Dose-dependent tissue tropism and efficacy of early BKI-1748 treatment in chronic Toxoplasma gondii infection in sheep

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 di...

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Bibliographic Details
Authors: Sánchez Sánchez, Roberto, Calero Bernal, Rafael, Velasco-Jiménez, Natalia, Gallego-Moreno, Irene, Pérez Díaz, Carmen, Bustamante Domínguez, Rocío, Choi, Ryan, Hulverson, Matthew A., Hemphill, Andrew, Van Voorhis, Wesley C., Ortega Mora, Luis Miguel
Format: article
Publication Date:2025
Country:España
Institution:Universidad Complutense de Madrid (UCM)
Repository:Docta Complutense
Language:English
OAI Identifier:oai:docta.ucm.es:20.500.14352/127320
Online Access:https://hdl.handle.net/20.500.14352/127320
Access Level:Open access
Keyword:636.09
Toxoplasma gondii
Sheep
Chronic infection
Tissue tropism
Food safety
BKI-1748
Veterinaria
3109 Ciencias Veterinarias
Description
Summary: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