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

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.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Schematical overview of sampling time points and treatment regimens.

Diagram showing the faecal (F) and urine (U) sample collection time points included in this study; baseline (bsl), baseline+24hours (bsl+24), two weeks (2wks), two weeks+24hours (2wks+24hrs), nine weeks (9wks) and two years (2yrs). Both praziquantel (PZQ) and albendazole (Alb) was administered to everyone at baseline and the end of the study (2yrs). An additional dose of PZQ was administered at the two week time point to the two treatments arm (2 Tx).

Fig 2. S. mansoni egg counts and CCA scores stratified by age groups and treatment arms.

a) and b) Boxplot with whiskers (5-95th percentile) showing S. mansoni EPG (mean of all obtained KK/individual) related to participant age for a) the one treatment arm (nbsl = 239, n9wks = 228, n2yrs = 186) and b) the two treatments group (nbsl = 206, n9wks = 200, n2yrs = 160) at three time points. Circles depict outliers. Medians are indicated with horizontal bars and the means with small “+”. The top and bottom of the box represent the 75th and 25th percentile respectively. c) and d) show mean CCA score ±95% CI stratified by age groups for c) the one treatment arm (nbsl = 238, n9wks = 211, n2yrs = 170) and d) the two treatments arm (nbsl = 206, n9wks = 188, n2yrs = 156) at three time points. The distribution for all samples per time point is shown at the far right on all subfigures.

Fig 3. Short term CCA scores in response to treatment.

The mean CCA scores with 95% confidence intervals stratified by age groupings are shown for a) baseline and baseline+24hours (ntotal = 392) and b) two weeks and two weeks + 24hours further stratified by treatment regimen (n1Tx = 147, n2Tx = 157). Only individuals, who gave a urine sample at a time point (bsl and/or 2wks) and another sample at +24hrs, are included. “Trace” is included as score 0,5.