2023/10/27 by Roberto Sánchez-Sánchez, Dennis Imhof, Yanina P. Hecker +13 · 1 voice · 1 citation
Immunology and Microbiology · Medicine · #Cytomegalovirus and herpesvirus research #Parasitic Infections and Diagnostics #Toxoplasma gondii Research Studies
paper · pdf · doi:10.1093/infdis/jiad470
openalex publication_date 2023/10/27 · openalex created_date 2023/10/28 · openalex updated_date 2026/07/28
Congenital toxoplasmosis in humans and in other mammalian species, such as small ruminants, is a well-known cause of abortion and fetal malformations. The calcium-dependent protein kinase 1 (CDPK1) inhibitor BKI-1748 has shown a promising safety profile for its use in humans and a good efficacy against Toxoplasma gondii infection in vitro and in mouse models. Ten doses of BKI-1748 given every other day orally in sheep at 15 mg/kg did not show systemic or pregnancy-related toxicity. In sheep experimentally infected at 90 days of pregnancy with 1000 TgShSp1 oocysts, the BKI-1748 treatment administered from 48 hours after infection led to complete protection against abortion and congenital infection. In addition, compared to infected/untreated sheep, treated sheep showed a drastically lower rectal temperature increase and none showed IgG seroconversion throughout the study. In conclusion, BKI-1748 treatment in pregnant sheep starting at 48 hours after infection was fully effective against congenital toxoplasmosis.