Molecular markers for metabolic resistance to insecticides

In the major malaria vectors including An. funestus and An. gambiae metabolic mechanisms are driving resistance to most insecticides, including pyrethroids. But, contrary to target-site resistance such as knockdown resistance (kdr) for which DNA-based markers have been detected for more than two decades, until of recent, no DNA-based molecular assays were available to easily track metabolic resistance and assess its impact on malaria control and transmission. However, a major breakthrough was recently achieved by our research group with the detection of DNA-markers for two cytochrome P450 genes (CYP6P9a and CYP6P9b) in An. funestus allowing the design, for the first time, of simple PCR assays to detect and track such P450-based metabolic resistance in the field.

Unfortunately, these resistance markers only explain resistance in southern Africa  as the genetic basis of pyrethroid resistance, and cross-resistance with other insecticide classes remains very complex in other African regions with different mechanisms, driven by distinct genes in the presence of barriers of gene flow. Moreover, no such markers currently exist for the other major vector An. gambiae. This is a major obstacle in designing effective resistance management strategies across the continent, hindering the control of these major malaria vectors and progress from malaria control to the ultimate goal of elimination.

Furthermore, with the approval of new insecticide classes by World Health Organization (WHO) for malaria control, it is imperative to learn from past mistakes (e.g. the case of pyrethroids) by anticipating and detecting potential resistance genes and markers before they become established in field populations which will prolong the effectiveness of such novel products and tools. Therefore, to help mitigate the impact of insecticide resistance on control interventions, we aim to Validate genomic markers for major metabolic mechanisms of insecticide resistance, and design of DNA-based field applicable diagnostic tools to easily detect and track resistance in the field.

Project detailsProject details

Diagnostics
Enabling Technologies & Assays
Insecticide Resistance

Sep 2020 — Mar 2024

$4.34M

Cameroon