Molecular basis of the escalation of insecticide resistance in malaria vectors and its impact on malaria control

Malaria prevention relies heavily on insecticide-based interventions including Long Lasting Insecticidal Nets (LLINs). Unfortunately, insecticide resistance threatens these tools. Worryingly, an escalation of resistance in Anopheles funestus, major malaria vector, is inducing an extensive loss of efficacy of all pyrethroid-LLINs including the newly introduced PBO-pyrethroid nets. If such super-resistance spreads Africa-wide, insecticide-based interventions could be compromised with catastrophic consequences. This super-resistance is likely driven by a dramatic increase in metabolic resistance and/or the development of a reduced penetration in super-resistant mosquitoes allowing them to now survive exposure to even PBO-pyrethroid nets and potentially conferring cross-resistance to other insecticide classes. Unfortunately, the molecular drivers of this super-resistance remain unknown preventing the design of diagnostic assays to track it and assess its impact on malaria control. Therefore, to help mitigate the impact of super-resistance, I will pursue the following aims: Aim 1: detecting molecular markers of the increased metabolic resistance driving the resistance escalation to insecticides in An. funestus; Aim 2: detecting genetic variants of the reduced penetration mechanism contributing to super-resistance, cross-resistance and design DNA-based assays to track it; Aim 3: establishing the impact of the escalation of resistance on the effectiveness of insecticide-based interventions and malaria transmission using molecular markers.