Citywide Wolbachia Male‑Release Trial: Key Findings for Clinicians and Public Health

A citywide Wolbachia male-release trial in Singapore was described as a cluster-randomized trial using a test-negative design evaluating repeated releases of male Aedes aegypti infected with the wAlbB strain of Wolbachia pipientis across urban neighborhoods.

Based on the trial results, investigators reported a lower risk of symptomatic dengue among residents in intervention areas, with protective efficacy ranging from 71–72% among residents with 3 to 12 months or more of Wolbachia mosquito exposure, corresponding to odds ratios of 0.28 to 0.29 (calculated as [1−odds ratio]×100). This two-year experiment divided neighborhoods into clusters and paired mosquito surveillance with laboratory-confirmed dengue diagnoses analyzed using a test-negative framework.

Researchers selected 15 geographic population clusters in Singapore and randomly assigned eight clusters to receive the intervention and seven clusters to serve as untreated controls. The intervention was sustained over a 24-month trial period. Outcome assessment included entomologic monitoring in the field and analysis of symptomatic dengue diagnosed through national reporting systems, with the primary endpoint defined as the odds ratio for Wolbachia exposure among laboratory-confirmed dengue cases compared with test-negative controls.

The intervention involved releases of male Aedes aegypti mosquitoes infected with the wAlbB strain of Wolbachia, leveraging cytoplasmic incompatibility in which mating between infected males and wild-type females produces nonviable offspring. In entomologic monitoring, baseline average adult female mosquito abundance (number of adult females trapped divided by number of traps) was 0.18 in intervention clusters and 0.19 in control clusters. From 3 months after initiation of releases through the end of the 24-month trial period, average abundance was 0.041 in intervention clusters and 0.277 in control clusters, reflecting suppression of wild-type female populations in intervention areas.

On the epidemiologic side, intention-to-treat analysis at 6 months or more showed that 6% of residents tested in intervention clusters were dengue-positive (354 of 5722 tests) compared with 21% in control clusters (1519 of 7080 tests). The investigators interpreted these findings as evidence that releases of Wolbachia-infected male mosquitoes can reduce vector populations and lower the risk of dengue infection, complementing existing dengue control measures.

Taken together, the research presents a citywide picture in which sustained releases of Wolbachia-infected male mosquitoes were associated with both entomologic suppression and a lower risk of symptomatic dengue in intervention clusters.

Key Takeaways:

• The report describes a randomized cluster experiment across multiple residential areas with sustained, twice-weekly sterile male releases over a two-year period.
• Investigators observed marked suppression of wild female Aedes aegypti in intervention clusters based on field trapping and counting.
• The research reports a lower symptomatic dengue positivity signal in intervention versus control areas and relays authors’ framing that the approach could complement other dengue control strategies, including vaccines.