Abstract
Hand, Foot, and Mouth Disease (HFMD) is a major public health issue in the Asia-Pacific region. Our research program aims to address unanswered questions about clinical, epidemiology, pathogen evolution, cost of illness, and host-genetic makers associated with severe HFMD in Vietnam. A multi-hospital-based observational study has been conducted at three referral hospitals in Ho Chi Minh City, Vietnam since 2013. Demographic, clinical data, and cost of illness were collected alongside clinical specimens. Multiplex PCR and next-generation sequencing were employed to identify enterovirus serotypes and to study pathogen evolution, respectively. A genome-wide association-based approach was used to explore genetic markers of disease severity. From 2013 to 2017, 2,191 HFMD patients were enrolled. More than twenty enterovirus serotypes were detected in 84.3 per cent of patients. EV-A71 was the major cause, accounting for 22 per cent of total number of cases, followed by CV-A6 (21%), CV-A16 (13%), and CV-A10 (8%). Interestingly, these four common enteroviruses replaced each other during the study period. EV-A71 and CV-A6 were the two most predominant viruses detected in 2013 and 2014. However, CV-A6 was replaced by CV-A16 and CV-A10 in 2015 and 2016, respectively. A total of 396 whole-genome sequences (EV-A71 (n = 200), CV-A6 (n = 98), CV-A10 (n = 66), and CV-A16 (n = 32)) were obtained. Phylogenetic analysis showed that EV-A71 subgenogroup B5 has replaced C4 in 2012, and, since then, B5 has continued to circulate predominantly, while C4 has been sporadically detected. All Vietnamese CV-A6 isolates belonged to genogroup A, which has caused large outbreaks of HFMD worldwide. Costs of illness varied between disease severities, ranging from $USD 244 [95% confidence interval (95% CI): 230–258] per patient for grade 2A (mild) to $USD 1984 (95% CI: 1,752–2,227) for grade 3 (severe). The genome-wide association study identified two genetic markers potentially associated with severe HFMD. The results highlight that active surveillance and understanding pathogen evolution are essential to inform public health in prioritizing the development of intervention strategies. Efforts to unravel the evolutionary process of Vietnamese CV-A10 and CV-A16 in relation to global strains are ongoing. An independent cohort is needed to replicate the preliminary findings of the genome-wide association study.
The public health utility of genome-wide association study results for smoking behavior
