Contact Bioassays with Phenoxybenzyl and Tetrafluorobenzyl Pyrethroids against Target-Site and Metabolic Resistant Mosquitoes

Abstract

BackgroundMosquito strains that exhibit increased tolerance to the chemical class of compounds with a sodium channel modulator mode of action (pyrethroids and pyrethrins) are typically described as “pyrethroid resistant”. Resistance to pyrethroids is an increasingly important challenge in the control of mosquito-borne diseases, such as malaria or dengue, because one of the main interventions (the distribution of large numbers of long-lasting insecticide-treated bed nets) currently relies entirely on long-lasting pyrethroids. Increasing tolerance of target insects against this class of insecticides lowers their impact in vector control. The current study suggests that the level of metabolic resistance depends on the structure of the molecule and that structurally different compounds may still be effective because detoxifying enzymes are unable to bind to these uncommon structures.MethodsTreated surface contact bioassays were performed on susceptible Aedes aegypti, East African knockdown resistance (kdr) Anopheles gambiae (strain RSP-H) and metabolically resistant Anopheles funestus (strain FUMOZ-R) with different pyrethroids, such as cypermethrin, ß-cyfluthrin, deltamethrin, permethrin and transfluthrin (alone and in combination with the synergist piperonyl butoxide). The nonfluorinated form of transfluthrin was also assessed as a single agent and in combination with piperonyl butoxide.ResultsAlthough the dosages for pyrethroids containing a phenoxybenzyl moiety have exhibited differences in terms of effectiveness among the three tested mosquito species, the structurally different transfluthrin with a polyfluorobenzyl moiety remained active in mosquitoes with upregulated P450 levels. In trials with transfluthrin mixed with piperonyl butoxide, the added synergist exhibited no efficacy-enhancing effect.ConclusionThe results of this study suggest that transfluthrin has the potential to control P450-mediated metabolically resistant mosquitoes because the structural formula of transfluthrin differs from that of the tested pyrethroids, which are used in vector control. The P450-detoxifying enzymes of the Anopheles funestus FUMOZ-R mosquitoes seem to bind preferably at the phenoxybenzyl moiety and appear to be unable to degrade transfluthrin with its tetrafluorobenzyl moiety. Inhibition of the class of monooxygenases by piperonyl butoxide revealed no increase of efficacy of the pure transfluthrin compound, which also indicates that the P450 enzymes potentially do not impact the efficacy of transfluthrin.

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

“…Unfortunately, the rate at which mosquitoes are becoming resistant to pyrethroids is alarming and represents an immediate, substantive threat to recent public gains made in the control of mosquito-borne diseases, malaria in particular [43,44]. It has been suggested that the tetrafluorobenzyl moiety of transfluthrin may make it more efficacious against some populations of pyrethroid-resistant mosquitoes than the conventional, non-volatile pyrethroids used for LLINs, IRS and impregnated clothes [45]. 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].…”

Effect of Metofluthrin-Impregnated Spatial Repellent Devices Combined with New Long-Lasting Insecticidal Nets (Olyset^® Plus) on Pyrethroid-Resistant Malaria Vectors and Malaria Prevalence: Field Trial in South-Eastern Malawi

“…Although the mechanism underlying the effectiveness of metofluthrin against pyrethroid-resistant mosquitoes has not yet been elucidated, it might be explained by the difference in chemical structure between the phenoxybenzyl alcohol-based pyrethroids, such as permethrin and deltamethrin, and tetrafluorobenzyl alcohol-based pyrethroids, such as transfluthrin and metofluthrin. Transfluthrin has the potential to control pyrethroid-resistant mosquitoes with P450-mediated enhanced metabolic factor, since the P450-detoxifying enzymes preferably bind at the phenoxybenzyl alcohol moiety, but not at the tetrafluorobenzyl moiety (24). Similarly, the resistance ratio of transfluthrin and metofluthrin was much smaller than that of permethrin against permethrin-resistant wild colonies of Culex quinquefasciatus Say (25).…”

Nebulización térmica intradomiciliar de la mezcla de flupyradifurona y transflutrina en mosquitos Aedes aegypti susceptibles y resistentes a piretroides en el Sur de México

“…25 En el caso de este formulado, se sabe que la transflutrina es un piretroide que carece del grupo difenoxibencilo característico del resto de los piretroides, sobre el cual inicia la degradación por las monooxigenasas o citocromos p450. 26 De la misma manera que en el caso de este formulado, aún cuando la resistencia metabólica por p450 estuviera alta en la población de mosquitos utilizada en este estudio, este componente en la mezcla eliminaría la ventaja de dicha resistencia. La nula recuperación a las 24 horas de individuos caídos a los 60 minutos parece confirmar lo anterior.…”