Nootkatone Is an Effective Repellent against Aedes aegypti and Aedes albopictus

SIMPLE SUMMARY: Nootkatone, a natural organic compound in grapefruit and Alaskan yellow cedar, may have use as an insecticide and repellent against Aedes mosquito vectors of arboviruses. Here, we tested nootkatone against two medically important mosquito vectors, Aedes aegypti and Aedes albopictus. The insecticide potential of nootkatone was tested for both species using bottle bioassays and the repellency/irritancy and biting inhibition bioassays (RIBB) were used as tests for the A. aegypti strains only. We analyzed nootkatone’s insecticide potential against the New Orleans and Vergel strains of A. aegypti and ATM-NJ95 and Coatzacoalcos strains of A. albopictus. These strains were chosen because the New Orleans and ATM-NJ95 were permethrin susceptible (PERM-S) and Vergel was a confirmed permethrin resistant (PERM-R) strain. Coatzalcalcos was of unknown permethrin susceptibility. Permethrin is a commonly used insecticide to control mosquito populations, and permethrin resistance is becoming widespread in mosquito populations. We therefore wanted to compare nootkatone’s efficacy (and possible synergy) in the background of permethrin-susceptible and -resistant vectors. Bottle bioassays confirmed that the PERM-R Vergel strain was significantly less sensitive to nootkatone compared to PERM-S A. aegypti (New Orleans) and both A. albopictus strains were at least as sensitive to nootkatone as the New Orleans strain. We also showed that Zika virus (ZIKV)-infected New Orleans mosquitoes were as susceptible to nootkatone as the mock-infected controls. The infected Vergel strain was significantly less sensitive to nootkatone exposure than the New Orleans, ATM-NJ95, or Coatzacoalcos mosquitoes. In general, our studies concluded that as an insecticide, nootkatone was approximately 1000× less sensitive than permethrin, making it ineffective against A. aegypti and A. albopictus. However, RIBB analyses determined that nootkatone-treated arms of human subjects inhibited host-seeking and biting by A. aegypti mosquitoes. RIBB studies concluded that 20% nootkatone repelled mosquitoes at a rate comparable to commercially available N,N-Diethyl-m-toluamide (DEET; 7%) or picaridin (5%). Nootkatone has the potential to be an efficacious repellent against adult Aedes mosquitoes. ABSTRACT: We tested a nootkatone product for insecticide activity against the most prominent vectors of Zika virus (ZIKV), Aedes aegypti, and Aedes albopictus. We tested the permethrin-resistant (PERM-R) Vergel strain of A. aegypti and the permethrin-susceptible (PERM-S) New Orleans strain of A. aegypti to determine if insecticide resistance affected their susceptibility to nootkatone. Bottle bioassays showed that the PERM-S strain (New Orleans) was more susceptible to nootkatone than the confirmed A. aegypti permethrin-resistant (PERM-R) strain, Vergel. The A. albopictus strain ATM-NJ95 was a known PERM-S strain and Coatzacoalcos permethrin susceptibility was unknown but proved to be similar to the ATM-NJ95 PERM-S phenotype. The A. albopictus strains (ATM-NJ95 and Coatzacoalcos) were as susceptible to nootkatone as the New Orleans strain. Bottle bioassays conducted with ZIKV-infected mosquitoes showed that the New Orleans (PERM-S) strain was as susceptible to nootkatone as the mock-infected controls, but the PERM-R strain was less susceptible to nootkatone than the mock-infected controls. Repellency/irritancy and biting inhibition bioassays (RIBB) of A. aegypti determined whether the nootkatone-treated arms of three human subjects prevented uninfected A. aegypti mosquitoes from being attracted to the test subjects and blood-feeding on them. The RIBB analyses data calculated the spatial activity index (SAI) and biting inhibition factor (BI) of A. aegypti at different nootkatone concentrations and then compared the SAI and BI of existing repellency products. We concluded that nootkatone repelled mosquitoes at a rate comparable to 7% DEET or 5% picaridin and has the potential to be an efficacious repellent against adult A. aegypti mosquitoes.