title: Sensitivity and Specificity of a Urine Circulating Anodic Antigen Test for the Diagnosis of Schistosoma haematobium in Low Endemic Settings.
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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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
  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.
authors.affiliation: Wolfson Wellcome Biomedical Laboratories, Department of Life Sciences, Natural History Museum, London, United Kingdom; Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Knopp
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Paul L A M
authors.initials: PL
authors.lastname: Corstjens
authors.affiliation: Biostatistics Department, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, United Kingdom.
authors.forename: Artemis
authors.initials: A
authors.lastname: Koukounari
authors.affiliation: Laboratory of Human Nutrition, Institute of Food, Nutrition, and Health, Eidgenössische Technische Hochschule (ETH) Zurich, Zurich, Switzerland.
authors.forename: Colin I
authors.initials: CI
authors.lastname: Cercamondi
authors.affiliation: Public Health Laboratory-Ivo de Carneri, Chake Chake, Pemba, United Republic of Tanzania.
authors.forename: Shaali M
authors.initials: SM
authors.lastname: Ame
authors.affiliation: Public Health Laboratory-Ivo de Carneri, Chake Chake, Pemba, United Republic of Tanzania.
authors.forename: Said M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Claudia J
authors.initials: CJ
authors.lastname: de Dood
authors.affiliation: Helminth Control Laboratory Unguja, Ministry of Health, Zanzibar Town, Unguja, United Republic of Tanzania.
authors.forename: Khalfan A
authors.initials: KA
authors.lastname: Mohammed
authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Jürg
authors.initials: J
authors.lastname: Utzinger
authors.affiliation: Wolfson Wellcome Biomedical Laboratories, Department of Life Sciences, Natural History Museum, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Rollinson
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Govert J
authors.initials: GJ
authors.lastname: van Dam
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D006023:Glycoproteins / Q000652:urine*; D015801:Helminth Proteins / Q000652:urine*; D006801:Humans; D007159:Immunologic Tests / Q000379:methods; D007195:Indian Ocean Islands; D007223:Infant; D008297:Male; D015995:Prevalence; D012548:Schistosoma haematobium / Q000276:immunology; D012553:Schistosomiasis haematobia / Q000175:diagnosis* / Q000276:immunology; D012680:Sensitivity and Specificity; D013636:Tanzania; D016482:Urinalysis / Q000379:methods*
chemical_list: D000947:Antigens, Helminth; D006023:Glycoproteins; D015801:Helminth Proteins; C090907:circulating anodic antigen, Schistosoma mansoni