Aedes aegypti abundance and insecticide resistance profiles in the Applying Wolbachia to Eliminate Dengue trial.

The Applying Wolbachia to Eliminate Dengue (AWED) trial was a parallel cluster randomised trial that demonstrated Wolbachia (wMel) introgression into Ae. aegypti populations reduced dengue incidence. In this predefined substudy, we compared between treatment arms, the relative abundance of Ae. aegypti and Ae. albopictus before, during and after wMel-introgression. Between March 2015 and March 2020, 60,084 BG trap collections yielded 478,254 Ae. aegypti and 17,623 Ae. albopictus. Between treatment arms there was no measurable difference in Ae. aegypti relative abundance before or after wMel-deployments, with a count ratio of 0.96 (95% CI 0.76, 1.21) and 1.00 (95% CI 0.85, 1.17) respectively. More Ae. aegypti were caught per trap per week in the wMel-intervention arm compared to the control arm during wMel deployments (count ratio 1.23 (95% CI 1.03, 1.46)). Between treatment arms there was no measurable difference in the Ae. albopictus population size before, during or after wMel-deployment (overall count ratio 1.10 (95% CI 0.89, 1.35)). We also compared insecticide resistance phenotypes of Ae. aegypti in the first and second years after wMel-deployments. Ae. aegypti field populations from wMel-treated and untreated arms were similarly resistant to malathion (0.8%), permethrin (1.25%) and cyfluthrin (0.15%) in year 1 and year 2 of the trial. In summary, we found no between-arm differences in the relative abundance of Ae. aegypti or Ae. albopictus prior to or after wMel introgression, and no between-arm difference in Ae. aegypti insecticide resistance phenotypes. These data suggest neither Aedes abundance, nor insecticide resistance, confounded the epidemiological outcomes of the AWED trial.

Reduced dengue incidence following deployments of Wolbachia-infected Aedes aegypti in Yogyakarta, Indonesia: a quasi-experimental trial using controlled interrupted time series analysis.

Background: Ae. aegypti mosquitoes stably transfected with the intracellular bacterium Wolbachia pipientis ( wMel strain) have been deployed for biocontrol of dengue and related arboviral diseases in multiple countries. Field releases in northern Australia have previously demonstrated near elimination of local dengue transmission from Wolbachia-treated communities, and pilot studies in Indonesia have demonstrated the feasibility and acceptability of the method. We conducted a quasi-experimental trial to evaluate the impact of scaled Wolbachia releases on dengue incidence in an endemic setting in Indonesia. Methods: In Yogyakarta City, Indonesia, following extensive community engagement, wMel Wolbachia-carrying mosquitoes were released every two weeks for 13-15 rounds over seven months in 2016-17, in a contiguous 5 km 2 area (population 65,000). A 3 km 2 area (population 34,000) on the opposite side of the city was selected a priori as an untreated control area. Passive surveillance data on notified hospitalised dengue patients was used to evaluate the epidemiological impact of Wolbachia deployments, using controlled interrupted time-series analysis. Results: Rapid and sustained introgression of wMel Wolbachia into local Ae. aegypti populations was achieved. Thirty-four dengue cases were notified from the intervention area and 53 from the control area (incidence 26 vs 79 per 100,000 person-years) during 24 months following Wolbachia deployment. This corresponded in the regression model to a 73% reduction in dengue incidence (95% confidence interval 49%,86%) associated with the Wolbachia intervention. Exploratory analysis including 6 months additional post-intervention observations showed a small strengthening of this effect (30 vs 115 per 100,000 person-years; 76% reduction in incidence, 95%CI 60%,86%). Conclusions: We demonstrate a significant reduction in dengue incidence following successful introgression of Wolbachia into local Ae. aegypti populations in an endemic setting in Indonesia. These findings are consistent with previous field trials in northern Australia, and support the effectiveness of this novel approach for dengue control.

Prevalence and Distribution of Dengue Virus in Aedes aegypti in Yogyakarta City before Deployment of Wolbachia Infected Aedes aegypti.

Indonesia is one of the countries where dengue infection is prevalent. In this study we measure the prevalence and distribution of dengue virus (DENV) DENV-infected Aedes aegypti in Yogyakarta City, Indonesia, during the wet season when high dengue transmission period occurred, as baseline data before implementation of a Wolbachia-infected Aedes aegypti trial for dengue control. We applied One-Step Multiplex Real Time PCR (RT-PCR) for the type-specific-detection of dengue viruses in field-caught adult Aedes aegypti mosquitoes. In a prospective field study conducted from December 2015 to May 2016, adult female Aedes aegypti were caught from selected areas in Yogyakarta City, and then screened by using RT-PCR. During the survey period, 36 (0.12%) mosquitoes from amongst 29,252 female mosquitoes were positive for a DENV type. In total, 22.20% of dengue-positive mosquitoes were DENV-1, 25% were DENV-2, 17% were DENV-3, but none were positive for DENV-4. This study has provided dengue virus infection prevalence in field-caught Aedes aegypti and its circulating serotype in Yogyakarta City before deployment of Wolbachia-infected Aedes aegypti.