Dengue Suppression by Male Wolbachia-Infected Mosquitoes.

Abstract

Wild-type female <i>Aedes aegypti</i> mosquitoes that mate with male <i>A. aegypti</i> mosquitoes that have been infected with the <i>w</i>AlbB strain of <i>Wolbachia pipientis</i> bacteria produce nonviable offspring owing to cytoplasmic incompatibility. Repeated releases of wolbachia-infected males can potentially suppress wild-type mosquito populations and reduce the risk of dengue virus infection. We conducted a trial involving the release of male <i>A. aegypti</i> mosquitoes infected with the <i>w</i>AlbB strain of wolbachia bacteria for the control of dengue in Singapore, a tropical city-state. In this cluster-randomized trial with test-negative controls, we divided 15 geographic population clusters into two groups: 8 clusters received deployments of male wolbachia-infected mosquitoes (intervention clusters) and 7 clusters received no deployments (control clusters). The primary end point was the diagnosis of symptomatic dengue virus infection of any severity caused by any serotype of the virus, as measured by the odds ratio for the distribution of wolbachia exposure among laboratory-confirmed reported dengue cases as compared with test-negative controls. A total of 393,236 residents lived in the intervention clusters, and 331,192 lived in the control clusters. Adult wild-type <i>A. aegypti</i> populations were suppressed across the intervention clusters. The baseline average abundance of the mosquitoes (number of adult female mosquitoes trapped divided by number of traps) was 0.18 and 0.19 in the intervention and control clusters, respectively; from 3 months after the initiation of the intervention until the end of the 24-month trial period, the average abundance was 0.041 and 0.277, respectively. In the intention-to-treat analysis at 6 months or more, the percentage of residents in the intervention clusters who were dengue-positive was lower than that in the control clusters (354 of 5722 tests [6%] vs. 1519 of 7080 tests [21%]). The protective efficacy of the intervention, calculated as (1 - odds ratio) × 100, ranged from 71 to 72% with 3 to 12 months or more of wolbachia mosquito exposure, as represented by odds ratios of 0.28 to 0.29. Release of sterile wolbachia-infected male <i>A. aegypti</i> mosquitoes reduced vector populations and the risk of dengue infection in Singapore. (Funded by the Singapore Ministry of Finance and others; ClinicalTrials.gov number, NCT05505682.).