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

## TL;DR

This study shows that the amount of Toxoplasma gondii in sheep meat depends on the infection dose and that early treatment with BKI-1748 can prevent chronic infection.

## Contribution

The study reveals dose-dependent tissue tropism and the efficacy of early BKI-1748 treatment in chronic T. gondii infection in sheep.

## Key findings

- Parasite DNA detection rates in tissues varied with the challenge dose in sheep.
- BKI-1748 treatment at early stages prevented chronic T. gondii infection in sheep.
- Low-dose infection mimics natural infection patterns in sheep edible tissues.

## Abstract

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.

•Tissue cyst distribution of T. gondii in sheep depends on challenge dose used.•Infection with 10 oocysts results in zoites detected in edible sheep tissues.•Early BKI-1748 treatment prevents the establishment of chronic infection in sheep.

Tissue cyst distribution of T. gondii in sheep depends on challenge dose used.

Infection with 10 oocysts results in zoites detected in edible sheep tissues.

Early BKI-1748 treatment prevents the establishment of chronic infection in sheep.