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

Abstract

Hand, foot and mouth disease (HFMD) is highly prevalent in the Asia Pacific region, particularly in Vietnam. To develop effective interventions and efficient vaccination programs, we inferred the age-time-specific transmission patterns of HFMD serotypes enterovirus A71 (EV-A71), coxsackievirus A6 (CV-A6), coxsackievirus A10 (CV-A10), coxsackievirus A16 (CV-A16) in Ho Chi Minh City, Vietnam from a case data collected during 2013-2018 and a serological survey data collected in 2015 and 2017. We proposed a catalytic model framework with good adaptability to incorporate maternal immunity using various mathematical functions. Our results indicate the high-level transmission of CV-A6 and CV-A10 which is not obvious in the case data, due to the variation of disease severity across serotypes. Our results provide statistical evidence supporting the strong association between severe illness and CV-A6 and EV-A71 infections. The HFMD dynamic pattern presents a cyclical pattern with large outbreaks followed by a decline in subsequent years. Additionally, we identify the age group with highest risk of infection as 1-2 years and emphasise the risk of future outbreaks as over 50% of children aged 6-7 years were estimated to be susceptible to CV-A16 and EV-A71. Our study highlights the importance of multivalent vaccines and active surveillance for different serotypes, supports early vaccination prior to 1 year old, and points out the potential utility for vaccinating children older than 5 years old in Vietnam.

Keywords: Catalytic model; Force of infection; Hand, foot and mouth disease; Serological data.

Fig. 1

The reported number of cases by age and calendar year in the case data and from the model estimation (Model $LinPw$) and the seroprevalence (seropositive threshold titre of 1:8) by age and calendar year in the serological survey data and from the model estimation (Model $LinPw$). a. The age-time-specific reported number of cases in case data and the corresponding estimation. b. The age-time-specific seroprevalence in serological survey data and the corresponding estimation. The solid points and the error bars are the data points and the 95% confidence intervals calculated by exact method (Liddell, 1984, Hirji, 2005) (no solid points for age group $[0,1)$ in b. for 2017 panel because the serological survey data does not include subjects with age $<$1 year old collected in 2017). The lines and the coloured areas are the estimated values and the 95% confidence intervals inferred from posterior distributions of the parameters. The colours correspond to 4 serotypes. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

The estimation of age-time-specific FOI from Model $LinPw$ and the distribution of reported cases in case data by time. a. The estimation of FOI. The solid points are the estimates. The coloured areas are the 95% confidence intervals inferred from posterior distributions of the parameters. The colours correspond to 4 serotypes. b. The reported number of cases by time and virus serotypes in case data. The solid points are the data points. The coloured areas are the 95% confidence intervals calculated by exact method (Liddell, 1984). The colours correspond to 4 serotypes. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

The estimation of seroprevalence by age, time and virus serotypes (Model $LinPw$). The solid points are the estimates. The coloured areas are the 95% confidence intervals inferred from posterior distributions of the parameters. The colours correspond to 4 serotypes. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)