breakup of the Soviet Union and unemployment of many of the weapons program's scientists, U.S. government officials have expressed 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.[103] Specific allegations made against Iraq in this respect, however, proved to be false.[104]
Concern has been expressed by some that artificial gene synthesis could be used to recreate the virus from existing digital genomes, for use in biological warfare.[105] Insertion of the synthesized smallpox DNA into existing related pox viruses could theoretically be used to recreate the virus.[105] The first step to mitigating this risk, it has been suggested, should be to destroy the remaining virus stocks so as to enable unequivocal criminalization of any possession of the virus.[106]
Notable cases
Famous historical figures who contracted smallpox include Lakota Chief Sitting Bull, Ramses V of Egypt,[107] 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),[108] George Washington (survived), king Louis XV in 1774 (died) and Maximilian III Joseph, Elector of Bavaria in 1777.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 Russia, Peter II of Russia died of the disease at 15 years of age. Also, prior to becoming Russian Emperor, Peter III caught the virus and suffered greatly from it. He was left scarred and disfigured. His wife, Catherine the Great, was spared but fear of the virus clearly had its effects on her. She feared for her son and heir Pavel's safety so much that she made sure that large crowds were kept at bay and sought to isolate him. Eventually, she decided to have herself inoculated by a Scottish doctor, Thomas Dimsdale. While this was considered a controversial method at the time, she succeeded. Her son Pavel was later inoculated as well. Catherine then sought to have inoculations throughout her empire stating: "My objective was, through my example, to save from death the multitude of my subjects who, not knowing the value of this technique, and frightened of it, were left in danger." By 1800, approximately 2 million inoculations were administered in the Russian Empire.[109]
In China, the Qing Dynasty had extensive protocols to protect Manchus from Peking's endemic smallpox.
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 Barbados in 1751.[110] Jackson developed the illness after being taken prisoner by the British during the American Revolution, and though he recovered, his brother Robert did not.[110] Lincoln contracted the disease during his Presidency, possibly from his son Tad, and was quarantined shortly after giving the Gettysburg address in 1863.[110]
Famous theologian Jonathan Edwards died of smallpox in 1758 following an inoculation.[111]
Soviet leader Joseph 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.[112]
Hungarian poet Ferenc Kölcsey, who wrote the Hungarian national anthem, lost his right eye to smallpox.[113]
Tradition and religion
India’s first records of smallpox can be found in a medical book that dates back to A.D. 400. This book describes a disease that sounds exceptionally like smallpox.[115] India, like China, created a goddess in response to its exposure to smallpox. The Hindu goddess Shitala was both worshipped and feared during her reign. It was believed that this goddess was both evil and kind and had the ability to inflict victims when angered, as well as calm the fevers of the already afflicted.[116] Portraits of the goddess show her holding a broom in her right hand to continue to move the disease and a pot of cool water in the other hand in an attempt to soothe victims.[115] Shrines were created where many India natives, both healthy and not, went to worship and attempt to protect themselves from this disease. Some Indian women, in an attempt to ward off Shitala, placed plates of cooling foods and pots of water on the roofs of their homes.[117]
In medieval times, several countries held a belief in the smallpox demon, who was blamed for the disease. Such beliefs were prominent in Japan, Europe, Africa, and other parts of the world. Nearly all cultures who believed in the demon also believed that it was afraid of the color red. This led to the red treatment, where victims and their rooms would be decorated in red. The practice spread to Europe in the 12th century and was practiced by (among others) Charles V of France and Elizabeth I of England.[2] Given scientific credibility by some studies by Finsen showing red light reduced scarring,[2] the belief persisted until the 1930s.
See also
- 1837–1838 smallpox epidemic (in the U.S.)
- Aral smallpox incident
- Biological warfare
- CCR5-Δ32
- Columbian Exchange
- Herd immunity
- List of cutaneous conditions
- List of epidemics
- Mathematics of mass vaccination
- Pandemic
- Population history of indigenous peoples of the Americas
- Smallpox 2002—film
- Smallpox demon
- What the Ancients Did for Us—a BBC documentary highlighting ancient inoculation procedures in India
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