An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the trea...

Autores
Krolewiecki, Alejandro Javier; Enbiale, Wendemagegn; Gandasegui, Javier; van Lieshout, Lisette; Kepha, Stella; Messa Junior, Augusto; Bengtson, Michel; Gelaye, Woyneshet; Escola, Valdemiro; Martinez Valladares, María; Cambra Pellejà, María; Algorta, Jaime; Martí Soler, Helena; Fleitas, Pedro; Ballester, Maria Rosa; Doyle, Stephen R.; Williams, Nana Aba; Legarda, Almudena; Mandomando, Inacio; Mwandawiro, Charles; Muñoz, José
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Soil-transmitted helminths (STH) are targeted for control through mass drug-administration campaigns to prevent morbidity affecting at-risk groups in endemic regions. Although broadly successful, the use of albendazole and mebendazole achieved variable progress, with deficiencies against Trichuris trichiura and a predictable low efficacy against Strongyloides stercoralis. Novel drug combinations offer a potential solution, providing they can be delivered safely and maintain efficacy against all STH species. Here we present the protocol of a clinical trial to evaluate a fixed-dose combination (FDC) tablet containing albendazole and ivermectin that will be compared against albendazole against STH. Methods: An adaptive phase II/III randomized controlled trial will be undertaken in STH endemic sites in Ethiopia, Kenya and Mozambique to evaluate an oral FDC of 400 mg albendazole and either 9- or 18 mg ivermectin. FDC will be administered as a single dose or single doses over three-consecutive days and assessed against a single dose of 400 mg albendazole. In the phase II trial, 126 T. trichiura-infected children weighting 15 to 45 kg will be treated in a dose-escalation manner to determine safety objectives. In the phase III trial, 1097 participants aged 5 to 18 years old infected with T. trichiura, hookworm and S. stercoralis will be recruited to determine safety and efficacy. The trial will be open-label with blinded outcome assessors. Cure rate measured 21-days after-treatment in duplicate Kato-Katz is the primary efficacy outcome. Secondary objectives include efficacy evaluation by quantitative polymerase chain reaction (PCR) as an outcome measurement, description of pharmacokinetic parameters, palatability and acceptability evaluations, and monitoring of anthelmintic resistance. Conclusions: This trial with registrational goals seeks to evaluate an innovative fixed-dose combination of albendazole and ivermectin co-formulated tablets, with the goal of providing an anthelmintic regimen with improved efficacy and spectrum of coverage against STH. ClinicalTrials.gov registration: NCT05124691 (18/11/2021).
Fil: Krolewiecki, Alejandro Javier. Universidad de Barcelona; España. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Enbiale, Wendemagegn. Bahir Dar University; Etiopía. Amsterdam Institute for Infection and Immunity; Países Bajos
Fil: Gandasegui, Javier. Universidad de Barcelona; España
Fil: van Lieshout, Lisette. Leiden University; Países Bajos
Fil: Kepha, Stella. Kenya Medical Research Institute; Kenia
Fil: Messa Junior, Augusto. Centro de Investigação em Saúde de Manhiça; Mozambique
Fil: Bengtson, Michel. Leiden University. Leiden University Medical Center.; Países Bajos
Fil: Gelaye, Woyneshet. Bahir Dar University; Etiopía
Fil: Escola, Valdemiro. Centro de Investigação em Saúde de Manhiça; Mozambique
Fil: Martinez Valladares, María. Universidad de León; España. Consejo Superior de Investigaciones Científicas; España
Fil: Cambra Pellejà, María. Universidad de León; España. Consejo Superior de Investigaciones Científicas; España
Fil: Algorta, Jaime. Liconsa Sa; España
Fil: Martí Soler, Helena. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; España
Fil: Fleitas, Pedro. Consejo Superior de Investigaciones Científicas; España. Universidad de Barcelona; España
Fil: Ballester, Maria Rosa. Centro de Investigación Biomédica en Red de Salud Mental; España. Institut d’Investigació Biomèdica Sant Pau; España
Fil: Doyle, Stephen R.. Wellcome Sanger Institute; Reino Unido
Fil: Williams, Nana Aba. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; España
Fil: Legarda, Almudena. Consejo Superior de Investigaciones Científicas; España. Universidad de Barcelona; España
Fil: Mandomando, Inacio. Centro de Investigação Em Saúde de Manhiça; Mozambique
Fil: Mwandawiro, Charles. Eastern and Southern Africa Centre of International Parasite Control; Kenia
Fil: Muñoz, José. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; España
Materia
ANTIHELMINTICS
STH
TRICHURIS TRICHIURA
HOOKWORM
ALBENDAZOLE
IVERMECTIN
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/244741

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oai_identifier_str oai:ri.conicet.gov.ar:11336/244741
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocolKrolewiecki, Alejandro JavierEnbiale, WendemagegnGandasegui, Javiervan Lieshout, LisetteKepha, StellaMessa Junior, AugustoBengtson, MichelGelaye, WoyneshetEscola, ValdemiroMartinez Valladares, MaríaCambra Pellejà, MaríaAlgorta, JaimeMartí Soler, HelenaFleitas, PedroBallester, Maria RosaDoyle, Stephen R.Williams, Nana AbaLegarda, AlmudenaMandomando, InacioMwandawiro, CharlesMuñoz, JoséANTIHELMINTICSSTHTRICHURIS TRICHIURAHOOKWORMALBENDAZOLEIVERMECTINhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Background: Soil-transmitted helminths (STH) are targeted for control through mass drug-administration campaigns to prevent morbidity affecting at-risk groups in endemic regions. Although broadly successful, the use of albendazole and mebendazole achieved variable progress, with deficiencies against Trichuris trichiura and a predictable low efficacy against Strongyloides stercoralis. Novel drug combinations offer a potential solution, providing they can be delivered safely and maintain efficacy against all STH species. Here we present the protocol of a clinical trial to evaluate a fixed-dose combination (FDC) tablet containing albendazole and ivermectin that will be compared against albendazole against STH. Methods: An adaptive phase II/III randomized controlled trial will be undertaken in STH endemic sites in Ethiopia, Kenya and Mozambique to evaluate an oral FDC of 400 mg albendazole and either 9- or 18 mg ivermectin. FDC will be administered as a single dose or single doses over three-consecutive days and assessed against a single dose of 400 mg albendazole. In the phase II trial, 126 T. trichiura-infected children weighting 15 to 45 kg will be treated in a dose-escalation manner to determine safety objectives. In the phase III trial, 1097 participants aged 5 to 18 years old infected with T. trichiura, hookworm and S. stercoralis will be recruited to determine safety and efficacy. The trial will be open-label with blinded outcome assessors. Cure rate measured 21-days after-treatment in duplicate Kato-Katz is the primary efficacy outcome. Secondary objectives include efficacy evaluation by quantitative polymerase chain reaction (PCR) as an outcome measurement, description of pharmacokinetic parameters, palatability and acceptability evaluations, and monitoring of anthelmintic resistance. Conclusions: This trial with registrational goals seeks to evaluate an innovative fixed-dose combination of albendazole and ivermectin co-formulated tablets, with the goal of providing an anthelmintic regimen with improved efficacy and spectrum of coverage against STH. ClinicalTrials.gov registration: NCT05124691 (18/11/2021).Fil: Krolewiecki, Alejandro Javier. Universidad de Barcelona; España. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Enbiale, Wendemagegn. Bahir Dar University; Etiopía. Amsterdam Institute for Infection and Immunity; Países BajosFil: Gandasegui, Javier. Universidad de Barcelona; EspañaFil: van Lieshout, Lisette. Leiden University; Países BajosFil: Kepha, Stella. Kenya Medical Research Institute; KeniaFil: Messa Junior, Augusto. Centro de Investigação em Saúde de Manhiça; MozambiqueFil: Bengtson, Michel. Leiden University. Leiden University Medical Center.; Países BajosFil: Gelaye, Woyneshet. Bahir Dar University; EtiopíaFil: Escola, Valdemiro. Centro de Investigação em Saúde de Manhiça; MozambiqueFil: Martinez Valladares, María. Universidad de León; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Cambra Pellejà, María. Universidad de León; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Algorta, Jaime. Liconsa Sa; EspañaFil: Martí Soler, Helena. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Fleitas, Pedro. Consejo Superior de Investigaciones Científicas; España. Universidad de Barcelona; EspañaFil: Ballester, Maria Rosa. Centro de Investigación Biomédica en Red de Salud Mental; España. Institut d’Investigació Biomèdica Sant Pau; EspañaFil: Doyle, Stephen R.. Wellcome Sanger Institute; Reino UnidoFil: Williams, Nana Aba. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Legarda, Almudena. Consejo Superior de Investigaciones Científicas; España. Universidad de Barcelona; EspañaFil: Mandomando, Inacio. Centro de Investigação Em Saúde de Manhiça; MozambiqueFil: Mwandawiro, Charles. Eastern and Southern Africa Centre of International Parasite Control; KeniaFil: Muñoz, José. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; EspañaBill & Melinda Gates Foundation2022-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/244741Krolewiecki, Alejandro Javier; Enbiale, Wendemagegn; Gandasegui, Javier; van Lieshout, Lisette; Kepha, Stella; et al.; An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocol; Bill & Melinda Gates Foundation; Gates Open Research; 6; 5-2022; 1-132572-4754CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://gatesopenresearch.org/articles/6-62/v1info:eu-repo/semantics/altIdentifier/doi/10.12688/gatesopenres.13615.1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:25Zoai:ri.conicet.gov.ar:11336/244741instacron: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:34982025-09-03 09:59:25.844CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocol
title An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocol
spellingShingle An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocol
Krolewiecki, Alejandro Javier
ANTIHELMINTICS
STH
TRICHURIS TRICHIURA
HOOKWORM
ALBENDAZOLE
IVERMECTIN
title_short An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocol
title_full An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocol
title_fullStr An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocol
title_full_unstemmed An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocol
title_sort An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocol
dc.creator.none.fl_str_mv Krolewiecki, Alejandro Javier
Enbiale, Wendemagegn
Gandasegui, Javier
van Lieshout, Lisette
Kepha, Stella
Messa Junior, Augusto
Bengtson, Michel
Gelaye, Woyneshet
Escola, Valdemiro
Martinez Valladares, María
Cambra Pellejà, María
Algorta, Jaime
Martí Soler, Helena
Fleitas, Pedro
Ballester, Maria Rosa
Doyle, Stephen R.
Williams, Nana Aba
Legarda, Almudena
Mandomando, Inacio
Mwandawiro, Charles
Muñoz, José
author Krolewiecki, Alejandro Javier
author_facet Krolewiecki, Alejandro Javier
Enbiale, Wendemagegn
Gandasegui, Javier
van Lieshout, Lisette
Kepha, Stella
Messa Junior, Augusto
Bengtson, Michel
Gelaye, Woyneshet
Escola, Valdemiro
Martinez Valladares, María
Cambra Pellejà, María
Algorta, Jaime
Martí Soler, Helena
Fleitas, Pedro
Ballester, Maria Rosa
Doyle, Stephen R.
Williams, Nana Aba
Legarda, Almudena
Mandomando, Inacio
Mwandawiro, Charles
Muñoz, José
author_role author
author2 Enbiale, Wendemagegn
Gandasegui, Javier
van Lieshout, Lisette
Kepha, Stella
Messa Junior, Augusto
Bengtson, Michel
Gelaye, Woyneshet
Escola, Valdemiro
Martinez Valladares, María
Cambra Pellejà, María
Algorta, Jaime
Martí Soler, Helena
Fleitas, Pedro
Ballester, Maria Rosa
Doyle, Stephen R.
Williams, Nana Aba
Legarda, Almudena
Mandomando, Inacio
Mwandawiro, Charles
Muñoz, José
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 ANTIHELMINTICS
STH
TRICHURIS TRICHIURA
HOOKWORM
ALBENDAZOLE
IVERMECTIN
topic ANTIHELMINTICS
STH
TRICHURIS TRICHIURA
HOOKWORM
ALBENDAZOLE
IVERMECTIN
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: Soil-transmitted helminths (STH) are targeted for control through mass drug-administration campaigns to prevent morbidity affecting at-risk groups in endemic regions. Although broadly successful, the use of albendazole and mebendazole achieved variable progress, with deficiencies against Trichuris trichiura and a predictable low efficacy against Strongyloides stercoralis. Novel drug combinations offer a potential solution, providing they can be delivered safely and maintain efficacy against all STH species. Here we present the protocol of a clinical trial to evaluate a fixed-dose combination (FDC) tablet containing albendazole and ivermectin that will be compared against albendazole against STH. Methods: An adaptive phase II/III randomized controlled trial will be undertaken in STH endemic sites in Ethiopia, Kenya and Mozambique to evaluate an oral FDC of 400 mg albendazole and either 9- or 18 mg ivermectin. FDC will be administered as a single dose or single doses over three-consecutive days and assessed against a single dose of 400 mg albendazole. In the phase II trial, 126 T. trichiura-infected children weighting 15 to 45 kg will be treated in a dose-escalation manner to determine safety objectives. In the phase III trial, 1097 participants aged 5 to 18 years old infected with T. trichiura, hookworm and S. stercoralis will be recruited to determine safety and efficacy. The trial will be open-label with blinded outcome assessors. Cure rate measured 21-days after-treatment in duplicate Kato-Katz is the primary efficacy outcome. Secondary objectives include efficacy evaluation by quantitative polymerase chain reaction (PCR) as an outcome measurement, description of pharmacokinetic parameters, palatability and acceptability evaluations, and monitoring of anthelmintic resistance. Conclusions: This trial with registrational goals seeks to evaluate an innovative fixed-dose combination of albendazole and ivermectin co-formulated tablets, with the goal of providing an anthelmintic regimen with improved efficacy and spectrum of coverage against STH. ClinicalTrials.gov registration: NCT05124691 (18/11/2021).
Fil: Krolewiecki, Alejandro Javier. Universidad de Barcelona; España. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Enbiale, Wendemagegn. Bahir Dar University; Etiopía. Amsterdam Institute for Infection and Immunity; Países Bajos
Fil: Gandasegui, Javier. Universidad de Barcelona; España
Fil: van Lieshout, Lisette. Leiden University; Países Bajos
Fil: Kepha, Stella. Kenya Medical Research Institute; Kenia
Fil: Messa Junior, Augusto. Centro de Investigação em Saúde de Manhiça; Mozambique
Fil: Bengtson, Michel. Leiden University. Leiden University Medical Center.; Países Bajos
Fil: Gelaye, Woyneshet. Bahir Dar University; Etiopía
Fil: Escola, Valdemiro. Centro de Investigação em Saúde de Manhiça; Mozambique
Fil: Martinez Valladares, María. Universidad de León; España. Consejo Superior de Investigaciones Científicas; España
Fil: Cambra Pellejà, María. Universidad de León; España. Consejo Superior de Investigaciones Científicas; España
Fil: Algorta, Jaime. Liconsa Sa; España
Fil: Martí Soler, Helena. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; España
Fil: Fleitas, Pedro. Consejo Superior de Investigaciones Científicas; España. Universidad de Barcelona; España
Fil: Ballester, Maria Rosa. Centro de Investigación Biomédica en Red de Salud Mental; España. Institut d’Investigació Biomèdica Sant Pau; España
Fil: Doyle, Stephen R.. Wellcome Sanger Institute; Reino Unido
Fil: Williams, Nana Aba. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; España
Fil: Legarda, Almudena. Consejo Superior de Investigaciones Científicas; España. Universidad de Barcelona; España
Fil: Mandomando, Inacio. Centro de Investigação Em Saúde de Manhiça; Mozambique
Fil: Mwandawiro, Charles. Eastern and Southern Africa Centre of International Parasite Control; Kenia
Fil: Muñoz, José. Universidad de Barcelona; España. Consejo Superior de Investigaciones Científicas; España
description Background: Soil-transmitted helminths (STH) are targeted for control through mass drug-administration campaigns to prevent morbidity affecting at-risk groups in endemic regions. Although broadly successful, the use of albendazole and mebendazole achieved variable progress, with deficiencies against Trichuris trichiura and a predictable low efficacy against Strongyloides stercoralis. Novel drug combinations offer a potential solution, providing they can be delivered safely and maintain efficacy against all STH species. Here we present the protocol of a clinical trial to evaluate a fixed-dose combination (FDC) tablet containing albendazole and ivermectin that will be compared against albendazole against STH. Methods: An adaptive phase II/III randomized controlled trial will be undertaken in STH endemic sites in Ethiopia, Kenya and Mozambique to evaluate an oral FDC of 400 mg albendazole and either 9- or 18 mg ivermectin. FDC will be administered as a single dose or single doses over three-consecutive days and assessed against a single dose of 400 mg albendazole. In the phase II trial, 126 T. trichiura-infected children weighting 15 to 45 kg will be treated in a dose-escalation manner to determine safety objectives. In the phase III trial, 1097 participants aged 5 to 18 years old infected with T. trichiura, hookworm and S. stercoralis will be recruited to determine safety and efficacy. The trial will be open-label with blinded outcome assessors. Cure rate measured 21-days after-treatment in duplicate Kato-Katz is the primary efficacy outcome. Secondary objectives include efficacy evaluation by quantitative polymerase chain reaction (PCR) as an outcome measurement, description of pharmacokinetic parameters, palatability and acceptability evaluations, and monitoring of anthelmintic resistance. Conclusions: This trial with registrational goals seeks to evaluate an innovative fixed-dose combination of albendazole and ivermectin co-formulated tablets, with the goal of providing an anthelmintic regimen with improved efficacy and spectrum of coverage against STH. ClinicalTrials.gov registration: NCT05124691 (18/11/2021).
publishDate 2022
dc.date.none.fl_str_mv 2022-05
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/11336/244741
Krolewiecki, Alejandro Javier; Enbiale, Wendemagegn; Gandasegui, Javier; van Lieshout, Lisette; Kepha, Stella; et al.; An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocol; Bill & Melinda Gates Foundation; Gates Open Research; 6; 5-2022; 1-13
2572-4754
CONICET Digital
CONICET
url http://hdl.handle.net/11336/244741
identifier_str_mv Krolewiecki, Alejandro Javier; Enbiale, Wendemagegn; Gandasegui, Javier; van Lieshout, Lisette; Kepha, Stella; et al.; An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocol; Bill & Melinda Gates Foundation; Gates Open Research; 6; 5-2022; 1-13
2572-4754
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://gatesopenresearch.org/articles/6-62/v1
info:eu-repo/semantics/altIdentifier/doi/10.12688/gatesopenres.13615.1
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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application/pdf
dc.publisher.none.fl_str_mv Bill & Melinda Gates Foundation
publisher.none.fl_str_mv Bill & Melinda Gates Foundation
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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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