Wolbachia-infected male Aedes aegypti mosquito releases stem dengue incidence

Releasing Wolbachia-infected male Aedes (A) aegypti mosquitoes were associated with a reduction in dengue incidence rates, a synthetic control study in Singapore has shown.

“We report the results of extensive field trials assessing the efficacy of deployments of male A aegypti mosquitoes infected with the wAlbB-SG strain of Wolbachia in reducing the incidence rate of dengue in Singapore as part of a suppression strategy,” said the researchers.

“Using a novel quasi-experimental approach, we identified that Wolbachia-infected male A aegypti mosquito releases protect against dengue incidence across all large-scale field trial release sites,” they said.

The researchers conducted large-scale field trials in Singapore involving the release of wAlbB-infected male A aegypti mosquitoes for dengue control via vector population suppression, from epidemiological week (EW) 27, 2018 to EW 26, 2022. The study comprised an at-risk population of individuals living in intervention sites (n=607,872) and those living in control sites (n=3,894,544). [Lancet Microbe 2024;5:e422-e432]

To adopt an expanding release strategy, two large towns (Yishun and Tampines) were chosen. For a targeted-release approach, two smaller towns (Bukit Batok and Choa Chu Kang) were selected. Releases were done twice weekly in high-rise public housing estates.

There was suppression of adult wildtype A aegypti populations across all sites, with the Gravitrap A aegypti index progressively reduced as Wolbachia coverage increased geographically. When more than 50-percent coverage was achieved in 2022, the overall Gravitrap A aegypti index for all sites was below 0.05. When sites had more than 6 months of Wolbachia releases, 80 percent suppressive efficacy on A aegypti abundance was achieved.

“Yearly intervention efficacies in the four trial sites and aggregate yearly intervention efficacies increased concomitantly with increased Wolbachia intervention coverage,” the researchers said.

In 2019, aggregate intervention efficacy was estimated to be 42.32 percent at 5.67-percent coverage. Intervention efficacy jumped to 57.65 percent as coverage increased to 23.3 percent in 2020, with an almost fourfold increase in the number of cases averted in 2020 vs 2019 (2,114.63 vs 516.9). According to the researchers, the increase might have been driven by the expansion of Wolbachia to two additional sites in 2020.

However, in 2021, intervention efficacy dropped to 48.52 percent as did the number of cases averted. This, according to the investigators, might have been due to 2021 being an interepidemic year.

“The highest level of intervention efficacy was achieved with 68.08-percent coverage in EW 26, 2022 (65.81 percent), with individual town intervention efficacies ranging from 52.85 percent to 72.21 percent for 2022. From EW1 to EW 26, 2022, Wolbachia interventions were associated with 906.88 cases being averted overall,” they explained.

Taken together, Wolbachia releases were projected to have an aggregate intervention efficacy of 56.88 percent (total cases) and 63.6 percent (clustered cases) from EW 1, 2019 to EW 26, 2022 in the four field trial sites, despite an aggregate coverage of only 34.49 percent in all sites during the trial period.

New vector control strategies warranted

Given the lack of therapeutics and good vaccines, conventional vector control remains the primary tool for mitigating the spread of dengue. However, these measures yield diminishing returns when populations of A aegypti plummet despite reports of successfully mitigating the dengue burden in Singapore. [PLoS Negl Trop Dis 2023;17:e0011400; Am J Epidemiol 2019;188:1529-1538]

“Against the backdrop of climate change and lowering herd immunity, conventional approaches for vector control are insufficient to mitigate dengue outbreaks. Therefore, there is a pertinent need for new vector control strategies,” the researchers said.

“Our results demonstrated the potential of Wolbachia-mediated incompatible insect technique (IIT) for strengthening dengue control in tropical cities, where dengue burden is the greatest,” they said. “This evidence is important given the urgent need for new forms of vector control to stem the global increase in dengue incidence.”

However, the researchers were quick to point out that this method should not be considered a complete replacement for conventional strategies. “[B]oth the entomological and epidemiological effects of the IIT are likely to be maximized if it is used to complement and enhance, rather than to replace, conventional vector control measures.”