Deaths of children during an outbreak of hand, foot, and mouth disease in Sarawak, Malaysia: Clinical and pathological characteristics of the disease

From April through June 1997, 29 previously healthy children aged <6 years (median, 1.5 years) in Sarawak, Malaysia, died of rapidly progressive cardi orespiratory failure during an outbreak of hand, foot, and mouth disease ca used primarily by enterovirus 71 (EV71). The case children were hospitalize d after a short illness (median duration, 2 days) that usually included fev er(in 100% of case children), oral ulcers (66%), and extremity rashes (62%) . The illness rapidly progressed to include seizures (28%), flaccid limb we akness (17%), or cardiopulmonary symptoms (of 24 children, 17 had chest rad iographs showing pulmonary edema, and 24 had echocardiograms showing left v entricular dysfunction), resulting in cardiopulmonary arrest soon after hos pitalization (median time, 9 h). Cardiac tissue from 10 patients showed nor mal myocardium, but central nervous system tissue from 5 patients showed in flammatory changes. Brain-stem specimens from 2 patients were available, an d both specimens showed extensive neuronal degeneration, inflammation, and necrosis, suggesting that a central nervous system infection was responsibl e for the disease, with the cardiopulmonary dysfunction being neurogenic in origin. EV71 and possibly an adenovirus, other enteroviruses, or unknown c ofactors are likely responsible for this rapidly fatal disease.