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

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.