Insecticide Resistance and Target-Site Mutations kdr, N1575Y, and Ace-1 in Anopheles gambiae s.l. Populations in a Low-Malaria-Transmission Zone in the Sudanian Region of Senegal

<b>Background/Objectives:</b> Significant progress in malaria control has been achieved through long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), raising hopes for malaria elimination. However, emerging insecticide resistance threatens these gains. This study assessed the susceptibility of <i>Anopheles gambiae s.l.</i> populations to public health insecticides, examined the frequencies of <i>kdr</i>, <i>Ace-1</i>, and <i>N1575Y</i> mutations, and explored their associations with phenotypic resistance in Dielmo and Ndiop, Senegal. <b>Methods</b>: <i>Anopheles</i> larvae collected between September and December 2022 were reared to adulthood. Adult mosquitoes were exposed to discriminating concentrations of various insecticides following WHO guidelines. Knockdown times (KDT50 and KDT95) for pyrethroids were calculated using the Probit model. RT-qPCR detected target-site mutations (<i>kdr</i>: <i>L1014F</i> and <i>L1014S</i>, <i>Ace-1</i>, <i>N1575Y</i>) and assessed correlations with phenotypic resistance. Species-specific PCR identified species within the <i>An. gambiae</i> complex. <b>Results/Conclusions</b>: The populations of Dielmo and Ndiop showed susceptibility to pirimiphos-methyl and bendiocarb, with no <i>Ace-1</i> mutation detected. Resistance to DDT and pyrethroids was observed. The knockdown times indicated that alphacypermethrin and lambdacyhalothrin were more effective than permethrin and deltamethrin. The <i>L1014F</i> allele was widespread, while <i>L1014S</i> was absent in Ndiop and low in Dielmo. The <i>N1575Y</i> mutation occurred only in populations with <i>L1014F</i>. The <i>L1014S</i> mutation was significantly associated with resistance to lambdacyhalothrin in both villages and to deltamethrin in Ndiop.