Phlebotomine sand flies are vectors of Leishmania major parasites and remain a significant global health problem due to the lack of efficacious control methods to reduce phlebotomine populations. One potential mechanism to control Phlebotomous papatasi in Sub-Saharan Africa is through the treatment of wild rodent populations with a systemic insecticide because rodents are the primary source for blood meals that are required for sand fly reproduction. Fipronil, a phenylpyrazole chemical that blocks the GABA-gated chloride channels, was found to be highly toxic to sand flies with a concentration required to kill 50% of flies (LC50) of 496 nM (95% CI: 414-578, Hillslope: 1.2; r2: 0.95). Importantly, blood feeding assays on rodents that had been treated with fipronil through oral exposure showed high systemicity of fipronil with &gt;95% sand fly mortality remaining 49 days after rodents were withdrawn from their fipronil-treated diet. Due to the potential for fipronil resistance to exist in wild sand fly populations, we tested the toxicity of isoxazoline and diamide insecticides to sand flies, which are highly specific inhibitors of ligand-gated chloride channels and ryanodine receptors, respectively. Both insecticial classes are known to have long in vivo-half lives in mammals. Fluralaner was initially tested through an artificial host feeding system to determine the inherent toxicity to P. papatasi and was found to be 1.3-fold more toxic when compared to fipronil with an LC50 of 382 nM (95% CI: 334-438, Hillslope: 2.8; r2: 0.97). The diamide insecticides were tested through an artificial host feeding system and chlorantraniliprole was found to be the most toxic molecule studied with an LC50 value 3-fold less than fluralaner (LC50: 100 nM). Interestingly, flubendiamide was non-toxic at 500 nM. The mammalian half-life of fluralaner and chlorantraniliprole are 4- and 6-fold longer than fipronil, suggesting these molecules are candidates to be used as an oral insecticide drug to control P. papatasi.

Repurposing isoxazoline and diamide insecticides to control the sand fly, Phlebotomus papatasi

2019 Fall National Meeting

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