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Background   Aedes albopictus  is an important dengue vector because of its aggressive biting behavior and rapid spread out of its native home range in Southeast Asia. Pyrethroids are widely used for adult mosquito control, and resistance to pyrethroids should be carefully monitored because vector control is the only effective method currently available to prevent dengue transmission. The voltage-gated sodium channel gene is the target site of pyrethroids, and mutations in this gene cause knockdown resistance ( kdr ). Previous studies reported various mutations in the voltage-gated sodium channel (VGSC) gene, but the spatial distribution of  kdr  mutations in  Ae .  albopictus  has not been systematically examined, and the association between  kdr  mutation and phenotypic resistance has not been established.    Methods  A total of 597  Ae .  albopictus  individuals from 12 populations across Asia, Africa, America and Europe were examined for mutations in the voltage-gated sodium channel gene. Three domains for a total of 1,107 bp were sequenced for every individual. Two populations from southern China were examined for pyrethroid resistance using the World Health Organization standard tube bioassay, and the association between  kdr  mutations and phenotypic resistance was tested.    Results  A total of 29 synonymous mutations were found across domain II, III and IV of the VGSC gene. Non-synonymous mutations in two codons of the VGSC gene were detected in 5 populations from 4 countries. A novel mutation at 1532 codon (I1532T) was found in Rome, Italy with a frequency of 19.7%. The second novel mutation at codon 1534 (F1534S) was detected in southern China and Florida, USA with a frequency ranging from 9.5–22.6%. The WHO insecticide susceptibility bioassay found 90.1% and 96.1% mortality in the two populations from southern China, suggesting resistance and probable resistance. Positive association between  kdr  mutations with deltamethrin resistance was established in these two populations.    Conclusions  Two novel  kdr  mutations, I1532T and F1534S were found in  Ae .  albopictus . This is the first report of I1532T mutations in Italy and F1534S mutation in China and US. Significant association between  kdr  mutation and protection from deltamethrin raised the possibility that  kdr  mutation may be a viable biomarker for pyrethroid resistance surveillance in  Ae .  albopictus . The patchy distribution of  kdr  mutations in  Ae .  albopictus  mosquitoes calls for developing global surveillance plan for pyrethroid resistance and developing countermeasures to mitigate the spread of resistance.

Multi-country Survey Revealed Prevalent and Novel F1534S Mutation in Voltage-Gated Sodium Channel (VGSC) Gene in Aedes albopictus