Insensitivity to the Spatial Repellent Action of Transfluthrin in Aedes aegypti: A Heritable Trait Associated with Decreased Insecticide Susceptibility

Abstract

BackgroundNew vector control paradigms expanding the use of spatial repellents are promising, but there are many gaps in our knowledge about how repellents work and how their long-term use might affect vector populations over time. Reported here are findings from a series of in vitro studies that investigated the plasticity and heritability of spatial repellent (SR) behaviors in Aedes aegypti exposed to airborne transfluthrin, including results that indicate a possible link between repellent insensitivity and insecticide resistance.Methodology/principal findingsA dual-choice chamber system was used to observe directional flight behaviors in Aedes aegypti mosquitoes exposed to passively emanating transfluthrin vapors (1.35 mg/m3). Individual SR responder and SR non-responder mosquitoes were identified, collected and maintained separately according to their observed phenotype. Subsequent testing included re-evaluation of behavioral responses in some mosquito cohorts as well as testing the progeny of selectively bred responder and non-responder mosquito strains through nine generations. At baseline (F0 generation), transfluthrin actively repelled mosquitoes in the assay system. F0 mosquitoes repelled upon initial exposure to transfluthrin vapors were no more likely to be repelled again by subsequent exposure 24h later, but repelled mosquitoes allowed to rest for 48h were subsequently repelled at a higher proportion than was observed at baseline. Selective breeding of SR responders for nine generations did not change the proportion of mosquitoes repelled in any generation. However, selective breeding of SR non-responders did produce, after four generations, a strain of mosquitoes that was insensitive to the SR activity of transfluthrin. Compared to the SR responder strain, the SR insensitive strain also demonstrated decreased susceptibility to transfluthrin toxicity in CDC bottle bioassays and a higher frequency of the V1016Ikdr mutation.Conclusions/significanceSR responses to volatile transfluthrin are complex behaviors with multiple determinants in Ae. aegypti. Results indicate a role for neurotoxic irritation of mosquitoes by sub-lethal doses of airborne chemical as a mechanism by which transfluthrin can produce SR behaviors in mosquitoes. Accordingly, how prolonged exposure to sub-lethal doses of volatile pyrethroids might impact insecticide resistance in natural vector populations, and how already resistant populations might respond to a given repellent in the field, are important considerations that warrant further monitoring and study. Results also highlight the critical need to develop new repellent active ingredients with novel mechanisms of action.

Reduced effectiveness of repellents in a pyrethroid‐resistant strain of Aedes aegypti (Diptera: culicidae) and its correlation with olfactory sensitivity

“…Our study also observed significant resistance to both the toxicity and repellency of pyrethrum, transfluthrin, and metofluthrin in the PR strain, similar to that observed for transfluthrin in a selected pyrethroid‐resistant strain of Ae. aegypti by Wagman et al . Similarly, Kawada et al .…”

“…30 Our study also observed significant resistance to both the toxicity and repellency of pyrethrum, transfluthrin, and metofluthrin in the PR strain, similar to that observed for transfluthrin in a selected pyrethroid-resistant strain of Ae. aegypti by Wagman et al 21 Similarly, Kawada et al 31 showed resistance to both contact repellency and lethality to permethrin and deltamethrin when tested on kdr-resistant Anopheles gambiae. In our study, the PR strain showed similar resistance in vapor and topical toxicity to these compounds, but showed different resistance ratios for repellency.…”

“…aegypti was exposed to transfluthrin, which acts as both an insecticide and repellent, it showed that mosquitoes had decreased sensitivity to both effects. 21 A recent study by Bowman et al, however, reported that pyrethroids maintained their repellent properties in knockdown resistant populations of Ae. aegypti mosquitoes from San Juan, Puerto Rico that showed high resistance when measured as mortality.…”

A low technology emanator treated with the volatile pyrethroid transfluthrin confers long term protection against outdoor biting vectors of lymphatic filariasis, arboviruses and malaria

“…However, distinct metabolic, knock-down and cuticular forms of resistance against pyrethroids have already been documented and more may emerge, [43,44] so it seems unlikely that the polyflurobenyl-modified pyrethroids alone will provide a panacea to address this “looming public health catastrophe” [43]. Furthermore, recent studies of Aedes aegypti indicate that physiological resistance to the lethal effects of transfluthrin may be associated with concomitantly decreased responsiveness to its repellent mode of action at sub-lethal doses [46]. …”

High‐throughput screening method for evaluating spatial repellency and vapour toxicity to mosquitoes

“…Among commercially available active ingredients, DEET remains the 'gold standard' contact repellent (Leal, 2014), although continuous usage can lead to resistance (Pellegrino et al, 2011;Stanczyk et al, 2013;Sugiharto et al, 2016). Similar concerns have been raised for volatile pyrethroids because of widespread kdr resistance to pyrethroid insecticides in the field and, furthermore, reduced sensitivity to transfluthrin was observed in laboratory-selected strains of Aedes aegypti from Belize (Wagman et al, 2015) and Puerto Rico (Agramonte et al, 2017).…”