Smallpox Classification and external resources
A child infected with smallpox
ICD-10	B03.
ICD-9	050
DiseasesDB	12219
MedlinePlus	001356
eMedicine	emerg/885
MeSH	D012899

Smallpox is an infectious disease unique to humans, caused by either of two virus variants named Variola major and Variola minor. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings A00-A79 - Bacterial infections and other intestinal infectious diseases and STDs (A00-A09 Intestinal Infectious diseases ( The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Virus classification involves naming and placing Viruses into a taxonomic system A DNA virus is a Virus that has DNA as its Genetic material and replicates using a DNA-dependent DNA polymerase. Poxviruses (members of the family Poxviridae) are viruses that can as a family infect both Vertebrate and Invertebrate animals Orthopoxvirus is a Genus of poxviruses that includes many Species isolated from Mammals such as Buffalopox virus An infectious disease is a clinically evident Disease resulting from the presence of Pathogenic microbial agents including Pathogenic viruses Pathogenic A virus (from the Latin virus meaning Toxin or Poison) is a sub-microscopic infectious agent that is unable ^[1] The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning spotted, or varus, meaning "pimple". Latin ( lingua Latīna, laˈtiːna is an Italic language, historically spoken in Latium and Ancient Rome. The term "smallpox" was first used in Europe in the 15th century to distinguish variola from the great pox (syphilis). Syphilis is a Sexually transmitted disease caused by the spirochetal Bacterium Treponema pallidum pallidum. ^[2]

Smallpox localizes in small blood vessels of the skin and in the mouth and throat. The blood vessels are part of the Circulatory system and function to transport Blood throughout the body In the skin, this results in a characteristic maculopapular rash, and later, raised fluid-filled blisters. A blister is a small pocket of fluid within the upper layers of the skin V. major produces a more serious disease and has an overall mortality rate of 30–35%. V. minor causes a milder form of disease (also known as alastrim, cottonpox, milkpox, whitepox, and Cuban itch) which kills ~1% of its victims. ^[3][4] Long-term complications of V. major infection include characteristic scars, commonly on the face, which occurred in 65–85% of survivors. ^[5] Blindness resulting from corneal ulceration and scarring, and limb deformities due to arthritis and osteomyelitis are less common complications, seen in about 2–5% of cases. Blindness is the condition of lacking Visual perception due to Physiological or Neurological factors See Corneal ulcers in animals for information about the condition in animals Osteomyelitis is an Infection of Bone or Bone marrow, usually caused by Pyogenic Bacteria or Mycobacteria.

Smallpox is believed to have emerged in human populations about 10,000 BC. ^[2] The disease killed an estimated 400,000 Europeans each year during the 18th century (including five reigning monarchs), and was responsible for a third of all blindness. The 18th century lasted from 1701 to 1800 in the Gregorian calendar, in accordance with the Anno Domini / Common Era numbering system ^[3] Between 20 and 60% of all those infected—and over 80% of infected children—died from the disease. ^[6]

During the 20th century, it is estimated that smallpox was responsible for 300–500 million deaths. The twentieth century of the Common Era began on ^[7][8] As recently as 1967, the World Health Organization (WHO) estimated that 15 million people contracted the disease and that two million died in that year. ^[9] After successful vaccination campaigns throughout the 19th and 20th centuries, the WHO certified the eradication of smallpox in 1979. Vaccination is the administration of Antigenic material (the Vaccine) to produce immunity to a disease The 19th century of the Common Era began on January 1, 1801 and ended on December 31, 1900, according to the Gregorian calendar ^[9] To this day, smallpox is the only human infectious disease to have been completely eradicated from nature. ^[10]

Cause

Electron micrograph of smallpox.

Smallpox is caused by infection with variola virus, which belongs to the genus Orthopoxvirus, the family Poxviridae, and subfamily chordopoxvirinae. Orthopoxvirus is a Genus of poxviruses that includes many Species isolated from Mammals such as Buffalopox virus Poxviruses (members of the family Poxviridae) are viruses that can as a family infect both Vertebrate and Invertebrate animals It affects mostly babies and young children. Variola virus is a large brick-shaped virus measuring approximately 302 to 350 nanometers by 244 to 270 nm,^[11] with a single linear double stranded DNA genome consisting of 186 kilobase pairs (kbp) and containing a hairpin loop at each end. A nanometre ( American spelling: nanometer, symbol nm) ( Greek: νάνος nanos dwarf; μετρώ metrό count) is a Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known In classical genetics the genome of a Diploid Organism including Eukarya refers to a full set of chromosomes or genes in a Gamete, thereby In Molecular biology, two Nucleotides on opposite complementary DNA or RNA strands that are connected via Hydrogen bonds are called Stem-loop intramolecular Base pairing is a pattern that can occur in single-stranded DNA or more commonly in RNA. ^[12] The two classic varieties of smallpox are variola major and variola minor. The closest viral relative is molluscum contagiosum, which like smallpox, infects only humans. Molluscum contagiosum ( MC) is a viral infection of the Skin or occasionally of the Mucous membranes. However, unlike variola species, molluscum infection is benign. The lifecycle of poxviruses is complicated by having multiple infectious forms, with differing mechanisms of cell entry. Poxviruses are unique among DNA viruses in that they replicate in the cytoplasm of the cell rather than in the nucleus. The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane. In order to replicate poxviruses produce a variety of specialized proteins not produced by other DNA viruses, the most important of which is a viral-associated DNA-dependent RNA polymerase. A DNA virus is a Virus that has DNA as its Genetic material and replicates using a DNA-dependent DNA polymerase. RNA polymerase ( RNAP or RNApol) is an Enzyme that produces RNA. Both enveloped and nonenveloped virions are infectious. Many Viruses (eg influenza and many animal viruses have viral envelopes covering their protein Capsids The envelopes are typically derived from portions of The viral envelop is made of modified Golgi membranes containing viral-specific polypeptides, including hemagglutinin. Hemagglutinin (HA or haemagglutinin ( British English) is an Antigenic Glycoprotein found on the surface of the Influenza Viruses ^[12] Infection with either variola major and variola minor confers immunity against the other. ^[4]

Four orthopoxviruses cause infection in humans: variola, vaccinia, cowpox, and monkeypox. Vaccinia virus ( VACV or VV) is a large complex enveloped Virus belonging to the Poxvirus family Cowpox is a Disease of the skin that is caused by a Virus known as the Cowpox virus. Monkeypox is a rare Infectious disease caused by Monkeypox virus. Variola virus infects only humans in nature, although primates and other animals have been infected in a laboratory setting. Vaccinia, cowpox, and monkeypox viruses can infect both humans and other animals in nature. ^[13]

Transmission

Transmission of smallpox occurs through inhalation of airborne variola virus, usually droplets expressed from the oral, nasal, or pharyngeal mucosa of an infected person. The pharynx (plural pharynges) is the part of the Neck and Throat situated immediately Posterior to (behind the Mouth and Nasal The mucous membranes (or mucosae; singular mucosa) are linings of mostly endodermal origin covered in Epithelium, which are involved in It is transmitted from one person to another primarily through prolonged face-to-face contact with an infected person, usually within a distance of 6 feet, but can also be spread through direct contact with infected bodily fluids or contaminated objects (fomites) such as bedding or clothing. A fomite is any inanimate object or Substance capable of carrying Infectious organisms (such as Germs or Parasites and hence transferring Rarely, smallpox has been spread by virus carried in the air in enclosed settings such as buildings, buses, and trains. ^[14] The virus can cross the placenta, but the incidence of congenital smallpox is relatively low. The placenta is an Ephemeral organ present in placental Vertebrates, such as Eutherial Mammals and Sharks during Gestation A congenital disorder is a disease or disorder that is present at birth ^[4] Smallpox is not notably infectious in the prodromal period and viral shedding is usually delayed until the appearance of the rash, which is often accompanied by lesions in the mouth and pharynx. In Medicine, a prodrome is an early non-specific Symptom (or set of symptoms indicating the start of a Disease before specific symptoms occur A lesion is any abnormal tissue found on or in an organism usually damaged by disease or trauma The virus can be transmitted throughout the course of the illness, but is most frequent during the first week of the rash, when most of the skin lesions are intact. ^[13] Infectivity wanes in 7 to 10 days when scabs form over the lesions, but the infected person is contagious until the last smallpox scab falls off. ^[15] Smallpox is highly contagious, but generally spreads more slowly and less widely than some other viral diseases, perhaps because transmission requires close contact and occurs after the onset of the rash. The overall rate of infection is also affected by the short duration of the infectious stage. In temperate areas, the number of smallpox infections were highest during the winter and spring. In tropical areas, seasonal variation was less evident and the disease was present throughout the year. ^[13] Age distribution of smallpox infections depends on acquired immunity. Immune system|Passive immunity|Innate immune system The adaptive immune system is composed of highly specialized systemic cells and processes that eliminate or prevent Pathogenic Vaccination immunity declines over time and is probably lost in all but the most recently vaccinated populations. Vaccination is the administration of Antigenic material (the Vaccine) to produce immunity to a disease Immunity is a material term that describes a state of having sufficient biological defenses to avoid Infection, Disease, or other unwanted biological invasion ^[4] Smallpox is not known to be transmitted by insects or animals and there is no asymptomatic carrier state. An asymptomatic carrier ( healthy carrier or just carrier) is a person or other organism that has contracted an Infectious disease, but who displays no symptoms ^[13]

Signs and symptoms

There are two clinical forms of smallpox. Variola major is the severe and most common form of smallpox, with a more extensive rash and higher fever. There are four types of variola major smallpox based on the Rao classification:^[16] ordinary, modified, flat, and hemorrhagic. Historically, variola major has an overall fatality rate of about 30%; however, flat and hemorrhagic smallpox are usually fatal. ^[17] In addition, a form called variola sine eruptione (smallpox without rash) is seen generally in vaccinated persons. This form is marked by a fever that occurs after the usual incubation period and can be confirmed only by antibody studies or, rarely, by virus isolation. ^[13]

Variola minor is a less common presentation of smallpox, and a much less severe disease, with historical death rates of 1% or less. ^[14] Subclinical (asymptomatic) infections with variola virus have also been noted, but are not believed to be common. ^[13]

The incubation period between contraction and the first obvious symptoms of the disease is around 12 days. Incubation period is the Time elapsed between exposure to a Pathogenic Organism, or Chemical or radiation, and when Symptoms Once inhaled, variola virus invades the oropharyngeal (mouth and throat) or the respiratory mucosa, migrates to regional lymph nodes, and begins to multiply. In living organisms a respiratory system functions to allow Gas exchange. A Lymph node ( lɪmf noʊd is an organ consisting of many types of cells and is a part of the Lymphatic system. In the initial growth phase the virus seems to move from cell to cell, but around the 12th day, lysis of many infected cells occurs and the virus is found in the bloodstream in large numbers (this is called viremia), and a second wave of multiplication occurs in the spleen, bone marrow, and lymph nodes. Lysis ( Greek, lysis from lyein = to separate refers to the death of a cell by breaking of the cellular membrane often by viral or osmotic Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells ��such as nutrients and oxygen—and transports Waste products Viremia (UK viraemia) is a medical condition where Viruses enter the Bloodstream and hence have access to the rest of the body The initial or prodromal symptoms are similar to other viral diseases such as influenza and the common cold: fever (at least 38. Acute viral nasopharyngitis or acute coryza, usually known as the common cold, is a highly contagious viral Infectious disease of the Fever (also known as pyrexia, from the Greek pyretos meaning fire or a febrile response, from the Latin word Febris 5 °C (101 °F)), muscle pain, malaise, headache, prostration, and as the digestive tract is commonly involved, nausea and vomiting and backache often occur. Muscle (from Latin musculus, diminutive of mus "mouse" is contractile tissue of the body and is derived from the Prostration is the placement of the body in a Reverentially or Submissively Prone position The prodrome, or preeruptive stage, usually lasts 2–4 days. By days 12–15 the first visible lesions—small reddish spots called enanthem—appear on mucous membranes of the mouth, tongue, palate, and throat, and temperature falls to near normal. The palate (ˈpælɨt is the roof of the Mouth in humans and Vertebrate animals These lesions rapidly enlarge and rupture, releasing large amounts of virus into the saliva. For the band see Saliva (band; for the village in Azerbaijan see Səliva. ^[4]

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

Smallpox virus preferentially attacks skin cells, causing the characteristic pimples (called macules) associated with the disease. The macule is the simplest dermatological Lesion. It is flat and can only be seen and not felt A rash develops on the skin 24 to 48 hours after lesions on the mucous membranes appear. Typically the macules first appear on the forehead, then rapidly spread to the whole face, proximal portions of extremities, the trunk, and lastly to distal portions of extremities. The process takes no more than 24 to 36 hours, after which no new lesions appear. ^[4] At this point Variola major infection can take several very different courses.

Ordinary

Ninety percent or more of smallpox cases among unvaccinated persons are of the ordinary type. ^[13] In this form of the disease, by the second day of the rash, the macules become raised papules. By the third or fourth day the papules fill with an opalescent fluid to become vesicles. This fluid becomes opaque and turbid within 24–48 hours, giving them the appearance of pustules; however, the so-called pustules are filled with tissue debris, not pus. Opacity is the measure of impenetrability to electromagnetic or other kinds of radiation especially visible Light. Turbidity is the cloudiness or haziness of a fluid caused by individual particles ( suspended solids) that are generally invisible to the Naked eye A pustule is a small collection of Pus in the top layer of Skin ( epidermis) or beneath it in the Dermis. ^[4]

By the sixth or seventh day, all the skin lesions have become pustules. Between 7 and 10 days the pustules mature and reach their maximum size. The pustules are sharply raised, typically round, tense, and firm to the touch. The pustules are deeply embedded in the dermis, giving them the feel of a small bead in the skin. Fluid slowly leaks from the pustules, and by the end of the second week the pustules deflate, and start to dry up, forming crusts (or scabs). By day 16-20 scabs have formed over all the lesions, which have started to flake off, leaving de-pigmented scars. For the drug referred to as "pigment" see Black tar heroin. ^[18]

Ordinary smallpox generally produces a discrete rash, in which the pustules stand out on the skin separately. The distribution of the rash is densest on the face; more dense on the extremities than on the trunk; and on the extremities, more dense on the distal parts than on the proximal. The palms of the hands and soles of the feet are involved in the majority of cases. In some cases, the blisters merge together into sheets, forming a confluent rash, which begin to detach the outer layers of skin from the underlying flesh. Patients with confluent smallpox often remain ill even after scabs have formed over all the lesions. In one case series, the case-fatality rate in confluent smallpox was 62%. ^[13]

Modified

Referring to the character of the eruption and the rapidity of its development, modified smallpox occurs mostly in previously vaccinated people. In this form the prodromal illness still occurs but may be less severe than in the ordinary type. There is usually no fever during evolution of the rash. The skin lesions tend to be fewer and evolve more quickly, are more superficial, and may not show the uniform characteristic of more typical smallpox. ^[18] Modified smallpox is rarely, if ever, fatal. This form of variola major is more easily confused with chickenpox. ^[13]

This man is suffering from severe hemorrhagic-type smallpox

Flat

In Flat-type smallpox (also called malignant smallpox) the lesions remain almost flush with the skin at the time when raised vesicles form in ordinary-type smallpox. It is unknown why some people develop this type of disease. Historically, flat-type smallpox accounted for 5%–10% of cases, and the majority (72%) were in children. ^[19] Flat smallpox is accompanied by a severe prodromal phase that lasts 3–4 days, prolonged high fever, and severe symptoms of toxemia. In Medicine, a prodrome is an early non-specific Symptom (or set of symptoms indicating the start of a Disease before specific symptoms occur The rash on the tongue and palate is usually extensive. The skin lesions mature very slowly and by the seventh or eighth day the lesions are flat and appear to be buried in the skin. Unlike ordinary-type smallpox, the vesicles contain very little fluid, are soft and velvety to the touch, and may contain hemorrhages. Flat-type smallpox is nearly always fatal. ^[13]

Hemorrhagic

Hemorrhagic smallpox is a severe form of smallpox that is accompanied by extensive bleeding into the skin, mucous membranes, and gastrointestinal tract. This form developed in perhaps 2% of infections and occurred mostly in adults. In hemorrhagic smallpox the skin does not blister, but remains smooth. Instead, bleeding occurs under the skin, making the skin look charred and black (this is known as black pox). Black pox is a Symptom of Smallpox that is caused by Bleeding under the Skin which makes the skin look Charred or black

In the early, or fulminating, form, hemorrhaging appears on the second or third day as sub-conjunctival bleeding turns the whites of the eyes deep red. The conjunctiva is a clear membrane that covers the Sclera (white part of the Eye) and lines the inside of the Eyelids It is made of lymphoid tissue Hemorrhagic smallpox also produces a dusky erythema, petechiae, and hemorrhages in the spleen, kidney, serosa, muscle, and, rarely, the epicardium, liver, testes, and bladder. Erythema is redness of the Skin caused by Capillary congestion A petechia (pɨˈtiːkiə plural petechiae (pɨˈtiːkɪiː is a small (1-2mm red or purple spot on the body caused by a minor Hemorrhage (broken Capillary In Anatomy, a serous membrane (or serosa) is a smooth membrane consisting of a thin layer of cells which excrete Serous fluid Epicardium describes the outer layer of Heart tissue (from Greek; epi- outer cardium heart The liver is a vital organ in the human body and is present in Vertebrates and some other animals The testicle (from Latin testiculus, diminutive of testis, meaning "witness" virility plural testes) is the male In Anatomy, the urinary bladder is a hollow muscular, and distensible (or elastic organ that sits on the Pelvic floor in Mammals It is the Death often occurs suddenly between the fifth and seventh days of illness, when only a few insignificant skin lesions are present. A later form of the disease occurs in patients who survive for 8–10 days. The hemorrhages appear in the early eruptive period, and the rash is flat and does not progress beyond the vesicular stage. ^[13] Patients in the early stage of disease show a decrease in platelets, prothrombin, and globulin, and an increase in circulating antithrombin. Platelets, or Thrombocytes, are small cytoplasmic bodies derived from cells They circulate in the Blood of Mammals and are involved Thrombin (activated Factor II ') is a Coagulation protein that has many effects in the coagulation cascade. Globulin is one of the two types of serum Proteins the other being albumin. Antithrombin (AT is a small protein molecule that inactivates several enzymes of the Coagulation system Patients in the late stage have significant thrombocytopenia; however, deficiency of coagulation factors is less severe. Thrombocytopenia (or -paenia, or thrombopenia in short is the presence of relatively few Platelets in Blood. Some in the late stage also show increased antithrombin. ^[4] This form of smallpox occurs in anywhere from 3–25% of fatal cases (depending on the virulence of the smallpox strain). ^[17]

Diagnosis

Smallpox virus pocks on the chorioallantoic membrane of a developing chick.

The clinical definition of smallpox is an illness with acute onset of fever greater than 101°F (38. 3°C) followed by a rash characterized by firm, deep seated vesicles or pustules in the same stage of development without other apparent cause.

Microscopically, one see's Guarnieri bodies, which are aggregates of the virus. Guarnieri bodies ( /gwaɹˈɲjeːˌɹi/ are found upon Microscopic Inspection of Epithelial cells of individuals suspected of having Guarnieri bodies appear as pink blobs. The absence of Guarnieri bodies cannot be used to rule out smallpox, however.

If a clinical case is observed, smallpox is confirmed using laboratory tests. The diagnosis of an orthopoxvirus infection can be made rapidly by electron microscopic examination of pustular fluid or scabs. However, all orthopoxviruses exhibit identical brick-shaped virions by electron microscopy. ^[4] Definitive laboratory identification of variola virus involves growing the virus on chorioallantoic membrane (part of a chicken embryo) and examining the resulting pock lesions under defined temperature conditions. An embryo (from Greek:, plural, lit "that which grows" from en- "in" + bryein "to swell be full" is a multicellular ^[20] Strains may be characterized by polymerase chain reaction (PCR) or restriction fragment length polymorphism (RFLP) analysis. A Restriction fragment length polymorphism (or RFLP, often pronounced as "rif-lip" is a variation in the DNA sequence of a Genome Serologic tests and enzyme linked immunosorbent assays (ELISA), which measure variola virus-specific immunoglobulin and antigen have also been developed to assist in the diagnosis of infection. Serology is the scientific study of blood serum. In practice the term usually refers to the Diagnostic identification of antibodies in the serum Enzyme-Linked ImmunoSorbent Assay, also called ELISA, Enzyme ImmunoAssay or EIA, is a biochemical technique used mainly in Immunology ^[21]

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

Prognosis

The overall case-fatality rate for ordinary-type smallpox is about 30%, but varies by pock distribution: ordinary type-confluent is fatal about 50–75% of the time, ordinary-type semi-confluent about 25–50% of the time, in cases where the rash is discrete the case-fatality rate is less than 10%. The overall fatality rate for children younger than 1 year of age is 40%–50%. Hemorrhagic and flat types have the highest fatality rates. The fatality rate for flat-type is 90% or greater and nearly 100% is observed in cases of hemorrhagic smallpox. The case-fatality rate for variola minor is 1% or less. ^[18] There is no evidence of chronic or recurrent infection with variola virus.

In fatal cases of ordinary smallpox, death usually occurs between the tenth and sixteenth days of the illness. The cause of death from smallpox is not clear, but the infection is now known to involve multiple organs. Circulating immune complexes, overwhelming viremia, or an uncontrolled immune response may be contributing factors. An immune complex is the combination of an Epitope with an Antibody directed against that epitope Viremia (UK viraemia) is a medical condition where Viruses enter the Bloodstream and hence have access to the rest of the body An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor ^[13] In early hemorrhagic smallpox, death occurs suddenly about six days after the fever develops. Cause of death in hemorrhagic cases involved heart failure, sometimes accompanied by pulmonary edema. Heart failure is a Cardiac condition that occurs when a problem with the structure or function of the Heart impairs its ability to supply Pulmonary Edema (American English or oedema (British English is swelling and/or fluid accumulation in the Lungs It leads to impaired gas exchange and may cause In late hemorrhagic cases, high and sustained viremia, severe platelet loss and poor immune response were often cited as causes of death. Platelets, or Thrombocytes, are small cytoplasmic bodies derived from cells They circulate in the Blood of Mammals and are involved ^[19] In flat smallpox modes of death are similar to those in burns, with loss of fluid, protein and electrolytes beyond the capacity of the body to replace or acquire, and fulminating sepsis. An electrolyte is any substance containing free Ions that behaves as an electrically conductive medium Sepsis is a serious medical condition characterized by a whole-body inflammatory state (called a Systemic inflammatory response syndrome or SIRS caused

Complications

Complications of smallpox arise most commonly in the respiratory system and range from simple bronchitis to fatal pneumonia. In living organisms a respiratory system functions to allow Gas exchange. Bronchitis is an Inflammation of the Bronchi. More specifically it may refer to Acute bronchitis, caused by viruses or bacteria and lasting Pneumonia is an inflammatory illness of the Lung. Frequently it is described as lung Parenchyma / alveolar inflammation and abnormal 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. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have When this occurs, the fever usually remains elevated. ^[13]

Other complications include encephalitis (1 in 500 patients), which is more common in adults and may cause temporary disability; permanent pitted scars, most notably on the face; and complications involving the eyes (2% of all cases). Encephalitis is an acute Inflammation of the Brain, commonly caused by a viral Infection. Pustules can form on the eyelid, conjunctiva, and cornea, leading to complications such as conjunctivitis, keratitis, corneal ulcer, iritis, iridocyclitis, and optic atrophy. The conjunctiva is a clear membrane that covers the Sclera (white part of the Eye) and lines the inside of the Eyelids It is made of lymphoid tissue The cornea is the transparent front part of the Eye that covers the iris, Pupil, and Anterior chamber. Conjunctivitis (commonly called " Pink Eye " or " Red Eye " in North America and " Madras eye " in India) is an inflammation Keratitis is a condition in which the Eye 's Cornea, the front part of the eye becomes inflamed See Corneal ulcers in animals for information about the condition in animals Iritis is a form of anterior Uveitis and refers to the Inflammation of the iris of the Eye. Iridocyclitis, a type of anterior Uveitis, is a condition in which the Uvea of the eye suffers Inflammation. Atrophy is the partial or complete Wasting away of a part of the Body. Blindness results in approximately 35% to 40% of eyes affected with keratitis and corneal ulcer. Blindness is the condition of lacking Visual perception due to Physiological or Neurological factors Hemorrhagic smallpox can cause subconjunctival and retinal hemorrhages. The vertebrate retina is a light sensitive part inside the inner layer of the Eye. In 2% to 5% of young children with smallpox, virions reach the joints and bone, causing osteomyelitis variolosa. Osteomyelitis is an Infection of Bone or Bone marrow, usually caused by Pyogenic Bacteria or Mycobacteria. Lesions are symmetrical, most common in the elbows, tibia, and fibula, and characteristically cause separation of an epiphysis and marked periosteal reactions. The tibia, shinbone, or shankbone is the larger and stronger of the two Bones in the Leg below the Knee in vertebrates and connects For other uses see Fibula (disambiguation The fibula or calf bone is a Bone located on the lateral side of the Tibia Epiphysis is the name for a rounded end of a long Bone. The epiphysis is filled with red Bone marrow, which produces Erythrocytes, or red blood cells Periosteum is a Membrane that lines the outer surface of all bones, except at the joints of Long bones. Swollen joints limit movement, and arthritis may lead to limb deformities, ankylosis, malformed bones, flail joints, and stubby fingers. Arthritis (from Greek arthro-, joint + -itis, inflammation plural arthritides is a group of conditions involving damage to the Joints of the body Ankylosis, or Anchylosis (from Greek αγκυλος bent crooked is a stiffness of a Joint, the result of Injury or Disease. ^[4]

Treatment

Smallpox vaccination within three days of exposure will prevent or significantly lessen the severity of smallpox symptoms in the vast majority of people. Vaccination four to seven days after exposure likely offers some protection from disease or may modify the severity of disease. ^[22] Other than vaccination, treatment of smallpox is primarily supportive, such as wound care and infection control, fluid therapy, and possible ventilator assistance. Flat and hemorrhagic types of smallpox are treated with the same therapies used to treat shock, such as fluid resuscitation. Patients with semi-confluent and confluent types of may have therapeutic issues similar to patients with extensive skin burns. A burn is a type of Injury that may be caused by Heat, cold, Electricity, Chemicals, Light, Radiation, or

No drug is currently approved for the treatment of smallpox. However, antiviral treatments have improved since the last large smallpox epidemics, and studies suggest that the antiviral drug cidofovir might be useful as a therapeutic agent. Antiviral drugs are a class of Medication used specifically for treating viral Infections Like Antibiotics for Bacteria, specific antivirals Cidofovir is an injectable Antiviral medication for the treatment of Cytomegalovirus (CMV Retinitis in patients with AIDS. The drug must be administered intravenously, however, and may cause serious renal toxicity. Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein. The kidneys are complicated organs that have numerous biological roles ^[23]

Prevention

Main articles: Inoculation and Smallpox vaccine

Smallpox inoculation sign, 1801

The first attempts to prevent smallpox were practiced in India as early as 1000 BC,^[24] and involved either nasal insufflation of powdered smallpox scabs, or scratching material from a smallpox lesion into the skin. Inoculation is the placement of something to where it will grow or reproduce and is most commonly used in respect of the introduction of a serum Vaccine, or antigenic substance The smallpox vaccine was the first successful vaccine ever to be developed India, officially the Republic of India (भारत गणराज्य inc-Latn Bhārat Gaṇarājya; see also other Indian languages) is a country This procedure was known as variolation and, if successful, produced lasting immunity to smallpox. Inoculation is the placement of something to where it will grow or reproduce and is most commonly used in respect of the introduction of a serum Vaccine, or antigenic substance Immunity is a material term that describes a state of having sufficient biological defenses to avoid Infection, Disease, or other unwanted biological invasion However, because the person was infected with variola virus, a severe infection could result, and the person could transmit smallpox to others. Variolation had a 0. 5–2% mortality rate; considerably less than the 20–30% mortality rate of the disease itself.

An account from letter by Lady Mary Wortley Montagu to Sarah Chiswell, dated 1 April 1717, from the Turkish Embassy describes this treatment:

. The Lady Mary Wortley Montagu ( 26 May 1689 &ndash 21 August 1762) was an English aristocrat and writer . . . The small-pox so fatal and so general amongst us is here entirely harmless by the invention of ingrafting (which is the term they give it). There is a set of old women who make it their business to perform the operation. Every autumn in the month of September, when the great heat is abated, people send to one another to know if any of their family has a mind to have the small-pox. They make parties for this purpose, and when they are met (commonly fifteen or sixteen together) the old woman comes with a nutshell full of the matter of the best sort of small-pox and asks what veins you please to have opened. She immediately rips open that you offer to her with a large needle (which gives you no more pain than a common scratch) and puts into the vein as much venom as can lye upon the head of her needle, and after binds up the little wound with a hollow bit of shell, and in this manner opens four or five veins. . . . The children or young patients play together all the rest of the day and are in perfect health till the eighth. Then the fever begins to seize them and they keep their beds two days, very seldom three. They have very rarely above twenty or thirty in their faces, which never mark, and in eight days time they are as well as before the illness. . . . There is no example of any one that has died in it, and you may believe I am very well satisfied of the safety of the experiment since I intend to try it on my dear little son. I am patriot enough to take pains to bring this useful invention into fashion in England, and I should not fail to write to some of our doctors very particularly about it if I knew any one of them that I thought had virtue enough to destroy such a considerable branch of their revenue for the good of mankind, but that distemper is too beneficial to them not to expose to all their resentment the hardy wight that should undertake to put an end to it. Perhaps if I live to return I may, however, have courage to war with them. . . . [2]

In March 1718 she had the embassy surgeon, Charles Maitland, inoculate her five-year-old son. Upon her return to England in 1721, Lady Montegu had her four-year-old daughter inoculated and invited friends to see the child, including Sir Hans Sloane, the King's physician. Despite a great deal of initial prejudice from physicians and the public, this method of controlled infection was used in England, parts of Europe, and the British colonies in the New World during most of the 18th century.

In 1796 Edward Jenner, a doctor in Berkeley, Gloucestershire, rural England, discovered that immunity to smallpox could be produced by inoculating a person with material from a cowpox lesion. Edward Jenner, FRS, ( May 17 1749 – January 26 1823) was an English scientist who studied his natural surroundings in Berkeley Berkeley (ˈbɑːkli is a town between the south bank of the River Severn and the M5 motorway within the Stroud district of Gloucestershire History See also History of Gloucestershire Gloucestershire is a historic county mentioned in the Anglo-Saxon Chronicle in the 10th century England is a Country which is part of the United Kingdom. Its inhabitants account for more than 83% of the total UK population whilst its mainland Cowpox is a Disease of the skin that is caused by a Virus known as the Cowpox virus. Cowpox is a poxvirus in the same family as variola. Jenner called the material used for inoculation vaccine, from the root word vacca, which is Latin for cow. A vaccine is a biological preparation which is used to establish or improve immunity to a particular disease Latin ( lingua Latīna, laˈtiːna is an Italic language, historically spoken in Latium and Ancient Rome. The procedure was much safer than variolation, and did not involve a risk of smallpox transmission. Vaccination to prevent smallpox was soon practiced all over the world. During the 19th century, the cowpox virus used for smallpox vaccination was replaced by vaccinia virus. Vaccinia virus ( VACV or VV) is a large complex enveloped Virus belonging to the Poxvirus family Vaccinia is in the same family as cowpox and variola but is genetically distinct from both. The origin of vaccinia virus and how it came to be in the vaccine are not known. ^[13]

Vaccination during the Smallpox Eradication and Measles Control Program in Niger, February, 1969. Niger ( or /ˈnaɪdʒɚ/) officially the Republic of Niger, is a Landlocked country in Western Africa, named after the Niger River.

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

The antibodies induced by vaccinia vaccine are cross-protective for other orthopoxviruses (such as monkeypox, cowpox, and variola (smallpox) viruses). Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily Neutralizing antibodies are detectable 10 days after first-time vaccination, and seven days after revaccination. Historically, the vaccine has been effective in preventing smallpox infection in 95% of those vaccinated. ^[22] Smallpox vaccination provides a high level of immunity for three to five years and decreasing immunity thereafter. If a person is vaccinated again later, immunity lasts even longer. Studies of smallpox cases in Europe in the 1950s and 1960s demonstrated that the fatality rate among persons vaccinated less than 10 years before exposure was 1. 3%; it was 7% among those vaccinated 11 to 20 years prior, and 11% among those vaccinated 20 or more years prior to infection. By contrast, 52% of unvaccinated persons died. ^[25]

There are side effects and risks associated with the smallpox vaccine. In the past, about 1,000 people for every 1 million people vaccinated for the first time experienced serious, but non-life-threatening, reactions including toxic or allergic reaction at the site of the vaccination (erythema multiforme), spread of the vaccinia virus to other parts of the body, and to other individuals. Allergy is a disorder of the Immune system often also referred to as Atopy. Erythema multiforme is a skin condition of unknown etiology possibly mediated by deposition of Immune complex ( mostly IgM) in the superficial microvasculature of the Potentially life-threatening reactions occurred in 14 to 52 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 who receive the vaccine may die as a result, most often the result of postvaccinial encephalitis or severe necrosis in the area of vaccination (called progressive vaccinia). Encephalitis is an acute Inflammation of the Brain, commonly caused by a viral Infection. Necrosis (in Greek Νεκρός = "dead" is the name given to unnatural Death of cells and living tissue. ^[22]

Routine childhood smallpox vaccination was discontinued in the United States in 1972. The United States of America —commonly referred to as the Routine vaccination of healthcare workers was discontinued in 1976, and among military recruits in 1990, though military members deploying to the Middle East have been known to receive it to this day. It is now primarily recommended for laboratory workers at risk for occupational exposure. ^[13] Mass smallpox vaccination was abandoned in most European countries in the early 1970s. ^[26]

Eradication

Since Jenner demonstrated the effectiveness of cowpox to protect humans from smallpox in 1796, various attempts were made to eliminate smallpox on a regional scale. As early as 1803, the Spanish Crown organized a mission (the Balmis expedition) to transport the vaccine to the Spanish colonies in the Americas and the Philippines, and establish mass vaccination programs there. Spain () or the Kingdom of Spain (Reino de España is a country located mostly in southwestern Europe on the Iberian Peninsula. Balmis Expedition was a three year mission to the Americas led by Dr Francisco Javier de Balmis with the aim of giving thousands the Smallpox vaccine. ^[27] In 1842, England banned inoculation, later progressing to mandatory vaccination. The UK Vaccination Acts of 1840 1853 and 1898 reflect the continuing argument over Vaccination policy in the United Kingdom. The British government introduced compulsory smallpox vaccination by an Act of Parliament in 1853. The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located ^[28] In the United States, from 1843 to 1855 first Massachusetts, and then other states required smallpox vaccination. Although some disliked these measures,^[29] coordinated efforts against smallpox went on, and the disease continued to diminish in the wealthy countries. By 1897, smallpox had largely been eliminated from the United States. ^[30] In Northern Europe a number of countries had eliminated smallpox by 1900, and by 1914, the incidence in most industrialized countries had decreased to comparatively low levels. Vaccination continued in industrialized countries, until the mid to late 1970s as protection against reintroduction. Australia and New Zealand are two notable exceptions, neither experienced endemic smallpox and never vaccinated widely; relying instead on protection by distance and strict quarantines. ^[31]

This 1980 photograph, taken at the CDC, shows three former directors of the Global Smallpox Eradication Program as they read the news that smallpox had been globally eradicated. The Centers for Disease Control and Prevention (or CDC) is an agency of the United States Department of Health and Human Services based in unincorporated

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 with over 100 years of experience working to improve health and living standards of the people ^[32] The campaign was successful in eliminating smallpox from all American countries except Argentina, Brazil, Colombia, and Ecuador. ^[31] In 1958 Professor Viktor Zhdanov, Deputy Minister of Health for the USSR, called on the World Health Assembly to undertake a global initiative to eradicate smallpox. The Union of Soviet Socialist Republics (USSR was a constitutionally Socialist state that existed in Eurasia from 1922 to 1991 Eradication is the reduction of an infectious disease's Prevalence in the global human population to zero The proposal (Resolution WHA11. 54) was accepted in 1959. ^[33] At this point, 2 million people were dying every year. Overall, however, progress towards eradication was disappointing, especially in Africa and in the Indian subcontinent. In 1967, the World Health Organization intensified the global smallpox eradication by contributuing $2. 4 million annually to the effort. An international team, the Smallpox Eradication unit, was formed under the leadership of an American, Donald Henderson. Donald Ainslie Henderson, known as DA Henderson, (born September 7, 1928) is an American Physician and Epidemiologist, whose work ^[34]

To eradicate smallpox, each outbreak had to be stopped from spreading, by isolation of cases and vaccination of everyone who lived close by. This process is known as "ring vaccination". The key to this strategy was monitoring of cases in a community (known as surveillance) and containment. The initial problem the WHO team faced was inadequate reporting of smallpox cases, as many cases did not come to the attention of the authorities. The fact that humans are the only reservoir for smallpox infection, and that carriers did not exist, played a significant role the eradication of smallpox. An asymptomatic carrier ( healthy carrier or just carrier) is a person or other organism that has contracted an Infectious disease, but who displays no symptoms The WHO established a network of consultants who assisted countries in setting up surveillance and containment activities. Early on donations of vaccine were provided primarily by the Soviet Union and the United States, but by 1973, more than 80% of all vaccine was produced in developing countries. ^[31]

The last major European outbreak of smallpox was in 1972 in Yugoslavia, after a pilgrim from Kosovo returned from the Middle East, where he had contracted the virus. The 1972 outbreak of smallpox in Yugoslavia was the last major outbreak of Smallpox in Europe. The Middle East is a Subcontinent with no clear boundaries often used as a synonym to Near East, in opposition to Far East. The epidemic infected 175 people, causing 35 deaths. Authorities declared martial law, enforced quarantine, and undertook massive re-vaccination of the population, enlisting the help of the WHO. Martial law is the system of rules that takes effect when the military takes control of the normal administration of justice In two months, the outbreak was over. Prior to this, there had been a smallpox outbreak in May–July of 1963 in Stockholm, Sweden, brought from the Far East by a Swedish sailor; this had been dealt with by quarantine measures and vaccination of local population. ('stɔkhɔlm is Sweden 's Capital and its largest City. It is the site of the national Swedish government, the parliament, and the "Sverige" redirects here For other uses see Sweden (disambiguation and Sverige (disambiguation. The Far East is a term often used by people in the Western world to refer to the countries of East Asia. ^[35]

By the end of 1975, smallpox persisted only in the Horn of Africa. The Horn of Africa (alternatively Northeast Africa, and sometimes Somali Peninsula; shortened to HOA) is a Peninsula in East Africa Conditions were very difficult in Ethiopia and Somalia, where there were few roads. Civil war, famine, and refugees made the task even more difficult. An intensive surveillance and containment and vaccination program was undertaken in the spring and summer of 1977. The last naturally occurring case of indigenous smallpox (Variola minor) was diagnosed in Ali Maow Maalin, a hospital cook in Merka, Somalia, on 26 October 1977. Ali Maow Maalin was the last person in the world known to be infected with naturally occurring Smallpox. Somalia ( Soomaaliya; الصومال) officially the Somali Republic ( Jamhuuriyadda Soomaaliya, جمهورية الصومال) and formerly known Events 740 - An Earthquake strikes Constantinople, causing much damage and death Also 1977 (album by Ash. Year 1977 ( MCMLXXVII) was a Common year starting on Saturday (link displays ^[13] The last naturally occurring case of the more deadly Variola major had been detected in October 1975 in a two-year-old Bangladeshi girl, Rahima Banu. ( Bengali: বাংলাদেশ inc-Latn Bangladesh) officially Rahima Banu (born 1973 was the last known person to be infected with naturally-incurring Variola major Smallpox. ^[36]

The global eradication of smallpox was certified, based on intense verification activities in countries, by a commission of eminent scientists on 9 December 1979 and subsequently endorsed by the World Health Assembly on 8 May 1980^[37][38] as Resolution WHA33. Events 536 - Byzantine General Belisarius enters Rome while the Ostrogothic garrison peacefully leaves the city Year 1979 ( MCMLXXIX) was a Common year starting on Monday (link displays the 1979 Gregorian calendar) Events 589 - Reccared summons the Third Council of Toledo 1450 - Jack Cade's Rebellion: Kentishmen Year 1980 ( MCMLXXX) was a Leap year starting on Tuesday (link displays the 1980 Gregorian calendar) 3. The first two sentences of the resolution read: "Having considered the development and results of the global program on smallpox eradication initiated by WHO in 1958 and intensified since 1967 … Declares solemnly that the world and its peoples have won freedom from smallpox, which was a most devastating disease sweeping in epidemic form through many countries since earliest time, leaving death, blindness and disfigurement in its wake and which only a decade ago was rampant in Africa, Asia and South America. "^[39]

Post-eradication

The last cases of smallpox in the world occurred in an outbreak of two cases (one of which was fatal) in Birmingham, England in 1978. Birmingham ( ˈbɜːmɪŋəm Ber -ming-um England is a Country which is part of the United Kingdom. Its inhabitants account for more than 83% of the total UK population whilst its mainland A medical photographer, Janet Parker, died from the disease on 11 September 1978,^[39] after which the scientist responsible for the unit, Professor Henry Bedson, committed suicide. Janet Parker (1938–1978 was the last known person to die from Smallpox. Events 9 - The Battle of the Teutoburg Forest ends 506 - The Bishops of Visigothic Gaul Year 1978 ( MCMLXXVIII) was a Common year starting on Sunday (link displays the 1978 Gregorian calendar) ^[2] In light of this accident, all known stocks of smallpox were destroyed or transferred to one of two WHO reference laboratories; the Centers for Disease Control and Prevention (CDC) in the United States and the State Research Center of Virology and Biotechnology VECTOR in Koltsovo, Russia where a regiment of troops guard it. The Centers for Disease Control and Prevention (or CDC) is an agency of the United States Department of Health and Human Services based in unincorporated The State Research Center of Virology and Biotechnology VECTOR, also known as the Vector Institute, is a highly sophisticated biological research center in Koltsovo Koltsovo may refer to Koltsovo Novosibirsk Oblast, an urban-type settlement in Novosibirsk Oblast Russia Koltsovo Yekaterinburg, a former In 1986, the World Health Organization recommended destruction of the virus, and later set the date of destruction to be 30 December 1993. Events 1460 - Wars of the Roses: Battle of Wakefield. 1816 - The Treaty of St Year 1993 ( MCMXCIII) was a Common year starting on Friday (link will display full 1993 Gregorian calendar) This was postponed to 30 June 1995. Events 350 - Roman usurper Nepotianus, of the Constantinian dynasty, is defeated and killed by troops of the Usurper Year 1995 ( MCMXCV) was a Common year starting on Sunday. Events of 1995 ^[40] In 2002 the policy of the WHO changed to be against its final destruction. ^[41] Destroying existing stocks would reduce the risk involved with ongoing smallpox research; the stocks are not needed to respond to a smallpox outbreak. ^[42] However, the stocks may be useful in developing new vaccines, antiviral drugs, and diagnostic tests. ^[43] The Russians were later accused of secretly continuing their program of producing weaponized smallpox. (citation needed)

In March 2004 smallpox scabs were found tucked inside an envelope in a book on Civil War medicine in Santa Fe, New Mexico. Coagulation is a complex process by which Blood forms Clots It is an important part of Hemostasis (the cessation of blood loss from a damaged vessel whereby Causes of the war See also Origins of the American Civil War, Timeline of events leading to the American Civil War The coexistence of a slave-owning South Santa Fe ( Navajo: Yootó is the Capital of the state of New Mexico. New Mexico ( is a state located in the southwestern region of the United States of America. ^[44] The envelope was labeled as containing the scabs and listed the names of the patients they came from. Assuming the contents could be dangerous, the librarian who found them did not open the envelope. The scabs ended up with employees from the CDC who responded quickly once informed of the discovery. The discovery raised concerns that smallpox DNA could be extracted from these and other scabs and used for a biological attack.

Biological warfare

The British may have used smallpox as a biological warfare agent during the French and Indian Wars (1754–63), against France and its Native American allies (see more information at Siege of Fort Pitt). Biological warfare (BW — known as a germ warfare, biological weapons and bioweaponry — is the use of any Pathogen ( Bacterium The French and Indian Wars is a name used in the United States for a series of conflicts in North America that represented the actions there that accompanied For indigenous peoples in the United States other than Hawaii and Alaska see also Native Americans in the United States. Pontiac's Rebellion was a war launched in 1763 by North American Indians who were dissatisfied with British policies in the Great Lakes region after It has been alleged that smallpox was also used as a weapon during the American Revolutionary War (1775–83). In this article the inhabitants of the thirteen colonies that supported the American Revolution are primarily referred to as "Americans" with occasional references to "Patriots" ^[45] During World War II, scientists from the United Kingdom, United States and Japan were involved in research into producing a biological weapon from smallpox. World War II, or the Second World War, (often abbreviated WWII) was a global military conflict which involved a majority of the world's nations, including The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located The United States of America —commonly referred to as the For a topic outline on this subject see List of basic Japan topics. ^[46] 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 preparation which is used to establish or improve immunity to a particular disease ^[45] The Soviet Union established a smallpox weapons factory in 1947 in the city of Zagorsk, 75 km to the northeast of Moscow. The Union of Soviet Socialist Republics (USSR was a constitutionally Socialist state that existed in Eurasia from 1922 to 1991 Sergiyev Posad (Се́ргиев Поса́д is a city and the administrative center of Sergiyevo-Posadsky District of Moscow Oblast, Russia Moscow (Москва́ romanised: Moskvá, IPA: see also other names) is the Capital and the largest city of ^[47]

An outbreak of weaponized smallpox may have occurred during its testing in the 1970s. General Prof. Peter Burgasov, former Chief Sanitary Physician of the Soviet Army, and a senior researcher within the Soviet program of biological weapons described the incident:

“On Vozrozhdeniya Island in the Aral Sea, the strongest recipes of smallpox were tested. The Red Army ( Russian: Рабоче-Крестьянская Красная Армия R aboche- K rest'yanskaya K rasnaya A rmiya History 1928 - Revolutionary Military Council signed a decree about weaponization of Typhus. This article is about the island For the album by Folk metal band Arkona, see Vozrozhdeniye. The Aral Sea ( Kazakh: Арал Теңізі Aral Tengizi, Orol dengizi Russian: Аральскοе мοре Tajik / Persian: Daryocha-i Suddenly I was informed that there were mysterious cases of mortalities in Aralsk. Aral, also known as Aralsk or Aral'sk, ( Kazakh: Арал, Russian: Аральск) is a small city in south-western A research ship of the Aral fleet came 15 km away from the island (it was forbidden to come any closer than 40 km). The lab technician of this ship took samples of plankton twice a day from the top deck. The smallpox formulation—400 gr. of which was exploded on the island—”got her” and she became infected. After returning home to Aralsk, she infected several people including children. All of them died. I suspected the reason for this and called the Chief of General Staff of Ministry of Defense and requested to forbid the stop of the Alma-Ata—Moscow train in Aralsk. Almaty ( Алматы; formerly known as Alma-Ata ( Алма-Ата) also Verniy, (Верный is the largest city in Kazakhstan Moscow (Москва́ romanised: Moskvá, IPA: see also other names) is the Capital and the largest city of As a result, the epidemic around the country was prevented. I called Andropov, who at that time was Chief of KGB, and informed him of the exclusive recipe of smallpox obtained on Vozrazhdenie Island. Yuri Vladimirovich Andropov (Ю́рий Влади́мирович Андро́пов Yuri Vladimirovich Andropov) ( &ndash 9 February 1984 was a Soviet politician ”^[48][49]

Others contend that the first patient may have contracted the disease while visiting Uyaly or Komsomolsk, two cities where the boat docked. Komsomolsk may refer to Komsomolsk-on-Amur, a city in Khabarovsk Krai Russia Komsomolsk Ivanovo Oblast, a town in Ivanovo Oblast Russia ^[50]

History

Eurasian epidemics

It is important to note that, although historical epidemics and pandemics are believed by some historians to have been early outbreaks of smallpox, contemporary records are not detailed enough to make a definite diagnosis at this distance. In Epidemiology, an epidemic (from Greek epi- upon + demos people is a classification of a disease that appears as new cases in a A pandemic (from Greek παν pan all + δήμος demos people is an Epidemic of Infectious disease that spreads through ^[29]

The Plague of Athens devastated the city of Athens in 430 BC, killing around a third of the population, according to Thucydides. The Plague of Athens was a devastating Epidemic which hit the City-state of Athens in ancient Greece during the second year of the Peloponnesian Athens (ˈæθənz Αθήνα Athina,) the Capital and largest city of Greece, dominates the Attica periphery as one of the world's Thucydides ( C 460 BC &ndash C 395 BC) ( Greek Θουκυδίδης Thoukydídēs) was a Greek Historians have long considered this an example of bubonic plague, but more recent examination of the reported symptoms led some scholars to believe the cause may have been measles, smallpox, typhus, or a viral hemorrhagic fever (like Ebola). Bubonic plague is the best-known manifestation of the bacterial disease plague, caused by the bacterium Yersinia pestis (formerly known as Measles (rubeola is a Disease caused by a virus specifically a Paramyxovirus of the genus Morbillivirus. Typhus is any of several similar diseases caused by Louse -borne bacteria The viral hemorrhagic Fevers ( VHFs') are a diverse group of animal and human illnesses that are caused by five distinct families of Ebola is the common term for a group of Viruses belonging to genus Ebolavirus, family Filoviridae, and for the disease which they

The Antonine Plague that swept through the Roman Empire and Italy in 165–180 is also thought to be either smallpox or measles. The Antonine Plague, 165 - 180 AD  also known as the Plague of Galen, was an ancient Pandemic, either of Smallpox or Measles The Roman Empire was the post-Republican phase of the ancient Roman civilization, characterised by an autocratic form of government and large territorial Italy (Italia officially the Italian Republic, (Repubblica Italiana is located on the Italian Peninsula in Southern Europe, and on the two largest ^[51][29] A second major outbreak of disease in the Empire, known as the Plague of Cyprian (251–266), was also either smallpox or measles. The Plague of Cyprian is the name given to a pandemic probably of Smallpox, that afflicted the Roman Empire from 251 AD onwards

The next major epidemic believed to be smallpox occurred in India. India, officially the Republic of India (भारत गणराज्य inc-Latn Bhārat Gaṇarājya; see also other Indian languages) is a country The exact date is unknown. Around 400 AD, an Indian medical book recorded a disease marked by pustules and boils, saying "the pustules are red, yellow, and white and they are accompanied by burning pain … the skin seems studded with grains of rice. " The Indian epidemic was thought to be punishment from a god, and the survivors created a goddess, Sitala, as the anthropomorphic personification of the disease. Sitala, Sītala Devi or Māri (Tamil is the Goddess of Smallpox or the Goddess of Disease in popular or non-Vedic ^[52][53][54] Smallpox was thus regarded as possession by Sitala. In Hinduism the goddess Sitala both causes and cures high fever, rashes, hot flashes and pustules. Hinduism is a religious tradition that originated in the Indian subcontinent. All of these are symptoms of smallpox.

Smallpox did not definitively enter Western Europe until about 581 when Bishop Gregory of Tours provided an eyewitness account that describes the characteristic findings of smallpox. Western Europe at its most general meaning means 'all the countries in the West of Europe ' ^[29] Most of the details about the epidemic that followed are lost, probably due to the scarcity of surviving written records of early medieval society.

Smallpox was a leading cause of death in the 18th century. The 18th century lasted from 1701 to 1800 in the Gregorian calendar, in accordance with the Anno Domini / Common Era numbering system It killed an estimated 400,000 Europeans each year in the 18th century, including five reigning European monarchs. ^[55] Most people became infected during their lifetimes, and about 30% of people infected with smallpox died from the disease. ^[56]

The Franco-Prussian War triggered a smallpox pandemic of 1870–1875 that claimed 500,000 lives. The Franco-Prussian War or Franco-German War, often referred to in France as the 1870 War ( 19 July, 1870 — 10 May, 1871 ^[57][58]

Epidemics in the Americas

After first contacts with Europeans and Africans, some believe that the death of 90–95% of the native population of the New World was caused by Old World diseases. The European peoples are the various Nations and Ethnic groups of Europe. The term African people can refer to people who live in Africa, or people who trace their ancestry to Indigenous inhabitants of Africa. The New World is one of the names used for the non-Eurasian/non-African parts of the Earth specifically the Americas and Australia. The Old World consists of those parts of Earth known to Europeans Asians and Africans in the 15th century ^[62] It is suspected that smallpox was the chief culprit and responsible for killing nearly all of the native inhabitants of the Americas. For more than 200 years, this disease affected all new world populations, mostly without intentional European transmission, from contact in the early 1500s to until possibly as late as the French and Indian Wars (1754–1767). ^[63]

In 1519 Hernán Cortés landed on the shores of what is now Mexico and was then the Aztec empire. Hernán Cortés de Monroy y Pizarro 1st Marqués del Valle de Oaxaca ( 1485&ndash December 2, The United Mexican States ( or commonly Mexico (ˈmɛksɪkoʊ () is a federal constitutional Republic in North America. Aztec is a term used to refer to certain ethnic groups of central Mexico, particularly those groups who spoke the Nahuatl language and who achieved political In 1520 another group of Spanish arrived in Mexico from Hispaniola, bringing with them the smallpox which had already been ravaging that island for two years. Hispaniola (from Spanish, La Española) is the second-largest and most populous Island of the Antilles, lying between the islands of When Cortés heard about the other group, he went and defeated them. In this contact, one of Cortés's men contracted the disease. When Cortés returned to Tenochtitlan, he brought the disease with him. There are some towns in Mexico which are spelled "Tenochtitlán" like San Lorenzo

Soon, the Aztecs rose up in rebellion against Cortés and his men. Outnumbered, the Spanish were forced to flee. In the fighting, the Spanish soldier carrying smallpox died. After the battle, the Aztecs contracted the virus from the invaders' bodies. Cortes would not return to the capital until August 1521. In the meantime smallpox devastated the Aztec population. It killed most of the Aztec army and 25% of the overall population. ^[64] A Spanish priest left this description: "As the Indians did not know the remedy of the disease…they died in heaps, like bedbugs. In many places it happened that everyone in a house died and, as it was impossible to bury the great number of dead, they pulled down the houses over them so that their homes become their tombs. " On Cortés's return, he found the Aztec army’s chain of command in ruins. In a Military context the chain of command is the line of authority and responsibility along which orders are passed within a Military unit and between different The soldiers who lived were still weak from the disease. Cortés then easily defeated the Aztecs and entered Tenochtitlán. ^[65] The Spaniards said that they could not walk through the streets without stepping on the bodies of smallpox victims.

The effects of smallpox on Tahuantinsuyu (or the Inca empire) were even more devastating. The Inca Empire (or Inka Empire) was the largest empire in Pre-Columbian America. Beginning in Colombia, smallpox spread rapidly before the Spanish invaders first arrived in the empire. Colombia (kəˈlʌmbɪə officially the Republic of Colombia () is a country in northwestern South America. The spread was probably aided by the efficient Inca road system. Among the many roads and trails constructed in pre-Columbian South America, the Inca road system, or Qhapaq Ñan was the most extensive Within months, the disease had killed the Sapa Inca Huayna Capac, his successor, and most of the other leaders. The God Emperor of the Inca Empire ( Quechua: Inka Qhapaq) of the Andes (the area including modern Peru, Ecuador, and Huayna Capac (Quechua Wayna Qhapaq "splendid youth" was the eleventh Sapa Inca (1464 &ndash 1527 of the Inca Empire and sixth of the Hanan Two of his surviving sons warred for power and, after a bloody and costly war, Atahualpa become the new Sapa Inca. Atahualpa, Atahuallpa, Atabalipa, or Atawallpa ( Quito – Cajamarca, August 29, 1533) was the last sovereign As Atahualpa was returning to the capital Cuzco, Francisco Pizarro arrived and through a series of deceits captured the young leader and his best general. ||} Cusco (also spelled Cuzco, and in the local Quechua language as Qusqu 'qos Francisco Pizarro González 1st Marqués de los Atabillos (c 1471 or 1476 &ndash 26 June 1541 was a Spanish Conquistador, conqueror of the Incan Empire Within a few years smallpox claimed between 60% and 90% of the Inca population,^[66] with other waves of European disease weakening them further. A handful of historians argue that a disease called Bartonellosis may have been responsible for some outbreaks of illness, but this opinion is in the scholarly minority. Bartonellosis is an Infectious disease produced by Bacteria of the Genus Bartonella. ^[67] The effects of smallpox were depicted in the ceramics of the Moche people of ancient Peru. The Moche civilization (alternately the Mochica culture Early Chimu Pre-Chimu Proto-Chimu etc Peru (Perú Piruw Piruw officially the Republic of Peru ( reˈpuβlika del peˈɾu is a country in western South America. ^[68]

Even after the two mighty empires of the Americas were defeated by the virus and disease, smallpox continued its march of death. In 1633 in Plymouth, Massachusetts, the Native Americans were struck by the virus. Native Americans in the United States are the indigenous peoples from the regions of North America now encompassed by the continental United States As it had done elsewhere, the virus wiped out entire population groups of Native Americans. It reached Mohawks in 1634,^[69] the Lake Ontario in 1636, and the lands of the Iroquois by 1679. Mohawk ( Kanienkeh, Kanienkehaka or Kanien’Kahake, meaning "People of the Flint" are an indigenous people of North America Lake Ontario is one of the five Great Lakes of North America. The Iroquois Confederacy (also known as the "League of Peace and Power" the "Five Nations" the "Six Nations" or the "People of the Longhouse During the 1770s, smallpox killed at least 30% of the West Coast Native Americans. The " West Coast " " Western Seaboard " or " Pacific Seaboard " are terms for the westernmost coastal states of the Western United States ^[70][71] Smallpox epidemic of 1780–1782 brought devastation and drastic depopulation among the Plains Indians. The Plains Indians are the Indigenous peoples who live on the plains and rolling hills of the Great Plains of North America. ^[72] By 1832, the federal government of the United States established a smallpox vaccination program for Native Americans. The United States of America —commonly referred to as the ^[73]

A particularly virulent sequence of smallpox outbreaks took place in Boston, Massachusetts. From 1636 to 1698, Boston endured six epidemics. In 1721, the most severe epidemic occurred. The entire population fled the city, bringing the virus to the rest of the Thirteen Colonies. The Thirteen Colonies were part of what became known as British America, a name that was used by Great Britain until the Treaty of Paris (1783 recognized the In the late 1770s, during the American Revolutionary War, smallpox returned once more and killed an estimated 125,000 people. Between 1775 and 1782, a Smallpox Epidemic raged across much of North America, killing more than 130000 people ^[74] Peter Kalm in his Travels in North America, described how in that period, the dying Indian villages became overrun with wolves feasting on the corpses and weakened survivors. The grey wolf or gray wolf ( Canis lupus) also known as the timber wolf or simply wolf, is a Mammal of the order Carnivora ^[75]

Famous sufferers and survivors

Famous historical figures who contracted smallpox include Ramesses V,^[38] the Kangxi Emperor, Shunzhi Emperor and Tongzhi Emperor of China (official history), Date Masamune of Japan (who lost an eye to the disease), and the Incan emperor Huayna Capac in 1527. Usermare Sekhepenre Ramesses V (also written Ramses and Rameses) was the fourth Pharaoh of the Twentieth dynasty of Egypt and was the son The Kangxi Emperor ( Mongolian Enkh Amgalan Khaan, May 4, 1654 &ndash December 20, 1722) was the third Emperor of The Shunzhi Emperor ( March 15, 1638 &ndash February 5, 1661) was the second emperor of the Manchu Qing dynasty The Tongzhi Emperor, born Zaichun ( April 27, 1856 &ndash January 12, 1875) was the ninth emperor of the Manchu ( September 5, 1567 – June 27, 1636) was a Japanese samurai of the Azuchi-Momoyama period through early Edo period. Huayna Capac (Quechua Wayna Qhapaq "splendid youth" was the eleventh Sapa Inca (1464 &ndash 1527 of the Inca Empire and sixth of the Hanan More recent public figures also include: Guru Har Krishan 8th Guru of the Sikhs in 1664, Peter III of Russia in 1744. Guru Har Krishan (ਗੁਰੂ ਹਰਿ ਕ੍ਰਿਸ਼ਨ ( 7 July, 1656 &ndash 30 March, 1664) was Peter III ( February 21, 1728 – July 17, 1762) (Пётр III Фëдорович Pyotr III Fyodorovitch) was Emperor ^[76] and Maximilian III Joseph, Elector of Bavaria. Maximilian III Joseph ( 28 March 1727 – 30 December 1777) was Prince-elector and Duke of Bavaria from 1745 to 1777

Families prominent in History the world over often had several people infected by and/or perish from the disease. For example, several relatives of Henry VIII survived the disease but were scarred by it. Henry VIII (28 June 1491 &ndash 28 January 1547 was King of England and Lord of Ireland, later King of Ireland and claimant to the Kingdom of These include his sister Margaret, Queen of Scotland, his fourth wife, Anne of Cleves, and his daughter, Elizabeth I of England in 1562 (as an adult she would often try to disguise the pockmarks with heavy makeup). Margaret Tudor ( 28 November, 1489 &ndash 18 October 1541) was the elder of the two surviving daughters of Henry VII of England Anne of Cleves Queen of England (22 September 1515&ndash16 July 1557 ( German: Anna von Jülich-Kleve-Berg) was the fourth wife of Henry VIII A more distant relative, Mary Queen of Scots, contracted the disease as a child but had no visible scarring.

In Europe, deaths from smallpox often impacted dynastic succession. Louis XV of France succeeded his great-grandfather Louis XIV through a series of deaths of smallpox or measles among those earlier in the succession line and he himself died of the disease in 1774. Louis XV (15 February 1710 &ndash 10 May 1774 ruled as King of France and of Navarre from 1 September 1715 until his death in 1774 Early years Birth and ancestry Louis XIV was born in the Château de Saint-Germain-en-Laye on September 5 1638 and bore the Heir apparent The son of Henry VIII, Edward VI, likely died from complications shortly after apparently recovering from the disease, thereby rendering all of his sire's infamous efforts to provide England with a male heir moot. Edward VI (12 October 1537 &ndash 6 July 1553 became King of England and Ireland on 28 January 1547 and was crowned on 20 February at the age of nine (His immediate successors were all females. ) William III lost his mother to the disease when he was only ten years old in 1660, and named his uncle Charles as legal guardian: her death from smallpox would indirectly spark a chain of events that would eventually lead to the permanent ousting of the Stuart line from the British throne and usher in a new age. William III or William of Orange (14 November 1650 &ndash 8 March 1702 He is informally known in Northern Ireland and Scotland as "King Billy"

Both George Washington and Abraham Lincoln, Presidents of the United States, contracted and recovered from the disease. George Washington (February 22 1732 December 14 1799 served as the first President of the United States of America (1789&ndash1797 and led the Abraham Lincoln (February 12 1809 &ndash April 15 1865 the sixteenth President of the United States, successfully led his country through its greatest internal Joseph Stalin, who was badly scarred by the disease early in life, often had photographs retouched to make his pockmarks less apparent. Joseph Stalin ( ნამდვილი გვარი ჯუღაშვილი|Iosif Vissarionovich Dzhugashvili; March 5 1953 was General Secretary of the Communist Party Lucky Luciano contracted disease in 1907 at the age of ten, upon coming to New York from Sicily. Charles "Lucky" Luciano (born Salvatore Lucania; November 24 1897 – January 26 1962 was a Sicilian Mobster.

See also

• 1837-38 smallpox epidemic (in the US)
• Biological warfare
• CCR5-Δ32
• Monkeypox
• Columbian Exchange
• Herd immunity
• The mathematics of mass vaccination
• Population history of American indigenous peoples
• Smallpox (film)- a fictional docudrama

References

Further reading

External links

• Smallpox Biosafety The Genetic Engineering of Smallpox: WHO’s Retreat from the Eradication of Smallpox Virus
• Photographs of eye damage due to smallpox
• Smallpox Images and Diagnosis Synopsis

Smallpox in history

• Inoculation for the Small-Pox defended—1750 article from Gentleman's Magazine
• Why Blame Smallpox? Revisionist argument regarding smallpox in sixteenth century Peru
• History of Smallpox in South Asia
• Small pox history in India