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. 2017 Dec 12;216(11):1371-1379.
doi: 10.1093/infdis/jix500.

Evolution and Spatiotemporal Dynamics of Enterovirus A71 Subgenogroups in Vietnam

Nguyen Thi Thanh Thao  1 , Celeste Donato  2 , Vu Thi Huyen Trang  1 , Nguyen Trung Kien  1 , Ph M Mai Thuy Trang  1 , Tran Quoc Khanh  1 , Dang Thi Nguyet  1 , October M Sessions  2 , Hoang Quoc Cuong  1 , Phan Trong Lan  1 , Vu Thi Que Huong  1 , H Rogier van Doorn  3 , Dhanasekaran Vijaykrishna  2   4
Affiliations

Evolution and Spatiotemporal Dynamics of Enterovirus A71 Subgenogroups in Vietnam

Nguyen Thi Thanh Thao et al. J Infect Dis. .

Abstract

Background: 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 analyzed (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 coestimate 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, emphasizing the need for improved EV-A71 surveillance and detailed genetic and antigenic characterization.

Keywords: Vietnam; enterovirus A71; hand foot and mouth disease; phylogenetics.

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Figures

Figure 1.
Figure 1.
Distribution of Vietnam EV-A71 strains analyzed in this study. A. Sample distribution from provinces in Vietnam over time. B. Subgenogroup distribution over time.
Figure 2.
Figure 2.
Maximum clade credibility (MCC) trees of EV-A71 subgenogroups. Nodes correspond to mean time of most recent common ancestors. Branches are colored by country of isolation. MCC trees with visible tip labels and 95% highest posterior density intervals are presented as Supplementary Figure 4A–G.
Figure 3.
Figure 3.
The relative genetic diversity of EV-A71 subgenogroups. Bayesian skyline plots were derived for global strains and a subset isolated in Vietnam. A measure of genetic diversity is given on the y axis with the 95% highest posterior density shown in solid color and the median as a dashed line.
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