Impact of Aedes aegypti 1016I and 1534C knockdown resistance genotypes on operational interventions

Authors: Estep Iii, Alden; Sanscrainte, Neil; FAROOQ, MUHAMMAD - Anastasia Mosquito Control District; LUCAS, KEIRA - Collier Mosquito Control District; HEINIG, REBECCA - Collier Mosquito Control District; Norris, Edmund; Becnel, James

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/17/2025
Publication Date: 3/24/2025
Citation: Estep Iii, A.S., Sanscrainte, N.D., Farooq, M., Lucas, K.J., Heinig, R.L., Norris, E.J., Becnel, J.J. 2025. Impact of Aedes aegypti 1016I and 1534C knockdown resistance genotypes on operational interventions. Scientific Reports. 10146. https://doi.org/10.1038/s41598-025-94738-z.
DOI: https://doi.org/10.1038/s41598-025-94738-z

Interpretive Summary: Resistance to pyrethroid insecticides is common and frequently strong in Aedes aegypti and, in the Western Hemisphere, much of the resistance is due to two specific mutations of the voltage gated sodium channel. These mutations have been well characterized in the laboratory but information about the effects of these mutations on standard operational interventions used by mosquito and vector control programs is poorly studied. In this study, we used a field population of Aedes aegypti from St. Augustine, Florida to isolate the six field relevant combinations of these two mutations. Using well known control strains and standard laboratory methods, we assessed the levels of resistance of each strain. This testing showed distinct levels of resistance based on the number of copies of the IC haplotype. We also tested the same strains in field sprays, in the wind tunnel, and for the ability to bite through permethrin-treated fabrics like military uniforms. We found that even moderate levels of resistance could compromise the effectiveness of field sprays and the treated fabric. We also found that the most intense resistance overcame even the synergized pyrethroid formulations used when resistance may be present. This results of this study provide valuable data that is directly relevant to operational mosquito control and is useful for making more effective operational control decisions as part of an integrated vector management program.

Technical Abstract: Insecticide resistance (IR) to pyrethroids is common in Aedes aegypti populations. Mutations in the voltage gated sodium channel have an influence on the IR phenotype. In much of the Western hemisphere, two of these knockdown resistance (kdr) mutations, V1016I and F1534C, are widely found and result in six kdr genotype combinations in field populations. Strong pyrethroid IR and the failure of permethrin treated uniforms have been linked to the presence of the homozygous double kdr genotype (IICC) but the effects of these various kdr combinations have not been rigorously examined. To better understand the impacts of kdr, we isolated three kdr haplotypes (VF, VC, & IC) in a field strain to produce six Ae. aegypti isoline strains with all common kdr genotypes. We then characterized the effects of these kdr genotypes by CDC bottle bioassay and topical application and found increasing resistance to permethrin and deltamethrin as the number of IC haplotypes increased. Neither enzymatic activity nor malathion IR increased as pyrethroid IR increased. Field and wind tunnel spray of a pyrethrin formulation showed even moderate resistance could significantly reduce knockdown and mortality. Studies with a synergized pyrethroid formulation showed effective recovery of mortality against all genotypes except for the IICC. In human bite studies, one or two IC haplotypes compromised the efficacy of permethrin treated fabrics. This study demonstrates that kdr mutations have distinct phenotypic effects in both the laboratory and operational interventions, and that the strength of negative impacts of kdr depend on the number of IC haplotypes present. Assessing kdr genotype is therefore critical for understanding target-site-mediated IR in Ae. aegypti.