%0 Journal Article
%A Sánchez Sánchez, Roberto
%A Imhof, Dennis
%A Hecker, Yanina Paola
%A Ferré Pérez, Ignacio
%A Re, Michela Tatiana
%A Moreno Gonzalo, Javier
%A Blanco Murcia, Francisco Javier
%A Mejías López, Elena
%A Hulverson, Matthew A.
%A Choi, Ryan
%A Arnold, Samuel L. M.
%A Ojo, Kayode K.
%A Barrett, Lynn K.
%A Hemphill, Andrew
%A Van Voorhis, Wesley C.
%A Ortega Mora, Luis Miguel
%T An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion and Congenital Infection in Sheep Experimentally Infected With Toxoplasma gondii
%D 2023
%@ 0022-1899
%U https://hdl.handle.net/20.500.14352/104468
%X 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.
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