Coût biologique de la résistance aux insecticides chez Anophèles funestus Giles, 1900 (Diptera: culicidae); un des vecteurs majeurs du paludisme en Afrique

Abstract

Insecticide resistance management strategies, such as rotation of insecticide classes, rely on the hypothesis that insecticide resistance is associated with a fitness costs that may cause selection against resistance alleles in the absence of insecticide selection pressure. However, fitness costs incurred in the life-traits and the ability of resistant malaria mosquitoes to transmit Plasmodium parasites through metabolic resistance have so far been difficult to establish due to lack of suitable molecular markers. In order to generate data which could help to improve malaria vector strategies, in this study we evaluated the impact of cytochrome P450-based ( AA-CYP6P9a insert ) and glutathione S-transferase mediated ( L119F-GSTe2 ) metabolic resistance on the life traits of Anopheles funestus and on key parameters of its vectorial capacity. Assesment of the impact of metabolic resistance of the life traits of mosquitoes for the L119F mutation in the GSTe2 gene have reduced fecundity and longer development time compared to heterozygote and homozygote susceptible individuals. However, it was observed that homozygote resistant mosquitoes live longer than those with the homozygote susceptible genotype showing that this mutation has a fitness costs on female fecundity and larval development time but has a benefit in terms of female’s longetivity. Similar results were observed for the CYP6P9a gene for both female fecundity and larval development time. However, for this gene, no significant difference was observed regarding the longevity of females with homozygote resistant genotype compared to those with the homozygote susceptible genotype. In addition, it has been noticed for this gene a significant increase frequency of the susceptible allele over 10 generations in the absence of insecticide selection pressure which could lead to the reversal of susceptibility. Assessment of the impact of metabolic resistance on the mating competitiveness of wild male An. Funestus identified a total of 15 mating swarm in TIBATI whereas 21 couples of An. Funestus were isolated from these swarms genotyping of the GSTe2 locus for the 119F mutation between mated and unmated males compared to those mated ( odds-ratio ( OR ) = 2.1, P= 0.03 ), highlighting a fitness costs of this mutation on the mating competitiveness. Furthermore, investigating the impact of metabolic resistance ( GST ) on Plasmodium infection in mosquitoes did not find a significant association ( x²=0.34 ; P=0.82 ) between different genotypes for the L119F-GSTe2 mutation and the Plasmodium infection status in the field collected whole mosquitoes ( from Mibellon and Obout ). However, by analyzing separately infection by oocysts and sporozoites, mosquitoes with homozygote resistant genotype were significantly more associated with sporozoite infection than heterozygotes ( odd-ratio ( OR ) = 2.5 ; P= 0.012 ) and susceptible homozygote individuals ( OR )= 2.10 ; P=0.013 ) suggesting that the parasite developed better in mosquitoes bearing the resistant allele of this mutation. These results show for the first time that metabolic resistance caused by cytochrome P450 and Gluthathione S-tranferase is associated with a fitness costs in malaria vectors. Therefore, earlier implementation of strategies based on rotation of insecticide could help to tackle pyrethroid resistance in the field. However, the fact that resistant mosquitoes for the L11SF mutation live longer and exhibit greater vectorial capacity suggests that GSTe2-based resistance probably increases the risk of malaria transmission in areas of high metabolic resistance to insecticides caused by this gene.