[F31] Delineating Barriers to the Effectiveness of Wolbachia-Based Interventions for Arboviral Risk Reduction
Ente: National Institute of Allergy and Infectious Diseases
Scadenza: 2028-08-15
Importo max: 50.114 EUR
Paese: US
Descrizione
PROJECT SUMMARY/ABSTRACT
Dengue and other Aedes-borne diseases pose a significant and increasing public health challenge in southern U.S. states and territories, where Aedes aegypti is established and local transmission has already occurred. At present, there is no effective prevention of Aedes-borne diseases in the U.S. Wolbachia-based interventions are a novel strategy for reducing arboviral transmission by Aedes aegypti, but their effectiveness has varied across settings. There is therefore an urgent need to identify the mechanisms driving inconsistent Wolbachia establishment such that these interventions can be optimized before wider implementation in areas at risk in the U.S. We have a unique opportunity to interrogate these mechanisms in Brazil, which is implementing large scale releases of Wolbachia-infected mosquitoes. My preliminary work has shown marked spatial heterogeneity in Wolbachia introgression across multiple Brazilian cities following releases. This proposal, which will be conducted entirely in the U.S., leverages longitudinal datasets and samples from Wolbachia release programs provided by our collaborators from three Brazilian cities, including the NIAID-sponsored EVITA Dengue cluster randomized controlled trial, to investigate two critical determinants of intervention success. Specifically, this proposal aims to: (1) delineate the meteorological and environmental factors that influence partial and complete Wolbachia loss in Ae. aegypti, and (2) determine how fine-scale Ae. aegypti population structure influences Wolbachia introgression dynamics after releases. For the first aim, I will integrate field measurements of Wolbachia introgression with molecular markers of Wolbachia loss to develop statistical and mathematical models characterizing patterns and drivers of loss. For the second aim, I will use whole-genome sequencing data to quantify genetic differentiation, connectivity, and kinship structure in Ae. aegypti populations prior to releases in Belo Horizonte. I will then assess whether these features predict spatial patterns of introgression following deployments. The successful completion of the proposed project will inform models to guide site selection, optimize the design of release plans, pinpoint modifiable landscape features that can improve introgression, and set benchmarks for the development of more resilient Wolbachia strains in the future, thus strengthening the evidence base necessary for scaling these interventions. Furthermore, by identifying environmental and genetic barriers to successful Wolbachia establishment, this project will generate operational guidance directly relevant to protecting Americans from dengue and other Aedes-borne diseases in high-risk regions. Finally, the proposed mentoring from experts in the field, didactic training, and skill building activities will prepare a U.S. physician-scientist in vector genomics, spatial epidemiology, and mathematical modeling and strengthen U.S. scien
Istituzione: YALE UNIVERSITY
PI: Paloma Mariana Carcamo
Progetto: 1F31AI203216-01
Settori: National Institute of Allergy and Infectious Diseases
Vai al bando originale
Registrati gratis su Bandolo per trovare bandi compatibili con la tua azienda.