Historical reconstruction of the earliest enterovirus A71 epidemics in Japan in the 1960s.

Enterovirus A71 was first isolated in California in 1969, with the earliest retrospective detection traced back to 1963 in the Netherlands, but its early spread remains unclear. Using age-specific seroprevalence data from children aged 1-10 years in Kawasaki City, Japan, collected annually from 1966-1973, we applied serocatalytic models to estimate annual force of infection during 1959-1973. Several models were tested, incorporating different assumptions about time-varying force of infection, age-dependent susceptibility, and seroreversion, to identify the best fit to the data. Model comparison identified the models with independent annual infection probability or two distinct outbreak periods, both including age-dependent force of infection and seroreversion, as optimal. All top models consistently identified two major transmission periods: 1961-1962 and 1968-1969. The two-outbreak model estimated mean attack rates of 21.8% and 37.8% for the earlier and later outbreaks under seroreversion, and 19.8% and 34.9% under age-dependent force of infection. Our findings provide evidence of enterovirus A71 circulation in Japan during two distinct periods in the 1960s, coinciding with early detections in Europe and the USA, suggesting global distribution by that decade. This study underscores the value of testing archived sera for reconstructing pathogen emergence and spread.