Dissecting the role of insecticide resistance in the spread of vector-borne disease (360G-Wellcome-202137_Z_16_Z)

Insecticide resistance is the greatest challenge to vector-borne disease control. The vector population that persists following insecticide-based interventions will be adapted to mitigate the effects of insecticide. Mechanisms of insecticide resistance, which may include increased detoxification or target site insensitivity, will impact vector behaviour and physiology in ways that aren’t fully understood. Resistance mechanisms may lead to either increased or decreased capacity through changes in fitness, immunity and behaviour. Research into the full spectrum of pleiotropic effects is needed to inform the use of limited insecticide-based tools while ensuring transmission risk is minimised. This proposal aims to develop multiple strains of insecticide resistant Aedes aegypti which will differ in their dominant resistance mechanism. A multi-resistant strain from Recife will be differentially exposed to a combination of insecticides and synergists to select for one of three naturally occurring metabolic resistance mechanisms. A strain from Cayman with 80% knockdown resistant allele frequency will also be used. Transcriptional profiles will be evaluated during the course of insecticide selection and resistance reversal to determine changes in the expression of resistance, detoxification, immunity and development genes. The validated set of strains will enable experimental work on vectorial capacity of resistant mosquitoes for multiple vector-borne diseases.