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

PLoS Negl Trop Dis. 2017 Nov 13;11(11):e0006054. doi: 10.1371/journal.pntd.0006054. eCollection 2017 Nov.

Abstract

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Anthelmintics / therapeutic use*
  • Antigens, Helminth / urine*
  • Child
  • Cohort Studies
  • Cross-Sectional Studies
  • Feces / parasitology
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Praziquantel / therapeutic use*
  • Reagent Strips
  • Schistosoma mansoni / immunology*
  • Schistosomiasis mansoni / drug therapy*
  • Schistosomiasis mansoni / epidemiology
  • Schistosomiasis mansoni / urine*
  • Sensitivity and Specificity
  • Single-Blind Method
  • Uganda / epidemiology
  • Young Adult

Substances

  • Anthelmintics
  • Antigens, Helminth
  • Reagent Strips
  • Praziquantel

Associated data

  • ClinicalTrials.gov/NCT00215267

Grants and funding

This study received financial support from the European Commission's Science and Technology for Development Programme (FP6-INCO-DEV Contract No: 517733 [MUSTSchistUKEMA]) and DBL- Centre for Health Research and Development, Copenhagen, Denmark. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.