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...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; |
|---|---|
| Format: | Article |
| Status: | Published version |
| Publication date: | 2019 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/132329 |
| Online Access: | https://hdl.handle.net/2445/132329 |
| Access Level: | Open access |
| Keyword: | Malaltia de Chagas Assaigs clínics Chagas' disease Clinical trials |
| _version_ | 1878730328425627648 |
|---|---|
| author | Parrado, Rudy |
| 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 |
| author_browse | Alonso-Vega, Cristina Alves, Fabiana Barra, Anabelle de la Flevaud, Laurence García, Lineth Gascón i Brustenga, Joaquim Illanes, Daniel Juiz, Natalia Ortiz, Lourdes Parrado, Rudy Ramírez, Juan Carlos Ribeiro, Isabela Schijman, Alejandro G. Torrico, Faustino |
| 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 |
| collection | Dipòsit Digital de la UB |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_1a14bc2b6d8c19d2f5a7aadd9cd25c42 |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/132329 |
| publishDate | 2019 |
| publishDateSort | 2019 |
| publisher | American Society for Microbiology |
| publisherStr | American Society for Microbiology |
| reponame_str | Dipòsit Digital de la UB |
| spelling | Usefulness of Serial Blood Sampling and PCR Replicates for Treatment Monitoring of Patients with Chronic Chagas Disease 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 Malaltia de Chagas Assaigs clínics Chagas' disease Clinical trials 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. American Society for Microbiology https://hdl.handle.net/2445/132329 |
| 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 |
| status_str | publishedVersion |
| title | 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_short | 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 |
| topic | Malaltia de Chagas Assaigs clínics Chagas' disease Clinical trials |
| topic_facet | Malaltia de Chagas Assaigs clínics Chagas' disease Clinical trials |
| url | https://hdl.handle.net/2445/132329 |