Sensitivity and Specificity of a Urine Circulating Anodic Antigen Test for the Diagnosis of Schistosoma haematobium in Low Endemic Settings

PLoS Negl Trop Dis. 2015 May 14;9(5):e0003752. doi: 10.1371/journal.pntd.0003752. eCollection 2015 May.

Abstract

Background: Elimination of schistosomiasis as a public health problem and interruption of transmission in selected areas are key goals of the World Health Organization for 2025. Conventional parasitological methods are insensitive for the detection of light-intensity infections. Techniques with high sensitivity and specificity are required for an accurate diagnosis in low-transmission settings and verification of elimination. We determined the accuracy of a urine-based up-converting phosphor-lateral flow circulating anodic antigen (UCP-LF CAA) assay for Schistosoma haematobium diagnosis in low-prevalence settings in Zanzibar, Tanzania.

Methodology: A total of 1,740 urine samples were collected in 2013 from children on Pemba Island, from schools where the S. haematobium prevalence was <2%, 2-5%, and 5-10%, based on a single urine filtration. On the day of collection, all samples were tested for microhematuria with reagent strips and for the presence of S. haematobium eggs with microscopy. Eight months later, 1.5 ml of urine from each of 1,200 samples stored at -20°C were analyzed by UCP-LF CAA assay, while urine filtration slides were subjected to quality control (QCUF). In the absence of a true 'gold' standard, the diagnostic performance was calculated using latent class analyses (LCA).

Principal findings: The 'empirical' S. haematobium prevalence revealed by UCP-LF CAA, QCUF, and reagent strips was 14%, 5%, and 4%, respectively. LCA revealed a sensitivity of the UCP-LF CAA, QCUF, and reagent strips of 97% (95% confidence interval (CI): 91-100%), 86% (95% CI: 72-99%), and 67% (95% CI: 52-81%), respectively. Test specificities were consistently above 90%.

Conclusions/significance: The UCP-LF CAA assay shows high sensitivity for the diagnosis of S. haematobium in low-endemicity settings. Empirically, it detects a considerably higher number of infections than microscopy. Hence, the UCP-LF CAA employed in combination with QCUF, is a promising tool for monitoring and surveillance of urogenital schistosomiasis in low-transmission settings targeted for elimination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Helminth / immunology
  • Antigens, Helminth / urine*
  • Child
  • Child, Preschool
  • Glycoproteins / urine*
  • Helminth Proteins / urine*
  • Humans
  • Immunologic Tests / methods
  • Indian Ocean Islands
  • Infant
  • Male
  • Prevalence
  • Schistosoma haematobium / immunology
  • Schistosomiasis haematobia / diagnosis*
  • Schistosomiasis haematobia / immunology
  • Sensitivity and Specificity
  • Tansania
  • Urinalysis / methods*

Substances

  • Antigens, Helminth
  • Glycoproteins
  • Helminth Proteins
  • circulating anodic antigen, Schistosoma mansoni

Grants and funding

This study received financial support from the University of Georgia Research Foundation Inc., which is funded by the Bill & Melinda Gates Foundation for the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) projects (prime award no. 50816, sub-award nos. RR374-053/4893206 and RR374-053/4692608). SK is financially supported by sub-award no. RR374-053/4893196. AK is funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley National Health System (NHS) Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NIHR, the NHS, or the UK Government Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.