Adult dengue vaccination in a low transmission setting: A modelling study in Singapore.

Dengue virus, with all four serotypes in cocirculation, has created significant epidemiological and economic burdens in Singapore. Despite integrated vector control programs, the magnitude and frequency of dengue outbreaks has increased over the last few decades, which highlights the limits of existing strategies. In this context, vaccination has emerged as a promising approach to enhance population immunity and complement ongoing efforts. Qdenga (TAK-003), a commercially available dengue vaccine, has been recommended by the World Health Organization Strategic Advisory Group of Experts (WHO-SAGE) for use in high-transmission settings. Although classified as a low transmission setting, Singapore faces a recurring public health burden from dengue, with high costs associated with both healthcare and sustained vector control. The age distribution of dengue in Singapore differs from high transmission settings, with more cases in young adults and hospitalizations concentrated among older individuals. These factors, combined with the complex efficacy profile of Qdenga, varying by baseline serostatus, infecting serotype, make it challenging to directly apply global vaccination recommendations to Singapore. Therefore, the population-level impact of introducing dengue vaccination remains uncertain, underscoring the need for context-specific evaluation. To estimate the potential public health impact of introducing routine dengue vaccination in Singapore, we develop an age-stratified, multi-serotype, compartmental transmission model informed by age-specific dengue seroprevalence and routine surveillance data. Our model predicts that vaccination can avert up to on average 9%, 12%, 7%, and 5% cases in DENV-1-4 dominant serotype scenarios respectively, over a 10-year routine vaccination program with 80% vaccine coverage. Moreover, dengue hospitalizations can be reduced up to 15% across all dominant serotype scenarios. Our results suggest that, in Singapore, targeting older age groups will be more beneficial than the 6-16-year window recommended by the WHO-SAGE for high-transmission settings. Vaccinating individuals aged 17-30 years achieves the greatest reduction in cases, whereas targeting those aged 51-70 years leads to the highest reduction in hospitalizations. Our model-based analysis provides useful insights to support policymakers and public health authorities in designing evidence-based, dengue vaccination strategies in Singapore. The findings also underscore the importance of tailoring dengue vaccination programs to local epidemiological conditions for effective disease control.