Accuracy of Urine Circulating Cathodic Antigen (CCA) Test for Schistosoma mansoni Diagnosis in Different Settings of Côte d'Ivoire

Background Promising 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. Methodology We 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 Findings Considering 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/Significance CCA-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.


Introduction
There is growing awareness, political commitment, and financial resources to control neglected tropical diseases (NTDs) [1][2][3]. Preventive chemotherapy, that is the repeated large-scale administration of drugs to at-risk populations, has become the key strategy for the control of several NTDs, including schistosomiasis [3][4][5]. Although the issue of diagnosis has received only token attention in the current era of preventive chemotherapy, its importance must be emphasized for rapid identification of highrisk communities warranting regular treatment, appraisal of drug efficacy, monitoring progress of control interventions, and improved patient management [6][7][8]. With regard to intestinal schistosomiasis due to Schistosoma mansoni and S. japonicum, the Kato-Katz technique is the most widely used diagnostic approach in epidemiological surveys [8,9]. Although the Kato-Katz technique is relatively simple to perform, it requires a minimum of equipment (i.e., microscope, chemicals, and test kit material) and well-trained laboratory technicians [10]. Moreover, a shortcoming of the Kato-Katz technique is the only low-to-moderate sensitivity for S. mansoni diagnosis in low endemicity areas [11][12][13]. Hence, multiple Kato-Katz thick smears are required to enhance sensitivity [14], but this poses operational challenges and strains financial resources.
The detection of circulating antigen of S. mansoni in urine has been suggested as an alternative to the Kato-Katz technique [15][16][17]. Indeed, both circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) can be detected in sera and urine of individuals infected with S. mansoni [18]. Both antigen-detecting assays are sensitive and specific and correlate with the presence and intensity of infection [19]. Antigen detection in urine using a rapid diagnostic test (RDT) based on an enzyme-linked immunosorbent assay (ELISA) technique is potentially useful and noninvasive and could change the management of infected individuals, particularly at the peripheral level in endemic countries where microscopes and qualified laboratory technicians are often not available [6,7]. A point-of-contact (POC) CCA urine test has been developed for the diagnosis of S. mansoni [15], which is now commercially available as a RDT in cassette form. In view of promising results obtained thus far [17,20,21], the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) initiated a multi-country study to assess the accuracy of a commercially available CCA cassette test for the diagnosis of S. mansoni.
The study reported here is part of this multi-country evaluation. We assessed the accuracy of a commercially available urine CCA cassette test (designated CCA-A) for S. mansoni diagnosis. Additionally, we employed an experimental formulation of the test (CCA-B). Nine Kato-Katz thick smears from each participant served as diagnostic 'gold' standard. In addition, our team employed the ether-concentration method on sodium acetateacetic acid-formalin (SAF)-fixed stool samples for the diagnosis of S. mansoni, urine filtration for the identification of S. haematobium eggs, and Hemastix dipsticks for the detection of microhematuria in urine. The study was carried out in south Côte d'Ivoire, in three settings where S. mansoni is endemic at different levels, whereas S. haematobium co-exists in one of the settings.

Ethics Statement
The study protocol was approved by the institutional research commission of the Swiss Tropical and Public Health Institute (Basel, Switzerland) and was cleared by the ethics committees of Basel (EKBB; reference no. 377/09) and Côte d'Ivoire (reference no. 1993 MSHP/CNER). District health and education authorities, village chiefs, parents/legal guardians, and participating children were informed about the purpose and procedures of the study. Parents/legal guardians provided written informed consent for their children to participate. Additionally, all children assented orally. Participation was voluntary and children could withdraw at any time without further obligation. All parasitological results were coded and treated confidentially. At the end of the study, children attending the schools involved in this study were treated with praziquantel (single 40 mg/kg oral dose) and albendazole (single 400 mg oral dose) free of charge, irrespective of the child's helminth infection status [22].

Study Area and Population
In October/November 2010, we carried out a cross-sectional survey in three epidemiological settings in the district of Azaguié, south Côte d'Ivoire. Azaguié is located approximately 40 km north of Abidjan, the economic capital of Côte d'Ivoire. The settings were selected after a pre-screening done in 10 schools. For the pre-screening, in each school, 25 children were randomly selected. All children attending grades 3-5 (CE1, CE2, and CM1) were given a unique number, lots including all numbers were closed and placed in a box, and finally 25 lots per school were drawn. The selected children provided a single stool and a single urine sample, which were examined for S. mansoni with triplicate Kato-Katz thick smears and S. haematobium with a single filtration, respectively. Based on this pre-screening, we selected the following sites, according to SCORE guidelines: setting A, low S. mansoni endemicity (i.e., prevalence: 10-24%); setting B, moderate S. mansoni endemicity (prevalence: 25-49%); and setting C, coendemic for S. mansoni and S. haematobium.

Sample Size
According to the literature, a single Kato-Katz thick smear for diagnosis of S. mansoni in low endemicity settings has a sensitivity of only 20-30% [23,24]. However, since our study was to be carried out in both low and moderate endemicity settings, we assumed that a single Kato-Katz thick smear has a maximum sensitivity of 60%. The sensitivity of the CCA test is reported to be 80% or higher [15,25]. Using these sensitivity estimates, a significance level of 5%, and a power of 80%, our sample size of complying children was calculated at 90. Assuming a compliance of 70% for the submission of each of three requested stool samples, the number of children to be included in each study setting was at least 199. To achieve this sample size, we selected by computer-based randomization 220 children aged 8-12 years from readily available school lists of Abbé-Begnini (setting A), Azaguié Gare (setting B), and M'Bromé/Makouguié (setting C).

Field Procedures
The purpose and procedures of the study were explained to the village authorities, the school directors, and the teachers of the selected schools. Teachers were invited to prepare class lists,

Author Summary
We aimed to assess the accuracy of a commercially available rapid diagnostic test for the detection of an infection with the blood fluke Schistosoma mansoni in urine. In total, 446 school children from three different settings of south Cô te d'Ivoire provided three stool and three urine samples. Stool samples were examined with the widely used Kato-Katz technique and analyzed with a microscope for S. mansoni eggs. Urine samples were examined with a filtration method for S. haematobium eggs and with a rapid diagnostic test for S. mansoni that is based on detecting circulating cathodic antigens (CCA). We used a commercially available test (designated CCA-A) and an experimental formulation (CCA-B). Examination of nine Kato-Katz thick smears per child revealed a prevalence of S. mansoni in the three settings of 32.9%, 53.1%, and 91.8%. The sensitivity of triplicate Kato-Katz from the first stool sample was comparable to a single CCA-A (47.9-94.2% vs. 56.3-89.6%), and significantly higher than the sensitivity of a single CCA-B test (10.4-75.0%). CCA-A showed a considerably lower specificity than CCA-B (76.9-84.2% vs. 96.7-100%). In the settings studied in south Cô te d'Ivoire, the CCA-A test holds promise for the diagnosis of S. mansoni, whereas results with CCA-B were suboptimal.
Accuracy of CCA Test for S. mansoni Diagnosis www.plosntds.org including names, sex, and age of the children attending grades 3-5. Next, the study was explained to the children in lay terms and they were provided with an information and consent sheet with further details of the study and children and parents' rights. Children who submitted a written informed consent from their parents/guardians and assented orally themselves were given a 125 ml plastic container labeled with a unique identifier (ID). Children were invited to return the containers filled with a fresh lime-sized morning stool sample the following day. Upon collection of the filled container, a new empty container was handed out for stool collection on the next day. This procedure was repeated over a week until most children had submitted a total of three stool samples. Each day, between 10:00 and 12:00 hours, participating children were provided with another empty container labeled with the respective ID for collection of urine samples.

Laboratory Procedures
Stool and urine samples were transferred to a laboratory at the Université de Cocody and processed the same day. From each stool sample, triplicate Kato-Katz thick smears were prepared, using 41.7 mg templates, following standard protocols [9]. In brief, triplicate Kato-Katz thick smears were prepared on microscope slides, labeled with a child's ID plus letter A, B, or C. Slides were allowed to clear for at least 30 min before quantitative examination under a microscope by experienced laboratory technicians. The number of S. mansoni and other helminth eggs (e.g., Ascaris lumbricoides, hookworm, and Trichuris trichiura) was counted and recorded for each species separately. For quality control, 10% of the Kato-Katz thick smears were re-examined by a senior technician.
In addition, from the second day stool sample, ,1 g of feces was weighed into plastic vials containing 10 ml of a SAF solution. Within 8 weeks, the SAF-fixed stool samples were processed with the ether-concentration method, following a standard protocol [12,26]. In brief, the stool-SAF solution was rigorously shaken and then poured through medical gauze placed on a plastic funnel into a conical glass tube. The conical tubes were centrifuged for 1 min at 5006 g. Subsequently, the supernatant was discarded and 7 ml of 0.85% sodium chloride (NaCl) solution and 2-3 ml ether were added to the pellet. Tubes were closed with a rubber stopper, manually shaken for ,30 sec and then centrifuged for 5 min at 5006g. This procedure leads to the separation of the suspension in four layers. The three top layers were discarded and the complete sediment layer was placed on a microscope slide, covered with a slip and subsequently examined under a microscope for helminth eggs (i.e., S. mansoni and soil-transmitted helminths) and intestinal protozoon cysts.
All urine samples were subjected to CCA-A (batch 32727) on the day of sample collection. The first urine sample was additionally subjected to CCA-B (batch 32686). Both CCA urine cassette assays were obtained from Rapid Medical Diagnostics (Pretoria, South Africa) and performed at ambient temperature, following the manufacturer's instructions. Briefly, one drop of urine was added to the well of the testing cassette and allowed to absorb. Once fully absorbed, one drop of buffer (provided with the CCA test kits) was added. The test results were read 20 min after adding the buffer. In case the control bands did not develop, the test was considered as invalid. Valid tests were scored as either negative or positive, the latter further stratified into 1+, 2+, or 3+ according to the visibility of the color reaction. All tests were read independently by two blinded investigators and in case of discordant results discussed with a third independent investigator until agreement was reached.
In addition to the CCA cassettes, each urine sample was subjected to a filtration method for S. haematobium egg counts and to a Hemastix dipstick (Siemens Healthcare Diagnostics GmbH; Eschborn, Germany) for microhematuria assessment on the day of sample collection. In brief, samples were shaken, and 10 ml of urine filtered through a 13-mm diameter small meshed filter (20 mm; Sefar AG; Heiden, Switzerland), which was then placed on a labeled slide and examined under a microscope for S. haematobium eggs [8]. For appraisal of microhematuria, a Hemastix dipstick was soaked in urine, left in the open air for 1 min, before scoring according to the manufacturer's instructions.

Statistical Analysis
Data were entered twice in a Microsoft Excel spreadsheet, transferred in EpiInfo version 6.4 (Centers for Disease Control and Prevention; Atlanta, GA, USA) and validated. Statistical analyses were done with STATA version 10 (Stata Corp.; College Station, TX, USA).
Only those children who had complete data records were included in the final analysis (i.e., nine Kato-Katz thick smears, a single ether-concentration, three CCA-A, one CCA-B, three urine filtrations, and three Hemastix dipsticks). To obtain a standardized measure of infection intensity, expressed as eggs per gram of stool (EPG), for each individual, we calculated the arithmetic mean S. mansoni fecal egg counts (FECs) from the nine Kato-Katz thick smears and multiplied by a factor 24. Infection intensity of S. mansoni was classified into light (1-99 EPG), moderate (100-399 EPG), and heavy ($400 EPG). Egg counts of S. haematobium were utilized to stratify into light (1-49 eggs/10 ml of urine) and heavy infection intensities ($50 eggs/10 ml of urine) [4].
As proposed by the SCORE secretariat, the results from nine Kato-Katz thick smears were considered our 'gold' standard. We determined the sensitivity (proportion of true-positives detected by the test) and specificity (proportion of true-negatives detected by the test) of single and multiple tests. As with some of our previous work, we used a second 'gold' standard by considering a positive test result (regardless of the test) as true-positive [29,30]. Hence, we combined results from all tests (i.e., nine Kato-Katz thick smears plus triplicate CCA-A, one CCA-B, and one ether-concentration) and therefore maximized specificity.
We employed an ordinal logistic regression approach, which is an extension of the general linear model to ordinal categorical outcomes to assess the correlation between CCA-A and CCA-B color reaction categories and S. mansoni FECs. The arithmetic mean FEC of three Kato-Katz thick smears per stool sample per day served as continuous explanatory variable, whereas the color reaction of the CCA test was considered as categorical outcome. This statistical procedure was also used to compare between the CCA test results considered as categorical outcome, and different infection intensity categories of S. mansoni (i.e., light, moderate, and heavy) utilized as categorical explanatory variables.
A logistic regression was performed to assess the association between CCA-A and CCA-B test results, expressed as binary outcome variable (negative/positive) with S. haematobium egg count as continuous explanatory variable and mircohematuria as categorical explanatory variable among children without a S. mansoni infection.
Non-overlapping 95% confidence intervals (CI) or p-val-ues#0.05 were considered as statistical significance. Figure 1 shows the adherence of school children to provide multiple stool and urine samples for a suite of diagnostic tests for detection of S. mansoni and S. haematobium infection. Overall, 674 school children aged 8-12 years were enrolled with slightly more boys than girls (343 vs. 331). The number of children in settings A, B and C was 234, 220 and 220, respectively. At least one stool or one urine sample was provided by 223, 178 and 206 children in settings A, B and C, respectively. Overall, 465 children submitted three stool samples, which were subjected to triplicate Kato-Katz thick smears. Results from a single ether-concentration method were available for 555 children. Three CCA-A test results were available for 489 children, whereas 545 children had the first urine sample additionally subjected to a CCA-B test. Finally, three urine filtrations for S. haematobium diagnosis and three Hemastix dipstick tests for appraisal of microhematuria were done for 489 children.

Study Adherence
Results on three stool samples (examined with nine Kato-Katz thick smears and a single ether-concentration) and three urine samples (examined with three CCA-A, one CCA-B, three urine filtrations and three Hemastix dipsticks) were available from a total of 446 children. Among them 48.7% (n = 217) were boys and the Accuracy of CCA Test for S. mansoni Diagnosis www.plosntds.org median age of the cohort was 10 years. All further analysis focused on this cohort of children. Urine filtration and Hemastix results. In settings A, B and C, according to triplicate urine filtrations, the prevalence of S. haematobium was 4.1%, 0.8% and 65.3% in setting A, B and C, respectively. With regard to Hemastix dipstick results, after exclusion of trace results, the prevalence of microhematuria in settings A, B and C was 5.3%, 6.7% and 44.6%. Traces of microhematuria were additionally found in 33, 34 and 78 urines tested in setting A, B and C, respectively.

Association between Kato-Katz and CCA Test Results
As indicated in Table 2, our ordinal logistic regression analysis showed that for an increase of S. mansoni infection intensity by 1 EPG, the likelihood of a stronger color reaction of the CCA-A (odds ratio (OR) = 1.07) and the CCA-B (OR = 1.03) is significant (both p,0.001). When S. mansoni FECs were not considered as continuous, but stratified according to pre-set thresholds into no, light, moderate and heavy infection intensity, we found that for each increase in infection intensity category, the likelihood of a stronger color reaction of both CCA-A (OR = 36.5) and CCA-B (OR = 25.2) is highly significant (both p,0.001). Figure 2 shows the correlation between infection intensity classes according to preset thresholds [22] and the percentage of infected individuals as determined by a single or triplicate CCA-A and a single CCA-B.

Diagnosis Accuracy of Different Tests
Agreement of the diagnostic assays. Table 3 shows the agreement between different diagnostic approaches and our first 'gold' standard (i.e., nine Kato-Katz thick smears derived from three stool samples) for the diagnosis of S. mansoni, stratified by study setting. The agreement between nine Kato-Katz thick smears and (i) a single Kato-Katz from the first stool sample was  Sensitivity and specificity of the diagnostic techniques. The sensitivity and specificity of the different diagnostic tests were determined for each of our two 'gold' standards ( In setting B, the lowest sensitivity of 13.0% was determined for a single ether-concentration test. The highest sensitivity was found for duplicate or triplicate CCA-A (both = 77%). Single CCA-A (69.6%), showed a slightly lower sensitivity than triplicate Kato-Katz thick smears (73.9%) from a single stool sample.
In setting C, the ether-concentration showed the lowest sensitivity (41.0%) for diagnosis of S. mansoni. A single (89.6%) and duplicate or triplicate CCA-A tests (both = 91%) did not show a higher sensitivity than triplicate Kato-Katz thick smears (94.2%).
Even when using a more rigorous diagnostic 'gold' standard (i.e., the combined results of nine Kato-Katz thick smears, plus triplicate CCA-A, a single CCA-B, and a single ether-concentration), very similar sensitivities were obtained. Table 3 shows that, if only S. mansoni-negative children were included in a logistic regression analysis and adjustments were made for S. haematobium egg counts and infection intensity classes, no significant association between the CCA-A positivity rate and S. haematobium egg counts was found (OR = 1.09; p = 0.121). There was also no significant association between the CCA-A positivity rate and microhematuria classes detected (p.0.05). Due to the small number of children found positive with the CCA-B test no logistic regression analysis was performed.

Discussion
For the rapid identification of populations at highest risk of schistosomiasis and other helminth infections that warrant preventive chemotherapy, as well as for monitoring progress of control interventions and new efforts toward elimination, assessment of drug efficacy, and improved patient management, the importance of an accurate diagnosis at the individual and population level must be emphasized [6,7,31]. The widely used Kato-Katz technique for the diagnosis of S. mansoni (and S. japonicum) has several shortcomings: in low endemicity settings this technique considerably underestimates the 'true' prevalence of infection [8,11,[32][33][34]. Moreover, a minimum of equipment and well trained laboratory technicians are needed for quality results. Promising results have been reported with a CCA urine test for the diagnosis of S. mansoni in different settings [17,35]. Some of the previous investigations, however, lacked a rigorous diagnostic 'gold' standard, as CCA test results were compared with singe or duplicate Kato-Katz thick smears from one or two stool samples [21,36].
Within the frame of a SCORE-funded multi-country study, we have now assessed the accuracy of a commercially available CCA urine cassette assay (CCA-A, batch 32727) and an experimental formulation (CCA-B, batch 32686) provided by the same manufacturer and tuned to have a higher specificity, which was Additionally, we performed a single ether-concentration test using SAF-fixed stool samples. The influence of S. haematobium infection and presence of microhematuria on the performance of the CCA test was determined. In all three settings, a single CCA-A showed a similarly high sensitivity than triplicate Kato-Katz thick smears from a single stool sample, but both approaches missed a considerable number of infections when considering nine Kato-Katz thick smears as 'gold' standard. As expected, CCA-B showed a higher specificity than CCA-A, but the sensitivity of CCA-B was considerably lower than that of CCA-A. Indeed, a single CCA-B showed a significantly lower sensitivity than a single CCA-A, and triplicate Kato-Katz thick smears, particularly in settings A and B where the endemicity of S. mansoni was lower than in setting C. We were surprised by the low sensitivity of the ether-concentration method for S. mansoni diagnosis, which warrants follow-up investigations. The CCA-A seems to be an appropriate test for the diagnosis of S. mansoni in our study area in south Côte d'Ivoire where the prevalence of S. mansoni is above 25% and no recent control efforts have been implemented. Importantly, the co-endemicity of S. haematobium did not influence the accuracy of the CCA-A for the diagnosis of S. mansoni. Additionally, a concurrent infection with    [27,28] [37,38].
The results of the experimental CCA-B formulation, which has been tested on a single urine sample from all children, are suboptimal. Indeed, only low sensitivities and a poor agreement with results of the Kato-Katz method were found, particularly in the lower endemicity areas (settings A and B). In our hands, despite high specificity, the CCA-B in its current formulation cannot be recommended for S. mansoni diagnosis in south Côte d'Ivoire.
The following issues speak for or against the application of the CCA-A versus the Kato-Katz method in helminth control programs or public health centers: at first view, in moderate-tohigh-risk communities for S. mansoni infections as found in our study in Côte d'Ivoire (i.e., prevalence above 25%), the collection of a single stool sample and its examination with triplicate Kato-Katz thick smears seems to be an acceptable approach for S. mansoni diagnosis. The advantage of the Kato-Katz method is that it can concurrently detect other helminth species, such as the three main soil-transmitted helminths (i.e., A. lumbricoides, hookworm, and T. trichiura), which is not possible with the CCA. However, the Kato-Katz method requires a minimum of equipment, including a microscope, and well trained laboratory technicians who can identify helminth species-specific eggs in the thick smears. For application of the CCA-A, no additional equipment and only a minimum of training are needed. However, it only detects S. mansoni and no concurrent soil-transmitted helminth infections. The cost of a single cassette (approximately US$ 2) is currently still out of reach of people at highest risk of intestinal schistosomiasis (i.e., poor rural dwellers in sub-Saharan Africa) [17]. However, the cost of triplicate Kato-Katz thick smears are likely higher than a single CCA test [10]. From a convenience and logistical point of view, the collection of urine samples for the CCA is more straightforward than collection of stool for the Kato-Katz method. Indeed, urine production is more convenient for the patient and can be done without special efforts on the spot and at the same day resulting in high compliance rates, while stool production is inconvenient and collection can render a second consultation necessary and thus further exacerbate costs [8,39]. The performance and sensitivity of the CCA test in low-risk communities (prevalence below 10%), identified by the application of multiple Kato-Katz thick smears on stool samples collected over multiple days, remains to be elucidated. Noteworthy, our study intended to test the CCA in a setting with a S. mansoni prevalence of 10-24% as requested by SCORE. However, we observed a considerable increase in the prevalence of S. mansoni when not only applying triplicate Kato-Katz from a single stool sample as in the pre-screening, but nine Kato-Katz thick smears overall from three stool samples: the observed prevalence increased from 17% to 34% in setting A, and from 36% to 54% in setting B. Due to this rigorous diagnostic approach we ended up with higher prevalences. Retrospectively, this had to be expected, as predicted by mathematical modeling and field observations [11,13]. If the CCA test proves to be more sensitive than multiple Kato-Katz thick smears in settings characterized by low prevalence and intensity of S. mansoni infection intensities, it will be a most useful test. For example, in areas where intense helminth control efforts have diminished the prevalence and intensity of S. mansoni infections and control programs are focusing elimination, population screenings are necessary to identify remaining S. mansoni hot-spots for targeted anthelmintic treatment and other interventions. For these largescale screenings the CCA-A would be an excellent tool due to its fast and easy application.
We conclude that in the current study area of south Côte d'Ivoire, where the prevalence and intensity of S. mansoni are still high, partially explained by the prior lack of control efforts, the CCA-A can become a useful method for S. mansoni diagnosis in health centers at the periphery and schistosomiasis control programs. On the other hand, while the specificity of the CCA-B test was high, its current formulation cannot be recommended for S. mansoni diagnosis. Clearly, there is a need to evaluate the CCA test in settings characterized by low S. mansoni prevalences and infection intensities to assess its potential role in schistosomi-asis control programs progressing toward transmission control and local elimination and for reliable individual diagnosis.

Supporting Information
Alternative Language Abstract S1 Genauigkeit des im Urin zirkulierenden kathodischen Antigen (CCA) Tests fü r die Diagnose von Schistosoma mansoni Infektionen in verschiedenen Gebieten der Cô te d'Ivoire -Translation of abstract into German by Stefanie Knopp.