Spatial Heterogeneity of Knockdown Resistance Mutations in the Dengue Vector Aedes Albopictus in Guangzhou, China

Background: The city of Guangzhou has been the epicenter of dengue fever in China since the 1990s, with Aedes albopictus being the primary vector. The main method used to control vectors and prevent dengue fever has been the application of chemical insecticides; however, this control strategy has resulted in the development of resistance to these insecticides in mosquitoes. Here we report our investigation of the patterns of knockdown resistance (kdr) mutations in 15 field populations of Ae. albopictus collected from 11 districts in Guangzhou. Results: Four mutant alleles (V1016G, F1534S, F1534C, F1534L) were detected in domain II and III of the voltagegated sodium channel (VGSC) gene. Various allele frequencies of kdr mutations were observed (3.1-25.9% for V1016G, 22.6-85.5% for F1534S, 0-29.0% for F1534L, 0.6-54.2% for F1534C). Seven kdr haplotypes (VF, VS, VL, VC, GF, GC, GS) were identified; the highest frequency of haplotypes was found for the single mutant haplotype VS (50.8%), followed by the wild-type VF haplotype (21.7%) and the single mutant haplotype VC (11.9%). Of the three double mutant haplotypes, GF was the most frequent (8.8%), followed by GC (1.2%) and GS (0.8%). Aedes albopictus showed spatial heterogeneity in deltamethrin resistance in populations collected in Guangzhou. We also observed significant differences in haplotype frequency. The frequency of the VC haplotype was significantly higher in high-risk dengue areas than in low-risk ones. Conclusions: The kdr allele V1016G was discovered for the first time in Guangzhou. Genetic isolation in mosquito populations and long-term insecticide selection seem to be responsible for the persistent, patchy distribution of kdr mutant alleles. The small-scale spatial heterogeneity in the distribution and frequency of kdr mutations may have important implications for vector control operations and insecticide resistance management strategies.