Dataset Information

The burden of hand, foot, and mouth disease among children under different vaccination scenarios in China: a dynamic modelling study.

ABSTRACT:

Background

Hand, foot, and mouth disease (HFMD) is a common illness in young children. A monovalent vaccine has been developed in China protecting against enterovirus-71, bivalent vaccines preventing HFMD caused by two viruses are under development.

Objective

To predict and compare the incidence of HFMD under different vaccination scenarios in China.

Methods

We developed a compartmental model to capture enterovirus transmission and the natural history of HFMD in children aged 0-5, and calibrated to reported cases in the same age-group from 2015 to 2018. We compared the following vaccination scenarios: different combinations of monovalent and bivalent vaccine; a program of constant vaccination to that of pulse vaccination prior to seasonal outbreaks.

Results

We estimate 1,982,819, 2,258,846, 1,948,522 and 2,398,566 cases from 2015 to 2018. Increased coverage of monovalent vaccine from 0 to 80% is predicted to decrease the cases by 797,262 (49.1%). Use of bivalent vaccine at an 80% coverage level would decrease the cases by 828,560. Use of a 2.0× pulse vaccination for the bivalent vaccine in addition to 80% coverage would reduce cases by over one million. The estimated R₀ for HFMD in 2015-2018 was 1.08, 1.10, 1.35 and 1.17.

Conclusions

Our results point to the benefit of bivalent vaccine and using a pulse vaccination in specific months over routine vaccination. Other ways to control HFMD include isolation of patients in the early stage of dissemination, more frequent hand-washing and ventilation, and better treatment options for patients.

SUBMITTER: Liu Z

PROVIDER: S-EPMC8259139 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundHand, foot, and mouth disease (HFMD) is a common childhood illness caused by serotypes of the Enterovirus A species in the genus Enterovirus of the Picornaviridae family. The disease has had a substantial burden throughout East and Southeast Asia over the past 15 y. China reported 9 million cases of HFMD between 2008 and 2013, with the two serotypes Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) being responsible for the majority of these cases. Three recent phase 3 clinical trials showed that inactivated monovalent EV-A71 vaccines manufactured in China were highly efficacious against HFMD associated with EV-A71, but offered no protection against HFMD caused by CV-A16. To better inform vaccination policy, we used mathematical models to evaluate the effect of prospective vaccination against EV-A71-associated HFMD and the potential risk of serotype replacement by CV-A16. We also extended the model to address the co-circulation, and implications for vaccination, of additional non-EV-A71, non-CV-A16 serotypes of enterovirus.Methods and findingsWeekly reports of HFMD incidence from 31 provinces in Mainland China from 1 January 2009 to 31 December 2013 were used to fit multi-serotype time series susceptible-infected-recovered (TSIR) epidemic models. We obtained good model fit for the two-serotype TSIR with cross-protection, capturing the seasonality and geographic heterogeneity of province-level transmission, with strong correlation between the observed and simulated epidemic series. The national estimate of the basic reproduction number, R0, weighted by provincial population size, was 26.63 for EV-A71 (interquartile range [IQR]: 23.14, 30.40) and 27.13 for CV-A16 (IQR: 23.15, 31.34), with considerable variation between provinces (however, predictions about the overall impact of vaccination were robust to this variation). EV-A71 incidence was projected to decrease monotonically with higher coverage rates of EV-A71 vaccination. Across provinces, CV-A16 incidence in the post-EV-A71-vaccination period remained either comparable to or only slightly increased from levels prior to vaccination. The duration and strength of cross-protection following infection with EV-A71 or CV-A16 was estimated to be 9.95 wk (95% confidence interval [CI]: 3.31, 23.40) in 68% of the population (95% CI: 37%, 96%). Our predictions are limited by the necessarily short and under-sampled time series and the possible circulation of unidentified serotypes, but, nonetheless, sensitivity analyses indicate that our results are robust in predicting that the vaccine should drastically reduce incidence of EV-A71 without a substantial competitive release of CV-A16.ConclusionsThe ability of our models to capture the observed epidemic cycles suggests that herd immunity is driving the epidemic dynamics caused by the multiple serotypes of enterovirus. Our results predict that the EV-A71 and CV-A16 serotypes provide a temporary immunizing effect against each other. Achieving high coverage rates of EV-A71 vaccination would be necessary to eliminate the ongoing transmission of EV-A71, but serotype replacement by CV-A16 following EV-A71 vaccination is likely to be transient and minor compared to the corresponding reduction in the burden of EV-A71-associated HFMD. Therefore, a mass EV-A71 vaccination program of infants and young children should provide significant benefits in terms of a reduction in overall HFMD burden.