Tackling insecticide resistance in the major African malaria vector Anopheles funestus: developing new molecular diagnostic tools, understanding the evolution of resistance and its impact on control interventions.

Insecticide-based interventions, notably Indoor Residual Spraying (IRS) and Long Lasting Insecticide Nets (LLINs), are critical for malaria control in Africa. The recent rapid selection of resistance to the available insecticides classes in the major malaria vector Anopheles funestus across Africa is threatening the continued effectiveness of these control tools. The international community has now recognised that if suitable resistance management strategies to preserve the efficacy of current i nsecticides are not developed, this resistance will have devastating public health consequences. Unfortunately, important knowledge gaps on resistance (molecular basis, evolution and fitness cost) and the lack of adequate molecular tools to track resistance are preventing the design and implementation of suitable resistance mitigation strategies. To fill these gaps, I aim in this project to improve the control of An. funestus Africa-wide, by detecting molecular markers to track resistance, by el ucidating patterns of evolution and spread of resistance and assessing the fitness cost of resistance and its impact on control interventions. The project has three broad aims: Aim 1: To establish molecular markers and user-friendly diagnostic assays for pyrethroid, DDT and carbamate resistance and cross-resistance in An. funestus Africa-wide using Next-Generation Sequencing and functional analyses. Aim 2: To predict the evolution and spread of resistance by defining patterns of gene flow and se lective sweeps in field populations. Aim 3: To assess the fitness cost of resistance and its impact on control interventions using experimental huts trials. This project will benefit from the knowledge and tools generated during my Wellcome Trust Career Development Fellowship.