Which virus is reason for Smallpox ?

Smallpox was an infectious disease caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, derived from varius ("spotted") or varus ("pimple"). The disease was originally known in English as the "pox"or "red plague"; the term "smallpox" was first used in Britain in the 15th century to distinguish variola from the "great pox" (syphilis).The last naturally occurring case of smallpox (Variola minor) was diagnosed on 26 October 1977.

Infection with smallpox is focused in small blood vessels of the skin and in the mouth and throat before disseminating. In the skin it results in a characteristic maculopapular rash and, later, raised fluid-filled blisters. V. major produced a more serious disease and had an overall mortality rate of 30–35 percent. V. minor caused a milder form of disease (also known as alastrim, cottonpox, milkpox, whitepox, and Cuban itch) which killed about 1 percent of its victimsLong-term complications of V. major infection included characteristic scars, commonly on the face, which occur in 65–85 percent of survivors.Blindness resulting from corneal ulceration and scarring, and limb deformities due to arthritis and osteomyelitis were less common complications, seen in about 2–5 percent of cases.

Smallpox is believed to have emerged in human populations about 10,000 BCThe earliest physical evidence of it is probably the pustular rash on the mummified body of Pharaoh Ramses V of EgyptThe disease killed an estimated 400,000 Europeans annually during the closing years of the 18th century (including five reigning monarchs)and was responsible for a third of all blindnessOf all those infected, 20–60 percent—and over 80 percent of infected children—died from the diseaseSmallpox was responsible for an estimated 300–500 million deaths during the 20th century. 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.

After vaccination campaigns throughout the 19th and 20th centuries, the WHO certified the global eradication of smallpox in 1979.[5] Smallpox is one of two infectious diseases to have been eradicated, the other being rinderpest, which was declared eradicated in 2011.

Classification

There were two clinical forms of smallpox. Variola major was the severe and most common form, with a more extensive rash and higher fever. Variola minor was a less common presentation, and a much less severe disease, with historical death rates of 1 percent or less. Subclinical (asymptomatic) 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 and could be confirmed only by antibody studies or, rarely, by virus isolation.

Signs and symptoms
The incubation period between contraction and the first obvious symptoms of the disease is around 12 days. Once inhaled, variola major virus invades the oropharyngeal (mouth and throat) or the respiratory mucosa, migrates to regional lymph nodes, and begins to multiply. In the initial growth phase the virus seems to move from cell to cell, but around the 12th day, lysis of many infected cells occurs and the virus is found in the bloodstream in large numbers (this is called viremia), and a second wave of multiplication occurs in the spleen, bone marrow, and lymph nodes. The initial or prodromal symptoms are similar to other viral diseases such as influenza and the common cold: fever of at least 38.3 °C (101 °F), muscle pain, malaise, headache and prostration. As the digestive tract is commonly involved, nausea and vomiting and backache often occur. The prodrome, or preeruptive stage, usually lasts 2–4 days. By days 12–15 the first visible lesions—small reddish spots called enanthem—appear on mucous membranes of the mouth, tongue, palate, and throat, and temperature falls to near normal. These lesions rapidly enlarge and rupture, releasing large amounts of virus into the saliva.

Smallpox virus preferentially attacks skin cells, causing the characteristic pimples (called macules) associated with the disease. A rash develops on the skin 24 to 48 hours after lesions on the mucous membranes appear. Typically the macules first appear on the forehead, then rapidly spread to the whole face, proximal portions of extremities, the trunk, and lastly to distal portions of extremities. The process takes no more than 24 to 36 hours, after which no new lesions appear.At this point variola major infection can take several very different courses, resulting in four types of smallpox disease based on the Rao classification:ordinary, modified, malignant (or flat), and hemorrhagic. Historically, smallpox has an overall fatality rate of about 30 percent; however, the malignant and hemorrhagic forms are usually fatal.

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 became raised papules. By the third or fourth day the papules filled with an opalescent fluid to become vesicles. This fluid became opaque and turbid within 24–48 hours, giving them the appearance of pustules; however, the so-called pustules were filled with tissue debris, not pus.

By the sixth or seventh day, all the skin lesions have became pustules. Between seven and ten days the pustules 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 deflated, and started to dry up, forming crusts (or scabs). By day 16–20 scabs had formed over all the lesions, which have 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 densest on the face; denser on the extremities than on the trunk; and on the extremities, denser on the distal parts than on the proximal. The palms of the hands and soles of the feet were involved in the majority of 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 have 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. In this form the prodromal illness still occurred but may be less severe than in the ordinary type. There is usually no fever during evolution of the rash. The skin lesions tended to be fewer and evolve more quickly, are more superficial, and may not show the uniform characteristic of more typical smallpox.Modified smallpox was rarely, if ever, fatal. This form of variola major is more easily confused with chickenpox.

Malignant
In malignant-type smallpox (also called flat smallpox) the lesions remained almost flush with the skin at the time when raised vesicles form in the ordinary type. It is unknown why some people developed this type. Historically, it accounted for 5–10 percent of cases, and the majority (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 toxemia. The rash on the tongue and palate was extensive. Skin lesions matured slowly 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.

Hemorrhagic

Hemorrhagic smallpox is a severe form that is accompanied by extensive bleeding into the skin, mucous membranes, and gastrointestinal tract. This form develops in approximately 2 percent 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 it look charred and black,hence this form of the disease is also known as black pox.

In the early, or fulminating form, hemorrhaging appears on the second or third day as sub-conjunctival bleeding turns the whites of the eyes deep red. Hemorrhagic smallpox also produces a dusky erythema, petechiae, and hemorrhages in the spleen, kidney, serosa, muscle, and, rarely, the epicardium, liver, testes, ovaries and bladder. Death often occurs suddenly between the fifth and seventh days of illness, when only a few insignificant skin lesions are present. A later form of the disease occurs in patients who survive for 8–10 days. The hemorrhages appear in the early eruptive period, and the rash is flat and does not progress beyond the vesicular stage. Patients in the early stage of disease show a decrease in coagulation factors (e.g. platelets, prothrombin, and globulin) and an increase in circulating antithrombin. Patients in the late stage have significant thrombocytopenia; however, deficiency of coagulation factors is less severe. Some in the late stage also show increased antithrombin.This form of smallpox occurs in anywhere from 3 to 25 percent of fatal cases depending on the virulence of the smallpox strain. Hemorrhagic smallpox is usually fatal.