The initial symptoms were similar to other viral diseases that are still extant, such as influenza and the common cold: fever of at least , 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.<unk>  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 infection could take several very different courses, which resulted in four types of<unk>  disease based on the Rao classification: ordinary, modified, malignant (or flat), and hemorrhagic<unk> . Historically, ordinary<unk>  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 around 12 days. Ordinary A child showing rash due to ordinary-type<unk>  (Variola major) Ninety percent or more of<unk>  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<unk>  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<unk>  often remained ill even after scabs had formed over all the lesions. In one case series, the case-fatality rate in confluent<unk>  was 62 percent. Modified Referring to the character of the eruption and the rapidity of its development, modified<unk>  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<unk> . Modified<unk>  was rarely, if ever, fatal. This form of variola major was more easily confused with chickenpox. Malignant Malignant hemorrhagic<unk>  in a baker during an 1896 epidemic in Gloucester, England. Died 8 days after admission. In malignant-type<unk>  (also called flat<unk>  the lesions remained almost flush with the skin at the time when raised vesicles would have formed in the ordinary type. It is unknown why some people developed this type. Historically, it accounted for 5–10 percent of cases, and most (72 percent) were children. Malignant<unk>  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<unk> , the vesicles contained little fluid, were soft and velvety to the touch, and may have contained hemorrhages. Malignant<unk>  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<unk> . If the person recovered, the lesions gradually faded and did not form scars or scabs. Hemorrhagic Hemorrhagic<unk>  is a severe form accompanied by extensive bleeding into the skin, mucous membranes, gastrointestinal tract, and viscera. This form develops in approximately two percent of infections and occurs mostly in adults. Pustules do not typically form in hemorrhagic<unk> . 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<unk>  has very rarely been caused by Variola minor. While bleeding may occur in mild cases and not affect outcomes, hemorrhagic<unk>  is typically fatal. Vaccination does not appear to provide any immunity to either form of hemorrhagic<unk>  and some cases even occurred among people that were revaccinated shortly before. It has two forms. Early Likely hemorrhagic<unk>  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<unk> ." The early or fulminant form of hemorrhagic<unk>  (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 the end or shortly before the end. 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<unk> , versus roughly 1% in nonpregnant women and adult males). The case fatality rate of early hemorrhagic<unk>  approaches 100%. Late There is also a later form of hemorrhagic<unk>  (referred to late hemorrhagic<unk> , or variolosa pustula hemorrhagica). The prodrome is severe and similar to that observed in early hemorrhagic<unk> , 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<unk> . 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<unk>  occurs anywhere from three to 25 percent of fatal cases, depending on the virulence of the<unk>  strain. Most people with the late-stage form die within eight to 10 days of illness. Among the few who recover, the hemorrhagic lesions gradually disappear after a long period of convalescence. The case fatality rate for late hemorrhagic<unk>  is around 90-95%. Pregnant women are slightly more likely to experience this form of the disease, though not as much as early hemorrhagic<unk> .
Smallpox
Monkeypox
Cowpox
Impetigo
Chickenpox
Sealpox
Molluscum contagiosum
Mumps