Usefulness of serial blood sampling and PCR replicates for treatment monitoring of patients with chronic Chagas disease

This work evaluated a serial blood sampling procedure to enhance the sensitivity of duplex real-time quantitative PCR (qPCR) for baseline detection and quantification of parasitic loads and posttreatment identification of failure in the context of clinical trials for treatment of chronic Chagas dise...

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Autores: Parrado, Rudy, Ramirez Gomez, Juan Carlos, de la Barra, Anabelle, Alonso Vega, Cristina, Juiz, Natalia Anahí, Ortiz, Lourdes, Illanes, Daniel, Torrico, Faustino, Gascon, Joaquim, Alves, Fabiana, Flevaud, Laurence, Garcia, Lineth, Schijman, Alejandro Gabriel, Ribeiro, Isabela
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/163418
Acceso en línea:http://hdl.handle.net/11336/163418
Access Level:acceso abierto
Palabra clave:BENZNIDAZOLE
CHAGAS DISEASE
CLINICAL TRIALS
PCR
RAVUCONAZOLE
TREATMENT MONITORING
TRYPANOSOMA CRUZI
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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oai_identifier_str oai:ri.conicet.gov.ar:11336/163418
network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv Usefulness of serial blood sampling and PCR replicates for treatment monitoring of patients with chronic Chagas disease
title Usefulness of serial blood sampling and PCR replicates for treatment monitoring of patients with chronic Chagas disease
spellingShingle Usefulness of serial blood sampling and PCR replicates for treatment monitoring of patients with chronic Chagas disease
Parrado, Rudy
BENZNIDAZOLE
CHAGAS DISEASE
CLINICAL TRIALS
PCR
RAVUCONAZOLE
TREATMENT MONITORING
TRYPANOSOMA CRUZI
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
title_short Usefulness of serial blood sampling and PCR replicates for treatment monitoring of patients with chronic Chagas disease
title_full Usefulness of serial blood sampling and PCR replicates for treatment monitoring of patients with chronic Chagas disease
title_fullStr Usefulness of serial blood sampling and PCR replicates for treatment monitoring of patients with chronic Chagas disease
title_full_unstemmed Usefulness of serial blood sampling and PCR replicates for treatment monitoring of patients with chronic Chagas disease
title_sort Usefulness of serial blood sampling and PCR replicates for treatment monitoring of patients with chronic Chagas disease
dc.creator.none.fl_str_mv Parrado, Rudy
Ramirez Gomez, Juan Carlos
de la Barra, Anabelle
Alonso Vega, Cristina
Juiz, Natalia Anahí
Ortiz, Lourdes
Illanes, Daniel
Torrico, Faustino
Gascon, Joaquim
Alves, Fabiana
Flevaud, Laurence
Garcia, Lineth
Schijman, Alejandro Gabriel
Ribeiro, Isabela
author Parrado, Rudy
author_facet Parrado, Rudy
Ramirez Gomez, Juan Carlos
de la Barra, Anabelle
Alonso Vega, Cristina
Juiz, Natalia Anahí
Ortiz, Lourdes
Illanes, Daniel
Torrico, Faustino
Gascon, Joaquim
Alves, Fabiana
Flevaud, Laurence
Garcia, Lineth
Schijman, Alejandro Gabriel
Ribeiro, Isabela
author_role author
author2 Ramirez Gomez, Juan Carlos
de la Barra, Anabelle
Alonso Vega, Cristina
Juiz, Natalia Anahí
Ortiz, Lourdes
Illanes, Daniel
Torrico, Faustino
Gascon, Joaquim
Alves, Fabiana
Flevaud, Laurence
Garcia, Lineth
Schijman, Alejandro Gabriel
Ribeiro, Isabela
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BENZNIDAZOLE
CHAGAS DISEASE
CLINICAL TRIALS
PCR
RAVUCONAZOLE
TREATMENT MONITORING
TRYPANOSOMA CRUZI
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic BENZNIDAZOLE
CHAGAS DISEASE
CLINICAL TRIALS
PCR
RAVUCONAZOLE
TREATMENT MONITORING
TRYPANOSOMA CRUZI
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
description This work evaluated a serial blood sampling procedure to enhance the sensitivity of duplex real-time quantitative PCR (qPCR) for baseline detection and quantification of parasitic loads and posttreatment identification of failure in the context of clinical trials for treatment of chronic Chagas disease, namely, DNDi-CH-E1224-001 (ClinicalTrials.gov registration no. NCT01489228) and the MSF-DNDi PCR Sampling Optimization Study (NCT01678599). Patients from Cochabamba (n 294), Tarija (n 257), and Aiquile (n 220) were enrolled. Three serial blood samples were collected at each time point, and qPCR triplicates were tested for each sample. The first two samples were collected during the same day and the third one 7 days later. A patient was considered PCR positive if at least one qPCR replicate was detectable. Cumulative results of multiple samples and qPCR replicates enhanced the proportion of pretreatment sample positivity from 54.8% to 76.2%, 59.5% to 77.8%, and 73.5% to 90.2% in Cochabamba, Tarija, and Aiquile cohorts, respectively. This strategy increased the detection of treatment failure from 72.9% to 91.7%, 77.8% to 88.9%, and 42.9% to 69.1% for E1224 low-, short-, and high-dosage regimens, respectively, and from 4.6% to 15.9% and 9.5% to 32.1% for the benznidazole arm in the DNDi-CH-E1224-001 and MSF-DNDi studies, respectively. The addition of the third blood sample and third qPCR replicate in patients with nondetectable PCR results in the first two samples gave a small, non-statistically significant improvement in qPCR positivity. No change in clinical sensitivity was seen with a blood volume increase from 5 to 10 ml. The monitoring of patients treated with placebo in the DNDi-CH-E1224-001 trial revealed fluctuations in parasitic loads and occasionally nondetectable results. In conclusion, a serial sampling strategy enhanced PCR sensitivity to detecting treatment failure during follow-up and has the potential for improving recruitment capacity in Chagas disease trials, which require an initial positive qPCR result for patient admission.
publishDate 2019
dc.date.none.fl_str_mv 2019-02
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/11336/163418
Parrado, Rudy; Ramirez Gomez, Juan Carlos; de la Barra, Anabelle; Alonso Vega, Cristina; Juiz, Natalia Anahí; et al.; Usefulness of serial blood sampling and PCR replicates for treatment monitoring of patients with chronic Chagas disease; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 63; 2; 2-2019; 1-12
0066-4804
CONICET Digital
CONICET
url http://hdl.handle.net/11336/163418
identifier_str_mv Parrado, Rudy; Ramirez Gomez, Juan Carlos; de la Barra, Anabelle; Alonso Vega, Cristina; Juiz, Natalia Anahí; et al.; Usefulness of serial blood sampling and PCR replicates for treatment monitoring of patients with chronic Chagas disease; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 63; 2; 2-2019; 1-12
0066-4804
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.01191-18
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355557/#:~:text=In%20conclusion%2C%20a%20serial%20sampling,qPCR%20result%20for%20patient%20admission.
info:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/AAC.01191-18
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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
_version_ 1799195657257353216
spelling Usefulness of serial blood sampling and PCR replicates for treatment monitoring of patients with chronic Chagas diseaseParrado, RudyRamirez Gomez, Juan Carlosde la Barra, AnabelleAlonso Vega, CristinaJuiz, Natalia AnahíOrtiz, LourdesIllanes, DanielTorrico, FaustinoGascon, JoaquimAlves, FabianaFlevaud, LaurenceGarcia, LinethSchijman, Alejandro GabrielRibeiro, IsabelaBENZNIDAZOLECHAGAS DISEASECLINICAL TRIALSPCRRAVUCONAZOLETREATMENT MONITORINGTRYPANOSOMA CRUZIhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1This work evaluated a serial blood sampling procedure to enhance the sensitivity of duplex real-time quantitative PCR (qPCR) for baseline detection and quantification of parasitic loads and posttreatment identification of failure in the context of clinical trials for treatment of chronic Chagas disease, namely, DNDi-CH-E1224-001 (ClinicalTrials.gov registration no. NCT01489228) and the MSF-DNDi PCR Sampling Optimization Study (NCT01678599). Patients from Cochabamba (n 294), Tarija (n 257), and Aiquile (n 220) were enrolled. Three serial blood samples were collected at each time point, and qPCR triplicates were tested for each sample. The first two samples were collected during the same day and the third one 7 days later. A patient was considered PCR positive if at least one qPCR replicate was detectable. Cumulative results of multiple samples and qPCR replicates enhanced the proportion of pretreatment sample positivity from 54.8% to 76.2%, 59.5% to 77.8%, and 73.5% to 90.2% in Cochabamba, Tarija, and Aiquile cohorts, respectively. This strategy increased the detection of treatment failure from 72.9% to 91.7%, 77.8% to 88.9%, and 42.9% to 69.1% for E1224 low-, short-, and high-dosage regimens, respectively, and from 4.6% to 15.9% and 9.5% to 32.1% for the benznidazole arm in the DNDi-CH-E1224-001 and MSF-DNDi studies, respectively. The addition of the third blood sample and third qPCR replicate in patients with nondetectable PCR results in the first two samples gave a small, non-statistically significant improvement in qPCR positivity. No change in clinical sensitivity was seen with a blood volume increase from 5 to 10 ml. The monitoring of patients treated with placebo in the DNDi-CH-E1224-001 trial revealed fluctuations in parasitic loads and occasionally nondetectable results. In conclusion, a serial sampling strategy enhanced PCR sensitivity to detecting treatment failure during follow-up and has the potential for improving recruitment capacity in Chagas disease trials, which require an initial positive qPCR result for patient admission.Fil: Parrado, Rudy. Universidad Mayor de San Simón; BoliviaFil: Ramirez Gomez, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: de la Barra, Anabelle. Universidad Mayor de San Simón; BoliviaFil: Alonso Vega, Cristina. Drugs for Neglected Diseases initiative; SuizaFil: Juiz, Natalia Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Ortiz, Lourdes. Universidad Autónoma Juan Misael Saracho; BoliviaFil: Illanes, Daniel. Universidad Mayor de San Simón; BoliviaFil: Torrico, Faustino. Fundación Ceades; BoliviaFil: Gascon, Joaquim. Barcelona Centre for International Health Research; EspañaFil: Alves, Fabiana. Drugs for Neglected Diseases Initiative; SuizaFil: Flevaud, Laurence. Médicins Sans Frontières; SuizaFil: Garcia, Lineth. Universidad Mayor de San Simón; BoliviaFil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Ribeiro, Isabela. Drugs for Neglected Diseases Initiative; SuizaAmerican Society for Microbiology2019-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/163418Parrado, Rudy; Ramirez Gomez, Juan Carlos; de la Barra, Anabelle; Alonso Vega, Cristina; Juiz, Natalia Anahí; et al.; Usefulness of serial blood sampling and PCR replicates for treatment monitoring of patients with chronic Chagas disease; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 63; 2; 2-2019; 1-120066-4804CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.01191-18info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355557/#:~:text=In%20conclusion%2C%20a%20serial%20sampling,qPCR%20result%20for%20patient%20admission.info:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/AAC.01191-18info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:59:26Zoai:ri.conicet.gov.ar:11336/163418instacron: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:34982024-05-08 13:59:26.404CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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