Seroprevalence of coxsackievirus A21 neutralizing antibodies in Yamagata, Japan, between 1976 and 2019; coxsackievirus A21 has rarely affected young children.

Although coxsackievirus A21 (CV-A21) has been associated with an acute respiratory infection (ARI) as well as poliomyelitis-like paralysis, reports of CV-A21 detection have been quite limited both globally and in Japan. CV-A21 strains were isolated from five sporadic pediatric cases with ARI in 2019 in Yamagata, Japan. Neutralizing antibodies (NT Abs) were then measured against CV-A21 using sera collected in 1976, 1985, 1999, 2009, and 2019 in Yamagata, to clarify the longitudinal epidemiology of CV-A21. The total Ab-positive rate in each year was 15.2% (35/233), 10.7% (30/281), 14.3% (28/196), 3.1% (7/236), and 1.3% (3/226), respectively. Ab-positive rates generally increased with age, especially between 1976 and 1999. Among the total Ab-positive cases, the Ab titers were relatively low; 50 cases belonged to the 1:8-1:16, 40 to 1:32-1:64, 12 to 1:128-1:256, and 1 to 1:1024< groups, respectively. No Ab-positive cases under the age of 10 were observed in any of the years analyzed. In conclusion, this study and previous works suggested that CV-A21 is a unique enterovirus, which is not transmitted readily among young children but causes sporadic ARI cases mainly among those ≥15 years of age in the community.