smallpox smallpox smallpox was an infectious disease caused by variola virus (often called smallpox virus) which belongs to the genus orthopoxvirus. the last naturally occurring case was diagnosed in october 1977, and the world health organization (who) certified the global eradication of the disease in 1980, making smallpox the only human disease to be eradicated. smallpoxother namesvariola, variola vera, pox, red plaguea child with smallpox in bangladesh in 1973. the bumps filled with thick fluid and a depression or dimple in the center are characteristic.specialtyinfectious diseasesymptoms early: fever, vomiting, mouth sores later: fluid filled blisters which scab over complicationsscarring of the skin, blindnessusual onset1 to 3 weeks following exposuredurationabout 4 weekscausesvariola major virus, variola minor virus (spread between people)diagnostic methodbased on symptoms and confirmed by pcrdifferential diagnosischickenpox, impetigo, molluscum contagiosum, monkeypoxpreventionsmallpox vaccinetreatmentsupportive caremedicationbrincidofovirprognosis30% risk of deathfrequencyeradicated (last wild case in 1977) the initial symptoms of the disease included fever and vomiting. this was followed by formation of ulcers in the mouth and a skin rash. over a number of days, the skin rash turned into the characteristic fluid-filled blisters 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. once the disease had developed, certain antiviral medications could potentially have helped, but such medications did not become available until after the disease was eradicated. the risk of death was about 30%, with higher rates among babies. often, those who survived had extensive scarring of their skin, and some were left blind. the earliest evidence of the disease dates to around 1500 bc in egyptian mummies. the disease historically occurred in outbreaks. 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 monarchs. as recently as 1967, 15 million cases occurred a year. inoculation 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 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 in 2011. the term "smallpox" was first used in england in the 16th century to distinguish the disease from syphilis, which was then known as the "great pox". other historical names for the disease include pox, speckled monster, and red plague. classification case fatality rate and frequency of smallpox by type and vaccination status according to rao case study type of disease case fatality rate (%)frequency (%) unvac.vac.unvac.vac. ordinary confluent 6226.322.84.6 ordinary semiconfluent 378.423.97 ordinary discrete 9.30.742.158.4 modified 002.125.3 flat 96.566.76.71.3 early hemorrhagic 1001000.71.4 late hemorrhagic 96.889.81.72.0 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) 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 viral culture. 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 external video smallpox (us army, 1967) on youtube the initial symptoms were similar to other viral diseases that are still extant, such as influenza and the common cold: fever of at least 38.3 °c (101 °f), muscle pain, malaise, headache and fatigue. as the digestive tract 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, 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 portions of extremities, the trunk, and lastly to distal 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 between contraction and the first obvious symptoms of the disease was 7–14 days. ordinary a child showing rash due to ordinary-type smallpox (variola major) at least 90% 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 papules. by the third or fourth day, the papules had filled with an opalescent fluid to become vesicles. this fluid became opaque and turbid within 24–48 hours, resulting in pustules. 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%. modified modified smallpox in a vaccinated 4 year old in cardiff, wales, 1962 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. malignant malignant hemorrhagic smallpox in a baker during an 1896 epidemic in gloucester, england. died 8 days after admission. 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% of cases, and most (72%) were children. malignant smallpox was accompanied by a severe prodromal phase that lasted 3–4 days, prolonged high fever, and severe symptoms of viremia. 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 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. this form develops in approximately 2% 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 likely hemorrhagic smallpox during a 1925 milwaukee, wisconsin epidemic in a patient who later died. patient described as an unvaccinated christian scientist, who "thought that he could by power of mind prevent smallpox." the early or fulminant form of hemorrhagic smallpox (referred to as purpura variolosa) begins with a prodromal phase characterized by a high fever, severe headache, and abdominal pain. the skin becomes dusky and erythematous, and this is rapidly followed by the development of petechiae and bleeding in the skin, conjunctiva and mucous membranes. 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 and bleeding in the spleen, kidney, serous membranes, skeletal muscles, pericardium, 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 cascade and an increase in circulating antithrombin. this form of smallpox occurs anywhere from 3% to 25% of fatal cases, depending on the virulence of the smallpox strain.