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

Abstract

Singapore experienced a large epidemic of hand, foot and mouth disease (HFMD) in 2000.After reviewing HFMD notifications from doctors and child-care centers, we found that the incidence of HFMD rose in September and declined at the end of October.During this period, 3,790 cases were reported.We performed enteroviral cultures on 311 and 157 specimens from 175 HFMD patients and 107 non-HFMD patients, respectively; human enterovirus 71 (HEV71) was the most frequently isolated virus from both groups.Most of the HFMD patients were <4 years of age.Three HFMD and two non-HFMD patients died.Specimens from two HFMD and both non-HFMD patients were culture positive for HEV71; a third HFMD patient was possibly associated with the virus.Autopsies performed on all three HFMD and one of the non-HFMD case-patients showed encephalitis, interstitial pneumonitis, and myocarditis.A preparedness plan for severe HFMD outbreaks provided for the prompt, coordinated actions needed to control the epidemic.and, foot and mouth disease (HFMD) is typically a benign and common self-limiting childhood disease, characterized by rapidly ulcerating vesicles in the mouth and lesions, usually vesicular, on the hands and feet (1).Lesions also frequently occur on the buttocks, but other parts of the body are usually not affected (2).HFMD is caused by a few serotypes of enteroviruses, most frequently coxsackie virus A16 (CAV16) and human enterovirus 71 (HEV71).Other viruses associated with the syndrome are coxsackie virus A (CAV) 4, 5, 9, and 10 and coxsackie virus B (CBV) 2 and 5 (1).The first recognized HFMD outbreak in Singapore occurred in 1970; the etiologic agent was unknown (3).Two other outbreaks were reported in 1972 and 1981 and involved 104 and 742 persons, respectively; in both outbreaks, CAV16 was implicated as the cause (4,5).After epidemics of HFMD in Sarawak, East Malaysia, and the Malaysian Peninsula in 1997 (6-8) and Taiwan in 1998 (9,10), which were associated with complications of encephalitis, myocarditis, and death, a system of surveillance for the disease, based on notifications from child-care centers, was implemented in Singapore in April 1998.Reporting the disease was made legally mandatory on October 1, 2000.Concurrent with the intensified surveillance, an interministry and interhospital HFMD Task Force, composed of representatives from the Ministries of Health, Environment, Education, and Community Development and Sports, as well as virologists and pediatricians, was created in 1998 to formulate a preparedness response plan to monitor and manage severe HFMD outbreaks in Singapore.At the end of 2000, Singapore experienced its largest known outbreak of HFMD.After media reports in September of HFMD-related deaths in Singaporean children, many patient samples were sent for virologic investigation to the Virology Laboratory of the Department of Pathology, Singapore General Hospital.Because the Virology Laboratory receives all requests for virus culture or enterovirus typing from the entire country, it was the repository of information on virtually all laboratory investigations during the HFMD epidemic.We describe the epidemiologic, virologic, and pathologic features of this epidemic. MethodsIn this study, we used a case definition for HFMD of fever, accompanied by oral ulcers and a rash, maculopapular or vesicular, on the hands and feet, with or without buttock involvement.We reviewed records of HFMD notifications to the Ministry of the Environment for the incidence and trend of the disease.All children with suspected HFMD reported by preschool centers were examined, and the cases were certified by family physicians.Cases reported by parents or school principals and teachers were excluded unless a medical certificate from a physician verified them.At the same time, Ministry of the Environment nurses conducted active case detection in both preschools and primary schools.All case-patients were identified by a unique national registration identification number, and duplicate reports were eliminated by the computer.Data obtained from samples received by the Virology Laboratory at Singapore General Hospital for enterovirus isolation during the epidemic were also analyzed.In addition to stool samples, samples included swabs of vesicles, mouth, throat, rectum, and ulcers, and samples from the brain, heart, lung, tonsil, lymph node, spleen, and intestine of those with fatal disease.The samples were added into HeLa, HEp-2, human embryonic lung fibroblasts, and human rhabdomyosarcoma