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

Abstract

Background: Ae. aegypti mosquitoes stably transfected with the intracellular bacterium Wolbachia pipientis (wMel strain) have been deployed for the 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 Wolbachiareleases on dengue incidence in an endemic setting in Indonesia. Methods and findings: In Yogyakarta City, Indonesia, following an extensive community engagement campaign, wMel Wolbachia-carrying mosquitoes were released every two weeks for 13−15 release rounds over seven months in 2016−17, in a contiguous 5 km2 area (population 65,000). A 3 km2 area (population 34,000) on the opposite side of the city was selected a priori as an untreated control area, on the basis of comparable socio-demographic characteristics and historical dengue incidence. Passive surveillance data on notified hospitalised dengue patients was used to evaluate the epidemiological impact of Wolbachia deployments, using controlled interrupted time series analysis. 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 the 24 months after Wolbachia was deployed. 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 an additional 6 months of 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: These findings demonstrate a significant reduction in dengue incidence following successful introgression of Wolbachia into local Ae. aegypti populations in an endemic setting in Indonesia. These results are consistent with previous field trials in northern Australia, and support the effectiveness of this novel approach for the control of dengue and other Aedes-borne diseases.

The RNAi Pathway Is Important to Control Mayaro Virus Infection in Aedes aegypti but not for Wolbachia-Mediated Protection

“…Furthermore, recent field trials demonstrated that deployment of the wMel strain into local Ae. aegypti populations can result in a reduction of local dengue transmission [16,17]. Despite the effectiveness of Wolbachia's viral protection, the mechanism(s) that underlies the ability of Wolbachia to control the virus replication is not well understood.…”

Designing Effective <em>Wolbachia</em> Release Programs for Mosquito and Arbovirus Control

“…The pathogen blocking effects of some Wolbachia strains form the basis of mosquito release programs to reduce dengue transmission (Figure 1B). When natural Aedes aegypti populations carry the wMel or wAlbB Wolbachia strains at a high frequency, this reduces the vector competence of the population, resulting in fewer dengue cases (Ryan et al, 2019, Nazni et al, 2019, Indriani et al, 2020. Wolbachia infections do not always provide protection against pathogens, and the strength of blocking depends on the pathogen (Teixeira et al, 2008), insect host (Lu et al, 2012), Wolbachia strain (Osborne et al, 2009, Ferguson et al, 2015 and environmental conditions (Murdock et al, 2014, Chrostek et al, 2020, Mancini et al, 2020a, Caragata et al, 2013.…”

“…Importantly, the Wolbachia strains in Ae. aegypti that are being released into the field, including wMel, have an overall suppressive effect on dengue transmission, both in laboratory (Ferguson et al, 2015, Carrington et al, 2017 and field trials (O'Neill et al, 2018, Ryan et al, 2019, Nazni et al, 2019, Indriani et al, 2020. However, given that pathogen blocking by Wolbachia is rarely complete, it is important to consider this variability when planning releases of Wolbachia-infected mosquitoes.…”

Effectiveness ofWolbachia-infected mosquito deployments in reducing the incidence of dengue and otherAedes-borne diseases in Niterói, Brazil: a quasi-experimental study

“…aegypti populations. 15–17 A recently completed cluster randomised trial of w Mel Wolbachia deployments in Yogyakarta, Indonesia, conclusively demonstrated the efficacy of the method, with a 77% reduction in dengue incidence in Wolbachia -treated neighbourhoods compared to untreated areas. 18 The Yogyakarta CRT included chikungunya and Zika as secondary endpoints, but insufficient cases were detected to permit an evaluation of efficacy against these arboviruses.…”