Dataset Information

Limited efficacy of repeated praziquantel treatment in Schistosoma mansoni infections as revealed by highly accurate diagnostics, PCR and UCP-LF CAA (RePST trial).

ABSTRACT:

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.

SUBMITTER: Hoekstra PT

PROVIDER: S-EPMC9822103 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Limited efficacy of repeated praziquantel treatment in Schistosoma mansoni infections as revealed by highly accurate diagnostics, PCR and UCP-LF CAA (RePST trial).

Hoekstra Pytsje T PT Casacuberta-Partal Miriam M van Lieshout Lisette L Corstjens Paul L A M PLAM Tsonaka Roula R Assaré Rufin K RK Silué Kigbafori D KD N'Goran Eliézer K EK N'Gbesso Yves K YK Brienen Eric A T EAT Roestenberg Meta M Knopp Stefanie S Utzinger Jürg J Coulibaly Jean T JT van Dam Govert J GJ

PLoS neglected tropical diseases 20221222 12

<h4>Background</h4>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.<h4>Methodology</h4>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 randoml ...[more]

PMID: 36548444

Similar Datasets

Project description:BackgroundMethodological applications of the high sensitivity genus-specific Schistosoma CAA strip test, allowing detection of single worm active infections (ultimate sensitivity), are discussed for efficient utilization in sample pooling strategies. Besides relevant cost reduction, pooling of samples rather than individual testing can provide valuable data for large scale mapping, surveillance, and monitoring.MethodThe laboratory-based CAA strip test utilizes luminescent quantitative up-converting phosphor (UCP) reporter particles and a rapid user-friendly lateral flow (LF) assay format. The test includes a sample preparation step that permits virtually unlimited sample concentration with urine, reaching ultimate sensitivity (single worm detection) at 100% specificity. This facilitates testing large urine pools from many individuals with minimal loss of sensitivity and specificity. The test determines the average CAA level of the individuals in the pool thus indicating overall worm burden and prevalence. When requiring test results at the individual level, smaller pools need to be analysed with the pool-size based on expected prevalence or when unknown, on the average CAA level of a larger group; CAA negative pools do not require individual test results and thus reduce the number of tests.ResultsStraightforward pooling strategies indicate that at sub-population level the CAA strip test is an efficient assay for general mapping, identification of hotspots, determination of stratified infection levels, and accurate monitoring of mass drug administrations (MDA). At the individual level, the number of tests can be reduced i.e. in low endemic settings as the pool size can be increased as opposed to prevalence decrease.ConclusionsAt the sub-population level, average CAA concentrations determined in urine pools can be an appropriate measure indicating worm burden. Pooling strategies allowing this type of large scale testing are feasible with the various CAA strip test formats and do not affect sensitivity and specificity. It allows cost efficient stratified testing and monitoring of worm burden at the sub-population level, ideally for large-scale surveillance generating hard data for performance of MDA programs and strategic planning when moving towards transmission-stop and elimination.

Project description:BackgroundSchistosomiasis is a neglected tropical disease burdening millions of people. One drug, praziquantel, is currently used for treatment and control. Clinically relevant drug resistance has not yet been described, but there is considerable heterogeneity in treatment outcomes, ranging from cure to only moderate egg reduction rates. The objectives of this study are to investigate potential worm-induced dysbacteriosis of the gut microbiota and to assess whether a specific microbiome profile could influence praziquantel response.MethodsUsing V3 and V4 regions of 16S rRNA genes, we screened the gut microbiota of 34 Schistosoma mansoni infected and uninfected children from Côte d'Ivoire. From each infected child one pre-treatment, one 24-hour and one 21-day follow-up sample after administering 60 mg/kg praziquantel or placebo, were collected.ResultsOverall taxonomic profiling and diversity indicators were found to be close to a "healthy" gut structure in all children. Slight overall compositional changes were observed between S. mansoni-infected and non-infected children. Praziquantel treatment was not linked to a major shift in the gut taxonomic profiles, thus reinforcing the good safety profile of the drug by ruling out off-targets effects on the gut microbes.16S rRNA gene of the Fusobacteriales order was significantly more abundant in cured individuals, both at baseline and 24 hours post-treatment. A real-time qPCR confirmed the over-abundance of Fusobacterium spp. in cured children. Fusobacterium spp. abundance could also be correlated with treatment induced S. mansoni egg-reduction.ConclusionsOur study suggests that neither a S. mansoni infection nor praziquantel administration triggers a significant effect on the microbial composition and that a higher abundance of Fusobacterium spp., before treatment, is associated with higher efficacy of praziquantel in the treatment of S. mansoni infections.Trial registrationInternational Standard Randomised Controlled Trial, number ISRCTN15280205 .

Dataset Information

Limited efficacy of repeated praziquantel treatment in Schistosoma mansoni infections as revealed by highly accurate diagnostics, PCR and UCP-LF CAA (RePST trial).

Background

Methodology

Principal findings

Conclusion/significance

Clinical trial registration

Publications

Limited efficacy of repeated praziquantel treatment in Schistosoma mansoni infections as revealed by highly accurate diagnostics, PCR and UCP-LF CAA (RePST trial).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets