Molecular evolutionary dynamics of enterovirus A71, coxsackievirus A16 and coxsackievirus A6 causing hand, foot and mouth disease in Thailand, 2000–2022

Abstract

Hand, foot and mouth disease (HFMD) is a public health threat worldwide, particularly in the Asia–Pacific region. Enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16), and CVA6 are the major pathogens causing HFMD outbreaks in several countries, including Thailand. We retrieved 385 VP1 nucleotide sequences, comprising 228 EV-A71, 33 CVA16, and 124 CVA6, deposited in the databases between 2000 and 2022 for molecular evolutionary characterization using Bayesian phylogeny. All EV-A71 identified belonged to genotype B, subgenotypes B4, and B5, and to genotype C, subgenotypes C1, C2, C4a, C4b, and C5. The analyzes demonstrated these viruses’ co-circulation and subgenotypic changes throughout the past two decades. The CVA16 was grouped in genotype B1, predominantly subgenotype B1a, and the CVA6 was grouped in subgenotype D3, clades 1–4. The tMRCA of EV-A71 genotypes B and C, CVA16 B1, and CVA6 D3 dated 1993.79, 1982.62, 1995.86, and 2007.31, respectively, suggesting that the viruses were likely introduced and cryptically circulated in Thailand before the HFMD cases were recognized. We demonstrated these viruses’ fluctuation and cyclical pattern throughout the two decades of observation. This study provided insight into evolutionary dynamics concerning molecular epidemiology and supported the selection of current genotype-matched vaccines, vaccine development, and implementation.

Beyond polio: Exploring non‐polio enteroviruses, global health preparedness, and the “Disease X” paradigm

“… 41 In 2022, research on EV‐A71 in China points to a worrying pattern in the effect and worldwide spread of NPEVs infections, with EV‐A71 being a special emphasis, as well as their potential to trigger pandemics. 42 Therefore, it is assumed that the following risk factors will likely lead to the emergence of a pandemic: human activity near wildlife; production of animal source foods with minimal employee supervision and an unclear supply chain; insect vectors; extremely high population density; limited surveillance and laboratory capacity. 43 , 44 , 45 Some countries still do not diagnose some enteroviruses adequately and this may be another risk factor of global spread to cause international public health emergency.…”

“…The next global health crisis most likely stems from a zoonotic event brought on by a virus that was transmitted to humans by animals, such as bats 41 . In 2022, research on EV‐A71 in China points to a worrying pattern in the effect and worldwide spread of NPEVs infections, with EV‐A71 being a special emphasis, as well as their potential to trigger pandemics 42 . Therefore, it is assumed that the following risk factors will likely lead to the emergence of a pandemic: human activity near wildlife; production of animal source foods with minimal employee supervision and an unclear supply chain; insect vectors; extremely high population density; limited surveillance and laboratory capacity 43–45 .…”