Dataset Information

Countrywide Reassessment of Schistosoma mansoni Infection in Burundi Using a Urine-Circulating Cathodic Antigen Rapid Test: Informing the National Control Program.

ABSTRACT: Following implementation of the national control program, a reassessment of Schistosoma mansoni prevalence was conducted in Burundi to determine the feasibility of moving toward elimination. A countrywide cluster-randomized cross-sectional study was performed in May 2014. At least 25 schools were sampled from each of five eco-epidemiological risk zones for schistosomiasis. Fifty randomly selected children 13-14 years of age per school were included for a single urine-circulating cathodic antigen (CCA) rapid test and, in a subset of schools, for duplicate Kato-Katz slide preparation from a single stool sample. A total of 17,331 children from 347 schools were tested using CCA. The overall prevalence of S. mansoni infection, when CCA trace results were considered negative, was 13.5% (zone range [zr] = 4.6-17.8%), and when CCA trace results were considered positive, it was 42.8% (zr = 34.3-49.9%). In 170 schools, prevalence of this infection determined using Kato-Katz method was 1.5% (zr = 0-2.7%). The overall mean intensity of S. mansoni infection determined using Kato-Katz was 0.85 eggs per gram (standard deviation = 10.86). A majority of schools (84%) were classified as non-endemic (prevalence = 0) using Kato-Katz; however, a similar proportion of schools were classified as endemic when CCA trace results were considered negative (85%) and nearly all (98%) were endemic when CCA trace results were considered positive. The findings of this nationwide reassessment using a CCA rapid test indicate that Schistosoma infection is still widespread in Burundi, although its average intensity is probably low. Further evidence is now needed to determine the association between CCA rapid test positivity and low-intensity disease transmission.

SUBMITTER: Ortu G

PROVIDER: S-EPMC5361543 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Countrywide Reassessment of <i>Schistosoma mansoni</i> Infection in Burundi Using a Urine-Circulating Cathodic Antigen Rapid Test: Informing the National Control Program.

Ortu Giuseppina G Ndayishimiye Onésime O Clements Michelle M Kayugi Donatien D Campbell Carl H CH Lamine Mariama Sani MS Zivieri Antonio A Magalhaes Ricardo Soares RS Binder Sue S King Charles H CH Fenwick Alan A Colley Daniel G DG Jourdan Peter Mark PM

The American journal of tropical medicine and hygiene 20170301 3

Following implementation of the national control program, a reassessment of <i>Schistosoma mansoni</i> prevalence was conducted in Burundi to determine the feasibility of moving toward elimination. A countrywide cluster-randomized cross-sectional study was performed in May 2014. At least 25 schools were sampled from each of five eco-epidemiological risk zones for schistosomiasis. Fifty randomly selected children 13-14 years of age per school were included for a single urine-circulating cathodic ...[more]

PMID: 28115675

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Project description:BackgroundPromising results have been reported for a urine circulating cathodic antigen (CCA) test for the diagnosis of Schistosoma mansoni. We assessed the accuracy of a commercially available CCA cassette test (designated CCA-A) and an experimental formulation (CCA-B) for S. mansoni diagnosis.MethodologyWe conducted a cross-sectional survey in three settings of Côte d'Ivoire: settings A and B are endemic for S. mansoni, whereas S. haematobium co-exists in setting C. Overall, 446 children, aged 8-12 years, submitted multiple stool and urine samples. For S. mansoni diagnosis, stool samples were examined with triplicate Kato-Katz, whereas urine samples were tested with CCA-A. The first stool and urine samples were additionally subjected to an ether-concentration technique and CCA-B, respectively. Urine samples were examined for S. haematobium using a filtration method, and for microhematuria using Hemastix dipsticks.Principal findingsConsidering nine Kato-Katz as diagnostic 'gold' standard, the prevalence of S. mansoni in setting A, B and C was 32.9%, 53.1% and 91.8%, respectively. The sensitivity of triplicate Kato-Katz from the first stool and a single CCA-A test was 47.9% and 56.3% (setting A), 73.9% and 69.6% (setting B), and 94.2% and 89.6% (setting C). The respective sensitivity of a single CCA-B was 10.4%, 29.9% and 75.0%. The ether-concentration technique showed a low sensitivity for S. mansoni diagnosis (8.3-41.0%). The specificity of CCA-A was moderate (76.9-84.2%); CCA-B was high (96.7-100%). The likelihood of a CCA-A color reaction increased with higher S. mansoni fecal egg counts (odds ratio: 1.07, p<0.001). A concurrent S. haematobium infection or the presence of microhematuria did not influence the CCA-A test results for S. mansoni diagnosis.Conclusion/significanceCCA-A showed similar sensitivity than triplicate Kato-Katz for S. mansoni diagnosis with no cross-reactivity to S. haematobium and microhematuria. The low sensitivity of CCA-B in our study area precludes its use for S. mansoni diagnosis.

Project description:BackgroundThe Kato-Katz technique is widely used for the diagnosis of Schistosoma mansoni, but shows low sensitivity in light-intensity infections. We assessed the accuracy of a commercially available point-of-care circulating cathodic antigen (POC-CCA) cassette test for the diagnosis of S. mansoni in preschool-aged children before and after praziquantel administration.MethodologyA 3-week longitudinal survey with a treatment intervention was conducted in Azaguié, south Côte d'Ivoire. Overall, 242 preschoolers (age range: 2 months to 5.5 years) submitted two stool and two urine samples before praziquantel administration, and 86 individuals were followed-up posttreatment. Stool samples were examined with duplicate Kato-Katz thick smears for S. mansoni. Urine samples were subjected to POC-CCA cassette test for S. mansoni, and a filtration method for S. haematobium diagnosis.Principal findingsBefore treatment, the prevalence of S. mansoni, as determined by quadruplicate Kato-Katz, single CCA considering 'trace' as negative (t-), and single CCA with 'trace' as positive (t+), was 23.1%, 34.3% and 64.5%, respectively. Using the combined results (i.e., four Kato-Katz and duplicate CCA(t-)) as diagnostic 'gold' standard, the sensitivity of a single Kato-Katz, a single CCA(t-) or CCA(t+) was 28.3%, 69.7% and 89.1%, respectively. Three weeks posttreatment, the sensitivity of a single Kato-Katz, single CCA(t-) and CCA(t+) was 4.0%, 80.0% and 84.0%, respectively. The intensity of the POC-CCA test band reaction was correlated with S. mansoni egg burden (odds ratio?=?1.2, p?=?0.04).Conclusions/significanceA single POC-CCA cassette test appears to be more sensitive than multiple Kato-Katz thick smears for the diagnosis of S. mansoni in preschool-aged children before and after praziquantel administration. The POC-CCA cassette test can be recommended for the rapid identification of S. mansoni infections before treatment. Additional studies are warranted to determine the usefulness of POC-CCA for assessing drug efficacy and monitoring the impact of control interventions.

Project description:BackgroundThe Kato-Katz thick smear is the standard test for the diagnosis of Schistosoma mansoni infection, but the sensitivity of this technique is low. As an alternative, (CCA) strip test has been evaluated with the conclusion that it may replace the Kato-Katz method in areas where prevalences are moderate or high. Therefore, this study was undertaken to evaluate the performance of the CCA strip test in the diagnosis and monitoring of S. mansoni infection in Sudan.Methodology489 stool and urine samples were collected from school children in endemic area of Sudan to determine the validity of CCA strip test based on duplicate Kato-Katz thick smear technique. Additional, 118 samples from known non schistosome-endemic area were collected to assess the CCA cross reactivity with other pathogens rather than schistosomiasis. The stability of CCA in urine samples was determined by consecutive examination of 40 positive CCA urine samples. 81 samples were used to evaluate the CCA strip test for the assessment of cure one week, three weeks and six weeks post Praziquantel treatment.Principal findingsAssuming parasitological test results as the gold standard, the sensitivity, specificity, positive predictive and negative predictive values of the CCA test were 96%, 85.4%, 78.5% and 97.5% respectively. There was no cross reactivity with other pathogens. The CCA strip test showed high accuracy in monitoring of treatment 93.8% and 100% after three and six weeks of administration of Praziquantel respectively. The stability of the CCA for long time in the urine revealed a safety transportation and shipment of the samples whenever it demanded.Conclusion/significanceThe uses of urine CCA strip test in the field would provide more accurate information on the epidemiology and monitoring of the Schistosoma mansoni infection in endemic areas of schistosomiasis than the conventional parasitological method. Moreover, The stability of CCA in urine samples confirms a safety transportation period of the samples whenever it required.

Project description:BackgroundDetermining Schistosoma mansoni infection rate and intensity is challenging due to the low sensitivity of the Kato-Katz (KK) test that underestimates the true disease prevalence. Circulating cathodic antigen (CCA) excreted in urine is constantly produced by adult worms and has been used as the basis of a simple, non-invasive point of care test (POC-CCA) for Schistosoma mansoni infections. Although the abundance of CCA in urine is proportional to worm burden, the POC-CCA test is marketed as a qualitative test, making it difficult to investigate the wide range of infection intensities. This study was designed to compare the prevalence and intensity of S. mansoni by KK and POC-CCA and quantify, on fresh and frozen (<-20°C) urine samples, CCA using the visual scores and the ESEquant LR3 reader.MethodologyStool and urine samples were collected from 759 school-aged children. The prevalence and intensity of S. mansoni were determined using KK and POC-CCA. The degree of the positivity of POC-CCA was estimated by quantifying CCA on fresh and frozen urine samples using visual scores and strip reader. The prevalence, the infection intensity as well the relative amounts of CCA were compared.ResultsThe S. mansoni infection rates inferred from POC-CCA and KK were 40.7% and 9.4% respectively. Good correlations were observed between infection intensities recorded by; i) the reader and visual scoring system on fresh (Rho = 0.89) and frozen samples (Rho = 0.97), ii) the reader on fresh urine samples and KK (epg) (Rho = 0.44). Nevertheless, 238 POC-CCA positive children were negative for KK, and sixteen of them had high levels of CCA. The correlation between results from the reader on fresh and frozen samples was good (Rho = 0.85). On frozen samples, CCA was not detected in 55 samples that were positive in fresh urine samples.ConclusionThis study confirmed the low sensitivity of KK and the high capacity of POC-CCA to provide reliable data on the prevalence and intensity of S. mansoni infections. The lateral flow reader enabled accurate quantification of CCA under field conditions on fresh and frozen urine samples with less time and effort than KK.

Project description:BACKGROUND:Intervention guidelines against Schistosoma mansoni are based on the Kato-Katz technique. However, Kato-Katz thick smears show low sensitivity, especially for light-intensity infections. The point-of-care circulating cathodic antigen (POC-CCA) is a promising rapid diagnostic test detecting antigen output of living worms in urine and results are reported as trace, 1+, 2+, and 3+. The use of POC-CCA for schistosomiasis mapping, control, and surveillance requires translation of the Kato-Katz prevalence thresholds into POC-CCA relative treatment cut-offs. Furthermore, the infection status of egg-negative but antigen-positive individuals and the intensity-dependent sensitivity of POC-CCA should be estimated to determine its suitability for verification of disease elimination efforts. METHODOLOGY:We used data from settings in Africa and the Americas characterized by a wide range of S. mansoni endemicity. We estimated infection intensity-dependent sensitivity and specificity of each test at the unit of the individual, using a hierarchical Bayesian egg-count model that removes the need to define a 'gold' standard applied to data with multiple Kato-Katz thick smears and POC-CCA urine cassette tests. A simulation study was carried out based on the model estimates to assess the relation of the two diagnostic tests for different endemicity scenarios. PRINCIPAL FINDINGS:POC-CCA showed high specificity (> 95%), and high sensitivity (> 95%) for moderate and heavy infection intensities, and moderate sensitivity (> 75%) for light infection intensities, and even for egg-negative but antigen-positive infections. A 10% duplicate slide Kato-Katz thick smear prevalence corresponded to a 15-40% prevalence of ? trace-positive POC-CCA, and 10-20% prevalence of ? 1+ POC-CCA. The prevalence of ? 2+ POC-CCA corresponded directly to single slide Kato-Katz prevalence for all prevalence levels. CONCLUSIONS/SIGNIFICANCE:The moderate sensitivity of POC-CCA, even for very light S. mansoni infections where the sensitivity of Kato-Katz is very low, and the identified relationship between Kato-Katz and POC-CCA prevalence thresholds render the latter diagnostic tool useful for surveillance and initial estimation of elimination of S. mansoni. For prevalence below 10% based on a duplicate slide Kato-Katz thick smear, we suggest using POC-CCA including trace results to evaluate treatment needs and propose new intervention thresholds that need to be validated in different settings.

Project description:BackgroundTwo Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This 'gold standard' has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings.Method/principle findingsIn a high S. mansoni endemic area of Uganda, three days of consecutive stool samples were collected from primary school-aged children (six - 12 years) at five time-points in year one: baseline, one-week-post-, four-weeks-post-, six-months-post-, and six-months-one-week-post-praziquantel and three time-points in years two and three: pre-, one-week-post- and four-weeks-post-praziquantel-treatment/retreatment (n = 1065). Two Kato-Katzs were performed on each stool. In parallel, one urine sample was collected and a single POC-CCA evaluated per child at each time-point in year one (n = 367). At baseline, diagnosis by two Kato-Katzs (sensitivity = 98.6%) or one POC-CCA (sensitivity = 91.7%, specificity = 75.0%) accurately predicted S. mansoni infections. However, one year later, a minimum of three Kato-Katzs, and two years later, five Kato-Katzs were required for accurate diagnosis (sensitivity >90%) and drug-efficacy evaluation. The POC-CCA was as sensitive as six Kato-Katzs four-weeks-post and six-months-post-treatment, if trace readings were classified as positive.Conclusions/significanceSix Kato-Katzs (two/stool from three stools) and/or one POC-CCA are required for M&E or drug-efficacy studies. Although unable to measure egg reduction rates, one POC-CCA appears to be more sensitive than six Kato-Katzs at four-weeks-post-praziquantel (drug efficacy) and six-months-post-praziquantel (M&E).

Project description: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.ClinicalTrials.gov NCT00215267.

Project description:BACKGROUND:Schistosomiasis is a neglected tropical disease caused by Schistosoma parasites. Intervention relies on identifying high-risk regions, yet rapid Schistosoma diagnostics (Kato-Katz stool assays (KK) and circulating cathodic antigen urine assays (CCA)) yield different prevalence estimates. We mapped S. mansoni prevalence and delineated at-risk regions using a survey of schoolchildren in Rwanda, where S. mansoni is an endemic parasite. We asked if different diagnostics resulted in disparities in projected infection risk. METHODS:Infection data was obtained from a 2014 Rwandan school-based survey that used KK and CCA diagnostics. Across 386 schools screened by CCA (N = 19,217). To allow for uncertainty when interpreting ambiguous CCA trace readings, which accounted for 28.8% of total test results, we generated two presence-absence datasets: CCA trace as positive and CCA trace as negative. Samples (N = 9,175) from 185 schools were also screened by KK. We included land surface temperature (LST) and the Normalized Difference Vegetation and Normalized Difference Water Indices (NDVI, NDWI) as predictors in geostatistical regressions. FINDINGS:Across 8,647 children tested by both methods, prevalence was 35.93% for CCA trace as positive, 7.21% for CCA trace as negative and 1.95% for KK. LST was identified as a risk factor using KK, whereas NDVI was a risk factor for CCA models. Models predicted high endemicity in Northern and Western regions of Rwanda, though the CCA trace as positive model identified additional high-risk areas that were overlooked by the other methods. Estimates of current burden for children at highest risk (boys aged 5-9 years) varied by an order of magnitude, with 671,856 boys projected to be infected by CCA trace as positive and only 60,453 projected by CCA trace as negative results. CONCLUSIONS:Our findings show that people in Rwanda's Northern, Western and capital regions are at high risk of S. mansoni infection. However, variation in identification of environmental risk factors and delineation of at-risk regions using different diagnostics likely provides confusing messages to disease intervention managers. Further research and statistical analyses, such as latent class analysis, can be used to improve CCA result classification and assess its use in guiding treatment regimes.

Dataset Information

Countrywide Reassessment of Schistosoma mansoni Infection in Burundi Using a Urine-Circulating Cathodic Antigen Rapid Test: Informing the National Control Program.

Publications

Countrywide Reassessment of <i>Schistosoma mansoni</i> Infection in Burundi Using a Urine-Circulating Cathodic Antigen Rapid Test: Informing the National Control Program.

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