Stability Challenges and Non-Target Effects of Mandelonitrile-Based Sugar Baits for Leishmaniasis Vector Control

Leishmaniasis is a vector-borne disease of global concern, transmitted by sand flies of the genera Lutzomyia and Phlebotomus. Attractive toxic sugar baits (ATSBs) have emerged as a promising alternative for vector control, leveraging the sugar-feeding behavior of adult sand flies. Mandelonitrile, a plant-derived compound with potent anti-Leishmania activity, has shown promise in reducing parasite load and sand fly longevity. However, key aspects such as bait stability and off-target effects remain poorly understood. In this study, we evaluated the stability of 70% sucrose-based sugar baits supplemented with methylparaben or sodium azide, and quantified mandelonitrile degradation over time using a GC-MS protocol adapted for high-sucrose matrices. We also assessed the physiological impact of mandelonitrile on the non-target model organism Drosophila melanogaster. Results demonstrated that methylparaben and sodium azide can stabilize sucrose solutions for up to seven days, although both compounds affected sand fly survival. Mandelonitrile was undetectable after one week, indicating rapid degradation or volatilization. In D. melanogaster, mandelonitrile reduced longevity and inhibited oviposition. This is the first report on the stability and off-target effects of mandelonitrile sugar baits, highlighting the need for improved formulations and thorough evaluation of their ecological safety, with the goal of developing transmission-blocking sugar baits for leishmaniasis control.