Target site kdr mutations in the voltage-gated sodium channel gene in pyrethroid-resistant Aedes aegypti from Saudi Arabia

In Saudi Arabia, many outbreaks and cases of dengue fever have been reported since 1994. Pyrethroid insecticides have been used intensively in the country since 1999. This constant use has likely provided intense selection pressure for the development of target site mutations in the voltage-gated sodium channel (VGSC) gene in Aedes aegypti that result in knockdown-resistance (kdr) against pyrethroids. Aedes aegypti in Jazan was assayed for the presence of known kdr mutations in domains IIS6 and IIIS6 of the VGSC gene using PCR amplification and sequencing.
Haplotype and nucleotide diversity of VGSC regions was lower in SA than Africa, the Americas and Southeast Asia, consistent with a relatively recent spread of Ae. aegypti into the country. The presence of three kdr mutations S989P, V1016G (IIS6) and F1534C (IIIS6) were detected for the first time in the Jazan region but have been reported elsewhere in SA (Jeddah and Makkah) previously. The S989P mutation was in perfect linkage with V1016G. Haplotype inference indicated that S989P+V1016G was on a different haplotypic background from F1534C. Mutations S989P+V1016G were present at a frequency of 0.30 and F1534C at 0.71. Of the six genotypes present, the majority (45%) were homozygous for F1534C. From the presence of SS+VV /FC genotypes in Jazan, we inferred the presence of haplotypes containing no kdr mutations, i.e. S+V /F. The presence of such haplotypes indicates that appropriate insecticide resistance management strategies have the potential to restore insecticide susceptibility to this population to prolong the effective use of pyrethroid insecticides.