Research Open Access
Like 0



(Skuse) is an important vector of arboviral diseases, including dengue, chikungunya and Zika virus disease. Monitoring insecticide resistance and mechanisms by which the mosquito develops resistance is crucial to minimise disease transmission.


To determine insecticide resistance status and mechanisms in from different geographical regions.


We sampled 33 populations of from Asia, Europe and South America, and tested these for susceptibility to permethrin, a pyrethroid insecticide. In resistant populations, the target site for pyrethroids, a voltage-sensitive sodium channel () was genotyped. Three resistant sub-strains, each harbouring a resistance allele homozygously, were established and susceptibilities to three different pyrethroids (with and without a cytochrome P450 inhibitor) were assayed.


Most populations of tested were highly susceptible to permethrin but a few from Italy and Vietnam (4/33), exhibited high-level resistance. Genotyping studies detected a knockdown resistance () allele V1016G in for the first time in . Two previously reported alleles, F1534C and F1534S, were also detected. The bioassays indicated that the strain homozygous for the V1016G allele showed much greater levels of pyrethroid resistance than other strains harbouring F1534C or F1534S.


The V1016G allele was detected in bothAsian and Italian populations, thus a spread of this allele beyond Italy in Europe cannot be ruled out. This study emphasises the necessity to frequently and regularly monitor the V1016G allele in , particularly where this mosquito species is the main vector of arboviruses.


Article metrics loading...

Loading full text...

Full text loading...



  1. Shono T. Pyrethroid resistance: Importance of the kdr-type mechanism. J Pestic Sci. 1985;10(1):141-6.  https://doi.org/10.1584/jpestics.10.141 
  2. Georghiou GP, Saito T. Pest Resistance to Pesticides. Plenum Press; 1983.
  3. Milani R. Mendelian behaviour of resistance to the knockdown action of DDT and correlation between knockdown and mortality in M. domestica L. Riv Parassitol. 1954;15:513-43.
  4. Lok C. Singapore's dengue haemorrhagic fever control programme: A case study on the successful control of Aedes aegypti and Aedes albopictus using mainly environmental measures as a part of integrated vector control. Tokyo: Southeast Asian Medical Information Center; 1985. 114 p.
  5. Gubler DJ, Kuno G. Dengue and dengue hemorrhagic fever. Cambridge: University Press; 1997.
  6. Moyes CL, Vontas J, Martins AJ, Ng LC, Koou SY, Dusfour I, et al. Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans. PLoS Negl Trop Dis. 2017;11(7):e0005625.  https://doi.org/10.1371/journal.pntd.0005625  PMID: 28727779 
  7. Smith LB, Kasai S, Scott JG. Pyrethroid resistance in Aedes aegypti and Aedes albopictus: Important mosquito vectors of human diseases. Pestic Biochem Physiol. 2016;133:1-12.  https://doi.org/10.1016/j.pestbp.2016.03.005  PMID: 27742355 
  8. Rinkevich FD, Du Y, Dong K. Diversity and convergence of sodium channel mutations involved in resistance to pyrethroids. Pestic Biochem Physiol. 2013;106(3):93-100.  https://doi.org/10.1016/j.pestbp.2013.02.007  PMID: 24019556 
  9. Hirata K, Komagata O, Itokawa K, Yamamoto A, Tomita T, Kasai S. A single crossing-over event in voltage-sensitive Na+ channel genes may cause critical failure of dengue mosquito control by insecticides. PLoS Negl Trop Dis. 2014;8(8):e3085.  https://doi.org/10.1371/journal.pntd.0003085  PMID: 25166902 
  10. Du Y, Nomura Y, Satar G, Hu Z, Nauen R, He SY, et al. Molecular evidence for dual pyrethroid-receptor sites on a mosquito sodium channel. Proc Natl Acad Sci USA. 2013;110(29):11785-90.  https://doi.org/10.1073/pnas.1305118110  PMID: 23821746 
  11. Hu Z, Du Y, Nomura Y, Dong K. A sodium channel mutation identified in Aedes aegypti selectively reduces cockroach sodium channel sensitivity to type I, but not type II pyrethroids. Insect Biochem Mol Biol. 2011;41(1):9-13.  https://doi.org/10.1016/j.ibmb.2010.09.005  PMID: 20869441 
  12. Kasai S, Ng LC, Lam-Phua SG, Tang CS, Itokawa K, Komagata O, et al. First detection of a putative knockdown resistance gene in major mosquito vector, Aedes albopictus. Jpn J Infect Dis. 2011;64(3):217-21. PMID: 21617306 
  13. Xu J, Bonizzoni M, Zhong D, Zhou G, Cai S, Li Y, et al. Multi-country survey revealed prevalent and novel F1534S mutation in voltage-gated sodium channel (VGSC) gene in Aedes albopictus. PLoS Negl Trop Dis. 2016;10(5):e0004696.  https://doi.org/10.1371/journal.pntd.0004696  PMID: 27144981 
  14. Aguirre-Obando OA, Martins AJ, Navarro-Silva MA. First report of the Phe1534Cys kdr mutation in natural populations of Aedes albopictus from Brazil. Parasit Vectors. 2017;10(1):160.  https://doi.org/10.1186/s13071-017-2089-5  PMID: 28347326 
  15. Chen H, Li K, Wang X, Yang X, Lin Y, Cai F, et al. First identification of kdr allele F1534S in VGSC gene and its association with resistance to pyrethroid insecticides in Aedes albopictus populations from Haikou City, Hainan Island, China. Infect Dis Poverty. 2016;5(1):31.  https://doi.org/10.1186/s40249-016-0125-x  PMID: 27133234 
  16. Pichler V, Bellini R, Veronesi R, Arnoldi D, Rizzoli A, Lia RP, et al. First evidence of resistance to pyrethroid insecticides in Italian Aedes albopictus populations 26 years after invasion. Pest Manag Sci. 2018;74(6):1319-27.  https://doi.org/10.1002/ps.4840  PMID: 29278457 
  17. Kasai S, Komagata O, Itokawa K, Shono T, Ng LC, Kobayashi M, et al. Mechanisms of pyrethroid resistance in the dengue mosquito vector, Aedes aegypti: target site insensitivity, penetration, and metabolism. PLoS Negl Trop Dis. 2014;8(6):e2948.  https://doi.org/10.1371/journal.pntd.0002948  PMID: 24945250 
  18. Finney DJ. Probit analysis 3rd ed. Cambridge: University Press; 1971.
  19. World Health Organization (WHO). Test procedures for insecticide resistance monitoring in malaria vector mosquitoes. 2nd ed. Geneva: WHO; 2016.
  20. Rudbeck L, Dissing J. Rapid, simple alkaline extraction of human genomic DNA from whole blood, buccal epithelial cells, semen and forensic stains for PCR. Biotechniques. 1998;25(4):588-90, 592.  https://doi.org/10.2144/98254bm09  PMID: 9793639 
  21. Davies TGE, Field LM, Usherwood PNR, Williamson MS. A comparative study of voltage-gated sodium channels in the Insecta: implications for pyrethroid resistance in Anopheline and other Neopteran species. Insect Mol Biol. 2007;16(3):361-75.  https://doi.org/10.1111/j.1365-2583.2007.00733.x  PMID: 17433068 
  22. Folmer O, Black M, Hoeh W, Lutz R, Vrijenhoek R. DNA primers for amplification of mitochondrial cytochrome c oxidase subunit I from diverse metazoan invertebrates. Mol Mar Biol Biotechnol. 1994;3(5):294-9. PMID: 7881515 
  23. Liu Z, Song W, Dong K. Persistent tetrodotoxin-sensitive sodium current resulting from U-to-C RNA editing of an insect sodium channel. Proc Natl Acad Sci USA. 2004;101(32):11862-7.  https://doi.org/10.1073/pnas.0307695101  PMID: 15280550 
  24. Smith CE. The history of dengue in tropical Asia and its probable relationship to the mosquito Aedes aegypti. J Trop Med Hyg. 1956;59(10):243-51. PMID: 13368255 
  25. Benedict MQ, Levine RS, Hawley WA, Lounibos LP. Spread of the tiger: global risk of invasion by the mosquito Aedes albopictus. Vector Borne Zoonotic Dis. 2007;7(1):76-85.  https://doi.org/10.1089/vbz.2006.0562  PMID: 17417960 
  26. Rezza G, Nicoletti L, Angelini R, Romi R, Finarelli AC, Panning M, et al. . Infection with chikungunya virus in Italy: an outbreak in a temperate region. Lancet. 2007;370(9602):1840-6.  https://doi.org/10.1016/S0140-6736(07)61779-6  PMID: 18061059 
  27. Manica M, Cobre P, Rosà R, Caputo B. Not in my backyard: effectiveness of outdoor residual spraying from hand-held sprayers against the mosquito Aedes albopictus in Rome, Italy. Pest Manag Sci. 2017;73(1):138-45.  https://doi.org/10.1002/ps.4315  PMID: 27174441 
  28. Williamson MS, Martinez-Torres D, Hick CA, Devonshire AL. Identification of mutations in the housefly para-type sodium channel gene associated with knockdown resistance (kdr) to pyrethroid insecticides. Mol Gen Genet. 1996;252(1-2):51-60.  https://doi.org/10.1007/BF02173204  PMID: 8804403 
  29. Kasai S, Sun H, Scott JG. Diversity of knockdown resistance alleles in a single house fly population facilitates adaptation to pyrethroid insecticides. Insect Mol Biol. 2017;26(1):13-24.  https://doi.org/10.1111/imb.12267  PMID: 27792261 
  30. Tsetsarkin KA, Vanlandingham DL, McGee CE, Higgs S. A single mutation in chikungunya virus affects vector specificity and epidemic potential. PLoS Pathog. 2007;3(12):e201.  https://doi.org/10.1371/journal.ppat.0030201  PMID: 18069894 
  31. Succo T, Leparc-Goffart I, Ferré JB, Roiz D, Broche B, Maquart M, et al. Autochthonous dengue outbreak in Nîmes, South of France, July to September 2015. Euro Surveill. 2016;21(21):30240.  https://doi.org/10.2807/1560-7917.ES.2016.21.21.30240  PMID: 27254729 
  32. Gjenero-Margan I, Aleraj B, Krajcar D, Lesnikar V, Klobučar A, Pem-Novosel I, et al. Autochthonous dengue fever in Croatia, August-September 2010. Euro Surveill. 2011;16(9):19805. PMID: 21392489 
  33. Sang S, Gu S, Bi P, Yang W, Yang Z, Xu L, et al. Predicting unprecedented dengue outbreak using imported cases and climatic factors in Guangzhou, 2014. PLoS Negl Trop Dis. 2015;9(5):e0003808.  https://doi.org/10.1371/journal.pntd.0003808  PMID: 26020627 
  34. Kutsuna S, Kato Y, Moi ML, Kotaki A, Ota M, Shinohara K, et al. Autochthonous dengue fever, Tokyo, Japan, 2014. Emerg Infect Dis. 2015;21(3):517-20.  https://doi.org/10.3201/eid2103.141662  PMID: 25695200 
  35. Sun H, Kasai S, Scott JG. Two novel house fly Vssc mutations, D600N and T929I, give rise to new insecticide resistance alleles. Pestic Biochem Physiol. 2017;143:116-21.  https://doi.org/10.1016/j.pestbp.2017.08.013  PMID: 29183579 

Data & Media loading...

Supplementary data

Submit comment
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error