Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease

Autores
De Salazar, Pablo M.; Sosa-Estani, Sergio Alejandro; Salvador, Fernando; Sulleiro Igual, Elena; Sánchez Montalvá, Adrián; Ribeiro, Isabela; Molina, Israel; Buckee, Caroline O.
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Currently available drugs against Trypanosoma cruzi infection, which causes 12000 deaths annually, have limitations in their efficacy, safety and tolerability. The evaluation of thera-peutic responses to available and new compounds is based on parasite detection in the bloodstream but remains challenging because a substantial proportion of infected individuals have undetectable parasitemia even when using diagnostic tools with the highest accu-racy. We characterize parasite dynamics which might impact drug efficacy assessments in chronic Chagas by analyzing pre-and post-treatment quantitative-PCR data obtained from blood samples collected regularly over a year. We show that parasitemia remains at a steady-state independently of the diagnostic sensitivity. This steady-state can be probabilis-tically quantified and robustly predicted at an individual level. Furthermore, individuals can be assigned to categories with distinct parasitological status, allowing a more detailed evaluation of the efficacy outcomes and adjustment for potential biases. Our analysis improves understanding of parasite dynamics and provides a novel background for optimizing future drug efficacy trials in Chagas disease. Trial Registration: original trial registered with ClinicalTrials.gov, number NCT01489228.
Fil: De Salazar, Pablo M.. Harvard University. Harvard School of Public Health; Estados Unidos
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. Drugs for Neglected Diseases Initiative; Brasil
Fil: Salvador, Fernando. Hospital Universitari Vall D'hebron; España. Instituto de Salud Carlos III; España
Fil: Sulleiro Igual, Elena. Hospital Universitari Vall D'hebron; España. Instituto de Salud Carlos III; España
Fil: Sánchez Montalvá, Adrián. Hospital Universitari Vall D'hebron; España. Instituto de Salud Carlos III; España
Fil: Ribeiro, Isabela. Drugs for Neglected Diseases Initiative; Suiza
Fil: Molina, Israel. Fundación Oswaldo Cruz; Brasil. Hospital Universitari Vall D'hebron; España. Instituto de Salud Carlos III; España
Fil: Buckee, Caroline O.. Harvard University. Harvard School of Public Health; Estados Unidos
Materia
CHAGAS DISEASE
BENZNIDAZOLE
TREATMENT
PCR
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:11336/213479
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas diseaseDe Salazar, Pablo M.Sosa-Estani, Sergio AlejandroSalvador, FernandoSulleiro Igual, ElenaSánchez Montalvá, AdriánRibeiro, IsabelaMolina, IsraelBuckee, Caroline O.CHAGAS DISEASEBENZNIDAZOLETREATMENTPCRhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Currently available drugs against Trypanosoma cruzi infection, which causes 12000 deaths annually, have limitations in their efficacy, safety and tolerability. The evaluation of thera-peutic responses to available and new compounds is based on parasite detection in the bloodstream but remains challenging because a substantial proportion of infected individuals have undetectable parasitemia even when using diagnostic tools with the highest accu-racy. We characterize parasite dynamics which might impact drug efficacy assessments in chronic Chagas by analyzing pre-and post-treatment quantitative-PCR data obtained from blood samples collected regularly over a year. We show that parasitemia remains at a steady-state independently of the diagnostic sensitivity. This steady-state can be probabilis-tically quantified and robustly predicted at an individual level. Furthermore, individuals can be assigned to categories with distinct parasitological status, allowing a more detailed evaluation of the efficacy outcomes and adjustment for potential biases. Our analysis improves understanding of parasite dynamics and provides a novel background for optimizing future drug efficacy trials in Chagas disease. Trial Registration: original trial registered with ClinicalTrials.gov, number NCT01489228.Fil: De Salazar, Pablo M.. Harvard University. Harvard School of Public Health; Estados UnidosFil: 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. Drugs for Neglected Diseases Initiative; BrasilFil: Salvador, Fernando. Hospital Universitari Vall D'hebron; España. Instituto de Salud Carlos III; EspañaFil: Sulleiro Igual, Elena. Hospital Universitari Vall D'hebron; España. Instituto de Salud Carlos III; EspañaFil: Sánchez Montalvá, Adrián. Hospital Universitari Vall D'hebron; España. Instituto de Salud Carlos III; EspañaFil: Ribeiro, Isabela. Drugs for Neglected Diseases Initiative; SuizaFil: Molina, Israel. Fundación Oswaldo Cruz; Brasil. Hospital Universitari Vall D'hebron; España. Instituto de Salud Carlos III; EspañaFil: Buckee, Caroline O.. Harvard University. Harvard School of Public Health; Estados UnidosPublic Library of Science2022-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/213479De Salazar, Pablo M.; Sosa-Estani, Sergio Alejandro; Salvador, Fernando; Sulleiro Igual, Elena; Sánchez Montalvá, Adrián; et al.; Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease; Public Library of Science; PLoS Neglected Tropical Diseases; 16; 11; 11-2022; 1-151935-27271935-2735CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0010828info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pntd.0010828info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:34:36Zoai:ri.conicet.gov.ar:11336/213479instacron: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 09:34:36.424CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease
title Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease
spellingShingle Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease
De Salazar, Pablo M.
CHAGAS DISEASE
BENZNIDAZOLE
TREATMENT
PCR
title_short Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease
title_full Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease
title_fullStr Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease
title_full_unstemmed Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease
title_sort Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease
dc.creator.none.fl_str_mv De Salazar, Pablo M.
Sosa-Estani, Sergio Alejandro
Salvador, Fernando
Sulleiro Igual, Elena
Sánchez Montalvá, Adrián
Ribeiro, Isabela
Molina, Israel
Buckee, Caroline O.
author De Salazar, Pablo M.
author_facet De Salazar, Pablo M.
Sosa-Estani, Sergio Alejandro
Salvador, Fernando
Sulleiro Igual, Elena
Sánchez Montalvá, Adrián
Ribeiro, Isabela
Molina, Israel
Buckee, Caroline O.
author_role author
author2 Sosa-Estani, Sergio Alejandro
Salvador, Fernando
Sulleiro Igual, Elena
Sánchez Montalvá, Adrián
Ribeiro, Isabela
Molina, Israel
Buckee, Caroline O.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CHAGAS DISEASE
BENZNIDAZOLE
TREATMENT
PCR
topic CHAGAS DISEASE
BENZNIDAZOLE
TREATMENT
PCR
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Currently available drugs against Trypanosoma cruzi infection, which causes 12000 deaths annually, have limitations in their efficacy, safety and tolerability. The evaluation of thera-peutic responses to available and new compounds is based on parasite detection in the bloodstream but remains challenging because a substantial proportion of infected individuals have undetectable parasitemia even when using diagnostic tools with the highest accu-racy. We characterize parasite dynamics which might impact drug efficacy assessments in chronic Chagas by analyzing pre-and post-treatment quantitative-PCR data obtained from blood samples collected regularly over a year. We show that parasitemia remains at a steady-state independently of the diagnostic sensitivity. This steady-state can be probabilis-tically quantified and robustly predicted at an individual level. Furthermore, individuals can be assigned to categories with distinct parasitological status, allowing a more detailed evaluation of the efficacy outcomes and adjustment for potential biases. Our analysis improves understanding of parasite dynamics and provides a novel background for optimizing future drug efficacy trials in Chagas disease. Trial Registration: original trial registered with ClinicalTrials.gov, number NCT01489228.
Fil: De Salazar, Pablo M.. Harvard University. Harvard School of Public Health; Estados Unidos
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. Drugs for Neglected Diseases Initiative; Brasil
Fil: Salvador, Fernando. Hospital Universitari Vall D'hebron; España. Instituto de Salud Carlos III; España
Fil: Sulleiro Igual, Elena. Hospital Universitari Vall D'hebron; España. Instituto de Salud Carlos III; España
Fil: Sánchez Montalvá, Adrián. Hospital Universitari Vall D'hebron; España. Instituto de Salud Carlos III; España
Fil: Ribeiro, Isabela. Drugs for Neglected Diseases Initiative; Suiza
Fil: Molina, Israel. Fundación Oswaldo Cruz; Brasil. Hospital Universitari Vall D'hebron; España. Instituto de Salud Carlos III; España
Fil: Buckee, Caroline O.. Harvard University. Harvard School of Public Health; Estados Unidos
description Currently available drugs against Trypanosoma cruzi infection, which causes 12000 deaths annually, have limitations in their efficacy, safety and tolerability. The evaluation of thera-peutic responses to available and new compounds is based on parasite detection in the bloodstream but remains challenging because a substantial proportion of infected individuals have undetectable parasitemia even when using diagnostic tools with the highest accu-racy. We characterize parasite dynamics which might impact drug efficacy assessments in chronic Chagas by analyzing pre-and post-treatment quantitative-PCR data obtained from blood samples collected regularly over a year. We show that parasitemia remains at a steady-state independently of the diagnostic sensitivity. This steady-state can be probabilis-tically quantified and robustly predicted at an individual level. Furthermore, individuals can be assigned to categories with distinct parasitological status, allowing a more detailed evaluation of the efficacy outcomes and adjustment for potential biases. Our analysis improves understanding of parasite dynamics and provides a novel background for optimizing future drug efficacy trials in Chagas disease. Trial Registration: original trial registered with ClinicalTrials.gov, number NCT01489228.
publishDate 2022
dc.date.none.fl_str_mv 2022-11
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/11336/213479
De Salazar, Pablo M.; Sosa-Estani, Sergio Alejandro; Salvador, Fernando; Sulleiro Igual, Elena; Sánchez Montalvá, Adrián; et al.; Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease; Public Library of Science; PLoS Neglected Tropical Diseases; 16; 11; 11-2022; 1-15
1935-2727
1935-2735
CONICET Digital
CONICET
url http://hdl.handle.net/11336/213479
identifier_str_mv De Salazar, Pablo M.; Sosa-Estani, Sergio Alejandro; Salvador, Fernando; Sulleiro Igual, Elena; Sánchez Montalvá, Adrián; et al.; Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease; Public Library of Science; PLoS Neglected Tropical Diseases; 16; 11; 11-2022; 1-15
1935-2727
1935-2735
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://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0010828
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pntd.0010828
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 Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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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score 13.070432

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