Oral Presentation 12th Australasian Virology Society Meeting 2024

Dengue virus genomic surveillance in the Applying Wolbachia to Eliminate Dengue (AWED) randomised trial reveals pan-genotype efficacy and disruption of focal virus transmission (#18)

Kathryn Edenborough 1 , Endah Supriyati 2 , Suzanne Dufault 3 , Eggi Arguni 2 4 , Citra Indriani 2 5 , Jai Denton 6 , R Tedjo Sasmono 7 , Riris Andono Ahmad 2 5 , Katherine L Anders 6 8 , Cameron Simmons 1 6
  1. Department of Microbiology, Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia
  2. Centre for Tropical Medicine, Faculty of Medicine Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
  3. Division of Biostatistics, School of Public Health, University of California, Berkeley, USA
  4. Department of Child Health, Faculty of Medicine Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
  5. Department of Epidemiology Biostatistics and Public Health, Faculty of Medicine Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
  6. World Mosquito Program, Monash University, Clayton, Victoria, Australia
  7. Eijkman Research Center for Molecular Biology, National Research and Innovation Agency, Bogor, Cibinong, Indonesia
  8. Department of Epidemiology and Preventive Medicine, Monash University, Prahran, Victoria, Australia

Indonesia has one of the highest dengue burdens globally. Innovative approaches to dengue control are urgently needed, with Wolbachia mosquito population replacement representing a sustainable, cost-effective, and evidence-based solution. The Wolbachia approach involves introgression of the wMel strain of the intracellular bacterium, Wolbachia pipientis, into Aedes aegypti mosquito populations to reduce their capacity to transmit dengue and other Ae. aegypti-transmitted arboviruses. The effectiveness of Wolbachia mosquito releases for dengue control has been shown reproducibly in Asia-Pacific and Latin American field trials, with pivotal efficacy data generated in the Applying Wolbachia to Eliminate Dengue (AWED) randomised control trial in Yogyakarta, Indonesia in 2018-2020. The AWED trial demonstrated a 77% reduction in virologically-confirmed dengue in 12 neighbourhoods randomly allocated to receive wMel-infected Ae. aegypti mosquito releases (treated clusters) as compared to 12 untreated clusters. As an extension to the AWED trial results reported previously1, we characterised the genomic diversity of dengue viruses (DENV) detected in the trial and evaluated genotype-specific wMel efficacy and microscale DENV transmission dynamics.

Among the 319 DENV genomes obtained from 318 trial participants, we identified diverse DENV lineages, constituting six genotypes across all four DENV serotypes: DENV-1 genotypes I and IV, DENV-2 Cosmopolitan, DENV-3 genotype I and DENV-4 genotypes I and II. We demonstrate the efficacy of wMel-infected Ae. aegypti releases in Yogyakarta was comparable for all of the six DENV genotypes, extending the pan-serotypic efficacy previously reported1. We observed a strong association between the genetic, spatial and temporal proximity of dengue case pairs resident in untreated clusters, and a disruption of this spatiotemporal structure in treated clusters. These findings have implications for the generalisability of Wolbachia efficacy to geographical settings in which similar genotypes circulate, and will inform the long-term monitoring of DENV in Wolbachia-treated areas.

  1. Utarini A et al. Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue. New England Journal of Medicine. 2021;384: 2177–2186.