RT Journal Article
T1 Dose-dependent tissue tropism and efficacy of early BKI-1748 treatment in chronic Toxoplasma gondii infection in sheep
A1 Sánchez Sánchez, Roberto
A1 Calero Bernal, Rafael
A1 Velasco-Jiménez, Natalia
A1 Gallego-Moreno, Irene
A1 Pérez Díaz, Carmen
A1 Bustamante Domínguez, Rocío
A1 Choi, Ryan
A1 Hulverson, Matthew A.
A1 Hemphill, Andrew
A1 Van Voorhis, Wesley C.
A1 Ortega Mora, Luis Miguel
AB The 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 consumption
PB Elsevier
YR 2025
FD 2025
LK https://hdl.handle.net/20.500.14352/127320
UL https://hdl.handle.net/20.500.14352/127320
LA eng
NO Sánchez-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.e00297
NO Credit authorship contribution statementRoberto 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, Conceptualization
NO United States Department of Agriculture (USDA)
NO National Institutes of Health (NIH, Bethesda, Maryland, USA)
NO Swiss National Science Foundation (SNSF) [
NO Comunidad de Madrid
DS Docta Complutense
RD 6 abr 2026