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...

Descripción completa

Detalles Bibliográficos
Autores: Parrado, Rudy, Ramírez, Juan Carlos, Barra, Anabelle de la, Alonso-Vega, Cristina, Juiz, Natalia, Ortiz, Lourdes, Illanes, Daniel, Torrico, Faustino, Gascón i Brustenga, Joaquim, Alves, Fabiana, Flevaud, Laurence, García, Lineth, Schijman, Alejandro G., Ribeiro, Isabela
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/132329
Acceso en línea:https://hdl.handle.net/2445/132329
Access Level:acceso abierto
Palabra clave:Malaltia de Chagas
Assaigs clínics
Chagas' disease
Clinical trials
id ES_1a14bc2b6d8c19d2f5a7aadd9cd25c42
oai_identifier_str oai:diposit.ub.edu:2445/132329
network_acronym_str ES
network_name_str España
repository_id_str
spelling Usefulness of Serial Blood Sampling and PCR Replicates for Treatment Monitoring of Patients with Chronic Chagas DiseaseParrado, RudyRamírez, Juan CarlosBarra, Anabelle de laAlonso-Vega, CristinaJuiz, NataliaOrtiz, LourdesIllanes, DanielTorrico, FaustinoGascón i Brustenga, JoaquimAlves, FabianaFlevaud, LaurenceGarcía, LinethSchijman, Alejandro G.Ribeiro, IsabelaMalaltia de ChagasAssaigs clínicsChagas' diseaseClinical trialsThis 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-CHE1224-001 (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.American Society for Microbiology2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/132329Articles publicats en revistes (ISGlobal)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: http://dx.doi.org/ 10.1128/AAC.01191-18Antimicrobial Agents and Chemotherapy, 2019, vol. 63, num. 2, p. e01191http://dx.doi.org/ 10.1128/AAC.01191-18cc by (c) American Society for Microbiology, 2019http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1323292026-05-27T06:46:51Z
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
Malaltia de Chagas
Assaigs clínics
Chagas' disease
Clinical trials
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
Ramírez, Juan Carlos
Barra, Anabelle de la
Alonso-Vega, Cristina
Juiz, Natalia
Ortiz, Lourdes
Illanes, Daniel
Torrico, Faustino
Gascón i Brustenga, Joaquim
Alves, Fabiana
Flevaud, Laurence
García, Lineth
Schijman, Alejandro G.
Ribeiro, Isabela
author Parrado, Rudy
author_facet Parrado, Rudy
Ramírez, Juan Carlos
Barra, Anabelle de la
Alonso-Vega, Cristina
Juiz, Natalia
Ortiz, Lourdes
Illanes, Daniel
Torrico, Faustino
Gascón i Brustenga, Joaquim
Alves, Fabiana
Flevaud, Laurence
García, Lineth
Schijman, Alejandro G.
Ribeiro, Isabela
author_role author
author2 Ramírez, Juan Carlos
Barra, Anabelle de la
Alonso-Vega, Cristina
Juiz, Natalia
Ortiz, Lourdes
Illanes, Daniel
Torrico, Faustino
Gascón i Brustenga, Joaquim
Alves, Fabiana
Flevaud, Laurence
García, Lineth
Schijman, Alejandro G.
Ribeiro, Isabela
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malaltia de Chagas
Assaigs clínics
Chagas' disease
Clinical trials
topic Malaltia de Chagas
Assaigs clínics
Chagas' disease
Clinical trials
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-CHE1224-001 (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
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/132329
url https://hdl.handle.net/2445/132329
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: http://dx.doi.org/ 10.1128/AAC.01191-18
Antimicrobial Agents and Chemotherapy, 2019, vol. 63, num. 2, p. e01191
http://dx.doi.org/ 10.1128/AAC.01191-18
dc.rights.none.fl_str_mv cc by (c) American Society for Microbiology, 2019
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) American Society for Microbiology, 2019
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 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 Articles publicats en revistes (ISGlobal)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869404084539228160
score 15.301603

Similares en LA Referencia