Insecticide Resistance Profiling of Anopheles coluzzii and Anopheles gambiae Populations in the Southern Senegal: Role of Target Sites and Metabolic Resistance Mechanisms

Abstract

The emergence and spread of insecticide resistance among the main malaria vectors is threatening the effectiveness of vector control interventions in Senegal. The main drivers of this resistance in the Anopheles gambiae complex (e.g., An. gambiae and Anopheles coluzzii) remains poorly characterized in Senegal. Here we characterized the main target site and metabolic resistances mechanisms among the An. gambiae and An. coluzzii populations from their sympatric and allopatric or predominance area in Senegal. Larvae and pupae of An. gambiae s.l. were collected, reared to adulthood, and then used for insecticides susceptibility and synergist assays using the WHO (World Health Organisation) test kits for adult mosquitoes. The TaqMan method was used for the molecular characterization of the main target site insecticide resistance mechanisms (Vgsc-1014F, Vgsc-1014S, N1575Y and G119S). A RT-qPCR (Reverse Transcriptase-quantitative Polymerase Chaine Reaction) was performed to estimate the level of genes expression belonging to the CYP450 (Cytochrome P450) family. Plasmodium infection rate was investigated using TaqMan method. High levels of resistance to pyrethroids and DDT and full susceptibility to organophosphates and carbamates where observed in all three sites, excepted a probable resistance to bendiocarb in Kedougou. The L1014F, L1014S, and N1575Y mutations were found in both species. Pre-exposure to the PBO (Piperonyl butoxide) synergist induced a partial recovery of susceptibility to permethrin and full recovery to deltamethrin. Subsequent analysis of the level of genes expression, revealed that the CYP6Z1 and CYP6Z2 genes were over-expressed in wild-resistant mosquitoes compared to the reference susceptible strain (Kisumu), suggesting that both the metabolic resistance and target site mutation involving kdr mutations are likely implicated in this pyrethroid resistance. The presence of both target-site and metabolic resistance mechanisms in highly pyrethroid-resistant populations of An. gambiae s.l. from Senegal threatens the effectiveness and the sustainability of the pyrethroid-based tools and interventions currently deployed in the country. The Kdr-west mutation is widely widespread in An. coluzzii sympatric population. PBO or Duo nets and IRS (Indoor Residual Spraying) with organophosphates could be used as an alternative measure to sustain malaria control in the study area.

Evolution of the Pyrethroids Target-Site Resistance Mechanisms in Senegal: Early Stage of the Vgsc-1014F and Vgsc-1014S Allelic Frequencies Shift

“…coluzzii especially in An . gambiae s.s. populations from the south-eastern part of the country [ 20 , 32 ]. The low frequency of Vgsc-1014F observed in An.…”

“…Over the past decade, Senegal has undertaken large up-scaling of pyrethroid-based vector control interventions, mainly through universal the coverage of LLIN and targeted IRS using pyrethroids in selected Senegalese health districts between 2007 and 2010 [ 18 ]. However, several reports of pyrethroid resistance amongst natural population of malaria vectors [ 14 , 19 , 20 , 21 ], could compromise the gain obtained. Moreover, although the co-occurrence of both Vgsc-1014F and Vgsc-1014S has been extensively reported from several wild populations across diverse ecological zones of the country [ 14 , 20 , 21 ], their evolutionary history and dynamic in the country remain unclear and under-investigated.…”

“…However, several reports of pyrethroid resistance amongst natural population of malaria vectors [ 14 , 19 , 20 , 21 ], could compromise the gain obtained. Moreover, although the co-occurrence of both Vgsc-1014F and Vgsc-1014S has been extensively reported from several wild populations across diverse ecological zones of the country [ 14 , 20 , 21 ], their evolutionary history and dynamic in the country remain unclear and under-investigated. Therefore, understanding the distribution and evolutionary processes of both Vgsc-1014F and Vgsc-1014S mutations amongst the natural An.…”

Insecticide Resistance in Vectors of Medically Important Parasitic Infections

“…sinensis in China and Southeast Asian countries [47]. In a recent study carried out by Yan et al, several genes have been identified which confer permethrin resistance to Culex pipiens quinquefasciatus, particularly, 2 CCEs, 6 GSTs, and 7 P450s gene were highly expressed [49].…”

“…determinants and point mutations associated with insecticide resistance in various insect vectors[18,40,43,45,46,[48][49][50][51][52][53][54][55][56][57][58].…”