Smallpox

From Wikipedia for FEVERv2
Jump to navigation Jump to search

"Variola" redirects here. Smallpox_sentence_0

For other uses, see Variola (disambiguation). Smallpox_sentence_1

Smallpox_table_infobox_0

SmallpoxSmallpox_header_cell_0_0_0
Other namesSmallpox_header_cell_0_1_0 Variola, variola vera, pox, red plagueSmallpox_cell_0_1_1
SpecialtySmallpox_header_cell_0_2_0 Infectious diseaseSmallpox_cell_0_2_1
SymptomsSmallpox_header_cell_0_3_0 Smallpox_cell_0_3_1
ComplicationsSmallpox_header_cell_0_4_0 Scarring of the skin, blindnessSmallpox_cell_0_4_1
Usual onsetSmallpox_header_cell_0_5_0 1 to 3 weeks following exposureSmallpox_cell_0_5_1
DurationSmallpox_header_cell_0_6_0 About 4 weeksSmallpox_cell_0_6_1
CausesSmallpox_header_cell_0_7_0 Variola major, Variola minor (spread between people)Smallpox_cell_0_7_1
Diagnostic methodSmallpox_header_cell_0_8_0 Based on symptoms and confirmed by PCRSmallpox_cell_0_8_1
Differential diagnosisSmallpox_header_cell_0_9_0 Chickenpox, impetigo, molluscum contagiosum, monkeypoxSmallpox_cell_0_9_1
PreventionSmallpox_header_cell_0_10_0 Smallpox vaccineSmallpox_cell_0_10_1
TreatmentSmallpox_header_cell_0_11_0 Supportive careSmallpox_cell_0_11_1
PrognosisSmallpox_header_cell_0_12_0 30% risk of deathSmallpox_cell_0_12_1
FrequencySmallpox_header_cell_0_13_0 Eradicated (last wild case in 1977)Smallpox_cell_0_13_1

Smallpox was an infectious disease caused by one of two virus variants, Variola major and Variola minor. Smallpox_sentence_2

The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) certified the global eradication of the disease in 1980. Smallpox_sentence_3

The risk of death after contracting the disease was about 30%, with higher rates among babies. Smallpox_sentence_4

Often those who survived had extensive scarring of their skin, and some were left blind. Smallpox_sentence_5

The initial symptoms of the disease included fever and vomiting. Smallpox_sentence_6

This was followed by formation of ulcers in the mouth and a skin rash. Smallpox_sentence_7

Over a number of days the skin rash turned into characteristic fluid-filled blisters with a dent in the center. Smallpox_sentence_8

The bumps then scabbed over and fell off, leaving scars. Smallpox_sentence_9

The disease was spread between people or via contaminated objects. Smallpox_sentence_10

Prevention was achieved mainly through the smallpox vaccine. Smallpox_sentence_11

Once the disease had developed, certain antiviral medication may have helped. Smallpox_sentence_12

The origin of smallpox is unknown; however, the earliest evidence of the disease dates to the 3rd century BCE in Egyptian mummies. Smallpox_sentence_13

The disease historically occurred in outbreaks. Smallpox_sentence_14

In 18th-century Europe, it is estimated that 400,000 people died from the disease per year, and that one-third of all cases of blindness were due to smallpox. Smallpox_sentence_15

Smallpox is estimated to have killed up to 300 million people in the 20th century and around 500 million people in the last 100 years of its existence, as well as six monarchs.As recently as 1967, 15 million cases occurred a year. Smallpox_sentence_16

Inoculation for smallpox appears to have started in China around the 1500s. Smallpox_sentence_17

Europe adopted this practice from Asia in the first half of the 18th century. Smallpox_sentence_18

In 1796 Edward Jenner introduced the modern smallpox vaccine. Smallpox_sentence_19

In 1967, the WHO intensified efforts to eliminate the disease. Smallpox_sentence_20

Smallpox is one of two infectious diseases to have been eradicated, the other being rinderpest in 2011. Smallpox_sentence_21

The term "smallpox" was first used in Britain in the early 16th century to distinguish the disease from syphilis, which was then known as the "great pox". Smallpox_sentence_22

Other historical names for the disease include pox, speckled monster, and red plague. Smallpox_sentence_23

Classification Smallpox_section_0

Smallpox_table_general_1

Case fatality rate (CFR) and frequency of smallpox by type and vaccination status according to Rao case studySmallpox_table_caption_1
Type of diseaseSmallpox_header_cell_1_0_0 Ordinary ConfluentSmallpox_cell_1_0_1 Ordinary SemiconfluentSmallpox_cell_1_0_2 Ordinary DiscreteSmallpox_cell_1_0_3 ModifiedSmallpox_cell_1_0_4 FlatSmallpox_cell_1_0_5 Early HemorrhagicSmallpox_cell_1_0_6 Late hemorrhagicSmallpox_cell_1_0_7
Vaccinated CFRSmallpox_cell_1_1_0 26.3%Smallpox_cell_1_1_1 8.4%Smallpox_cell_1_1_2 0.7%Smallpox_cell_1_1_3 0%Smallpox_cell_1_1_4 66.7%Smallpox_cell_1_1_5 100%Smallpox_cell_1_1_6 89.8%Smallpox_cell_1_1_7
Unvaccinated CFRSmallpox_cell_1_2_0 62%Smallpox_cell_1_2_1 37%Smallpox_cell_1_2_2 9.3%Smallpox_cell_1_2_3 0%Smallpox_cell_1_2_4 96.5%Smallpox_cell_1_2_5 100%Smallpox_cell_1_2_6 96.8%Smallpox_cell_1_2_7
Vaccinated FrequencySmallpox_cell_1_3_0 4.6%Smallpox_cell_1_3_1 7%Smallpox_cell_1_3_2 58.4%Smallpox_cell_1_3_3 25.3%Smallpox_cell_1_3_4 1.3%Smallpox_cell_1_3_5 1.4%Smallpox_cell_1_3_6 2.0%Smallpox_cell_1_3_7
Unvaccinated FrequencySmallpox_cell_1_4_0 22.8%Smallpox_cell_1_4_1 23.9%Smallpox_cell_1_4_2 42.1%Smallpox_cell_1_4_3 2.1%Smallpox_cell_1_4_4 6.7%Smallpox_cell_1_4_5 0.7%Smallpox_cell_1_4_6 1.7%Smallpox_cell_1_4_7

There were two forms of the smallpox virus. Smallpox_sentence_24

Variola major was the severe and most common form, with a more extensive rash and higher fever. Smallpox_sentence_25

It could result in confluent smallpox, which had a high death rate of about 30%. Smallpox_sentence_26

Variola minor was a less common presentation, causing a less severe disease, typically discrete smallpox, with historical death rates of 1% or less. Smallpox_sentence_27

Subclinical (asymptomatic) infections with Variola virus were noted but were not common. Smallpox_sentence_28

In addition, a form called variola sine eruptione (smallpox without rash) was seen generally in vaccinated persons. Smallpox_sentence_29

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 viral culture. Smallpox_sentence_30

In addition, there were two very rare and fulminating types of smallpox, the malignant and hemorrhagic forms, which were usually fatal. Smallpox_sentence_31

Signs and symptoms Smallpox_section_1

The initial symptoms were similar to other viral diseases that are still extant, such as influenza and the common cold: fever of at least 38.3 °C (101 °F), muscle pain, malaise, headache and fatigue. Smallpox_sentence_32

As the digestive tract was commonly involved, nausea, vomiting and backache often occurred. Smallpox_sentence_33

The early prodromal stage usually lasted 2–4 days. Smallpox_sentence_34

By days 12–15, the first visible lesions – small reddish spots called enanthem – appeared on mucous membranes of the mouth, tongue, palate, and throat, and temperature fell to near-normal. Smallpox_sentence_35

These lesions rapidly enlarged and ruptured, releasing large amounts of virus into the saliva. Smallpox_sentence_36

Smallpox virus tended to attack skin cells, causing the characteristic pimples, or macules, associated with the disease. Smallpox_sentence_37

A rash developed on the skin 24 to 48 hours after lesions on the mucous membranes appeared. Smallpox_sentence_38

Typically the macules first appeared on the forehead, then rapidly spread to the whole face, proximal portions of extremities, the trunk, and lastly to distal portions of extremities. Smallpox_sentence_39

The process took no more than 24 to 36 hours, after which no new lesions appeared. Smallpox_sentence_40

At this point, variola major infection could take several very different courses, which resulted in four types of smallpox disease based on the Rao classification: ordinary, modified, malignant (or flat), and hemorrhagic smallpox. Smallpox_sentence_41

Historically, ordinary smallpox had an overall fatality rate of about 30%, and the malignant and hemorrhagic forms were usually fatal. Smallpox_sentence_42

The incubation period between contraction and the first obvious symptoms of the disease was around 12 days. Smallpox_sentence_43

Ordinary Smallpox_section_2

Ninety percent or more of smallpox cases among unvaccinated persons were of the ordinary type. Smallpox_sentence_44

In this form of the disease, by the second day of the rash the macules had become raised papules. Smallpox_sentence_45

By the third or fourth day, the papules had filled with an opalescent fluid to become vesicles. Smallpox_sentence_46

This fluid became opaque and turbid within 24–48 hours, resulting in pustules. Smallpox_sentence_47

By the sixth or seventh day, all the skin lesions had become pustules. Smallpox_sentence_48

Between seven and ten days the pustules had matured and reached their maximum size. Smallpox_sentence_49

The pustules were sharply raised, typically round, tense, and firm to the touch. Smallpox_sentence_50

The pustules were deeply embedded in the dermis, giving them the feel of a small bead in the skin. Smallpox_sentence_51

Fluid slowly leaked from the pustules, and by the end of the second week, the pustules had deflated and began to dry up, forming crusts or scabs. Smallpox_sentence_52

By day 16–20 scabs had formed over all of the lesions, which had started to flake off, leaving depigmented scars. Smallpox_sentence_53

Ordinary smallpox generally produced a discrete rash, in which the pustules stood out on the skin separately. Smallpox_sentence_54

The distribution of the rash was most dense on the face, denser on the extremities than on the trunk, and denser on the distal parts of the extremities than on the proximal. Smallpox_sentence_55

The palms of the hands and soles of the feet were involved in most cases. Smallpox_sentence_56

Sometimes, the blisters merged into sheets, forming a confluent rash, which began to detach the outer layers of skin from the underlying flesh. Smallpox_sentence_57

Patients with confluent smallpox often remained ill even after scabs had formed over all the lesions. Smallpox_sentence_58

In one case series, the case-fatality rate in confluent smallpox was 62 percent. Smallpox_sentence_59

Modified Smallpox_section_3

Referring to the character of the eruption and the rapidity of its development, modified smallpox occurred mostly in previously vaccinated people. Smallpox_sentence_60

It is rare in unvaccinated people, with 1–2% of cases being modified compared to around 25% in vaccinated people. Smallpox_sentence_61

In this form, the prodromal illness still occurred but may have been less severe than in the ordinary type. Smallpox_sentence_62

There was usually no fever during the evolution of the rash. Smallpox_sentence_63

The skin lesions tended to be fewer and evolved more quickly, were more superficial, and may not have shown the uniform characteristic of more typical smallpox. Smallpox_sentence_64

Modified smallpox was rarely, if ever, fatal. Smallpox_sentence_65

This form of variola major was more easily confused with chickenpox. Smallpox_sentence_66

Malignant Smallpox_section_4

In malignant-type smallpox (also called flat smallpox) the lesions remained almost flush with the skin at the time when raised vesicles would have formed in the ordinary type. Smallpox_sentence_67

It is unknown why some people developed this type. Smallpox_sentence_68

Historically, it accounted for 5–10 percent of cases, and most (72 percent) were children. Smallpox_sentence_69

Malignant smallpox was accompanied by a severe prodromal phase that lasted 3–4 days, prolonged high fever, and severe symptoms of viremia. Smallpox_sentence_70

The prodromal symptoms continued even after the onset of rash. Smallpox_sentence_71

The rash on the mucous membranes (enanthem) was extensive. Smallpox_sentence_72

Skin lesions matured slowly, were typically confluent or semi-confluent, and by the seventh or eighth day they were flat and appeared to be buried in the skin. Smallpox_sentence_73

Unlike ordinary-type smallpox, the vesicles contained little fluid, were soft and velvety to the touch, and may have contained hemorrhages. Smallpox_sentence_74

Malignant smallpox was nearly always fatal. Smallpox_sentence_75

Often, a day or two before death, the lesions turned ashen gray, which, along with abdominal distension, was a bad prognostic sign. Smallpox_sentence_76

If the person recovered, the lesions gradually faded and did not form scars or scabs. Smallpox_sentence_77

Hemorrhagic Smallpox_section_5

Hemorrhagic smallpox is a severe form accompanied by extensive bleeding into the skin, mucous membranes, gastrointestinal tract, and viscera. Smallpox_sentence_78

This form develops in approximately 2 percent of infections and occurs mostly in adults. Smallpox_sentence_79

Pustules do not typically form in hemorrhagic smallpox. Smallpox_sentence_80

Instead, bleeding occurs under the skin, making it look charred and black, hence this form of the disease is also referred to as variola nigra or "black pox." Smallpox_sentence_81

Hemorrhagic smallpox has very rarely been caused by Variola minor. Smallpox_sentence_82

While bleeding may occur in mild cases and not affect outcomes, hemorrhagic smallpox is typically fatal. Smallpox_sentence_83

Early Smallpox_section_6

The early or fulminant form of hemorrhagic smallpox (referred to as purpura variolosa) begins with a prodromal phase characterized by a high fever, severe headache, and abdominal pain. Smallpox_sentence_84

The skin becomes dusky and erythematous, and this is rapidly followed by the development of petechiae and bleeding in the skin, conjunctiva and mucous membranes. Smallpox_sentence_85

Autopsy reveals petechiae and bleeding in the spleen, kidney, serous membranes, skeletal muscles, pericardium, liver, gonads and bladder. Smallpox_sentence_86

Death often occurs suddenly between the fifth and seventh days of illness, when only a few insignificant skin lesions are present. Smallpox_sentence_87

Some people survive a few days longer, during which time the skin detaches and fluid accumulates under it, rupturing at the slightest injury. Smallpox_sentence_88

Historically, this condition was frequently misdiagnosed, with the correct diagnosis made only at autopsy. Smallpox_sentence_89

It is more likely to occur in pregnant women than in the general population (approximately 16% of cases in unvaccinated pregnant women were early hemorrhagic smallpox, versus roughly 1% in nonpregnant women and adult males). Smallpox_sentence_90

The case fatality rate of early hemorrhagic smallpox approaches 100%. Smallpox_sentence_91

Late Smallpox_section_7

There is also a later form of hemorrhagic smallpox (referred to as flat or late hemorrhagic smallpox, or variolosa pustula hemorrhagica). Smallpox_sentence_92

The prodrome is severe and similar to that observed in early hemorrhagic smallpox, and the fever persists throughout the course of the disease. Smallpox_sentence_93

Bleeding appears in the early eruptive period (but later than that seen in purpura variolosa), and the rash is often flat and does not progress beyond the vesicular stage. Smallpox_sentence_94

Sometimes the rash forms pustules which bleed at the base and then undergo the same process as in ordinary smallpox. Smallpox_sentence_95

This form of the disease is characterized by a decrease in all of the elements of the coagulation cascade and an increase in circulating antithrombin. Smallpox_sentence_96

This form of smallpox occurs in anywhere from 3 to 25 percent of fatal cases, depending on the virulence of the smallpox strain. Smallpox_sentence_97

Most people with the late-stage form die within 8 to 12 days of illness. Smallpox_sentence_98

Among the few who recover, the hemorrhagic lesions gradually disappear after a long period of convalescence. Smallpox_sentence_99

The case fatality rate for late hemorrhagic smallpox is 90 percent or greater. Smallpox_sentence_100

Cause Smallpox_section_8

Smallpox_table_infobox_2

Variola virusSmallpox_header_cell_2_0_0
Virus classification Variola_virusSmallpox_header_cell_2_1_0
(unranked):Smallpox_cell_2_2_0 VirusSmallpox_cell_2_2_1
Realm:Smallpox_cell_2_3_0 VaridnaviriaSmallpox_cell_2_3_1
Kingdom:Smallpox_cell_2_4_0 BamfordviraeSmallpox_cell_2_4_1
Phylum:Smallpox_cell_2_5_0 NucleocytoviricotaSmallpox_cell_2_5_1
Class:Smallpox_cell_2_6_0 PokkesviricetesSmallpox_cell_2_6_1
Order:Smallpox_cell_2_7_0 ChitoviralesSmallpox_cell_2_7_1
Family:Smallpox_cell_2_8_0 PoxviridaeSmallpox_cell_2_8_1
Genus:Smallpox_cell_2_9_0 OrthopoxvirusSmallpox_cell_2_9_1
Species:Smallpox_cell_2_10_0 †Variola virusSmallpox_cell_2_10_1

Smallpox was caused by infection with Variola virus, which belongs to the family Poxviridae, subfamily Chordopoxvirinae, and genus Orthopoxvirus. Smallpox_sentence_101

Evolution Smallpox_section_9

The date of the appearance of smallpox is not settled. Smallpox_sentence_102

It most likely evolved from a terrestrial African rodent virus between 68,000 and 16,000 years ago. Smallpox_sentence_103

The wide range of dates is due to the different records used to calibrate the molecular clock. Smallpox_sentence_104

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. Smallpox_sentence_105

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. Smallpox_sentence_106

This clade further diverged into two subclades at least 800 years ago. Smallpox_sentence_107

A second estimate has placed the separation of variola from Taterapox (an Orthopoxvirus of some African rodents including gerbils) at 3,000 to 4,000 years ago. Smallpox_sentence_108

This is consistent with archaeological and historical evidence regarding the appearance of smallpox as a human disease which suggests a relatively recent origin. Smallpox_sentence_109

If the mutation rate is assumed to be similar to that of the herpesviruses, the divergence date of variola from Taterapox has been estimated to be 50,000 years ago. Smallpox_sentence_110

While this is consistent with the other published estimates, it suggests that the archaeological and historical evidence is very incomplete. Smallpox_sentence_111

Better estimates of mutation rates in these viruses are needed. Smallpox_sentence_112

Examination of a strain that dates from c. 1650 found that this strain was basal to the other presently sequenced strains. Smallpox_sentence_113

The mutation rate of this virus is well modeled by a molecular clock. Smallpox_sentence_114

Diversification of strains only occurred in the 18th and 19th centuries. Smallpox_sentence_115

Virology Smallpox_section_10

Variola is a large brick-shaped virus measuring approximately 302 to 350 nanometers by 244 to 270 nm, with a single linear double stranded DNA genome 186 kilobase pairs (kbp) in size and containing a hairpin loop at each end. Smallpox_sentence_116

The two classic varieties of smallpox are variola major and variola minor. Smallpox_sentence_117

Four orthopoxviruses cause infection in humans: variola, vaccinia, cowpox, and monkeypox. Smallpox_sentence_118

Variola infects only humans in nature, although primates and other animals have been infected in an experimental setting. Smallpox_sentence_119

Vaccinia, cowpox, and monkeypox viruses can infect both humans and other animals in nature. Smallpox_sentence_120

The life cycle of poxviruses is complicated by having multiple infectious forms, with differing mechanisms of cell entry. Smallpox_sentence_121

Poxviruses are unique among DNA viruses in that they replicate in the cytoplasm of the cell rather than in the nucleus. Smallpox_sentence_122

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. Smallpox_sentence_123

Both enveloped and unenveloped virions are infectious. Smallpox_sentence_124

The viral envelope is made of modified Golgi membranes containing viral-specific polypeptides, including hemagglutinin. Smallpox_sentence_125

Infection with either variola major or variola minor confers immunity against the other. Smallpox_sentence_126

Transmission Smallpox_section_11

Transmission occurred through inhalation of airborne Variola virus, usually droplets expressed from the oral, nasal, or pharyngeal mucosa of an infected person. Smallpox_sentence_127

It was transmitted from one person to another primarily through prolonged face-to-face contact with an infected person, usually within a distance of 1.8 m (6 feet), but could also be spread through direct contact with infected bodily fluids or contaminated objects (fomites) such as bedding or clothing. Smallpox_sentence_128

Rarely, smallpox was spread by virus carried in the air in enclosed settings such as buildings, buses, and trains. Smallpox_sentence_129

The virus can cross the placenta, but the incidence of congenital smallpox was relatively low.Smallpox was not notably infectious in the prodromal period and viral shedding was usually delayed until the appearance of the rash, which was often accompanied by lesions in the mouth and pharynx. Smallpox_sentence_130

The virus can be transmitted throughout the course of the illness, but this happened most frequently during the first week of the rash, when most of the skin lesions were intact. Smallpox_sentence_131

Infectivity waned in 7 to 10 days when scabs formed over the lesions, but the infected person was contagious until the last smallpox scab fell off. Smallpox_sentence_132

Smallpox was highly contagious, but generally spread more slowly and less widely than some other viral diseases, perhaps because transmission required close contact and occurred after the onset of the rash. Smallpox_sentence_133

The overall rate of infection was also affected by the short duration of the infectious stage. Smallpox_sentence_134

In temperate areas, the number of smallpox infections was highest during the winter and spring. Smallpox_sentence_135

In tropical areas, seasonal variation was less evident and the disease was present throughout the year. Smallpox_sentence_136

Age distribution of smallpox infections depended on acquired immunity. Smallpox_sentence_137

Vaccination immunity declined over time and was probably lost within thirty years. Smallpox_sentence_138

Smallpox was not known to be transmitted by insects or animals and there was no asymptomatic carrier state. Smallpox_sentence_139

Mechanism Smallpox_section_12

Once inhaled, the variola virus invaded the mucus membranes of the mouth, throat, and respiratory tract. Smallpox_sentence_140

From there, it migrated to regional lymph nodes, and began to multiply. Smallpox_sentence_141

In the initial growth phase, the virus seemed to move from cell to cell, but by around the 12th day, widespread lysis of infected cells occurred and the virus could be found in the bloodstream in large numbers, a condition known as viremia. Smallpox_sentence_142

This resulted in a second wave of multiplication in the spleen, bone marrow, and lymph nodes. Smallpox_sentence_143

Diagnosis Smallpox_section_13

The clinical definition of ordinary smallpox is an illness with acute onset of fever equal to or greater than 38.3 °C (101 °F) followed by a rash characterized by firm, deep-seated vesicles or pustules in the same stage of development without other apparent cause. Smallpox_sentence_144

When a clinical case was observed, smallpox was confirmed using laboratory tests. Smallpox_sentence_145

Microscopically, poxviruses produce characteristic cytoplasmic inclusion bodies, the most important of which are known as Guarnieri bodies, and are the sites of viral replication. Smallpox_sentence_146

Guarnieri bodies are readily identified in skin biopsies stained with hematoxylin and eosin, and appear as pink blobs. Smallpox_sentence_147

They are found in virtually all poxvirus infections but the absence of Guarnieri bodies could not be used to rule out smallpox. Smallpox_sentence_148

The diagnosis of an orthopoxvirus infection can also be made rapidly by electron microscopic examination of pustular fluid or scabs. Smallpox_sentence_149

All orthopoxviruses exhibit identical brick-shaped virions by electron microscopy. Smallpox_sentence_150

If particles with the characteristic morphology of herpesviruses are seen this will eliminate smallpox and other orthopoxvirus infections. Smallpox_sentence_151

Definitive laboratory identification of Variola virus involved growing the virus on chorioallantoic membrane (part of a chicken embryo) and examining the resulting pock lesions under defined temperature conditions. Smallpox_sentence_152

Strains were characterized by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Smallpox_sentence_153

Serologic tests and enzyme linked immunosorbent assays (ELISA), which measured Variola virus-specific immunoglobulin and antigen were also developed to assist in the diagnosis of infection. Smallpox_sentence_154

Chickenpox was commonly confused with smallpox in the immediate post-eradication era. Smallpox_sentence_155

Chickenpox and smallpox could be distinguished by several methods. Smallpox_sentence_156

Unlike smallpox, chickenpox does not usually affect the palms and soles. Smallpox_sentence_157

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. Smallpox_sentence_158

A variety of laboratory methods were available for detecting chickenpox in the evaluation of suspected smallpox cases. Smallpox_sentence_159

Smallpox_unordered_list_0

  • Smallpox_item_0_0
  • Smallpox_item_0_1
  • Smallpox_item_0_2

Prevention Smallpox_section_14

Main article: Smallpox vaccine Smallpox_sentence_160

The earliest procedure used to prevent smallpox was inoculation with variola minor (known as variolation after the introduction of smallpox vaccine to avoid possible confusion), which likely occurred in India, Africa, and China well before the practice arrived in Europe. Smallpox_sentence_161

The idea that inoculation originated in India has been challenged, as few of the ancient Sanskrit medical texts described the process of inoculation. Smallpox_sentence_162

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. Smallpox_sentence_163

If successful, inoculation produced lasting immunity to smallpox. Smallpox_sentence_164

Because the person was infected with Variola virus, a severe infection could result, and the person could transmit smallpox to others. Smallpox_sentence_165

Variolation had a 0.5–2 percent mortality rate, considerably less than the 20–30 percent mortality rate of the disease. Smallpox_sentence_166

Two reports on the Chinese practice of inoculation were received by the Royal Society in London in 1700; one by Dr. Martin Lister who received a report by an employee of the East India Company stationed in China and another by Clopton Havers. Smallpox_sentence_167

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. Smallpox_sentence_168

According to Voltaire (1742), the Turks derived their use of inoculation from neighbouring Circassia. Smallpox_sentence_169

Voltaire does not speculate on where the Circassians derived their technique from, though he reports that the Chinese have practiced it "these hundred years". Smallpox_sentence_170

In 1721, Cotton Mather and colleagues provoked controversy in Boston by inoculating hundreds. Smallpox_sentence_171

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. Smallpox_sentence_172

Cowpox is a poxvirus in the same family as variola. Smallpox_sentence_173

Jenner called the material used for inoculation vaccine from the root word vacca, which is Latin for cow. Smallpox_sentence_174

The procedure was much safer than variolation and did not involve a risk of smallpox transmission. Smallpox_sentence_175

Vaccination to prevent smallpox was soon practiced all over the world. Smallpox_sentence_176

During the 19th century, the cowpox virus used for smallpox vaccination was replaced by vaccinia virus. Smallpox_sentence_177

Vaccinia is in the same family as cowpox and variola, but is genetically distinct from both. Smallpox_sentence_178

The origin of vaccinia virus and how it came to be in the vaccine are not known. Smallpox_sentence_179

The current formulation of smallpox vaccine is a live virus preparation of infectious vaccinia virus. Smallpox_sentence_180

The vaccine is given using a bifurcated (two-pronged) needle that is dipped into the vaccine solution. Smallpox_sentence_181

The needle is used to prick the skin (usually the upper arm) a number of times in a few seconds. Smallpox_sentence_182

If successful, a red and itchy bump develops at the vaccine site in three or four days. Smallpox_sentence_183

In the first week, the bump becomes a large blister (called a "Jennerian vesicle") which fills with pus, and begins to drain. Smallpox_sentence_184

During the second week, the blister begins to dry up and a scab forms. Smallpox_sentence_185

The scab falls off in the third week, leaving a small scar. Smallpox_sentence_186

The antibodies induced by vaccinia vaccine are cross-protective for other orthopoxviruses, such as monkeypox, cowpox, and variola (smallpox) viruses. Smallpox_sentence_187

Neutralizing antibodies are detectable 10 days after first-time vaccination, and seven days after revaccination. Smallpox_sentence_188

Historically, the vaccine has been effective in preventing smallpox infection in 95 percent of those vaccinated. Smallpox_sentence_189

Smallpox vaccination provides a high level of immunity for three to five years and decreasing immunity thereafter. Smallpox_sentence_190

If a person is vaccinated again later, immunity lasts even longer. Smallpox_sentence_191

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 percent; it was 7 percent among those vaccinated 11 to 20 years prior, and 11 percent among those vaccinated 20 or more years prior to infection. Smallpox_sentence_192

By contrast, 52 percent of unvaccinated persons died. Smallpox_sentence_193

There are side effects and risks associated with the smallpox vaccine. Smallpox_sentence_194

In the past, about 1 out of 1,000 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. Smallpox_sentence_195

Potentially life-threatening reactions occurred in 14 to 500 people out of every 1 million people vaccinated for the first time. Smallpox_sentence_196

Based on past experience, it is estimated that 1 or 2 people in 1 million (0.000198 percent) 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). Smallpox_sentence_197

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. Smallpox_sentence_198

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). Smallpox_sentence_199

By 1986, routine vaccination had ceased in all countries. Smallpox_sentence_200

It is now primarily recommended for laboratory workers at risk for occupational exposure. Smallpox_sentence_201

However, the possibility of smallpox virus being used as a biological weapon has rekindled interest in the development of newer vaccines. Smallpox_sentence_202

Treatment Smallpox_section_15

Smallpox vaccination within three days of exposure will prevent or significantly lessen the severity of smallpox symptoms in the vast majority of people. Smallpox_sentence_203

Vaccination four to seven days after exposure can offer some protection from disease or may modify the severity of disease. Smallpox_sentence_204

Other than vaccination, treatment of smallpox is primarily supportive, such as wound care and infection control, fluid therapy, and possible ventilator assistance. Smallpox_sentence_205

Flat and hemorrhagic types of smallpox are treated with the same therapies used to treat shock, such as fluid resuscitation. Smallpox_sentence_206

People with semi-confluent and confluent types of smallpox may have therapeutic issues similar to patients with extensive skin burns. Smallpox_sentence_207

In July 2018, the Food and Drug Administration approved tecovirimat, the first drug approved for treatment of smallpox. Smallpox_sentence_208

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. Smallpox_sentence_209

The drug must be administered intravenously, and may cause serious kidney toxicity. Smallpox_sentence_210

ACAM2000 is a smallpox vaccine developed by Acambis. Smallpox_sentence_211

It was approved for use in the United States by the U.S. FDA on August 31, 2007. Smallpox_sentence_212

It contains live vaccinia virus, cloned from the same strain used in an earlier vaccine, Dryvax. Smallpox_sentence_213

While the Dryvax virus was cultured in the skin of calves and freeze-dried, ACAM2000s virus is cultured in kidney epithelial cells (Vero cells) from an African green monkey. Smallpox_sentence_214

Efficacy and adverse reaction incidence are similar to Dryvax. Smallpox_sentence_215

The vaccine is not routinely available to the US public; it is, however, used in the military and maintained in the Strategic National Stockpile. Smallpox_sentence_216

Prognosis Smallpox_section_16

The overall case-fatality rate for ordinary-type smallpox is about 30 percent, but varies by pock distribution. Smallpox_sentence_217

Ordinary type-confluent is fatal about 50–75 percent of the time, ordinary-type semi-confluent about 25–50 percent of the time, in cases where the rash is discrete the case-fatality rate is less than 10 percent. Smallpox_sentence_218

The overall fatality rate for children younger than 1 year of age is 40–50 percent. Smallpox_sentence_219

Hemorrhagic and flat types have the highest fatality rates. Smallpox_sentence_220

The fatality rate for flat or late hemorrhagic type smallpox is 90 percent or greater and nearly 100 percent is observed in cases of early hemorrhagic smallpox. Smallpox_sentence_221

The case-fatality rate for variola minor is 1 percent or less. Smallpox_sentence_222

There is no evidence of chronic or recurrent infection with Variola virus. Smallpox_sentence_223

In cases of flat smallpox in vaccinated people, the condition was extremely rare but less lethal, with one case series showing a 66.7% death rate. Smallpox_sentence_224

In fatal cases of ordinary smallpox, death usually occurs between the tenth and sixteenth days of the illness. Smallpox_sentence_225

The cause of death from smallpox is not clear, but the infection is now known to involve multiple organs. Smallpox_sentence_226

Circulating immune complexes, overwhelming viremia, or an uncontrolled immune response may be contributing factors. Smallpox_sentence_227

In early hemorrhagic smallpox, death occurs suddenly about six days after the fever develops. Smallpox_sentence_228

Cause of death in early hemorrhagic cases involved heart failure, sometimes accompanied by pulmonary edema. Smallpox_sentence_229

In late hemorrhagic cases, high and sustained viremia, severe platelet loss and poor immune response were often cited as causes of death. Smallpox_sentence_230

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. Smallpox_sentence_231

Complications Smallpox_section_17

Complications of smallpox arise most commonly in the respiratory system and range from simple bronchitis to fatal pneumonia. Smallpox_sentence_232

Respiratory complications tend to develop on about the eighth day of the illness and can be either viral or bacterial in origin. Smallpox_sentence_233

Secondary bacterial infection of the skin is a relatively uncommon complication of smallpox. Smallpox_sentence_234

When this occurs, the fever usually remains elevated. Smallpox_sentence_235

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 percent of all cases). Smallpox_sentence_236

Pustules can form on the eyelid, conjunctiva, and cornea, leading to complications such as conjunctivitis, keratitis, corneal ulcer, iritis, iridocyclitis, and optic atrophy. Smallpox_sentence_237

Blindness results in approximately 35 percent to 40 percent of eyes affected with keratitis and corneal ulcer. Smallpox_sentence_238

Hemorrhagic smallpox can cause subconjunctival and retinal hemorrhages. Smallpox_sentence_239

In 2 to 5 percent of young children with smallpox, virions reach the joints and bone, causing osteomyelitis variolosa. Smallpox_sentence_240

Lesions are symmetrical, most common in the elbows, tibia, and fibula, and characteristically cause separation of an epiphysis and marked periosteal reactions. Smallpox_sentence_241

Swollen joints limit movement, and arthritis may lead to limb deformities, ankylosis, malformed bones, flail joints, and stubby fingers. Smallpox_sentence_242

History Smallpox_section_18

Main article: History of smallpox Smallpox_sentence_243

Disease emergence Smallpox_section_19

The earliest credible clinical evidence of smallpox is found in the descriptions of smallpox-like disease in medical writings from ancient India (as early as 1500 BCE), and China (1122 BCE), as well as a study of the Egyptian mummy of Ramses V, who died more than 3000 years ago (1145 BCE). Smallpox_sentence_244

It has been speculated that Egyptian traders brought smallpox to India during the 1st millennium BCE, where it remained as an endemic human disease for at least 2000 years. Smallpox_sentence_245

Smallpox was probably introduced into China during the 1st century CE from the southwest, and in the 6th century was carried from China to Japan. Smallpox_sentence_246

In Japan, the epidemic of 735–737 is believed to have killed as much as one-third of the population. Smallpox_sentence_247

At least seven religious deities have been specifically dedicated to smallpox, such as the god Sopona in the Yoruba religion in West Africa. Smallpox_sentence_248

In India, the Hindu goddess of smallpox, Shitala, was worshipped in temples throughout the country. Smallpox_sentence_249

A different viewpoint is that smallpox emerged 1588 CE and the earlier reported cases were incorrectly identified as smallpox. Smallpox_sentence_250

The timing of the arrival of smallpox in Europe and south-western Asia is less clear. Smallpox_sentence_251

Smallpox is not clearly described in either the Old or New Testaments of the Bible or in the literature of the Greeks or Romans. Smallpox_sentence_252

While some have identified the Plague of Athens – which was said to have originated in "Ethiopia" and Egypt – or the plague that lifted Carthage's 396 BCE siege of Syracuse – with smallpox, many scholars agree it is very unlikely such a serious disease as variola major would have escaped being described by Hippocrates if it had existed in the Mediterranean region during his lifetime. Smallpox_sentence_253

While the Antonine Plague that swept through the Roman Empire in 165–180 CE may have been caused by smallpox, Saint Nicasius of Rheims became the patron saint of smallpox victims for having supposedly survived a bout in 450, and Saint Gregory of Tours recorded a similar outbreak in France and Italy in 580, the first use of the term variola; other historians speculate that Arab armies first carried smallpox from Africa into Southwestern Europe during the 7th and 8th centuries. Smallpox_sentence_254

In the 9th century the Persian physician, Rhazes, provided one of the most definitive descriptions 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). Smallpox_sentence_255

During the Middle Ages several smallpox outbreaks occurred in Europe. Smallpox_sentence_256

However, smallpox had not become established there until the population growth and mobility marked by the Crusades allowed it to do so. Smallpox_sentence_257

By the 16th century, smallpox had become entrenched across most of Europe, where it had a mortality rate as high as 30 percent. Smallpox_sentence_258

This endemic occurrence of smallpox in Europe is of particular historical importance, as successive exploration and colonization by Europeans tended to spread the disease to other nations. Smallpox_sentence_259

By the 16th century, smallpox had become a predominant cause of morbidity and mortality throughout much of the world. Smallpox_sentence_260

There were no credible descriptions of smallpox-like disease in the Americas before the westward exploration by Europeans in the 15th century CE. Smallpox_sentence_261

Smallpox was introduced into the Caribbean island of Hispaniola in 1509, and into the mainland in 1520, when Spanish settlers from Hispaniola arrived in Mexico, inadvertently carrying smallpox with them. Smallpox_sentence_262

Because the native Amerindian population had no acquired immunity to this new disease, their peoples were decimated by epidemics. Smallpox_sentence_263

Such disruption and population losses were an important factor in the Spanish achieving conquest of the Aztecs and the Incas. Smallpox_sentence_264

Similarly, English settlement of the east coast of North America in 1633 in Plymouth, Massachusetts was accompanied by devastating outbreaks of smallpox among Native American populations, and subsequently among the native-born colonists. Smallpox_sentence_265

Case fatality rates during outbreaks in Native American populations were as high as 80–90%. Smallpox_sentence_266

Smallpox was introduced into Australia in 1789 and again in 1829; though colonial surgeons, who by 1829 were attempting to distinguish between smallpox and chickenpox (which could be almost equally fatal to Aborigines), were divided as to whether the 1829–1830 epidemic was chickenpox or smallpox. Smallpox_sentence_267

Although smallpox was never endemic on the continent, it has been described as the principal cause of death in Aboriginal populations between 1780 and 1870. Smallpox_sentence_268

By the mid-18th century, smallpox was a major endemic disease everywhere in the world except in Australia and in small islands untouched by outside exploration. Smallpox_sentence_269

In 18th century Europe, smallpox was a leading cause of death, killing an estimated 400,000 Europeans each year. Smallpox_sentence_270

Up to 10 percent of Swedish infants died of smallpox each year, and the death rate of infants in Russia might have been even higher. Smallpox_sentence_271

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. Smallpox_sentence_272

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. Smallpox_sentence_273

By the mid-20th century, variola minor occurred along with variola major, in varying proportions, in many parts of Africa. Smallpox_sentence_274

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. Smallpox_sentence_275

Infection with v. minor induces immunity against the more deadly variola major form. Smallpox_sentence_276

Thus, as v. minor spread all over the US, into Canada, the South American countries and Great Britain, it became the dominant form of smallpox, further reducing mortality rates. Smallpox_sentence_277

Eradication Smallpox_section_20

See also: Smallpox vaccine and Inoculation Smallpox_sentence_278

The first clear reference to smallpox inoculation was made by the Chinese author Wan Quan (1499–1582) in his Douzhen xinfa (痘疹心法) published in 1549, with earliest hints of the practice in China during the 10th century. Smallpox_sentence_279

In China, powdered smallpox scabs were blown up the noses of the healthy. Smallpox_sentence_280

People would then develop a mild case of the disease and from then on were immune to it. Smallpox_sentence_281

The technique did have a 0.5–2.0% mortality rate, but that was considerably less than the 20–30% mortality rate of the disease itself. Smallpox_sentence_282

Two reports on the Chinese practice of inoculation were received by the Royal Society in London in 1700; one by Dr. Martin Lister who received a report by an employee of the East India Company stationed in China and another by Clopton Havers. Smallpox_sentence_283

Voltaire (1742) reports that the Chinese had practiced smallpox inoculation "these hundred years". Smallpox_sentence_284

Variolation had also been witnessed in Turkey by Lady Mary Wortley Montagu, who later introduced it in the UK. Smallpox_sentence_285

An early mention of the possibility of smallpox's eradication was made in reference to the work of Johnnie Notions, a self-taught inoculator from Shetland, Scotland. Smallpox_sentence_286

Notions found success in treating people from at least the late 1780s through a method devised by himself despite having no formal medical background. Smallpox_sentence_287

His method involved exposing smallpox pus to peat smoke, burying it in the ground with camphor for up to 8 years, and then inserting the matter into a person's skin using a knife, and covering the incision with a cabbage leaf. Smallpox_sentence_288

He was reputed not to have lost a single patient. Smallpox_sentence_289

Arthur Edmondston, in writings on Notions' technique that were published in 1809, stated, "Had every practitioner been as uniformly successful in the disease as he was, the small-pox might have been banished from the face of the earth, without injuring the system, or leaving any doubt as to the fact." Smallpox_sentence_290

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. Smallpox_sentence_291

In Russia in 1796, the first child to receive this treatment was bestowed the name "Vaccinov" by Catherine the Great, and was educated at the expense of the nation. Smallpox_sentence_292

The introduction of the vaccine to the New World took place in Trinity, Newfoundland in 1800 by Dr. Smallpox_sentence_293 John Clinch, boyhood friend and medical colleague of Jenner. Smallpox_sentence_294

As early as 1803, the Spanish Crown organized the Balmis expedition to transport the vaccine to the Spanish colonies in the Americas and the Philippines, and establish mass vaccination programs there. Smallpox_sentence_295

The U.S. Smallpox_sentence_296 Congress passed the Vaccine Act of 1813 to ensure that safe smallpox vaccine would be available to the American public. Smallpox_sentence_297

By about 1817, a very solid state vaccination program existed in the Dutch East Indies. Smallpox_sentence_298

In British India a program was launched to propagate smallpox vaccination, through Indian vaccinators, under the supervision of European officials. Smallpox_sentence_299

Nevertheless, British vaccination efforts in India, and in Burma in particular, were hampered by 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. Smallpox_sentence_300

By 1832, the federal government of the United States established a smallpox vaccination program for Native Americans. Smallpox_sentence_301

In 1842, the United Kingdom banned inoculation, later progressing to mandatory vaccination. Smallpox_sentence_302

The British government introduced compulsory smallpox vaccination by an Act of Parliament in 1853. Smallpox_sentence_303

In the United States, from 1843 to 1855, first Massachusetts and then other states required smallpox vaccination. Smallpox_sentence_304

Although some disliked these measures, coordinated efforts against smallpox went on, and the disease continued to diminish in the wealthy countries. Smallpox_sentence_305

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. Smallpox_sentence_306

Vaccination continued in industrialized countries as protection against reintroduction until the mid to late 1970s. Smallpox_sentence_307

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. Smallpox_sentence_308

The first hemisphere-wide effort to eradicate smallpox was made in 1950 by the Pan American Health Organization. Smallpox_sentence_309

The campaign was successful in eliminating smallpox from all countries of the Americas except Argentina, Brazil, Colombia, and Ecuador. Smallpox_sentence_310

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. Smallpox_sentence_311

The proposal (Resolution WHA11.54) was accepted in 1959. Smallpox_sentence_312

At this point, 2 million people were dying from smallpox every year. Smallpox_sentence_313

Overall, the progress towards eradication was disappointing, especially in Africa and in the Indian subcontinent. Smallpox_sentence_314

In 1966 an international team, the Smallpox Eradication Unit, was formed under the leadership of an American, Donald Henderson. Smallpox_sentence_315

In 1967, the World Health Organization intensified the global smallpox eradication by contributing $2.4 million annually to the effort, and adopted the new disease surveillance method promoted by Czech epidemiologist Karel Raška. Smallpox_sentence_316

In the early 1950s, an estimated 50 million cases of smallpox occurred in the world each year. Smallpox_sentence_317

To eradicate smallpox, each outbreak had to be stopped from spreading, by isolation of cases and vaccination of everyone who lived close by. Smallpox_sentence_318

This process is known as "ring vaccination". Smallpox_sentence_319

The key to this strategy was the monitoring of cases in a community (known as surveillance) and containment. Smallpox_sentence_320

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. Smallpox_sentence_321

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. Smallpox_sentence_322

The WHO established a network of consultants who assisted countries in setting up surveillance and containment activities. Smallpox_sentence_323

Early on, donations of vaccine were provided primarily by the Soviet Union and the United States, but by 1973, more than 80 percent of all vaccine was produced in developing countries. Smallpox_sentence_324

The Soviet Union provided one and a half billion doses between 1958 and 1979, as well as medical staff. Smallpox_sentence_325

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. Smallpox_sentence_326

The epidemic infected 175 people, causing 35 deaths. Smallpox_sentence_327

Authorities declared martial law, enforced quarantine, and undertook widespread re-vaccination of the population, enlisting the help of the WHO. Smallpox_sentence_328

In two months, the outbreak was over. Smallpox_sentence_329

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. Smallpox_sentence_330

By the end of 1975, smallpox persisted only in the Horn of Africa. Smallpox_sentence_331

Conditions were very difficult in Ethiopia and Somalia, where there were few roads. Smallpox_sentence_332

Civil war, famine, and refugees made the task even more difficult. Smallpox_sentence_333

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. Smallpox_sentence_334

As the campaign neared its goal, Fenner and his team played an important role in verifying eradication. Smallpox_sentence_335

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. Smallpox_sentence_336

The last naturally occurring case of the more deadly Variola major had been detected in October 1975 in a three-year-old Bangladeshi girl, Rahima Banu. Smallpox_sentence_337

The global eradication of smallpox was certified, based on intense verification activities, by a commission of eminent scientists on 9 December 1979 and subsequently endorsed by the World Health Assembly on 8 May 1980. Smallpox_sentence_338

The first two sentences of the resolution read: Smallpox_sentence_339

Costs and benefits Smallpox_section_21

The cost of the eradication effort, from 1967 to 1979, was roughly $300 million US dollars. Smallpox_sentence_340

Roughly a third came from the developed world, which had largely eradicated smallpox decades earlier. Smallpox_sentence_341

The United States, the largest contributor to the program, has reportedly recouped that investment every 26 days since in money not spent on (a) vaccinations and (b) the costs of incidence. Smallpox_sentence_342

Post-eradication Smallpox_section_22

Further information: Smallpox virus retention debate Smallpox_sentence_343

The last case of smallpox in the world occurred in an outbreak in the United Kingdom in 1978. Smallpox_sentence_344

A medical photographer, Janet Parker, contracted the disease at the University of Birmingham Medical School and died on 11 September 1978. Smallpox_sentence_345

Although it has remained unclear how Parker became infected, the source of the infection was established to be the smallpox virus grown for research purposes at the Medical School laboratory. Smallpox_sentence_346

All known stocks of smallpox worldwide were subsequently destroyed or transferred to two WHO-designated reference laboratories with BSL-4 facilities – the United States' Centers for Disease Control and Prevention (CDC) and Russia's State Research Center of Virology and Biotechnology VECTOR. Smallpox_sentence_347

WHO first recommended destruction of the virus in 1986 and later set the date of destruction to be 30 December 1993. Smallpox_sentence_348

This was postponed to 30 June 1999. Smallpox_sentence_349

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. Smallpox_sentence_350

Destroying existing stocks would reduce the risk involved with ongoing smallpox research; the stocks are not needed to respond to a smallpox outbreak. Smallpox_sentence_351

Some scientists have argued that the stocks may be useful in developing new vaccines, antiviral drugs, and diagnostic tests; a 2010 review by a team of public health experts appointed by WHO concluded that no essential public health purpose is served by the U.S. and Russia continuing to retain virus stocks. Smallpox_sentence_352

The latter view is frequently supported in the scientific community, particularly among veterans of the WHO Smallpox Eradication Program. Smallpox_sentence_353

In March 2004, smallpox scabs were found inside an envelope in a book on Civil War medicine in Santa Fe, New Mexico. Smallpox_sentence_354

The envelope was labeled as containing scabs from a vaccination and gave scientists at the CDC an opportunity to study the history of smallpox vaccination in the United States. Smallpox_sentence_355

On July 1, 2014, six sealed glass vials of smallpox dated 1954, along with sample vials of other pathogens, were discovered in a cold storage room in an FDA laboratory at the National Institutes of Health location in Bethesda, Maryland. Smallpox_sentence_356

The smallpox vials were subsequently transferred to the custody of the CDC in Atlanta, where virus taken from at least two vials proved viable in culture. Smallpox_sentence_357

After studies were conducted, the CDC destroyed the virus under WHO observation on February 24, 2015. Smallpox_sentence_358

In 2017, Canadian scientists recreated an extinct horse pox virus to demonstrate that the smallpox virus can be recreated in a small lab at a cost of about $100,000, by a team of scientists without specialist knowledge. Smallpox_sentence_359

This makes the retention controversy moot since the virus can be easily recreated even if all samples are destroyed. Smallpox_sentence_360

Although the scientists performed the research to help development of new vaccines as well as trace smallpox's history, the possibility of the techniques being used for nefarious purposes was immediately recognized, raising questions on dual use research and regulations. Smallpox_sentence_361

In September 2019, the Russian lab housing smallpox samples experienced a gas explosion that injured one worker. Smallpox_sentence_362

It did not occur near the virus storage area, and no samples were compromised, but the incident prompted a review of risks to containment. Smallpox_sentence_363

Society and culture Smallpox_section_23

Biological warfare Smallpox_section_24

The British used smallpox as a biological warfare agent at the Siege of Fort Pitt during the French and Indian Wars (1754–1763) against France and its Native American allies. Smallpox_sentence_364

British officers, including the top British commanding generals, ordered, sanctioned, paid for and conducted the use of smallpox against the Native Americans. Smallpox_sentence_365

As described by historians, "there is no doubt that British military authorities approved of attempts to spread smallpox among the enemy", and "it was deliberate British policy to infect the Indians with smallpox". Smallpox_sentence_366

On 24 June 1763, William Trent, a local trader and commander of the Fort Pitt militia, wrote, "Out of our regard for them, we gave them two Blankets and an Handkerchief out of the Small Pox Hospital. Smallpox_sentence_367

I hope it will have the desired effect." Smallpox_sentence_368

The effectiveness of this effort to broadcast the disease is unknown. Smallpox_sentence_369

There are also accounts that smallpox was used as a weapon during the American Revolutionary War (1775–1783). Smallpox_sentence_370

According to a theory put forward in Journal of Australian Studies (JAS) by independent researcher Christopher Warren, British marines used smallpox in 1789 against indigenous tribes in New South Wales. Smallpox_sentence_371

This theory was also considered earlier in Bulletin of the History of Medicine and by David Day. Smallpox_sentence_372

However it is disputed by some medical academics, including Professor Jack Carmody, who in 2010 claimed that the rapid spread of the outbreak in question was more likely indicative of chickenpox—a more infectious disease which, at the time, was often confused, even by surgeons, with smallpox, and was in fact comparably deadly to Aborigines and to other peoples without natural immunity to it. Smallpox_sentence_373

Carmody noted that in the 8-month voyage of the First Fleet and the following 14 months there were no reports of smallpox amongst the colonists and that, since smallpox has an incubation period of 10–12 days, it is unlikely it was present in the First Fleet; however, Warren argued in the JAS article that the likely source was bottles of smallpox virus possessed by First Fleet surgeons. Smallpox_sentence_374

Ian and Jennifer Glynn, in The life and death of smallpox, confirm that bottles of "variolous matter" were carried to Australia for use as a vaccine, but think it unlikely the virus could have survived till 1789. Smallpox_sentence_375

In 2007, Christopher Warren offered evidence that the British smallpox may have been still viable. Smallpox_sentence_376

However, the only non-Aborigine reported to have died in this outbreak was a seaman called Joseph Jeffries, who was recorded as being of "American Indian" origin. Smallpox_sentence_377

W. S. Carus, an expert in biological weapons, has written that there is circumstantial evidence that smallpox was deliberately introduced to the Aboriginal population. Smallpox_sentence_378

However Carmody and the Australian National University's Boyd Hunter continue to support the chickenpox hypothesis. Smallpox_sentence_379

In a 2013 lecture at the Australian National University , Carmody pointed out that chickenpox, unlike smallpox, was known to be present in the colony. Smallpox_sentence_380

He also suggested that all C18th (and earlier) identifications of smallpox outbreaks were dubious because: “surgeons . Smallpox_sentence_381

. Smallpox_sentence_382

. Smallpox_sentence_383

would have been unaware of the distinction between smallpox and chickenpox - the latter having traditionally been considered a milder form of smallpox.” Smallpox_sentence_384

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. Smallpox_sentence_385

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. Smallpox_sentence_386

In 1947 the Soviet Union established a smallpox weapons factory in the city of Zagorsk, 75 km to the northeast of Moscow. Smallpox_sentence_387

An outbreak of weaponized smallpox occurred during testing at a facility on an island in the Aral Sea in 1971. Smallpox_sentence_388

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: Smallpox_sentence_389

Others contend that the first patient may have contracted the disease while visiting Uyaly or Komsomolsk-on-Ustyurt, two cities where the boat docked. Smallpox_sentence_390

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. Smallpox_sentence_391

The inspectors were met with evasion and denials from the Soviet scientists, and were eventually ordered out of the facility. Smallpox_sentence_392

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. Smallpox_sentence_393

Alibek's stories about the former Soviet program's smallpox activities have never been independently verified. Smallpox_sentence_394

In 1997, the Russian government announced that all of its remaining smallpox samples would be moved to the Vector Institute in Koltsovo. Smallpox_sentence_395

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. Smallpox_sentence_396

Specific allegations made against Iraq in this respect proved to be false. Smallpox_sentence_397

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. Smallpox_sentence_398

Insertion of the synthesized smallpox DNA into existing related pox viruses could theoretically be used to recreate the virus. Smallpox_sentence_399

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. Smallpox_sentence_400

Notable cases Smallpox_section_25

Famous historical figures who contracted smallpox include Lakota Chief Sitting Bull, Ramses V, the Kangxi Emperor (survived), Shunzhi Emperor and Tongzhi Emperor (refer to the official history) of China, Emperor Komei of Japan (died of smallpox in 1867), and Date Masamune of Japan (who lost an eye to the disease). Smallpox_sentence_401

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 (causing a civil war of succession in the Inca empire and the eventual conquest by the Spaniards). Smallpox_sentence_402

More recent public figures include Guru Har Krishan, 8th Guru of the Sikhs, in 1664, Louis I of Spain in 1724 (died), Peter II of Russia in 1730 (died), George Washington (survived), Louis XV of France in 1774 (died) and Maximilian III Joseph of Bavaria in 1777 (died). Smallpox_sentence_403

Prominent families throughout the world often had several people infected by and/or perish from the disease. Smallpox_sentence_404

For example, several relatives of Henry VIII of England survived the disease but were scarred by it. Smallpox_sentence_405

These include his sister Margaret, his wife Anne of Cleves, and his two daughters: Mary I in 1527 and Elizabeth I in 1562. Smallpox_sentence_406

Elizabeth tried to disguise the pockmarks with heavy makeup. Smallpox_sentence_407

Mary, Queen of Scots, contracted the disease as a child but had no visible scarring. Smallpox_sentence_408

In Europe, deaths from smallpox often changed dynastic succession. Smallpox_sentence_409

Louis XV of France succeeded his great-grandfather Louis XIV through a series of deaths of smallpox or measles among those higher in the succession line. Smallpox_sentence_410

He himself died of the disease in 1774. Smallpox_sentence_411

Peter II of Russia died of the disease at 14 years of age. Smallpox_sentence_412

Also, prior to becoming emperor, Peter III of Russia caught the virus and suffered greatly from it. Smallpox_sentence_413

He was left scarred and disfigured. Smallpox_sentence_414

His wife, Catherine the Great, was spared but fear of the virus clearly had its effects on her. Smallpox_sentence_415

She feared for the safety of her son, Paul, so much that she made sure that large crowds were kept at bay and sought to isolate him. Smallpox_sentence_416

Eventually, she decided to have herself inoculated by a British doctor, Thomas Dimsdale. Smallpox_sentence_417

While this was considered a controversial method at the time, she succeeded. Smallpox_sentence_418

Paul was later inoculated as well. Smallpox_sentence_419

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." Smallpox_sentence_420

By 1800, approximately 2 million inoculations were administered in the Russian Empire. Smallpox_sentence_421

In China, the Qing dynasty had extensive protocols to protect Manchus from Peking's endemic smallpox. Smallpox_sentence_422

U.S. Presidents George Washington, Andrew Jackson, and Abraham Lincoln all contracted and recovered from the disease. Smallpox_sentence_423

Washington became infected with smallpox on a visit to Barbados in 1751. Smallpox_sentence_424

Jackson developed the illness after being taken prisoner by the British during the American Revolution, and though he recovered, his brother Robert did not. Smallpox_sentence_425

Lincoln contracted the disease during his presidency, possibly from his son Tad, and was quarantined shortly after giving the Gettysburg address in 1863. Smallpox_sentence_426

Famous theologian Jonathan Edwards died of smallpox in 1758 following an inoculation. Smallpox_sentence_427

Soviet leader Joseph Stalin fell ill with smallpox at the age of seven. Smallpox_sentence_428

His face was badly scarred by the disease. Smallpox_sentence_429

He later had photographs retouched to make his pockmarks less apparent. Smallpox_sentence_430

Hungarian poet Ferenc Kölcsey, who wrote the Hungarian national anthem, lost his right eye to smallpox. Smallpox_sentence_431

Tradition and religion Smallpox_section_26

In the face of the devastation of smallpox, various smallpox gods and goddesses have been worshipped throughout parts of the Old World, for example in China and in India. Smallpox_sentence_432

In China, the smallpox goddess was referred to as T'ou-Shen Niang-Niang. Smallpox_sentence_433

Chinese believers actively worked to appease the goddess and pray for her mercy, by such measures as referring to smallpox pustules as "beautiful flowers" as a euphemism intended to avert offending the goddess, for example (the Chinese word for smallpox is , literally "heaven flower"). Smallpox_sentence_434

In a related New Year's Eve custom it was prescribed that the children of the house wear ugly masks while sleeping, so as to conceal any beauty and thereby avoid attracting the goddess, who would be passing through sometime that night. Smallpox_sentence_435

If a case of smallpox did occur, shrines would be set up in the homes of the victims, to be worshipped and offered to as the disease ran its course. Smallpox_sentence_436

If the victim recovered, the shrines were removed and carried away in a special paper chair or boat for burning. Smallpox_sentence_437

If the patient did not recover, the shrine was destroyed and cursed, so as to expel the goddess from the house. Smallpox_sentence_438

In the Yoruba language smallpox is known as ṣọ̀pọ̀ná, but it also written as shakpanna, shopona, ṣhapana, and ṣọpọnọ. Smallpox_sentence_439

The word is a combination of 3 words, the verb ṣán, meaning to cover or plaster (referring to the pustules characteristic of smallpox), kpa or pa, meaning to kill, and enia, meaning human. Smallpox_sentence_440

Roughly translated, it means One who kills a person by covering them with pustules. Smallpox_sentence_441

Among the Yorùbá people of West Africa, and also in Dahomean religion, Trinidad, and in Brazil, The deity Sopona, also known as Obaluaye, is the deity of smallpox and other deadly diseases (like leprosy, HIV/AIDS, and fevers). Smallpox_sentence_442

One of the most feared deities of the orisha pantheon, smallpox was seen as a form of punishment from Shopona. Smallpox_sentence_443

Worship of Shopona was highly controlled by his priests, and it was believed that priests could also spread smallpox when angered. Smallpox_sentence_444

However, Shopona was also seen as a healer who could cure the diseases he inflicted, and he was often called upon his victims to heal them. Smallpox_sentence_445

The British government banned the worship of the god because it was believed his priests were purposely spreading smallpox to their opponents. Smallpox_sentence_446

India's first records of smallpox can be found in a medical book that dates back to 400 CE. Smallpox_sentence_447

This book describes a disease that sounds exceptionally like smallpox. Smallpox_sentence_448

India, like China and the Yorùbá, created a goddess in response to its exposure to smallpox. Smallpox_sentence_449

The Hindu goddess Shitala was both worshipped and feared during her reign. Smallpox_sentence_450

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. Smallpox_sentence_451

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. Smallpox_sentence_452

Shrines were created where many India natives, both healthy and not, went to worship and attempt to protect themselves from this disease. Smallpox_sentence_453

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. Smallpox_sentence_454

In cultures that did not recognize a smallpox deity, there was often nonetheless a belief in smallpox demons, who were accordingly blamed for the disease. Smallpox_sentence_455

Such beliefs were prominent in Japan, Europe, Africa, and other parts of the world. Smallpox_sentence_456

Nearly all cultures who believed in the demon also believed that it was afraid of the color red. Smallpox_sentence_457

This led to the invention of so-called red treatment, where victims and their rooms would be decorated in red. Smallpox_sentence_458

The practice spread to Europe in the 12th century and was practiced by (among others) Charles V of France and Elizabeth I of England. Smallpox_sentence_459

Afforded scientific credibility through the studies by Niels Ryberg Finsen showing that red light reduced scarring, this belief persisted even until the 1930s. Smallpox_sentence_460

See also Smallpox_section_27

Smallpox_unordered_list_1


Credits to the contents of this page go to the authors of the corresponding Wikipedia page: en.wikipedia.org/wiki/Smallpox.