To our knowledge, this study provides the first comprehensive epidemiologic and virologic survey of HFMD, CVA16, and HEV71 infection in Vietnam. Similar to the situation in other countries, HEV71 infection was associated with a subset of HFMD cases in which acute neurologic disease developed. Our epidemiologic and phylogenetic data suggest that both CVA16 and HEV71 circulate endemically in southern Vietnam.
Nearly one third of the HEV71-associated HFMD cases identified in our study were complicated by acute neurologic disease. The case-fatality rates of 1.7% in all identified HEV71 infections and 5.9% in HEV71 acute neurologic disease cases are higher than those observed in other studies (7
). However, the case-fatality rates calculated in our study may overestimate the true values because only HFMD patients who were brought for treatment at a major children’s hospital were included in the study. The best estimates of case-fatality rates for HEV71 infection have come from a large seroepidemiologic study of the 1998 HFMD epidemic in Taiwan (32
); the authors estimated a case-fatality rate of 96.96 per 100,000 population in infants <1 year of age, declining to 6.64 per 100,000 population in children >5 years of age. To rigorously determine the incidence and case-fatality rate of HEV71 infection in southern Vietnam, a similar population-based seroepidemiologic study should be undertaken.
Although cases of HFMD were identified throughout the year, 2 periods of increased prevalence were identified—from March through May and from September through December. In southern Vietnam, these months are interim periods between the dry and wet seasons. CVA16 was the predominant virus isolated in the first period, and HEV71 infection was the predominant virus isolated in the second period. Ongoing epidemiologic surveillance will be necessary to determine whether this pattern of HFMD and enterovirus activity recurs in a regular annual cycle.
Phylogenetic analysis based on nucleotide sequence alignment of the complete VP1 gene of 23 representative strains of HEV71 from southern Vietnam showed that they belonged to 3 subgenogroups, C1, C4, and to the previously undescribed subgenogroup C5. Since 1997, 2 genetically distinct major lineages (B, C) of HEV71 have circulated in different parts of the Asia-Pacific region (6
). Viruses belonging to genogroup B have predominated in Southeast Asia, whereas viruses belonging to genogroup C have predominated in northern Asia (6
). Before 1997, HEV71 strains belonging to subgenogroup C1 were identified in several small outbreaks around the world (15
). Since 1997, subgenogroup C1 viruses have circulated endemically in the Asia-Pacific region and have been found to cocirculate as a minor subgenogroup together with a predominant HEV71 subgenogroup during several outbreaks (6
). In this study, subgenogroup C1 viruses comprised only 1.1% of HEV71 strains isolated, indicating low-level circulation. Viruses belonging to subgenogroup C2 have circulated widely in the Asia-Pacific region between 1998 and 2000 (9
) and were responsible for the large outbreak in Taiwan in 1998 (6
). Two new genetic lineages of genogroup C, subgenogroups C3 and C4, have emerged recently in northern Asia. Viruses belonging to subgenogroup C3 first appeared in the People’s Republic of China in 1998 (6
) and reemerged in South Korea in 2000 (6
). Viruses belonging to subgenogroup C4 were first identified in the People’s Republic of China in 1998 and again in 2000 (35
) before their identification in southern Vietnam during 2005. Furthermore, a new subgenogroup, C5, circulated widely in southern Vietnam throughout 2005 and became the predominant virus strain identified during the second half of the year.
Our data indicate that the molecular epidemiology of HEV71 in southern Vietnam conforms to the northern Asian epidemiologic pattern of endemic circulation of genogroup C virus strains, with evidence of the ongoing evolution of new subgenogroups, similar to that observed for genogroup B HEV71 strains in Southeast Asia (6
). Furthermore, the year-round isolation and circulation of multiple independent genetic lineages of HEV71 (36
) suggest that this virus circulates endemically within the human population of southern Vietnam.
In conclusion, this study has established that HEV71 circulates endemically in southern Vietnam and thus represents a substantial threat to the health of children in this region. Improvements in public sanitation and personal hygiene alone are unlikely to prevent HEV71 transmission within the community. A vaccine is necessary to prevent HEV71-induced neurologic disease in susceptible children. However, until such a vaccine is available, virus activity in the community must be monitored through the establishment and maintenance of sentinel surveillance.