In recent years, enterovirus 71 (EV71) has been a cause of numerous outbreaks of hand-foot-and-mouth disease, with severe neurological complications in the Asia-Pacific region. The reemergence in Taiwan of EV71 genotype B5 in 2008 resulted in the largest outbreak of EV71 in Taiwan in the past 11 years. Phylogenetic analyses indicated that dominant genotype changes from B to C or C to B occurred at least three times between 1986 and 2008. Furthermore, antigenic cartography of EV71 by using neutralization tests revealed that the reemerging EV71 genotype B5 strains formed a separate cluster which was antigenically distinct from the B4 and C genotypes. Moreover, analyses of full-length genomic sequences of EV71 circulating in Taiwan during this period showed the occurrence of intra-and interserotypic recombination. Therefore, continuous surveillance of EV71 including the monitoring of genetic evolution and antigenic changes is recommended and may contribute to the development of a vaccine for EV71.The genus Enterovirus ([EV] family Picornaviridae) contains numerous viruses that are pathogenic to humans. Human EVs (HEVs) have been classified into four species, HEV-A, HEV-B, HEV-C, and HEV-D, based on their sequence homologies (48). In contrast to other etiological agents of hand-foot-and-mouth disease that tend to cause mild and self-limiting disease, EV71 infection is often associated with other clinical manifestations including acute neurologic symptoms, such as poliomyelitis-like paralysis, encephalitis, aseptic meningitis, shock, and cardiac dysfunction (32).Since 1969, when EV71 was first isolated in California, EV71-associated outbreaks have been reported worldwide (42). EV71 infection reached epidemic proportions, causing sporadic cases or outbreaks and then becoming prevalent around the AsiaPacific region including Australia, Malaysia, Singapore, Japan, China, and Taiwan for the past 12 years (1, 16-18, 20, 25, 26, 28, 46, 53). Phylogenetic studies have classified EV71 into genotypes A, B, and C, which can be further subdivided into subgentotypes B1 to B5 and C1 to C5 (7,8,17,20,22,25,28,41,45,52,53). These reports indicated that the dominant EV71 strains circulating in the Asia-Pacific region varied genetically, suggesting that the virus was evolving.Intertypic or intratypic recombination of EV71 has been reported to occur frequently in the region encoding the nonstructural proteins and could potentially influence the replication, tissue tropism, and virulence of EV71 (10,11,18). These studies emphasized the importance of full-genome sequencing for the surveillance of EV71 evolution. Therefore, to analyze the evolution of EV71, we performed phylogenetic analysis of the Taiwan isolates from 1986 and from 1998 and 2008 based on the complete genomic sequences. In addition, neutralizing activities of human antiserum against the various subgenotypes of EV71 were investigated to evaluate the antigenic changes of EV71. We found evidence for intertypic and intratypic recombination and demonstrated variation in anti...

Enterovirus (EV) infections are common. There are more than 60 known serotypes, and each has different epidemiologic or medical importance. Over 700 physicians from 75% of basic administrative units of Taiwan participated in the "Sentinel Physician Surveillance of Infectious Disease" and reported weekly to the Center for Disease Control-Taiwan with data on various infections. Data of laboratory-confirmed EV infections from this surveillance between 2000 and 2005 was analyzed. EV serotypes were determined by immunofluorescence staining and/or viral VP1 sequence analysis. A total of 12,236 EV cases, or approximately 1,300-2,500 per year, were identified, and 52% of the cases occurred between April and July. The median age was 3 years, and 57.6% of patients were male. Coxsackievirus A (CA) 16 and EV71, which primarily manifest as hand-foot-and-mouth disease, were the most prevalent serotypes every year except 2004. Other prevalent serotypes and associated symptoms varied from year to year. Echovirus (E) 30 and E6, which are associated with aseptic meningitis, were prevalent in 2001 and 2002, CA4 and CA10, which cause herpangina, were predominant in 2004, and coxsackievirus B (CB) 4 and CB3, which are associated with neonatal febrile disease, were most common in 2004 and 2005, respectively. Some of these epidemics overlapped with outbreaks of the same serotypes in other Asian Pacific countries. Of all serotypes, EV71 was associated with the highest number of severe complications in patients. Surveying the epidemic pattern, disease spectra, and severity associated with each EV serotype provided important information for public health and medical personnel.

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