Knockdown Resistance (KDR) Mutations in Aedes: Global Distribution and Its Role in Vector Control Failures
DOI:
https://doi.org/10.46799/adv.v4i11.772Keywords:
aedes, knockdown resistance, voltage-gated sodium channel, pyrethroid resistance, vector controlAbstract
Aedes aegypti and Aedes albopictus are major mosquito vectors of dengue, Zika, and other arboviral diseases, while pyrethroid insecticides remain widely used in vector control programs worldwide. However, repeated insecticide exposure has contributed to the selection and spread of knockdown resistance (kdr) mutations in the voltage-gated sodium channel (VGSC) gene, potentially reducing insecticide susceptibility and compromising vector control effectiveness. This literature review aimed to examine the global distribution of kdr mutations in Aedes mosquitoes, evaluate their associations with pyrethroid resistance, and discuss their implications for vector control strategies. A systematic literature search was conducted across PubMed, Scopus, ScienceDirect, and Google Scholar for studies published between 2018 and 2025. Of the 2,850 records initially identified, 14 studies met the inclusion criteria following the screening process. The findings indicated that kdr substitutions, including F1534C, V1016G, V1016I, V410L, S989P, and I1532T, were geographically widespread but unevenly distributed across regions and mosquito species. Studies from Africa reported V1016I and V410L, while investigations in Asia identified V1016G and F1534C in association with reduced pyrethroid susceptibility. Evidence from the Americas highlighted the coexistence of multiple insecticide resistance mechanisms. Combinations of kdr substitutions, particularly F1534C occurring alongside V1016G, V410L, or S989P, were associated with stronger resistance phenotypes in certain populations than individual substitutions. Metabolic resistance mechanisms frequently co-occurred with target-site resistance, and the use of the synergist piperonyl butoxide (PBO) did not consistently restore insecticide susceptibility. These findings suggested that kdr mutations represent a substantial challenge to pyrethroid-based vector control, although resistance detected through laboratory bioassays cannot be directly interpreted as evidence of operational control failure under field conditions. Integrated resistance surveillance combining molecular detection of kdr mutations, standardized phenotypic susceptibility bioassays, and assessment of metabolic resistance mechanisms is therefore essential to inform insecticide selection, improve resistance management, and sustain the effectiveness of available vector control interventions.
References
Al Nazawi, A. M., & Weetman, D. (2023). Age-dependence of susceptibility to single and repeated deltamethrin exposure in pyrethroid-resistant Aedes aegypti strains. Current Research in Parasitology & Vector-Borne Diseases, 3, Article 100121. https://doi.org/10.1016/j.crpvbd.2023.100121
Chaves, L. F., Valerín Cordero, J. A., Delgado, G., Aguilar-Avendaño, C., Maynes, E., Gutiérrez Alvarado, J. M., Ramírez Rojas, M., Romero, L. M., & Marín Rodríguez, R. (2021). Modeling the association between Aedes aegypti ovitrap egg counts, multi-scale remotely sensed environmental data and arboviral cases at Puntarenas, Costa Rica (2017–2018). Current Research in Parasitology & Vector-Borne Diseases, 1, Article 100014. https://doi.org/10.1016/j.crpvbd.2021.100014
Chung, H.-H., Teng, H.-J., Huang, C.-G., Tsai, I.-J., Chen, H.-J., Komagata, O., Kasai, S., Tsai, K.-H., & Chen, S.-L. (2025). First detection of the S989P+V1016G+D1763Y haplotype and expansion of voltage-gated sodium channel mutations in Aedes aegypti in Taiwan in 2016–2023. PLOS Neglected Tropical Diseases, 19(1), Article e0012768. https://doi.org/10.1371/journal.pntd.0012768
Chung, H.-H., Tsai, C.-H., Teng, H.-J., & Tsai, K.-H. (2022). The role of voltage-gated sodium channel genotypes in pyrethroid resistance in Aedes aegypti in Taiwan. PLOS Neglected Tropical Diseases, 16(9), Article e0010780. https://doi.org/10.1371/journal.pntd.0010780
Francis, S., Frank, C., Buchanan, L., Green, S., Stennett-Brown, R., Gordon-Strachan, G., Rubio-Palis, Y., Grant, C., Alexander-Lindo, R. L., Nwokocha, C., Robinson, D., & Delgoda, R. (2021). Challenges in the control of neglected insect vector diseases of human importance in the Anglo-Caribbean. One Health, 13, Article 100316. https://doi.org/10.1016/j.onehlt.2021.100316
Granada, Y., Mejía-Jaramillo, A. M., Zuluaga, S., & Triana-Chávez, O. (2021). Molecular surveillance of resistance to pyrethroids insecticides in Colombian Aedes aegypti populations. PLOS Neglected Tropical Diseases, 15(12), Article e0010001. https://doi.org/10.1371/journal.pntd.0010001
Helvecio, E., Romão, T. P., de Carvalho-Leandro, D., de Oliveira, I. F., Cavalcanti, A. E. H. D., Reimer, L., de Paiva Cavalcanti, M., de Oliveira, A. P. S., Paiva, P. M. G., Napoleão, T. H., Wallau, G. L., de Melo Neto, O. P., Melo-Santos, M. A. V., Ayres, C. F. J., & Oliveira, C. M. F. (2020). Polymorphisms in GSTE2 is associated with temephos resistance in Aedes aegypti. Pesticide Biochemistry and Physiology, 165, Article 104464. https://doi.org/10.1016/j.pestbp.2019.10.002
Huang, Q., Zhou, Y., Xu, J., Zhou, G., Guo, Q., Duan, Y., Zheng, G., Zhu, M., Zhong, S., Zhong, D., Fu, F., Wen, S., Jiang, Y., He, T., Liu, S., Lu, G., Li, Y., & Li, T. (2025). Mechanisms of pyrethroid resistance in Culicidae mosquitoes from Hainan Island, China. Parasites & Vectors, 18, Article 411. https://doi.org/10.1186/s13071-025-07052-y
Keumeni, C. R., Yougang, A. P., Njiokou, F., Clarke, S. E., Lines, J., Wondji, C., & Kamgang, B. (2025). Association of knockdown resistance mutations with pyrethroid resistance in Aedes aegypti, a major arbovirus vector in Cameroon. Parasites & Vectors, 18, Article 296. https://doi.org/10.1186/s13071-025-06943-4
Liu, Q., Zhang, H., Hou, J., Wang, J., Li, T., Wu, Y., Li, C., Liu, Q., Xing, D., Gong, Z., & Zhao, T. (2024). Resistance of Aedes albopictus (Diptera: Culicidae) larvae and adults to insecticides based on bioassays and knockdown resistance (kdr) mutations in Zhejiang Province, China. Ecotoxicology and Environmental Safety, 284, Article 117007. https://doi.org/10.1016/j.ecoenv.2024.117007
Lokossou, A. S., Aikpon, R., Dossou, M., Adjottin, B., Dossou-Sognon, F. U., Konkon, A., Bakary, H., Mamam, H. A., Abotsi, Y., Akpo, E., Akanni-Ediko, R., & Yadouleton, A. (2025). First report of the pyrethroid-resistance-associated V1016I mutation in Aedes aegypti at the seaport of Cotonou, Benin, West Africa. Tropical Medicine and Health, 53, Article 125. https://doi.org/10.1186/s41182-025-00806-5
Maestre-Serrano, R., Flórez-Rivadeneira, Z., Castro-Camacho, J. M., Soto-Arenilla, E., Gómez-Camargo, D., Pareja-Loaiza, P., Ponce-Garcia, G., Juache-Villagrana, A. E., & Flores, A. E. (2023). Spatial distribution of pyrethroid resistance and kdr mutations in Aedes aegypti from La Guajira, Colombia. Insects, 14(1), Article 31. https://doi.org/10.3390/insects14010031
Ridha, M. R., Yudhastuti, R., Notobroto, H. B., Hidajat, M. C., Diyanah, K. C., Jassey, B., & Rahmah, G. M. (2025). A systematic review of insecticide resistance in Aedes aegypti (Diptera: Culicidae) and implications for dengue control in Indonesia. Veterinary World, 18(3), 658–672. https://doi.org/10.14202/vetworld.2025.658-672
Rodríguez, M. M., Ruiz, A., Piedra, L., Gutierrez, G., Rey, J., Cruz, M., & Bisset, J. A. (2020). Multiple insecticide resistance in Aedes aegypti (Diptera: Culicidae) from Boyeros municipality, Cuba and associated mechanisms. Acta Tropica, 212, Article 105680. https://doi.org/10.1016/j.actatropica.2020.105680
Silva, J. J., Kouam, C. N., & Scott, J. G. (2021). Levels of cross-resistance to pyrethroids conferred by the Vssc knockdown resistance allele 410L+1016I+1534C in Aedes aegypti. PLOS Neglected Tropical Diseases, 15(7), Article e0009549. https://doi.org/10.1371/journal.pntd.0009549
Solis-Santoyo, F., Rodriguez, A. D., Penilla-Navarro, R. P., Sanchez, D., Castillo-Vera, A., Lopez-Solis, A. D., Vazquez-Lopez, E. D., Lozano, S., Black, W. C., IV, & Saavedra-Rodriguez, K. (2021). Insecticide resistance in Aedes aegypti from Tapachula, Mexico: Spatial variation and response to historical insecticide use. PLOS Neglected Tropical Diseases, 15(9), Article e0009746. https://doi.org/10.1371/journal.pntd.0009746
Soni, M., Bhattacharya, C., Sharma, J., & Dutta, P. (2018). Bioassay and molecular study for detection of insecticide resistance dengue causing mosquito vectors. Indian Journal of Medical Microbiology, 36(3), 435–438. https://doi.org/10.4103/ijmm.IJMM_18_120
Su, X., Guo, Y., Deng, J., Xu, J., Zhou, G., Zhou, T., Li, Y., Zhong, D., Kong, L., Wang, X., Liu, M., Wu, K., Yan, G., & Chen, X.-G. (2019). Fast emerging insecticide resistance in Aedes albopictus in Guangzhou, China: Alarm to the dengue epidemic. PLOS Neglected Tropical Diseases, 13(9), Article e0007665. https://doi.org/10.1371/journal.pntd.0007665
Toé, H. K., Zongo, S., Guelbeogo, M. W., Kamgang, B., Viana, M., Tapsoba, M., Sanou, A., Traoré, A., McCall, P. J., & Sagnon, N. (2022). Multiple insecticide resistance and first evidence of V410L kdr mutation in Aedes (Stegomyia) aegypti (Linnaeus) from Burkina Faso. Medical and Veterinary Entomology, 36(3), 309–319. https://doi.org/10.1111/mve.12602
Uemura, N., Itokawa, K., Komagata, O., & Kasai, S. (2024). Recent advances in the study of knockdown resistance mutations in Aedes mosquitoes with a focus on several remarkable mutations. Current Opinion in Insect Science, 63, Article 101178. https://doi.org/10.1016/j.cois.2024.101178
Zhou, G., Li, Y., Jeang, B., Wang, X., Cummings, R. F., Zhong, D., & Yan, G. (2022). Emerging mosquito resistance to piperonyl butoxide-synergized pyrethroid insecticide and its mechanism. Journal of Medical Entomology, 59(2), 638–647. https://doi.org/10.1093/jme/tjab231







