An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion and Congenital Infection in Sheep Experimentally Infected With Toxoplasma gondii.

Autor:	Sánchez-Sánchez R; SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Madrid, Spain., Imhof D; Institute of Parasitology, Vetsuisse Faculty, University of Berne, Berne, Switzerland., Hecker YP; SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Madrid, Spain.; Institute of Innovation for Agricultural Production and Sustainable Development (IPADS, Balcarce), INTA-CONICET, Balcarce, Argentina., Ferre I; SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Madrid, Spain., Re M; SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Madrid, Spain.; Animal Medicine and Surgery Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Madrid, Spain., Moreno-Gonzalo J; SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Madrid, Spain.; Animal Medicine and Surgery Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Madrid, Spain., Blanco-Murcia J; SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Madrid, Spain.; Animal Medicine and Surgery Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Madrid, Spain., Mejías-López E; Animal Medicine and Surgery Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Madrid, Spain., Hulverson MA; Center for Emerging and Re-emerging Infectious Diseases, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA., Choi R; Center for Emerging and Re-emerging Infectious Diseases, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA., Arnold SLM; Department of Pharmaceutics, University of Washington, Seattle, Washington, USA., Ojo KK; Center for Emerging and Re-emerging Infectious Diseases, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA., Barrett LK; Center for Emerging and Re-emerging Infectious Diseases, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA., Hemphill A; Institute of Parasitology, Vetsuisse Faculty, University of Berne, Berne, Switzerland., Van Voorhis WC; Center for Emerging and Re-emerging Infectious Diseases, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA., Ortega-Mora LM; SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Madrid, Spain.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2024 Feb 14; Vol. 229 (2), pp. 558-566.
DOI:	10.1093/infdis/jiad470
Abstrakt:	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. Competing Interests: Potential conflicts of interest . W. C. V. V. is the President and co-owner of ParaTheraTech Inc, a company that is developing BKIs for animal health. He did not perform the experiments, nor interpret the results of the experiments, but did edit this article and helped plan the experiments. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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