**Background:** Chagas disease, caused by Trypanosoma cruzi, affects an estimated 6,469,283 people in the Americas as of 2019. Vector control relies heavily on indoor pyrethroid spraying, but resistance and recolonization from sylvatic refugia limit its effectiveness. Xenointoxication—treating vertebrate hosts with systemic insecticides to kill blood-feeding vectors—has shown promise in dogs but has not been evaluated in poultry or against North American triatomine species. Chickens are abundant in Chagas-endemic regions and are common blood-meal hosts for triatomines, though they are not competent T. cruzi reservoirs. This study evaluated three systemic insecticides (fluralaner, fenbendazole, ivermectin) administered orally to chickens for their ability to kill Triatoma gerstaeckeri, the most common triatomine species encountered by humans in Texas.
**Methods:** Eighty female Hy-line W-36 chickens (average weight 1.34 kg, age 18–38 weeks) were used. Chickens were assigned to one of four groups: fluralaner (Bravecto® chewable tablet, 3.6 mg/kg BW, given twice 7 days apart), fenbendazole (Safe-Guard® AquaSol, 1 mg/kg BW in drinking water daily for 5 days), ivermectin (Ivomec® Pour-On, 0.4 mg/kg BW in drinking water daily for 5 days), or untreated controls. Third- to fifth-instar T. gerstaeckeri nymphs (F2–F3 generations from wild Texas populations) were allowed to feed on chickens at 0, 3, 7, 14, 28, and 56 days post-treatment (DPT). Each trial used three triatomines per chicken, fed for 45 minutes under red light. Feeding success, engorgement level (0–3 scale), and survival were recorded daily for 10 days post-feeding. Kaplan–Meier survival curves and logistic regression were used for analysis. Serum concentrations of fluralaner and fenbendazole were measured by liquid chromatography tandem mass spectrometry (LC-QQQ). A total of 234 triatomines were used across all trials.
**Key Results:** Feeding success averaged 77.4% across all treatments (range 68.6–83.3%). Treatment, life stage, and DPT did not significantly affect feeding success or engorgement level. Only fluralaner produced mortality in T. gerstaeckeri. At 3 DPT, all triatomines that fed on fluralaner-treated chickens died within 4 days. At 7 DPT, 90% died within 10 days; at 14 DPT, 50% died within 10 days. No mortality was observed at 28 or 56 DPT. All triatomines that fed on control, ivermectin-, or fenbendazole-treated chickens survived at all time points. Logistic regression showed that triatomines with an engorgement score of 3 were 77% less likely to die than those with a score of 1 (OR 0.23, 95% CI 0.08–0.64, P = 0.01). Serum fluralaner concentrations ranged from 93.5 ng/ml to below the limit of quantification (2.5 ng/ml) and were detectable only at 3, 7, and 14 DPT. All fenbendazole serum samples were below 5 ng/ml at all time points.
**Clinical Implications:** This study provides the first evidence that fluralaner treatment of chickens can kill North American triatomine vectors via xenointoxication. The effect was limited to the first 14 days post-treatment, corresponding to detectable serum drug levels. Fluralaner's efficacy window is shorter in chickens than the up to 7 months reported in dogs, but it could still be useful in integrated vector management, particularly when combined with other interventions such as housing improvements and insecticide spraying. Neither fenbendazole nor ivermectin showed any triatomine mortality under the dosing regimens used. The lack of feeding deterrence suggests treated chickens would not divert vectors to humans. Future research should evaluate fluralaner against other triatomine species, assess field effectiveness, and explore formulations such as Exzolt™ (a poultry-specific fluralaner product) that could be added to drinking water for easier delivery.