An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion and Congenital Infection in Sheep Experimentally Infected With Toxoplasma gondii.
J Infect Dis
; 229(2): 558-566, 2024 Feb 14.
Article
em En
| MEDLINE
| ID: mdl-37889572
ABSTRACT
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 15â
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 48â
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 48â
hours after infection was fully effective against congenital toxoplasmosis.
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Base de dados:
MEDLINE
Assunto principal:
Toxoplasma
/
Aborto Espontâneo
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Toxoplasmose
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Toxoplasmose Congênita
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Doenças Transmissíveis
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article