Establishment of wMel Wolbachia in Aedes aegypti mosquitoes and reduction of local dengue transmission in Cairns and surrounding locations in northern Queensland, Australia.

Background: The wMel strain of Wolbachia has been successfully introduced into Aedes aegypti mosquitoes and subsequently shown in laboratory studies to reduce transmission of a range of viruses including dengue, Zika, chikungunya, yellow fever, and Mayaro viruses that cause human disease. Here we report the entomological and epidemiological outcomes of staged deployment of Wolbachia across nearly all significant dengue transmission risk areas in Australia. Methods: The  wMel strain of  Wolbachia was backcrossed into the local  Aedes aegypti genotype (Cairns and Townsville backgrounds) and mosquitoes were released in the field by staff or via community assisted methods. Mosquito monitoring was undertaken and mosquitoes were screened for the presence of  Wolbachia. Dengue case notifications were used to track dengue incidence in each location before and after releases. Results: Empirical analyses of the Wolbachia mosquito releases, including data on the density, frequency and duration of Wolbachia mosquito releases, indicate that Wolbachia can be readily established in local mosquito populations, using a variety of deployment options and over short release durations (mean release period 11 weeks, range 2-22 weeks). Importantly, Wolbachia frequencies have remained stable in mosquito populations since releases for up to 8 years. Analysis of dengue case notifications data demonstrates near-elimination of local dengue transmission for the past five years in locations where Wolbachia has been established. The regression model estimate of Wolbachia intervention effect from interrupted time series analyses of case notifications data prior to and after releases, indicated a 96% reduction in dengue incidence in Wolbachia treated populations (95% confidence interval: 84 - 99%). Conclusion: Deployment of the wMel strain of Wolbachia into local Ae. aegypti populations across the Australian regional cities of Cairns and most smaller regional communities with a past history of dengue has resulted in the reduction of local dengue transmission across all deployment areas

Scaled deployment of Wolbachia to protect the community from dengue and other Aedes transmitted arboviruses.

Background: A number of new technologies are under development for the control of mosquito transmitted viruses, such as dengue, chikungunya and Zika that all require the release of modified mosquitoes into the environment. None of these technologies has been able to demonstrate evidence that they can be implemented at a scale beyond small pilots. Here we report the first successful citywide scaled deployment of Wolbachia in the northern Australian city of Townsville. Methods: The wMel strain of Wolbachia was backcrossed into a local Aedes aegypti genotype and mass reared mosquitoes were deployed as eggs using mosquito release containers (MRCs). In initial stages these releases were undertaken by program staff but in later stages this was replaced by direct community release including the development of a school program that saw children undertake releases. Mosquito monitoring was undertaken with Biogents Sentinel (BGS) traps and individual mosquitoes were screened for the presence of Wolbachia with a Taqman qPCR or LAMP diagnostic assay. Dengue case notifications from Queensland Health Communicable Disease Branch were used to track dengue cases in the city before and after release. Results: Wolbachia was successfully established into local Ae. aegypti mosquitoes across 66 km 2 in four stages over 28 months with full community support.  A feature of the program was the development of a scaled approach to community engagement. Wolbachia frequencies have remained stable since deployment and to date no local dengue transmission has been confirmed in any area of Townsville after Wolbachia has established, despite local transmission events every year for the prior 13 years and an epidemiological context of increasing imported cases. Conclusion: Deployment of Wolbachia into Ae. aegypti populations can be readily scaled to areas of ~60km 2 quickly and cost effectively and appears in this context to be effective at stopping local dengue transmission

GraphData_Figure 3.docx

Data underlying Figure 3 of O'Neill et al 2018 Gates Open Researc

Successful introgression of wMel Wolbachia into Aedes aegypti populations in Fiji, Vanuatu and Kiribati.

Pacific Island countries have experienced periodic dengue, chikungunya and Zika outbreaks for decades. The prevention and control of these mosquito-borne diseases rely heavily on control of Aedes aegypti mosquitoes, which in most settings are the primary vector. Introgression of the intracellular bacterium Wolbachia pipientis (wMel strain) into Ae. aegypti populations reduces their vector competence and consequently lowers dengue incidence in the human population. Here we describe successful area-wide deployments of wMel-infected Ae. aegypti in Suva, Lautoka, Nadi (Fiji), Port Vila (Vanuatu) and South Tarawa (Kiribati). With community support, weekly releases of wMel-infected Ae. aegypti mosquitoes for between 2 to 5 months resulted in wMel introgression in nearly all locations. Long term monitoring confirmed a high, self-sustaining prevalence of wMel infecting mosquitoes in almost all deployment areas. Measurement of public health outcomes were disrupted by the Covid19 pandemic but are expected to emerge in the coming years

<i>w</i>Mel introgression in two areas in South Tarawa, Kiribati.

A) South Tarawa, Kiribati showing the two release areas: Betio (left) and Bairiki (right). B) Introgression of wMel. The line (left axis) represents the percent of Ae. aegypti tested that were infected with wMel Wolbachia, between May 2018 and December 2019. The bars (right axis) indicate the number of Ae. aegypti tested. Data points with less than five screened mosquitos have been omitted. Shaded orange areas indicate wMel mosquito release times. Map produced in QGIS version 3.16.1 using the enumeration area boundaries freely available from the Pacific Data Hub (https://pacificdata.org/data/dataset/2010_kir_phc_admin_boundaries) and OpenMapTiles basemap layer (https://openmaptiles.org/) with CARTO light design (https://carto.com/).</p

Suspected dengue cases notified in Port Vila from January 2016 –January 2022 by (A) hospitalisation status and (B) diagnostic test result.

Blue shading indicates release period for Wolbachia (wMel)-infected Ae. aegypti. Suspected dengue cases without any laboratory diagnostic testing are included in panel A, but excluded from panel B.</p

DENV Prevalence in <i>Wolbachia</i>-infected Mosquitoes.

Pacific Island countries have experienced periodic dengue, chikungunya and Zika outbreaks for decades. The prevention and control of these mosquito-borne diseases rely heavily on control of Aedes aegypti mosquitoes, which in most settings are the primary vector. Introgression of the intracellular bacterium Wolbachia pipientis (wMel strain) into Ae. aegypti populations reduces their vector competence and consequently lowers dengue incidence in the human population. Here we describe successful area-wide deployments of wMel-infected Ae. aegypti in Suva, Lautoka, Nadi (Fiji), Port Vila (Vanuatu) and South Tarawa (Kiribati). With community support, weekly releases of wMel-infected Ae. aegypti mosquitoes for between 2 to 5 months resulted in wMel introgression in nearly all locations. Long term monitoring confirmed a high, self-sustaining prevalence of wMel infecting mosquitoes in almost all deployment areas. Measurement of public health outcomes were disrupted by the Covid19 pandemic but are expected to emerge in the coming years.</div

Total (A) and laboratory-confirmed (B) dengue cases notified in Kiribati from January 2017 –August 2022 by recorded location of residence.

Cases with an ‘address’ location recorded were classified either as resident in the Wolbachia-release areas of Betio and Bairiki or in non-release areas (all locations other than Betio and Bairiki). Laboratory-confirmed dengue cases include those with a positive dengue NS1 and/or IgM diagnostic test result recorded. Blue shading indicates the Wolbachia release period. (TIF)</p

Release & monitoring of <i>w</i>Mel-infected <i>Ae</i>. <i>aegypti</i> within six areas of Nadi and five areas of Lautoka, Fiji.

Each release area was divided into a grid with 100 x 100 meter squares. Grid squares lacking mosquito releases were omitted. Release gradient was determined by using GPS coordinates of each release event and assigning the number of wMel-infected mosquitos to a corresponding grid square. Monitoring numbers were determined in the same way. Map produced in QGIS version 3.16.1 using boundaries aggregated from the enumeration area boundaries freely available from the Pacific Data Hub (https://pacificdata.org/data/dataset/2007_fji_phc_admin_boundaries) and OpenMapTiles basemap layer (https://openmaptiles.org/) with CARTO light design (https://carto.com/)). (PNG)</p