Limited efficacy of repeated praziquantel treatment in Schistosoma mansoni infections as revealed by highly accurate diagnostics, PCR and UCP-LF CAA (RePST trial)
Copyright: © 2022 Hoekstra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited..
BACKGROUND: Most studies assessing praziquantel (PZQ) efficacy have used relatively insensitive diagnostic methods, thereby overestimating cure rate (CR) and intensity reduction rate (IRR). To determine accurately PZQ efficacy, we employed more sensitive DNA and circulating antigen detection methods.
METHODOLOGY: A sub-analysis was performed based on a previously published trial conducted in children from Côte d'Ivoire with a confirmed Schistosoma mansoni infection, who were randomly assigned to a standard (single dose of PZQ) or intense treatment group (4 repeated doses of PZQ at 2-week intervals). CR and IRR were estimated based on PCR detecting DNA in a single stool sample and the up-converting particle lateral flow (UCP-LF) test detecting circulating anodic antigen (CAA) in a single urine sample, and compared with traditional Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA).
PRINCIPAL FINDINGS: Individuals positive by all diagnostic methods (i.e., KK, POC-CCA, PCR, and UCP-LF CAA) at baseline were included in the statistical analysis (n = 125). PCR showed a CR of 45% (95% confidence interval (CI) 32-59%) in the standard and 78% (95% CI 66-87%) in the intense treatment group, which is lower compared to the KK results (64%, 95% CI 52-75%) and 88%, 95% CI 78-93%). UCP-LF CAA showed a significantly lower CR in both groups, 16% (95% CI 11-24%) and 18% (95% CI 12-26%), even lower than observed by POC-CCA (31%, 95% CI 17-35% and 36%, 95% CI 26-47%). A substantial reduction in DNA and CAA-levels was observed after the first treatment, with no further decrease after additional treatment and no significant difference in IRR between treatment groups.
CONCLUSION/SIGNIFICANCE: The efficacy of (repeated) PZQ treatment was overestimated when using egg-based diagnostics (i.e. KK and PCR). Quantitative worm-based diagnostics (i.e. POC-CCA and UCP-LF CAA) revealed that active Schistosoma infections are still present despite multiple treatments. These results stress the need for using accurate diagnostic tools to monitor different PZQ treatment strategies, in particular when moving toward elimination of schistosomiasis.
CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, NCT02868385.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
PLoS neglected tropical diseases - 16(2022), 12 vom: 27. Dez., Seite e0011008 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hoekstra, Pytsje T [VerfasserIn] |
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| Links: |
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| Themen: |
6490C9U457 |
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| Anmerkungen: |
Date Completed 10.01.2023 Date Revised 08.02.2023 published: Electronic-eCollection ClinicalTrials.gov: NCT02868385 Citation Status MEDLINE |
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| doi: |
10.1371/journal.pntd.0011008 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM350599831 |
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| 100 | 1 | |a Hoekstra, Pytsje T |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Limited efficacy of repeated praziquantel treatment in Schistosoma mansoni infections as revealed by highly accurate diagnostics, PCR and UCP-LF CAA (RePST trial) |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Revised 08.02.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a ClinicalTrials.gov: NCT02868385 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright: © 2022 Hoekstra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | ||
| 520 | |a BACKGROUND: Most studies assessing praziquantel (PZQ) efficacy have used relatively insensitive diagnostic methods, thereby overestimating cure rate (CR) and intensity reduction rate (IRR). To determine accurately PZQ efficacy, we employed more sensitive DNA and circulating antigen detection methods | ||
| 520 | |a METHODOLOGY: A sub-analysis was performed based on a previously published trial conducted in children from Côte d'Ivoire with a confirmed Schistosoma mansoni infection, who were randomly assigned to a standard (single dose of PZQ) or intense treatment group (4 repeated doses of PZQ at 2-week intervals). CR and IRR were estimated based on PCR detecting DNA in a single stool sample and the up-converting particle lateral flow (UCP-LF) test detecting circulating anodic antigen (CAA) in a single urine sample, and compared with traditional Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA) | ||
| 520 | |a PRINCIPAL FINDINGS: Individuals positive by all diagnostic methods (i.e., KK, POC-CCA, PCR, and UCP-LF CAA) at baseline were included in the statistical analysis (n = 125). PCR showed a CR of 45% (95% confidence interval (CI) 32-59%) in the standard and 78% (95% CI 66-87%) in the intense treatment group, which is lower compared to the KK results (64%, 95% CI 52-75%) and 88%, 95% CI 78-93%). UCP-LF CAA showed a significantly lower CR in both groups, 16% (95% CI 11-24%) and 18% (95% CI 12-26%), even lower than observed by POC-CCA (31%, 95% CI 17-35% and 36%, 95% CI 26-47%). A substantial reduction in DNA and CAA-levels was observed after the first treatment, with no further decrease after additional treatment and no significant difference in IRR between treatment groups | ||
| 520 | |a CONCLUSION/SIGNIFICANCE: The efficacy of (repeated) PZQ treatment was overestimated when using egg-based diagnostics (i.e. KK and PCR). Quantitative worm-based diagnostics (i.e. POC-CCA and UCP-LF CAA) revealed that active Schistosoma infections are still present despite multiple treatments. These results stress the need for using accurate diagnostic tools to monitor different PZQ treatment strategies, in particular when moving toward elimination of schistosomiasis | ||
| 520 | |a CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, NCT02868385 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a 6490C9U457 |2 NLM | |
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| 650 | 7 | |a Antigens, Helminth |2 NLM | |
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| 700 | 1 | |a van Lieshout, Lisette |e verfasserin |4 aut | |
| 700 | 1 | |a Corstjens, Paul L A M |e verfasserin |4 aut | |
| 700 | 1 | |a Tsonaka, Roula |e verfasserin |4 aut | |
| 700 | 1 | |a Assaré, Rufin K |e verfasserin |4 aut | |
| 700 | 1 | |a Silué, Kigbafori D |e verfasserin |4 aut | |
| 700 | 1 | |a N'Goran, Eliézer K |e verfasserin |4 aut | |
| 700 | 1 | |a N'Gbesso, Yves K |e verfasserin |4 aut | |
| 700 | 1 | |a Brienen, Eric A T |e verfasserin |4 aut | |
| 700 | 1 | |a Roestenberg, Meta |e verfasserin |4 aut | |
| 700 | 1 | |a Knopp, Stefanie |e verfasserin |4 aut | |
| 700 | 1 | |a Utzinger, Jürg |e verfasserin |4 aut | |
| 700 | 1 | |a Coulibaly, Jean T |e verfasserin |4 aut | |
| 700 | 1 | |a van Dam, Govert J |e verfasserin |4 aut | |
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