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

Autores
Sánchez Sánchez, Roberto; Imhof, Dennis; Hecker, Yanina; Ferre, Ignacio; Re, Michela; Moreno Gonzalo, Javier; Blanco Murcia, Javier; Mejías López, Elena; Hulverson, Matthew; Choi, Ryan; Ojo, Kayode; Barrett, Lynn; Hemphill, Andrew; Van Voorhis, Wesley; Ortega Mora, Luis Miguel
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión aceptada
Descripción
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.
EEA Balcarce
Fil: Sánchez Sánchez, Roberto. Universidad Complutense de Madrid. Facultad de Veterinaria; España
Fil: Imhof, Dennis. University of Berne. Vetsuisse Faculty. Institute of Parasitology; Suiza
Fil: Hecker, Yanina Paola. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina
Fil: Ferre, Ignacio. Universidad Complutense de Madrid. Facultad de Veterinaria; España
Fil: Re, Michela. Universidad Complutense de Madrid. Facultad de Veterinaria; España
Fil: Moreno Gonzalo, Javier. Universidad Complutense de Madrid. Facultad de Veterinaria; España
Fil: Blanco Murcia, Javier. Universidad Complutense de Madrid. Facultad de Veterinaria; España
Fil: Mejías López, Elena. Universidad Complutense de Madrid. Facultad de Veterinaria; España
Fil: Hulverson, Matthew. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados Unidos
Fil: Choi, Ryan. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados Unidos
Fil: Arnold, Samuel. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados Unidos
Fil: Ojo, Kayode. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados Unidos
Fil: Barrett, Lynn. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados Unidos
Fil: Hemphill, Andrew. University of Berne. Vetsuisse Faculty. Institute of Parasitology; Suiza
Fil: Van Voorhis, Wesley. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados Unidos
Fil: Ortega Mora, Luis Miguel. Universidad Complutense de Madrid. Facultad de Veterinaria; España
Fuente
The Journal of Infectious Diseases 229 (2) : 558-566 (February 2024)
Materia
Oveja
Aborto
Infección Experimental
Sanidad Animal
Ewes
Abortion
Toxoplasma Gondii
Exprimental Infection
Animal Health
Nivel de accesibilidad
acceso restringido
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/17776
Acceder
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oai_identifier_str oai:localhost:20.500.12123/17776
network_acronym_str INTADig
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network_name_str INTA Digital (INTA)
spelling An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion and Congenital Infection in Sheep Experimentally Infected With Toxoplasma gondiiSánchez Sánchez, RobertoImhof, DennisHecker, YaninaFerre, IgnacioRe, MichelaMoreno Gonzalo, JavierBlanco Murcia, JavierMejías López, ElenaHulverson, MatthewChoi, RyanOjo, KayodeBarrett, LynnHemphill, AndrewVan Voorhis, WesleyOrtega Mora, Luis MiguelOvejaAbortoInfección ExperimentalSanidad AnimalEwesAbortionToxoplasma GondiiExprimental InfectionAnimal HealthCongenital 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.EEA BalcarceFil: Sánchez Sánchez, Roberto. Universidad Complutense de Madrid. Facultad de Veterinaria; EspañaFil: Imhof, Dennis. University of Berne. Vetsuisse Faculty. Institute of Parasitology; SuizaFil: Hecker, Yanina Paola. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; ArgentinaFil: Ferre, Ignacio. Universidad Complutense de Madrid. Facultad de Veterinaria; EspañaFil: Re, Michela. Universidad Complutense de Madrid. Facultad de Veterinaria; EspañaFil: Moreno Gonzalo, Javier. Universidad Complutense de Madrid. Facultad de Veterinaria; EspañaFil: Blanco Murcia, Javier. Universidad Complutense de Madrid. Facultad de Veterinaria; EspañaFil: Mejías López, Elena. Universidad Complutense de Madrid. Facultad de Veterinaria; EspañaFil: Hulverson, Matthew. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados UnidosFil: Choi, Ryan. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados UnidosFil: Arnold, Samuel. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados UnidosFil: Ojo, Kayode. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados UnidosFil: Barrett, Lynn. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados UnidosFil: Hemphill, Andrew. University of Berne. Vetsuisse Faculty. Institute of Parasitology; SuizaFil: Van Voorhis, Wesley. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados UnidosFil: Ortega Mora, Luis Miguel. Universidad Complutense de Madrid. Facultad de Veterinaria; EspañaOxford University Pressinfo:eu-repo/date/embargoEnd/2025-05-172024-05-17T10:12:54Z2024-05-17T10:12:54Z2023-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/17776https://academic.oup.com/jid/article-abstract/229/2/558/73310600022-1899https://doi.org/10.1093/infdis/jiad470The Journal of Infectious Diseases 229 (2) : 558-566 (February 2024)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/restrictedAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-09-04T09:50:23Zoai:localhost:20.500.12123/17776instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-04 09:50:23.526INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion and Congenital Infection in Sheep Experimentally Infected With Toxoplasma gondii
title An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion and Congenital Infection in Sheep Experimentally Infected With Toxoplasma gondii
spellingShingle An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion and Congenital Infection in Sheep Experimentally Infected With Toxoplasma gondii
Sánchez Sánchez, Roberto
Oveja
Aborto
Infección Experimental
Sanidad Animal
Ewes
Abortion
Toxoplasma Gondii
Exprimental Infection
Animal Health
title_short An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion and Congenital Infection in Sheep Experimentally Infected With Toxoplasma gondii
title_full An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion and Congenital Infection in Sheep Experimentally Infected With Toxoplasma gondii
title_fullStr An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion and Congenital Infection in Sheep Experimentally Infected With Toxoplasma gondii
title_full_unstemmed An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion and Congenital Infection in Sheep Experimentally Infected With Toxoplasma gondii
title_sort An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion and Congenital Infection in Sheep Experimentally Infected With Toxoplasma gondii
dc.creator.none.fl_str_mv Sánchez Sánchez, Roberto
Imhof, Dennis
Hecker, Yanina
Ferre, Ignacio
Re, Michela
Moreno Gonzalo, Javier
Blanco Murcia, Javier
Mejías López, Elena
Hulverson, Matthew
Choi, Ryan
Ojo, Kayode
Barrett, Lynn
Hemphill, Andrew
Van Voorhis, Wesley
Ortega Mora, Luis Miguel
author Sánchez Sánchez, Roberto
author_facet Sánchez Sánchez, Roberto
Imhof, Dennis
Hecker, Yanina
Ferre, Ignacio
Re, Michela
Moreno Gonzalo, Javier
Blanco Murcia, Javier
Mejías López, Elena
Hulverson, Matthew
Choi, Ryan
Ojo, Kayode
Barrett, Lynn
Hemphill, Andrew
Van Voorhis, Wesley
Ortega Mora, Luis Miguel
author_role author
author2 Imhof, Dennis
Hecker, Yanina
Ferre, Ignacio
Re, Michela
Moreno Gonzalo, Javier
Blanco Murcia, Javier
Mejías López, Elena
Hulverson, Matthew
Choi, Ryan
Ojo, Kayode
Barrett, Lynn
Hemphill, Andrew
Van Voorhis, Wesley
Ortega Mora, Luis Miguel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Oveja
Aborto
Infección Experimental
Sanidad Animal
Ewes
Abortion
Toxoplasma Gondii
Exprimental Infection
Animal Health
topic Oveja
Aborto
Infección Experimental
Sanidad Animal
Ewes
Abortion
Toxoplasma Gondii
Exprimental Infection
Animal Health
dc.description.none.fl_txt_mv 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.
EEA Balcarce
Fil: Sánchez Sánchez, Roberto. Universidad Complutense de Madrid. Facultad de Veterinaria; España
Fil: Imhof, Dennis. University of Berne. Vetsuisse Faculty. Institute of Parasitology; Suiza
Fil: Hecker, Yanina Paola. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina
Fil: Ferre, Ignacio. Universidad Complutense de Madrid. Facultad de Veterinaria; España
Fil: Re, Michela. Universidad Complutense de Madrid. Facultad de Veterinaria; España
Fil: Moreno Gonzalo, Javier. Universidad Complutense de Madrid. Facultad de Veterinaria; España
Fil: Blanco Murcia, Javier. Universidad Complutense de Madrid. Facultad de Veterinaria; España
Fil: Mejías López, Elena. Universidad Complutense de Madrid. Facultad de Veterinaria; España
Fil: Hulverson, Matthew. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados Unidos
Fil: Choi, Ryan. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados Unidos
Fil: Arnold, Samuel. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados Unidos
Fil: Ojo, Kayode. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados Unidos
Fil: Barrett, Lynn. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados Unidos
Fil: Hemphill, Andrew. University of Berne. Vetsuisse Faculty. Institute of Parasitology; Suiza
Fil: Van Voorhis, Wesley. University of Washington. Department of Medicine. Division of Allergy and Infectious Diseases. Center for Emerging and Re-emerging Infectious Diseases; Estados Unidos
Fil: Ortega Mora, Luis Miguel. Universidad Complutense de Madrid. Facultad de Veterinaria; España
description 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.
publishDate 2023
dc.date.none.fl_str_mv 2023-10
2024-05-17T10:12:54Z
2024-05-17T10:12:54Z
info:eu-repo/date/embargoEnd/2025-05-17
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/17776
https://academic.oup.com/jid/article-abstract/229/2/558/7331060
0022-1899
https://doi.org/10.1093/infdis/jiad470
url http://hdl.handle.net/20.500.12123/17776
https://academic.oup.com/jid/article-abstract/229/2/558/7331060
https://doi.org/10.1093/infdis/jiad470
identifier_str_mv 0022-1899
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/restrictedAccess
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Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv restrictedAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv The Journal of Infectious Diseases 229 (2) : 558-566 (February 2024)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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