Circulating Cathodic Antigen Test Research Articles

Impact of Praziquantel on Schistosomiasis Infection and the Status of Proteinuria and Hematuria among School Children Living in <i>Schistosoma mansoni</i>-Endemic Communities in Northwestern Tanzania

The aim of the study was to assess the effect of praziquantel (PZQ) treatment on hematuria, proteinuria and the status of eGFR following treatment in school children infected with S. mansoni. A cohort study among 6 - 13 years old children was conducted in the Lake Zone region of Tanzania to assess S. mansoni infection using a circulating cathodic antigen (CCA), Kato Kartz while urine dipstick to screen for urine protein levels and red blood cells. A blood sample was taken for every child to determine creatinine levels and later a status of estimated glomerular filtration rate (eGFR). The prevalence of S. mansoni infection was 64%, 46%, and 24% at baseline, 6 months, and 1 year respectively using CCA test. There was a 62.5% reduction in S. mansoni infection from baseline (p 2 was zero at six month. There was a 50% reduction in proteinuria and hematuria after 1 year (p S. mansoni using CCA test, reductions in proteinuria, and hematuria in school children in Tanzania. There was complete remission in eGFR 2 from 3.9% to 0% at 6 months. This suggests that praziquantel is effective, but there is still a need for integrated strategies to minimize reinfections.

A study on positive school children as indicators of schistosomiasis status in their families.

This study aimed to evaluate schistosomiasis positive school children as indicators of infection in their families. Four hundred and sixteen stool samples of children from two primary schools were examined microscopically for Schistosoma mansoni (S. mansoni) after Kato-Katz. Equal numbers from families of schistosomiasis positive and negative school children were examined by Kato-Katz. Circulating cathodic antigen (CCA) cassette test was performed on 100 Kato-Katz negative children to detect missed S. mansoni cases if any. S. mansoni infection rates among the primary school children were 15.3% and 1.6% in high and low prevalence schools respectively. Sixty five percent of school children had light intensity infection. Family members were either negative or exhibited a prevalence rate as low as 5-6% whether related to positive or negative children. A higher infection rate of S. mansoni was detected by the CCA test compared to the Kato-Katz. Conclusively, children can be good indicators of their particular families in areas of limited resources and low endemicity. Efforts are required to permit large scale use of CCA cassette test.

Rapid clearance of Schistosoma mansoni circulating cathodic antigen after treatment shown by urine strip tests in a Ugandan fishing community - Relevance for monitoring treatment efficacy and re-infection.

Schistosomiasis control and elimination has priority in public health agendas in several sub-Saharan countries. However, achieving these goals remains a substantial challenge. In order to assess progress of interventions and treatment efficacy it is pertinent to have accurate, feasible and affordable diagnostic tools. Detection of Schistosoma mansoni infection by circulating cathodic antigen (CCA) in urine is an attractive option as this measure describes live worm infection noninvasively. In order to interpret treatment efficacy and re-infection levels, knowledge about clearance of this antigen is necessary. The current study aims to investigate, whether antigen clearance as a proxy for decreasing worm numbers is reflected in decreasing CCA levels in urine shortly after praziquantel treatment. Here CCA levels are measured 24 hours post treatment in response to both a single and two treatments. The study was designed as a series of cross-sectional urine and stool sample collections from 446 individuals nested in a two-arm randomised single blinded longitudinal clinical trial cohort matched by gender and age (ClinicalTrials.gov Identifier: NCT00215267) receiving one or two praziquantel treatments. CCA levels in urine were determined by carbon-conjugated monoclonal antibody lateral flow strip assay and eggs per gram faeces for S. mansoni and soil-transmitted helminths by Kato-Katz. Significant correlations between CCA levels and S. mansoni egg count at every measured time point were found and confirmed the added beneficial effect of a second treatment at two weeks after baseline. Furthermore, presence of hookworm was found not to be a confounder for CCA test specificity. Twenty-four hours post treatment measures of mean CCA scores showed significant reductions. In conclusion, removal of CCA in response to treatment is detectable as a decline in CCA in urine already after 24 hours. This has relevance for use and interpretation of laboratory based and point-of-care CCA tests in terms of treatment efficacy and re-infection proportions as this measure provides information on the presence of all actively feeding stages of S. mansoni, which conventional faecal microscopy methods do not accurately reflect.Trial registrationClinicalTrials.gov NCT00215267

Intestinal schistosomiasis and the associated transmission factors in pre-school aged children in villages surrounding Lake Rweru in Bugesera District, Rwanda

Background: Schistosomiasis is a waterborne snail-transmitted parasitic disease and is a major public health problem in sub-Saharan Africa, affecting populations living where water supply and sanitation are poor and inadequate. Pre-school aged children (PSAC) have often been ignored in disease control and prevention programs, as a result very little information is available on the prevalence or intensity of schistosomiasis in this age group. Objective: This study was conducted to determine the prevalenceand intensity of intestinal schistosomiasis among PSAC, and determine factors associated with infection transmission in PSAC in villages surrounding Lake Rweru in Bugesera District, Rwanda. Methods: This was a cross-sectional study involving 256 PSAC aged 12-59 months. Double Kato-Katz (KK) stool smears and the point of care circulating cathodic antigen (CCA) test were used to diagnose S. mansoni in stool and urine samples, respectively. A questionnaire in the local language (Kinyarwanda) was administered to parents/guardians of the PSAC to determine factors associated with schistosomiasis transmission in the area. Results: Based on the KK stool smears, no S. mansoni infection was found in any of the PSAC identified. However, using the point of care CCA test, 16.9% of the PSAC tested positive, when trace was considered as positive. The information collected on questionnaire showed a significant association between infection with S. mansoni (based on the CCA test) and visits to the lake especially, when the children accompanied their parents/guardians, or older children ( P <0.000). Conclusion: The prevalence of S. mansoni in the study population was low on CCA test and the infection was associated with going to the lake by the children when they accompanied their parents/guardians or older siblings.The children who go to the lake should prevent direct contact with lake’s water.These results call for the need to consider including a point of care screening tool for S. mansoni infections among preschool children as well as a prevention program targeting this age group in the study area. Keywords: Intestinal schistosomiasis prevalence, Pre-school children, Rwanda

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

BackgroundPoint‐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.ObjectivesTo 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 methodsWe searched the electronic databases MEDLINE, EMBASE, BIOSIS, MEDION, and Health Technology Assessment (HTA) without language restriction up to 30 June 2014.Selection criteriaWe 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 analysisTwo 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 resultsWe 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. haematobiumUrine reagent test strips versus microscopyCompared 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 assayCompared 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. mansoniCompared 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' conclusionsAmong 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.23 April 2019No update plannedOtherReliable evidence with clear conclusions. All eligible published studies found in the last search (30 Jun, 2014) were included.

Evaluation of circulating cathodic antigen (CCA) urine-cassette assay as a survey tool for Schistosoma mansoni in different transmission settings within Bugiri District, Uganda

Diagnosis of schistosomiasis at the point-of-care (POC) is a growing topic in neglected tropical disease research. There is a need for diagnostic tests which are affordable, sensitive, specific, user-friendly, rapid, equipment-free and delivered to those who need it, and POC is an important tool for disease mapping and guiding mass deworming. The aim of present study was to evaluate the relative diagnostic performance of two urine-circulating cathodic antigen (CCA) cassette assays, one commercially available and the other in experimental production, against results obtained using the standard Kato-Katz faecal smear method (six thick smears from three consecutive days), as a ‘gold-standard’, for Schistosoma mansoni infection in different transmission settings in Uganda. Our study was conducted among 500 school children randomly selected across 5 schools within Bugiri district, adjacent to Lake Victoria in Uganda. Considering results from the 469 pupils who provided three stool samples for the six Kato-Katz smears, 293 (76%) children had no infection, 109 (23%) were in the light intensity category, while 42 (9%) and 25 (5%) were in the moderate and heavy intensity categories respectively. Following performance analysis of CCA tests in terms of sensitivity, specificity, negative and positive predictive values, overall performance of the commercially available CCA test was more informative than single Kato-Katz faecal smear microscopy, the current operational field standard for disease mapping. The current CCA assay is therefore a satisfactory method for surveillance of S. mansoni in an area where disease endemicity is declining due to control interventions. With the recent resolution on schistosomiasis elimination by the 65th World Health Assembly, the urine POC CCA test is an attractive tool to augment and perhaps replace the Kato-Katz sampling within ongoing control programmes.

The Urine Circulating Cathodic Antigen (CCA) Dipstick: A Valid Substitute for Microscopy for Mapping and Point-Of-Care Diagnosis of Intestinal Schistosomiasis

BackgroundThe World Health Organization now recommends the provision of praziquantel treatment to preschool-aged children infected with schistosomiasis. For intestinal schistosomiasis the current operational field diagnostic standard is examination of a thick Kato-Katz smear by microscopy prepared from a single stool specimen, and although pragmatic, this methodology has well-known shortcomings. Here, as a potential alternative, the performance of the urine circulating cathodic antigen (CCA) dipstick test was assessed in terms of disease-mapping and point-of-care diagnosis for intestinal schistosomiasis in preschool-aged children. Our manuscript reports on findings at baseline and at the end of a one-year longitudinal treatment study.Methodology/Principal FindingsA total of 925 children (mean age 2.8 years) were initially recruited from six lakeshore villages representative of high, moderate and low levels of disease transmission. At baseline, all children were tested for intestinal schistosomiasis by microscopic examination of duplicate Kato-Katz smears prepared from a single stool faecal, by antigen detection with the urine CCA dipstick test and by serology with a commercially available ELISA test (as ‘gold-standard’) that measures host antibody titres to soluble egg antigens. As a point-of-care diagnosis, the urine CCA dipstick test achieved sensitivity and specificity values ranging from 52.5–63.2% and 57.7–75.6%, respectively, with faecal microscopy achieving very high specificities (>87%) but sensitivities as low as 16.7% in the low transmission setting.Conclusion/SignificanceThe urine CCA test was shown to be more effective than faecal microscopy especially in lower transmission settings. The diagnostic performance of this test was not significantly impacted by treatment history or co-infections with other intestinal helminths.

Notes on the use of urine-CCA dipsticks for detection of intestinal schistosomiasis in preschool children

Urine-dipstick diagnostic tests that detect schistosome circulating cathodic antigen (CCA) have the potential to provide more sensitive and rapid testing for intestinal schistosomiasis in field-based surveys; this is especially so when examining preschool children, from whom it may be difficult to obtain consecutive stool samples. To assess the performance of urine dipsticks, 569 preschool children from four villages along the shore of Lake Albert, Uganda, were screened for Schistosoma mansoni by Kato-Katz (K-K) examination of a single stool sample and CCA urine dipsticks. The prevalence of infection was 32.2% by K-K and 40.0% by CCA tests. Sensitivity and specificity were influenced by whether ‘trace’ results from the CCA test were characterised as positive or negative for infection with S. mansoni; ambiguities around this issue need to be resolved. Nevertheless, the CCA test showed particular promise for routine epidemiological screening in this setting.

Evaluation of Circulating Cathodic Antigen (CCA) Urine-Tests for Diagnosis of Schistosoma mansoni Infection in Cameroon

BackgroundThe Kato-Katz is the most common diagnostic method for Schistosoma mansoni infection. However, the day-to-day variability in host egg-excretion and its low detection sensitivity are major limits for its use in low transmission zones and after widespread chemotherapy. We evaluated the accuracy of circulating cathodic antigen (CCA) urine-assay as a diagnostic tool of S. mansoni. In comparison, a low sensitive CCA test (CCA-L) was assessed.MethodologyThe study was conducted in three settings: two foci with single S. mansoni infections (settings A and B), and one mixed S. mansoni – S. haematobium focus (setting C). Stool and urine samples were collected from school-children on three consecutive days. Triplicate Kato-Katz readings were performed per stool sample. Each urine sample was tested with one CCA and only the first urine sample was subjected to CCA-L. Urine samples were also examined for S. haematobium eggs using the filtration method and for microhaematuria using urine reagent strips. Overall, 625 children provided three stool and three urine samples.Principal FindingsConsidering nine Kato-Katz thick smears as ‘reference’ diagnostic test, the prevalence of S. mansoni was 36.2%, 71.8% and 64.0% in settings A, B and C, respectively. The prevalence of S. haematobium in setting C was 12.0%. The sensitivities of single Kato-Katz, CCA and CCA-L from the first stool or urine samples were 58%, 82% and 46% in setting A, 56.8%, 82.4% and 68.8% in setting B, and 49.0%, 87.7% and 55.5% in setting C. The respective specificities were 100%, 64.7% and 100%; 100%, 62.3% and 91.3%; and 100%, 42.5% and 92.0%. Mixed infection with S. haematobium did not influence the CCA test results for S. mansoni diagnosis.Conclusions/SignificanceUrine CCA revealed higher sensitivity than CCA-L and triplicate Kato-Katz, and produced similar prevalence as nine Kato-Katz. It seems an attractive method for S. mansoni diagnosis.

Evaluation of Urine CCA Assays for Detection of Schistosoma mansoni Infection in Western Kenya

Although accurate assessment of the prevalence of Schistosoma mansoni is important for the design and evaluation of control programs, the most widely used tools for diagnosis are limited by suboptimal sensitivity, slow turn-around-time, or inability to distinguish current from former infections. Recently, two tests that detect circulating cathodic antigen (CCA) in urine of patients with schistosomiasis became commercially available. As part of a larger study on schistosomiasis prevalence in young children, we evaluated the performance and diagnostic accuracy of these tests—the carbon test strip designed for use in the laboratory and the cassette format test intended for field use. In comparison to 6 Kato-Katz exams, the carbon and cassette CCA tests had sensitivities of 88.4% and 94.2% and specificities of 70.9% and 59.4%, respectively. However, because of the known limitations of the Kato-Katz assay, we also utilized latent class analysis (LCA) incorporating the CCA, Kato-Katz, and schistosome-specific antibody results to determine their sensitivities and specificities. The laboratory-based CCA test had a sensitivity of 91.7% and a specificity of 89.4% by LCA while the cassette test had a sensitivity of 96.3% and a specificity of 74.7%. The intensity of the reaction in both urine CCA tests reflected stool egg burden and their performance was not affected by the presence of soil transmitted helminth infections. Our results suggest that urine-based assays for CCA may be valuable in screening for S. mansoni infections.

Epidemiology and control of intestinal schistosomiasis on the Sesse Islands, Uganda: integrating malacology and parasitology to tailor local treatment recommendations

BackgroundIntestinal schistosomiasis is often widespread among the populations living around Lake Victoria and on its islands. The Sesse Island group (containing some 84 islands), however, is typically assumed to be a low prevalence zone, with limited transmission, but has never been surveyed in detail. Here, we present a rapid mapping assessment, bringing together snail and parasite information, at 23 sites for the presence of intermediate host snails and at 61 sites for the prevalence of intestinal schistosomiasis in school-aged children (N = 905). Two different diagnostic tools were used and compared at 45 of these sites: Kato-Katz thick faecal smears and circulating cathodic antigen (CCA) urine dipsticks.ResultsBiomphalaria snails were found at 11 sites but in low numbers; none was found shedding schistosome cercariae. At 22 out of the 45 sites, local prevalence by urine and/or stool diagnostics was in excess of 50%, although mean prevalence of intestinal schistosomiasis overall was 34.6% (95% confidence intervals (CI) = 31.0-38.3%) by Kato-Katz and 46.5% (95% CI = 42.7-50.4%) by CCA if 'trace' reactions were considered infection-positive (if considered infection-negative, mean prevalence was 28.1% (95% CI = 24.7-31.7%)). Diagnostic congruence between CCA and Kato-Katz was poor and significant discordance in estimated prevalence by location was found, with each often inferring different mass drug administration regimes.ConclusionsAccurate estimation of schistosome prevalence is important for determining present and future treatment needs with praziquantel; the wide range of schistosome prevalence across the Sesse Island group requires a treatment regime largely tailored to each island. In high prevalence locations, further malacological sampling is required to confirm the extent of local transmission, especially on the northern islands within the group. The observation that different diagnostic tests can provide varying results in terms of estimating prevalence by location, and hence change treatment recommendations, suggests that care must be taken in interpreting raw prevalence data. In particular, further research into the reasons for the differences in the poorer performance of the CCA test should be pursued.

Performance of circulating cathodic antigen (CCA) urine-dipsticks for rapid detection of intestinal schistosomiasis in schoolchildren from shoreline communities of Lake Victoria

For disease surveillance and mapping within large-scale control programmes, RDTs are becoming popular. For intestinal schistosomiasis, a commercially available urine-dipstick which detects schistosome circulating cathodic antigen (CCA) in host urine is being increasingly applied, however, further validation is needed. In this study, we compared the CCA urine-dipstick test against double thick Kato-Katz faecal smears from 171 schoolchildren examined along the Tanzanian and Kenyan shorelines of Lake Victoria. Diagnostic methods were in broad agreement; the mean prevalence of intestinal schistosomiasis inferred by Kato-Katz examination was 68.6% (95% confidence intervals (CIs) = 60.7-75.7%) and 71.3% (95% CIs = 63.9-78.8%) by CCA urine-dipsticks. There were, however, difficulties in precisely 'calling' the CCA test result, particularly in discrimination of 'trace' reactions as either putative infection positive or putative infection negative, which has important bearing upon estimation of mean infection prevalence; considering 'trace' as infection positive mean prevalence was 94.2% (95% CIs = 89.5-97.2%). A positive association between increasing intensity of the CCA urine-dipstick test band and faecal egg count was observed. Assigning trace reactions as putative infection negative, overall diagnostic sensitivity (SS) of the CCA urine-dipstick was 87.7% (95% CIs = 80.6-93.0%), specificity (SP) was 68.1% (95% CIs = 54.3-80.0%), positive predictive value (PPV) was 86.1% (95% CIs = 78.8-91.7%) and negative predictive value (NPV) was 71.1% (95% CIs = 57.2-82.8%). To assist in objective defining of the CCA urine-dipstick result, we propose the use of a simple colour chart and conclude that the CCA urine-dipstick is a satisfactory alternative, or supplement, to Kato-Katz examination for rapid detection of intestinal schistosomiasis.

Use of circulating cathodic antigen strips for the diagnosis of urinary schistosomiasis

Rapid diagnostic tests are needed for the implementation and monitoring of national schistosomiasis control programmes. The field applicability of the circulating cathodic antigen (CCA) urine reagent strip for the diagnosis of Schistosoma haematobium infection was evaluated among 265 pre- and primary schoolchildren aged 2-19 years in a rural area of Zimbabwe. The CCA strip was compared with egg detection before and six weeks after treatment with praziquantel. Pre-treatment prevalence (overall 40.4%) and intensity of infection, as determined by egg counts, increased with age. CCA and parasitological results were significantly correlated (P<0.001), although concordance was slight (kappa=0.21). Discordant results were mainly attributable to CCA-positive, egg-negative individuals. Correlations and levels of agreement improved significantly with age (P<0.001, kappa=0.40) and intensity of infection (P<0.001). Praziquantel treatment led to 'cure' in 90.9% and 70.5% of children as measured by the egg detection and CCA methods, respectively. An arbitrary gold standard was constructed that included both CCA and egg detection results. Using this standard, the sensitivities of the CCA test were 88.2% and 95.8%, respectively, for pre- and post-treatment results. The improved version that is field applicable now has an acceptable role in the field diagnosis of S. haematobium.

Use of circulating cathodic antigen (CCA) dipsticks for detection of intestinal and urinary schistosomiasis

An evaluation of a commercially available antigen capture dipstick that detects schistosome circulating cathodic antigen (CCA) in urine was conducted in representative endemic areas for intestinal and urinary schistosomiasis in Uganda and Zanzibar, respectively. Under field-based conditions, the sensitivity (SS) and specificity (SP) of the dipstick was 83 and 81% for detection of Schistosoma mansoni infections while positive predictive (PPV) and negative predictive values (NPV) were 84%. Light egg-positive infections were sometimes CCA-negative while CCA-positives included egg-negative children. A positive association between faecal egg output and intensity of CCA test band was observed. Estimating prevalence of intestinal schistosomiasis by school with dipsticks was highly correlated ( r = 0.95) with Kato-Katz stool examinations, typically within ±8.5%. In Zanzibar, however, dipsticks totally failed to detect S. haematobium despite examining children with egg-patent schistosomiasis. This was also later corroborated by further surveys in Niger and Burkina Faso. Laboratory testing of dipsticks with aqueous adult worm lysates from several reference species showed correct functioning, however, dipsticks failed to detect CCA in urine from S. haematobium-infected hamsters. While CCA dipsticks are a good alternative, or complement, to stool microscopy for field diagnosis of intestinal schistosomiasis, they have no proven value for field diagnosis of urinary schistosomiasis. At approximately US $2.6 per dipstick, they are presently too expensive to be cost-effective for wide scale use in disease mapping surveys unless Lot Quality Assurance Sampling (LQAS) strategies are developed.