Estimating the force of infection of four dengue serotypes from serological studies in two regions of Vietnam

Abstract

Dengue is endemic in Vietnam with circulation of all four serotypes (DENV1-4) all year-round. It is hard to estimate the disease's true serotype-specific transmission patterns from cases due to its high asymptomatic rate, low reporting rate and complex immunity and transmission dynamics. Seroprevalence studies have been used to great effect for understanding patterns of dengue transmission. We tested 991 population serum samples (ages 1-30 years, collected 2013 to 2017), 531 from Ho Chi Minh City and 460 from Khanh Hoa in Vietnam, using a flavivirus protein microarray assay. By applying our previously developed inference framework to the antibody profiles from this assay, we can (1) determine proportions of a population that have not been infected or infected, once, or more than once, and (2) infer the infecting serotype in those infected once. With these data, we then use mathematical models to estimate the force of infection (FOI) for all four DENV serotypes in HCMC and KH over 35 years up to 2017. Models with time-varying or serotype-specific DENV FOI assumptions fit the data better than constant FOI. Annual dengue FOI ranged from 0.005 (95%CI: 0.003-0.008) to 0.201 (95%CI: 0.174-0.228). FOI varied across serotypes, higher for DENV1 (95%CI: 0.033-0.048) and DENV2 (95%CI: 0.018-0.039) than DENV3 (95%CI: 0.007-0.010) and DENV4 (95%CI: 0.010-0.016). The use of the PMA on serial age-stratified cross-sectional samples increases the amount of information on transmission and population immunity, and should be considered for future dengue serological surveys, particularly to understand population immunity given vaccines with differential efficacy against serotypes, however, there remains limits to what can be inferred even using this assay.

Fig 1. Age-specific and serotype-specific dengue seroprevalence in two locations in Vietnam (2013–2017).

The serotype-specific immune status distribution seen are with 95% confidence interval. Positive includes all those with primary and post-primary immune statuses (non-negative).

Fig 2. Dengue seroprevalence with immune status predicted by Model C.

Immune status was classified as negative, primary and post-primary. Individuals who had antibodies to DENV include primary and post-primary infections. The year is the year of sample collection. The serotype of those primary infections was further inferred by model D.

Fig 3. Annual FOI estimates.

Results by location with 95% credible interval from four assumptions: constant over time and non-serotype specific (Model 1), constant over time and serotype-specific (Model 2), time-varying (vary yearly but is common to all age groups) and non-serotype specific (Model 3), and time-varying (vary yearly but is common to all age groups) and serotype-specific (Model 4).

Fig 4. Observed data compared to estimated data from model 3 (the best model according to the Akaike information criterion (AICc)).

The Y-axis presents the proportion of dengue immune status regarding naive (left), primary infection with serotype-specific (middle) and post-primary infection (right) of the population in Ho Chi Minh from 2013 to 2017.