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.

Anna O Kildemoes,Edridah M Tukahebwa,André M Deelder,Claudia J De Dood,Shona Wilson,Birgitte J Vennervald,Narcis B Kabatereine,Pascal Magnussen,Govert J Van Dam,Jennifer Keiser

doi:10.1371/journal.pntd.0006054

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 registrationClinicalTrials.gov NCT00215267

Highlights

The ambitious London declaration prompted by the WHO 2012 roadmap to combat neglected tropical diseases commits to global schistosomiasis control by 2020 [1, 2]
Demographic, occupational, S. mansoni morbidity and infection intensity (KK) data including dose related treatment effect were reported in Tukahebwa et al 2013 and Koukounari et al 2013 [21, 22]
For antigen-based diagnostic tools, it is necessary to know whether the detected antigen is removed from circulation in response to treatment, as it is otherwise impossible to interpret whether this tool can be used to evaluate re-infection levels and treatment efficacy

Summary

Introduction

The ambitious London declaration prompted by the WHO 2012 roadmap to combat neglected tropical diseases commits to global schistosomiasis control by 2020 [1, 2]. For elimination strategies, where low infection intensities and focal epidemiology must be addressed in the later stages of a control programme, a test--treat approach based on point-of-care tests, preferably incorporated in integrated disease control programmes, becomes relevant in contrast to continuous reliance on mass drug administration only protocols. Schistosoma spp. worm antigens, which are released by living worms, are attractive targets compared to specific antibodies as they enable identification of currently infected individuals compared to individuals with previous infection. This is very relevant for assessing treatment efficacy as praziquantel kills adult schistosomes and mature eggs, but does not affect the immature worm and egg stages [6,7,8]

Methods

Results

Discussion

Conclusion