Seroepidemiology of enterovirus A71 infection in prospective cohort studies of children in southern China, 2013-2018

Abstract

Enterovirus A71 (EV-A71)–related hand, foot, and mouth disease (HFMD) imposes a substantial clinical burden in the Asia Pacific region. To inform policy on the introduction of the EV-A71 vaccine into the National Immunization Programme, we investigated the seroepidemiological characteristics of EV-A71 in two prospective cohorts of children in southern China conducted between 2013 and 2018. Our results show that maternal antibody titres declined rapidly in neonates, with over half becoming susceptible to EV-A71 at 1 month of age. Between 6 months and 2 years of age, over 80% of study participants were susceptible, while one third remained susceptible at 5 years old. The highest incidence of EV-A71 infections was observed in children aged 5-6 months. Our findings support EV-A71 vaccination before 6 months for birth cohorts in southern China, potentially with a one-time catch-up vaccination for children 6 months-5 years old. More regionally representative longitudinal seroepidemiological studies are needed to further validate these findings.

Age-time-specific transmission of hand-foot-and-mouth disease enterovirus serotypes in Vietnam: A catalytic model with maternal immunity

“…Linear functions, estimating a faster decline in maternal immunity than exponential functions (Supplementary Fig. 23), aligns closer with the serological cohort study indicating complete maternal antibody loss before 1 year old ( Nguyen Tran et al, 2011 , Yang et al, 2022 ). Particularly, models assuming no maternal immunity demonstrate significantly poorer fits to the data compared to those with maternal immunity, as shown in the obviously larger DIC value when assuming no maternal immunity (1,984 for model constructing FOI with piecewise function, 2,098 for model constructing FOI with Farrington’s function, see Supplementary Fig.…”

“…Our inference of the HFMD age-structure transmission pattern provides useful insights into the implementation of vaccine programs in the region, especially the optimal vaccine age group and target vaccine age group to efficiently control the virus transmission and reduce the risk of severe illness. New-born infants were protected by maternal antibodies which were decreased to undetectable level by 1 year old ( Nguyen Tran et al, 2011 , Zhou et al, 2022 , Fu et al, 2016 , Yang et al, 2022 ). Children of age 1 to 2 years are estimated to be the most vulnerable to HFMD infections, given the highest risk of infection and the lowest cumulative immune protection, which was also observed in the case data of East and South China ( Le et al, 2022 , Di et al, 2014 ).…”

“…(1) . For maternal immunity, we assumed that all new-born infants were protected by maternal immunity, and maternal immunity gradually diminished and completely disappeared before age 1 year old ( Nguyen Tran et al, 2011 , Zhou et al, 2022 , Fu et al, 2016 , Yang et al, 2022 ). Sensitivity test was conducted with different proportion of infants born with maternal immunity.…”

“…Previous studies included maternal immunity under the catalytic model framework by using the analytic function of Susceptible-Infectious-Recovered (SIR) model with maternal immunity or assuming a delay of infection with pre-fixed maternal immunity waning length ( Pons-Salort et al, 2023 , Zhao et al, 2016 ). For HFMD, there is little research applying the models assuming the existence of maternal immunity while maternal immunity of HFMD is supported by various serological evidence from previous studies ( Nguyen Tran et al, 2011 , Zhou et al, 2022 , Fu et al, 2016 , Yang et al, 2022 ). Given that HFMD is a disease primarily infecting children, neglecting maternal immunity during modelling may introduce bias to the estimations.…”