Phylogenetic Analysis of the VP1 Coding Region of Coxsackievirus A6 Detected in Hand-foot-and-mouth Disease During Surveillance from 2019 to 2024 in Japan

Hand, foot, and mouth disease (HFMD) caused by enteroviruses is common in children. Recently, coxsackievirus A6 (CVA6) has been identified as a major causative agent. In this study, we conducted a phylogenetic analysis of a part of the VP1 coding region of 194 CVA6 strains detected directly in 767 nasopharyngeal swab or stool samples of HFMD patients in Japan from 2019 to 2024. The detected CVA6 strains were classified into genotype D. Moreover, the strains detected from before 2019 to 2023 belonged to a cluster (cluster 1 and 2), whereas most of the strains detected in 2024 belonged to another cluster (cluster 3). Genetic identity among all detected CVA6 strains was 89.1-100%, and genetic identity within the cluster for each detected strain was 90.6-100% for the before 2019 (cluster 1) strains, 92.6-100% for the 2019-2023 (cluster 2) strains, and 94.5-100% for the 2024 (cluster 3) strains. Most of the strains detected in 2024 were similar to the strains detected in China in 2023, suggesting that the influx of new strains caused the 2024 outbreak in Japan. HFMD is one of the most prevalent diseases worldwide and its pathogenicity and antigenicity may change over time. Surveillance of the influx of new strains from outside Japan will become increasingly important.