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J Infect Dis ; 229(2): 558-566, 2024 Feb 14.
Article En | MEDLINE | ID: mdl-37889572

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.


Abortion, Spontaneous , Communicable Diseases , Toxoplasma , Toxoplasmosis, Congenital , Toxoplasmosis , Pregnancy , Humans , Female , Mice , Sheep , Animals , Toxoplasmosis, Congenital/drug therapy , Toxoplasmosis, Congenital/prevention & control , Mammals
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