Deaths of Children during an Outbreak of Hand, Foot, and Mouth Disease in Sarawak, Malaysia: Clinical and Pathological Characteristics of the Disease

Abstract

From April through June 1997, 29 previously healthy children aged <6 years (median, 1.5 years) in Sarawak, Malaysia, died of rapidly progressive cardiorespiratory failure during an outbreak of hand, foot, and mouth disease caused primarily by enterovirus 71 (EV71). The case children were hospitalized after a short illness (median duration, 2 days) that usually included fever (in 100% of case children), oral ulcers (66%), and extremity rashes (62%). The illness rapidly progressed to include seizures (28%), flaccid limb weakness (17%), or cardiopulmonary symptoms (of 24 children, 17 had chest radiographs showing pulmonary edema, and 24 had echocardiograms showing left ventricular dysfunction), resulting in cardiopulmonary arrest soon after hospitalization (median time, 9 h). Cardiac tissue from 10 patients showed normal myocardium, but central nervous system tissue from 5 patients showed inflammatory changes. Brain-stem specimens from 2 patients were available, and both specimens showed extensive neuronal degeneration, inflammation, and necrosis, suggesting that a central nervous system infection was responsible for the disease, with the cardiopulmonary dysfunction being neurogenic in origin. EV71 and possibly an adenovirus, other enteroviruses, or unknown cofactors are likely responsible for this rapidly fatal disease.

Epidemic Hand, Foot and Mouth Disease Caused by Human Enterovirus 71, Singapore

“…In these aspects, this outbreak is similar to those that occurred in Malaysia and Taiwan in recent years (6,7,9,10).…”

Pathogenesis study of enterovirus 71 infection in rhesus monkeys

“…6,26,27 These symptoms suggest the presence of lesions in the CNS of the monkeys. In this study, physical examination of the monkeys that were infected via these four routes revealed that the muscle tension in the limbs was in the normal range, and no herpes-like skin lesions were observed on the hands, feet or mouths.…”

Phylogenetic evidence for a recent spread of two populations of human enterovirus 71 in European countries

“…Neurological cases with a high case fatality rate were first recorded in Bulgaria in 1975, where they were mainly associated with poliomyelitis-like paralysis, and in Hungary in 1978 (Chumakov et al, 1979;Nagy et al, 1982). The recent outbreaks in Asia were also associated with a high incidence of neurotropic complications (Chan et al, 2000); a case fatality rate of 0.6 % was noted during the outbreaks in 2008 (Huang et al, 2009). Fatal cases in children under 5 years of age were mainly associated with neurogenic pulmonary oedema (Chinese Center for Disease Control and Prevention and the World Health Organization, 2008; Ho et al, 1999).…”