Assessing the efficacy of incompatible insect technique coupled with sterile insect technique (IIT-SIT) to manage large dengue clusters: study protocol for a randomized controlled trial

Abstract Background Aedes -borne diseases are expected to increase in geographical coverage and intensity due to climate change and rapid urbanization. It has been demonstrated that Wolbachia- mediated incompatible insect technique coupled with sterile insect technique (IIT-SIT) is highly effective in suppressing Aedes populations and subsequently reducing dengue risk. However, the efficacy of the tool in mitigating ongoing transmission is unknown. Methods We therefore outline a randomized controlled trial to be conducted in high-rise public housing estates in Singapore to assess the efficacy of IIT-SIT to mitigate active dengue transmission. Specifically, the study will determine whether the release of male Wolbachia -infected Aedes aegypti mosquitoes, applied on top of conventional vector control measures, can curtail the growth of dengue clusters (defined operationally by the Singapore National Environment Agency (NEA) as two or more reported dengue cases within a 150-m radius and with illness onset dates within 14 days of each other). This study will randomize eligible clusters into intervention/control arms in real time. Clusters assigned to the intervention arm will receive IIT-SIT treatment until cluster extinction (i.e., when no further cases are linked to the cluster). This trial closely mimics how IIT-SIT could be used as an additional tool for outbreak management, by treating areas with active dengue transmission in real-time. Conventional vector control measures will be carried out as per NEA’s usual outbreak management practices in both intervention and control clusters. The intervention efficacy will be estimated through two primary endpoints: (1) probability of cluster extinction, as estimated from the time-to-cluster extinction among intervention versus control clusters; and (2) final size of the dengue cluster, as estimated by the difference in the final number of dengue cases in intervention versus control clusters. Discussion This study will provide evidence from a randomized controlled trial for the efficacy of IIT-SIT in curbing ongoing transmission and provide an epidemiological basis for integrating IIT-SIT into the existing arsenal of outbreak management tools. The trial will assess the technology’s feasibility for operationalization, and identify difficulties in implementation prior to larger-scale use for outbreak control. Trial registration ClinicalTrials.gov, identifier: NCT06894901. Registered on 20 March 2025. Prospectively registered.