Short-course Benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): A non-inferiority randomized controlled trial study protocol

Autores
Cafferata, María L.; Toscani, María A.; Althabe, Fernando; Belizan, Jose; Bergel, Eduardo; Berrueta, Mabel; Capparelli, Edmund V.; Ciganda, Álvaro; Danesi, Emmaría; Dumonteil, Eric; Gibbons, Luz; Gulayin, Pablo Elías; Herrera, Claudia; Momper, Jeremiah D.; Rossi, Steven; Shaffer, Jeffrey G.; Schijman, Alejandro Gabriel; Sosa-Estani, Sergio Alejandro; Stella, Candela B.; Klein, Karen; Buekens, Pierre
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Retrospective observational studies suggest that transmission of Trypanosoma cruzi does not occur in treated women when pregnant later in life. The level of parasitemia is a known risk factor for congenital transmission. Benznidazole (BZN) is the drug of choice for Preconceptional treatment to reduce parasitic load.The fear of treatment-related side effects limits the implementation of the Argentine guideline recommending BZN 60d/300 mg (or equivalent) treatment of T. cruzi seropositive women during the postpartum period to prevent transmission in a future pregnancy. A short and low dose BZN treatment might reduce major side effects and increase compliance, but its efficacy to reduce T. cruzi parasitic load compared to the standard 60d/300 mg course is not yet established. Clinical trials testing alternative BZN courses among women of reproductive age are urgently needed.Methods and design: We are proposing to perform a double-blinded, non-inferiority randomized controlled trial comparing a short low dose 30-day treatment with BZN 150 mg/day (30d/150 mg) vs. BZN 60d/300 mg. We will recruit not previously treated T. cruzi seropositive women with a live birth during the postpartum period in Argentina, randomize them at 6 months postpartum, and follow them up with the following specific aims:Specific aim 1: to measure the effect of BZN 30d/150 mg compared to 60d/300 mg preconceptional treatment on parasitic load measured by the frequency of positive Polymerase Chain Reaction (PCR) (primary outcome) and by real-time quantitative PCR (qPCR), immediately and 10 months after treatment.Specific aim 2: to measure the frequency of serious adverse events and/or any adverse event leading to treatment interruption.
Fil: Cafferata, María L.. Instituto de Efectividad Clínica y Sanitaria; Argentina. Unicem; Uruguay
Fil: Toscani, María A.. Instituto de Efectividad Clínica y Sanitaria; Argentina
Fil: Althabe, Fernando. Organizacion Mundial de la Salud; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina
Fil: Belizan, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina
Fil: Bergel, Eduardo. Instituto de Efectividad Clínica y Sanitaria; Argentina
Fil: Berrueta, Mabel. Instituto de Efectividad Clínica y Sanitaria; Argentina
Fil: Capparelli, Edmund V.. University of California; Estados Unidos
Fil: Ciganda, Álvaro. Instituto de Efectividad Clínica y Sanitaria; Argentina
Fil: Danesi, Emmaría. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Centro Nacional de Diagnóstico e Investigaciones Endemo-epidémicas; Argentina
Fil: Dumonteil, Eric. University of Tulane; Estados Unidos
Fil: Gibbons, Luz. Instituto de Efectividad Clínica y Sanitaria; Argentina
Fil: Gulayin, Pablo Elías. Instituto de Efectividad Clínica y Sanitaria; Argentina
Fil: Herrera, Claudia. University of Tulane; Estados Unidos
Fil: Momper, Jeremiah D.. University of California; Estados Unidos
Fil: Rossi, Steven. University of California; Estados Unidos
Fil: Shaffer, Jeffrey G.. University of Tulane; Estados Unidos
Fil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Sosa-Estani, Sergio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina
Fil: Stella, Candela B.. Instituto de Efectividad Clínica y Sanitaria; Argentina
Fil: Klein, Karen. Instituto de Efectividad Clínica y Sanitaria; Argentina
Fil: Buekens, Pierre. University of Tulane; Estados Unidos
Materia
BENZNIDAZOLE
CHAGAS DISEASE
PRECONCEPTION CARE
RANDOMIZED CONTROLLED TRIAL
TRYPANOSOMA CRUZI
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/142515
Acceder
id CONICETDig_5c7d63efde3f7afc52946f265cdf7a76
oai_identifier_str oai:ri.conicet.gov.ar:11336/142515
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Short-course Benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): A non-inferiority randomized controlled trial study protocolCafferata, María L.Toscani, María A.Althabe, FernandoBelizan, JoseBergel, EduardoBerrueta, MabelCapparelli, Edmund V.Ciganda, ÁlvaroDanesi, EmmaríaDumonteil, EricGibbons, LuzGulayin, Pablo ElíasHerrera, ClaudiaMomper, Jeremiah D.Rossi, StevenShaffer, Jeffrey G.Schijman, Alejandro GabrielSosa-Estani, Sergio AlejandroStella, Candela B.Klein, KarenBuekens, PierreBENZNIDAZOLECHAGAS DISEASEPRECONCEPTION CARERANDOMIZED CONTROLLED TRIALTRYPANOSOMA CRUZIhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Background: Retrospective observational studies suggest that transmission of Trypanosoma cruzi does not occur in treated women when pregnant later in life. The level of parasitemia is a known risk factor for congenital transmission. Benznidazole (BZN) is the drug of choice for Preconceptional treatment to reduce parasitic load.The fear of treatment-related side effects limits the implementation of the Argentine guideline recommending BZN 60d/300 mg (or equivalent) treatment of T. cruzi seropositive women during the postpartum period to prevent transmission in a future pregnancy. A short and low dose BZN treatment might reduce major side effects and increase compliance, but its efficacy to reduce T. cruzi parasitic load compared to the standard 60d/300 mg course is not yet established. Clinical trials testing alternative BZN courses among women of reproductive age are urgently needed.Methods and design: We are proposing to perform a double-blinded, non-inferiority randomized controlled trial comparing a short low dose 30-day treatment with BZN 150 mg/day (30d/150 mg) vs. BZN 60d/300 mg. We will recruit not previously treated T. cruzi seropositive women with a live birth during the postpartum period in Argentina, randomize them at 6 months postpartum, and follow them up with the following specific aims:Specific aim 1: to measure the effect of BZN 30d/150 mg compared to 60d/300 mg preconceptional treatment on parasitic load measured by the frequency of positive Polymerase Chain Reaction (PCR) (primary outcome) and by real-time quantitative PCR (qPCR), immediately and 10 months after treatment.Specific aim 2: to measure the frequency of serious adverse events and/or any adverse event leading to treatment interruption.Fil: Cafferata, María L.. Instituto de Efectividad Clínica y Sanitaria; Argentina. Unicem; UruguayFil: Toscani, María A.. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Althabe, Fernando. Organizacion Mundial de la Salud; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Belizan, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Bergel, Eduardo. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Berrueta, Mabel. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Capparelli, Edmund V.. University of California; Estados UnidosFil: Ciganda, Álvaro. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Danesi, Emmaría. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Centro Nacional de Diagnóstico e Investigaciones Endemo-epidémicas; ArgentinaFil: Dumonteil, Eric. University of Tulane; Estados UnidosFil: Gibbons, Luz. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Gulayin, Pablo Elías. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Herrera, Claudia. University of Tulane; Estados UnidosFil: Momper, Jeremiah D.. University of California; Estados UnidosFil: Rossi, Steven. University of California; Estados UnidosFil: Shaffer, Jeffrey G.. University of Tulane; Estados UnidosFil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Sosa-Estani, Sergio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Stella, Candela B.. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Klein, Karen. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Buekens, Pierre. University of Tulane; Estados UnidosBioMed Central2020-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/142515Cafferata, María L.; Toscani, María A.; Althabe, Fernando; Belizan, Jose; Bergel, Eduardo; et al.; Short-course Benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): A non-inferiority randomized controlled trial study protocol; BioMed Central; Reproductive Health; 17; 1; 8-2020; 1-231742-4755CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://reproductive-health-journal.biomedcentral.com/articles/10.1186/s12978-020-00972-1info:eu-repo/semantics/altIdentifier/doi/10.1186/s12978-020-00972-1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:01:11Zoai:ri.conicet.gov.ar:11336/142515instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:01:11.524CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Short-course Benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): A non-inferiority randomized controlled trial study protocol
title Short-course Benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): A non-inferiority randomized controlled trial study protocol
spellingShingle Short-course Benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): A non-inferiority randomized controlled trial study protocol
Cafferata, María L.
BENZNIDAZOLE
CHAGAS DISEASE
PRECONCEPTION CARE
RANDOMIZED CONTROLLED TRIAL
TRYPANOSOMA CRUZI
title_short Short-course Benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): A non-inferiority randomized controlled trial study protocol
title_full Short-course Benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): A non-inferiority randomized controlled trial study protocol
title_fullStr Short-course Benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): A non-inferiority randomized controlled trial study protocol
title_full_unstemmed Short-course Benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): A non-inferiority randomized controlled trial study protocol
title_sort Short-course Benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): A non-inferiority randomized controlled trial study protocol
dc.creator.none.fl_str_mv Cafferata, María L.
Toscani, María A.
Althabe, Fernando
Belizan, Jose
Bergel, Eduardo
Berrueta, Mabel
Capparelli, Edmund V.
Ciganda, Álvaro
Danesi, Emmaría
Dumonteil, Eric
Gibbons, Luz
Gulayin, Pablo Elías
Herrera, Claudia
Momper, Jeremiah D.
Rossi, Steven
Shaffer, Jeffrey G.
Schijman, Alejandro Gabriel
Sosa-Estani, Sergio Alejandro
Stella, Candela B.
Klein, Karen
Buekens, Pierre
author Cafferata, María L.
author_facet Cafferata, María L.
Toscani, María A.
Althabe, Fernando
Belizan, Jose
Bergel, Eduardo
Berrueta, Mabel
Capparelli, Edmund V.
Ciganda, Álvaro
Danesi, Emmaría
Dumonteil, Eric
Gibbons, Luz
Gulayin, Pablo Elías
Herrera, Claudia
Momper, Jeremiah D.
Rossi, Steven
Shaffer, Jeffrey G.
Schijman, Alejandro Gabriel
Sosa-Estani, Sergio Alejandro
Stella, Candela B.
Klein, Karen
Buekens, Pierre
author_role author
author2 Toscani, María A.
Althabe, Fernando
Belizan, Jose
Bergel, Eduardo
Berrueta, Mabel
Capparelli, Edmund V.
Ciganda, Álvaro
Danesi, Emmaría
Dumonteil, Eric
Gibbons, Luz
Gulayin, Pablo Elías
Herrera, Claudia
Momper, Jeremiah D.
Rossi, Steven
Shaffer, Jeffrey G.
Schijman, Alejandro Gabriel
Sosa-Estani, Sergio Alejandro
Stella, Candela B.
Klein, Karen
Buekens, Pierre
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BENZNIDAZOLE
CHAGAS DISEASE
PRECONCEPTION CARE
RANDOMIZED CONTROLLED TRIAL
TRYPANOSOMA CRUZI
topic BENZNIDAZOLE
CHAGAS DISEASE
PRECONCEPTION CARE
RANDOMIZED CONTROLLED TRIAL
TRYPANOSOMA CRUZI
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Retrospective observational studies suggest that transmission of Trypanosoma cruzi does not occur in treated women when pregnant later in life. The level of parasitemia is a known risk factor for congenital transmission. Benznidazole (BZN) is the drug of choice for Preconceptional treatment to reduce parasitic load.The fear of treatment-related side effects limits the implementation of the Argentine guideline recommending BZN 60d/300 mg (or equivalent) treatment of T. cruzi seropositive women during the postpartum period to prevent transmission in a future pregnancy. A short and low dose BZN treatment might reduce major side effects and increase compliance, but its efficacy to reduce T. cruzi parasitic load compared to the standard 60d/300 mg course is not yet established. Clinical trials testing alternative BZN courses among women of reproductive age are urgently needed.Methods and design: We are proposing to perform a double-blinded, non-inferiority randomized controlled trial comparing a short low dose 30-day treatment with BZN 150 mg/day (30d/150 mg) vs. BZN 60d/300 mg. We will recruit not previously treated T. cruzi seropositive women with a live birth during the postpartum period in Argentina, randomize them at 6 months postpartum, and follow them up with the following specific aims:Specific aim 1: to measure the effect of BZN 30d/150 mg compared to 60d/300 mg preconceptional treatment on parasitic load measured by the frequency of positive Polymerase Chain Reaction (PCR) (primary outcome) and by real-time quantitative PCR (qPCR), immediately and 10 months after treatment.Specific aim 2: to measure the frequency of serious adverse events and/or any adverse event leading to treatment interruption.
Fil: Cafferata, María L.. Instituto de Efectividad Clínica y Sanitaria; Argentina. Unicem; Uruguay
Fil: Toscani, María A.. Instituto de Efectividad Clínica y Sanitaria; Argentina
Fil: Althabe, Fernando. Organizacion Mundial de la Salud; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina
Fil: Belizan, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina
Fil: Bergel, Eduardo. Instituto de Efectividad Clínica y Sanitaria; Argentina
Fil: Berrueta, Mabel. Instituto de Efectividad Clínica y Sanitaria; Argentina
Fil: Capparelli, Edmund V.. University of California; Estados Unidos
Fil: Ciganda, Álvaro. Instituto de Efectividad Clínica y Sanitaria; Argentina
Fil: Danesi, Emmaría. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Centro Nacional de Diagnóstico e Investigaciones Endemo-epidémicas; Argentina
Fil: Dumonteil, Eric. University of Tulane; Estados Unidos
Fil: Gibbons, Luz. Instituto de Efectividad Clínica y Sanitaria; Argentina
Fil: Gulayin, Pablo Elías. Instituto de Efectividad Clínica y Sanitaria; Argentina
Fil: Herrera, Claudia. University of Tulane; Estados Unidos
Fil: Momper, Jeremiah D.. University of California; Estados Unidos
Fil: Rossi, Steven. University of California; Estados Unidos
Fil: Shaffer, Jeffrey G.. University of Tulane; Estados Unidos
Fil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Sosa-Estani, Sergio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina
Fil: Stella, Candela B.. Instituto de Efectividad Clínica y Sanitaria; Argentina
Fil: Klein, Karen. Instituto de Efectividad Clínica y Sanitaria; Argentina
Fil: Buekens, Pierre. University of Tulane; Estados Unidos
description Background: Retrospective observational studies suggest that transmission of Trypanosoma cruzi does not occur in treated women when pregnant later in life. The level of parasitemia is a known risk factor for congenital transmission. Benznidazole (BZN) is the drug of choice for Preconceptional treatment to reduce parasitic load.The fear of treatment-related side effects limits the implementation of the Argentine guideline recommending BZN 60d/300 mg (or equivalent) treatment of T. cruzi seropositive women during the postpartum period to prevent transmission in a future pregnancy. A short and low dose BZN treatment might reduce major side effects and increase compliance, but its efficacy to reduce T. cruzi parasitic load compared to the standard 60d/300 mg course is not yet established. Clinical trials testing alternative BZN courses among women of reproductive age are urgently needed.Methods and design: We are proposing to perform a double-blinded, non-inferiority randomized controlled trial comparing a short low dose 30-day treatment with BZN 150 mg/day (30d/150 mg) vs. BZN 60d/300 mg. We will recruit not previously treated T. cruzi seropositive women with a live birth during the postpartum period in Argentina, randomize them at 6 months postpartum, and follow them up with the following specific aims:Specific aim 1: to measure the effect of BZN 30d/150 mg compared to 60d/300 mg preconceptional treatment on parasitic load measured by the frequency of positive Polymerase Chain Reaction (PCR) (primary outcome) and by real-time quantitative PCR (qPCR), immediately and 10 months after treatment.Specific aim 2: to measure the frequency of serious adverse events and/or any adverse event leading to treatment interruption.
publishDate 2020
dc.date.none.fl_str_mv 2020-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/142515
Cafferata, María L.; Toscani, María A.; Althabe, Fernando; Belizan, Jose; Bergel, Eduardo; et al.; Short-course Benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): A non-inferiority randomized controlled trial study protocol; BioMed Central; Reproductive Health; 17; 1; 8-2020; 1-23
1742-4755
CONICET Digital
CONICET
url http://hdl.handle.net/11336/142515
identifier_str_mv Cafferata, María L.; Toscani, María A.; Althabe, Fernando; Belizan, Jose; Bergel, Eduardo; et al.; Short-course Benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): A non-inferiority randomized controlled trial study protocol; BioMed Central; Reproductive Health; 17; 1; 8-2020; 1-23
1742-4755
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://reproductive-health-journal.biomedcentral.com/articles/10.1186/s12978-020-00972-1
info:eu-repo/semantics/altIdentifier/doi/10.1186/s12978-020-00972-1
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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