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Objective: To study the diagnosis and outcomes in people admitted to hospital with a diagnosis of severe malaria in areas with differing intensities of malaria transmission., Design: Prospective observational study of children and adults over the course a year., Setting: 10 hospitals in north east Tanzania., Participants: 17,313 patients were admitted to hospital; of these 4474 (2851 children aged under 5 years) fulfilled criteria for severe disease., Main Outcome Measure: Details of the treatment given and outcome. Altitudes of residence (a proxy for transmission intensity) measured with a global positioning system., Results: Blood film microscopy showed that 2062 (46.1%) of people treated for malaria had Plasmodium falciparum (slide positive). The proportion of slide positive cases fell with increasing age and increasing altitude of residence. Among 1086 patients aged > or = 5 years who lived above 600 metres, only 338 (31.1%) were slide positive, while in children < 5 years living in areas of intense transmission (< 600 metres) most (958/1392, 68.8%) were slide positive. Among 2375 people who were slide negative, 1571 (66.1%) were not treated with antibiotics and of those, 120 (7.6%) died. The case fatality in slide negative patients was higher (292/2412, 12.1%) than for slide positive patients (142/2062, 6.9%) (P < 0.001). Respiratory distress and altered consciousness were the strongest predictors of mortality in slide positive and slide negative patients and in adults as well as children., Conclusions: In Tanzania, malaria is commonly overdiagnosed in people presenting with severe febrile illness, especially in those living in areas with low to moderate transmission and in adults. This is associated with a failure to treat alternative causes of severe infection. Diagnosis needs to be improved and syndromic treatment considered. Routine hospital data may overestimate mortality from malaria by over twofold.