Male Wolbachia-infected Aedes aegypti deployments suppresses Aedes aegypti populations: a large-scale cluster-randomised controlled trial

Background: Wild-type female Aedes aegypti which mates with male Wolbachia-infected Aedes aegypti mosquito produces infertile offspring due to cytoplasmic incompatibility. Sustained releases of Wolbachia-infected males can potentially suppress wild-type mosquito populations. Methods: We conducted a large-scale cluster-randomised trial using Wolbachia-mediated incompatible insect technique-sterile insect technique (IIT-SIT) for the control of dengue in Singapore. This involved releases of male wAlbB-infected Ae. aegypti mosquitoes which were irradiated prior to releases to sterilise residual females to avoid an establishment of wAlbB-infected Ae. aegypti mosquitoes in the field. Fifteen clusters, comprising an estimated 730,328 residents, were randomised into two arms: 8 clusters received deployments of male wAlbB-infected Ae. aegypti (intervention clusters) and 7 clusters received no deployments (control clusters). All clusters practised baseline vector control measures. We assessed the impact of Wolbachia releases on Ae. aegypti and Ae. albopictus abundance using a differences-in-differences framework. The interaction-weighted estimator was used to account for the staggered adoption setting and the dynamic effect of releasing male wAlbB-infected Ae. aegypti on wild-type Ae. aegypti and Ae. albopictus abundance. Results: Intervention clusters which received male wAlbB-infected Ae. aegypti had increasing reductions in Ae. aegypti abundance when subject to longer periods of intervention. In the 0–25 weeks following release, intervention efficacies (IE) were moderate (0-12 weeks: 29.15% [21.80%, 35.24%], 13-25 weeks: 60.35% [50.85%, 66.77%]). Whereas one year post intervention, reductions in Ae. aegypti abundance in intervention clusters were sustained at around 90% (52-103 weeks range: 90.20%–91.26%). Concomitantly, 78-weeks post intervention to the end of intervention, there was an increase in Ae. albopictus abundance in intervention clusters (78-103 weeks range: -32.43% – -63.10%). However, the average weekly increase in the Ae. albopictus abundance due to male wAlbB-infected Ae. aegypti releases was low and estimated to range between 0.0103 – 0.0482. Conclusion: Our results demonstrate the high efficacy of Wolbachia-mediated IIT-SIT in reducing Ae. aegypti abundance.