Rapid clearance of Schistosoma mansoni circulating cathodic antigen after treatment shown by urine strip tests in a Ugandan fishing community - Relevance for monitoring treatment efficacy and re-infection
ClinicalTrials.gov NCT00215267.
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| Published in | PLoS neglected tropical diseases Vol. 11; no. 11; p. e0006054 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Public Library of Science
13.11.2017
Public Library of Science (PLoS) |
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| Online Access | Get full text |
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| Abstract | ClinicalTrials.gov NCT00215267. |
|---|---|
| AbstractList | Schistosomiasis control and elimination has priority in public health agendas in several sub-Saharan countries. However, achieving these goals remains a substantial challenge. In order to assess progress of interventions and treatment efficacy it is pertinent to have accurate, feasible and affordable diagnostic tools. Detection of Schistosoma mansoni infection by circulating cathodic antigen (CCA) in urine is an attractive option as this measure describes live worm infection noninvasively. In order to interpret treatment efficacy and re-infection levels, knowledge about clearance of this antigen is necessary. The current study aims to investigate, whether antigen clearance as a proxy for decreasing worm numbers is reflected in decreasing CCA levels in urine shortly after praziquantel treatment. Here CCA levels are measured 24 hours post treatment in response to both a single and two treatments. The study was designed as a series of cross-sectional urine and stool sample collections from 446 individuals nested in a two-arm randomised single blinded longitudinal clinical trial cohort matched by gender and age (ClinicalTrials.gov Identifier: NCT00215267) receiving one or two praziquantel treatments. CCA levels in urine were determined by carbon-conjugated monoclonal antibody lateral flow strip assay and eggs per gram faeces for S. mansoni and soil-transmitted helminths by Kato-Katz. Significant correlations between CCA levels and S. mansoni egg count at every measured time point were found and confirmed the added beneficial effect of a second treatment at two weeks after baseline. Furthermore, presence of hookworm was found not to be a confounder for CCA test specificity. Twenty-four hours post treatment measures of mean CCA scores showed significant reductions. In conclusion, removal of CCA in response to treatment is detectable as a decline in CCA in urine already after 24 hours. This has relevance for use and interpretation of laboratory based and point-of-care CCA tests in terms of treatment efficacy and re-infection proportions as this measure provides information on the presence of all actively feeding stages of S. mansoni, which conventional faecal microscopy methods do not accurately reflect.TRIAL REGISTRATIONClinicalTrials.gov NCT00215267. ClinicalTrials.gov NCT00215267. Schistosomiasis control and elimination has priority in public health agendas in several sub-Saharan countries. However, achieving these goals remains a substantial challenge. In order to assess progress of interventions and treatment efficacy it is pertinent to have accurate, feasible and affordable diagnostic tools. Detection of Schistosoma mansoni infection by circulating cathodic antigen (CCA) in urine is an attractive option as this measure describes live worm infection noninvasively. In order to interpret treatment efficacy and re-infection levels, knowledge about clearance of this antigen is necessary. The current study aims to investigate, whether antigen clearance as a proxy for decreasing worm numbers is reflected in decreasing CCA levels in urine shortly after praziquantel treatment. Here CCA levels are measured 24 hours post treatment in response to both a single and two treatments. The study was designed as a series of cross-sectional urine and stool sample collections from 446 individuals nested in a two-arm randomised single blinded longitudinal clinical trial cohort matched by gender and age (ClinicalTrials.gov Identifier: NCT00215267) receiving one or two praziquantel treatments. CCA levels in urine were determined by carbon-conjugated monoclonal antibody lateral flow strip assay and eggs per gram faeces for S. mansoni and soil-transmitted helminths by Kato-Katz. Significant correlations between CCA levels and S. mansoni egg count at every measured time point were found and confirmed the added beneficial effect of a second treatment at two weeks after baseline. Furthermore, presence of hookworm was found not to be a confounder for CCA test specificity. Twenty-four hours post treatment measures of mean CCA scores showed significant reductions. In conclusion, removal of CCA in response to treatment is detectable as a decline in CCA in urine already after 24 hours. This has relevance for use and interpretation of laboratory based and point-of-care CCA tests in terms of treatment efficacy and re-infection proportions as this measure provides information on the presence of all actively feeding stages of S. mansoni, which conventional faecal microscopy methods do not accurately reflect. Trial registration ClinicalTrials.gov NCT00215267 Schistosomiasis control and elimination has priority in public health agendas in several sub-Saharan countries. However, achieving these goals remains a substantial challenge. In order to assess progress of interventions and treatment efficacy it is pertinent to have accurate, feasible and affordable diagnostic tools. Detection of Schistosoma mansoni infection by circulating cathodic antigen (CCA) in urine is an attractive option as this measure describes live worm infection noninvasively. In order to interpret treatment efficacy and re-infection levels, knowledge about clearance of this antigen is necessary. The current study aims to investigate, whether antigen clearance as a proxy for decreasing worm numbers is reflected in decreasing CCA levels in urine shortly after praziquantel treatment. Here CCA levels are measured 24 hours post treatment in response to both a single and two treatments. The study was designed as a series of cross-sectional urine and stool sample collections from 446 individuals nested in a two-arm randomised single blinded longitudinal clinical trial cohort matched by gender and age (ClinicalTrials.gov Identifier: NCT00215267) receiving one or two praziquantel treatments. CCA levels in urine were determined by carbon-conjugated monoclonal antibody lateral flow strip assay and eggs per gram faeces for S. mansoni and soil-transmitted helminths by Kato-Katz. Significant correlations between CCA levels and S. mansoni egg count at every measured time point were found and confirmed the added beneficial effect of a second treatment at two weeks after baseline. Furthermore, presence of hookworm was found not to be a confounder for CCA test specificity. Twenty-four hours post treatment measures of mean CCA scores showed significant reductions. In conclusion, removal of CCA in response to treatment is detectable as a decline in CCA in urine already after 24 hours. This has relevance for use and interpretation of laboratory based and point-of-care CCA tests in terms of treatment efficacy and re-infection proportions as this measure provides information on the presence of all actively feeding stages of S. mansoni, which conventional faecal microscopy methods do not accurately reflect. Trial registration ClinicalTrials.gov NCT00215267 Schistosomiasis control and elimination has priority in public health agendas in several sub-Saharan countries. However, achieving these goals remains a substantial challenge. In order to assess progress of interventions and treatment efficacy it is pertinent to have accurate, feasible and affordable diagnostic tools. Detection of Schistosoma mansoni infection by circulating cathodic antigen (CCA) in urine is an attractive option as this measure describes live worm infection noninvasively. In order to interpret treatment efficacy and re-infection levels, knowledge about clearance of this antigen is necessary. The current study aims to investigate, whether antigen clearance as a proxy for decreasing worm numbers is reflected in decreasing CCA levels in urine shortly after praziquantel treatment. Here CCA levels are measured 24 hours post treatment in response to both a single and two treatments. The study was designed as a series of cross-sectional urine and stool sample collections from 446 individuals nested in a two-arm randomised single blinded longitudinal clinical trial cohort matched by gender and age (ClinicalTrials.gov Identifier: NCT00215267) receiving one or two praziquantel treatments. CCA levels in urine were determined by carbon-conjugated monoclonal antibody lateral flow strip assay and eggs per gram faeces for S. mansoni and soil-transmitted helminths by Kato-Katz. Significant correlations between CCA levels and S. mansoni egg count at every measured time point were found and confirmed the added beneficial effect of a second treatment at two weeks after baseline. Furthermore, presence of hookworm was found not to be a confounder for CCA test specificity. Twenty-four hours post treatment measures of mean CCA scores showed significant reductions. In conclusion, removal of CCA in response to treatment is detectable as a decline in CCA in urine already after 24 hours. This has relevance for use and interpretation of laboratory based and point-of-care CCA tests in terms of treatment efficacy and re-infection proportions as this measure provides information on the presence of all actively feeding stages of S. mansoni, which conventional faecal microscopy methods do not accurately reflect. Schistosomiasis control and elimination has priority in public health agendas in several sub-Saharan countries. However, achieving these goals remains a substantial challenge. In order to assess progress of interventions and treatment efficacy it is pertinent to have accurate, feasible and affordable diagnostic tools. Detection of Schistosoma mansoni infection by circulating cathodic antigen (CCA) in urine is an attractive option as this measure describes live worm infection noninvasively. In order to interpret treatment efficacy and re-infection levels, knowledge about clearance of this antigen is necessary. The current study aims to investigate, whether antigen clearance as a proxy for decreasing worm numbers is reflected in decreasing CCA levels in urine shortly after praziquantel treatment. Here CCA levels are measured 24 hours post treatment in response to both a single and two treatments. The study was designed as a series of cross-sectional urine and stool sample collections from 446 individuals nested in a two-arm randomised single blinded longitudinal clinical trial cohort matched by gender and age (ClinicalTrials.gov Identifier: NCT00215267) receiving one or two praziquantel treatments. CCA levels in urine were determined by carbon-conjugated monoclonal antibody lateral flow strip assay and eggs per gram faeces for S . mansoni and soil-transmitted helminths by Kato-Katz. Significant correlations between CCA levels and S . mansoni egg count at every measured time point were found and confirmed the added beneficial effect of a second treatment at two weeks after baseline. Furthermore, presence of hookworm was found not to be a confounder for CCA test specificity. Twenty-four hours post treatment measures of mean CCA scores showed significant reductions. In conclusion, removal of CCA in response to treatment is detectable as a decline in CCA in urine already after 24 hours. This has relevance for use and interpretation of laboratory based and point-of-care CCA tests in terms of treatment efficacy and re-infection proportions as this measure provides information on the presence of all actively feeding stages of S . mansoni , which conventional faecal microscopy methods do not accurately reflect. Large scale efforts to control schistosomiasis in several sub-Saharan countries are in progress. In order to accurately monitor the effect of interventions, we need diagnostic tools which are highly specific, sensitive, affordable and easy to use and implement. For Schistosoma mansoni detection the circulating cathodic antigen (CCA) is an attractive option as this antigen is a measure of actively feeding worms and can be measured in urine samples. However, knowledge about how fast this antigen is cleared in response to treatment with praziquantel is necessary for interpretation of consecutive measures based on CCA in order to use this tool optimally. Here we show that CCA is already significantly reduced 24 hours after treatment both in single and double treatment regimens in a community sample from Musoli Village, Uganda. Furthermore, the data supports interpretation of trace measures of CCA as positive since the majority of individuals with trace measures respond to treatment. These observations provide a basis for extended use of CCA-based tools in monitoring treatment efficacy and possibilities for logistically advantageous prevalence screening strategies. Schistosomiasis control and elimination has priority in public health agendas in several sub-Saharan countries. However, achieving these goals remains a substantial challenge. In order to assess progress of interventions and treatment efficacy it is pertinent to have accurate, feasible and affordable diagnostic tools. Detection of Schistosoma mansoni infection by circulating cathodic antigen (CCA) in urine is an attractive option as this measure describes live worm infection noninvasively. In order to interpret treatment efficacy and re-infection levels, knowledge about clearance of this antigen is necessary. The current study aims to investigate, whether antigen clearance as a proxy for decreasing worm numbers is reflected in decreasing CCA levels in urine shortly after praziquantel treatment. Here CCA levels are measured 24 hours post treatment in response to both a single and two treatments. The study was designed as a series of cross-sectional urine and stool sample collections from 446 individuals nested in a two-arm randomised single blinded longitudinal clinical trial cohort matched by gender and age (ClinicalTrials.gov Identifier: NCT00215267) receiving one or two praziquantel treatments. CCA levels in urine were determined by carbon-conjugated monoclonal antibody lateral flow strip assay and eggs per gram faeces for S. mansoni and soil-transmitted helminths by Kato-Katz. Significant correlations between CCA levels and S. mansoni egg count at every measured time point were found and confirmed the added beneficial effect of a second treatment at two weeks after baseline. Furthermore, presence of hookworm was found not to be a confounder for CCA test specificity. Twenty-four hours post treatment measures of mean CCA scores showed significant reductions. In conclusion, removal of CCA in response to treatment is detectable as a decline in CCA in urine already after 24 hours. This has relevance for use and interpretation of laboratory based and point-of-care CCA tests in terms of treatment efficacy and re-infection proportions as this measure provides information on the presence of all actively feeding stages of S. mansoni, which conventional faecal microscopy methods do not accurately reflect.ClinicalTrials.gov NCT00215267. |
| Audience | Academic |
| Author | Vennervald, Birgitte J Tukahebwa, Edridah M Kabatereine, Narcis B de Dood, Claudia J Magnussen, Pascal Kildemoes, Anna O Deelder, André M Wilson, Shona van Dam, Govert J |
| AuthorAffiliation | 5 Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands 4 Centre for Medical Parasitology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark 7 Department of Pathology, University of Cambridge, Cambridge, United Kingdom 1 Section for Parasitology and Aquatic Pathobiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Swiss Tropical and Public Health Institute, SWITZERLAND 2 Vector Control Division, Ministry of Health, Kampala, Uganda 3 Schistosomiasis Control Initiative, Ministry of Health, Kampala, Uganda 6 Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands |
| AuthorAffiliation_xml | – name: Swiss Tropical and Public Health Institute, SWITZERLAND – name: 5 Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands – name: 4 Centre for Medical Parasitology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark – name: 1 Section for Parasitology and Aquatic Pathobiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark – name: 2 Vector Control Division, Ministry of Health, Kampala, Uganda – name: 6 Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands – name: 7 Department of Pathology, University of Cambridge, Cambridge, United Kingdom – name: 3 Schistosomiasis Control Initiative, Ministry of Health, Kampala, Uganda |
| Author_xml | – sequence: 1 givenname: Anna O orcidid: 0000-0001-5150-1153 surname: Kildemoes fullname: Kildemoes, Anna O organization: Section for Parasitology and Aquatic Pathobiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark – sequence: 2 givenname: Birgitte J surname: Vennervald fullname: Vennervald, Birgitte J organization: Section for Parasitology and Aquatic Pathobiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark – sequence: 3 givenname: Edridah M surname: Tukahebwa fullname: Tukahebwa, Edridah M organization: Vector Control Division, Ministry of Health, Kampala, Uganda – sequence: 4 givenname: Narcis B surname: Kabatereine fullname: Kabatereine, Narcis B organization: Schistosomiasis Control Initiative, Ministry of Health, Kampala, Uganda – sequence: 5 givenname: Pascal surname: Magnussen fullname: Magnussen, Pascal organization: Centre for Medical Parasitology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark – sequence: 6 givenname: Claudia J surname: de Dood fullname: de Dood, Claudia J organization: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands – sequence: 7 givenname: André M surname: Deelder fullname: Deelder, André M organization: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands – sequence: 8 givenname: Shona surname: Wilson fullname: Wilson, Shona organization: Department of Pathology, University of Cambridge, Cambridge, United Kingdom – sequence: 9 givenname: Govert J surname: van Dam fullname: van Dam, Govert J organization: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29131820$$D View this record in MEDLINE/PubMed |
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| Copyright | COPYRIGHT 2017 Public Library of Science 2017 Public Library of Science. 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: circulating cathodic antigen after treatment shown by urine strip tests in a Ugandan fishing community - Relevance for monitoring treatment efficacy and re-infection. PLoS Negl Trop Dis 11(11): e0006054. https://doi.org/10.1371/journal.pntd.0006054 2017 Kildemoes et al 2017 Kildemoes et al 2017 Public Library of Science. 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: circulating cathodic antigen after treatment shown by urine strip tests in a Ugandan fishing community - Relevance for monitoring treatment efficacy and re-infection. PLoS Negl Trop Dis 11(11): e0006054. https://doi.org/10.1371/journal.pntd.0006054 |
| Copyright_xml | – notice: COPYRIGHT 2017 Public Library of Science – notice: 2017 Public Library of Science. 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: circulating cathodic antigen after treatment shown by urine strip tests in a Ugandan fishing community - Relevance for monitoring treatment efficacy and re-infection. PLoS Negl Trop Dis 11(11): e0006054. https://doi.org/10.1371/journal.pntd.0006054 – notice: 2017 Kildemoes et al 2017 Kildemoes et al – notice: 2017 Public Library of Science. 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: circulating cathodic antigen after treatment shown by urine strip tests in a Ugandan fishing community - Relevance for monitoring treatment efficacy and re-infection. PLoS Negl Trop Dis 11(11): e0006054. https://doi.org/10.1371/journal.pntd.0006054 |
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| Publisher | Public Library of Science Public Library of Science (PLoS) |
| Publisher_xml | – name: Public Library of Science – name: Public Library of Science (PLoS) |
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| SubjectTerms | Adolescent Adult Aged Animals Anthelmintics - therapeutic use Antigens Antigens, Helminth - urine Biology and Life Sciences Care and treatment Child Cohort Studies Cohorts Collections Countries Cross-Sectional Studies Detection Diagnosis Diagnostic software Diagnostic systems Earth Sciences Ecology and Environmental Sciences Effectiveness Eggs Feces - parasitology Female Fishing Fishing communities Funding Gender Health aspects Human blood fluke Humans Infections Infectious diseases Levels Longitudinal Studies Male Medicine and Health Sciences Microscopy Middle Aged Monoclonal antibodies Objectives Parasitology Physiological aspects Praziquantel Praziquantel - therapeutic use Public health Reagent Strips Removal Schistosoma mansoni Schistosoma mansoni - immunology Schistosomiasis Schistosomiasis mansoni - drug therapy Schistosomiasis mansoni - epidemiology Schistosomiasis mansoni - urine Sensitivity and Specificity Single-Blind Method Soil Specificity Supervision Systematic review Tropical diseases Uganda - epidemiology Urine Young Adult |
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| Title | Rapid clearance of Schistosoma mansoni circulating cathodic antigen after treatment shown by urine strip tests in a Ugandan fishing community - Relevance for monitoring treatment efficacy and re-infection |
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