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. 2021 Jun 24:12:689658.
doi: 10.3389/fmicb.2021.689658. eCollection 2021.

Coxsackievirus A16 in Southern Vietnam

Le Nguyen Truc Nhu  1 , Le Nguyen Thanh Nhan  2 , Nguyen To Anh  1 , Nguyen Thi Thu Hong  1 , Hoang Minh Tu Van  1   3 , Tran Tan Thanh  1 , Vu Thi Ty Hang  1 , Do Duong Kim Han  1 , Nguyen Thi Han Ny  1 , Lam Anh Nguyet  1 , Du Tuan Quy  2 , Phan Tu Qui  4 , Truong Huu Khanh  2 , Nguyen Thanh Hung  2 , Ha Manh Tuan  3 , Nguyen Van Vinh Chau  4 , Guy Thwaites  1   5 , H Rogier van Doorn  1   5 , Le Van Tan  1
Affiliations

Coxsackievirus A16 in Southern Vietnam

Le Nguyen Truc Nhu et al. Front Microbiol. .

Abstract

Background: Hand, Foot and Mouth Disease (HFMD) is a major public health concern in the Asia-Pacific region. Most recent HFMD outbreaks have been caused by enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16), CVA10, and CVA6. There has been no report regarding the epidemiology and genetic diversity of CVA16 in Vietnam. Such knowledge is critical to inform the development of intervention strategies. Materials and Methods: From 2011 to 2017, clinical samples were collected from in- and outpatients enrolled in a HFMD research program conducted at three referral hospitals in Ho Chi Minh City (HCMC), Vietnam. Throat or rectal swabs positive for CVA16 with sufficient viral load were selected for whole genome sequencing and evolutionary analysis. Results: Throughout the study period, 320 CVA16 positive samples were collected from 2808 HFMD patients (11.4%). 59.4% of patients were male. The median age was 20.8 months (IQR, 14.96-31.41). Patients resided in HCMC (55.3%), Mekong Delta (22.2%), and South East Vietnam (22.5%). 10% of CVA16 infected patients had moderately severe or severe HFMD. CVA16 positive samples from 153 patients were selected for whole genome sequencing, and 66 complete genomes were obtained. Phylogenetic analysis demonstrated that Vietnamese CVA16 strains belong to a single genogroup B1a that clusters together with isolates from China, Japan, Thailand, Malaysia, France and Australia. The CVA16 strains of the present study were circulating in Vietnam some 4 years prior to its detection in HFMD cases. Conclusion: We report for the first time on the molecular epidemiology of CVA16 in Vietnam. Unlike EV-A71, which showed frequent replacement between subgenogroups B5 and C4 every 2-3 years in Vietnam, CVA16 displays a less pronounced genetic alternation with only subgenogroup B1a circulating in Vietnam since 2011. Our collective findings emphasize the importance of active surveillance for viral circulation in HFMD endemic countries, critical to informing outbreak response and vaccine development.

Keywords: Vietnam; coxsackievirus A16; evolution; hand foot mouth disease; picornavirus.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Enterovirus prevalence among HFMD cases in Vietnam during 2011–2017. The left Y axis shows the proportions of enterovirus serotypes detected among cases enrolled in the present study and the proportions of CVA16 cases included for whole genome sequencing. The right Y axis shows number of HFMD cases enrolled in the study between 2011 and 2017.
FIGURE 2
FIGURE 2
Maximum likelihood tree of CVA16 of Vietnam and global strains based on VP1 sequence. Vietnamese isolates (red-colored branch) belong to genogroup B1a containing strains from China, Thailand, Malaysia, Japan, France, and Germany.
FIGURE 3
FIGURE 3
Maximum clade credibility trees demonstrating the phylogeography of CVA16 isolates in Vietnam. The tree was constructed using VP1 sequences of Vietnamese sequences and branches are colored by regions.
FIGURE 4
FIGURE 4
Estimated relative genetic diversity of CVA16 in Vietnam by Bayesian skyline plot using VP1 sequence dataset.
See this image and copyright information in PMC

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