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Hand, foot and mouth disease is usually caused by either coxsackievirus A16 or enterovirus 71 (EV71). Coxsackievirus A16 infection usually causes mild disease. Outbreaks of severe, and sometimes fatal, hand, foot and mouth disease with encephalitis and myocarditis have been reported from Bulgaria, Hungary, Malaysia, Singapore and Taiwan. These severe outbreaks have been related to EV71. A follow‐up study in Taiwan (Luan‐Yin Chang and colleagues. New England Journal of Medicine 2007;356:1226–34; see also Perspective, ibid: 1204–5) has shown that neurological development is particularly impaired in children who develop cardiopulmonary failure after CNS involvement in the acute phase of EV71 infection.
A severe EV71 epidemic occurred in Taiwan in 1998, and between 1998 and 2003 a total of 621 children were treated for EV71 infection at two major hospitals. They presented with hand, foot and mouth disease, herpangina or fever. A total of 232 of these patients had CNS involvement. Twenty five patients died in the acute phase and 14 died later. The follow‐up cohort consisted of 142 patients with CNS involvement in the acute phase: 61 with mild CNS involvement (group 1), 53 with severe CNS involvement (group 2) and 28 with cardiopulmonary failure after CNS involvement (group 3). Median follow‐up was 2.9 years (1.0–7.4 years). The children in group 3 were younger at disease onset (median age 0.7 years) than those in groups 1 and 2 (2.0 and 2.3 years). All patients in group 1 (usually with aseptic meningitis) recovered without neurological sequelae. In group 2, 32 patients had had encephalitis, all of whom made a good neurological recovery apart from one who was left with a mild facial palsy. Sixteen patients had had a poliomyelitis‐like syndrome and nine of these had unilateral limb weakness and atrophy on follow‐up. Five patients had had acute encephalomyelitis and one of these had unilateral limb weakness and atrophy. Of the 28 patients in group 3, 21 (75%) had neurological sequelae. Eighteen had unilateral limb weakness and atrophy, 17 had dysphagia and needed tube feeding, 16 needed ventilator support because of central hypoventilation, seven had facial palsy, five had seizures and psychomotor retardation secondary to hypoxia, and four had seizures alone. Delayed development on the Denver Developmental Screening Test (DDST II) and low full scale IQ (<85) on the Wechsler Intelligence Scale for Children (WISC‐III) were much more common in group 3 than in group 2 (75% vs 5% and 50% vs 5% of those tested).
Among children with EV71 infection and severe acute neurological disease, those who went on to develop acute cardiopulmonary failure in the acute phase of the illness were much more likely to have neurological or cognitive impairment on follow‐up.