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

Abstract

BackgroundElimination 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.MethodologyA 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 FindingsThe ‘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/SignificanceThe 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.

New diagnostic tools in schistosomiasis

“…Using urine as a non-invasive sample methodology, the UCP-LF CAA assay has recently been used to evaluate advanced schistosomiasis japonica screening and control programmes in China, showing evidence that triplicate Kato-Katz thick smears might underestimate the prevalence of active S. japonicum infections by a factor of 10 compared with the UCP-LF CAA assay [41]. Applying the UCP-LF CAA test for S. haematobium diagnosis in a close-to-elimination setting in Zanzibar, United Republic of Tanzania, showed that the empirical prevalence revealed with the UCP-LF CAA was several-fold higher than the prevalence detected with a single urine filtration [42]. Noteworthy, the IHAs applied as the firstline screening tool in China fell short in about 50% of active cases.…”

“…The use of a flow diagram detailing the design of the study, methods for recruitment, order of test execution, flow of participants and presentation of decisive and indecisive test results is strongly encouraged [38,39]. Moreover, the validation of existing and new tools for schistosomiasis diagnosis is making progress [40][41][42], most prominently in multi-country studies [43]. Table 2 summarises a host of methods that are being used for schistosomiasis diagnosis.…”

Seasonal variations in Schistosoma haematobium egg excretion in school-age girls in rural KwaZulu-Natal Province, South Africa

“…[6,22] Therefore, urine microscopy for S. haematobium ova continues to be a preferred field diagnostic test. However, our results indicate that urine microscopy should be done during the hot season in SA, ensuring as little underestimation of prevalence as possible.…”

Sm‐p80‐based vaccine trial in baboons: efficacy when mimicking natural conditions of chronic disease, praziquantel therapy, immunization, and Schistosoma mansoni re‐encounter

“…Urine samples were tested with the UCAA50 assay as described elsewhere . For the standard CAA50 assay, urine samples were extracted with an equal volume of 4% w/v trichloroacetic acid (TCA).…”

“…Urine samples were tested with the UCAA50 assay as described elsewhere. 28,37 For the standard CAA50 assay, urine samples were extracted with an equal volume of 4% w/v trichloroacetic acid (TCA). Note that 20 L of the TCA-soluble fraction (TCAsupernatant, consisting of 50% v/v urine and 2% w/v TCA) was added to a tube containing 100 L assay buffer (100 mM HEPES pH 7.5, 270 mM NaCl, 0.5% v/v Tween-20, 1% w/v BSA).…”