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 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 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. 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.

Reduced competence to arboviruses following the sustainable invasion ofWolbachiainto nativeAedes aegyptifrom Niterói, Southeastern Brazil

“…In contrast, the utilization of strains associated with low-to-mild fitness costs, albeit with generally lower PI, allow fewer individuals to be released in the field in order to promote an efficient invasion. Fulfilling these criteria, the strain w Mel has been advocated as a standard choice for field release, collecting successful trials in Australia, Brazil and Indonesia (Garcia et al, 2019; Hoffmann et al, 2014, 2011; Indriani et al, 2020; O’Neill et al, 2019; Ryan et al, 2019; Tantowijoyo et al, 2020). Nonetheless, due to its beneficial attributes in warmer climates, keeping density levels high and stable, w AlbB has proven a second option and suitable alternative to w Mel, as shown by a recent trial held in Malaysia (Nazni et al, 2019).…”

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 w Mel 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.…”

“…aegypti . Recently, several strains of the endosymbiont Wolbachia pipientis (Alphaproteobacteria: Ricketsiales ) have been used in integrated arboviral control programs around the world [ 14 , 15 , 16 , 17 ]. On account of the fact that Ae.…”

“…Wolbachia -induced resistance to arbovirus infection in mosquitoes can provide us with a powerful approach to control mosquito-transmitted diseases [ 16 , 17 ] yet the cellular and molecular mechanisms that underlies the ability of Wolbachia to affect the replication of arboviruses are not well understood. Recent studies have hypothesized that this viral protection may be due to priming of major innate immune pathways, because they observed numerous immune genes to be upregulated in Wolbachia -infected versus uninfected mosquitoes [ 25 ].…”

Host-shift as the cause of emerging infectious diseases: Experimental approaches using Drosophila-virus interactions

“…When Wolbachia infected mosquitoes were released into the wild, the bacterium spread through the mosquito populations by cytoplasmic incompatibility (Hoffmann et al, 2011;Walker et al, 2011). Large field trials have shown that this approach can decrease dengue prevalence in human populations (Indriani et al, 2020;Ryan et al, 2020). A great advantage of this method to control arboviruses is that Wolbachia can block the replication of not only dengue virus, but also chikungunya, yellow fever, Zika and West Nile viruses (Moreira et al, 2009;Glaser and Meola, 2010;van den Hurk et al, 2012;Aliota et al, 2016).…”