Page 1 of 17 Title: Targeting Vaccinations for the Licensed Dengue Vaccine: Considerations for Serosurvey Design

Objective: WHO recommends countries consider dengue vaccination in geographic settings only where epidemiological data indicate a high burden of disease. In defining target populations, WHO recommend that prior infection with any dengue serotype should be >70% seroprevalence. Here we address considerations for serosurvey design in the context of the newly licensed CYD-TDV vaccine. Methods: To explore how the design of seroprevalence surveys (age range, survey size) would affect estimates of the force of infection, for every combination of age range, total survey size, transmission setting, and test sensitivity/specificity, 100 age-specific seroprevalence surveys were simulated using a beta-binomial distribution and a simple catalytic model. The transmission intensity was then re-estimated using a MetropolisHastings Markov Chain Monte-Carlo algorithm. Findings: Sampling from a wide age range led to more accurate estimates than having a larger sample size. This finding was consistent across all transmission settings. The optimal age range to sample from differed by transmission intensity, with younger and older ages being important in high and low transmission settings respectively. The optimum test sensitivity and specificity given an imperfect test also differed by transmission setting with high sensitivity being important in high transmission settings and high specificity important in low transmission settings. Conclusions: When assessing the suitability for vaccination by seroprevalence surveys, countries should ensure that an appropriate age range is sampled, taking into account epidemiological evidence about the local burden of dengue.