Circulating antigen tests and urine reagent strips for diagnosis of active schistosomiasis in endemic areas

  • Review
  • Diagnostic

Authors

  • Eleanor A Ochodo,

    Corresponding author
    1. Academic Medical Center, University of Amsterdam, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam, Netherlands
    2. Stellenbosch University, Centre for Evidence-based Health Care, Faculty of Medicine and Health Sciences, Cape Town, South Africa
    • Eleanor A Ochodo, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, 1100 DD, Netherlands. eleanor.ochodo@gmail.com. eochodo@sun.ac.za.

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  • Gowri Gopalakrishna,

    1. Academic Medical Center, University of Amsterdam, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam, Netherlands
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  • Bea Spek,

    1. Academic Medical Center, University of Amsterdam, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam, Netherlands
    2. Hanze University Groningen, Department of Speech and Language Pathology, Groningen, Netherlands
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  • Johannes B Reitsma,

    1. University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, Netherlands
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  • Lisette van Lieshout,

    1. Leiden University Medical Center, Department of Parasitology, Leiden, Netherlands
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  • Katja Polman,

    1. Institute of Tropical Medicine, Department of Biomedical Sciences, Antwerp, Belgium
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  • Poppy Lamberton,

    1. Imperial College London, Department of Infectious Disease Epidemiology, London, UK
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  • Patrick MM Bossuyt,

    1. Academic Medical Center, University of Amsterdam, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam, Netherlands
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  • Mariska MG Leeflang

    1. Academic Medical Center, University of Amsterdam, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam, Netherlands
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Abstract

Background

Point-of-care (POC) tests for diagnosing schistosomiasis include tests based on circulating antigen detection and urine reagent strip tests. If they had sufficient diagnostic accuracy they could replace conventional microscopy as they provide a quicker answer and are easier to use.

Objectives

To summarise the diagnostic accuracy of: a) urine reagent strip tests in detecting active Schistosoma haematobium infection, with microscopy as the reference standard; and b) circulating antigen tests for detecting active Schistosoma infection in geographical regions endemic for Schistosoma mansoni or S. haematobium or both, with microscopy as the reference standard.

Search methods

We searched the electronic databases MEDLINE, EMBASE, BIOSIS, MEDION, and Health Technology Assessment (HTA) without language restriction up to 30 June 2014.

Selection criteria

We included studies that used microscopy as the reference standard: for S. haematobium, microscopy of urine prepared by filtration, centrifugation, or sedimentation methods; and for S. mansoni, microscopy of stool by Kato-Katz thick smear. We included studies on participants residing in endemic areas only.

Data collection and analysis

Two review authors independently extracted data, assessed quality of the data using QUADAS-2, and performed meta-analysis where appropriate. Using the variability of test thresholds, we used the hierarchical summary receiver operating characteristic (HSROC) model for all eligible tests (except the circulating cathodic antigen (CCA) POC for S. mansoni, where the bivariate random-effects model was more appropriate). We investigated heterogeneity, and carried out indirect comparisons where data were sufficient. Results for sensitivity and specificity are presented as percentages with 95% confidence intervals (CI).

Main results

We included 90 studies; 88 from field settings in Africa. The median S. haematobium infection prevalence was 41% (range 1% to 89%) and 36% for S. mansoni (range 8% to 95%). Study design and conduct were poorly reported against current standards.

Tests for S. haematobium

Urine reagent test strips versus microscopy

Compared to microscopy, the detection of microhaematuria on test strips had the highest sensitivity and specificity (sensitivity 75%, 95% CI 71% to 79%; specificity 87%, 95% CI 84% to 90%; 74 studies, 102,447 participants). For proteinuria, sensitivity was 61% and specificity was 82% (82,113 participants); and for leukocyturia, sensitivity was 58% and specificity 61% (1532 participants). However, the difference in overall test accuracy between the urine reagent strips for microhaematuria and proteinuria was not found to be different when we compared separate populations (P = 0.25), or when direct comparisons within the same individuals were performed (paired studies; P = 0.21).

When tests were evaluated against the higher quality reference standard (when multiple samples were analysed), sensitivity was marginally lower for microhaematuria (71% vs 75%) and for proteinuria (49% vs 61%). The specificity of these tests was comparable.

Antigen assay

Compared to microscopy, the CCA test showed considerable heterogeneity; meta-analytic sensitivity estimate was 39%, 95% CI 6% to 73%; specificity 78%, 95% CI 55% to 100% (four studies, 901 participants).

Tests for S. mansoni

Compared to microscopy, the CCA test meta-analytic estimates for detecting S. mansoni at a single threshold of trace positive were: sensitivity 89% (95% CI 86% to 92%); and specificity 55% (95% CI 46% to 65%; 15 studies, 6091 participants) Against a higher quality reference standard, the sensitivity results were comparable (89% vs 88%) but specificity was higher (66% vs 55%). For the CAA test, sensitivity ranged from 47% to 94%, and specificity from 8% to 100% (four studies, 1583 participants).

Authors' conclusions

Among the evaluated tests for S. haematobium infection, microhaematuria correctly detected the largest proportions of infections and non-infections identified by microscopy.

The CCA POC test for S. mansoni detects a very large proportion of infections identified by microscopy, but it misclassifies a large proportion of microscopy negatives as positives in endemic areas with a moderate to high prevalence of infection, possibly because the test is potentially more sensitive than microscopy.

Plain language summary

How well do point-of-care tests detect Schistosoma infections in people living inendemic areas?

Schistosomiasis, also known as bilharzia, is a parasitic disease common in the tropical and subtropics. Point-of-care tests and urine reagent strip tests are quicker and easier to use than microscopy. We estimate how well these point-of-care tests are able to detect schistosomiasis infections compared with microscopy.

We searched for studies published in any language up to 30 June 2014, and we considered the study’s risk of providing biased results.

What do the results say?

We included 90 studies involving almost 200,000 people, with 88 of these studies carried out in Africa in field settings. Study design and conduct were poorly reported against current expectations. Based on our statistical model, we found:

• Among the urine strips for detecting urinary schistosomiasis, the strips for detecting blood were better than those detecting protein or white cells (sensitivity and specificity for blood 75% and 87%; for protein 61% and 82%; and for white cells 58% and 61%, respectively).
• For urinary schistosomiasis, the parasite antigen test performance was worse (sensitivity, 39% and specificity, 78%) than urine strips for detecting blood.
• For intestinal schistosomiasis, the parasite antigen urine test, detected many infections identified by microscopy but wrongly labelled many uninfected people as sick (sensitivity, 89% and specificity, 55%).

What are the consequences of using these tests?

If we take 1000 people, of which 410 have urinary schistosomiasis on microscopy testing, then using the strip detecting blood in the urine would misclassify 77 uninfected people as infected, and thus may receive unnecessary treatment; and it would wrongly classify 102 infected people as uninfected, who thus may not receive treatment.

If we take 1000 people, of which 360 have intestinal schistosomiasis on microscopy testing, then the antigen test would misclassify 288 uninfected people as infected. These people may be given unnecessary treatment. This test also would wrongly classify 40 infected people as uninfected who thus may not receive treatment.

Conclusion of review

For urinary schistosomiasis, the urine strip for detecting blood leads to some infected people being missed and some non-infected people being diagnosed with the condition, but is better than the protein or white cell tests. The parasite antigen test is not accurate.

For intestinal schistosomiasis, the parasite antigen urine test classifies many microscopy negative people as being infected. This finding may be explained by the low sensitivity of microscopy.

Background

Target condition being diagnosed

Schistosomiasis, also known as bilharzia, is the second major parasitic disease affecting tropical and subtropical regions after malaria. It is caused by trematode worms of the genus Schistosoma (Gryseels 2012). The latest estimates show that schistosomiasis is endemic in 76 countries, with 779 million people at risk of infection and approximately 207 million people currently infected. Sub-Saharan Africa accounts for more than 90% of current cases of schistosomiasis (Engels 2002; WHO 2010; Gryseels 2012). The global burden of disease in 2004 was estimated at 13 to 15 million disability-adjusted life-years (DALYs) lost as the result of schistosomiasis (King 2010a). These estimates could be an underestimate resulting from the low sensitivity of routinely used diagnostic tests (King 2010a; King 2010b).

Five main schistosome species are known to infect man (Schistosoma mansoni, Schistosoma haematobium,Schistosoma japonicum, Schistosoma intercalatum, and Schistosoma mekongi), of which S. mansoni, S. haematobium, and S. japonicum have the greatest impact on morbidity (Gryseels 2006). The focus of this review will be on diagnosing infection caused by S. mansoni and S. haematobium, as they are more widespread globally and account for most infections and associated morbidity worldwide. These species cause intestinal schistosomiasis and urogenital schistosomiasis, respectively. As outlined in Appendix 1, urogenital schistosomiasis presents with blood in urine (haematuria), proteins in urine (proteinuria), or white blood cells in urine (leukocyturia). In its chronic form, it presents with major bladder, kidney, and genital pathologies including chronic renal failure. Intestinal schistosomiasis presents with abdominal pain and in its chronic and severe forms can present with enlarged liver (hepatomegaly), abdomen distended with fluid (ascites), and liver failure.

Currently, no vaccine is available to protect against schistosomal infection (Rollinson 2009; Bethony 2011). If left untreated, schistosomal infection may result in chronic disease. The current drug of choice is praziquantel, which is cheap (costing less than USD 0.15 per treatment) and safe and causes few side effects. Praziquantel however is ineffective against the eggs and larval forms of schistosome worms (Gryseels 2012; Rollinson 2013). Mass praziquantel treatment of populations at risk of infection is now routine in many endemic areas (WHO 2010; Rollinson 2013). Reinfections rapidly occur as the result of recurrent direct contact with water bodies infected with schistosomal parasites (WHO/TDR 2006; Rollinson 2009; Rollinson 2013). No strong evidence of clinically relevant drug resistance is available (Geerts 2001; Doenhoff 2002; Fenwick 2003; Doenhoff 2009; Greenberg 2013). However reports have described heterogeneities in egg reduction rates and in systematic non-clearers of infection after treatment with praziquantel (Black 2009; Melman 2009; Ahmed 2012). In the long run, mass treatment has limitations related to cost-effectiveness (French 2010), poor sustainability (Utzinger 2009), poor drug compliance by individuals (Guo 2005; Croce 2010), and increased drug selection pressure (Greenberg 2013).

Accurate and affordable diagnostic tools are essential for providing targeted treatment and for maximizing the success of control of schistosomiasis in endemic areas; they are required for monitoring drug efficacy as well. Diagnosis of schistosomiasis can be performed directly or indirectly. Direct methods include detection of schistosome eggs in urine or stool by microscopy, detection of schistosome antigens in serum or urine samples, and detection of Schistosoma-specific DNA in urine, stool, or blood. Indirect methods include questionnaires, biochemical tests (urine reagent strips for microhaematuria/proteinuria/leukocyturia), antibody tests, ultrasonography, computed tomography (CT) scan, magnetic resonance imaging (MRI) scan, endoscopy, and cystoscopy (Feldmeier 1993; Rabello 1997; Doenhoff 2004; Bichler 2006; Gryseels 2012; Cavalcanti 2013).

Currently no gold standard is recommended for the detection of schistosomiasis. Microscopy is the most widely used test for diagnosing schistosomiasis and, although imperfect, it is commonly used as the reference standard in practice. Its sensitivity has been shown to vary with intensity of infection, prevalence of infection, sample preparation techniques, stool consistency, and circadian and day-to-day variation of egg counts in stool and/or urine (Doehring 1983; Doehring 1985a; Rabello 1992; Feldmeier 1993; Rabello 1997; van Lieshout 2000; Knopp 2008). This becomes particularly pertinent as control programmes progress and sensitivity of microscopy decreases as the result of reduced infection intensity. Repeated measurements over multiple days from multiple samples and/or multiple smears/slides taken from each sample has been shown to increase sensitivity (Knopp 2008; da Frota 2011; Siqueira 2011; Deelder 2012); however this task increases the time taken to perform the survey and therefore becomes logistically expensive (van Lieshout 2000; Legesse 2007).

Index test(s)

Urine reagent strips and circulating antigen tests are used as alternatives to microscopy for diagnosis of schistosomiasis. Compared with microscopy, urine reagent strips used to detect microhaematuria or proteinuria as a proxy for S. haematobium infection are cheap, quick, and easy to use (Mott 1985; Brooker 2009); have no technical requirements; and are less influenced by the circadian production of schistosome eggs (Murare 1987; Lengeler 1991b). Furthermore, some studies have shown that the sensitivity of these strips is higher than that of urine filtration (French 2007; Robinson 2009), and that a single test with microhaematuria strips is more sensitive than a single test with urine filtration (Taylor 1990)—features that make these strips suitable for screening of urogenital schistosomiasis in the field. However, results should be interpreted against the background of risk for schistosomiasis, as well as any other signs and symptoms that could be indicative of other diseases. Microhaematuria and proteinuria are non-specific signs that could also result from other ailments such as urogenital infection, malignancy, immune system disorders, metabolic disorders, and trauma.

Circulating antigen tests (circulating anodic antigen (CAA) and circulating cathodic antigen (CCA)) have also been evaluated as replacements for microscopy in the diagnosis of infection due to S. haematobium or S. mansoni. These tests can differentiate between active and past infections, as the circulating antigens are probably present only when there is active infection (Doenhoff 2004). As circulating antigens are released from living worms, antigen levels may correlate directly with parasite load, whilst microscopy does not. This may make the CCA POC test useful in monitoring the dynamics of worm burdens and clearance of worms after treatment (Cavalcanti 2013; Rollinson 2013). However, the sensitivity of these tests has been shown to vary with prevalence of disease and intensity of infection (De Jonge 1988; De Jonge 1989; van Lieshout 1992; De Clerq 1997; Stothard 2006; Ayele 2008; Obeng 2008; Midzi 2009; Colley 2013).

This review evaluates the urine CCA POC test, urine CCA and CAA enzyme-linked immunosorbent assay (ELISA), and serum CCA and CAA ELISA. The urine CCA POC test is a lateral flow assay that uses a nitrocellulose strip with a monoclonal antibody–coated test line to detect the presence of Schistosoma-specific CCA antigen in urine. When urine from an infected individual flows through the strip, the antigen will bind to the test line, which becomes visible with the binding of added labelled monoclonal antibodies (van Dam 2004). Of note, the urine CCA POC test was developed based on the performance of the ELISA format (Brooker 2009). The urine CCA ELISA was found to have the best diagnostic performance, followed by the serum CAA assay for S. mansoni (Polman 1995; van Lieshout 1995; van Lieshout 2000). Therefore, although they are not rapid tests, the accuracy measures of ELISA tests will be systematically assessed, as the summary measures obtained may guide the ongoing development of improved POC tests.

So far, a range of accuracy measures have been reported for urine reagent tests and for circulating antigen tests. Diagnostic and treatment strategies in endemic areas vary with results of these tests (Appendix 2) and depend on financial and human resource capacity.

Clinical pathway

Patients suspected of having active S. haematobium or S. mansoni infection in endemic settings.

Prior test(s)

As outlined in Appendix 2, current practice in endemic settings is to use urine reagent strips as a replacement for microscopy or as a triage test (before microscopy), or circulating antigen tests as a replacement for microscopy. In line with practice in disease control programmes, we focus on the role of these tests as alternatives to microscopy. We will not consider prior testing with other tests, as this is rarely done in public health programmes.

Role of index test(s)

We are interested in the following purposes for testing.

  • Reagent strips to detect microhaematuria, proteinuria, or leukocyturia as a replacement test for microscopy for S. haematobium infection.

  • CCA point-of-care test as a replacement test for microscopy for S. haematobium or S. mansoni infection.

Alternative test(s)

Apart from the two test types mentioned above, a range of other tests can be used to screen for schistosomiasis. However, all are used in different situations and in different circumstances than the tests mentioned above.

Questionnaires have been used for the initial rapid screening for urinary schistosomiasis in high-risk communities in endemic areas (Lengeler 1991a; Feldmeier 1993; Chitsulo 1995). These questionnaires rely on self-reporting of blood in urine. Studies have shown that questionnaires demonstrate moderate to high sensitivities and specificities when used to screen individuals for urogenital schistosomiasis in high-prevalence areas but low sensitivity and specificity in low-prevalence areas (Lengeler 1991a; Lengeler 1991b; Brooker 2009). Questionnaires for intestinal schistosomiasis have been shown to be less sensitive and specific than those for urogenital schistosomiasis (WHO/TDR 2006; Brooker 2009). Symptoms of intestinal schistosomiasis are associated with many other diseases, which often overlap in range. As co-infection is the norm rather than a rare occurrence, the questionnaires are less specific. The accuracy of questionnaires has been shown to be influenced by age and gender. When questionnaires are used repeatedly in the same area, respondents are prone to give biased answers, as they know the consequences of the answers they give. Thus, recall bias may interfere with the accuracy of the test. Consequently, relying on questionnaires may become ineffective, making this screening method unsuitable even for follow-up of patients after treatment (Ansell 1997; Guyatt 1999; Lengeler 2002). As questionnaires are recommended mainly for initial rapid screening and not for routine screening for schistosomiasis, they will not be evaluated in this review.

Serology tests are alternative tests for the diagnosis of schistosomiasis. These tests detect antibodies against worm antigens, egg antigens (soluble egg antigens (SEAs)), or eosinophil cationic proteins (ECPs) (Reimert 1991; Feldmeier 1993; ITM 2007). Available methods include ELISA, indirect immunofluorescence assay (IFA), and indirect haemagglutination assay (IHA). Antibody tests demonstrate high sensitivity even in areas with light infection and therefore can be used in areas with low endemicity. However these tests fall short in distinguishing current active infection from past infection, have low specificity in endemic areas because of cross-reactivity with antigens of other helminths, and often show antibody levels that remain elevated after treatment; therefore they yield many false-positive results (Doenhoff 2004; Cavalcanti 2013). Antibody tests may have a role in checking for maintained exposure to schistosomiasis in areas that are moving towards elimination (Rollinson 2013).

The ECP test is an indirect marker of S. haematobium infection and related morbidity (Reimert 2000; Vennervald 2004). Other test examples include rectal biopsy (ITM 2007), cystoscopy and endoscopy, radiological methods (Bichler 2006), FLOTAC (a novel faecal egg count technique) (Knopp 2009; Glinz 2010), and molecular tests using polymerase chain reaction (PCR) (Ten Hove 2008; Oliveira 2010; Knopp 2011). However these tests may be expensive or may require trained laboratory personnel and an elaborate laboratory infrastructure.

Rationale

For improved mapping to ensure effective selective (or targeted) treatment and for accurate data on treatment success with praziquantel, appropriate diagnostic tests are urgently required. When a test for diagnosing schistosomiasis is considered, a test with high sensitivity is paramount, especially when infection is being monitored within a disease control programme. False-negative results lead to missed treatment and subsequently to more advanced disease or, if occurring after praziquantel treatment, may lead to overestimated cure rates and potentially undetected cases of praziquantel resistance and the spread of the disease. High specificity is also required, as unnecessary treatment due to false-positive results could reduce cost-effectiveness in current control programme strategies through potentially inaccurate classification of prevalence levels or in future targeted treatment control programmes (WHO/TDR 2006). On the other hand, a test for mapping of disease (to get an estimation of disease prevalence in an endemic area) may not need sensitivity and specificity as high as those required for monitoring of disease.

There is currently no recommended gold standard for the detection of active schistosomiasis. However, because microscopy is the most commonly used test in practice and is often used as the reference test in studies, we selected it for use as the reference standard within this review to detect S. haematobium and S. mansoni. The primary concern with microscopy is the possibility of missing infected cases (because of its low and varied sensitivity), especially in areas with low intensity of infection. This means that truly infected cases may be missed and misclassified as non-infected by microscopy. Therefore when comparing an index test against microscopy, the number of false-positives (potentially true cases classified as positive by the index test and classified as negative by the reference test) may be high, and the index test may present with low specificity. Increasing the sensitivity of microscopy by taking multiple measurements may reduce the number of true cases wrongly classified as non-infected by microscopy. An index test compared against a more sensitive reference test (microscopy with multiple measurements) may have higher specificity because the number of false-positives will be low. Our review will therefore also investigate the effect of the quality of the reference standard on the sensitivity and specificity of the index tests being evaluated.

In this case, a test considered as a replacement for microscopy should have comparable sensitivity or should be less costly, portable, faster, and easier to use or interpret, and it should be less demanding logistically. Point-of-care tests based on circulating antigen detection and biochemical urine reagent strips in particular are being included (or developed) in disease control strategies, as they are easy to use and interpret, require minimal laboratory infrastructure, are cost-effective, reduce patient waiting time and potentially therefore reduce loss to follow-up, and may have comparable or higher sensitivity to microscopy (Loubiere 2010). The results of this review may guide policy makers on appropriate diagnostic tests to use and may help identify research gaps in diagnostic testing for schistosomiasis in endemic areas.

Objectives

With the goals of making recommendations and informing policy makers on which tests to use and identifying research gaps, these were our primary objectives:

  • To obtain summary estimates of the diagnostic accuracy of urine reagent strip tests for microhaematuria, proteinuria, and leukocyturia in detecting active S. haematobium infection, with microscopy of urine as the reference standard.

  • To obtain summary estimates of the diagnostic accuracy of circulating antigen tests—a urine POC circulating cathodic antigen (CCA) test, a urine and serum CCA enzyme-linked immunosorbent assay (ELISA) test, and a urine and serum circulating anodic antigen (CAA) test—for detection of active Schistosoma infection in geographical regions endemic for S. mansoni or S. haematobium or both, with microscopy as the reference standard.

  • To compare the accuracy of the above index tests.

  • To investigate potential sources of heterogeneity in the diagnostic accuracy of the tests listed above.

Secondary objectives

To investigate whether age and gender of participants, positivity thresholds, prevalence of infection, intensity of infection, quality of the reference standard, effects of praziquantel treatment, infection stage, mixed infections, and the methodological quality of included studies can explain observed heterogeneity in estimates of test accuracy.

Methods

Criteria for considering studies for this review

Types of studies

We included primary observational studies that compared the results of one or more of the index tests versus the reference standard. These studies could be cross-sectional in design, cohort studies, or diagnostic case-control studies with cases and controls sampled from the same patient population.

We included studies that provide participant data. Only studies in which true-positives (TPs), true-negatives (TNs), false-positives (FPs), and false-negatives (FNs) were reported or could be extracted from the data were included.

We excluded case-control studies with healthy controls, controls from non-endemic areas, or controls with alternative diagnoses (patients with diseases similar to schistosomiasis), as specificity may be overestimated (Rutjes 2005). False-positive test results may occur when an alternative disease produces the same pathophysiological changes as the target condition. We also excluded studies that enrolled only participants with proven schistosomiasis, as sensitivity may be overestimated.

Participants

Participants had to be individuals residing in regions where S. haematobium and S. mansoni infections were endemic. We excluded articles that studied travelers originating from non-endemic countries, as they were typically screened with other tests such as antibody tests.

Index tests

We included studies that evaluated the following tests.

Urine reagent strip tests

A urine reagent strip test is a biochemical semiquantitative test. It is regarded as an indirect indicator of S. haematobium infection or morbidity, as it detects microhaematuria, proteinuria, or leukocyturia (white blood cells in urine) that can develop as a consequence of schistosomal infection (Doehring 1985b;Doehring 1988). This test is cheap and easy to use for rapid screening of urinary schistosomiasis (Feldmeier 1993; Gryseels 2006; Gryseels 2012).

The results of urine reagent tests used to measure haematuria are scored as 0 (negative), trace-positive (tr), 1+ (5 to 10 erythrocytes/μL), 2++ (10 to 50 erythrocytes/μL), or 3+++ (50 to 250 erythrocytes/μL). For proteinuria, results are scored as 0 (negative), trace-positive (tr), 1+ (30 mg protein/dL), 2++ (100 mg protein/dL), or 3+++ (500 mg protein/dL) (Murare 1987).

Antigen tests

Antigen tests are based on detection of schistosome antigens in the serum and urine of individuals (Gryseels 2006; WHO/TDR 2006; Gryseels 2012). The main circulating antigens are adult worm gut–associated circulating antigens, and CAA and CCA are the main focus of research.

The CCA dipstick is scored according to test band reaction intensity as negative (-), trace-positive (tr), single-positive (+), double-positive (++), and triple-positive (+++) (Stothard 2006). ELISA results are continuous, and positivity thresholds may vary. To estimate the accuracy of ELISA tests, ELISA must have been evaluated against the reference standard only.

Target conditions

Active infection with S. haematobium.

Active infection with S. mansoni.

Reference standards

S. haematobium

For diagnosis of S. haematobium infection, the reference standard is microscopy of urine for examination of schistosome eggs. To increase sensitivity, urine samples can be concentrated by sedimentation, filtration, or centrifugation techniques (Gryseels 2006), or more samples can be examined (Feldmeier 1993). We therefore included studies that use all of these concentration techniques, and to estimate the effect of the quality of the reference standard, we accepted studies using microscopy on a single urine sample (lower-quality reference standard) and studies performing microscopy on multiple urine samples (higher-quality reference standard).

S. mansoni

For diagnosis of S. mansoni infection, microscopic examination of schistosome eggs in stool is the reference standard. Sensitivity is increased by preparing a faecal thick smear using the Kato-Katz (KK) method (Gryseels 2006) or by examining multiple stool samples (Feldmeier 1993). To estimate the effect of the quality of the reference standard, we accepted studies using microscopy on a single stool sample (lower-quality reference standard) and studies performing microscopy on multiple stool samples (higher-quality reference standard).

It is important to note that some regions experience mixed infections of S. haematobium and S. mansoni. In such situations, microscopy of both stool and urine samples must be carried out to confirm infection.

Search methods for identification of studies

Electronic searches

We searched the electronic databases MEDLINE, EMBASE, BIOSIS, MEDION, and HTA (Health Technology Assessment). The MEDLINE search strategy is outlined in Appendix 3. We further translated the MEDLINE search to EMBASE and BIOSIS databases to identify additional records. To avoid missing studies, we did not use a diagnostic search filter. We performed the searches on 12 January 2012 and repeated them on 16 November 2012, 29 August 2013, and 30 June 2014.

Searching other resources

We looked through reference lists of relevant reviews and studies and websites of the World Health Organization (WHO), the Schistosomiasis Control Initiative (SCI), and the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE). When possible, we contacted study authors to request extra information.

Data collection and analysis

Selection of studies

Two independent review authors first looked through titles and abstracts to identify potentially eligible studies. Full-text articles of these studies were obtained and assessed for study eligibility by two independent review authors using the predefined inclusion and exclusion criteria. Disagreements were resolved through discussion and by consultation with a third review author when necessary.

Data extraction and management

Two independent review authors extracted data onto a data extraction form. 

The following data were extracted.

  • Study authors, publication year, and journal.

  • Study design.

  • Study participants—age, sex.

  • Prevalence of schistosomiasis.

  • Treatment status of participants with praziquantel—treatment status before study or post treatment.

  • Reference standard (microscopy), including number of samples per individual and exact volume of stool/urine examined.

  • Index tests—urine and serum circulating antigen tests (CCA and CAA) and urine reagent strips.

  • Urine reagent strips—signs measured (microhaematuria, proteinuria, leukocyturia).

  • Sample preparation techniques—time of day urine/stool sample was taken, intensity of infection—egg counts in urine and stool by microscopy.

  • Presence of missing or unavailable test results.

  • Numbers of TPs, FNs, FPs, and FNs.

Assessment of methodological quality

We used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool to assess risk of bias and concerns for applicability of the included studies (Whiting 2011) (Appendix 4). Disagreements were resolved through consensus or by consultation with a third review author. We extracted data using signalling questions and scored for risk of bias and concerns for applicability under the four main domains: participant selection, index test, reference standard, and participant flow.

Statistical analysis and data synthesis

Comparisons of index test versus the reference standard

We analyzed data for the two target conditions (S. haematobium andS. mansoni) separately. Only one included study (Ashton 2011) evaluated the ability of a test to detect S. haematobium and/orS. mansoni in an area of mixed infection.

Among studies reporting sufficient data for calculating sensitivity and specificity, we plotted their sensitivity and specificity in both forest plots and receiver operating characteristic (ROC) space using the software Review Manager 5.2. We performed a meta-analysis using the statistical software SAS version 9.2 for test types that had sufficient data points (four or more data points) to be pooled by the statistical models and those that did not demonstrate substantial heterogeneity in ROC space (Macaskill 2010 ). These tests included the reagent strip for microhaematuria, the reagent strip for proteinuria, the reagent strip for leukocyturia, the CCA POC test for S. haematobium, and the CCA POC test for S. mansoni.

The statistical model selected to perform the overall meta-analysis depended on the variability of the positivity thresholds, as discussed below. Data for urine reagent strips and urine CCA POC tests were ordinal. These tests are typically scored as 0, trace, 1+, 2+, and 3+, or as 0, 1+, 2+, and 3+.

When data from a test had multiple thresholds, we used the hierarchical summary receiver operating characteristic model (HSROC) to perform the overall meta-analysis. This model estimates the underlying ROC curve, which describes how sensitivity and specificity of the included studies trade off with each other as thresholds vary. It allows for variation in the parameters of accuracy, thresholds between studies, and the shape of the underlying ROC curve (Rutter 2001; Macaskill 2010). Because this method models sensitivity and specificity indirectly, we calculated average sensitivities and average specificities from the output of the model.

When data from a test had one or a common threshold, we used the bivariate random-effects model to perform the overall meta-analysis. This method models sensitivity and specificity directly at a common threshold (Reitsma 2005; Macaskill 2010).

We included all studies in the overall meta-analysis, whether or not a positivity threshold was included. We assumed that different thresholds were used for the studies that did not report their thresholds, and we used the HSROC model to perform the overall meta-analysis. For urine reagent strips for microhaematuria and proteinuria, many studies did not report a positivity threshold (n = 41 for microhaematuria and n = 25 for proteinuria). Some studies (n = 2) provided data points at both thresholds of trace and +1. When data points were provided at both thresholds, we selected the data point at threshold trace for the overall analysis; we selected the first stipulated positivity threshold. Leukocyturia had five overall data points, with four data points at threshold trace and one at +1. The CCA POC for S. haematobium had four overall data points, with two at threshold trace and two at +1.

All studies evaluating CCA POC for S. mansoni reported positivity thresholds; five provided data points at both thresholds trace and +1. When data points were provided at both thresholds, we selected the data point at threshold trace for the overall analysis; we selected the first stipulated positivity threshold. The overall analysis therefore contained 15 data points with threshold ≥ trace, for which we used the bivariate model for meta-analysis.

Comparisons of index tests

We compared the accuracy of the reagent strips for microhaematuria in detecting S. haematobium versus the accuracy of the reagent strips for proteinuria. These were the only tests with sufficient data to enable comparisons between different types of tests. Tests were compared by adding the co-variate test type to the HSROC model and allowing this to have an effect on the accuracy, threshold, and shape parameters. We performed indirect comparisons and direct comparisons; in the latter, we included only studies that applied both index tests in the same individuals.

Investigations of heterogeneity

We investigated heterogeneity by examining the forest plots and statistically by including co-variates in the HSROC or bivariate model, by conducting subgroup analysis, and by performing sensitivity analysis. In the HSROC model, we investigated whether these co-variates affect the parameters of this model—accuracy, threshold, and shape—whereas in the bivariate model, we investigated whether these co-variates affect sensitivity and specificity.

We did not investigate the effects of infection stage and mixed infection caused by poor reporting and insufficient data for these items.

We investigated the following sources of heterogeneity: quality of the reference standard, positivity threshold, age, gender (proportion of female participation), intensity of infection, prevalence of infection, effect of praziquantel treatment, and QUADAS-2 risk of bias domains. Of these, the co-variates gender (proportion of female participation) and prevalence of infection were analyzed as a continuous co-variate. The rest were analyzed as categorical co-variates.

We classified studies that used single-measurement microscopy (one stool and/or one slide or smear) and those that did not report how the reference standard was conducted as using lower-quality reference standards because single measurements are more likely to miss diseased individuals. We assumed that studies that used multiple measurements of microscopy were likely to report this, given the relevance of this additional effort. Reference standards that used multiple urine or stool samples or multiple slides or smears were classified as higher-quality reference standards.

For the age co-variate, many mixed adult/children studies did not state the proportions of adults or children. Some did not state the age of participants. As accuracy data were not provided for age subgroups in most studies, we dichotomized the age co-variate into the groups 'all ages' and 'children only'. We assumed that studies that did not state the age had included participants of all ages.

Because the proportions of female and male participants were poorly reported at the test level and at the level of the 2 × 2 tables, we analyzed the co-variate of gender as a continuous variable at the study level. For this co-variate, gender indicated the proportion of female participation. We focused on females because gender may influence accuracy estimates through factors associated with females, such as menstruation and genitourinary tract infection (Hall 1999; French 2007; Brooker 2009).

The World Health Organization (WHO) recommendations (WHO 2002) categorize intensity of infection for S. haematobium as follows: < 50 eggs/10 mL (light) and ≥ 50 eggs/10 mL (heavy) and intensity of S. mansoni as follows: 1 to 99 eggs per gram (epg) (light), 100 to 399 epg (moderate), and ≥ 400 epg (heavy). In our review, the intensity of infection was reported in different ways (arithmetic mean or range of infection, or geometric mean or range of infection, or proportions of participants with light/moderate/heavy infection) and for most included studies was not reported at all (63% and 65% for microhaematuria and proteinuria, respectively). We used the reported estimates of mean (arithmetic/geometric) or median intensity of infection to classify our studies according to WHO recommendations. We classified as unclear studies that reported only proportions of participants with light/moderate/heavy infections or did not report estimates of intensity of infection.

We examined the effects of treatment with praziquantel on the sensitivity and specificity of the testtype microhaematuria because it was the only test with sufficient data to investigate this. Nine studies provided data on praziquantel treatment; seven were follow-up studies with praziquantel given at variable intervals (King 1988_a (one year), NGoran 1989 (one month), Kitange 1993 (one year), Lengeler 1993 (one month), Shaw 1998 (six weeks), Magnussen 2001 (one year), French 2007 (one year)), and two indicated that praziquantel had been given before the baseline study was performed (Abdel-Wahab 1992 (two years), Bogoch 2012 (two years)). When multiple follow-up studies were performed, we selected data for the first follow-up evaluation (Shaw 1998; French 2007). However, pooling of results of all studies with varying time intervals would likely introduce a lot of heterogeneity, bias our summary estimates, and lead to overestimates of sensitivity, because studies with long time intervals were likely to have a greater number of participants reinfected compared with studies done at shorter time intervals. We opted to present estimates of sensitivity and specificity of individual studies evaluating the performance of microhaematuria post treatment in the ROC space.

We added the following co-variates one by one to the HSROC model for microhaematuria and proteinuria and to the bivariate model for CCA POC for S. mansoni: quality of the reference standard, age, gender, and prevalence of infection. We then performed a subgroup analysis for the co-variates—quality of the reference standard, age, positivity threshold, and intensity of infection—for all three index tests.

Sensitivity analyses

We performed a sensitivity analysis to check the robustness of results when filtration was used as a concentration for urine microscopy for S. haematobium, and to estimate sensitivity and specificity for studies with low risk of bias according to the QUADAS domains, along with participant selection, participant flow, and the reference standard.

Assessment of reporting bias

We did not assess reporting bias. Methods of assessing reporting bias for diagnostic accuracy studies are still being refined. For instance, the Deeks test, a test that has been proposed for use in diagnostic accuracy studies, has low power to detect funnel plot asymmetry, especially when a lot of heterogeneity is present (Macaskill 2010). The studies included in our review showed a lot of heterogeneity; therefore assessments for reporting bias may not yield conclusive results.

Results

Results of the search

Our search yielded 17,477 hits. After the titles and abstracts were screened, 152 full texts were retrieved, and after full texts were assessed, 90 articles were deemed suitable for inclusion; 62 were excluded. One study author whom we contacted responded to our request for information, but the data submitted did not meet our eligibility criteria. No additional eligible studies were found through additional searches. This review contains results derived from 90 articles. The search results can be seen in Figure 1.

Figure 1.

Study flow diagram.

* Reasons for exclusion can be found in the table of Characteristics of excluded studies.

Included studies

Details of included studies can be found in the Characteristics of included studies table. We included 90 studies containing 197,411 participants. Of these included studies, 88 were carried out in Africa, one in South America (Surinam), and one in Asia (Yemen). Only one study was conducted in a hospital setting (antenatal clinic, outpatient setting). The other tests were performed in a field setting (village/school/military camp). S. haematobium was evaluated in most studies (n = 74); 16 evaluated S. mansoni. One study evaluated both species. Eighty studies reported the age of study participants; most of these were conducted in children (n = 50; 62.5%). Median prevalence of S. haematobium infection was 41% (range 1% to 89%), and that of S. mansoni infection was 36% (range 8% to 95%). Median female participation was 50% (Q1 46; Q3 53) for studies that reported gender (n = 46; 51%). Most of the included studies (n = 73; 81%) did not report on the status of praziquantel treatment in the study setting before the baseline study was performed. Eighty-one studies used a cross-sectional design; six were cohort studies (longitudinal studies with follow-up), and three were case-control studies with controls from the same population (nested case-control studies). We included 84 English studies and six French studies. One study (Colley 2013), which was retrieved through an updated search, provided recent data for studies retrieved previously (Coulibaly 2011; Shane 2011; Tchuente 2012). In this case, we gathered data for the 2 × 2 tables from the most recent publication (Colley 2013).

Excluded studies

Full details of excluded studies can be found in the Characteristics of excluded studies table. We excluded 62 articles after reading the full texts. We excluded 17 case-control studies with healthy controls or with controls from non-endemic areas of schistosomiasis. We could not extract data from 2 × 2 tables for 16 studies. Twelve studies were not test accuracy studies, and four studies enrolled only patients proven to have schistosomiasis. Six studies used reference standards other than microscopy, four studies used other index tests to diagnose schistosomiasis that did not fulfil our inclusion criteria, and three studies performed similar tests on the same population as those reported by other already included studies.

Methodological quality of included studies

Figure 2 and Appendix 5 show results of the quality appraisal of the 60 included studies. Using the QUADAS-2 tool, we evaluated these studies for risk of bias in the following domains: participant selection, index test, reference standard, and participant flow. In general, poor reporting of quality items hindered our evaluation of quality. We therefore rated the risk of bias for these domains largely as unclear. In the participant selection domain, about 75% of studies were rated as having unclear risk of bias. For index tests, unclear risk of bias ranged from 80% to about 98% (about 98% for reagent strips for microhaematuria, about 95% for reagent strips for proteinuria, and about 80% for CCA POC testing). None of the studies had high risk of bias in the index test domain. For the reference standard, about 50% of the studies had high risk of bias, whereas the other half had unclear risk of bias. For the participant flow domain, about 75% of the studies had low risk of bias, and the remaining studies had unclear risk. Concerns for applicability for all four domains were predominantly low.

Figure 2.

Risk of bias and applicability concerns graph: review authors' judgements about each domain presented as percentages across included studies.

Findings

A summary of the main findings can be found in Summary of findings 1 and Summary of findings 2. Below we present in detail the overall findings for each index test.

Urine reagent strips

For microhaematuria

A total of 74 evaluations of the reagent strip for microhaematuria were performed with a total of 102,447 individuals. All evaluations were conducted in Africa. Median prevalence of S. haematobium was 42% (range 1% to 87%), and median female participation was 49% (Q1 49; Q3 53). Most of these evaluations were conducted with a lower-quality reference standard of only one slide/person (n = 63; 85%), and most evaluations were carried out in mixed populations of adults and children (n = 40; 54%). These evaluations were described in articles published between the years 1979 and 2014; a large proportion (n = 43; 58%) were published between 1979 and 1999. Over these four decades, no clear pattern was evident for effects of year of study on sensitivity and specificity of microhaematuria (see forest plot in Appendix 6). However, the forest plot shows greater heterogeneity for sensitivity compared with specificity.

A large range of test brands were used to estimate the sensitivity and specificity of microhaematuria, as shown in Appendix 7. Most evaluations (n = 25; 34%) were performed with the brand from the manufacturer Ames.

The forest plot (Figure 3) and the HSROC curve (Figure 4) for the reagent strip for microhaematuria reveal heterogeneity for estimates of both sensitivity and specificity.

Figure 3.

Forest plot of sensitivity and specificity of the urine reagent strip for microhaematuria.

Squares represent sensitivity and specificity of one study, the black line its confidence interval.

Figure 4.

Summary ROC plot of sensitivity versus specificity of the urine reagent strip for microhaematuria.

The size of the points is proportional to the study sample size. The solid line shows the summary ROC curve.

Meta-analytical sensitivity and specificity (95% confidence interval (CI)) of data at mixed thresholds were 75% (71% to 79%) and 87% (84% to 90%).

For proteinuria

A total of 46 evaluations of the reagent strip for proteinuria were performed with a total of 82,113 individuals. All evaluations were conducted in Africa. Median prevalence of S. haematobium was 51% (range 4% to 89%), and median female participation was 50% (Q1 46; Q3 53). Most of these evaluations were conducted with a lower-quality reference standard (n = 36; 78%), and most were carried out in mixed populations of adults and children (n = 28; 61%). These evaluations were described in articles published between the years 1979 and 2014; the largest proportion (n = 27; 59%) were published before the year 2000. Over these four decades, no clear pattern was evident for effects of year of study on sensitivity and specificity of proteinuria (see forest plot in Appendix 8).

A large range of test brands were used to estimate the sensitivity and specificity of proteinuria, as shown in Appendix 9. Most evaluations (n = 17; 37%) were performed using the brand from the manufacturer Ames.

The forest plot (Figure 5) and the HSROC plot (Figure 6) for the reagent strip for proteinuria reveal greater heterogeneity for estimates of sensitivity than specificity. Meta-analytical sensitivity and specificity (95% CI) of data at mixed thresholds were 61% (53% to 68%) and 82% (77% to 88%).

Figure 5.

Forest plot of sensitivity and specificity of the urine reagent strip for proteinuria.

Squares represent the sensitivity and specificity of one study, the black line its confidence interval.

Figure 6.

Summary ROC plot of sensitivity versus specificity of the urine reagent strip for proteinuria.

The size of the points is proportional to the study sample size. The solid line shows the summary ROC curve.

For leukocyturia

A total of five evaluations of the reagent strip for leukocyturia were performed with data from four publications and a total of 1532 individuals. Of these evaluations, two were carried out with a higher-quality reference standard (40%). Median prevalence of S. haematobium was 34% (range 4% to 77%), and median female participation was 100% (Q1 68; Q3 100). All evaluations except one were conducted in Africa in mixed populations of adults and children. These evaluations were described in articles published between the years 1992 and 2000; most (n = 3) were published before the year 2000. Two different test brands were evaluated. Most evaluations (n = 3; 60%) were done using the Nephur-test from Boehringer Mannheim.

The forest plot (Figure 7) and the HSROC plot (Figure 8) for the reagent strip for leukocyturia reveal greater heterogeneity for estimates of specificity than sensitivity. The ROC plot also reveals poor accuracy of the test, as most study points lie close to the diagonal line. Meta-analytical sensitivity and specificity (95% CI) of data at mixed thresholds were 58% (44% to 71%) and 61% (34% to 88%).

Figure 7.

Forest plot of sensitivity and specificity of the urine reagent strip for leukocyturia.

Squares represent the sensitivity and specificity of one study, the black line its confidence interval.

Figure 8.

Summary ROC plot of sensitivity versus specificity of the urine reagent strip for leukocyturia.

The size of the points is proportional to the study sample size. The solid line shows the summary ROC curve.

Urine CCA POC test

For S. haematobium

A total of four evaluations of the CCA POC test for S. haematobium were performed on data derived from four publications with a total population of 901 individuals. Median prevalence of S. haematobium was 40% (range 31% to 48%), and median female participation was 47% (Q1 40; Q3 51). Most of these evaluations were conducted with a lower-quality reference standard (n = 3; 75%). All evaluations were conducted in Africa. All evaluations included data from children only. These evaluations were described in articles published between the years 2008 and 2011. Four different test brands were evaluated.

Forest plots (Figure 9) and ROC plots (Figure 10) for this test reveal a high degree of heterogeneity for estimates of both sensitivity and specificity. The ROC plot also reveals poor accuracy of the test, as the study points lie close to the diagonal line. Meta-analytical sensitivity and specificity (95% CI) of data at mixed thresholds were 39% (6% to 73%) and 78% (55% to 100%).

Figure 9.

Forest plot of the sensitivity and specificity of the urine CCA POC test for S. haematobium.

Squares represent the sensitivity and specificity of one study, the black line its confidence interval.

Figure 10.

Summary ROC plot of sensitivity versus specificity of the urine CCA POC test for S. haematobium.

The size of the points is proportional to the study sample size. The solid line shows the summary ROC curve.

For S. mansoni

A total of 15 evaluations of the CCA POC test for S. mansoni were performed on data derived from 13 publications with a total population of 6091 individuals. Median prevalence of S. mansoni was 36% (range 8% to 68%), and median female participation was 49% (Q1 48; Q3 51). Most of these evaluations were conducted with a lower-quality reference standard (n = 10; 67%). All evaluations were conducted in Africa, and all except one included data from children only. These 15 evaluations were described in articles published between the years 2007 and 2014. Two different test brands were evaluated: Rapid Diagnostic Tests from Pretoria South Africa and Schistosomiasis One Step Test from EVL Holland, as shown in Appendix 10. Most evaluations (n = 9) were performed using the Rapid Diagnostic Tests from South Africa.

The forest plot for this test reveals greater heterogeneity for estimates of specificity versus estimates of sensitivity (Figure 11). Meta-analytical sensitivity and specificity (95% CI) of data at a threshold ≥ trace positive were 89% (86% to 92%) and 55% (46% to 65%) (Figure 12).

Figure 11.

Forest plot of sensitivity and specificity of the urine CCA POC test for S. mansoni.

Squares represent the sensitivity and specificity of one study, the black line its confidence interval. Colley 2013 was a study that included data for 5 studies (done in different countries). Some of the studies had been published earlier (Coulibaly 2011, Erko 2013, Shane 2011, Tchuente 2012). In this case, we used data from Colley 2013, which provided the most recent and updated data.

Figure 12.

Summary ROC plot of sensitivity versus specificity of the urine CCA POC test for S. mansoni.

The size of the points is proportional to the study sample size. The thick black point shows the average value for sensitivity and specificity. The inner ellipse around the black spot represents the 95% confidence regions around the summary estimates. The outer ellipse represents the prediction region.

For mixed infection

One study assessed the capability of the POC test to detect schistosomiasis in an area of mixed S. haematobium and S. mansoni infection. This evaluation was conducted in Africa (Southern Sudan) in children only and was published in 2011. The brand used was Rapid Diagnostic Tests from Pretoria, South Africa. The sensitivity of the test was 66%, and the specificity was 79%. No meta-analysis was performed for this test because of insufficient data.

CAA ELISA test

Serum

A total of five evaluations of the serum CAA test for S. mansoni were performed on data derived from four publications (total population 1583, years of publication 1995 to 1998). Median prevalence of S. mansoni was 93% (range 28% to 96%), and median female participation was 49% (Q1 49; Q3 51). All of these evaluations were conducted using relatively higher-quality reference standards (n = 5; 100%). All were in-house assays, and one study involved only children. Sensitivity of the serum CAA ELISA for S. mansoni ranged from 47% to 94%, and specificity ranged from 8% to 100% (Appendix 11). The ROC plot (Appendix 12) reveals a lot of scatter of the estimates of sensitivity and specificity provided by the included studies.

A total of three evaluations of the serum CAA test forS. haematobium were performed on data derived from three publications (total population 990, years of publication 1995 to 1999). Median prevalence of S. haematobium was 38% (range 18% to 57%). Only one study provided data on gender proportions (female participation was 54%). Two of the three evaluations were conducted using a higher-quality reference standard (67%). All were in-house assays, and all were carried out in mixed populations of adults and children. Sensitivity of the serum CAA test for S. haematobium ranged from 55% to 97%, and specificity ranged from 24% to 57% (Appendix 13; Appendix 14).

Urine

Only one evaluation of the urine CAA test for S. mansoni was performed on data derived from one publication (total population 204, year of publication 1995).. This was an in-house assay and was done on data obtained from a mixed population of adults and children. Sensitivity of this test was 10%, and specificity was 99%.

Only one evaluation of the urine CAA test for S. haematobium was performed on data derived from one publication (total population 370, year of publication 1999). This in-house assay was performed on data obtained from a mixed population of adults and children. Sensitivity of this test was 16%, and specificity was 94%.

CCA ELISA test

Serum

Two evaluations of the urine CCA test for S. mansoni were performed on data derived from two publications (total population 569, year of publication 1995). Both were in-house assays performed on data obtained from a mixed population of adults and children. Sensitivity of this test ranged from 36% to 85%, and specificity was 50% to 93% (Appendix 15).

Only one evaluation of the urine CCA test for S. haematobium was performed on data derived from one publication (total population 370, year of publication 1999). This in-house assay was performed on data obtained from a mixed population of adults and children. Sensitivity of this test was 3%, and specificity was 90%.

Urine

Two evaluations of the urine CCA test for S. mansoni were performed on data derived from two publications (total population 560, year of publication 1995). Both were in-house assays, and neither involved children only. Sensitivity of this test ranged from 62% to 97%, and specificity from 27% to 84% (Appendix 16).

Only one evaluation of the urine CCA test for S. haematobium was performed on data derived from one publication (total population 370, year of publication 1999). This in-house assay did not involve children only. Sensitivity of this test was 78%, and specificity was 70%.

Comparisons of accuracy between reagent strips for microhaematuria and proteinuria

Results of comparisons between microhaematuria and proteinuria are outlined in the Summary of findings 1. We first compared accuracy in all studies (indirect comparisons); we then limited the comparison to paired studies (direct comparisons). No statistically significant difference between the accuracy of microhaematuria and that of proteinuria was observed when the tests were compared in different populations using all studies (P = 0.25) (Figure 13). This can be demonstrated in the ROC curve showing the curves of tests as close together and crossing. The difference in accuracy also was not statistically significant when the tests were directly compared in the same individuals (P = 0.21) (Figure 14). A statistically significant difference in the threshold parameter was noted when the tests were compared in different populations using all studies (P < 0.0001), and when the tests were directly compared in the same individuals (P = 0.0009). This could imply that one test has a different operating threshold when compared with the other, and although overall accuracy is not statistically significantly different, sensitivity and specificity may be different under field circumstances.

Figure 13.

Summary ROC plot of sensitivity versus specificity showing the indirect comparison between microhaematuria and proteinuria (all studies). The solid lines show the summary ROC curves.

Figure 14.

Summary ROC plot of sensitivity and specificity showing the direct comparison between microhaematuria and proteinuria (paired studies). Study points of microhaematuria and proteinuria from the same study are joined by a dotted line. The solid lines show the summary ROC curves.

Investigations of heterogeneity

Co-variates in the models

The co-variates quality of reference standard, age, gender (% female participation), prevalence of infection, and intensity of infection were added to the HSROC model. We investigated whether these co-variates affect the parameters of the HSROC model, that is, accuracy, threshold, and shape.

For the reagent strip for microhaematuria, the co-variates age (P = 0.002) and gender (% female participation) (P = 0.02) had statistically significant effects only on the threshold parameter of the HSROC model.

For the reagent strip for proteinuria, the co-variates quality of reference standard (P = 0.01) and prevalence of infection (P value 0.007) had statistically significant effects on the accuracy parameter. Accuracy was higher with the higher-quality reference standard and in settings with higher prevalence. Other co-variates did not have a statistically significant effect on any of the other parameters of the HSROC model.

For CCA POC used to detect S. mansoni, no co-variate had a statistically significant effect on sensitivity or on specificity.

Subgroup analysis

Table 1, Table 2, and Table 3 outline the results of subgroup analyses on the tests microhaematuria, proteinuria, and CCA POC for S. mansoni. When these tests were evaluated against the higher-quality reference standard (ie when multiple samples were analyzed), sensitivity was lower for microhaematuria (71% vs 76%) and proteinuria (49% vs 68%) than with a lower-quality reference standard. Specificity of these tests was lower for microhaematuria (85% vs 87%) but higher for proteinuria (83% vs 78%). In contrast, sensitivity was similar (88%) and specificity was higher for the CCA POC test for S. mansoni (66% vs 55%) when measured against a higher-quality reference standard in comparison with a lower-quality reference standard.

Table 1. Sources of heterogeneity for urine reagent strip for microhaematuria
  1. aInsufficient data for synthesis.

Group Co-variate Subgroup n (N = 74) Sensitivity (95% CI) Specificity (95% CI)
Overall    0.75 (0.71-0.79) 0.87 (0.84-0.90)
Subgroup analysisReference standardHigher quality (> 1 sample)100.71 (0.62-0.80)0.85 (0.78-0.93)
  Lower quality (1 sample)640.76 (0.71-0.80)0.87 (0.84-0.90)
 Threshold≥ +1230.80 (0.73-0.85)0.85 (0.78-0.92)
 AgeChildren340.77 (0.71-0.82)0.91 (0.87-0.93)
 Intensity of infectionLight280.73 (0.66-0.79)0.88 (0.84-0.92)
      
Sensitivity analysisConcentrationFiltration only620.73 (0.69-0.78)0.86 (0.82-0.89)
 QUADAS Patient SelectionLow risk of bias160.77 (0.70-0.86)0.86 (0.79-0.92)
 QUADAS Reference StandardLow risk of biasa1--
 QUADAS Flow and TimingLow risk of bias430.77 (0.72-0.82)0.87 (0.83-0.90)
Table 2. Sources of heterogeneity for urine reagent strip for proteinuria
  1. aInsufficient data for synthesis.

Group Co-variate Subgroup n (N = 46) Sensitivity (95% CI) Specificity (95% CI)
Overall    0.61 (0.53-0.68) 0.82 (0.77-0.88)
Subgroup analysisReference standardHigher quality (> 1 sample)90.49 (0.28-0.70)0.83 (0.76-0.90)
  Lower quality (1 sample)370.68 (0.60-0.76)0.78 (0.69-0.87)
 Threshold≥ +1130.69 (0.56-0.81)0.72 (0.54-0.90)
 AgeChildren180.67 (0.56-0.76)0.81 (0.74-0.87)
 Intensity of infectionLight150.60 (0.43-0.77)0.83 (0.73-0.93)
      
Sensitivity analysisConcentrationFiltration only350.62 (0.52-0.71)0.80 (0.73-0.86)
 QUADAS Patient SelectionLow risk of bias110.64 (0.50-0.79)0.81 (0.70-0.93)
 QUADAS Reference StandardLow risk of biasa1- 
 QUADAS Flow and TimingLow risk of bias360.67 (0.59-0.76)0.82 (0.73-0.88)
Table 3. Sources of heterogeneity for CCA POC test for S. mansoni
  1. aThree studies had data points for evaluations with both a lower- and a higher-quality reference standard.

    bFive studies had data points at both thresholds: trace and +1.

    cInsufficient data for synthesis.

Group Co-variate Subgroup n (N = 15) Sensitivity (95% CI) Specificity (95% CI)
Overall    0.89 (0.86-0.92) 0.55 (0.46-0.65)
Subgroup analysisReference standarda    
  Higher quality (> 1 sample)50.88 (0.82-0.92)0.66 (0.46-0.82)
  Lower quality (1 sample)130.88 (0.85-0.91)0.55 (0.45-0.66)
 Positivity thresholdb> +150.72 (0.60-0.82)0.85 (0.71-0.93)
 AgeChildren140.90 (0.86-0.92)0.56 (0.46-0.66)
 Intensity of infectionLightc3--
      
Sensitivity analysisQUADAS Patient SelectionLow risk of biasc3--
 QUADAS Reference StandardLow risk of biasc0--
 QUADAS Flow and TimingLow risk of bias110.87 (0.84-0.90)0.57 (0.49-0.65)

Microhaematuria and proteinuria had higher sensitivity (77% vs 73% and 67% vs 56%) in children than in mixed populations of adults and children. Specificity was higher for microhaematuria (91% vs 82%) but was comparable for proteinuria (81% vs 82%) in children compared with mixed populations of adults and children. All except one study of CCA POC for S. mansoni were carried out with children. At a positivity threshold ≥ 1, sensitivity of CCA POC for S. mansoni was lower (72% vs 89%) and specificity higher (85% vs 55%) than at a positivity threshold of trace positive. In the light-intensity subgroup, sensitivity was slightly lower for microhaematuria (73% vs 75%) and specificity was slightly higher (88% vs 87%) compared with results of the overall analysis. In contrast, sensitivity (60% vs 61%) and specificity (83% vs 82%) for proteinuria were comparable. Data were insufficient to permit estimation of the sensitivity and specificity of CCA POC for S. mansoni in light-intensity settings.

The forest plot (Figure 15) and the ROC plot (Figure 16) demonstrating sensitivity and specificity for microhaematuria after praziquantel treatment show a lot of variation in the estimates (predominantly for sensitivity) of the individual studies.

Figure 15.

Forest plot of sensitivity and specificity of the urine reagent strip for microhaematuria for studies done after treatment with praziquantel.

Squares represent the sensitivity and specificity of one study, the black line its confidence interval.

Figure 16.

Summary ROC plot of sensitivity and specificity of the urine reagent strip for microhaematuria for studies done after treatment with praziquantel.

The size of the points is proportional to the study sample size

Sensitivity analysis

For microhaematuria, when the analysis was limited to studies that used filtration only as the concentration method for urine microscopy, sensitivity (73% (69% to 78%) vs 76% (72% to 80%)) was lower and specificity was comparable (86% (82% to 89%) vs 86% (82% to 89%)) with those produced by the overall analysis. For proteinuria, when the analysis was limited to studies that used filtration only as the concentration method for urine microscopy, sensitivity was comparable (62% (52% to 71%) vs 61% (53% to 69%) and specificity was lower (80% (73% to 86%) than those produced by the overall analysis (83% (77% to 88%)) (Table 1; Table 2; Table 3).

Sensitivities and specificities of microhaematuria were comparable when analysis was limited to studies with low risk of bias for the participant flow domain. Sensitivity of proteinuria was higher when limited to studies with low risk of bias for the participant selection domain (64%) and the participant flow domain (67%). Specificity on the other hand was comparable for these two domains. Sensitivity and specificity of CCA POC for S. mansoni were comparable when limited to studies with low risk of bias for the participant flow domain (Table 1; Table 2; Table 3). Data were insufficient to allow estimation of sensitivity and specificity for studies with low risk of bias in the other domains—reference standard and participant selection—for the CCA POC test for S. mansoni.

As part of post hoc analyses, we noted that three evaluations showed substantial heterogeneity for the tests microhaematuria (Aryeetey 2000; sensitivity 55%, specificity 36%), proteinuria (Aryeetey 2000; sensitivity 38%, specificity 11%), and CCA POC for S.mansoni (Standley 2010; sensitivity 99%, specificity 19%). We excluded these evaluations in sensitivity analyses for the respective tests and found the following results. Results for microhaematuria (sensitivity 75%, specificity 87%) and proteinuria (sensitivity 61%, specificity 82%) were similar to those of the overall analysis. For CCA POC for S. mansoni, sensitivity was comparable (88% vs 89%) and specificity was slightly higher (58% vs 55%) compared with those of the overall analysis.

Summary of findings

Summary of findings 1. Summary of findings table for tests to detect S. haematobium
  1. a Studies were insufficient to provide summary estimates for the CAA tests.

    When the tests were evaluated against the higher-quality reference standard (ie when multiple samples were analyzed), sensitivity was lower for microhaematuria (71% vs 76%) and proteinuria (49% vs 61%) in comparison with a lower-quality reference standard. The specificity of these tests was comparable.

    In light-intensity settings, sensitivity was slightly lower for microhaematuria (73% vs 76%) and specificity was slightly higher (88% vs 86%) compared with results of the overall analysis. In contrast, sensitivity (60% vs 61%) and specificity (83% vs 83%) for proteinuria were comparable.

    Microhaematuria and proteinuria had higher sensitivity (77% vs 73% and 67% vs 56%) in children than in mixed populations of adults and children. Specificity was higher for microhaematuria (91% vs 82%) but specificity was comparable for proteinuria (81% vs 82%) in children compared with mixed populations of adults and children.

    For the effects of risk of bias, sensitivities and specificities of microhaematuria were comparable when limited to studies with low risk of bias for the participant flow domain. Sensitivity of proteinuria was higher when limited to studies with low risk of bias for the participant selection domain (64%) and the participant flow domain (67%). Specificity on the other hand was comparable for these 2 domains.

    Abbreviations: TPs (true-positives), FPs (false-positives), FNs (false-negatives).

What is the diagnostic accuracy of circulating antigen tests and biochemical urine reagent strips in detecting S. haematobium infection?
Patients/PopulationPeople residing in areas endemic for S. haematobium infection (74 out of 90 studies)
Prior treatment with praziquantel before baseline studyYes (6 studies), No (11 studies), Unclear (57 studies)
Prior testingNone
SettingsField settings (villages and schools) and 1 outpatient clinic in Africa
Index tests

Circulating cathodic antigen test (CCA)

Circulating anodic antigen test (CAA)a

Urine reagent strips to detect microhaematuria, proteinuria, and leukocyturia

Reference standardUrine microscopy
ImportanceThese tests are being used as replacements for conventional microscopy in disease control programmes for schistosomiasis, as they are rapid, are easier to use and interpret, and may have comparable sensitivity to microscopy. As control programmes gain impetus and infection intensities decrease, higher sensitivities become a prerequisite for future diagnostics
StudiesCross-sectional (n = 62), cohort (n = 6), and case-control studies with controls from same population (n = 3)
Quality concernsPoor reporting of participant characteristics, index test and reference standard methods, and intensity of infection were common concerns. The risk of bias assessment for most included studies was largely unclear for the QUADAS domains Patient Selection, Index Tests, and Reference Tests
Test types Number of evaluations Summary estimates
(95% CI)
In 1000 people tested
    Infected cases
S. haematobium

Missed cases

(FNs)

False-

positives

(FPs)

All positives  

(TPs + FPs)

Biochemical urine reagent strips      
For microhaematuria74

Sens = 75% (71% to 79%)

Spec = 87% (84% to 90%)

41010277384
For proteinuria46

Sens = 61% (53% to 68%)

Spec = 82% (77% to 88%)

410160106356
For leukocyturia5

Sens = 58% (44% to 71%)

Spec = 61% (34% to 88%)

410172230468
Circulating cathodic antigen test (CCA)      
Urine POC test4

Sens = 39% (6% to 73%)

Spec = 78% (55% to 100%)

41025094254
Comparisons      
Comparison Comparison type Number of evaluations and differences in overall accuracy Explanation   
Microhaematuria vs proteinuriaAll studies74 microhaematuria vs proteinuria, difference in accuracy (P = 0.25)We found no evidence of a statistically significant difference in overall accuracy when microhaematuria and proteinuria are carried out and compared in different individualsProteinuria would be expected to miss 14% more cases than microhaematuriaProteinuria would be expected to falsely identify 5% more cases than microhaematuria 
 

Paired studies

(tests done in the same individuals)

44 microhaematuria vs proteinuria, differences in accuracy (P = 0.21)We found no evidence of a statistically significant difference in overall accuracy when microhaematuria and proteinuria are carried out and compared in the same individuals 
Summary of findings 2. Summary of findings table for tests to detect S. mansoni
  1. a Studies were insufficient to provide summary estimates for CAA tests.

    When measured against a higher-quality reference standard, sensitivity of CCA POC for S. mansoni was comparable (88% vs 88%) but specificity was higher (66% vs 55%) than when measured against a lower-quality reference standard.

    At a positivity threshold ≥ 1, sensitivity of CCA POC for S. mansoni was lower (72% vs 87%) and specificity higher (85% vs 61%) than at a positivity threshold of trace-positive.

    Data were insufficient to estimate the sensitivity of CCA POC for S. mansoni in light-intensity settings.

    For the effects of risk of bias, sensitivity and specificity of CCA POC for S. mansoni were comparable when limited to studies with low risk of bias for the participant flow domain.

    Abbreviations: TPs (true-positives), FPs (false-positives), FNs (false-negatives).

What is the diagnostic accuracy of circulating antigen tests for S. mansoni infection?
Patients/PopulationPeople residing in areas endemic for S. mansoni infection (16 out of 90 studies)
Prior treatment with praziquantel before baseline studyYes (1 study), No (5 studies), Unclear (10 studies)
Prior testingNone
SettingsField settings (villages, schools, and military camp) in Africa and South America
Index tests

Circulating cathodic antigen test (CCA)

Circulating anodic antigen test (CAA)a

Reference standardStool microscopy
ImportanceThese tests are being used as replacements for conventional microscopy in disease control programmes for schistosomiasis, as they are rapid, are easier to use and interpret, and may have comparable sensitivity to microscopy. As control programmes gain impetus and infection intensities decrease, higher sensitivities become a prerequisite for future diagnostics
StudiesCross-sectional studies
Quality concernsPoor reporting of participant characteristics, index test and reference standard methods, and intensity of infection were common concerns. The risk of bias assessment for most included studies was largely unclear for the QUADAS domains Patient Selection, Index Tests, and Reference Tests
Test types Number of evaluations Summary
estimates
(95% CI)
In 1000 people tested
    Infected cases
S. mansoni

Missed cases

(FNs)

False-positives

(FPs)

All
positives (TPs + FPs)
Circulating cathodic antigen test (CCA)      
Urine POC test15Sens = 89% (86% to 92%); Spec = 55% (46% to 65%)36040288608

Discussion

Summary of main results

This review focused on analyzing the accuracy of urine reagent strips for the diagnosis of S. haematobium and of circulating antigen tests for the detection of S. haematobium and S. mansoni infections. Microscopy was used as the reference standard, and 90 studies were found to fit our inclusion criteria; data from these studies were used in this review. The main results, including average sensitivities and specificities for tests included in the meta-analyses, are reported in Summary of findings 1 and Summary of findings 2.

Most of the studies included in our overall meta-analyses used a ‘lower-quality reference test’: microhaematuria 81%, proteinuria 73%, leukocyturia 60%, circulating cathodic antigen point-of-care (CCA POC) for S. haematobium 75%, and CCA POC for S. mansoni 81%. This implies that infections missed by single-sample microscopy may have increased the number of false-positives identified by the index tests, consequently leading to lower estimates of specificity.

Our overall analyses suggest that among the tests used to detect S. haematobium, the urine reagent strip for microhaematuria detects the largest proportion of schistosome infections identified by microscopy (sensitivity 75%); it also detects the largest proportion of non-infections identified by microscopy (specificity 87%). Proteinuria follows suit, with sensitivity of 61% and specificity of 82%.

The superior performance of microhaematuria over proteinuria was not statistically significant when the comparison was performed both indirectly (using all studies) and directly (using paired studies) within the HSROC model. When measured against a higher-quality reference standard (multiple measurements), microhaematuria had both lower sensitivity (71% vs 75%) and lower specificity (85% vs 87%) than were seen with a lower-quality reference standard. Proteinuria on the other hand, when measured against a higher-quality reference standard, had lower sensitivity (49% vs 61%) and higher specificity (82% vs 78%) versus a lower-quality reference standard. Increasing the sensitivity of microscopy by taking multiple measurements may reduce the number of true cases wrongly classified as non-infected by microscopy. An index test compared against a more sensitive reference test (higher quality) may have higher specificity because the number of false-positives will be low. The lower specificity for microhaematuria may be due in part to poor reporting of how the reference standard was conducted in some studies.

Our results suggest that the urine reagent strip when used to detect leukocyturia is limited by low sensitivity (58%) and specificity (61%) and is not useful in practice. The low sensitivity for leukocyturia could be explained by the variations in morbidity caused by S. haematobium. Not all infected people have leukocyturia; therefore the proportion of false-negatives is higher. The CCA POC test has very low sensitivity (39%) to detect S. haematobium and specificity of 78% and may not be suitable for mapping or estimation of infection, because it misses very many infections identified by microscopy.

The CCA POC test for S. mansoni detected a large proportion of infections identified by microscopy (sensitivity 89%). However, it also detected a lower proportion of the non-infected cases identified by microscopy (specificity 55%). The low specificity can be explained by the fact that most studies in the overall analyses were measured against a lower-quality reference standard. When compared with a higher-quality reference standard, the CCA POC test had comparable sensitivity (88%) but higher specificity (66%). Arguably, if the reference standard had been even better, this specificity might have increased further.

As studies were insufficient, we were unable to generate summary estimates for the circulating antigen enzyme-linked immunosorbent assay (ELISA) tests (CCA and circulating anodic antigen (CAA)). Estimates of sensitivity and specificity from the included studies evaluating these tests ranged widely.

Results of our assessment of risk of bias of the included studies were largely unclear because of poor reporting of items in these studies.

Application of the meta-analysis to a hypothetical cohort

Summary of findings 1 and Summary of findings 2 apply the results of the meta-analyses to a hypothetical cohort of 1000 individuals suspected of having active S. haematobium and/or active S. mansoni infection in a field setting. We illustrate the impact of using microhaematuria, proteinuria, leukocyturia, and CCA POC for S. haematobium in a setting with a prevalence of S. haematobium infection of 41%, and the impact of using CCA POC for S. mansoni in a setting with a prevalence of S. mansoni infection of 36%. These are the estimates of median prevalence of infection obtained from all studies included in this review.

Delivery of population-based control programmes such as treatment with praziquantel requires knowledge of prevalence estimates of schistosomal infections (Colley 2014). This helps the clinician in determining whether mass drug treatment should be administered in settings of very high prevalence, or targeted treatment in settings of low prevalence. We have included descriptions of the performance of these tests in estimating the prevalence (index test positives (TP + FP)) of S. haematobium and S. mansoni infections.

S. haematobium infection

If the point estimates of the tests for S. haematobium are applied to a hypothetical cohort of 1000 individuals suspected of having active S. haematobium infection, among whom 410 actually have the infection, the strip for microhaematuria would be expected to miss (102) and falsely identify (77) the least number of cases. This test would identify 384 positive cases in total.

For the other tests (in increasing order of missed cases): The strip for proteinuria would be expected to miss 160 cases and to falsely identify 106 cases; proteinuria would be expected to miss 14% more cases than microhaematuria and to falsely identify 5% more cases than microhaematuria; leukocyturia would be expected to miss 172 cases and to falsely identify 230 cases; and the CCA POC test would be expected to miss 250 cases and to falsely identify 130 cases. In total, the strips for proteinuria, leukocyturia, and the CCA POC test would identify 356, 468, and 254 positive cases, respectively.

Overall, when infection is mapped, the prevalence of microhaematuria would seem to be 38%—close to the true prevalence of 41%. The prevalence of proteinuria would seem to be 36%, that of leukocyturia 47%, and that of CCA POC 25%. In cases of mass treatment, the ultimate consequences of these numbers would depend on the minimal prevalence needed to start mass treatment.

S. mansoni infection

If the point estimates for the CCA POC test are applied to the same hypothetical cohort of 1000 individuals suspected of having active S. mansoni infection, among whom 360 actually have the infection, the CCA POC test would be expected to miss 40 cases and to falsely identify 288 cases. In total, the test would identify 608 positive cases (for an observed prevalence of 61%).

Comparison with other reports

The absence of a suitable gold standard for active schistosomiasis is reflected in the existing literature, where different reference standards are used with subsequent variation in accuracy (especially with specificity) of the index test (Koukounari 2009; Coulibaly 2011; Tchuente 2012; Colley 2013; Erko 2013; King 2013;Lodh 2013; Sousa-Figueiredo 2013).

A meta-analysis was recently published that assessed the accuracy of urine reagent strips for microhaematuria against conventional microscopy as a reference standard (King 2013). Unlike King’s review, our review also estimated the accuracy of other urine reagent strips for proteinuria and leukocyturia. To guide decision making, it is important to show which of these tests fares better. Our analyses suggest that microhaematuria has higher sensitivity than proteinuria and leukocyturia.

Compared with results from King’s meta-analysis (King 2013), our estimate of sensitivity for microhaematuria was lower (75% vs 81%) but specificity was comparable (87% vs 89%). This difference may be attributed to the method of meta-analysis used. King used the HSROC regression following a Bayesian Monte Carlo Markov chain approach (Dendukuri 2012), and we used the HSROC model recommended in the Cochrane Handbook for Systematic Reviews of Interventions (Macaskill 2010). With regard to sources of heterogeneity, some of our results are also comparable with those of King 2013. For instance, King found through multi-variable regression modelling that the urine heme dipstick performed better in children than in mixed populations of adults and children (Relative diagnostic odds ratio = 3.16). In our review, we found that sensitivity and specificity were higher in studies on children compared with studies on mixed populations of adults and children. We strongly confirm that this test is therefore highly suitable for mass mapping of school-aged children in endemic areas. Again our analyses show that sensitivity of the urine heme dipstick was slightly lower in settings of low intensity (73%) compared with that of the overall estimate (75%). This finding was similar to the findings of King, which showed that sensitivity of the urine heme dipstick was lower in settings of lower infection intensity (65%) in the subgroup analysis than in the overall analysis (81%). However it should be noted that our definition of light intensity differed from that used by King. We selected the more commonly used World Health Organization (WHO) recommended cutoff of < 50 eggs per 10 mL, whereas King defined low intensity as ≤ 100 eggs/10 mL. This could explain in part why our sensitivity estimates were higher than those of King in settings of light intensity.

A key difference between our review and that of King 2013 concerned the effects of treatment on the estimate of sensitivity of the heme dipstick. In a subgroup of eight studies with mixed post-treatment evaluations of one year (n = 6), six months (n = 1), and one month (n = 1), King’s review produced a lower summary estimate of sensitivity (72%) in the subgroup of treated populations as compared with the overall analysis (81%). King considered treatment evaluations with praziquantel and metrifonate, whereas we focused on studies that evaluated the effects of praziquantel treatment, as this is the current drug of choice. Because studies reported varied time intervals between treatment and retesting, we opted not to pool the estimates of studies, as this would likely produce biased overestimates of sensitivity and specificity. Studies with long time intervals were likely to include greater numbers of participants reinfected compared with studies carried out at shorter time intervals, and their results may be confounded by repeated treatments provided by national programmes.

A recently published multi-centre evaluation of CCA POC tests done in five African countries (Colley 2013) recommended that the CCA POC test for S. mansoni (evaluated with a positivity threshold ≥ trace positive) was a sufficiently sensitive and specific tool for mapping intestinal schistosomiasis in moderate- to high-prevalence areas, and therefore it was a viable alternative to microscopy (Colley 2013). After acknowledging the absence of a gold standard, this multi-centre study used latent class analysis (modelling results from CCA POC, Kato-Katz, and PCR) to generate an overall estimate of 86% sensitivity and 72% specificity of the CCA POC based on data from 4405 school-age children. Using microscopy only (KK) as the reference standard, our review, which incorporated all include study results along with findings of additional studies, produced a comparable summary estimate of 89% sensitivity but a lower summary estimate of 55% specificity at a threshold of trace positive. Differences in specificity could be explained by the reference standard and indicate that some of the false-positives identified by CCA POC are indeed likely to be true infections that are not detected by standard microscopy.

Few studies have fully evaluated the accuracy of the circulating antigen ELISA tests (CCA and CAA). The serum CAA ELISA test is currently being converted to a point-of-care format for S. mansoni (Corstjens 2008) andS. haematobium (van Dam 2013) with promising results of analytical sensitivity and specificity. In our review, sensitivity of the included studies evaluating the serum CAA ELISA test for S. mansoni ranged widely from 47% to 94%, and specificity ranged widely from 8% to 100%. Sensitivity of the included studies evaluating the serum CAA ELISA test for S. haematobium ranged from 55% to 97%, and specificity was low, ranging from 24% to 57%. However, the studies included in our review were carried out before the year 2000 with in-house tests. The tests currently being developed are most likely improved versions; therefore additional studies analyzing the clinical sensitivity and specificity of the serum ELISA tests are needed for conclusive determination of whether they are suitable for the diagnosis of active schistosomiasis.

Strengths and weaknesses of the review

Strengths

We have evaluated the accuracy of POC tests currently in use and tests that have recently been transformed into POC tests for detection of active schistosomiasis in endemic areas. This makes our review relevant to current practice. To avoid missing studies, we did not use a search filter, and we did not limit our search by publication year or language; also to limit bias, data extraction was performed by two people independently.

Weaknesses

Choice of the reference standard

In light of the absence of a suitable gold standard for active schistosomiasis and the presence of other proposed alternative reference standards, evaluation of index tests with only microscopy as the reference standard may be considered a shortcoming of our review. However because microscopy remains the most commonly used test and therefore reference test, we wanted our review to be applicable to current practice. Our review provides better insight into the proportion of cases detected and the proportion of cases misclassified by urine reagent strips and CCA POC tests when microscopy is used as the reference standard. A more reliable way of evaluating whether an index test can replace microscopy would be to compare the accuracy of microscopy, urine reagent strips, and circulating antigen tests against other proposed reference standards in the same set of participants (direct comparison studies). A few studies have compared the accuracy of one or more KK smears and CCA POC against a reference standard comprising six or more KK smears (Coulibaly 2011; Tchuente 2012; Erko 2013) or against PCR as the reference test (Lodh 2013) (see comparisons in Appendix 17). All of these studies have shown the CCA POC test to be more sensitive but less specific than single or double KK. More direct comparative studies and reviews are needed to reliably confirm this finding and to identify sources of variation in results.

Quality of included studies

Poor and inconsistent reporting of participant characteristics such as clinical status of participants, intensity of infection, administration of praziquantel treatment, and conduct of the study limited our investigations of sources of heterogeneity and risk of bias assessment.

In our review, the reporting of intensity of infection was unclear (reported in different ways (arithmetic mean or range of infection or geometric mean or range of infection or proportions with light/moderate/heavy infections) or not reported at all) for a large proportion of the included studies (microhaematuria 44%, proteinuria 42%, and CCA POC 45%). It was therefore difficult to effectively investigate its influence on the accuracy of the evaluated tests. It was also a challenge to fully investigate the effects of praziquantel treatment on the accuracy of the evaluated tests because 82% of the studies did not report the treatment status of participants before the start of the study. The effects of intensity of infection and the effects of praziquantel treatment on the accuracy of diagnostic tests for schistosomiasis are currently an important concern for national control programmes, particularly as praziquantel treatments progress, with subsequent decreases in infection intensities. Indeed, in areas where the force of infection and associated morbidity have been greatly reduced, some programmes are beginning to focus on elimination. It is therefore of vital importance that highly sensitive tests are used for monitoring, and that highly sensitive and specific tests are used in efficacy studies before and after treatment.

Applicability of findings to the review question

Our concern about the applicability of the included studies to our review question was low, as assessed by QUADAS-2. As all but one study were carried out in Africa, and all but one study were conducted in field settings, our results are highly applicable for use in endemic communities for which disease control programmes are often targeted. However, one area that may limit the applicability of our findings to the review question is our investigation into sources of heterogeneity such as effects of praziquantel treatment and risk of bias assessment on the accuracy estimates of evaluated tests. As discussed earlier, poor and inconsistent reporting limited this investigation. In light of the ongoing disease control programmes, fully showing any variation in test accuracy associated with effects of praziquantel treatment would be useful for policy makers. Knowing the risk of bias of included studies would also help in objective assessments of the strength of the evidence. Study authors therefore are encouraged to use the Standards for Reporting of Diagnostic Accuracy Studies (STARD) guidelines (Bossuyt 2003) in reporting the design and conduct of their studies.

Authors' conclusions

Implications for practice

Among the tests evaluated for S. haematobium infection, microhaematuria has detected the largest proportion of infections and non-infections identified by microscopy. This test could continue to serve as a replacement test for microscopy for initial mapping or estimation of S. haematobium infection, particularly in endemic areas with moderate to high prevalence of infection.

The CCA POC test for S. mansoni detects a very large proportion of infections identified by microscopy but misclassifies many microscopy-negatives as -positives in endemic areas with moderate to high prevalence of infection. This may occur because the test is potentially more sensitive than microscopy. Nevertheless, healthcare workers should interpret the results with care when using this test for initial mapping or estimation of S. mansoni infection, as some of the positives may still be false-positives, in particular when trace-positive is used as the threshold.

Besides assessment of the accuracy of a test, the choice of a suitable diagnostic test should be made in light of cost and logistical considerations. Costs for microscopy (USD per examination, 0.3 for a single thick KK smear) (Cavalcanti 2013) and for reagent strips for microhaematuria (USD 0.32) (Legesse 2008) are comparable, but the strips are easier to use and interpret and therefore are not logistically challenging in field settings. The CCA POC tests are more costly (USD 2.6 per examination) (Cavalcanti 2013) but are rapid and easy to use and interpret, are highly portable, and require fewer technical personnel than microscopy; they are also suitable for field screening and diagnosis.

Implications for research

As control programmes progress with expected subsequent decreases in prevalence and intensity of infection, we highlight the importance of additional primary research conducted to identify a suitable clinical reference standard for active schistosomiasis.

Additional studies comparing the accuracy of microscopy, circulating antigen tests, and urine reagent strips versus other proposed reference standards are needed if a suitable replacement for microscopy in practice is to be reliably recommended.

Further studies to identify other sensitive tests to detect active S. haematobium and S. mansoni infections and further evaluations of the CAA test as a future POC test for serum or urine are also needed.

For suitable tests to be reliably recommended for monitoring effects of praziquantel treatment in disease control programmes, additional follow-up studies are required to evaluate the effects of praziquantel treatment on intensity of infection and accuracy of urine reagent strips and circulating antigen tests.

Further research on cost-effectiveness of diagnostic tests in areas of different endemicity is also needed, as cost is a key deciding factor in resource-limited settings.

Finally, authors of primary test accuracy studies should be encouraged to use the STARD guidelines when reporting the design and conduct of their studies. This will enable systematic reviewers to better synthesize the data and to draw conclusions on risk of bias in studies of test accuracy.

Acknowledgements

We thank René Spijker, MSc (Dutch Cochrane Centre, University of Amsterdam), for assisting in the development of the search strategy of this project.

Data

Presented below are all the data for all of the tests entered into the review.

Test 1.

Microhaematuria.

Test 2.

Microhaematuria after treatment.

Test 3.

CCA POC mansoni trace threshold.

Test 4.

Proteinuria.

Test 5.

Leukocyturia.

Test 6.

CCA POC mansoni +1 threshold.

Test 7.

CCA POC mansoni with good reference standard.

Test 8.

CCA POC haematobium.

Test 10.

CCA POC mixed species.

Test 11.

Serum CAA ELISA mansoni.

Test 12.

Serum CAA ELISA haematobium.

Test 13.

Urine CAA ELISA mansoni.

Test 14.

Urine CAA ELISA haematobium.

Test 15.

Serum CCA ELISA mansoni.

Test 16.

Serum CCA ELISA haematobium.

Test 17.

Urine CCA ELISA mansoni.

Test 19.

Urine CCA ELISA haematobium.

Appendices

Appendix 1. Geographical distribution, infection, and morbidity of S. haematobium and S. mansoni

Species Geographical distributiona Number infected (millions) Morbidity (millions)
S. haematobiumAfrica, Middle EastIn SSA (112)b

Urogenital schistosomiasisa

Signs and symptoms:

Haematuria (blood in urine), proteinuria (proteins in urine), leukocyturia (white blood cells in urine), urinary obstruction, hydronephrosis,

chronic renal failure, bladder cancer, genital lesions, vaginal bleeding, pain during sexual intercourse, nodules in the vulva, infertility, pathology in prostrate and seminal vesicles

 

In SSAb:

Haematuria (71)

Dysuria (32)

Minor bladder pathology (76)

Major bladder pathology (24)

Major hydronephrosis (9.6)

 

S. mansoniAfrica, Middle East, the Caribbean, South AmericaIn SSA (54)b

Intestinal schistosomiasisa

Signs and symptoms:

Abdominal pain, blood in stool, portal hypertension, ascites

 

In SSAb:

Diarrhoea (0.78)

Blood in stool (4.4)

Hepatomegaly (8.5)

Abbreviations: SSA = sub-Saharan Africa.

a WHO 2010.

b van der Werf 2003.

c WHO/TDR 2006.

Appendix 2. Diagnostic and treatment strategies

Figure 17

Figure 17.

Diagnostic and treatment strategies. Abbreviations: +ve = positive; -ve = negative; CAA = circulating anodic antigen; CCA = circulating cathodic antigen; M+ = microscopy positive; M- = microscopy negative; U+ = urine reagent strips positive; U- = urine reagent strips negative; Rx = treatment; No Rx = no treatment.

Abbreviations: +ve = positive; -ve = negative; CAA = circulating anodic antigen; CCA = circulating cathodic antigen; M+ = microscopy positive; M- = microscopy negative; U+ = urine reagent strips positive; U- = urine reagent strips negative; Rx = treatment; No Rx = no treatment.

Appendix 3. MEDLINE search strategy via Ovid SP platform

Limits: limited to human studies

Line # Term
1(anodic adj3 antigen*).ti,ab.
2(cathodic adj3 antigen*).ti,ab.
3exp Enzyme-Linked Immunosorbent Assay/
4exp Immunoenzyme Techniques/
5hematuria/ or exp proteinuria/
6leukocyturia.ti,ab.
7leucocyturia.ti,ab.
8h?ematuria.ti,ab.
9proteinuria.ti,ab.
10albuminuria.ti,ab.
11CCA.ti,ab.
12CAA.ti,ab.
13urinalysis.ti,ab.
14elisa.ti,ab.
15eia.ti,ab.
16exp Reagent Strips/ or dipstick.mp.
17(reagent adj3 strip*).ti,ab.
18(test adj3 strip*).ti,ab.
19haemastix.ti,ab.
  
20"schistosoma mansoni".ti,ab. or "schistosoma haematobium".ti,ab.
21exp Glycoproteins/
22exp Antigens, Helminth/
23exp Helminth Proteins/
24exp Schistosoma haematobium/
25exp Antibodies, Monoclonal/
26exp Schistosoma mansoni/
27or/1-26
28schistosomiasis/ or schistosomiasis haematobia/ or schistosomiasis mansoni/
29schistosomiasis.ti,ab.
30bilharzia*.ti,ab.
31or/28-30
32animals/ not humans/
33exp Letter/
34exp Case Reports/
35or/32-34
3627 and 31
3736 not 35

With use of the Ovid platform, this MEDLINE search was translated automatically to suit the EMBASE and BIOSIS databases to identify additional records. In the search interface, under 'resource selected,' with the link 'change,' one can select the desired database.

Appendix 4. QUADAS tool

We used the QUADAS-2 tool. The signalling questions under the four recommended domains are outlined in questions 7 to 10 on the data extraction form.

The scoring guidance for these questions was as follows.

Flow diagram

For questions 7 and 8, drawing a flow diagram of the study may be helpful (this is not mandatory). Flow charts of patients display how many patients were eligible for the study, how many were actually recruited, how many received the index test, how many received the reference standard, etc. In addition, the numbers of true- and false-positives and true- and false-negatives are displayed. If necessary, please draw a flow diagram for the primary study in the space provided on page 8 of the extraction form.

7. Patient selection (patient selection domain)

These questions will help assess risks of bias in the study design.

a. Please cite here the selection criteria

Please list in the space provided the selection criteria used to recruit patients into the study. You can also cite the page number in the article on which the selection criterion was written.

If no criteria were reported, indicate “Not reported/NR” in the space provided. If the criterion was unclear, please indicate “Unclear,” and explain your answer.

b. Stage of disease

Participants recruited into the study may be without symptoms or with symptoms. Please indicate the disease stage for participants. If the study clearly reports that both asymptomatic and symptomatic cases were evaluated, please tick the appropriate box provided (both A and S). If the study does not clearly report the clinical status of the participants, please tick the box ‘Unclear.’ A box N/A has been provided. If S. m for example was not evaluated in the study, please tick this box. The same applies to S. h. A comment box is provided for any comments that you may have.

c. What was the study design?

Please indicate the design of the study by ticking one of the choices provided.

We will not include case-control studies that incorporate healthy controls, alternative diagnosis controls, or controls from non-endemic areas. Research has shown that this type of study overestimates accuracy measures. Healthy controls are those who have been confirmed as disease–free. Alternative diagnosis controls are controls who have symptoms similar to those of the disease under study.

If the design is not stated or is unclear, please tick the appropriate boxes. If necessary, insert comment into the box provided.

d. Was a consecutive or random sample of patients enrolled?
  • Yes: when the authors report random patient sampling or consecutive enrolment.

  • No: when patients were selected, for example, based on previous (reference or index) test results.

  • Unclear: there seems to be no problem, but the study authors do not explicitly state that patients were enrolled consecutively.

e. Did the study avoid inappropriate exclusions?
  • Yes: No patients were excluded after inclusion.

  • No: For example, when patients with mild disease were excluded, because they are more difficult to detect.

  • Unclear: not reported or insufficient information given to permit a decision.

f. Could the selection of patients have introduced bias?
  • High: if one or more of the questions above (7 d-e) was answered with ‘no.’

  • Low: if all questions were answered with ‘yes’ (7 d-e), or if at most one question was answered with ‘unclear.’

  • Unclear: for any other combination of answers (eg if two or more questions were unclear and the other(s) was/were answered with ‘yes.’

g. Is there a concern that the included patients do not match the review question?
  • High concern: when participants are those who do not reside in endemic areas, such as tourists, healthy controls, or controls with alternative diagnoses.

  • Low concern: when participants in the study are those who reside in schistosomiasis endemic areas. This group will include those at risk of infection, those who are infected but asymptomatic, or those who are infected with symptoms.

  • Unclear: scored when information is insufficient to permit a decision.

8. Patient flow and timing (Flow and Timing domain)

a. Was there an appropriate interval between index test(s) and reference standard?
  • Yes: if urine/stool samples are examined by both the reference standard and the index standard at the same time, or if the time period is less than one week.

  • No: if time period between index and reference standards is longer than one week.

  • Unclear: if no or insufficient information on time period is provided.

b. Did all patients receive a reference standard? (focus on those included in 2 × 2 table)
  • Yes: scored when the whole sample or a random selection of the sample or a selection of the sample with consecutive series receive verification using the reference standard.

  • No: scored when a part of the sample that is non-randomly or non-consecutively selected receives verification with the reference standard.

  • Unclear: scored when no or insufficient information is provided to ascertain whether the whole sample or a random selection of the sample received verification with a reference standard.

c. Did patients receive the same reference standard?
  • Yes: scored when study participants are tested with the same reference standard, urine/stool microscopy, regardless of index test result.

  • No: scored when microscopy is used with different urine concentration techniques depending on index test results for S. haematobium.

  • Unclear: scored when no or insufficient information is provided on the different reference standards used.

d. Were all patients included in the analysis?
  • Yes: scored when the patients who were included in the study were also included in the analysis.

  • No: scored when some patients/results are missing.

  • Unclear: scored when no or insufficient information is provided to permit a judgement.

e. Could the conduct or interpretation of the flow and timing have introduced bias?
  • High: if two or more questions above (8 a-d) were answered with ‘no.’

  • Low: if all questions were answered with ‘yes’; or at least three and the other one with unclear.

  • Unclear: for any other combination of answers (eg all questions were unclear; three were unclear and the last one was ‘yes’).

Please state the tests under evaluation in the study.

Indicate the tests that have been evaluated for S. mansoni and/or S. haematobium in the study by ticking the appropriate boxes for the respective species. If a species was not evaluated, please tick the box ‘not applicable.’

9. Index tests (Index test domain)

a. Was quality control done?

To ensure reliability or good quality of results, a sample of slides may be cross-checked by a second person, by an expert, or by a reference laboratory. Please indicate whether this was done in the study. If information given is unclear, please tick the box ‘unclear.’ If not reported, tick the box ‘not stated.’ If necessary, provide comment in the box provided.

b. Were the index test results interpreted without knowledge of the results of the reference standard?
  • Yes: when results of the index tests are interpreted without knowledge of reference test results, or when index tests are done before the reference standard.

  • No: when results of the index tests are interpreted with knowledge of reference test results in cases when reference tests were used before the index tests.

  • Unclear: when information on when the index and reference tests were interpreted is insufficient.

  • Not stated: when no information was reported on this item.

c. If a threshold was used, was it prespecified?
  • Yes: when the study authors report the use of one prespecified cutoff value. A prespecified threshold also includes statements such as, “the test was scored according to manufacturer’s instructions.”

  • No: when multiple cutoff values were tested and the best one chosen afterwards.

  • Unclear: when only one cutoff value was used, but this was not explicitly stated in the Methods section.

  • Not stated: when no information was reported on this item.

  • Could the conduct or interpretation of the index test have introduced bias?

    • High: if two or more questions above (9 a-c) were answered with ‘no.’

    • Low: if questions (9 a-c) were answered with ‘yes.’

    • Unclear: for any other combination of answers (eg both questions were unclear; one was unclear and one was ‘yes’).

10. Reference test (Reference Test domain)

The reference test for S.h that this review will evaluate is urine microscopy.

The following questions (10 A (h-k)) are part of the QUADAS tool and will be used to assess for risk of bias in how the reference test is carried out.

A. S. haematobium
h. Was quality control done?

To ensure reliability or good quality of results, a sample of slides may be cross-checked by a second person, by an expert, or by a reference laboratory. Please indicate whether this was done in the study. If information given is unclear, please tick the box ‘unclear.’ If not reported, tick the box ‘not stated.’ If necessary, insert comment into the box provided.

i. Is the reference standard likely to correctly classify the target condition?
  • Yes: if measures to increase sensitivity are used (eg concentration techniques, multiple slides examined, stool sampled over a number of days. The recommended reference std for microscopy is one carried out on 3 stools or 3 urine samples (grading as follows: 1 sample; poor; 2 samples; moderate; 3 samples; good).

  • No: for example, if only ill children are sampled for the reference standard, or if stool samples with blood are thrown away to avoid contaminating technicians

  • Unclear: scored when information on the reference standard used or sample preparation technique used was insufficient.

j. Were the reference standard results interpreted without knowledge of results of the index test?
  • Yes: when results of the reference tests are interpreted without knowledge of index test results in cases when reference tests are used before the index standard.

  • No: when results of the reference tests are interpreted with knowledge of the index test results in cases in which index tests are used before reference tests.

  • Unclear: when information on when the index and reference tests were interpreted is insufficient.

  • Not stated: when no information on this item was reported.

k. Could the conduct or interpretation of the reference standard have introduced bias?
  • High: if one or both questions above (a-b) were answered with ‘no.’

  • Low: if both questions were answered with ‘yes.’

  • Unclear: if both questions were unclear; or one was unclear and one was ‘yes.’

B. S. mansoni

Tick the appropriate box for the index tests used to detect S. m in the article.

These questions for S.m should be tackled in a similar fashion to those for S. haematobium.

a. Reference standard

The reference test for S.m that this review will evaluate is microscopy of stool that is prepared by the Kato-Katz method.

b. Was quality control done?

To ensure reliability or good quality of results, a sample of slides may be cross-checked by a second person, by an expert, or by a reference laboratory. Please indicate whether this was done in the study. If information given is unclear, please tick the box ‘unclear.’ If not reported, tick the box ‘not stated.’ If necessary, insert comment into the box provided.

The questions 10 B (i-l) are part of the QUADAS tool and will be used to assess for risk of bias in how the reference test is carried out. Instructions for these questions are similar to those for S. haematobium given above.

Appendix 5. Risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study

Figure 18

Figure 18.

Risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study. The blank cells refer to information that is not applicable to the stated study.

Appendix 6. Effect of year of study on the accuracy of microhaematuria

Figure 19

Figure 19.

Forest plot showing effect of year of study on sensitivity and specificity of microhaematuria.

Appendix 7. Effect of test brand on accuracy of microhaematuria

Figure 20

Figure 20.

Summary ROC plot showing effect of test brand on sensitivity and specificity of microhaematuria.

Appendix 8. Effect of year of study on the accuracy of proteinuria

Figure 21

Figure 21.

Forest plot showing effect of year of study on sensitivity and specificity of proteinuria.

Appendix 9. Effect of test brand on accuracy of proteinuria

Figure 22

Figure 22.

Summary ROC plot showing effect of test brand on sensitivity and specificity of proteinuria.

Appendix 10. Effect of test brand on accuracy of CCA POC S. mansoni

Figure 23

Figure 23.

Summary ROC plot showing effect of test brand on sensitivity and specificity of CCA POC mansoni.

Appendix 11. Forest plot of sensitivity and specificity of serum CAA ELISA for S. mansoni

Figure 24

Figure 24.

Forest plot of sensitivity and specificity of serum CAA ELISA for S. mansoni.

Squares represent the sensitivity and specificity of one study, the black line its confidence interval.

Squares represent the sensitivity and specificity of one study. The black line shows its confidence interval.

Appendix 12. Summary ROC plot of sensitivity versus specificity of serum CAA ELISA for S. mansoni

Figure 25

Figure 25.

Summary ROC plot of sensitivity versus specificity of serum CAA ELISA for S. mansoni.

The size of the points is proportional to the study sample size.

The size of the points is proportional to the study sample size.

Appendix 13. Forest plot of sensitivity and specificity of serum CAA ELISA for S. haematobium

Figure 26

Figure 26.

Forest plot of sensitivity and specificity of serum CAA ELISA for S. haematobium.

Squares represent the sensitivity and specificity of one study, the black line its confidence interval.

Squares represent sensitivity and specificity of one study. The black line shows its confidence interval.

Appendix 14. Summary ROC plot of sensitivity versus specificity of serum CAA ELISA for S. haematobium

Figure 27

Figure 27.

Summary ROC plot of sensitivity versus specificity of serum CAA ELISA for S. haematobium.

The size of the points is proportional to the study sample size

The size of the points is proportional to the study sample size.

Appendix 15. Forest plot of sensitivity and specificity of serum CCA ELISA for S. mansoni

Figure 28

Figure 28.

Forest plot of sensitivity and specificity of serum CCA ELISA for S. mansoni.

Squares represent the sensitivity and specificity of one study, the black line its confidence interval.

Squares represent sensitivity and specificity of one study. The black line shows its confidence interval.

Appendix 16. Forest plot of sensitivity and specificity of urine CCA ELISA for S. mansoni

Figure 29

Figure 29.

Forest plot of sensitivity and specificity of urine CCA ELISA for S. mansoni.

Squares represent the sensitivity and specificity of one study, the black line its confidence interval.

Squares represent sensitivity and specificity of one study. The black line shows its confidence interval.

Appendix 17. Comparison of KK smears and CCA POC against other reference standards (as reported by study authors)

Study Ref std Index test
   KK 1 CCA
    Sensitivity Specificity Sensitivity Specificity
Coulibaly 2011_Setting C9KK1 KK83 (76-88)100 (77-100)90 (83-94)85 (55-99)
 2 KK86 (80-91)100 (77-100)  
 3 KK94 (89-97)100 (77-100)  
      
Tchuente 20129KK1 KK54 (49-59)10084 (81-88)61 (55-68)
 3 KK68 (64-74)100  
      
Erko 20136KK1 KK70 (65-75)10093 (90-96)65 (59-70)
 2 KK81 (77-85)100  
      
Lodh 2013PCR1 KK57 (47-68)100 (69-100)67 (56-77)60 (26-88)

Feedback

Feedback from Dr Charles King, 17 March 2015

Summary

Point 1:

I feel that the current review's results and conclusions are misleading. The inappropriate analysis used in the HSROC estimation results in incorrect conclusions about the diagnostic performance of both antigen tests and dipsticks. The main objection I have is to the use of microscopic detection of eggs as the reference standard for the diagnosis of Schistosoma infection. Microscopy to detect S. mansoni or S. japonicum eggs in stool or S. haematobium eggs in filtered urine has long been known to be poorly sensitive for moderate and low intensity infections. When subjects are repeatedly tested for 7-15 days in a row, single day egg visualization has a sensitivity of 40-60%. The poor performance of microscopy for S. mansoni has been well documented by de Vlas and colleagues [1, 2] for S. japonicum by Carabin, et al.[3] and Hubbard, et al. [4] and for S. haematobium by Savioli et al.[5] and Warren, et al [6], among others.

Point 2:

Given the lack of a true ‘gold standard’ and a sensitivity by microscopy of ˜50%, a more appropriate approach for the review would have been Latent Class Analysis (LCA), in which results from two or more imperfect tests are used together to estimate an unmeasured ‘true’ infection status. In stating that the antigen test 'misclassify' (i.e., have poor specificity), the review claims that a person with a positive POC CCA and negative stool examination is not infected. In fact, several lines of evidence appear to indicate that many if not most of those who have negative stool examinations but positive POC CCA results are, in fact, infected. [7, 8, 9, 10, 11]

Point 3:

I would also encourage the authors to include results from populations or areas without significant Schistosoma risk. Measuring results among persons with very low pre-test probability of infection can contribute greatly to assessing the specificity of new tests.

Point 4:

Could the authors revisit the data using the LCA approach of Dendukuri, et al., 2012 [12] for situations in which there is no gold standard? Their SAS code is available online, and the reanalysis could be done in a matter of a day. A revised review, reflecting the LCA approach, would do much to remove the confusion about these tests in policy circles.

I agree with the conflict of interest statement below:

I certify that I have no affiliations with or involvement in any organization or entity with a financial interest in the subject matter of my feedback.

References

1. de Vlas SJ, Engels D, Rabello AL, Oostburg BF, Van Lieshout L, Polderman AM, Van Oortmarssen GJ, Habbema JD, Gryseels B, 1997. Validation of a chart to estimate true Schistosoma mansoni prevalences from simple egg counts. Parasitology 114 ( Pt 2): 113-21.

2. de Vlas SJ, Gryseels B, 1992. Underestimation of Schistosoma mansoni prevalences. Parasitol Today 8: 274-277.

3. Carabin H, Marshall CM, Joseph L, Riley S, Olveda R, McGarvey ST, 2005. Estimating the intensity of infection with Schistosoma japonicum in villagers of Leyte, Philippines. Part I: A Bayesian cumulative logit model. The Schistosomiasis Transmission & Ecology Project (STEP). Am J Trop Med Hyg 72: 745-753.

4. Hubbard A, Liang S, Maszle D, Qiu D, Gu X, Spear RC, 2002. Estimating the distribution of worm burden and egg excretion of Schistosoma japonicum by risk group in Sichuan Province, China. Parasitology 125: 221-31.

5. Savioli L, Hatz C, Dixon H, Kisumku UM, Mott KE, 1990. Control of morbidity due to Schistosoma haematobium on Pemba Island: egg excretion and hematuria as indicators of infection. Am J Trop Med Hyg 43: 289-295.

6. Warren KS, Arap Siongok TK, Hauser HB, Ouma JH, Peters PAS, 1978. Quantification of infection with Schistosoma haematobium in relation to epidemiology and selective population chemotherapy. I. Minimal number of daily egg counts in urine necessary to establish intensity of infection. Journal of Infectious Diseases 138: 849-55.

7. Tchuem Tchuente, LA, Kuete Fouodo, CJ, Kamwa Ngassam, RI, Sumo, L, Dongmo Noumedem, C, Kenfack, CM, Gipwe, NF, Nana, ED, Stothard, JR, Rollinson, D. Evaluation of circulating cathodic antigen (CCA) urine-tests for diagnosis of Schistosoma mansoni infection in Cameroon. 2012. PLoS Negl Trop Dis. 6(7):e1758.

8. Colley, DG, Binder S, Campbell C, King CH, Tchuem Tchuenté LA, N'Goran EK, Erko B, Karanja DM, Kabatereine NB, van Lieshout L, Rathbun S. A five-country evaluation of a point-of-care circulating cathodic antigen urine assay for the prevalence of Schistosoma mansoni. 2013. Am J Trop Med Hyg. 88(3):426-32.

9. Lamberton, PH, Kabatereine NB, Oguttu DW, Fenwick A, Webster JP. 2014. Sensitivity and specificity of multiple Kato-Katz thick smears and a circulating cathodic antigen test for Schistosoma mansoni diagnosis pre- and post-repeated-praziquantel treatment. PLoS Negl Trop Dis. 8(9):e3139.

10. Adriko, M, Standley CJ, Tinkitina B, Tukahebwa EM, Fenwick A, Fleming FM, Sousa-Figueiredo JC, Stothard JR, Kabatereine NB. 2014. Evaluation of circulating cathodic antigen (CCA) urine-cassette assay as a survey tool for Schistosoma mansoni in different transmission settings within Bugiri District, Uganda. Acta Trop (2014) 136:50-7.

11. Mwinzi, P, Kittur, N, Ochola, E, Cooper, PJ, Campbell, CH, Jr., King, CH, Colley, DG. 2015. Additional evaluation of the Point-of-Contact Circulating Cathodic Antigen assay for Schistosoma mansoni infection. Front. Public Health. doi: 10.3389/fpubh.2015.00048

12. Dendukuri N, Schiller I, Joseph L, Pai M, 2012. Bayesian meta-analysis of the accuracy of a test for tuberculous pleuritis in the absence of a gold standard reference. Biometrics 68: 1285-1293.

Reply

Point 1:

We would like to thank Professor King for his comment, although we do believe that the analysis used was appropriate. The limitations of microscopy as a reference standard have been acknowledged several times in our review. In the main text, we interpret the sensitivity of all tests as percentage of microscopy positives retrieved by the index test; and the specificity as microscopy negatives found negative by the index test. We therefore believe that our review gives better insight in the proportion of cases detected and missed by microscopy, which is still a commonly used tool in practice. Our discussion and conclusion within the main text and abstract reflect this. However we agree that the final line of the Plain Language Summary may be misleading, and we have therefore corrected this, incorporating the likely low sensitivity of egg counts (see below).

Moreover, attempts have been made by researchers to improve the quality of the microscopy (by increasing the number of samples or slides used) as the reference standard. A higher quality reference standard may be expected to detect more of the lower intensity infections. We showed how this affects the index test’s estimates. For S. mansoni, in studies with a higher quality reference standard the specificity of the POC-CCA increased. This strongly supports our, and your, conclusion that the apparent low specificity of POC-CCA is due to low sensitivity of the microscopy reference standard. POC-CCA may be more sensitive than Kato-Katz, particularly in low endemicity areas. Conversely, for S.haematobium the sensitivity of microhaematuria was lower in studies using a higher quality reference standard. The extra infections found by the higher quality reference standard were not picked up by microhaematuria dipsticks.

Point 2:

The proposed latent class analysis (LCA) approach for meta-analysis of diagnostic accuracy data takes into account the imperfect nature of the reference standard to come to a ‘true’ sensitivity and specificity. However, in latent class models, the target condition is a statistical entity and is not defined in a clinical way. The interpretation and use of accuracy results based on latent class models may therefore be challenging in practice, as clinicians are unclear about the target condition or what the results stand for. This target condition may reflect infection status, but there may also be another, unknown underlying latent patient status that does not necessarily correlate with infection. At least in our meta-analyses, we know what the limitations are and we know how to interpret the results.

We agree that ‘misclassify’ may not be the appropriate term and we will replace it in the abstract of the review with the first update. We have corrected the Plain Language Summary, incorporating the likely low sensitivity of egg counts. The end of the plain language summary now states

"For intestinal schistosomiasis, the parasite antigen urine test classifies many microscopy negative people as being infected. This finding may be explained by the low sensitivity of microscopy."

Point 3:

We understand the value of assessing the accuracy of these tests in non-endemic areas. However, we wanted to focus our review to endemic populations where disease control programs are mostly based and where diagnostic methods and control interventions are mostly applied. Yet, in the discussion we have included comments on the high specificity of POC-CCA tests in non-endemic areas. This was to strengthen our argument that the low specificity calculated from our meta analyses is likely due to low sensitivity of the commonly used reference standard (i.e. microscopy).

Point 4:

As explained above, the interpretation of LCA results may not be as straightforward as indicated. Moreover, the validity of results produced by LCA models depends on the specifications of the statistical model and the assumptions made when modelling the data. Especially determining the appropriate levels of dependence between tests complicates interpretation and the actual conduct of the models.

In summary, we whole heartedly agree on the potential benefits of LCA, but would like to see more research done on the validity, variability and interpretation of the models before using it at a regular basis and accepting it as the true gold standard approach for these meta-analyses in infectious diseases.

Contributors

All authors contributed to drafting this response.

What's new

DateEventDescription
8 July 2015Feedback has been incorporatedFeedback from Dr Charles King and responses from authors incorporated into the review.
8 July 2015AmendedReview amended to incorporate small change in Plain Language Summary and feedback from contributor.

Contributions of authors

Writing of first draft of review: Eleanor Ochodo.

Methodological advice: Mariska Leeflang, Johannes Reitsma, Patrick Bossuyt.

Content advice: Lisette Van Lieshout, Katja Polman, Poppy Lamberton.

Data collection: Eleanor Ochodo, Gowri Gopalakrishna, Bea Spek, Mariska Leeflang, Lisette Van Lieshout, Katja Polman, Poppy Lamberton.

Data analysis: Eleanor Ochodo, Mariska Leeflang, Johannes Reitsma.

Contributions to manuscript drafts: Eleanor Ochodo, Mariska Leeflang, Johannes Reitsma, Patrick Bossuyt, Lisette Van Lieshout, Katja Polman, Poppy Lamberton, Gowri Gopalakrishna, Bea Spek.

Agreement with final draft of review: Eleanor Ochodo, Gowri Gopalakrishna, Bea Spek, Poppy Lamberton, Lisette Van Lieshout, Katja Polman, Johannes Reitsma, Patrick Bossuyt, Mariska Leeflang.

Declarations of interest

The review authors have reported no conflicts of interest.

Sources of support

Internal sources

  • Academic Medical Centre Medical Research; University of Amsterdam, Netherlands.

    Funding PhD project of EAO

  • Dutch Cochrane Centre, Netherlands.

    Technical support

External sources

  • No sources of support supplied

Differences between protocol and review

Title of the review: To make the title of the review more specific to the tests that we evaluated, we have changed the title from "Rapid diagnostic tests for human schistosomiasis in endemic areas" to "Circulating antigen tests and urine reagent strips for diagnosis of active schistosomiasis in endemic areas."

We used QUADAS-2 to assess the methodological quality of studies included in the review. In the protocol, we stated that we would use the original QUADAS tool to assess quality and planned to perform a sensitivity analysis of the individual quality (QUADAS) items 4, 7, 8, 10, and 11, to explore whether the results that we found are robust for methodological challenges. Items 10 and 11 are not included in QUADAS-2. We instead assessed whether reference tests could classify the target condition as a co-variate.

In the protocol, we stated that we would analyze the intensity of infection as numerical co-variates. Because of poor reporting, we converted the data into categorical co-variates, including intensity of infection (light, moderate, heavy, unclear).

In the protocol, we also stated that we would estimate the sensitivity of urine reagent strips and urine CCA POC at positivity thresholds of +1 and ≥ +1. Instead we estimated the accuracy at thresholds > trace and > +1, as these data were most commonly provided.

As part of the post hoc analyses, we noted that three evaluations had substantial heterogeneity for the tests microhaematuria (Aryeetey 2000; sensitivity 55%, specificity 36%), proteinuria (Aryeetey 2000; sensitivity 38%, specificity 11%), and CCA POC for S. mansoni (Standley 2010; sensitivity 99%, specificity 19%). We excluded these evaluations in sensitivity analyses for the respective tests, as shown in the Results section.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Abdel-Wahab 1992

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Egypt

Sample size: 422

Age range: 12 to 16 years

Participants: school children whose parents gave consent

Setting: field study

Praziquantel status before study: About half of the included children gave a history of receiving PZQ in past 2 years

Index testsRS-Microhaematuria, RS-Proteinuria, RS-Leukocyturia (Combur-Test, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Leukocyturia
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
    
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Unclear  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Unclear  
    

Abdel-Wahab 2000

Study characteristics
Patient samplingCross-sectional design; multi-stage stratified random sampling
Patient characteristics and setting

Species: S. haematobium

Country: Egypt

Sample size: 5214

Age range: 5 to 25 years

Participants: residents from villages in Fayoum Governorate

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Unclear  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Adriko 2014_6KK

Study characteristics
Patient samplingCross-sectional design; random sampling
Patient characteristics and setting

Species: S. mansoni

Country: Uganda

Sample size: 469

Age range: 7 to 13 years

Participants: children from 5 schools categorized into 3 settings

Setting: field study

Praziquantel status before study: Annual mass treatment had been administered 5 years before study began

Index testsCCA POC test
Target condition and reference standard(s) S. mansoni infection measured by stool microscopy (6 Kato-Katz smears)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Adriko 2014_settingA

Study characteristics
Patient samplingCross-sectional design; random sampling
Patient characteristics and setting

Species: S. mansoni

Country: Uganda

Sample size: 100

Age range: 7 to 13 years

Participants: children from 1 school from low endemic setting (setting A)

Setting: field study

Praziquantel status before study: Annual mass treatment had been administered 5 years before study began

Index testsCCA POC test
Target condition and reference standard(s) S. mansoni infection measured by stool microscopy (2 Kato-Katz smears from 1 stool sample)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Adriko 2014_settingB

Study characteristics
Patient samplingCross-sectional design; random sampling
Patient characteristics and setting

Species: S. mansoni

Country: Uganda

Sample size: 200

Age range: 7 to 13 years

Participants: children from 2 schools from moderate endemic setting (setting B)

Setting: field study

Praziquantel status before study: Annual mass treatment had been administered 5 years before study began

Index testsCCA POC test
Target condition and reference standard(s) S. mansoni infection measured by stool microscopy (2 Kato-Katz smears from 1 stool sample)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Adriko 2014_settingC

Study characteristics
Patient samplingCross-sectional design; random sampling
Patient characteristics and setting

Species: S. mansoni

Country: Uganda

Sample size: 200

Age range: 7 to 13 years

Participants: children from 2 schools from high endemic setting (setting C)

Setting: field study

Praziquantel status before study: Annual mass treatment had been administered 5 years before study began

Index testsCCA POC test
Target condition and reference standard(s) S. mansoni measured by stool microscopy (2 Kato-Katz smears from 1 stool sample)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Alsherbiny 1999

Study characteristics
Patient samplingCross-sectional design; consecutive enrolment
Patient characteristics and setting

Species: S. haematobium

Country: Egypt

Sample size: 370

Age range: 5 to 75 years

Participants: Occupants > 5 years of age living in Behbeet Village willing to provide a stool, urine, and blood sample

Setting: field study

Praziquantel status before study: not reported

Index testsCAA ELISA-Serum and Urine; CCA ELISA-Serum and Urine (in-house assays)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test CCA ELISA
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test CAA ELISA
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?No  
    

Anosike 2001

Study characteristics
Patient samplingCross-sectional design; consecutive sampling
Patient characteristics and setting

Species: S. haematobium

Country: Nigeria

Sample size: 1173

Age range: not reported

Participants: all participating households in 7 communities

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Medi-Test Combi-9, Macherey Nagel, Düren, Germany)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Aryeetey 2000

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Ghana

Sample size: 370

Age range: > 5 years

Participants: All participants aged 5 years and above from the 3 study areas

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Hema-Combi-Stix, Bayer Diagnostics, Sudbury, UK)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Unclear  
    

Ashton 2011

Study characteristics
Patient samplingNested case-control design; unclear sampling
Patient characteristics and setting

Species: S. haematobium and S. mansoni

Country: Ivory Coast

Sample size: 370

Age range: 5 to 16 years

Participants: enrolled children within a study, rapid mapping for soil-transmitted helminthiasis

Setting: field study

Praziquantel status before study: not reported

Index testsCCA POC test (Rapid Medical Diagnostics, Pretoria, South Africa)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method) and S. mansoni infection by stool microscopy (Kato-Katz)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?No  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Yes  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Ayele 2008

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Ethiopia

Sample size: 206

Age range: 4 to 21 years

Participants: school children from 1 school, born and grown up in the area, and not moved since birth

Setting: field

Praziquantel status before study: not reported

Index testsRS-Microhamaturia (Combur 10 test, Roche GmbH, Mannheim, Germany); CCA POC test (European Veterinary Laboratory (EVL), Woerden, Holland)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Bassiouny 2014

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Yemen

Sample size: 696

Age range: 10 to 16 years

Participants: primary school children from fifth and sixth grades and first and second grades of preparatory education

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Urocolor 9, Standard Diagnostics Inc., Suwon City, Kyonggi Province, Korea)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (sedimentation method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Birrie 1995_settingA

Study characteristics
Patient samplingCross-sectional design; consecutive sampling
Patient characteristics and setting

Species: S. haematobium

Country: Ethiopia

Sample size: 156

Age range: 0 to > 40 years

Participants: all residents invited for checkup (low endemic area)

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Multistix Reagent Strips, Ames-Miles, Elkhart, IN, USA)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?No  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Unclear  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Unclear  
    

Birrie 1995_settingB

Study characteristics
Patient samplingCross-sectional design; consecutive sampling
Patient characteristics and setting

Species: S. haematobium

Country: Ethiopia

Sample size: 121

Age range: 0 to > 40 years

Participants: all residents invited for checkup (moderate endemic area)

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Multistix Reagent Strips, Ames-Miles, Elkhart, IN, USA)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?No  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Unclear  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Unclear  
    

Birrie 1995_settingC

Study characteristics
Patient samplingCross-sectional design; consecutive sampling
Patient characteristics and setting

Species: S. haematobium

Country: Ethiopia

Sample size: 224

Age range: 0 to > 40 years

Participants: all residents invited for checkup (high endemic area)

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Multistix Reagent Strips, Ames-Miles, Elkhart, IN, USA)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?No  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Unclear  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Unclear  
    

Bogoch 2012

Study characteristics
Patient samplingCross-sectional design; consecutive sampling
Patient characteristics and setting

Species: S. haematobium

Country: Ghana

Sample size: 280

Age range: 1 to 77 years

Participants: all willing to participate in voluntary screening and treatment

Setting: field study

Praziquantel status before study: 2 years before study

Index testsRS-Microhaematuria (Combur 10 Test, Roche GmbH, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (centrifugation method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Bosompem 1996

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Ghana

Sample size: 229

Age range: 1 to 86 years

Participants: volunteers

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Ames-Miles, Tokyo, Japan)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (centrifugation method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?No  
Were all patients included in the analysis?Unclear  
    

Bosompem 2004

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Ghana

Sample size: 141

Age range: not reported

Participants: Urine samples were collected from 90 individuals with symptoms and 51 asymptomatic individuals

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Haemacombrix Strips, Millipore Corp., Billerica, MA, USA)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Unclear  
    

Colley 2013_Uganda

Study characteristics
Patient samplingCross-sectional design; consecutive sampling
Patient characteristics and setting 
Index testsCCA POC cassette test (Rapid Medical Diagnostics; Pretoria, South Africa)
Target condition and reference standard(s) S. mansoni as measured by stool microscopy (1 KK smear)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Unclear  
Were all patients included in the analysis?Unclear  
    

Cooppan 1987

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: South Africa

Sample size: 941

Age range: 4 to 20 years

Participants: school children belonging to most infected age group were examined at selected localities

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Labstix, Ames, Ames, IA, USA)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?No  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?No  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Coulibaly 2011_9KK

Study characteristics
Patient samplingCross-sectional design; consecutive sampling
Patient characteristics and setting

Species: S. mansoni

Country: Ivory Coast

Sample size: 146

Age range: 8 to 12 years

Participants: children from grades 3 to 5 attending the schools selected for participation in the study

Setting: field study (low endemic area)

Praziquantel status before study: not reported

Index testsCCA POC test (Rapid Medical Diagnostics, Pretoria, South Africa)
Target condition and reference standard(s) S. mansoni infection measured by stool microscopy (Kato-Katz)
Flow and timing 
Comparative 
NotesIn Coulibaly 2011_9KK, the index test was measured against a higher-quality reference standard (9 Kato-Katz smears)
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Yes  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?No  
    

Coulibaly 2011_Colley2013

Study characteristics
Patient samplingCross-sectional design; consecutive sampling
Patient characteristics and setting

Species: S. mansoni

Country: Ivory Coast

Sample size: 146

Age range: 8 to 12 years

Participants: children from grades 3 to 5 attending the schools selected for participation in the study

Setting: field study (low endemic area)

Praziquantel status before study: not reported

Index testsCCA POC test (Rapid Medical Diagnostics, Pretoria, South Africa)
Target condition and reference standard(s) S. mansoni infection measured by stool microscopy (Kato-Katz)
Flow and timing 
Comparative 
NotesThis article describes part of a multi-centre study (Colley 2013). This was similar to Coulibaly 2011_9KK, but this article presented 2-by-2 tables of the CCA POC measured against the first daily stool specimen (triplicate KK smears on 1 stool sample)
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Yes  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?No  
    

Coulibaly 2013_4KK,

Study characteristics
Patient samplingCohort design; consecutive sampling
Patient characteristics and setting

Species: S. mansoni

Country: Cote D'ivoire

Sample size: 367

Age range: < 6 years

Participants: all preschool children from 2 villages

Setting: field study

Praziquantel status before study: reported that there had been no treatment in the area

Index testsCCAPOC cassette test (Rapid Medical Diagnostics, Pretoria, South Africa)
Target condition and reference standard(s) S. mansoni as measured by stool microscopy (4 Kato-Katz smears)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Yes  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Yes  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?No  
    

De Clerq 1995

Study characteristics
Patient samplingCross-sectional design; consecutive sampling
Patient characteristics and setting

Species: S. haematobium

Country: Mali

Sample size: 441

Age range: not reported

Participants: Blood and urine samples were collected from 182 and 271 people in the villages of Kassa and Boro

Setting: field study

Praziquantel status before study: no prior drugs

Index testsCAA ELISA Serum (in-house assay)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test CAA ELISA
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

El-Morshedy 1996

Study characteristics
Patient samplingCross-sectional design; random sampling
Patient characteristics and setting

Species: S. mansoni

Country: Egypt

Sample size: 257

Age range: 20 to 25 years

Participants: Cohort consisted of 257 men, treated, infected cases in a military camp

Setting: military camp

Praziquantel status before study: no prior drugs

Index testsCAA ELISA Serum (in-house assay)
Target condition and reference standard(s) S. mansoni infection measured by stool microscopy (Kato-Katz)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?No  
   Low
DOMAIN 2: Index Test CAA ELISA
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?No  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

El-Sayed 1995

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Egypt

Sample size: 280

Age range: 4 to 36 years

Participants: permanent settlers who agreed to participate in study

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Chemistrip, Boehringer, Indianapolis, IN, USA)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Yes  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?   
Were all patients included in the analysis?   
    

Eltoum 1992

Study characteristics
Patient samplingCross-sectional design; random sampling
Patient characteristics and setting

Species: S. haematobium

Country: Sudan

Sample size: 425

Age range: 3 to 39 years

Participants: asymptomatic and symptomatic participants randomly selected from population

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Ames-Miles, Elkhart, IN, USA)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?No  
    

Erko 2013_6KK

Study characteristics
Patient samplingCross sectional design; unclear sampling
Patient characteristics and setting

Species: S. mansoni

Country: Ethiopia

Sample size: 620

Age range: 8 to 12 years

Participants: children from a village in Western Kenya

Setting: field study

Praziquantel status before study: reported that there had been no treatment in the area

Index testsCCA POC cassette test (Rapid Medical Diagnostics, Pretoria, South Africa)
Target condition and reference standard(s) S. mansoni as measured by stool microscopy (3 Kato-Katz smears on 3 stool samples (6KK))
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Yes  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Erko 2013_Colley 2013

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. mansoni

Country: Ethiopia

Sample size: 620

Age range: 8 to 12 years

Participants: children from a village in Western Kenya

Setting: field study

Praziquantel status before study: reported that there had been no treatment in the area

Index testsCCA POC cassette test (Rapid Medical Diagnostics, Pretoria, South Africa)
Target condition and reference standard(s) S. mansoni as measured by stool microscopy (3 Kato-Katz smears on 1 stool sample)
Flow and timing 
Comparative 
NotesThis article describes part of a multi-centre study (Colley 2013). This was similar to Erko 2013_6KK, but in this article 2 × 2 tables of the CCA POC measured against the first daily stool specimen (triplicate KK smears on 1 stool sample) were presented
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Yes  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Etard 2004

Study characteristics
Patient samplingCross-sectional design; consecutive sampling
Patient characteristics and setting

Species: S. haematobium

Country: Mali

Sample size: 2873

Age range: 10 to 22 years

Participants: families from 14 villages

Setting: field study

Praziquantel status before study: Half of the villages had received mass treatment

Index testsRS-Microhaematuria (Ecur test, Boehringer- Mannheim, Germany)
Target condition and reference standard(s) S. haematobium measured with urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Yes  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Fatiregun 2005

Study characteristics
Patient samplingCross-sectional design; consecutive sampling
Patient characteristics and setting

Species: S. haematobium

Country: Nigeria

Sample size: 592

Age range: 11 to 20 years

Participants: all students of junior classes

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Combi-9 Multi-Strip, Macherey Nagel, Düren, Germany)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

French 2007

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Tanzania

Sample size: 1976

Age range: 6 to 19 years

Participants: school children from 24 sentinel schools

Setting: field study

Praziquantel status before study: Participants were already receiving praziquantel as part of a World Health Organization (WHO) programme, but no time interval was provided

Index testsRS-Microhaematuria (Haemastix, Bayer, Glasgow, UK)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Unclear  
    

Gabr 2000

Study characteristics
Patient samplingCross-sectional design; random sampling
Patient characteristics and setting

Species: S. haematobium

Country: Egypt

Sample size: 12,134

Age range: 0 to > 55years

Participants: Randomization took place at village and household levels

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Combur-Test, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Unclear  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?No  
    

Gigase 1988

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Chad

Sample size: 195

Age range: 7 to 19 years

Participants: children from a village

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Hema-Combi-Stix) (Combur-Test, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (centrifugation method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Gundersen 1996

Study characteristics
Patient samplingCross-sectional design; consecutive sampling
Patient characteristics and setting

Species: S. haematobium

Country: Malawi

Sample size: 260

Age range: 6 to 19 years

Participants: all women of childbearing age (range 15 to 47 years) willing to provide samples, irrespective of complaints

Setting: outpatient department, hospital

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Combur Test 9, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Leukocyturia
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Hall 1999

Study characteristics
Patient samplingCross-sectional design; random sampling
Patient characteristics and setting

Species: S. haematobium

Country: Ghana

Sample size: 786

Age range: 6 to 16 years

Participants: school-age children from 10 communities

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Hemastix, Bayer, Glasgow, UK)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?No  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?No  
Were all patients included in the analysis?Yes  
    

Hammad 1997

Study characteristics
Patient samplingCross-sectional design; random sampling
Patient characteristics and setting

Species: S. haematobium

Country: Egypt

Sample size: 11,970

Age range: not reported

Participants: participants interviewed and willing to participate in study

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Chemstrip-4 OB, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Yes  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Hammam 2000_a

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Egypt

Sample size: 9555

Age range: 0 > 55 years

Participants: residents from villages and households in Assiut Governorate

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Combur-Test, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Unclear  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Unclear  
Were all patients included in the analysis?Unclear  
    

Hammam 2000_b

Study characteristics
Patient samplingCross-sectional design; multi-stage stratified cluster sample
Patient characteristics and setting

Species: S. haematobium

Country: Egypt

Sample size: 12,327

Age range: 0 to > 55years

Participants: residents from villages and households in Qena Governorate

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Combur-Test, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?No  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Unclear  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Houmsou 2011

Study characteristics
Patient samplingCross-sectional; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Nigeria

Sample size: 1124

Age range: 3 to 27 years

Participants: those interviewed and willing to participate in study

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Medi-Test Combi 9, Macherey-Nagel, Düren, Germany)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Yes  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Kassim 1989

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Nigeria

Sample size: 922

Age range: 5 to 14 years

Participants: school children from Epe and surrounding communities in SW Nigeria

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Labstix, Ames, Ames, IA, USA)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (centrifugation method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Unclear  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Kiliku 1991

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species:S. haematobium

Country: Kenya

Sample size: 426

Age range: not reported

Participants: sample of all participants in Kwale District

Setting: field study

Praziquantel status before study: no prior drug given

Index testsRS-Microhaematuria, RS-Proteinuria (Uro-Labstix III, Miles-Sanko Co., Ltd., Osaka, Japan)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?No  
Was quality control done?Yes  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?No  
Was quality control done?Yes  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?No  
Were all patients included in the analysis?Yes  
    

King 1988_a

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Kenya

Sample size: 2628

Age range: 4 to 21 years

Participants: students registered at 5 local primary and secondary schools

Setting: field study

Praziquantel status before study: before and after study; follow-up evaluation 1 year after PZQ and metrifonate given

Index testsRS-Microhaematuria, RS-Proteinuria (Chemstrip 5 Indicator Dipsticks, Roche Diagnostics, Montreal, Quebec Canada)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

King 1988_b

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Kenya

Sample size: 639

Age range: 0 to 60+ years

Participants: residents of a village who submitted urine samples

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Combur-Test, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Kitange 1993

Study characteristics
Patient samplingCohort design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Tanzania

Sample size: 253

Age range: not reported

Participants: children in classes 1 to 7 in Melela primary school

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (BM Test 5L, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (centrifugation method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?No  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?No  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Unclear  
Were all patients included in the analysis?Unclear  
    

Legesse 2007

Study characteristics
Patient samplingCross sectional design; unclear sampling
Patient characteristics and setting

Species: S. mansoni

Country: Ethiopia

Sample size: 251

Age range: 5 to 75 years

Participants: those > 5 years recruited through house-to-house visits

Setting: field study

Praziquantel status before study: not reported

Index testsCCA POC test (Schistosomiasis One Step Test, BV European, Veterinary Laboratory, Woerden, The Netherlands)
Target condition and reference standard(s) S. mansoni infection measured by stool microscopy (Kato-Katz)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?No  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Unclear
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Legesse 2008

Study characteristics
Patient samplingCross-sectional design; random sampling
Patient characteristics and setting

Species: S. mansoni

Country: Ethiopia

Sample size: 184

Age range: 5 to 22 years

Participants: primary school children

Setting: field study

Praziquantel status before study: not reported

Index testsCCA POC test (Schistosomiasis One Step Test, BV European, Veterinary Laboratory, Woerden, The Netherlands)
Target condition and reference standard(s) S. mansoni infection measured by stool microscopy (Kato-Katz)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Lengeler 1993

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Tanzania

Sample size: 1208

Age range: 11 to 15 years

Participants: school children who were willing to participate and provided a urine sample

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Combur 9 Multistix, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Mafe 1997

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Nigeria

Sample size: 1056

Age range: 5 to > 60 years

Participants: individuals residing in 4 lakeside villages

Setting: field study

Praziquantel status before study: no prior drugs given

Index testsRS-Microhaematuria (Ames Chemical Reagent Strip, Ames Labs, Ames, IA, USA)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Mafe 2000

Study characteristics
Patient samplingCross-sectional design; consecutive sampling
Patient characteristics and setting

Species: S. haematobium

Country: Nigeria

Sample size: 529

Age range: mean 11 years

Participants: school children in Borgo local government area

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Sangur Sticks, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Magnussen 2001

Study characteristics
Patient samplingCohort design; consecutive sampling
Patient characteristics and setting

Species: S. haematobium

Country: Tanzania

Sample size: 170

Age range: 11 to 17 years

Participants: All children in class 5 in each school in the district were selected

Setting: field study

Praziquantel status before study: given prior, but time interval not stated

Index testsRS-Microhaematuria (Haemastix, Ames Labs, Ames, IA, USA; Bayer Diagnostics, Sudbury, UK)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Unclear  
    

Midzi 2009

Study characteristics
Patient samplingCross-sectional design; random sampling
Patient characteristics and setting

Species: S. haematobium

Country: Zimbabwe

Sample size: 265

Age range: 2 to 19 years

Participants: preschool and primary school children

Setting: field study

Praziquantel status before study: not reported

Index testsCCA POC test (Van Dam version)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Yes  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Morenikeji 2014

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Uganda

Sample size: 432

Age range: 7 to 13 years

Participants: primary school children

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Medi-Test Combi 10, Standard Diagnostics Inc., Suwon City, Kyonggi Province, Korea)
Target condition and reference standard(s) S. haematobium infection measured bu urine microscopy (centrifugation)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Mott 1985a_1

Study characteristics
Patient samplingCohort design; consecutive sampling
Patient characteristics and setting

Species: S. haematobium

Country: Ghana

Sample size: 562

Age range: 5 to 64 years

Participants: those from 5 settlements interviewed and samples collected

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Neostix-3, Ames Labs, Ames, IA, USA)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Mott 1985a_2

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Zambia

Sample size: 656

Age range: 0 to 64 years

Participants: those in Mutenda

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Neostix-3, Ames Labs, Ames, IA, USA)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Mtasiwa 1996

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Tanzania

Sample size: 404

Age range: 7 to 15 years

Participants: Urine samples were drawn from 404 pupils, including those with frank haematuria

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Sangur Reagent Sticks, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) 
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Unclear  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Murare 1987

Study characteristics
Patient samplingCohort design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Zimbabwe

Sample size: 232

Age range: 9 to 14 years

Participants: school children from a school chosen on basis of previous studies

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Medi-Test Combi-7, Macherey-Nagel, Düren, Germany)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Navaratnam 2012

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. mansoni

Country: Uganda

Sample size: 569

Age range: 1 to 5 years

Participants: preschool children living in 4 villages in Buliisa District

Setting: field study

Praziquantel status before study: not reported

Index testsCCA POC test (Rapid Medical Diagnostics, Pretoria, South Africa)
Target condition and reference standard(s) S. mansoni infection measured by stool microscopy (Kato-Katz)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Ndamukong 2001

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Cameroon

Sample size: 347

Age range: 5 to 16 years

Participants: primary school children attending 6 primary schools

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Haemastix and Albustix, Bayer, Pittsburgh, PA, USA)
Target condition and reference standard(s) S. haematobium measured by urine microscopy
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Ndlovu 1996

Study characteristics
Patient samplingNested case-control design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Zimbabawe

Sample size: 179

Age range: > 5 years

Participants: egg-positives and egg-negatives, resulting in 96 cases and 83 controls from same population

Setting: field study

Praziquantel status before study: not reported

Index testsCAA ELISA Serum (in-house assay)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?No  
Did the study avoid inappropriate exclusions?Unclear  
   Unclear
DOMAIN 2: Index Test CAA ELISA
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?No  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Unclear  
Were all patients included in the analysis?Unclear  
    

Nduka 1995

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Nigeria

Sample size: 1165

Age range: 6 to 21 years

Participants: school children from a rural town

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Medi-Test Combi-9, Macherey Nagel, Düren, Germany)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Ndyomugyenyi 2001

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Tanzania

Sample size: 483

Age range: 5 to 19 years

Participants: children from 3 primary schools

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Multistix, Ames Labs, Ames, IA, USA; Bayer Diagnostics, Tarrytown, NY, USA)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

NGoran 1989

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Ivory Coast

Sample size: 1059

Age range: not reported

Participants: inhabitants of village of Nguessan Pokoukro, present on the day of examination

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Hemastix) (Combur-Test, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Unclear  
Were all patients included in the analysis?Yes  
    

NGoran 1998

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Ivory Coast

Sample size: 1336

Age range: 12.2 +/- 1.6 years

Participants: school children from 14 schools in town of Toumoudi

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Sangur-Test, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Ngándu 1988

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Zambia

Sample size: 412

Age range: 6 to 19 years

Participants: school children from 9 primary schools

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Bili-Labstix, Miles, Bridgend, UK)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?No  
    

Nmorsi 2005

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Nigeria

Sample size: 300

Age range: 5 to 60 years

Participants: volunteers; excluded were patients with allergy and skin infections

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Haemastix, Ames Laboratories, Ames, IA, USA), RS-Proteinuria (Albustix, Ames Laboratories)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (centrifugation method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?No  
   Unclear
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Unclear  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Nwaorgu 1992

Study characteristics
Patient samplingCross-sectional design; random sampling
Patient characteristics and setting

Species: S. haematobium

Country: Nigeria

Sample size: 437

Age range: 0 to 35+ years

Participants: permanent settlers who agreed to participate in study

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (L-Combur, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?No  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?No  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Ofori 1986

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Ghana

Sample size: 118

Age range: not reported

Participants: urine specimens collected from 118 pupils

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (N-Multistix SG, Ames, Glasgow, England)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Okeke 2014_settingA

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Nigeria

Sample size: 296

Age range: 5 to 13 years

Participants: primary school children from Niger Lake, a low endemic setting (setting A)

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Medi-Test Combi-9, Macherey-Nagel, Düren, Germany)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (sedimentation method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?No  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?No  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Okeke 2014_settingB

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Nigeria

Sample size: 184

Age range: 5 to 13 years

Participants: primary school children from Nigercem, a moderate endemic setting (setting B)

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Medi-Test Combi-9, Macherey-Nagel, Düren, Germany)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (sedimentation method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Onayade 1996

Study characteristics
Patient samplingCross-sectional design; consecutive sampling
Patient characteristics and setting

Species: S. haematobium

Country: Nigeria

Sample size: 105

Age range: 8 to 16 years

Participants: all grade 4 to 6 pupils with minimum age of 4

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Proteinuria (N-Multistix, Ames Labs, Ames, IA, USA)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (sedimentation method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?No  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Poggensee 2000_settingA

Study characteristics
Patient samplingCross-sectional design; non–probability-based sampling procedure
Patient characteristics and setting

Species: S. haematobium

Country: Tanzania

Sample size: 175

Age range: 15 to 60 years

Participants: women of childbearing age

Setting: field study (low endemic setting)

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria, RS-Leukocyturia (Nephur-Test + Leuco, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?No  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Leukocyturia
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Poggensee 2000_settingB

Study characteristics
Patient samplingCross-sectional design; non–probability-based sampling procedure
Patient characteristics and setting

Species: S. haematobium

Country: Tanzania

Sample size: 128

Age range: 15 to 60 years

Participants: women of childbearing age

Setting: field study (high endemic setting)

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria, RS-Leukocyturia (Nephur-Test + Leuco, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?No  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Leukocyturia
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Polman 1995

Study characteristics
Patient samplingCross-sectional design; random sampling
Patient characteristics and setting

Species: S. mansoni

Country: Senegal

Sample size: 422

Age range: 0 to 77 years

Participants: 10% of the households (all members) from an updated census list

Setting: field study

Praziquantel status before study: not reported

Index testsCAA ELISA Serum; CCA ELISA Serum and Urine (in-house)
Target condition and reference standard(s) S. mansoni infection measured by stool microscopy (Kato-Katz)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test CCA ELISA
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test CAA ELISA
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Unclear  
    

Pugh 1980

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Nigeria

Sample size: 5367

Age range: 5 to > 36 years

Participants: males 5 to 25 years of age from 3 villages and all participants over 4 years from 2 study areas

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria; RS-Proteinuria (Labstix, Ames Labs, Berlin, Germany)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Unclear  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?No  
    

Rasendramino 1998

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Madagascar

Sample size: 574

Age range: > 5 years

Participants: all inhabitants of a village > 5 years

Setting: field study

Praziquantel status before study: Study reports that no praziquantel was administered before the study

Index testsRS-Microhaematuria, RS-Proteinuria, RS-Leukocyturia (Nephur 7 test, Roche Diagnostics, Montreal, Quebec, Canada)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Leukocyturia
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Robinson 2009

Study characteristics
Patient samplingNested case-control design; quasi-random 2-stage cluster sampling method
Patient characteristics and setting

Species: S. haematobium

Country: Sudan

Sample size: 677

Age range: 5 to 16 years

Participants: In each selected household, children were asked to provide a urine sample

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Hemastix Bayer Diagnostics, Bridgend, UK)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?No  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?No  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?No  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Rollinson 2005

Study characteristics
Patient samplingCross-sectional design; random sampling
Patient characteristics and setting

Species: S. haematobium

Country: Tanzania

Sample size: 280

Age range: 10 to 22 years

Participants: children from 2 schools

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Hemastix, Bayer, Pittsburgh, PA, USA)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?No  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?No  
    

Sarda 1985

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Tanzania

Sample size: 2418

Age range: 7 to 19 years

Participants: children from 12 schools

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (N-Multistix, Ames Labs, Ames, IA, USA)
Target condition and reference standard(s) S. haematobium measured by urine microscopy(filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?No  
    

Sarda 1986

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Kenya

Sample size: 1300

Age range: 6 to 19 years

Participants: school children from various schools

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (N-Multistix Ames Labs, Ames, IA, USA)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Unclear  
Were the reference standard results interpreted without knowledge of the results of the index tests?Yes  
Was quality control done?Yes  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Savioli 1990

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Tanzania

Sample size: 879

Age range: 5 to 19 years

Participants: children in a village

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Hemastix, Ames-Miles Laboratories, Elkhart, IN, USA)
Target condition and reference standard(s) S. haematobium measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Unclear  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?No  
    

Sellin 1982

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Burkina Faso

Sample size: 1162

Age range: not reported

Participants: people from a high endemic village in Upper Volta

Setting: field study

Praziquantel status before study: treatment given after baseline study and follow-up accuracy study done 1 year later

Index testsRS-Microhaematuria, RS-Proteinuria (Laboratoires Ames, Paris, France)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Shane2011_Colley2013

Study characteristics
Patient samplingCross-sectional design; consecutive sampling
Patient characteristics and setting

Species: S. mansoni

Country: Kenya

Sample size: 1845 (updated from Colley 2013)

Age range: 1 to 15 years

Participants: children from a village in Western Kenya

Setting: field study

Praziquantel status before study: reported that there had been no treatment in the area

Index testsCCA POC cassette (Rapid Medical Diagnostics, Pretoria, South Africa)
Target condition and reference standard(s) S. mansoni infection measured by stool microscopy (Kato-Katz smears)
Flow and timing 
Comparative 
NotesThis article was part of a multi-centre study (Colley 2013). In this article, 2-by-2 tables of the CCA POC measured against the first daily stool specimen (duplicate KK smears on 1 stool sample) were presented
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Yes  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Yes  
Was quality control done?Yes  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Shaw 1998

Study characteristics
Patient samplingCohort design; random sampling
Patient characteristics and setting

Species: S. haematobium

Country: Senegal

Sample size: 857

Age range: 4 to > 40

Participants: individuals in households invited to participate

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Ames Labs, Ames, IA, USA; Bayer Diagnostics, Gent, Belgium)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Standley 2010

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. mansoni

Country: Eastern Lake Victoria (Tanzania and Kenya)

Sample size: 171

Age range: 6 to 17 years

Participants: school children selected in 11 schools by headmaster

Setting: field study

Praziquantel status before study: not reported

Index testsCCA POC test (Rapid Medical Diagnostics, Pretoria, South Africa)
Target condition and reference standard(s) S. mansoni infection measured by stool microscopy (Kato-Katz)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?No  
Was quality control done?Yes  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Yes  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Unclear  
    

Stephenson 1984

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Kenya

Sample size: 359

Age range: 6 to 16 years

Participants: Children from 2 primary schools not previously tested were examined

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Ames N-Multistix, Ames Labs, Ames, IA, USA)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Unclear  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Stothard 2006

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. mansoni

Country: Uganda

Sample size: 270

Age range: 11 years

Participants: children from 9 sentinel schools of matched sexes

Setting: field study

Praziquantel status before study: not reported

Index testsCCA POC test (Schistosomiasis One Step Test, EVL, Woerden, Holland)
Target condition and reference standard(s) S. mansoni infection measured by stool microscopy (Kato-Katz)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Stothard 2009a

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Tanzania

Sample size: 150

Age range: 8 to 14 years

Participants: children from 5 schools

Setting: field study

Praziquantel status before study: annual MDA 11 months before the study

Index testsCCA POC test (Leiden University Medical Centre, Leiden, The Netherlands)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Unclear  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Stothard 2009b

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Tanzania

Sample size: 66

Age range: 9 to 15 years

Participants: school children

Setting: field study

Praziquantel status before study: Likely, children enrolled were already part of a 'kick out schistosomiasis' campaign

Index testsRS-Microhaematuria (Hemastix, Bayer, Sudbury, UK)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?No  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Tanner 1983_1

Study characteristics
Patient samplingCross-sectional design; random sampling
Patient characteristics and setting

Species: S. haematobium

Country: Liberia

Sample size: 267

Age range: 0 to 15 years

Participants: school children from 3 villages

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Labstix, Ames, Glasgow, England)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Unclear  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Tanner 1983_2

Study characteristics
Patient samplingCross-sectional design; random sampling
Patient characteristics and setting

Species: S. haematobium

Country: Tanzania

Sample size: 548

Age range: 0 to 15 years

Participants: children from 1 village and river plain

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria (Blood Sangur Test, Boehringer, Mannheim FRG), RS-Proteinuria (Protein Albym Test, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Unclear  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?Yes  
    

Tchuente 2012_9KK

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. mansoni

Country: Cameroon

Sample size: 138

Age range: 7 to 15 years

Participants: children who provided all 3 samples

Setting: field study (low endemicity)

Praziquantel status before study: not reported

Index testsCCA POC test (Rapid Medical Diagnostics, Pretoria, South Africa)
Target condition and reference standard(s) 
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Yes  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Unclear  
Were all patients included in the analysis?Unclear  
    

Tchuente 2012_Colley2013

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. mansoni

Country: Cameroon

Sample size: 138

Age range: 7 to 15 years

Participants: children who provided all 3 samples

Setting: field study (low endemicity)

Praziquantel status before study: not reported

Index testsCCA POC test (Rapid Medical Diagnostics, Pretoria, South Africa)
Target condition and reference standard(s) S. mansoni infection measured by stool microscopy (Kato-Katz)
Flow and timing 
Comparative 
NotesThis article describes part of a multi-centre study (Colley 2013), which was similar to Tchuente 2012_9KK, but in this article, 2-by-2 tables of the CCA POC measured against the first daily stool specimen (triplicate KK smears on 1 stool sample) were presented
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test CCA POC
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Yes  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?No  
    

Traore 1998

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Mali

Sample size: 1041

Age range: 2 to 25+ years

Participants: all inhabitants in a village older than 2 years

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Combur-9, Boehringer, Mannheim, Germany)
Target condition and reference standard(s) S. haematobium measured with urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Yes  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Yes  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Unclear  
If a threshold was used, was it pre-specified?Unclear  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?Yes  
Were the reference standard results interpreted without knowledge of the results of the index tests?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?Yes  
Did all patients receive the same reference standard?Yes  
Were all patients included in the analysis?No  
    

Ugbomoiko 2009a

Study characteristics
Patient samplingCross-sectional design; unclear sampling
Patient characteristics and setting

Species: S. haematobium

Country: Nigeria

Sample size: 447

Age range: 3 to 17 years

Participants: all school children except girls who had menstruated within 5 days of sample collection

Setting: field study

Praziquantel status before study: not reported

Index testsRS-Microhaematuria, RS-Proteinuria (Medi-Test Combi-9, Analyticon Biotechnologies, Rosbach vor der Höhe, Germany)
Target condition and reference standard(s) S. haematobium infection measured by urine microscopy (filtration method)
Flow and timing 
Comparative 
Notes 
Methodological quality
ItemAuthors' judgementRisk of biasApplicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?Unclear  
Was a case-control design avoided?Yes  
Did the study avoid inappropriate exclusions?Unclear  
   Low
DOMAIN 2: Index Test RS-Microhaematuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 2: Index Test RS-Proteinuria
Were the index test results interpreted without knowledge of the results of the reference standard?Yes  
If a threshold was used, was it pre-specified?Yes  
Was quality control done?Unclear  
   Low
DOMAIN 3: Reference Standard
Is the r