PT - JOURNAL ARTICLE AU - Nancy M. Endersby-Harshman AU - AboElgasim Ali AU - Basim Alhumrani AU - Mohammed Abdullah Alkuriji AU - Mohammed B. Al-Fageeh AU - Abdulaziz Al-Malik AU - Mohammed S. Alsuabeyl AU - Samia Elfekih AU - Ary A. Hoffmann TI - Voltage-sensitive sodium channel (<em>Vssc</em>) mutations associated with pyrethroid insecticide resistance in <em>Aedes aegypti</em> (L.) from Jeddah, Kingdom of Saudi Arabia – baseline information for a <em>Wolbachia</em> release program AID - 10.1101/2021.01.26.428347 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.01.26.428347 4099 - http://biorxiv.org/content/early/2021/01/27/2021.01.26.428347.short 4100 - http://biorxiv.org/content/early/2021/01/27/2021.01.26.428347.full AB - Background Dengue suppression often relies on control of the mosquito vector, Aedes aegypti, through applications of insecticides of which the pyrethroid group has played a dominant role. Insecticide resistance is prevalent in Ae. aegypti around the world and the resulting reduction of insecticide efficacy is likely to exacerbate the impact of dengue. Dengue has been a public health problem in Saudi Arabia, particularly in Jeddah, since its discovery there in the 1990s and insecticide use for vector control is widespread throughout the city. An alternative approach to insecticide use, based on blocking dengue transmission in mosquitoes by the endosymbiont Wolbachia, is being trialled in Jeddah following the success of this approach in Australia and Malaysia. Knowledge of insecticide resistance status of mosquito populations in Jeddah is a prerequisite for establishing a Wolbachia-based dengue control program as releases of Wolbachia mosquitoes succeed when resistance status of the release population is similar to that of the wild population.Methods WHO resistance bioassays of mosquitoes with deltamethrin, permethrin and DDT were used in conjunction with TaqMan® SNP Genotyping Assays to characterise mutation profiles of Ae. aegypti from Jeddah.Results Screening of the voltage sensitive sodium channel (Vssc), the pyrethroid target-site, revealed mutations at codons 989, 1016 and 1534 in Ae. aegypti from two districts of Jeddah. The triple mutant homozygote (1016G/1534C/989P) was confirmed from Al Safa and Al Rawabi. Bioassays with pyrethroids (Type I and II) and DDT showed that mosquitoes were resistant to each of these compounds based on WHO definitions. An association between Vssc mutations and resistance was established for the Type II pyrethroid, deltamethrin, with one genotype (989P/1016G/1534F) conferring a survival advantage over two others (989S/1016V/1534C and the triple heterozygote). An indication of synergism of Type I pyrethroid activity with piperonyl butoxide suggests that detoxification by cytochrome P450s accounts for some of the pyrethroid resistance response in Ae. aegypti populations from Jeddah.Conclusions The results provide a baseline for monitoring and management of resistance as well as knowledge of Vssc genotype frequencies required in Wolbachia release populations to ensure homogeneity with the target field population.Competing Interest StatementThe authors have declared no competing interest.