To sustain the effectiveness of these interventions it is imperative to implement suitable insecticide resistance management (IRM) strategies to reduce the negative impact of such resistance. However, increasing insecticide resistance in malaria vector species presents a major challenge to these vector control interventions and likely contributed to the increase in malaria incidence in the last 2 years (WHO 2018). Significant efforts have been made globally to eliminate malaria leading to consistent reduction in malaria cases and mortality in Africa by 42% and 66%, respectively (Bhatt et al. Malaria control relies mainly on insecticide-based interventions, notably pyrethroid-based long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS). This study shows that the P450-mediated metabolic resistance imposes a high fitness cost in malaria vectors supporting that a resistance management strategy based on rotation could help mitigate the impact of such resistance. In this hybrid strain, a significant decrease of the resistant CYP6P9a-RR genotype was observed after ten generations ( χ 2 = 6.6 P = 0.01) suggesting a reversal of P450-based resistance in the absence of selection.
However, CYP6P9a does not impact the longevity as no difference was observed in the life span of mosquitoes with different genotypes ( χ 2 = 1.6 P = 0.9). This fitness cost was further supported by the late pupation of homozygote resistant than susceptible mosquitoes (OR = 2.50 P < 0.01). CYP6P9a also imposes a significant fitness cost on the larval development as homozygote resistant larvae (CYP6P9a-RR) developed significantly slower than heterozygote and homozygote susceptible mosquitoes ( χ 2 = 11.2 P = 0.0008). Genotyping the CYP6P9a-R resistance allele in oviposited females revealed that CYP6P9a negatively impacts the fecundity as homozygote susceptible mosquitoes (CYP6P9a-SS) lay more eggs than heterozygote (OR = 2.04: P = 0.01) and homozygote resistant mosquitoes. Reciprocal crosses were performed between a pyrethroid susceptible (FANG) and resistant (FUMOZ-R) laboratory strains and the hybrid strains showed intermediate resistance. Here, we deciphered the fitness cost associated with the CYP6P9a (P450-mediated metabolic resistance) in the major African malaria vector Anopheles funestus. Elucidating the fitness cost and potential reversal of metabolic resistance is crucial to design suitable resistance management strategies. Metabolic resistance threatens the sustainability of pyrethroid-based malaria control interventions.
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