Usefulness of serial blood sampling and PCR replicates for treatment monitoring of patients with chronic Chagas disease
- 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
- Año de publicación
- 2019
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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.
Fil: Parrado, Rudy. Universidad Mayor de San Simón; Bolivia
Fil: Ramirez Gomez, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: de la Barra, Anabelle. Universidad Mayor de San Simón; Bolivia
Fil: Alonso Vega, Cristina. Drugs for Neglected Diseases initiative; Suiza
Fil: Juiz, Natalia Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Ortiz, Lourdes. Universidad Autónoma Juan Misael Saracho; Bolivia
Fil: Illanes, Daniel. Universidad Mayor de San Simón; Bolivia
Fil: Torrico, Faustino. Fundación Ceades; Bolivia
Fil: Gascon, Joaquim. Barcelona Centre for International Health Research; España
Fil: Alves, Fabiana. Drugs for Neglected Diseases Initiative; Suiza
Fil: Flevaud, Laurence. Médicins Sans Frontières; Suiza
Fil: Garcia, Lineth. Universidad Mayor de San Simón; Bolivia
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: Ribeiro, Isabela. Drugs for Neglected Diseases Initiative; Suiza - Materia
-
BENZNIDAZOLE
CHAGAS DISEASE
CLINICAL TRIALS
PCR
RAVUCONAZOLE
TREATMENT MONITORING
TRYPANOSOMA CRUZI - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/163418
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T10:07:41Zoai: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:34982025-09-29 10:07:41.657CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| 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 |
| 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 |
| topic |
BENZNIDAZOLE CHAGAS DISEASE CLINICAL TRIALS PCR RAVUCONAZOLE TREATMENT MONITORING TRYPANOSOMA CRUZI |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| dc.description.none.fl_txt_mv |
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. Fil: Parrado, Rudy. Universidad Mayor de San Simón; Bolivia Fil: Ramirez Gomez, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: de la Barra, Anabelle. Universidad Mayor de San Simón; Bolivia Fil: Alonso Vega, Cristina. Drugs for Neglected Diseases initiative; Suiza Fil: Juiz, Natalia Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Ortiz, Lourdes. Universidad Autónoma Juan Misael Saracho; Bolivia Fil: Illanes, Daniel. Universidad Mayor de San Simón; Bolivia Fil: Torrico, Faustino. Fundación Ceades; Bolivia Fil: Gascon, Joaquim. Barcelona Centre for International Health Research; España Fil: Alves, Fabiana. Drugs for Neglected Diseases Initiative; Suiza Fil: Flevaud, Laurence. Médicins Sans Frontières; Suiza Fil: Garcia, Lineth. Universidad Mayor de San Simón; Bolivia 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: Ribeiro, Isabela. Drugs for Neglected Diseases Initiative; Suiza |
| 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 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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publishedVersion |
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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 |
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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 |
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info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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openAccess |
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American Society for Microbiology |
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American Society for Microbiology |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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