Selection dynamics and efficacy of insecticide resistance management in knock-down resistant Aedes aegypti

Insecticide resistance is a major challenge in mosquito control and disease prevention, with knock-down resistance (kdr) being a common mechanism. This work investigates the V1016I and F1534C kdr mutations in Aedes aegypti to better understand insecticide resistance evolution and management. We analyzed both male and female mosquitoes across six kdr genotypes, including heterozygotes, assessing deltamethrin resistance and life history traits. Additionally, we compared the efficacy of low-dose and high-dose-refugee treatments with traditional high-dose deltamethrin treatment and no insecticide over ten generations. Our findings indicate that male mosquitoes exhibit similar resistance profiles to females when accounting for sex and weight differences, suggesting males can be included in resistance surveillance, enhancing sample sizes. Resistance profiles showed that kdr mutations were incompletely recessive, suggesting their persistence in heterozygous individuals even in the absence of insecticide pressure. Heterozygous males developed significantly faster than the homozygous males, potentially providing a reproductive advantage. Blood-feeding success was significantly reduced for the double homozygous susceptible kdr genotype, indicating a potential fitness benefit of these kdr mutations. All other fitness measurements showed no significant differences between genotypes. Regarding treatment efficacy, the high-dose-refugee treatment was more effective than the low-dose and high-dose treatments, creating less selective pressure for kdr mutations while still offering moderate population control. However, populations without insecticide exposure showed no reduction in resistance frequency. Overall, this work indicates that kdr mutations are likely to persist in mosquito populations despite reduced insecticide pressure, highlighting the necessity for new insecticide chemistries and alternative control strategies.