smallpox
   HOME

TheInfoList



OR:

Smallpox was an
infectious disease An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmiss ...
caused by variola virus (often called smallpox virus) which belongs to the genus
Orthopoxvirus ''Orthopoxvirus'' is a genus of viruses in the family ''Poxviridae'' and subfamily ''Chordopoxvirinae''. Vertebrates, including mammals and humans, and arthropods serve as natural hosts. There are 12 species in this genus. Diseases associated wi ...
. The last naturally occurring case was diagnosed in October 1977, and the
World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainme ...
(WHO) certified the global eradication of the disease in 1980, making it the only human disease to be eradicated. The initial symptoms of the disease included
fever Fever, also referred to as pyrexia, is defined as having a temperature Temperature is a physical quantity that expresses quantitatively the perceptions of hotness and coldness. Temperature is measurement, measured with a thermometer. Th ...
and vomiting. This was followed by formation of ulcers in the mouth and a
skin rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cra ...
. Over a number of days, the skin rash turned into the characteristic fluid-filled
blister A blister is a small pocket of body fluid (lymph, Serum (blood), serum, Plasma (blood), plasma, blood, or pus) within the Epidermis, upper layers of the skin, usually caused by forceful rubbing (friction), burning, freezing, chemical exposure or ...
s with a dent in the center. The bumps then scabbed over and fell off, leaving scars. The disease was spread between people or via contaminated objects. Prevention was achieved mainly through the
smallpox vaccine The smallpox vaccine is the first vaccine to be developed against a contagious disease. In 1796, British physician Edward Jenner demonstrated that an infection with the relatively mild cowpox virus conferred immunity against the deadly smallpox ...
. Once the disease had developed, certain
antiviral medication Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do no ...
may have helped. The risk of death was about 30%, with higher rates among babies. Often, those who survived had extensive
scarring A scar (or scar tissue) is an area of fibrosis, fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other Organ (anatomy), organs, and biological tissue, ...
of their skin, and some were left blind. The earliest evidence of the disease dates to around 1500 BCE in Egyptian
mummies A mummy is a dead human or an animal whose soft tissues and Organ (anatomy), organs have been preserved by either intentional or accidental exposure to Chemical substance, chemicals, extreme cold, very low humidity, or lack of air, so that th ...
. The disease historically occurred in
outbreaks In epidemiology, an outbreak is a sudden increase in occurrences of a disease when cases are in excess of normal expectancy for the location or season. It may affect a small and localized group or impact upon thousands of people across an entire ...
. 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 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. Earlier deaths included six European
monarch A monarch is a head of stateWebster's II New College DictionarMonarch Houghton Mifflin. Boston. 2001. p. 707. Life tenure, for life or until abdication, and therefore the head of state of a monarchy. A monarch may exercise the highest authority ...
s. As recently as 1967, 15 million cases occurred a year.
Inoculation Inoculation is the act of implanting a pathogen or other microorganism. It may refer to methods of artificial induction of immunity, artificially inducing immunity against various infectious diseases, or it may be used to describe the spreading ...
for smallpox appears to have started in China around the 1500s. Europe adopted this practice from Asia in the first half of the 18th century. In 1796,
Edward Jenner Edward Jenner, (17 May 1749 – 26 January 1823) was a British physician and scientist who pioneered the concept of vaccines, and created the smallpox vaccine, the world's first vaccine. The terms ''vaccine'' and ''vaccination'' are derived f ...
introduced the modern smallpox vaccine. In 1967, the WHO intensified efforts to eliminate the disease. Smallpox is one of two infectious diseases to have been eradicated, the other being
rinderpest Rinderpest (also cattle plague or steppe murrain) was an infectious viral disease of cattle, domestic water buffalo, buffalo, and many other species of even-toed ungulates, including gaurs, African Buffalo, buffaloes, large antelope, deer, giraff ...
in 2011. The term "smallpox" was first used in Britain in the early 16th century to distinguish the disease from
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, and ...
, which was then known as the "great pox". Other historical names for the disease include pox, speckled monster, and red plague.


Classification

There are two forms of the smallpox, ''variola major'' is the severe and most common form, with a more extensive rash and higher fever. Variola minor is a less common presentation, causing less severe disease, typically discrete smallpox, with historical death rates of 1% or less. Subclinical (
asymptomatic In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection but experiences no Signs and symptoms, symptoms. Whenever a medical condition fails to show noticeable symptoms after a diagnosis it migh ...
) infections with variola virus were noted but were not common. 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 Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic organism, a chemical, or ionizing radiation, radiation, and when symptoms and signs are first apparent. In a typical infect ...
and could be confirmed only by
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and Viral disease, viruses. The antibody recognizes a unique m ...
studies or, rarely, by
viral culture Viral culture is a laboratory technique in which samples of a virus are placed to different cell lines which the virus being tested for its ability to infect. If the cells show changes, known as cytopathic effects, then the culture is positive. ...
. In addition, there were two very rare and fulminating types of smallpox, the malignant (flat) and hemorrhagic forms, which were usually fatal.


Signs and symptoms

The initial symptoms were similar to other viral diseases that are still extant, such as
influenza Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms ...
and the
common cold The common cold or the cold is a virus, viral infectious disease of the upper respiratory tract that primarily affects the Respiratory epithelium, respiratory mucosa of the human nose, nose, throat, Paranasal sinuses, sinuses, and larynx. Si ...
: fever of at least ,
muscle pain Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of Acute disease, acute myalgia is the overuse of a muscle or Muscle group, gro ...
,
malaise As a medical term, malaise is a feeling of general suffering, discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. The word has existed in French language, French since at least the 12th century ...
, headache and fatigue. As the
digestive tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ Organ may refer to: Biology * Org ...
was commonly involved, nausea, vomiting, and backache often occurred. The early prodromal stage usually lasted 2–4 days. By days 12–15, the first visible lesions – small reddish spots called '' enanthem'' – appeared on mucous membranes of the mouth, tongue,
palate The palate () is the roof of the mouth in humans and other mammals. It separates the oral cavity from the nasal cavity. A similar structure is found in crocodilians, but in most other tetrapods, the oral and nasal cavities are not truly separ ...
, and throat, and the temperature fell to near-normal. These lesions rapidly enlarged and ruptured, releasing large amounts of virus into the saliva. Variola virus tended to attack skin cells, causing the characteristic pimples, or macules, associated with the disease. A rash developed on the skin 24 to 48 hours after lesions on the mucous membranes appeared. Typically the macules first appeared on the forehead, then rapidly spread to the whole face,
proximal Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek language, Greek roots, describe something in its standard anatomical position. Th ...
portions of extremities, the trunk, and lastly to
distal Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek language, Greek roots, describe something in its standard anatomical position. Th ...
portions of extremities. The process took no more than 24 to 36 hours, after which no new lesions appeared. At this point, variola major disease 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. Historically, ordinary smallpox had an overall fatality rate of about 30%, and the malignant and hemorrhagic forms were usually fatal. The modified form was almost never fatal. In early hemorrhagic cases, hemorrhages occurred before any skin lesions developed. The
incubation period Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic organism, a chemical, or ionizing radiation, radiation, and when symptoms and signs are first apparent. In a typical infect ...
between contraction and the first obvious symptoms of the disease was 7–14 days.


Ordinary

Ninety percent or more of smallpox cases among unvaccinated persons were of the ordinary type. In this form of the disease, by the second day of the rash the macules had become raised ''
papule A papule is a small, well-defined bump in the skin lesion, skin. It may have a rounded, pointed or flat top, and may have a umbilication, dip. It can appear with a Peduncle (anatomy), stalk, be thread-like or look warty. It can be soft or firm a ...
s''. By the third or fourth day, the papules had filled with an opalescent fluid to become '' vesicles''. This fluid became
opaque Opacity or opaque may refer to: * Impediments to (especially, visible) light: ** Opacities, absorption coefficients ** Opacity (optics), property or degree of blocking the transmission of light * Metaphors derived from literal optics: ** In lingui ...
and turbid within 24–48 hours, resulting in
pustule A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of ...
s. By the sixth or seventh day, all the skin lesions had become pustules. Between seven and ten days the pustules had matured and reached their maximum size. The pustules were sharply raised, typically round, tense, and firm to the touch. The pustules were deeply embedded in the dermis, giving them the feel of a small bead in the skin. 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. By day 16–20 scabs had formed over all of the lesions, which had started to flake off, leaving depigmented scars. Ordinary smallpox generally produced a discrete rash, in which the pustules stood out on the skin separately. 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. The palms of the hands and soles of the feet were involved in most cases. Sometimes, the blisters merged into sheets, forming a confluent rash, which began to detach the outer layers of skin from the underlying flesh. Patients with confluent smallpox often remained ill even after scabs had formed over all the lesions. In one case series, the case-fatality rate in confluent smallpox was 62 percent.


Modified

Referring to the character of the eruption and the rapidity of its development, modified smallpox occurred mostly in previously vaccinated people. It was rare in unvaccinated people, with one case study showing 1–2% of modified cases compared to around 25% in vaccinated people. In this form, the prodromal illness still occurred but may have been less severe than in the ordinary type. There was usually no fever during the evolution of the rash. 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. Modified smallpox was rarely, if ever, fatal. This form of variola major was more easily confused with
chickenpox Chickenpox, also known as varicella, is a highly Infectious disease, contagious disease caused by the initial infection with varicella zoster virus (VZV). The disease results in a characteristic skin rash that forms Vesicle (dermatology), sma ...
.


Malignant

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. It is unknown why some people developed this type. Historically, it accounted for 5–10 percent of cases, and most (72 percent) were children. Malignant smallpox was accompanied by a severe prodromal phase that lasted 3–4 days, prolonged high fever, and severe symptoms of
viremia Viremia is a medical condition where virus A virus is a wikt:submicroscopic, submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plan ...
. The prodromal symptoms continued even after the onset of the rash. The rash on the mucous membranes ( enanthem) was extensive. 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. Unlike ordinary-type smallpox, the vesicles contained little fluid, were soft and velvety to the touch, and may have contained hemorrhages. Malignant smallpox was nearly always fatal and death usually occurred between the 8th and 12th day of illness. Often, a day or two before death, the lesions turned ashen gray, which, along with abdominal distension, was a bad prognostic sign. This form is thought to be caused by deficient
cell-mediated immunity Cell-mediated immunity or cellular immunity is an immune response that does not involve antibody, antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific Cytotoxic T cell, cytotoxic T-lymphocytes, and the rel ...
to smallpox. If the person recovered, the lesions gradually faded and did not form scars or scabs.


Hemorrhagic

Hemorrhagic smallpox is a severe form accompanied by extensive bleeding into the skin, mucous membranes, gastrointestinal tract, and
viscera In biology, an organ is a collection of Tissue (biology), tissues joined in a structural unit to serve a common function. In the biological organization, hierarchy of life, an organ lies between Tissue (biology), tissue and an organ system. Tiss ...
. This form develops in approximately two percent of infections and occurs mostly in adults. Pustules do not typically form in hemorrhagic smallpox. 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". Hemorrhagic smallpox has very rarely been caused by variola minor virus. While bleeding may occur in mild cases and not affect outcomes, hemorrhagic smallpox is typically fatal. Vaccination does not appear to provide any immunity to either form of hemorrhagic smallpox and some cases even occurred among people that were revaccinated shortly before. It has two forms.


Early

The early or
fulminant Fulminant () is a medical descriptor for any event or process that occurs suddenly and escalates quickly, and is intense and severe to the point of lethality, i.e., it has an explosion, explosive character. The word comes from Latin ''fulmināre'' ...
form of hemorrhagic smallpox (referred to as ''purpura variolosa'') begins with a prodromal phase characterized by a high fever, severe headache, and abdominal pain. The skin becomes dusky and erythematous, and this is rapidly followed by the development of
petechia A petechia () is a small red or purple spot (≤4 mm in diameter) that can appear on the skin, conjunctiva, retina, and Mucous membrane, mucous membranes which is caused by haemorrhage of capillaries. The word is derived from Italian , 'freckle,' ...
e and bleeding in the skin,
conjunctiva The conjunctiva is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the human eye, eye). It is composed of non-keratinized, stratified squamous epithelium with goblet cells, stratified columnar epi ...
and mucous membranes. Death often occurs suddenly between the fifth and seventh days of illness, when only a few insignificant skin lesions are present. Some people survive a few days longer, during which time the skin detaches and fluid accumulates under it, rupturing at the slightest injury. People are usually conscious until death or shortly before. Autopsy reveals
petechiae A petechia () is a small red or purple spot (≤4 mm in diameter) that can appear on the skin, conjunctiva, retina, and mucous membranes which is caused by haemorrhage of capillaries. The word is derived from Italian , 'freckle,' of obscure or ...
and bleeding in the spleen, kidney, serous membranes, skeletal muscles,
pericardium The pericardium, also called pericardial sac, is a double-walled sac containing the heart and the roots of the great vessels. It has two layers, an outer layer made of strong connective tissue (fibrous pericardium), and an inner layer made of ...
, liver, gonads and bladder. Historically, this condition was frequently misdiagnosed, with the correct diagnosis made only at autopsy. This form 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). The case fatality rate of early hemorrhagic smallpox approaches 100%.


Late

There is also a later form of hemorrhagic smallpox (referred to late hemorrhagic smallpox, or ''variolosa pustula hemorrhagica''). The prodrome is severe and similar to that observed in early hemorrhagic smallpox, and the fever persists throughout the course of the disease. 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. Hemorrhages in the mucous membranes appear to occur less often than in the early hemorrhagic form. Sometimes the rash forms pustules which bleed at the base and then undergo the same process as in ordinary smallpox. This form of the disease is characterized by a decrease in all of the elements of the
coagulation Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a thrombus, blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The m ...
cascade and an increase in circulating
antithrombin Antithrombin (AT) is a small glycoprotein Glycoproteins are proteins which contain oligosaccharide chains Covalent bond, covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a translation (genetics), ...
. This form of smallpox occurs anywhere from three to 25 percent of fatal cases, depending on the virulence of the smallpox strain. Most people with the late-stage form die within eight to 10 days of illness. Among the few who recover, the hemorrhagic lesions gradually disappear after a long period of convalescence. The case fatality rate for late hemorrhagic smallpox is around 90-95%. Pregnant women are slightly more likely to experience this form of the disease, though not as much as early hemorrhagic smallpox.


Cause

Smallpox was caused by infection with variola virus, which belongs to the family ''
Poxviridae ''Poxviridae'' is a family of double-stranded DNA viruses. Vertebrates and arthropods serve as natural hosts. There are currently 83 species in this family, divided among 22 genera, which are divided into two subfamilies. Diseases associated with ...
'', subfamily ''
Chordopoxvirinae ''Chordopoxvirinae'' is a subfamily of viruses A virus is a wikt:submicroscopic, submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals an ...
'', and genus ''
Orthopoxvirus ''Orthopoxvirus'' is a genus of viruses in the family ''Poxviridae'' and subfamily ''Chordopoxvirinae''. Vertebrates, including mammals and humans, and arthropods serve as natural hosts. There are 12 species in this genus. Diseases associated wi ...
''.


Evolution

The date of the appearance of smallpox is not settled. It most probably evolved from a terrestrial African rodent virus between 68,000 and 16,000 years ago. The wide range of dates is due to the different records used to calibrate the
molecular clock The molecular clock is a figurative term for a technique that uses the mutation rate of biomolecules to deduce the time in prehistory Prehistory, also known as pre-literary history, is the period of human history between the use of the ...
. One
clade A clade (), also known as a monophyletic group or natural group, is a group of organisms that are monophyly, monophyletic – that is, composed of a common ancestor and all its lineage (evolution), lineal descendants – on a phylogenetic tree. ...
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 (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 virus from Taterapox (an
Orthopoxvirus ''Orthopoxvirus'' is a genus of viruses in the family ''Poxviridae'' and subfamily ''Chordopoxvirinae''. Vertebrates, including mammals and humans, and arthropods serve as natural hosts. There are 12 species in this genus. Diseases associated wi ...
of some African rodents including
gerbil The Mongolian gerbil or Mongolian jird (''Meriones unguiculatus'') is a small rodent Rodents (from Latin Latin (, or , ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. L ...
s) at 3,000 to 4,000 years ago. This is consistent with archaeological and historical evidence regarding the appearance of smallpox as a human disease which suggests a relatively recent origin. If the mutation rate is assumed to be similar to that of the
herpesvirus ''Herpesviridae'' is a large family Family (from la, familia) is a Social group, group of people related either by consanguinity (by recognized birth) or Affinity (law), affinity (by marriage or other relationship). The purpose of the famil ...
es, the divergence date of variola virus from Taterapox has been estimated to be 50,000 years ago. 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. Examination of a strain that dates from c. 1650 found that this strain was basal to the other presently sequenced strains. The mutation rate of this virus is well modeled by a molecular clock. Diversification of strains only occurred in the 18th and 19th centuries.


Virology

Variola virus is large brick-shaped and is approximately 302 to 350
nanometer file:EM Spectrum Properties edit.svg, 330px, Different lengths as in respect to the electromagnetic spectrum, measured by the metre and its derived scales. The nanometre is often used to express dimensions on an atomic scale and mostly in the Mol ...
s by 244 to 270 nm, with a single linear double stranded DNA
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding gene ...
186 kilobase pairs (kbp) in size and containing a
hairpin loop Stem-loop intramolecular base pairing is a pattern that can occur in single-stranded RNA. The structure is also known as a hairpin or hairpin loop. It occurs when two regions of the same strand, usually complementary in nucleotide sequence when ...
at each end. Four orthopoxviruses cause infection in humans: variola,
vaccinia ''Vaccinia virus'' (VACV or VV) is a large, complex, Viral envelope, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 base pair, kbp in length, which encodes approximately 250 genes ...
,
cowpox Cowpox is an infectious disease caused by the ''cowpox virus'' (CPXV). It presents with large vesicle (dermatology), blisters in the skin, a fever and lymphadenopathy, swollen glands, historically typically following contact with an infected cow, ...
, and
monkeypox Monkeypox (also called mpox by the World_Health_Organization, WHO) is an infectious viral disease that can occur in humans and some other animals. Symptoms include fever, lymphadenopathy, swollen lymph nodes, and a rash that forms blisters and ...
. Variola virus infects only humans in nature, although primates and other animals have been infected in an experimental setting. Vaccinia, cowpox, and monkeypox viruses can infect both humans and other animals in nature. The life cycle of poxviruses is complicated by having multiple infectious forms, with differing mechanisms of cell entry. Poxviruses are unique among human DNA viruses in that they replicate in the
cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryote, eukaryotic Cell (biology), cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear envelope, nuc ...
of the cell rather than in the
nucleus Nucleus (plural, : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA ...
. 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 A virus is a wikt:submicroscopic, submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and ...
are infectious. The viral envelope is made of modified Golgi membranes containing viral-specific polypeptides, including
hemagglutinin In molecular biology, hemagglutinins (or ''haemagglutinin'' in British English) (from the Greek , 'blood' + Latin , 'glue') are receptor-binding membrane fusion glycoproteins produced by viruses in the ''Paramyxoviridae'' family. Hemagglutinins ar ...
. Infection with either variola major virus or variola minor virus confers immunity against the other.


Variola major

The more common, infectious form of the disease was caused by the variola major virus strain.


Variola minor

Variola minor virus, also called alastrim, was a less common form of the virus, and much less deadly. Although variola minor had the same incubation period and pathogenetic stages as smallpox, it is believed to have had a mortality rate of less than 1%, as compared to smallpox's 30%. Like variola major, variola minor was spread through inhalation of the virus in the air, which could occur through face-to-face contact or through fomites. Infection with variola minor virus conferred immunity against the more dangerous variola major virus. Because variola minor was a less debilitating disease than smallpox, people were more frequently ambulant and thus able to infect others more rapidly. As such, variola minor swept through the United States, Great Britain, and South Africa in the early 20th century, becoming the dominant form of the disease in those areas and thus rapidly decreasing mortality rates. Along with variola major, the minor form has now been totally eradicated from the globe. The last case of indigenous variola minor was reported in a Somali cook, Ali Maow Maalin, in October 1977, and smallpox was officially declared eradicated worldwide in May 1980. Variola minor was also called white pox, kaffir pox, Cuban itch, West Indian pox, milk pox, and pseudovariola.


Genome composition

The
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding gene ...
of variola major virus is about 186,000 base pairs in length. It is made from linear double stranded DNA and contains the
coding sequence The coding region of a gene, also known as the coding sequence (CDS), is the portion of a gene's DNA or RNA that codes for protein. Studying the length, composition, regulation, splicing, structures, and functions of coding regions compared to non ...
for about 200
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian inheritance#History, Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanin ...
s. The genes are usually not overlapping and typically occur in blocks that point towards the closer terminal region of the genome. The coding sequence of the central region of the genome is highly consistent across
orthopoxvirus ''Orthopoxvirus'' is a genus of viruses in the family ''Poxviridae'' and subfamily ''Chordopoxvirinae''. Vertebrates, including mammals and humans, and arthropods serve as natural hosts. There are 12 species in this genus. Diseases associated wi ...
es, and the arrangement of genes is consistent across chordopoxviruses The center of the variola virus genome contains the majority of the essential viral genes, including the genes for structural
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metabo ...
s,
DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all life, living organisms acting as the most essential part for heredity, biologi ...
,
transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...
, and
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
synthesis. The ends of the genome vary more across strains and species of
orthopoxvirus ''Orthopoxvirus'' is a genus of viruses in the family ''Poxviridae'' and subfamily ''Chordopoxvirinae''. Vertebrates, including mammals and humans, and arthropods serve as natural hosts. There are 12 species in this genus. Diseases associated wi ...
es. These regions contain proteins that modulate the hosts' immune systems, and are primarily responsible for the variability in
virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host (biology), host. The Pathogen#Pathogenicity, pathogen ...
across the
orthopoxvirus ''Orthopoxvirus'' is a genus of viruses in the family ''Poxviridae'' and subfamily ''Chordopoxvirinae''. Vertebrates, including mammals and humans, and arthropods serve as natural hosts. There are 12 species in this genus. Diseases associated wi ...
family. These terminal regions in poxviruses are inverted terminal repetitions (ITR) sequences. These sequences are identical but oppositely oriented on either end of the genome, leading to the genome being a continuous loop of DNA Components of the ITR sequences include an incompletely base paired A/T rich
hairpin loop Stem-loop intramolecular base pairing is a pattern that can occur in single-stranded RNA. The structure is also known as a hairpin or hairpin loop. It occurs when two regions of the same strand, usually complementary in nucleotide sequence when ...
, a region of roughly 100 base pairs necessary for resolving concatomeric DNA (a stretch of DNA containing multiple copies of the same sequence), a few
open reading frame In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible read ...
s, and short tandemly repeating sequences of varying number and length. The ITRs of
poxviridae ''Poxviridae'' is a family of double-stranded DNA viruses. Vertebrates and arthropods serve as natural hosts. There are currently 83 species in this family, divided among 22 genera, which are divided into two subfamilies. Diseases associated with ...
vary in length across strains and species. The coding sequence for most of the viral proteins in variola major virus have at least 90% similarity with the genome of
vaccinia ''Vaccinia virus'' (VACV or VV) is a large, complex, Viral envelope, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 base pair, kbp in length, which encodes approximately 250 genes ...
, a related virus used for
vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...
against smallpox.


Gene expression

Gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. T ...
of variola virus occurs entirely within the
cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryote, eukaryotic Cell (biology), cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear envelope, nuc ...
of the host
cell Cell most often refers to: * Cell (biology) The cell is the basic structural and functional unit of life forms. Every cell consists of a cytoplasm enclosed within a Cell membrane, membrane, and contains many biomolecules such as proteins, D ...
, and follows a distinct progression during infection. After entry of an infectious
virion A virus is a wikt:submicroscopic, submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and ...
into a host cell, synthesis of viral
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
can be detected within 20 minutes. About half of the viral genome is transcribed prior to the replication of viral DNA. The first set of expressed genes are transcribed by pre-existing viral machinery packaged within the infecting virion. These genes encode the factors necessary for viral DNA synthesis and for transcription of the next set of expressed genes. Unlike most DNA viruses,
DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all life, living organisms acting as the most essential part for heredity, biologi ...
in variola virus and other poxviruses takes place within the cytoplasm of the infected cell. The exact timing of DNA replication after infection of a host cell varies across the
poxviridae ''Poxviridae'' is a family of double-stranded DNA viruses. Vertebrates and arthropods serve as natural hosts. There are currently 83 species in this family, divided among 22 genera, which are divided into two subfamilies. Diseases associated with ...
. Recombination of the genome occurs within actively infected cells. Following the onset of viral DNA replication, an intermediate set of genes codes for
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding to ...
s of late gene expression. The products of the later genes include transcription factors necessary for transcribing the early genes for new virions, as well as viral
RNA polymerase In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the d ...
and other essential enzymes for new viral particles. These proteins are then packaged into new infectious virions capable of infecting other cells.


Research

Two live samples of variola major virus remain, one in the United States at the
CDC The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services The United States Department of He ...
in Atlanta, and one at the Vector Institute in Koltsovo, Russia. Research with the remaining virus samples is tightly controlled, and each research proposal must be approved by the WHO and the
World Health Assembly The World Health Assembly (WHA) is the forum through which the World Health Organization (WHO) is governed by its 194 World Health Organization#Membership, member states. It is the world's highest health policy setting body and is composed of he ...
(WHA). Most research on poxviruses is performed using the closely related ''
Vaccinia virus ''Vaccinia virus'' (VACV or VV) is a large, complex, enveloped virus A virus is a wikt:submicroscopic, submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all lif ...
'' as a model organism. Vaccinia virus, which is used to vaccinate for smallpox, is also under research as a
viral vector Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cell (biology), cells. This process can be performed inside a living organism (''in vivo'') or in cell culture (''in vitro''). Viruses have evolved spec ...
for
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
s for unrelated diseases. The genome of variola major virus was first sequenced in its entirety in the 1990s. The complete coding sequence is publicly available online.The current reference sequence for variola major virus was sequenced from a strain that circulated in India in 1967. In addition, there are sequences for samples of other strains that were collected during the WHO eradication campaign. A genome browser for a complete database of annotated sequences of variola virus and other poxviruses is publicly available through the Viral Bioinformatics Resource Center.


Genetic engineering

The WHO currently bans
genetic engineering Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of Genetic engineering techniques, technologies used to change the gene ...
of the variola virus. However, in 2004, a committee advisory to the WHO voted in favor of allowing editing of the genome of the two remaining samples of variola major virus to add a
marker gene In biology Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of Cell (biology), cells ...
. This gene, called GFP, or green fluorescent protein, would cause live samples of the virus to glow green under fluorescent light. The insertion of this gene, which would not influence the
virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host (biology), host. The Pathogen#Pathogenicity, pathogen ...
of the virus, would be the only allowed modification of the genome. The committee stated the proposed modification would aid in research of treatments by making it easier to assess whether a potential treatment was effective in killing viral samples. The recommendation could only take effect if approved by the WHA. When the WHA discussed the proposal in 2005, it refrained from taking a formal vote on the proposal, stating that it would review individual research proposals one at a time. Addition of the GFP gene to the ''
Vaccinia ''Vaccinia virus'' (VACV or VV) is a large, complex, Viral envelope, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 base pair, kbp in length, which encodes approximately 250 genes ...
'' genome is routinely performed during research on the closely related ''
Vaccinia virus ''Vaccinia virus'' (VACV or VV) is a large, complex, enveloped virus A virus is a wikt:submicroscopic, submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all lif ...
''.


Controversies

The public availability of the variola virus complete sequence has raised concerns about the possibility of illicit synthesis of infectious virus. ''
Vaccinia ''Vaccinia virus'' (VACV or VV) is a large, complex, Viral envelope, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 base pair, kbp in length, which encodes approximately 250 genes ...
'', a cousin of the variola virus, was artificially synthesized in 2002 by
NIH The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government The federal government of the United States (U.S. federal government or U ...
scientists. They used a previously established method that involved using a recombinant viral genome to create a self-replicating bacterial
plasmid A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from gDNA, chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; ...
that produced viral particles. In 2016, another group synthesized the
horsepox ''Orthopoxvirus'' is a genus of viruses in the family ''Poxviridae'' and subfamily ''Chordopoxvirinae''. Vertebrates, including mammals and humans, and arthropods serve as natural hosts. There are 12 species in this genus. Diseases associated wi ...
virus using publicly available sequence data for horsepox. The researchers argued that their work would be beneficial to creating a safer and more effective
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
for smallpox, although an effective vaccine is already available. The horsepox virus had previously seemed to have gone extinct, raising concern about potential revival of variola major and causing other scientists to question their motives. Critics found it especially concerning that the group was able to recreate viable virus in a short time frame with relatively little cost or effort. Although the WHO bans individual laboratories from synthesizing more than 20% of the genome at a time, and purchases of smallpox genome fragments are monitored and regulated, a group with malicious intentions could compile, from multiple sources, the full synthetic genome necessary to produce viable virus.


Transmission

Transmission occurred through inhalation of airborne variola virus, usually droplets expressed from the oral, nasal, or pharyngeal
mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue ...
of an infected person. It was transmitted from one person to another primarily through prolonged face-to-face contact with an infected person, usually, within a distance of , but could also be spread through direct contact with infected bodily fluids or contaminated objects (
fomite A fomite () or fomes () is any inanimate object that, when contaminated with or exposed to infectious agents (such as pathogenic bacteria, viruses or fungi), can transfer disease to a new host (biology), host. Transfer of pathogens by fomites A fo ...
s) such as bedding or clothing. Rarely, smallpox was spread by virus carried in the air in enclosed settings such as buildings, buses, and trains. The virus can cross the
placenta The placenta is a temporary embryonic and later fetal organ (anatomy), organ that begins embryonic development, developing from the blastocyst shortly after implantation (embryology), implantation. It plays critical roles in facilitating nutrien ...
, but the incidence of
congenital A birth defect, also known as a congenital disorder, is an abnormal condition that is present at childbirth, birth regardless of its cause. Birth defects may result in disability, disabilities that may be physical disability, physical, intellect ...
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
lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or Trauma (medicine), trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no ...
s in the mouth and pharynx. 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. 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 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. The overall rate of infection was also affected by the short duration of the infectious stage. In
temperate In geography, the temperate climates of Earth occur in the middle latitudes (23.5° to 66.5° N/S of Equator), which span between the tropics and the polar regions of Earth. These zones generally have wider temperature ranges throughout t ...
areas, the number of smallpox infections was highest during the winter and spring. In tropical areas, seasonal variation was less evident and the disease was present throughout the year. Age distribution of smallpox infections depended on acquired immunity.
Vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...
immunity declined over time and was probably lost within thirty years. Smallpox was not known to be transmitted by insects or animals and there was no asymptomatic carrier state.


Mechanism

Once inhaled, the variola virus invaded the mucus membranes of the mouth, throat, and respiratory tract. From there, it migrated to regional
lymph nodes A lymph node, or lymph gland, is a kidney-shaped Organ (anatomy), organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphoc ...
and began to multiply. In the initial growth phase, the virus seemed to move from cell to cell, but by around the 12th day, widespread
lysis Lysis ( ) is the breaking down of the cell membrane, membrane of a Cell (biology), cell, often by virus, viral, enzyme, enzymic, or osmosis, osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of ...
of infected cells occurred and the virus could be found in the bloodstream in large numbers, a condition known as
viremia Viremia is a medical condition where virus A virus is a wikt:submicroscopic, submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plan ...
. This resulted in the second wave of multiplication in the
spleen The spleen is an organ (biology), organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .
,
bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...
, and lymph nodes.


Diagnosis

The clinical definition of ordinary smallpox is an illness with acute onset of fever equal to or greater than followed by a rash characterized by firm, deep-seated vesicles or pustules in the same stage of development without other apparent cause. When a clinical case was observed, smallpox was confirmed using laboratory tests.
Microscopically Microscopy is the technical field of using microscope A microscope () is a laboratory equipment, laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating sm ...
, poxviruses produce characteristic
cytoplasmic In cell biology, the cytoplasm is all of the material within a eukaryote, eukaryotic Cell (biology), cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear envelope, nuc ...
inclusion bodies Inclusion bodies are aggregates of specific types of protein found in neurons, a number of tissue (biology), tissue cells including red blood cells, bacteria, viruses, and plants. Inclusion bodies of aggregations of multiple proteins are also found ...
, the most important of which are known as Guarnieri bodies, and are the sites of
viral replication Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through the generation of abundant copies of its genome an ...
. 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 could not be used to rule out smallpox. The diagnosis of an orthopoxvirus infection can also be made rapidly by electron microscopic examination of pustular fluid or scabs. All orthopoxviruses exhibit identical brick-shaped
virions A virus is a wikt:submicroscopic, submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and ...
by electron microscopy. If particles with the characteristic morphology of
herpesvirus ''Herpesviridae'' is a large family Family (from la, familia) is a Social group, group of people related either by consanguinity (by recognized birth) or Affinity (law), affinity (by marriage or other relationship). The purpose of the famil ...
es are seen this will eliminate smallpox and other orthopoxvirus infections. Definitive laboratory identification of variola virus involved growing the virus on chorioallantoic membrane (part of a chicken
embryo An embryo is an initial stage of development of a multicellular organism. In organisms that Sexual reproduction, reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell ...
) and examining the resulting pock lesions under defined temperature conditions. Strains were characterized by
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...
(PCR) and restriction fragment length polymorphism (RFLP) analysis. 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.
Chickenpox Chickenpox, also known as varicella, is a highly Infectious disease, contagious disease caused by the initial infection with varicella zoster virus (VZV). The disease results in a characteristic skin rash that forms Vesicle (dermatology), sma ...
was commonly confused with smallpox in the immediate post-eradication era. Chickenpox and smallpox could 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 were available for detecting chickenpox in the evaluation of suspected smallpox cases. File:Smallpox CAM.png, Smallpox virus lesions on the chorioallantoic membrane of a developing chick. File:Smallpox versus chickenpox english plain.svg, In contrast to the rash in smallpox, the rash in
chickenpox Chickenpox, also known as varicella, is a highly Infectious disease, contagious disease caused by the initial infection with varicella zoster virus (VZV). The disease results in a characteristic skin rash that forms Vesicle (dermatology), sma ...
occurs mostly on the torso, spreading less to the limbs. File:Female smallpox patient -- late-stage confluent maculopapular scarring.jpg, An Italian female smallpox patient whose skin displayed the characteristics of late-stage confluent maculopapular scarring, 1965.


Prevention

The earliest procedure used to prevent smallpox was
inoculation Inoculation is the act of implanting a pathogen or other microorganism. It may refer to methods of artificial induction of immunity, artificially inducing immunity against various infectious diseases, or it may be used to describe the spreading ...
with variola minor virus (known as variolation after the introduction of
smallpox vaccine The smallpox vaccine is the first vaccine to be developed against a contagious disease. In 1796, British physician Edward Jenner demonstrated that an infection with the relatively mild cowpox virus conferred immunity against the deadly smallpox ...
to avoid possible confusion), which likely occurred in India, Africa, and China well before the practice arrived in Europe. The idea that inoculation originated in India has been challenged, as few of the ancient
Sanskrit Sanskrit (; attributively , ; nominalization, nominally , , ) is a classical language belonging to the Indo-Aryan languages, Indo-Aryan branch of the Indo-European languages. It arose in South Asia after its predecessor languages had Trans-cul ...
medical texts described the process of inoculation. 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 The Ming dynasty (), officially the Great Ming, was an Dynasties in Chinese history, imperial dynasty of China, ruling from 1368 to 1644 following the collapse of the Mongol Empire, Mongol-led Yuan dynasty. The Ming dynasty was the last ort ...
. If successful, inoculation produced lasting immunity to smallpox. Because the person was infected with variola virus, a severe infection could result, and the person could transmit smallpox to others. Variolation had a 0.5–2 percent mortality rate, considerably less than the 20–30 percent mortality rate of the disease. Two reports on the Chinese practice of
inoculation Inoculation is the act of implanting a pathogen or other microorganism. It may refer to methods of artificial induction of immunity, artificially inducing immunity against various infectious diseases, or it may be used to describe the spreading ...
were received by the
Royal Society The Royal Society, formally The Royal Society of London for Improving Natural Knowledge, is a learned society and the United Kingdom's national academy of sciences. The society fulfils a number of roles: promoting science and its benefits, ...
in London in 1700; one by Dr.
Martin Lister Martin Lister FRS (12 April 1639 – 2 February 1712) was an English naturalist and physician. His daughters Anne and Susanna were two of his illustrators and engravers. J. D. Woodley, ‘Lister , Susanna (bap. 1670, d. 1738)’, Oxford Dic ...
who received a report by an employee of the
East India Company The East India Company (EIC) was an English, and later British, joint-stock company founded in 1600 and dissolved in 1874. It was formed to Indian Ocean trade, trade in the Indian Ocean region, initially with the East Indies (the Indian subco ...
stationed in China and another by
Clopton Havers Clopton Havers (24 February 1657 – April 1702) was an English physician A physician (American English), medical practitioner (English in the Commonwealth of Nations, Commonwealth English), medical doctor, or simply doctor, is a hea ...
.
Lady Mary Wortley Montagu Lady Mary Wortley Montagu (née Pierrepont; 15 May 168921 August 1762) was an English Aristocracy (class), aristocrat, writer, and poet. Born in 1689, Lady Mary spent her early life in England. In 1712, Lady Mary married Edward Wortley Montagu ...
observed smallpox inoculation during her stay in the
Ottoman Empire The Ottoman Empire, * ; is an archaic version. The definite article forms and were synonymous * and el, Оθωμανική Αυτοκρατορία, Othōmanikē Avtokratoria, label=none * info page on book at Martin Luther University) ...
, writing detailed accounts of the practice in her letters, and enthusiastically promoted the procedure in England upon her return in 1718. According to
Voltaire François-Marie Arouet (; 21 November 169430 May 1778) was a French Age of Enlightenment, Enlightenment writer, historian, and philosopher. Known by his ''Pen name, nom de plume'' M. de Voltaire (; also ; ), he was famous for his wit, and his ...
(1742), the Turks derived their use of inoculation from neighbouring
Circassia Circassia (; also known as Cherkessia in some sources; ady, Адыгэ Хэку, Адыгей, lit=, translit=Adıgə Xəku, Adıgey; ; ota, چرکسستان, Çerkezistan; ) was a country and a historical region in the along the northeast ...
. Voltaire does not speculate on where the Circassians derived their technique from, though he reports that the Chinese have practiced it "these hundred years". In 1721,
Cotton Mather Cotton Mather (; February 12, 1663 – February 13, 1728) was a History of New England, New England Puritan clergyman and a prolific writer. Educated at Harvard University, Harvard College, in 1685 he joined his father Increase Mather, Increas ...
and colleagues provoked controversy in Boston by inoculating hundreds. After publishing ''The present method of inoculating for the small-pox'' in 1767, Dr Thomas Dimsdale was invited to Russia to variolate the Empress
Catherine the Great Catherine II (born Sophie of Anhalt-Zerbst; 2 May 172917 November 1796), most commonly known as Catherine the Great, was the reigning empress of Russia from 1762 to 1796. She came to power following the overthrow of her husband, Peter III of Rus ...
of Russia and her son, Grand Duke Paul, which he successfully did in 1768. In 1796,
Edward Jenner Edward Jenner, (17 May 1749 – 26 January 1823) was a British physician and scientist who pioneered the concept of vaccines, and created the smallpox vaccine, the world's first vaccine. The terms ''vaccine'' and ''vaccination'' are derived f ...
, a doctor in
Berkeley, Gloucestershire Berkeley ( ) is a market town and civil parishes in England, parish in the Stroud (district), Stroud District in Gloucestershire, England. It lies in the Vale of Berkeley between the east bank of the River Severn and the M5 motorway. The town is ...
, 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 A root (or root word) is the core of a word that is irreducible into more meaningful elements. In morphology, a root is a morphologically simple unit which can be left bare or to which a prefix or a suffix In linguistics, a suffix is an affi ...
''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 the vaccinia virus. Vaccinia is in the same family as cowpox and variola virus but is genetically distinct from both. The origin of the vaccinia virus and how it came to be in the vaccine are not known. The current formulation of the smallpox vaccine is a live virus preparation of the infectious vaccinia virus. The vaccine is given using a bifurcated (two-pronged) needle that is dipped into the vaccine solution. The needle is used to prick the skin (usually the upper arm) several times in a few seconds. If successful, a red and itchy bump develops at the vaccine site in three or four days. In the first week, the bump becomes a large blister (called a "Jennerian vesicle") which fills with pus and begins to drain. During the second week, the blister begins to dry up, and a scab forms. The scab falls off in the third week, leaving a small scar. The
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform ...
induced by the 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 percent of those vaccinated. Smallpox vaccination provides a high level of immunity for three to five years and decreasing immunity thereafter. If a person is vaccinated again later, the 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 percent; it was 7 percent among those vaccinated 11 to 20 years prior, and 11 percent among those vaccinated 20 or more years before infection. By contrast, 52 percent of unvaccinated persons died. There are side effects and risks associated with the smallpox vaccine. 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 Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allerg ...
at the site of the vaccination ( erythema multiforme), spread of the vaccinia virus to other parts of the body, and spread to other individuals. Potentially life-threatening reactions occurred in 14 to 500 people out of every 1 million people vaccinated for the first time. Based on past experience, it is estimated that 1 or 2 people in 1 million (0.000198 percent) who receive the vaccine may die as a result, most often the result of postvaccinial
encephalitis Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, halluci ...
or severe
necrosis Necrosis () is a form of cell injury which results in the premature death of Cell (biology), cells in living Tissue (biology), tissue by Autolysis (biology), autolysis. Necrosis is caused by factors external to the cell or tissue, such as infec ...
in the area of vaccination (called
progressive vaccinia Progressive vaccinia is a rare cutaneous condition caused by the vaccinia virus, characterized by painless but progressive necrosis and ulceration. Presentation Complications Opportunistic fungal, protozoal, or bacterial infections and the vaccini ...
). 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. 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). By 1986, routine vaccination had ceased in all countries. It is now primarily recommended for laboratory workers at risk for occupational exposure. However, the possibility of variola virus being used as a biological weapon has rekindled interest in the development of newer vaccines. The smallpox vaccine is also effective in, and therefore administered for, the prevention of
monkeypox Monkeypox (also called mpox by the World_Health_Organization, WHO) is an infectious viral disease that can occur in humans and some other animals. Symptoms include fever, lymphadenopathy, swollen lymph nodes, and a rash that forms blisters and ...
.


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 the disease. Other than vaccination, treatment of smallpox is primarily supportive, such as wound care and infection control, fluid therapy, and possible
ventilator A ventilator is a piece of medical technology Health technology is defined by the World Health Organization as the "application of organized knowledge and skills in the form of devices, medicines, vaccines, procedures, and systems developed t ...
assistance. Flat and hemorrhagic types of smallpox are treated with the same therapies used to treat shock, such as
fluid resuscitation Fluid replacement or fluid resuscitation is the medical practice of replenishing bodily fluid lost through sweating, bleeding, fluid shifts or other pathologic processes. Fluids can be replaced with oral rehydration therapy Oral rehydration the ...
. People with semi-confluent and confluent types of smallpox may have therapeutic issues similar to patients with extensive skin
burn A burn is an injury to skin, or other tissues, caused by heat, cold, electricity, chemicals, friction, or ultraviolet radiation (like sunburn). Most burns are due to heat from hot liquids (called scalding), solids, or fire. Burns occur mainl ...
s. In July 2018, the
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
approved
tecovirimat Tecovirimat, sold under the brand name Tpoxx among others, is an Antiviral drug, antiviral medication with activity against orthopoxviruses such as smallpox and monkeypox. It is the first antipoxviral drug approved in the United States. It is an ...
, the first drug approved for treatment of smallpox.
Antiviral Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do no ...
treatments have improved since the last large smallpox epidemics, and studies suggest that the antiviral drug
cidofovir Cidofovir, brand name Vistide, is a topical or injectable Antiviral drug, antiviral medication primarily used as a treatment for cytomegalovirus (CMV) retinitis (an infection of the retina of the eye) in people with AIDS. Cidofovir was approved ...
might be useful as a therapeutic agent. The drug must be administered
intravenously Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
, and may cause serious
kidney The kidneys are two reddish-brown bean-shaped organ (anatomy), organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal ...
toxicity.
ACAM2000 ACAM2000 is a smallpox vaccine manufactured by Sanofi Pasteur Biologics Co. The vaccine provides protection against smallpox for people determined to be at high risk for smallpox infection. Background Smallpox is considered a biological threa ...
is a
smallpox vaccine The smallpox vaccine is the first vaccine to be developed against a contagious disease. In 1796, British physician Edward Jenner demonstrated that an infection with the relatively mild cowpox virus conferred immunity against the deadly smallpox ...
developed by Acambis. It was approved for use in the United States by the U.S. FDA on August 31, 2007. It contains live
vaccinia ''Vaccinia virus'' (VACV or VV) is a large, complex, Viral envelope, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 base pair, kbp in length, which encodes approximately 250 genes ...
virus, cloned from the same strain used in an earlier
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
, Dryvax. While the Dryvax virus was cultured in the skin of calves and freeze-dried, ACAM2000s virus is cultured in kidney epithelial cells (
Vero cell Vero cells are a lineage of cell (biology), cells used in cell cultures. The 'Vero' lineage was isolated from kidney epithelial cells extracted from an African green monkey (''Chlorocebus'' sp.; formerly called ''Cercopithecus aethiops'', this gro ...
s) from an African green monkey. Efficacy and adverse reaction incidence are similar to Dryvax. The vaccine is not routinely available to the US public; it is, however, used in the military and maintained in the
Strategic National Stockpile The Strategic National Stockpile (SNS), originally called the National Pharmaceutical Stockpile (NPS), is the United States' national repository of antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It i ...
. In June 2021, brincidofovir was approved for medical use in the United States for the treatment of human smallpox disease caused by variola virus.


Prognosis

The mortality rate from variola minor is approximately 1%, while the mortality rate from variola major is approximately 30%. Ordinary type-confluent is fatal about 50–75% of the time, ordinary-type semi-confluent about 25–50% of the time, in cases where the rash is discrete the case-fatality rate is less than 10%. The overall fatality rate for children younger than 1 year of age is 40–50%. Hemorrhagic and flat types have the highest fatality rates. The fatality rate for flat or late hemorrhagic type smallpox is 90% or greater and nearly 100% is observed in cases of early hemorrhagic smallpox. The case-fatality rate for variola minor is 1% or less. There is no evidence of chronic or recurrent infection with variola virus. 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. In fatal cases of ordinary smallpox, death usually occurs between days 10-16 of the illness. The cause of death from smallpox is not clear, but the infection is now known to involve multiple organs. Circulating
immune complex An immune complex, sometimes called an antigen-antibody complex or antigen-bound antibody, is a molecule formed from the binding of multiple antigens to Antibody, antibodies. The bound antigen and antibody act as a unitary object, effectively an ...
es, overwhelming viremia, or an uncontrolled
immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, Parasitism, parasites, and Fungus ...
may be contributing factors. In early hemorrhagic smallpox, death occurs suddenly about six days after the fever develops. The cause of death in early hemorrhagic cases is commonly due to heart failure and
pulmonary edema Pulmonary edema, also known as pulmonary congestion, is excessive edema, liquid accumulation in the parenchyma, tissue and pulmonary alveolus, air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia an ...
. In late hemorrhagic cases, high and sustained viremia, severe platelet loss and poor immune response were often cited as causes of death. In flat smallpox modes of death are similar to those in burns, with loss of fluid, protein and
electrolyte An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electron The electron ( or ) is a subatomic particle with a negative one elementary charge, elementary electr ...
s, and fulminating
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
.


Complications

Complications of smallpox arise most commonly in the respiratory system and range from simple
bronchitis Bronchitis is inflammation of the bronchi (large and medium-sized airways) in the lungs that causes coughing. Bronchitis usually begins as an infection in the nose, ears, throat, or sinuses. The infection then makes its way down to the bronchi. S ...
to fatal
pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of phlegm, productive or dry cough, chest pain, fever, ...
. 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. Other complications include
encephalitis Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, halluci ...
(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 The conjunctiva is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the human eye, eye). It is composed of non-keratinized, stratified squamous epithelium with goblet cells, stratified columnar epi ...
, and
cornea The cornea is the transparency (optics), transparent front part of the human eye, eye that covers the Iris (anatomy), iris, pupil, and Anterior chamber of eyeball, anterior chamber. Along with the anterior chamber and Lens (anatomy), lens, the c ...
, leading to complications such as
conjunctivitis Conjunctivitis, also known as pink eye, is inflammation of the conjunctiva, outermost layer of the white part of the eye and the inner surface of the eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness, or itchiness may ...
,
keratitis Keratitis is a condition in which the eye's cornea The cornea is the transparency (optics), transparent front part of the human eye, eye that covers the Iris (anatomy), iris, pupil, and Anterior chamber of eyeball, anterior chamber. Along w ...
,
corneal ulcer Corneal ulcer is an inflammatory or, more seriously, infective condition of the cornea involving disruption of its epithelial layer with involvement of the corneal Stroma of cornea, stroma. It is a common condition in humans particularly in the ...
,
iritis Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and in ...
, iridocyclitis, and atrophy of the optic nerve. Blindness results in approximately 35-40% of eyes affected with keratitis and corneal ulcer. Hemorrhagic smallpox can cause subconjunctival and
retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs Mollusca is the second-largest phylum of invertebrate animals after the Arthropoda, the members of whi ...
l hemorrhages. In 2-5% of young children with smallpox, virions reach the joints and bone, causing ''
osteomyelitis Osteomyelitis (OM) is an infection of bone tissue, bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humeru ...
variolosa''. Bony lesions are symmetrical, most common in the elbows, legs, and characteristically cause separation of the
epiphysis The epiphysis () is the rounded end of a long bone The long bones are those that are longer than they are wide. They are one of five types of bone A bone is a rigid organ Organ may refer to: Biology * Organ (biology), a part of an ...
and marked periosteal reactions. Swollen joints limit movement, and arthritis may lead to limb deformities,
ankylosis Ankylosis is a stiffness of a joint due to abnormal adhesion and rigidity of the bones of the joint, which may be the result of injury or disease. The rigidity may be complete or partial and may be due to inflammation of the tendinous or muscular ...
, malformed bones, flail joints, and stubby fingers. Between 65 and 80% of survivors are marked with deep pitted scars (pockmarks), most prominent on the face.


History


Disease emergence

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),''Vaccine and Serum Evils'', by Herbert M. Shelton, p. 5 and China (1122 BCE), Originally published as as well as a study of the Egyptian
mummy A mummy is a dead human or an animal whose soft tissues and Organ (anatomy), organs have been preserved by either intentional or accidental exposure to Chemical substance, chemicals, extreme cold, very low humidity, or lack of air, so that th ...
of
Ramses V Usermaatre Sekheperenre Ramesses V (also written Ramses and Rameses) was the fourth pharaoh Pharaoh (, ; Egyptian language, Egyptian: ''wikt:pr ꜥꜣ, pr ꜥꜣ''; cop, , Pǝrro; Biblical Hebrew: ''Parʿō'') is the vernacular term oft ...
, who died more than 3000 years ago (1145 BCE). It has been speculated that Egyptian traders brought smallpox to India during the 1st millennium BCE, where it remained as an
endemic Endemism is the state of a species In biology, a species is the basic unit of Taxonomy (biology), classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of or ...
human disease for at least 2000 years. 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. In Japan, the epidemic of 735–737 is believed to have killed as much as one-third of the population. At least seven religious deities have been specifically dedicated to smallpox, such as the god Sopona in the
Yoruba religion The Yoruba religion (Yoruba language, Yoruba: Ìṣẹ̀ṣe), or Isese, comprises the traditional religious and spiritual concepts and practice of the Yoruba people. Its homeland is in present-day Southwestern Nigeria, which comprises the majo ...
in West Africa. In India, the Hindu goddess of smallpox, Shitala, was worshipped in temples throughout the country. A different viewpoint is that smallpox emerged 1588 CE and the earlier reported cases were incorrectly identified as smallpox. The timing of the arrival of smallpox in Europe and south-western Asia is less clear. Smallpox is not clearly described in either the Old or
New Testament The New Testament grc, Ἡ Καινὴ Διαθήκη, Transliteration, transl. ; la, Novum Testamentum. (NT) is the second division of the Christian biblical canon. It discusses the teachings and person of Jesus in Christianity, Jesus, as ...
s of the Bible or in the literature of the Greeks or Romans. While some have identified the
Plague of Athens The Plague of Athens ( grc, Λοιμὸς τῶν Ἀθηνῶν}, ) was an epidemic that devastated the city-state of History of Athens, Athens in ancient Greece during the second year (430 BC) of the Peloponnesian War when an Athenian victory st ...
 – which was said to have originated in "
Ethiopia Ethiopia, , om, Itiyoophiyaa, so, Itoobiya, ti, ኢትዮጵያ, Ítiyop'iya, aa, Itiyoppiya officially the Federal Democratic Republic of Ethiopia, is a landlocked country in the Horn of Africa. It shares borders with Eritrea to the ...
" 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 Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek physician of the Classical Greece, classical period who is considered one of the most outstanding figures ...
if it had existed in the Mediterranean region during his lifetime. While the Antonine Plague that swept through the
Roman Empire The Roman Empire ( la, Imperium Romanum ; grc-gre, Βασιλεία τῶν Ῥωμαίων, Basileía tôn Rhōmaíōn) was the post-Roman Republic, Republican period of ancient Rome. As a polity, it included large territorial holdings aro ...
in 165180 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 Gregory of Tours (30 November 538 – 17 November 594 AD) was a Gallo-Roman History, historian and Bishops of Tours, Bishop of Tours, which made him a leading prelate of the area that had been previously referred to as Gaul by the Romans. He ...
recorded a similar outbreak in France and Italy in 580, the first use of the term ''variola''. Other historians speculate that
Arab The Arabs (singular: Arab; singular ar, عَرَبِيٌّ, DIN 31635: , , plural ar, عَرَب, DIN 31635: , Arabic pronunciation: ), also known as the Arab people, are an ethnic group mainly inhabiting the Arab world in Western Asia, ...
armies first carried smallpox from Africa into Southwestern Europe during the 7th and 8th centuries. 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 Measles is a highly contagious infectious disease caused by Measles morbillivirus, measles virus. Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever, often ...
and
chickenpox Chickenpox, also known as varicella, is a highly Infectious disease, contagious disease caused by the initial infection with varicella zoster virus (VZV). The disease results in a characteristic skin rash that forms Vesicle (dermatology), sma ...
in his ''Kitab fi al-jadari wa-al-hasbah'' (''The Book of Smallpox and Measles''). During the
Middle Ages In the history of Europe, the Middle Ages or medieval period lasted approximately from the late 5th to the late 15th centuries, similar to the Post-classical, post-classical period of World history (field), global history. It began with t ...
several smallpox outbreaks occurred in Europe. However, smallpox had not become established there until the population growth and mobility marked by the
Crusades The Crusades were a series of religious wars initiated, supported, and sometimes directed by the Latin Church in the medieval period. The best known of these Crusades are those to the Holy Land in the period between 1095 and 1291 that were in ...
allowed it to do so. By the 16th century, smallpox had become entrenched across most of Europe, where it had a mortality rate as high as 30 percent. 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. By the 16th century, smallpox had become a predominant cause of morbidity and mortality throughout much of the world. There were no credible descriptions of smallpox-like disease in the
Americas The Americas, which are sometimes collectively called America, are a landmass comprising the totality of North America, North and South America. The Americas make up most of the land in Earth's Western Hemisphere and comprise the New World. ...
before the westward exploration by Europeans in the 15th century CE. Smallpox was introduced into the Caribbean island of
Hispaniola Hispaniola (, also ; es, La Española; Latin and french: Hispaniola; ht, Ispayola; tnq, Ayiti or Quisqueya) is an island in the Caribbean that is part of the Greater Antilles. Hispaniola is the most populous island in the West Indies, and th ...
in 1507, and into the mainland in 1520, when Spanish settlers from Hispaniola arrived in Mexico, inadvertently carrying smallpox with them. Because the native
Amerindian The Indigenous peoples of the Americas are the inhabitants of the Americas before the arrival of the European colonization of the Americas, European settlers in the 15th century, and the ethnic groups who now identify themselves with those peopl ...
population had no acquired immunity to this new disease, their peoples were decimated by epidemics. Such disruption and population losses were an important factor in the Spanish achieving conquest of the
Aztec The Aztecs () were a Mesoamerican culture that flourished in central Mexico in the post-classic period from 1300 to 1521. The Aztec people included different Indigenous peoples of Mexico, ethnic groups of central Mexico, particularly those g ...
s and the
Inca The Inca Empire (also Quechuan and Aymaran spelling shift, known as the Incan Empire and the Inka Empire), called ''Tawantinsuyu'' by its subjects, (Quechuan languages, Quechua for the "Realm of the Four Parts",  "four parts together" ) wa ...
s. Similarly, English settlement of the east coast of North America in 1633 in
Plymouth, Massachusetts Plymouth (; historically known as Plimouth and Plimoth) is a town in Plymouth County, Massachusetts, United States. Located in Greater Boston, the town holds a place of great prominence in American history, folklore, and culture, and is known as ...
was accompanied by devastating outbreaks of smallpox among Native American populations, and subsequently among the native-born colonists. Case fatality rates during outbreaks in Native American populations were as high as 90%. Smallpox was introduced into
Australia Australia, officially the Commonwealth of Australia, is a sovereign country comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands. With an area of , Australia is the largest country by ...
in 1789 and again in 1829, though colonial surgeons, who by 1829 were attempting to distinguish between smallpox and
chickenpox Chickenpox, also known as varicella, is a highly Infectious disease, contagious disease caused by the initial infection with varicella zoster virus (VZV). The disease results in a characteristic skin rash that forms Vesicle (dermatology), sma ...
(which could be almost equally fatal to Aborigines), were divided as to whether the 1829–1830 epidemic was chickenpox or smallpox. 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. By the mid-18th century, smallpox was a major endemic disease everywhere in the world except in Australia and small islands untouched by outside exploration. In 18th century Europe, smallpox was a leading cause of death, killing an estimated 400,000 Europeans each year. Up to 10 percent of Swedish infants died of smallpox each year, and the death rate of infants in
Russia Russia (, , ), or the Russian Federation, is a List of transcontinental countries, transcontinental country spanning Eastern Europe and North Asia, Northern Asia. It is the List of countries and dependencies by area, largest country in the ...
might have been even higher. The widespread use of
variolation Variolation was the method of inoculation first used to immunize individuals against smallpox (''Variola'') with material taken from a patient or a recently variolated individual, in the hope that a mild, but protective, infection would result. Var ...
in a few countries, notably Great Britain, its North American colonies, and China, somewhat reduced the impact of smallpox among the wealthy classes during the latter part of the 18th century, but a real reduction in its incidence did not occur until vaccination became a common practice toward the end of the 19th century. Improved vaccines and the practice of re-vaccination led to a substantial reduction in cases in Europe and North America, but smallpox remained almost unchecked everywhere else in the world. By the mid-20th century, variola minor occurred along with variola major, in varying proportions, in many parts of Africa. Patients with variola minor experience only a mild systemic illness, are often ambulant throughout the course of the disease, and are therefore able to more easily spread disease. Infection with variola minor virus induces immunity against the more deadly variola major form. Thus, as variola 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.


Eradication

The first clear reference to smallpox inoculation was made by the Chinese author Wan Quan (1499–1582) in his () published in 1549, with earliest hints of the practice in China during the 10th century. In China, powdered smallpox scabs were blown up the noses of the healthy. People would then develop a mild case of the disease and from then on were immune to it. 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. Two reports on the Chinese practice of
inoculation Inoculation is the act of implanting a pathogen or other microorganism. It may refer to methods of artificial induction of immunity, artificially inducing immunity against various infectious diseases, or it may be used to describe the spreading ...
were received by the
Royal Society The Royal Society, formally The Royal Society of London for Improving Natural Knowledge, is a learned society and the United Kingdom's national academy of sciences. The society fulfils a number of roles: promoting science and its benefits, ...
in London in 1700; one by Dr.
Martin Lister Martin Lister FRS (12 April 1639 – 2 February 1712) was an English naturalist and physician. His daughters Anne and Susanna were two of his illustrators and engravers. J. D. Woodley, ‘Lister , Susanna (bap. 1670, d. 1738)’, Oxford Dic ...
who received a report by an employee of the
East India Company The East India Company (EIC) was an English, and later British, joint-stock company founded in 1600 and dissolved in 1874. It was formed to Indian Ocean trade, trade in the Indian Ocean region, initially with the East Indies (the Indian subco ...
stationed in China and another by
Clopton Havers Clopton Havers (24 February 1657 – April 1702) was an English physician A physician (American English), medical practitioner (English in the Commonwealth of Nations, Commonwealth English), medical doctor, or simply doctor, is a hea ...
.
Voltaire François-Marie Arouet (; 21 November 169430 May 1778) was a French Age of Enlightenment, Enlightenment writer, historian, and philosopher. Known by his ''Pen name, nom de plume'' M. de Voltaire (; also ; ), he was famous for his wit, and his ...
(1742) reports that the Chinese had practiced smallpox inoculation "these hundred years".
variolation Variolation was the method of inoculation first used to immunize individuals against smallpox (''Variola'') with material taken from a patient or a recently variolated individual, in the hope that a mild, but protective, infection would result. Var ...
had also been witnessed in
Turkey Turkey ( tr, Türkiye ), officially the Republic of Türkiye ( tr, Türkiye Cumhuriyeti, links=no ), is a transcontinental country located mainly on the Anatolia, Anatolian Peninsula in Western Asia, with a East Thrace, small portion on th ...
by
Lady Mary Wortley Montagu Lady Mary Wortley Montagu (née Pierrepont; 15 May 168921 August 1762) was an English Aristocracy (class), aristocrat, writer, and poet. Born in 1689, Lady Mary spent her early life in England. In 1712, Lady Mary married Edward Wortley Montagu ...
, who later introduced it in the UK. 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 Shetland, also called the Shetland Islands and formerly Zetland, is a subarctic archipelago in Scotland lying between Orkney, the Faroe Islands and Norway. It is the northernmost region of the United Kingdom. The islands lie about to the no ...
, Scotland. Notions found success in treating people from at least the late 1780s through a method devised by himself despite having no formal medical background. His method involved exposing smallpox pus to
peat Peat (), also known as turf (), is an accumulation of partially Decomposition, decayed vegetation or organic matter. It is unique to natural areas called peatlands, bogs, mires, Moorland, moors, or muskegs. The peatland ecosystem covers and ...
smoke, burying it in the ground with
camphor Camphor () is a waxy, colorless solid with a strong aroma. It is classified as a terpenoid and a cyclic ketone. It is found in the wood of the camphor laurel (''Cinnamomum camphora''), a large evergreen tree found in East Asia; and in the kap ...
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. He was reputed not to have lost a single patient. 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." The English physician
Edward Jenner Edward Jenner, (17 May 1749 – 26 January 1823) was a British physician and scientist who pioneered the concept of vaccines, and created the smallpox vaccine, the world's first vaccine. The terms ''vaccine'' and ''vaccination'' are derived f ...
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. In Russia in 1796, the first child to receive this treatment was bestowed the name "Vaccinov" by
Catherine the Great Catherine II (born Sophie of Anhalt-Zerbst; 2 May 172917 November 1796), most commonly known as Catherine the Great, was the reigning empress of Russia from 1762 to 1796. She came to power following the overthrow of her husband, Peter III of Rus ...
, and was educated at the expense of the nation. The introduction of the vaccine to the New World took place in Trinity, Newfoundland in 1800 by Dr. John Clinch, boyhood friend and medical colleague of Jenner. 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. The
U.S. Congress The United States Congress is the legislature of the federal government of the United States. It is Bicameralism, bicameral, composed of a lower body, the United States House of Representatives, House of Representatives, and an upper body, ...
passed the Vaccine Act of 1813 to ensure that safe smallpox vaccine would be available to the American public. By about 1817, a robust state vaccination program existed in the
Dutch East Indies The Dutch East Indies, also known as the Netherlands East Indies ( nl, Nederlands(ch)-Indië; ), was a Dutch colony consisting of what is now Indonesia. It was formed from the nationalised trading posts of the Dutch East India Company, whic ...
. On August 26, 1807,
Bavaria Bavaria ( ; ), officially the Free State of Bavaria (german: Freistaat Bayern, link=no ), is a state in the south-east of Germany Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the sec ...
became the first country in the world to introduce compulsory vaccinations.
Baden Baden (; ) is a historical territory in South Germany, in earlier times on both sides of the Upper Rhine but since the Napoleonic Wars only East of the Rhine. History The margraves of Baden originated from the House of Zähringen. Baden is ...
followed in 1809,
Prussia Prussia, , Old Prussian: ''Prūsa'' or ''Prūsija'' was a Germans, German state on the southeast coast of the Baltic Sea. It formed the German Empire under Prussian rule when it united the German states in 1871. It was ''de facto'' dissolved ...
in 1815,
Württemberg Württemberg ( ; ) is a historical German territory roughly corresponding to the cultural and linguistic region of Swabia. The main town of the region is Stuttgart. Together with Baden and Hohenzollern, two other historical territories, Wü ...
in 1818,
Sweden Sweden, formally the Kingdom of Sweden,The United Nations Group of Experts on Geographical Names states that the country's formal name is the Kingdom of SwedenUNGEGN World Geographical Names, Sweden./ref> is a Nordic countries, Nordic c ...
in 1816 and the
German Empire The German Empire (),Herbert Tuttle wrote in September 1881 that the term "Reich" does not literally connote an empire as has been commonly assumed by English-speaking people. The term literally denotes an empire – particularly a hereditary ...
in 1874 through the Reichs Vaccination Act. In Lutheran Sweden, the Protestant clergy played a pioneering role in voluntary smallpox vaccination as early as 1800. The first vaccination was carried out in Liechtenstein in 1801, and from 1812 it was mandatory to vaccinate. In
British India The provinces of India, earlier presidencies of British India and still earlier, presidency towns, were the administrative divisions of British governance on the Indian subcontinent. Collectively, they have been called British India. In one ...
a program was launched to propagate smallpox vaccination, through Indian vaccinators, under the supervision of European officials. Nevertheless, British vaccination efforts in India, and in
Burma Myanmar, ; UK pronunciations: US pronunciations incl. . Note: Wikipedia's IPA conventions require indicating /r/ even in British English although only some British English speakers pronounce r at the end of syllables. As John Wells explai ...
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. By 1832, the federal government of the United States established a smallpox vaccination program for Native Americans. 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. In the United States, from 1843 to 1855, first
Massachusetts Massachusetts (Massachusett language, Massachusett: ''Muhsachuweesut assachusett writing systems, məhswatʃəwiːsət'' English: , ), officially the Commonwealth of Massachusetts, is the most populous U.S. state, state in the New England ...
and then other states required smallpox vaccination. Although some disliked these measures, coordinated efforts against smallpox went on, and the disease continued to diminish in the wealthy countries. 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 as protection against reintroduction until the mid to late 1970s.
Australia Australia, officially the Commonwealth of Australia, is a sovereign country comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands. With an area of , Australia is the largest country by ...
and
New Zealand New Zealand ( mi, Aotearoa ) is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and over 700 List of islands of New Zealand, smaller islands. It is the ...
are two notable exceptions; neither experienced endemic smallpox and never vaccinated widely, relying instead on protection by distance and strict quarantines. The first hemisphere-wide effort to eradicate smallpox was made in 1950 by the
Pan American Health Organization The Pan American Health Organization (PAHO) is an international public health agency working to improve the health and living standards of the people of the Americas. It is part of the United Nations system, serving as the Regional Office for ...
. The campaign was successful in eliminating smallpox from all countries of the Americas except Argentina, Brazil, Colombia, and Ecuador. In 1958 Professor Viktor Zhdanov, Deputy Minister of Health for the
USSR The Soviet Union,. officially the Union of Soviet Socialist Republics. (USSR),. was a List of former transcontinental countries#Since 1700, transcontinental country that spanned much of Eurasia from 1922 to 1991. A flagship communist state, ...
, called on the
World Health Assembly The World Health Assembly (WHA) is the forum through which the World Health Organization (WHO) is governed by its 194 World Health Organization#Membership, member states. It is the world's highest health policy setting body and is composed of he ...
to undertake a global initiative to eradicate smallpox. The proposal (Resolution WHA11.54) was accepted in 1959. At this point, 2 million people were dying from smallpox every year. Overall, the progress towards eradication was disappointing, especially in Africa and in the
Indian subcontinent The Indian subcontinent is a list of the physiographic regions of the world, physiographical region in United Nations geoscheme for Asia#Southern Asia, Southern Asia. It is situated on the Indian Plate, projecting southwards into the Indian O ...
. In 1966 an international team, the Smallpox Eradication Unit, was formed under the leadership of an American, Donald Henderson. 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 Disease surveillance is an epidemiology, epidemiological practice by which the spread of disease is monitored in order to establish patterns of progression. The main role of disease surveillance is to predict, observe, and minimize the harm cause ...
method promoted by Czech epidemiologist Karel Raška. In the early 1950s, an estimated 50 million cases of smallpox occurred in the world each year. To eradicate smallpox, each outbreak had to be stopped from spreading, by isolation of cases and vaccination of everyone who lived close by. This process is known as "ring vaccination". The key to this strategy was the monitoring of cases in a community (known as surveillance) and containment. The initial problem the WHO team faced was inadequate reporting of smallpox cases, as many cases did not come to the attention of the authorities. The fact that humans are the only reservoir for smallpox infection and that carriers did not exist played a significant role in the eradication of smallpox. The WHO established a network of consultants who assisted countries in setting up surveillance and containment activities. Early on, donations of vaccine were provided primarily by the Soviet Union and the United States, but by 1973, more than 80 percent of all vaccine was produced in developing countries. The Soviet Union provided one and a half billion doses between 1958 and 1979, as well as the medical staff. The last major European outbreak of smallpox was in 1972 in Yugoslavia, after a pilgrim from
Kosovo Kosovo ( sq, Kosova or ; sr-Cyrl, Косово ), officially the Republic of Kosovo ( sq, Republika e Kosovës, links=no; sr, Република Косово, Republika Kosovo, links=no), is a international recognition of Kosovo, partiall ...
returned from the Middle East, where he had contracted the virus. The epidemic infected 175 people, causing 35 deaths. Authorities declared
martial law Martial law is the imposition of direct military control of normal civil functions or suspension of civil law by a government, especially in response to an emergency where civil forces are overwhelmed, or in an military occupation, occupied t ...
, enforced quarantine, and undertook widespread re-vaccination of the population, enlisting the help of the WHO. In two months, the outbreak was over. Prior to this, there had been a smallpox outbreak in May–July 1963 in
Stockholm Stockholm () is the Capital city, capital and List of urban areas in Sweden by population, largest city of Sweden as well as the List of urban areas in the Nordic countries, largest urban area in Scandinavia. Approximately 980,000 people liv ...
, Sweden, brought from the
Far East The ''Far East'' was a European term to refer to the geographical regions that includes East and Southeast Asia Southeast Asia, also spelled South East Asia and South-East Asia, and also known as Southeastern Asia, South-eastern Asia or S ...
by a Swedish sailor; this had been dealt with by quarantine measures and vaccination of the local population. By the end of 1975, smallpox persisted only in the
Horn of Africa The Horn of Africa (HoA), also known as the Somali Peninsula, is a large peninsula and Geopolitics, geopolitical region in East Africa.Robert Stock, ''Africa South of the Sahara, Second Edition: A Geographical Interpretation'', (The Guilford P ...
. Conditions were very difficult in
Ethiopia Ethiopia, , om, Itiyoophiyaa, so, Itoobiya, ti, ኢትዮጵያ, Ítiyop'iya, aa, Itiyoppiya officially the Federal Democratic Republic of Ethiopia, is a landlocked country in the Horn of Africa. It shares borders with Eritrea to the ...
and
Somalia Somalia, , Osmanya script: 𐒈𐒝𐒑𐒛𐒐𐒘𐒕𐒖; ar, الصومال, aṣ-Ṣūmāl officially the Federal Republic of SomaliaThe ''Federal Republic of Somalia'' is the country's name per Article 1 of thProvisional Constitut ...
, 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 Frank John Fenner (21 December 1914 – 22 November 2010) was an Australian scientist with a distinguished career in the field of virology Virology is the Scientific method, scientific study of biological viruses. It is a subfield of microb ...
. As the campaign neared its goal, Fenner and his team played an important role in verifying eradication. The last naturally occurring case of indigenous smallpox (variola minor) was diagnosed in
Ali Maow Maalin Ali Maow Maalin ( so, Cali Macow Macallin; also Mao Moallim and Mao' Mo'allim; 1954 – 22 July 2013) was a Somali hospital cook and health worker from Merca who is the last person known to have been infected with naturally occurring ''alastrim, ...
, a hospital cook in Merca,
Somalia Somalia, , Osmanya script: 𐒈𐒝𐒑𐒛𐒐𐒘𐒕𐒖; ar, الصومال, aṣ-Ṣūmāl officially the Federal Republic of SomaliaThe ''Federal Republic of Somalia'' is the country's name per Article 1 of thProvisional Constitut ...
, on 26 October 1977. The last naturally occurring case of the more deadly variola major had been detected in October 1975 in a three-year-old
Bangladesh Bangladesh (}, ), officially the People's Republic of Bangladesh, is a country in South Asia. It is the List of countries and dependencies by population, eighth-most populous country in the world, with a population exceeding 165 million pe ...
i girl, Rahima Banu. 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. The first two sentences of the resolution read:


Costs and benefits

The cost of the eradication effort, from 1967 to 1979, was roughly US$300 million. Roughly a third came from the developed world, which had largely eradicated smallpox decades earlier. The United States, the largest contributor to the program, has reportedly recouped that investment every 26 days since in money not spent on vaccinations and the costs of incidence.


Post-eradication

The last case of smallpox in the world occurred in an outbreak in the United Kingdom in 1978. A medical photographer, Janet Parker, contracted the disease at the
University of Birmingham Medical School The University of Birmingham Medical School is one of Britain's largest and oldest medical school A medical school is a tertiary educational institution, or part of such an institution, that teaches medicine, and awards a professional degre ...
and died on 11 September 1978. Although it has remained unclear how Parker became infected, the source of the infection was established to be the variola virus grown for research purposes at the Medical School laboratory. 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 The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency, under the United S ...
(CDC) and the Soviet Union's (now Russia's) State Research Center of Virology and Biotechnology VECTOR. WHO first recommended destruction of the virus in 1986 and later set the date of destruction to be 30 December 1993. This was postponed to 30 June 1999. 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. Destroying existing stocks would reduce the risk involved with ongoing smallpox research; the stocks are not needed to respond to a smallpox outbreak. 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.Comments on the Scientific Review of Variola Virus Research, 1999–2010.
Advisory Group of Independent Experts to review the smallpox research program (AGIES) WHO document WHO/HSE/GAR/BDP/2010.4
The latter view is frequently supported in the scientific community, particularly among veterans of the WHO Smallpox Eradication Program. On March 31, 2003, smallpox scabs were found inside an envelope in an 1888 book on
Civil War A civil war or intrastate war is a war between organized groups within the same Sovereign state, state (or country). The aim of one side may be to take control of the country or a region, to achieve independence for a region, or to change go ...
medicine in
Santa Fe, New Mexico Santa Fe ( ; , Spanish for 'Holy Faith'; tew, Oghá P'o'oge, Tewa for 'white shell water place'; tiw, Hulp'ó'ona, label=Tiwa language, Northern Tiwa; nv, Yootó, Navajo for 'bead + water place') is the capital of the U.S. state of New Mexico. ...
. 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. 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 The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late 1 ...
location in
Bethesda, Maryland Bethesda () is an unincorporated area, unincorporated, census-designated place in southern Montgomery County, Maryland, Montgomery County, Maryland. It is located just northwest of Washington, D.C. It takes its name from a local church, the Bethe ...
. 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. After studies were conducted, the CDC destroyed the virus under WHO observation on February 24, 2015. In 2017, Canadian scientists recreated an extinct horse pox virus to demonstrate that the variola virus can be recreated in a small lab at a cost of about $100,000, by a team of scientists without specialist knowledge. This makes the retention controversy irrelevant since the virus can be easily recreated even if all samples are destroyed. 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. In September 2019, the Russian lab housing smallpox samples experienced a gas explosion that injured one worker. It did not occur near the virus storage area, and no samples were compromised, but the incident prompted a review of risks to containment.


Society and culture


Biological warfare

In 1763,
Pontiac's War Pontiac's War (also known as Pontiac's Conspiracy or Pontiac's Rebellion) was launched in 1763 by a loose confederation of Native Americans in the United States, Native Americans dissatisfied with British rule in the Great Lakes region following ...
broke out as a Native American confederacy led by Pontiac attempted to counter British control over the
Great Lakes The Great Lakes, also called the Great Lakes of North America, are a series of large interconnected freshwater lakes in the mid-east region of North America that connect to the Atlantic Ocean via the Saint Lawrence River. There are five lakes ...
region. A group of Native American warriors laid siege to British-held Fort Pitt on June 22. In response,
Henry Bouquet Henry Bouquet (born Henri Louis Bouquet; 1719 – 2 September 1765) was a Swiss mercenary The Swiss mercenaries (german: Reisläufer) were a powerful infantry force constituted by professional soldiers originating from the cantons of th ...
, the commander of the fort, ordered his subordinate Simeon Ecuyer to give smallpox-infested blankets from the infirmary to a
Delaware Delaware ( ) is a U.S. state, state in the Mid-Atlantic (United States), Mid-Atlantic region of the United States, bordering Maryland to its south and west; Pennsylvania to its north; and New Jersey and the Atlantic Ocean to its east. The s ...
delegation outside the fort. Bouquet had discussed this with his superior, Sir Jeffrey Amherst, who wrote to Bouquet stating: "Could it not be contrived to send the small pox among the disaffected tribes of Indians? We must on this occasion use every stratagem in our power to reduce them." Bouquet agreed with the proposal, writing back that "I will try to inocculate the Indians by means of Blankets that may fall in their hands". 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. I hope it will have the desired effect." The effectiveness of this effort to broadcast the disease is unknown. There are also accounts that smallpox was used as a weapon during the
American Revolutionary War The American Revolutionary War (April 19, 1775 – September 3, 1783), also known as the Revolutionary War or American War of Independence, was a major war of the American Revolution. Widely considered as the war that secured the independence of t ...
(1775–1783). According to a theory put forward in ''Journal of Australian Studies'' (''JAS'') by independent researcher Christopher Warren,
Royal Marines The Corps of Royal Marines (RM), also known as the Royal Marines Commandos, are the UK's special operations capable commando force, amphibious warfare, amphibious light infantry and also one of the :Fighting Arms of the Royal Navy, five fighti ...
used smallpox in 1789 against indigenous tribes in
New South Wales ) , nickname = , image_map = New South Wales in Australia.svg , map_caption = Location of New South Wales in AustraliaCoordinates: , subdivision_type = Country , subdivision_name = Australia , established_title = Before federation , es ...
. This theory was also considered earlier in ''Bulletin of the History of Medicine'' and by David Day. 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 Chickenpox, also known as varicella, is a highly Infectious disease, contagious disease caused by the initial infection with varicella zoster virus (VZV). The disease results in a characteristic skin rash that forms Vesicle (dermatology), sma ...
—a more infectious disease which, at the time, was often confused, even by surgeons, with smallpox, and may have been comparably deadly to Aborigines and other peoples without natural immunity to it. Carmody noted that in the 8-month voyage of the
First Fleet The First Fleet was a fleet of 11 Age of sail, ships that brought the first European and African settlers to Australia. It was made up of two Royal Navy vessels, three store ships and six penal transportation, convict transports. On 13 May 1 ...
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 variola virus possessed by First Fleet surgeons. 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. In 2007, Christopher Warren offered evidence that the British smallpox may have been still viable. 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. W. S. Carus, an expert in biological weapons, has written that there is circumstantial evidence that smallpox was deliberately introduced to the Aboriginal population. However Carmody and the Australian National University's Boyd Hunter continue to support the chickenpox hypothesis. In a 2013 lecture at the Australian National University, Carmody pointed out that chickenpox, unlike smallpox, was known to be present in the Sydney Cove colony. He also suggested that all c. 18th century (and earlier) identifications of smallpox outbreaks were dubious because: "surgeons … would have been unaware of the distinction between smallpox and chickenpox – the latter having traditionally been considered a milder form of smallpox." During
World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the World War II by country, vast majority of the world's countries—including all of the great power ...
, scientists from the United Kingdom, United States, and Japan (
Unit 731 , short for Manshu Detachment 731 and also known as the Kamo Detachment and Ishii Unit, was a covert Biological warfare, biological and chemical warfare research and development unit of the Imperial Japanese Army that engaged in unethical h ...
of the
Imperial Japanese Army The was the official ground-based armed force of the Empire of Japan The also known as the Japanese Empire or Imperial Japan, was a historical nation-state and great power that existed from the Meiji Restoration in 1868 until t ...
) were involved in research into producing a biological weapon from smallpox. 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 A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
. In 1947, the
Soviet Union The Soviet Union,. officially the Union of Soviet Socialist Republics. (USSR),. was a List of former transcontinental countries#Since 1700, transcontinental country that spanned much of Eurasia from 1922 to 1991. A flagship communist state, ...
established a smallpox weapons factory in the city of Zagorsk, 75 km to the northeast of Moscow. An outbreak of weaponized smallpox occurred during testing at a facility on an island in the
Aral Sea The Aral Sea ( ; kk, Арал теңізі, Aral teñızı; uz, Орол денгизи, Orol dengizi; kaa, Арал теңизи, Aral teńizi; russian: Аральское море, Aral'skoye more) was an endorheic basin, endorheic lake lyi ...
in 1971. General Prof. Peter Burgasov, former Chief Sanitary Physician of the
Soviet Army uk, Радянська армія , image = File:Communist star with golden border and red rims.svg , alt = , caption = Emblem of the Soviet Army , start_date ...
and a senior researcher within the
Soviet program of biological weapons The Soviet Union covertly operated the world's largest, longest, and most sophisticated biological weapons program, thereby violating its obligations as a party to the 1972 Biological Weapons Convention.Leitenberg, M., Zilinskas, R., & Kuhn, J. ...
, described the incident: Others contend that the first patient may have contracted the disease while visiting Uyaly or Komsomolsk-on-Ustyurt, two cities where the boat docked. 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. In 1992, Soviet defector
Ken Alibek Kanatzhan "Kanat" Alibekov ( kk, Қанатжан Байзақұлы Әлібеков, Qanatjan Baizaqūly Älıbekov; russian: Канатжан Алибеков, Kanatzhan Alibekov; born 1950), known as Kenneth "Ken" Alibek since 1992, is a Kazak ...
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
warhead A warhead is the forward section of a device that contains the explosive agent or toxic (biological, chemical, or nuclear) material that is delivered by a missile, rocket (weapon), rocket, torpedo, or bomb. Classification Types of warheads inc ...
s 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. 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. Specific allegations made against Iraq in this respect proved to be false. Concern has been expressed by some that
artificial gene synthesis Artificial gene synthesis, or simply gene synthesis, refers to a group of methods that are used in synthetic biology to construct and assemble genes from nucleotides ''De novo synthesis, de novo''. Unlike DNA synthesis in living cells, artificial ...
could be used to recreate the virus from existing digital genomes, for use in biological warfare. Insertion of the synthesized smallpox DNA into existing related pox viruses could theoretically be used to recreate the virus.. The first step to mitigating this risk, it has been suggested, should be to destroy the remaining virus stocks to enable unequivocal criminalization of any possession of the virus.


Notable cases

Famous historical figures who contracted smallpox include Lakota Chief
Sitting Bull Sitting Bull ( lkt, Tȟatȟáŋka Íyotake ; December 15, 1890) was a Hunkpapa Lakota people, Lakota leader who led his people during years of resistance against United States government policies. He was killed by Indian agency police on the S ...
,
Ramses V Usermaatre Sekheperenre Ramesses V (also written Ramses and Rameses) was the fourth pharaoh Pharaoh (, ; Egyptian language, Egyptian: ''wikt:pr ꜥꜣ, pr ꜥꜣ''; cop, , Pǝrro; Biblical Hebrew: ''Parʿō'') is the vernacular term oft ...
, the
Kangxi Emperor The Kangxi Emperor (4 May 1654– 20 December 1722), also known by his temple name Emperor Shengzu of Qing, born Xuanye, was the third emperor of the Qing dynasty, and the second Qing emperor to rule over China proper China proper, I ...
(survived),
Shunzhi Emperor The Shunzhi Emperor (15 March 1638 – 5 February 1661) was the second emperor An emperor (from la, imperator, via fro, empereor) is a monarch, and usually the sovereignty, sovereign ruler of an empire or another type of imperial re ...
and
Tongzhi Emperor The Tongzhi Emperor (27 April 1856 – 12 January 1875), born Zaichun of the Aisin Gioro clan, was the ninth List of emperors of the Qing dynasty, Emperor of the Qing dynasty, and the eighth Qing emperor to rule over China proper. His reign, from 1 ...
of China, Emperor Komei of Japan (died of smallpox in 1867), and
Date Masamune was a regional ruler of Japan's Azuchi–Momoyama period through early Edo period. Heir to a long line of powerful ''daimyō'' in the Tōhoku region, he went on to found the modern-day city of Sendai. An outstanding tactician, he was made all ...
of Japan (who lost an eye to the disease). Cuitláhuac, the 10th
tlatoani ''Tlatoani'' ( , "one who speaks, ruler"; plural ' or tlatoque) is the Classical Nahuatl term for the ruler of an , a pre-Hispanic state. It is the noun form of the verb "tlahtoa" meaning "speak, command, rule". As a result, it has been variousl ...
(ruler) of the
Aztec The Aztecs () were a Mesoamerican culture that flourished in central Mexico in the post-classic period from 1300 to 1521. The Aztec people included different Indigenous peoples of Mexico, ethnic groups of central Mexico, particularly those g ...
city of
Tenochtitlan , ; es, Tenochtitlan also known as Mexico-Tenochtitlan, ; es, México-Tenochtitlan was a large Mexican in what is now the historic center of Mexico City. The exact date of the founding of the city is unclear. The date 13 March 1325 was ...
, died of smallpox in 1520, shortly after its introduction to the
Americas The Americas, which are sometimes collectively called America, are a landmass comprising the totality of North America, North and South America. The Americas make up most of the land in Earth's Western Hemisphere and comprise the New World. ...
, and the Incan emperor
Huayna Capac Huayna Capac (with many alternative transliterations; 1464/1468–1524) was the third Sapa Inca, Sapan Inka of the Inca Empire, born in Tomebamba, Tumipampa sixth of the Hanan dynasty, and eleventh of the Inca civilization. Subjects commonly appro ...
died of it in 1527 (causing a civil war of succession in the Inca empire and the eventual conquest by the Spaniards). More recent public figures include
Guru Har Krishan Guru Har Krishan (Gurmukhi Gurmukhī ( pa, ਗੁਰਮੁਖੀ, , Shahmukhi alphabet, Shahmukhi: ) is an abugida developed from the Laṇḍā scripts, standardized and used by the second Sikh gurus, Sikh guru, Guru Angad (1504–1552) ...
, 8th Guru of the Sikhs, in 1664,
Louis I of Spain Louis I (Luis Felipe Fernando Joseph; 25 August 1707 – 31 August 1724) was List of Spanish monarchs, King of Spain from 15 January 1724 until his death in August the same year. His reign is List of shortest reigning monarchs of all time, one of ...
in 1724 (died),
Peter II of Russia Peter II Alexeyevich (russian: Пётр II, Пётр Алексеевич, ''Pyotr Vtoroy'', ''Pyotr Alekseyevich'', – ) reigned as Emperor of Russia from 1727 until his untimely death at the age of 14. He was the only son of Tsarevich Alexei ...
in 1730 (died),
George Washington George Washington (February 22, 1732, 1799) was an American military officer, statesman, and Founding Fathers of the United States, Founding Father who served as the first president of the United States from 1789 to 1797. Appointed by the ...
(survived),
Louis XV of France Louis XV (15 February 1710 – 10 May 1774), known as Louis the Beloved (french: le Bien-Aimé), was King of France from 1 September 1715 until his death in 1774. He succeeded his great-grandfather Louis XIV at the age of five. Until he reached ...
in 1774 (died) and Maximilian III Joseph of Bavaria in 1777 (died). Prominent families throughout the world often had several people infected by and/or perish from the disease. For example, several relatives of
Henry VIII of England Henry VIII (28 June 149128 January 1547) was King of England from 22 April 1509 until his death in 1547. Henry is best known for his Wives of Henry VIII, six marriages, and for his efforts to have his first marriage (to Catherine of Aragon) ...
survived the disease but were scarred by it. These include his sister
Margaret Margaret is a female first name, derived via French () and Latin () from grc, μαργαρίτης () meaning "pearl". The Greek is borrowed from Indo-Iranian languages, Persian. Margaret has been an English name since the 11th century, and r ...
, his wife
Anne of Cleves Anne of Cleves (german: Anna von Kleve; 1515 – 16 July 1557) was List of English royal consorts, Queen of England from 6 January to 12 July 1540 as the Wives of Henry VIII, fourth wife of King Henry VIII. Not much is known about Anne before 1 ...
, and his two daughters:
Mary I Mary I (18 February 1516 – 17 November 1558), also known as Mary Tudor, and as "Bloody Mary" by her Protestant opponents, was List of English monarchs, Queen of England and List of Irish monarchs, Ireland from July 1553 and Queen of Sp ...
in 1527 and
Elizabeth I Elizabeth I (7 September 153324 March 1603) was List of English monarchs, Queen of England and List of Irish monarchs, Ireland from 17 November 1558 until her death in 1603. Elizabeth was the last of the five House of Tudor monarchs and is ...
in 1562. Elizabeth tried to disguise the pockmarks with heavy makeup.
Mary, Queen of Scots Mary, Queen of Scots (8 December 1542 – 8 February 1587), also known as Mary Stuart or Mary I of Scotland, was List of Scottish monarchs, Queen of Scotland from 14 December 1542 until her forced abdication in 1567. The only surviving legitima ...
, contracted the disease as a child but had no visible scarring. In Europe, deaths from smallpox often changed dynastic succession.
Louis XV of France Louis XV (15 February 1710 – 10 May 1774), known as Louis the Beloved (french: le Bien-Aimé), was King of France from 1 September 1715 until his death in 1774. He succeeded his great-grandfather Louis XIV at the age of five. Until he reached ...
succeeded his great-grandfather
Louis XIV Louis XIV (Louis Dieudonné; 5 September 16381 September 1715), also known as Louis the Great () or the Sun King (), was List of French monarchs, King of France from 14 May 1643 until his death in 1715. His reign of 72 years and 110 days is the Li ...
through a series of deaths of smallpox or measles among those higher in the succession line. He himself died of the disease in 1774.
Peter II of Russia Peter II Alexeyevich (russian: Пётр II, Пётр Алексеевич, ''Pyotr Vtoroy'', ''Pyotr Alekseyevich'', – ) reigned as Emperor of Russia from 1727 until his untimely death at the age of 14. He was the only son of Tsarevich Alexei ...
died of the disease at 14 years of age. Also, before becoming emperor,
Peter III of Russia Peter may refer to: People * List of people named Peter {{expand list, date=August 2020 Peter is a common name. Peter (given name), As a given name, it is generally derived from Peter the Apostle, born Simon, whom Jesus renamed "Peter" after he ...
caught the virus and suffered greatly from it. He was left scarred and disfigured. His wife,
Catherine the Great Catherine II (born Sophie of Anhalt-Zerbst; 2 May 172917 November 1796), most commonly known as Catherine the Great, was the reigning empress of Russia from 1762 to 1796. She came to power following the overthrow of her husband, Peter III of Rus ...
, was spared but fear of the virus clearly had its effects on her. She feared for the safety of her son,
Paul Paul may refer to: *Paul (given name) Paul () is a common masculine given name in countries and ethnicities with a Christian heritage (Eastern Orthodox Church, Eastern Orthodoxy, Catholic Church, Catholicism, Protestantism) and, beyond Europe, ...
, 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 British doctor, Thomas Dimsdale. While this was considered a controversial method at the time, she succeeded. Paul 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. In China, the
Qing dynasty The Qing dynasty ( ), officially the Great Qing,, was a Manchu people, Manchu-led Dynasties in Chinese history, imperial dynasty of China and the last orthodox dynasty in Chinese history. It emerged from the Later Jin (1616–1636), La ...
had extensive protocols to protect
Manchu The Manchus (; ) are a Tungusic East Asian ethnic group An ethnic group or an ethnicity is a grouping of people who identity (social science), identify with each other on the basis of shared attributes that distinguish them from other g ...
s from
Peking } Beijing ( ; ; ), Chinese postal romanization, alternatively romanized as Peking ( ), is the Capital city, capital of the China, People's Republic of China. It is the center of power and development of the country. Beijing is the world's Li ...
's endemic smallpox. U.S. Presidents
George Washington George Washington (February 22, 1732, 1799) was an American military officer, statesman, and Founding Fathers of the United States, Founding Father who served as the first president of the United States from 1789 to 1797. Appointed by the ...
,
Andrew Jackson Andrew Jackson (March 15, 1767 – June 8, 1845) was an American lawyer, planter, general, and statesman who served as the seventh president of the United States The president of the United States (POTUS) is the head of state and ...
, and
Abraham Lincoln Abraham Lincoln ( ; February 12, 1809 – April 15, 1865) was an American lawyer, politician, and statesman who served as the 16th president of the United States from 1861 until his assassination in 1865. Lincoln led the nation throu ...
all contracted and recovered from the disease. Washington became infected with smallpox on a visit to
Barbados Barbados is an island country in the Lesser Antilles of the West Indies, in the Caribbean region of the Americas, and the most easterly of the Caribbean Islands. It occupies an area of and has a population of about 287,000 (2019 estimate). ...
in 1751. Jackson developed the illness after being taken prisoner by the British during the American Revolution, and though he recovered, his brother Robert did not. Lincoln contracted the disease during his presidency, possibly from his son Tad, and was quarantined shortly after giving the Gettysburg address in 1863. Famous theologian Jonathan Edwards died of smallpox in 1758 following an inoculation.
Soviet The Soviet Union,. officially the Union of Soviet Socialist Republics. (USSR),. was a List of former transcontinental countries#Since 1700, transcontinental country that spanned much of Eurasia from 1922 to 1991. A flagship communist state, ...
leader
Joseph Stalin Joseph Vissarionovich Stalin (born Ioseb Besarionis dze Jughashvili; – 5 March 1953) was a Georgian revolutionary and Soviet The Soviet Union,. officially the Union of Soviet Socialist Republics. (USSR),. was a List of former ...
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. Hungarian poet Ferenc Kölcsey, who wrote the Hungarian national anthem, lost his right eye to smallpox.


Tradition and religion

In the face of the devastation of smallpox, various smallpox gods and goddesses have been worshipped throughout parts of the
Old World The "Old World" is a term for Afro-Eurasia that originated in Europe , after Europeans became aware of the existence of the Americas. It is used to contrast the continents of Africa, Europe, and Asia, which were previously thought of by thei ...
, for example in China and India. In China, the smallpox goddess was referred to as T'ou-Shen Niang-Niang (). 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 A euphemism () is an innocuous word or expression used in place of one that is deemed Profanity, offensive or suggests something unpleasant. Some euphemisms are intended to amuse, while others use bland, inoffensive terms for concepts that the us ...
intended to avert offending the goddess, for example (the Chinese word for smallpox is , literally "heaven flower"). 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. 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. If the victim recovered, the shrines were removed and carried away in a special paper chair or boat for burning. If the patient did not recover, the shrine was destroyed and cursed, to expel the goddess from the house. In the
Yoruba language Yoruba (, ; Yor. '; Ajami script, Ajami: ) is a language spoken in West Africa, primarily in South West (Nigeria), Southwestern Middle Belt, and Central Nigeria. It is spoken by the Ethnic group, ethnic Yoruba people. The number of Yoruba speake ...
smallpox is known as ṣọpọná, but it was also written as shakpanna, shopona, ṣhapana, and ṣọpọnọ. 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. Roughly translated, it means One who kills a person by covering them with pustules. 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). One of the most feared deities of the
orisha Orishas (singular: orisha) are spirits that play a key role in the Yoruba religion of West Africa and several African diaspora religions, religions of the African diaspora that derive from it, such as Cuban, Dominican and Puerto Rican Santería a ...
pantheon, smallpox was seen as a form of punishment from Shopona. Worship of Shopona was highly controlled by his priests, and it was believed that priests could also spread smallpox when angered. 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. The British government banned the worship of the god because it was believed his priests were purposely spreading smallpox to their opponents. India's first records of smallpox can be found in a medical book that dates back to 400 CE. This book describes a disease that sounds exceptionally like smallpox. India, like China and the Yorùbá, 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 affected. 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 patients. Shrines were created where many Indian 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. 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. 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 invention of the so-called red treatment, where patients 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 Charles V (21 January 1338 – 16 September 1380), called the Wise (french: le Sage; la, Sapiens), was King of France France France (), officially the French Republic ( ), is a country primarily located in Western Europe. I ...
and
Elizabeth I of England Elizabeth I (7 September 153324 March 1603) was List of English monarchs, Queen of England and List of Irish monarchs, Ireland from 17 November 1558 until her death in 1603. Elizabeth was the last of the five House of Tudor monarchs and is ...
. Afforded scientific credibility through the studies by
Niels Ryberg Finsen Niels Ryberg Finsen (15 December 1860 – 24 September 1904) was a Faroese people, Faroese-Icelanders, Icelandic physician and scientist. In 1903, he was awarded the Nobel Prize in Physiology or Medicine, Nobel Prize in Medicine and Physiology "i ...
showing that red light reduced scarring, this belief persisted even until the 1930s.


See also

* List of epidemics * Population history of indigenous peoples of the Americas#Depopulation from disease


References


Further reading

* * Henderson, Donald Ainslie. ''Smallpox: the death of a disease: the inside story of eradicating a worldwide killer''. Prometheus Books, 2009. * * * *


External links


Smallpox Biosafety: A Website About Destruction of Smallpox Virus Stocks




Center for Biosecurity


Virus Pathogen Database and Analysis Resource (ViPR): Poxviridae

Episode 1 (of 4): Vaccines
of the
BBC Four BBC Four is a British free-to-air Public service broadcasting in the United Kingdom, public broadcast television channel owned and operated by the BBC. It was launched on 2 March 2002
and PBS show
Extra Life: A Short History of Living Longer
(2021) {{Authority control Chordopoxvirinae Eradicated diseases Virus-related cutaneous conditions Wikipedia medicine articles ready to translate