Adult dengue vaccination in Singapore: A modelling study to inform policy

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 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 by 12%-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. Authors summarySingapore is experiencing more frequent dengue outbreaks, which impose a substantial burden through treatment costs and sustained vector control programs. Vaccination is a key public health measure that can help ease this burden by complementing existing control efforts. In clinical trials, Qdenga (TAK-003) demonstrated consistent protections against DENV-1 and DENV-2 among vaccine recipients irrespective of their baseline serostatus, but uncertainty remains for DENV-3 and DENV-4. Although WHO-SAGE recommended its use among children aged 6-16 years in high dengue transmission setting, uncertainty arises when extrapolating these recommendations to low transmission settings like Singapore. Moreover, unlike high transmission settings, Singapore currently shows a different age pattern of dengue burden, with higher incidence in young adults and more severe outcomes among older individuals, highlighting the need to contextualize these global recommendations using country-specific data and modelling approaches. To address this, we developed a detailed modelling framework that integrates local epidemiological characteristics and operational aspects of vaccine implementation and evaluated the potential impact of introducing a routine vaccination program in Singapore. We show that, with 80% coverage, vaccination can avert up to 12% of reported cases and 15% of hospitalizations over a 10-year period, with impact varying mainly by circulating serotype and target age group. Our findings suggest that in low-transmission settings like Singapore, vaccinating adults will achieve a greater public health impact than targeting children, as currently recommended for high-transmission settings by WHO-SAGE. These findings provide timely evidence to support national policy discussions on dengue vaccination in Singapore and other low-transmission settings, where adult disease burden is substantial.