Sánchez Sánchez, RobertoCalero Bernal, RafaelVelasco-Jiménez, NataliaGallego-Moreno, IrenePérez Díaz, CarmenBustamante Domínguez, RocíoChoi, RyanHulverson, Matthew A.Hemphill, AndrewVan Voorhis, Wesley C.Ortega Mora, Luis Miguel2025-11-252025-11-252025Sánchez-Sánchez, R., Calero-Bernal, R., Velasco-Jiménez, N., Gallego-Moreno, I., Pérez-Díaz, C., Bustamante, R., Choi, R., Hulverson, M. A., Hemphill, A., Van Voorhis, W. C., & Ortega-Mora, L. M. (2025). Dose-dependent tissue tropism and efficacy of early BKI-1748 treatment in chronic Toxoplasma gondii infection in sheep. Food and Waterborne Parasitology, 41, e00297. https://doi.org/10.1016/j.fawpar.2025.e0029710.1016/j.fawpar.2025.e00297https://hdl.handle.net/20.500.14352/127320Credit authorship contribution statement Roberto Sánchez-Sánchez: Writing – review & editing, Writing – original draft, Methodology, Investigation, Formal analysis, Conceptualization. Rafael Calero-Bernal: Writing – review & editing, Methodology, Conceptualization. Natalia Velasco-Jiménez: Writing – review & editing, Investigation. Irene Gallego-Moreno: Writing – review & editing, Investigation. Carmen Pérez-Díaz: Writing – review & editing, Investigation. Rocío Bustamante: Writing – review & editing, Investigation. Ryan Choi: Writing – review & editing, Investigation. Matthew A. Hulverson: Writing – review & editing, Investigation. Andrew Hemphill: Writing – review & editing, Funding acquisition. Wesley C. Van Voorhis: Writing – review & editing, Project administration, Funding acquisition. Luis Miguel Ortega-Mora: Writing – review & editing, Project administration, Funding acquisition, ConceptualizationThe presence of microscopic cysts of the zoonotic apicomplexan parasite Toxoplasma gondii in mutton is relatively common. Toxoplasma gondii is frequently transmitted to humans through the consumption of raw or undercooked meat and infected people may suffer from neurological, ocular and pregnancy disorders. Experimental infections in sheep have provided clues on the T. gondii tissue tropism during the chronic stage of infection. However, data regarding infections involving low challenge doses is lacking. Following challenge of sheep with 1000 sporulated oocysts of the Type II TgShSp1 strain, parasite DNA was detected in all sheep at 62 days post-challenge, with detection rates of 87 %, 79 %, 66 % and 66 % in the brain, heart, tongue and biceps femoris muscle, respectively. By contrast, after challenge of sheep with a dose of 10 oocysts, parasite DNA was detected in tissues of only 5 out of 8 animals (62.5 %). The biceps femoris muscle was the most frequently infected tissue (parasite DNA detection rate of 50 %), resembling the pattern observed in naturally infected sheep. In addition, the administration of multiple doses of the compound BKI-1748, which reached therapeutic concentrations in plasma and cerebrospinal fluid, to infected sheep at 2 and 7 days post-challenge prevented the establishment of the chronic T. gondii infection in the treated animals. Therefore, BKI-1748 could be a promising tool for improving safety in mutton intended for human consumptionengAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article2405-6766https://doi.org/10.1016/j.fawpar.2025.e00297open access636.09Toxoplasma gondiiSheepChronic infectionTissue tropismFood safetyBKI-1748Veterinaria3109 Ciencias Veterinarias