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Evolution and spatio-temporal dynamics of Enterovirus A71 subgenogroups in Vietnam

Enterovirus A71 (EV-A71) is the major cause of severe hand, foot and mouth disease and viral encephalitis in children across the Asia-Pacific region, including in Vietnam which has experienced a high burden of disease in recent years. Multiple subgenogroups (C1, C4, C5 and B5) concurrently circulate in the region with a large variation in epidemic severity. The relative differences in their evolution and epidemiology were examined within Vietnam and globally. METHODS: A total of 752 VP1 gene sequences were analysed (413 generated in this study combined with 339 obtained from GenBank), collected from patients in 36 provinces in Vietnam during 2003-2013 along with epidemiological metadata. Globally representative VP1 gene datasets of subgenogroups were used to co-estimate time-resolved phylogenies and relative genetic diversity to infer virus origins and regional transmission network. RESULTS: Despite frequent virus migration between countries, the highest genetic diversity of individual subgenogroups was maintained independently for several years in specific Asian countries representing genogroup-specific sources of EV-A71 diversity. CONCLUSION: This study highlights a persistent transmission network of EV-A71, with specific Asian countries seeding other countries in the region and beyond, emphasising the need for improved EV-A71 surveillance and detailed genetic and antigenic characterisation.

Enterovirus A71 (EV-A71) is the major cause of severe hand, foot and mouth disease and viral encephalitis in children across the Asia-Pacific region, including in Vietnam which has experienced a high burden of disease in recent years. Multiple subgenogroups (C1, C4, C5 and B5) concurrently circulate in the region with a large variation in epidemic severity. The relative differences in their evolution and epidemiology were examined within Vietnam and globally.

METHODS:

A total of 752 VP1 gene sequences were analysed (413 generated in this study combined with 339 obtained from GenBank), collected from patients in 36 provinces in Vietnam during 2003-2013 along with epidemiological metadata. Globally representative VP1 gene datasets of subgenogroups were used to co-estimate time-resolved phylogenies and relative genetic diversity to infer virus origins and regional transmission network.

RESULTS:

Despite frequent virus migration between countries, the highest genetic diversity of individual subgenogroups was maintained independently for several years in specific Asian countries representing genogroup-specific sources of EV-A71 diversity.

CONCLUSION:

This study highlights a persistent transmission network of EV-A71, with specific Asian countries seeding other countries in the region and beyond, emphasising the need for improved EV-A71 surveillance and detailed genetic and antigenic characterisation.