Point-of-care Circulating Cathodic Antigen Test Research Articles

Efficacy and safety of prazequantel for the treatment of Schistosoma mansoni infection across different transmission settings in Amhara Regional State, northwest Ethiopia.

Schistosoma mansoni and S. haematobium infections have been public health problems in Ethiopia, S. mansoni being more prevalent. To reduce the burden of schistosomiasis, a national school-based prazequantel (PZQ) mass drug administration (MDA) program has been implemented since November 2015. Nevertheless, S. mansoni infection is still a major public health problem throughout the country. Reduced efficacy of PZQ is reported by a few studies in Ethiopia, but adequate data in different geographical settings is lacking. Hence, this study aimed to assess the efficacy and safety of PZQ for the treatment of S. mansoni infection across different transmission settings in Amhara Regional State, northwest Ethiopia. A school-based single-arm prospective cohort study was conducted from February to June, 2023 among 130 S. mansoni-infected school-aged children (SAC). Forty-two, 37, and 51 S. mansoni-infected SAC were recruited from purposely selected schools located in low, moderate, and high transmission districts, respectively. School-aged children who were tested positive both by Kato Katz (KK) using stool samples and by the point of care circulating cathodic antigen (POC-CCA) test using urine samples at baseline were treated with a standard dose of PZQ and followed for 21 days for the occurrence of adverse events. After three weeks post-treatment, stool and urine samples were re-tested using KK and POC-CCA. Then the cure rate (CR), egg reduction rate (ERR), and treatment-associated adverse events were determined. The data were analyzed using SPSS version 21. Out of the total 130 study participants, 110 completed the follow-up. The CR and ERR of PZQ treatment were 88.2% (95%CI: 82.7-93.6) and 93.5% (95%CI: 85.4-98.5), respectively, by KK. The CR of PZQ based on the POC-CCA test was 70.9% (95%CI: 62.7-79.1) and 75.5% (95%CI: 67.3-83.6) depending on whether the interpretation of 'trace' results was made as positive or negative, respectively. After treatment on the 21st day, 78 and 83 participants tested negative both by KK and POC-CCA, with respective interpretations of 'trace' POC-CCA test results as positive or negative. The CR in low, moderate and high transmission settings was 91.7%, 91.2% and 82.5%, respectively (p = 0.377) when evaluated by KK. The CR among SAC with a light infection at baseline (95.7%) by KK was higher than that of moderate (81.5%) and heavy (64.3%) infections (χ2 = 12.53, p = 0.002). Twenty-six (23.6%) participants manifested at least one adverse event. Eleven (10.0%), eight (7.3%), six (5.5%), and three (2.7%) participants complained about abdominal pain, nausea, headache, and anorexia, respectively. All adverse events were mild, needing no intervention. Occurrence of adverse events was slightly higher in high endemic areas (32.5%) than moderate (23.5%) and low endemic areas (p = 0.279). A single dose of 40 mg/kg PZQ was efficacious and safe for the treatment of S. mansoni infection when it was evaluated by the KK test, but a lower efficacy was recorded when it was evaluated by the POC-CCA test. However, the POC-CCA test's specificity, clearance time of CCA from urine after treatment, and interpretation of weakly reactive (trace) test results need further research.

Evaluation of the Urine POC-CCA Test Accuracy in the Detection of Schistosoma mansoni Infection: A Systematic Review and Meta-Analysis.

Schistosomiasis is a common public health problem throughout the world and Schistosoma mansoni is the most prevalent species in Africa. Most endemic countries use the Kato-Katz (KK) stool smear examination for diagnosis, mapping, and monitoring of intervention programs. However, its poor sensitivity calls for an urgency to evaluate and use more accurate diagnostic tools, of which detection of circulating cathodic antigen (CCA) in urine seems promising. Studies published until May 2022 were searched from PubMed, Google Scholar, and grey literature for systematic review and meta-analysis following the PRISMA guideline. Eligible studies were selected based on preset inclusion and exclusion criteria. Quality of included studies was assessed using the QUADAS-2 tool. Heterogeneity between studies was assessed using Cochrane Q test and I 2 test statistics. Data were analyzed using Review Manager 5.4.1 and Meta-DiSc 1.4 software programs. Thirty-seven studies published in 29 papers and enrolling 21159 study participants were included for analysis. Overall analysis of Point-of-Care Circulating Cathodic Antigen (POC-CCA) test against KK reference standard revealed a pooled sensitivity and specificity of 0.86 (95% CI: 0.85-0.87) and 0.66 (95% CI: 0.65-0.67), respectively. Subgroup analysis among 24 studies comparing single POC-CCA with test single KK revealed a high sensitivity (0.88) but low specificity (0.66). Based on findings of 24 studies, the area under the curve (AUC) for the systematic receiver operating characteristic (SROC) curve was 0.7805, indicating that the POC-CCA test effectively separates those with the disease from those who do not have it. Higher sensitivity estimates of 0.93 and 0.90 were reported when comparisons were made between test results of 2 urine and 1 stool samples, and 3 urine and 3 stool samples, respectively. Single POC-CCA test resulted in a pooled sensitivity estimate of 0.81 (95% CI: 0.78-0.84) as evaluated by the polymerase chain reaction (PCR) reference test. The POC-CCA test has higher sensitivity than KK and may serve as a routine diagnostic alternative for disease diagnosis, mapping, and monitoring of interventions. However, its accuracy should further be evaluated at different transmission settings and infection intensity.

Evaluation of the epidemiological situation of intestinal schistosomiasis using the POC-CCA parasite antigen test and the Kato-Katz egg count test in school-age children in endemic villages in western Côte d'Ivoire.

Schistosomiasis is an endemic disease in Côte d'Ivoire. We compared the conventional Kato Katz (KK) test and a more sensitive but rarely used method, the point-of-care circulating cathodic antigen (POC-CCA), in order to contribute to the development of a more appropriate strategy for the control and elimination of intestinal schistosomiasis in western Côte d'Ivoire. A cross-sectional epidemiological survey was conducted in eight elementary schools in the Guémon and Cavally regions from February to December 2020. Selected schoolchildren provided stool and urine samples to detect the presence of Schistosoma mansoni eggs and parasite antigen using the KK and POC-CCA tests, respectively. A total of 554 schoolchildren were included in the study. The overall prevalence of intestinal schistosomiasis was 10% and 67% for KK and POC-CCA, respectively. The POC-CCA detected an infection rate of 100%, while the KK yielded a rate of 42%. In schools, prevalence ranged from 27 to 100% with POC-CCA and from 0 to 42% with KK. Swimming, fishing, washing clothes, and dishwashing were significantly associated with the onset of infection and high intensities. The epidemiological risk factors for intestinal schistosomiasis updated here using KK and POC-CCA diagnostic methods showed that prevalence was much higher than previously estimated using the KK. The POC-CCA is more sensitive and ways should be considered to improve its specificity in order to improve the diagnosis.

Diagnosis of Schistosomiasis without a Microscope: Evaluating Circulating Antigen (CCA, CAA) and DNA Detection Methods on Banked Samples of a Community-Based Survey from DR Congo.

Detection of Schistosoma eggs in stool or urine is known for its low sensitivity in diagnosing light infections. Alternative diagnostics with better sensitivity while remaining highly specific, such as real-time PCR and circulating antigen detection, are progressively used as complementary diagnostic procedures but have not yet replaced microscopy. This study evaluates these alternative methods for the detection of Schistosoma infections in the absence of microscopy. Schistosomiasis presence was determined retrospectively in 314 banked stool and urine samples, available from a previous survey on the prevalence of taeniasis in a community in the Democratic Republic of the Congo, using real-time PCR, the point-of-care circulating cathodic antigen (POC-CCA) test, as well as the up-converting particle lateral flow circulating anodic antigen (UCP-LF CAA) test. Schistosoma DNA was present in urine (3%) and stool (28%) samples, while CCA (28%) and CAA (69%) were detected in urine. Further analysis of the generated data indicated stool-based PCR and the POC-CCA test to be suitable diagnostics for screening of S. mansoni infections, even in the absence of microscopy. A substantial proportion (60%) of the 215 CAA-positive cases showed low antigen concentrations, suggesting that even PCR and POC-CCA underestimated the “true” number of schistosome positives.

A cluster randomized controlled trial for assessing POC-CCA test based praziquantel treatment for schistosomiasis control in pregnant women and their young children: study protocol of the freeBILy clinical trial in Madagascar

BackgroundMass drug administration (MDA) of praziquantel is one of the main control measures against human schistosomiasis. Although there are claims for including pregnant women, infants and children under the age of 5 years in high-endemic regions in MDA campaigns, they are usually not treated without a diagnosis. Diagnostic tools identifying infections at the primary health care centre (PHCC) level could therefore help to integrate these vulnerable groups into control programmes. freeBILy (fast and reliable easy-to-use-diagnostics for eliminating bilharzia in young children and mothers) is an international consortium focused on implementing and evaluating new schistosomiasis diagnostic strategies. In Madagascar, the study aims to determine the effectiveness of a test-based schistosomiasis treatment (TBST) strategy for pregnant women and their infants and children up until the age of 2 years.MethodsA two-armed, cluster-randomized, controlled phase III trial including 5200 women and their offspring assesses the impact of TBST on child growth and maternal haemoglobin in areas of medium to high endemicity of Schistosoma mansoni. The participants are being tested with the point of care-circulating cathodic antigen (POC-CCA) test, a commercially available urine-based non-invasive rapid diagnostic test for schistosomiasis. In the intervention arm, a POC-CCA-TBST strategy is offered to women during pregnancy and 9 months after delivery, for their infants at 9 months of age. In the control arm, study visit procedures are the same, but without the POC-CCA-TBST procedure. All participants are being offered the POC-CCA-TBST 24 months after delivery. This trial is being integrated into the routine maternal and child primary health care programmes at 40 different PHCC in Madagascar’s highlands. The purpose of the trial is to assess the effectiveness of the POC-CCA-TBST for controlling schistosomiasis in young children and mothers.DiscussionThis trial assesses a strategy to integrate pregnant women and their children under the age of 2 years into schistosomiasis control programmes using rapid diagnostic tests. It includes local capacity building for clinical trials and large-scale intervention research.Trial registrationPan-African Clinical Trial Register PACTR201905784271304. Retrospectively registered on 15 May 2019

Performance of the point-of-care circulating cathodic antigen test in the diagnosis of schistosomiasis japonica in a human cohort from Northern Samar, the Philippines

BackgroundZoonotic schistosomiasis, caused by Schistosoma japonicum, remains a major public health problem in the Philippines. This study aimed to evaluate the commercially available rapid diagnostic point-of-care circulating cathodic antigen (POC-CCA) test in detecting individuals infected with S. japonicum in a human cohort from an endemic area for schistosomiasis japonica in the Philippines.MethodsClinical samples were collectedin 18 barangays endemic for S. japonicum infection in Laoang and Palapag municipalities, Northern Samar, the Philippines, in 2015. The presence of CCA in filter-concentrated urine samples (n = 412) was evaluated using the commercial kits and the results were converted to images, which were further analyzed by ImageJ software to calculate R values. The diagnostic performance of the immunochromatographic POC-CCA test was compared using the Kato-Katz (KK) procedure, in-house enzyme-linked immunosorbent assays (ELISAs) and droplet digital (dd) PCR assays as reference.ResultsThe POC-CCA test was able to detect S. japonicum-infected individuals in the cohort with an eggs per gram of faeces (EPG) more than or equal to 10 with sensitivity/specificity values of 63.3%/93.3%. However, the assay showed an inability to diagnose schistosomiasis japonica infections in all cohort KK-positive individuals, of which the majority had an extremely low egg burden (EPG: 1–9). The prevalence of S. japonicum infection in the total cohort determined by the POC-CCA test was 12.4%, only half of that determined by the KK method (26.2%). When compared with the ELISAs and ddPCR assays as a reference, the POC-CCA assay was further shown to be a test with low sensitivity. Nevertheless, the assay exhibited significant positive correlations with egg burden determined by the KK technique and the target gene copy number index values determined by the ddPCR assays within the entire cohort.ConclusionsBy using in silico image analysis, the POC-CCA cassette test could be converted to a quantitative assay to avoid reader-variability. Because of its low sensitivity, the commercially available POC-CCA assay had limited potential for determining the status of a S. japonicum infection in the target cohort. The assay should be applied with caution in populations where schistosome parasites (especially S. japonicum) are present at low infection intensity.Graphic abstract

Accuracy of Two Circulating Antigen Tests for the Diagnosis and Surveillance of Schistosoma mansoni Infection in Low-Endemicity Settings of Côte d'Ivoire.

ABSTRACT.In low-endemicity settings, current tools for the diagnosis and surveillance of schistosomiasis are often inaccurate in detecting true infection. We assessed the accuracy of an up-converting phosphor lateral flow circulating anodic antigen (UCP-LF CAA) test and a point-of-care circulating cathodic antigen (POC-CCA) urine cassette test for the diagnosis of Schistosoma mansoni. Our study was conducted in eight schools of western Côte d’Ivoire. Fifty children, aged 9–12 years, were enrolled per school. From each child, a single urine specimen and two stool specimens were collected over consecutive days for diagnostic work-up. Urine samples were subjected to UCP-LF CAA and POC-CCA tests. From each stool sample, triplicate Kato-Katz thick smears were examined. Overall, 378 children had complete data records. The prevalence of S. mansoni, as assessed by six Kato-Katz thick smears, was 4.0%. The UCP-LF CAA and POC-CCA tests revealed S. mansoni prevalence of 25.4% and 30.7%, respectively, when considering trace results as positive, and prevalence of 23.3% and 10.9% when considering trace results as negative. In the latter case, based on a composite “gold” standard, the sensitivity of UCP-LF CAA (80.7%) was considerably higher than that of POC-CCA (37.6%) and six Kato-Katz thick smears (13.8%). The negative predictive value of UCP-LF CAA, POC-CCA, and six Kato-Katz thick smears was 92.8%, 79.8%, and 74.1%, respectively. Our results confirm that UCP-LF CAA is more accurate than Kato-Katz and POC-CCA for the diagnosis of S. mansoni in low-endemicity settings.

High Egg Reduction Rate but poor clearance of Circulating Cathodic Antigen three weeks after Praziquantel treatment among school children on Ijinga Island, north-western Tanzania

Traditionally, efficacy of Praziquantel (PZQ) is monitored using Parasitological Cure Rates and Egg Reduction Rates applying Kato Katz (KK) technique. This parasitological technique has a number of limitations. Recently, the Point-of-Care Circulating Cathodic Antigen (POC-CCA) rapid test which is a highly sensitive technique, has emerged as a promising candidate to be used for evaluating the efficacy of PZQ. A prospective longitudinal study was conducted among 399 school children aged 7–17 years on Ijinga Island, north-western Tanzania. At baseline and three weeks after treatment, stool and urine samples were collected from participating school children and screened for S. mansoni infection using the KK technique as well as POC-CCA test. All S. mansoni infected children at baseline were treated with 40mg/kg of PZQ and followed up after three weeks. At baseline, the overall prevalence of S. mansoni infection was 56.6% (95%CI: 51.7–61.4) and 99.7% (95%CI: 98.2–99.9) (considering trace as positive) using KK technique and POC-CCA test, respectively. Three weeks after treatment, the prevalence of S. mansoni was 0.92% using the KK technique and 97.7% when applying the POC-CCA test. The parasitological cure rates based on KK technique and POC-CCA were 99.1% (95%CI: 97.5–99.8) and 2.3% (95%CI: 1.2–4.5). Egg Reduction Rate was 99.1%. Based on WHO guidelines using the KK technique, at three weeks point, the efficacy of PZQ is satisfactory. However, the assessment of the efficacy of PZQ using POC-CCA tests needs further evaluation.

Prevalence, infection intensity and geographical distribution of schistosomiasis among pre-school and school aged children in villages surrounding Lake Nyasa, Tanzania

Planning and implementation of schistosomiasis control activities requires an understanding of the prevalence, intensity of infection and geographical distribution of the disease in different epidemiological settings. Although, Tanzania is known to be highly endemic to schistosomiasis, there is paucity of data on the geographical distribution of schistosomiasis in potential large water bodies in the country. Thus, the present study was conducted to determine the prevalence, infection intensities and geographical distribution of schistosomiasis along villages located on the shoreline of Lake Nyasa, southern Tanzania. A cross-sectional study was conducted among 1560 children aged 1–13 years old living in villages located along the shoreline of Lake Nyasa. A single urine and stool sample was obtained from each participating child and screened for S.mansoni using Kato Katz (KK) technique to detect eggs and using point-of-care circulating Cathodic Antigen (POC-CCA) test to detect antigen in urine. Urine filtration technique was used to screen for S.haematobium eggs in urine samples. Villages/primary school were mapped using geographical information system and prevalence map was generated using ArcView GIS software. The overall prevalence of S.mansoni based on KK technique and POC-CCA test was 15.1% (95%CI: 13.4–16.9) and 21.8% (95%CI: 18.5–25.3) respectively. The prevalence S.haematobium was 0.83% (95%CI: 0.5–1.4) and that of haematuria was 0.9%. The arithmetic mean egg intensities for S.haematobium and S.mansoni were 18.5 mean eggs/10 ml (95%CI: 5.9–57.6) of urine and 34.7 mean epg (95%CI: 27.7–41.7) respectively. Villages located on the southern end of the lake had significantly high prevalence of S.mansoni than those located on the northern part (χ2 = 178.7838, P = 0.001). Cases of S.haematobium were detected only in three villages. Both S.mansoni and S.haematobium infections occur in villages located along the shoreline of Lake Nyasa at varying prevalence. These finding provide insights that can provide guidance in planning and implementation of MDA approach and other recommended measures such as improvement in sanitation, provision of clean water and behaviour changes through public health education.

Diagnostic comparison of stool exam and point-of-care circulating cathodic antigen (POC-CCA) test for schistosomiasis mansoni diagnosis in a high endemicity area in northeastern Brazil.

This study aimed to evaluate the performance of the point-of-care circulating cathodic antigen (POC-CCA) test in a highly endemic area in Brazil, comparing it to the Kato-Katz (KK) technique for sensitivity, specificity and the intensity of the reaction of the test in relation to the parasitic load. The community in Sergipe, Brazil, participated in the study, providing three stool samples, one of urine (POC-CCA) and fingers tick blood sample was tested by enzyme-linked immunosorbent assay (ELISA). Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, kappa coefficient and Spearman's correlation were calculated for the POC-CCA test using the KK as the reference. The prevalence of schistosomiasis by KK testing was 48.82%; POC-CCA (t+) 66.14%; POC-CCA (t-) 45.24%. ELISA results showed 100% agreement in individuals with high and moderate eggs per gram (EPG). POC-CCA presented good diagnostic performance in individuals with medium and high EPG, but there were a high number of false negatives in individuals with low intensity infections. As observed, POC-CCA-filter test improves accuracy and sensitivity compared to a conventional test.

Cross-reaction of POC-CCA urine test for detection of Schistosoma mekongi in Lao PDR: a cross-sectional study

BackgroundThe point-of-care circulating cathodic antigen (POC-CCA) test is increasingly used as a rapid diagnostic method for Schistosoma mansoni infection. The test has good sensitivity, although false positive results have been reported among pregnant women and patients with urine infections and hematuria. We validated the POC-CCA test’s ability to diagnose Schistosoma mekongi infection in Lao People’s Democratic Republic (Lao PDR), where S. mekongi is endemic. Of particular interest was the test’s specificity and possible cross-reactivity with other helminth infections.MethodsWe conducted a cross-sectional study of children and adults in the provinces of Champasack (Schistosoma mekongi and Opisthorchis viverrini endemic), Savannakhet (O. viverrini endemic) and Luang Prabang (soil-transmitted helminths endemic) between October 2018 and April 2019. POC-CCA and urine dipstick tests were administered to all study participants, while an additional pregnancy test was offered to women. Two stool samples were collected from participants and examined with a Kato-Katz test (two smears per stool). Logistic regression was used to associate potential confounding factors (predictors) with POC-CCA test results (outcome).ResultsIn S. mekongi-endemic Champasack, 11.5% (n = 366) and 0.5% (n = 2) of study participants had positive POC-CCA and Kato-Katz test results, respectively. Only one of the two Kato-Katz positive patients was also POC-CCA positive. In Champasack and Luang Prabang, where S. mekongi is not endemic, the POC-CCA test yielded (presumably) false positive results for 6.0% (n = 22) and 2.5% (n = 9) of study participants, respectively, while all of the Kato-Katz tests were negative. POC-CCA positive test results were significantly associated with O. viverrini infection (1.69, 95% confidence interval (CI): 1.02–2.77, P = 0.042), increased leukocytes (adjusted Odds Ratio (aOR) = 1.58, 95% CI: 1.15–2.17, P = 0.005) and hematuria (aOR = 1.50, 95% CI: 1.07–2.10, P = 0.019) if the observed trace was counted as a positive test result. Two pregnant women from Champasack province had POC-CCA positive tests.ConclusionsWe observed a cross-reaction between the POC-CCA test and O. viverrini infection. To some extent, we can confirm previous observations asserting that POC-CCA provides false positive results among patients with urinary tract infections and hematuria. In S. mekongi-endemic areas, POC-CCA can be applied cautiously for surveillance purposes, keeping in mind the considerable risk of false positive results and its unknown sensitivity.

Test, Treat, Track, Test, and Treat Active Surveillance toward Elimination of Schistosomiasis: A Feasibility Study.

.We assessed the feasibility of using a test, treat, track, test, and treat (5T) active surveillance strategy to identify and treat individuals with schistosomiasis in three very low-prevalence villages in Kafr El Sheikh Governorate, Egypt. Primary index cases (PICs) were identified using the point-of-care circulating cathodic antigen (POC-CCA) assay in schools, in rural health units (retesting individuals with positive Kato–Katz examinations over the previous 6 months), and at potential water transmission sites identified by PICs and field observations. Primary cases identified potential second-generation cases—people with whom they shared water activities—who were then tracked, tested, and treated if infected. Those sharing water activities with second-generation cases were also tested. The yield of PICs from the three venues were 128 of 3,576 schoolchildren (3.6%), 42 of 696 in rural health units (6.0%), and 83 of 1,156 at water contact sites (7.2%). There were 118 second- and 19 third-generation cases identified. Persons testing positive were treated with praziquantel. Of 388 persons treated, 368 (94.8%) had posttreatment POC-CCA tests 3–4 weeks after treatment, and 81.8% (301) became negative. The 67 persons remaining positive had negative results after a second treatment. Therefore, all those found positive, treated, and followed up were negative following one or two treatments. Analysis of efforts as expressed in person-hours indicates that 4,459 person-hours were required for these 5T activities, with nearly 65% of that time spent carrying out interviews, treatments, and evaluations following treatment. The 5T strategy appears feasible and acceptable as programs move toward elimination.

Evaluation of serum-based real-time PCR to detect Schistosoma mansoni infection before and after treatment

BackgroundTo detect acute schistosomiasis, low-intensity infections, or to verify the success of treatment with praziquantel, highly sensitive test methods are required. The aim of this study was therefore to demonstrate the performance of Schistosoma mansoni specific DNA detection in serum and urine using real-time polymerase chain reaction (PCR) in an endemic area before and after treatment.MethodsThe study pursued a 1-week and 20-weeks longitudinal design with a treatment intervention among 36 study participants aged 18 to 70 years in the community of Kayenze, a fishing village in Ilemela district on the southern shore of Lake Victoria in north-western Tanzania between February and June 2018. Blood, urine and stool samples were collected from each participant to diagnose Schistosoma mansoni infection before and two times after treatment with praziquantel using serum- and urine based real-time PCR, point-of-care circulating cathodic antigen (POC-CCA) rapid diagnostic test and the microscopic Kato-Katz (KK) method. Kappa coefficient (κ) was used to estimate the agreement between these diagnostic tests compared to a combined “gold standard” of positive results by serum-based real-time PCR and/or positive egg counts determined by KK. Kendall’s Tau rank correlation was used to examine the relationship between cycle threshold (Ct)-values and egg counts and the Wilcoxon signed-rank test was used to compare the median Ct-values of the different examination time points.ResultsBy using the combined “gold standard” of the parasitological Kato-Katz test and/or serum-based real-time PCR, a S. mansoni prevalence of 77.1% could be determined at baseline. In terms of sensitivity, serum-based real-time PCR (96.3%) and POC-CCA assay (77.8%) showed the highest results. The detection of DNA from urine samples showed the lowest sensitivity (33.3%). Treatment with praziquantel resulted in a significantly reduced prevalence of S. mansoni. No infection could be detected by Kato-Katz, with the POC-CCA test only 33.3%. The analysis of the median Ct values over time (which were determined by the serum-based real-time PCR) showed that the Ct decreases significantly shortly after treatment (from 30.3 to 28) and increases above baseline level (34.9) three months later.ConclusionsThe data presented here show that the serum-based real-time PCR exhibits excellent diagnostic accuracy, in contrast to the use of urine as sample material for S. mansoni DNA detection. However, as circulating DNA does not necessarily reflect the persistence of living worms in schistosomiasis, this method is less well suited to verify the success of treatment with praziquantel.

The use of the circulating cathodic antigen (CCA) urine cassette assay for the diagnosis and assessment of cure of Schistosoma mansoni infections in an endemic area of the Amazon region.

INTRODUCTION Schistosomiasis is a poverty-related disease that affects people in 78 countries worldwide. This study aimed to evaluate the point-of-care circulating cathodic antigen (POC-CCA) test performance using sensitive parasitological methods as a reference standard (RS) in individuals before and after treatment. METHODS The RS was established by combining the results of 16 Kato-Katz slides and the Helmintex® method. Positivity rates of the POC-CCA test and Kato-Katz and Helmintex® methods were calculated before treatment and 30 days afterward. Furthermore, the sensitivity, specificity, accuracy, and kappa coefficient before treatment were determined by comparing the methods. The cure rate was defined 30 days after treatment. RESULTS Among the 217 participants, the RS detected a total of 63 (29.0%) positive individuals. The POC-CCA test identified 79 (36.4%) infections. The evaluation of POC-CCA test performance in relation to the RS revealed a sensitivity of 61.9%, specificity of 74.0%, accuracy of 70.5%, and kappa coefficient of 0.33. Out of the 53 remaining participants after treatment, a total of 45 (81.1%) showed egg negative results, and 8 (18.9%) were egg positive according to the RS. A total of 5 (9.4%) egg-positive and 37 (69.8%) egg-negative individuals were positive by the POC-CCA test. CONCLUSIONS Our data show that the POC-CCA test has potential as an auxiliary tool for the diagnosis of Schistosoma mansoni infection, yielding better results than 16 Kato-Katz slides from three different stool samples. However, the immunochromatographic test lacks sufficient specificity and sensitivity for verifying the cure rate after treatment.

Translating preventive chemotherapy prevalence thresholds for Schistosoma mansoni from the Kato-Katz technique into the point-of-care circulating cathodic antigen diagnostic test.

BackgroundIntervention 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.MethodologyWe 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 findingsPOC-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/significanceThe 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.

Integrating use of point-of-care circulating cathodic antigen rapid diagnostic tests by community health workers during mass drug administration campaigns to improve uptake of praziquantel treatment among the adult population at Kome Island, North-Western Tanzania: a cluster randomized community trial

BackgroundThe major drawback of the community-based mass drug administration (MDA) approach against schistosomiasis is that treatment is offered blindly without testing for the targeted infection. This partly contributes to the low treatment coverage. One approach to overcome this limitation is to introduce a diagnostic component in the treatment approach. This will improve drug uptake and compliance to treatment. This study is conducted to assess the feasibility and acceptability of integrating point-of-care Circulating Cathodic Antigen (POC-CCA) test to community-based directed MDA in improving treatment coverage and compliance with treatment among adults.MethodsThis is a randomized control community trial in which 30 clusters were randomly assigned to either an intervention or control arm to evaluate two interventions on treatment coverage and compliance with treatment. In each cluster, 150 adult participants were enrolled. Community Health Workers (CHW) in both arms were trained on all aspects of praziquantel (PZQ) distribution and management of mild side effects. In the intervention arm, CHWs had additional training on how to use POC-CCA to diagnose intestinal schistosomiasis. In the intervention arm, participants were tested using POC-CCA test for presence of intestinal schistosomiasis and treated based on test results, while in the control arm, participants were treated with PZQ without testing. The primary outcome measure was the proportion of participants provided with PZQ between the two arms and geographical clusters. Secondary outcomes were prevalence of S. mansoni infection based on the POC-CCA test conducted by CHWs, ability of CHWs to use the POC-CCA test accurately and safely and community acceptability of the POC-CCA test results from CHWs. Both quantitative and qualitative techniques have been used to collect data at study endpoint.DiscussionThe study will generate evidence on the importance of integrating a diagnostic component into the community directed MDA conducted by CHWs. Findings will generate discussion on the current MDA policy and practice in Tanzania.Trial registrationPACTR201804003343404 (25/4/2018).

Sensitivity and specificity of point-of-care circulating Cathodic antigen test before and after praziquantel treatment in diagnosing Schistosoma mansoni infection in adult population co-infected with human immunodeficiency virus-1, North-Western Tanzania

BackgroundThe effect of Human Immunodeficiency Virus-1 (HIV-1) on CD4+ Th2 cells is hypothesized to affect parasitological diagnosis of Schistosoma mansoni using Kato Katz technique. Thus, the use of more sensitive technique such as Point-of-Care Circulating Cathodic Antigen (POC-CCA) test is recommended. However, the sensitivity of this diagnostic test in diagnosing S.mansoni infection and the usefulness of it in monitoring efficacy of praziquantel drug in presence of HIV-1 co-infection remains inconclusive. The Primary objective of the present study was to assess accuracy of the POC-CCA test in diagnosing S.mansoni infection before and after praziquantel treatment in adult population co-infected with HIV -1.MethodsA prospective longitudinal study was conducted among individuals aged 15–55 years at Igalagala village, north-western Tanzania. At baseline and 4 weeks after treatment, a single stool and urine samples were collected from each participants. Kato Katz (KK) technique and Point-of-Care Circulating Cathodic Antigen tests were used for diagnosis of Schistosoma mansoni.ResultsAt baseline, based on KK and POC-CCA, the prevalence of S.mansoni was 57.8% (95%CI: 52.9–62.4) and 87.5% (95%CI: 83.9–90.4). Based on KK technique and POC-CCA test, 3.6% and 5.7% of the study participants were co-infected with S.mansoni and HIV-1. At baseline, in the general population, the sensitivities of POC-CCA test using KK technique and combine gold standard were 96.3%(95%CI: 93.1–98.3) and 97.6%(95%CI:95.5–98.9) respectively. In the HIV-1 seropositive group, at baseline, the sensitivities of POC-CCA test using KK technique and combined gold standards, were 93.3%(95%CI:68.1–99.8) and 96%(95CI%:79.6–99.9). Four weeks after treatment, in general population, the sensitivities of POC-CCA test using KK technique and combined gold standards were 47.8%(95%CI:26.8–69.4) and 84.4%(95%CI:74.4–91.7). In the HIV-1 seropositive group, using KK technique, the sensitivity was 100% (95%CI:2.5–100).ConclusionThe sensitivity of POC-CCA in diagnosing S.mansoni infection was higher than KK technique in adult individuals likely to have low infection intensity and co-infected with HIV-1. However, its sensitivity decreases following praziquantel treatment but remained higher than Kato Katz technique. If the goal of the post-treatment is to identify uncured individuals, then POC-CCA test offers the best choice.

Diagnostic Performance of Kato Katz Technique and Point-of-Care Circulating Cathodic Antigen Rapid Test in Diagnosing Schistosoma mansoni Infection in HIV-1 Co-Infected Adults on the Shoreline of Lake Victoria, Tanzania.

Background: The diagnostic performance of the Kato Katz (KK) technique and the point-of-care circulating cathodic antigen (POC-CCA) test in detecting S. mansoni infection in the presence of the human immunodeficiency virus-1 (HIV-1) infection has remained inconclusive. The present cross-sectional survey compared the diagnostic performance of the KK technique and the POC-CCA test in diagnosing S. mansoni infection in an adult population co-infected with HIV-1 in northwestern Tanzania. Methods: Single urine and stool samples from 979 adults were screened for S. mansoni infection using both the KK technique and POC-CCA tests. To compare the performance of the two diagnostic tests a combined artificial gold standard was created, based on either an egg-positive KK technique or a POC-CCA-positive test. Results: Based on the KK technique, the prevalence of S. mansoni was 47.3% (463/979, 95% CI: 44.2–50.4), as compared to 60.5% by the POC-CCA test (592/979; 95% CI: 57.4–63.5). The overall sensitivity and specificity of the POC-CCA test were 92.5% (95% CI: 89.4–94.9) and 73.3% (95% CI: 69.6–76.8), respectively. In the HIV-1 seropositive group, the sensitivity and specificity of the POC-CCA test were 78.1% (95% CI: 60.0–90.7) and 45.9% (95% CI: 35.8–56.3). Using a combined gold standard, the sensitivity of the POC-CCA test increased to >90% in both subgroups whereas that of the KK technique in the HIV-1 seropositive group was low (49.5%; 95% CI: 39.6–59.5). Conclusion: In the presence of HIV-1 co-infection, the KK technique attained a very low sensitivity. The POC-CCA test offers the best option for the rapid screening of S. mansoni infection in communities with a high prevalence of HIV-1 infection.

Comparing the performance of circulating cathodic antigen and Kato-Katz techniques in evaluating Schistosoma mansoni infection in areas with low prevalence in selected counties of Kenya: a cross-sectional study

BackgroundKato-Katz technique has been the mainstay test in Schistosoma mansoni diagnosis in endemic areas. However, recent studies have documented its poor sensitivity in evaluating Schistosoma mansoni infection especially in areas with lower rates of transmission. It’s the primary diagnostic tool in monitoring impact of the Kenya national school based deworming program on infection transmission, but there is need to consider a more sensitive technique as the prevalence reduces. Therefore, this study explored the relationship between results of the stool-based Kato-Katz technique with urine-based point-of-care circulating cathodic antigen (POC-CCA) test in view to inform decision-making by the program in changing from Kato-Katz to POC-CCA test.MethodsWe used two cross-sectional surveys conducted pre- and post- mass drug administration (MDA) using praziquantel in a representative random sample of children from 18 schools across 11 counties. A total of 1944 children were randomly sampled for the study. Stool and urine samples were tested for S. mansoni infection using Kato-Katz and POC-CCA methods, respectively. S. mansoni prevalence using each technique was calculated and 95% confidence intervals obtained using binomial regression model. Specificity (Sp) and sensitivity (Sn) were determined using 2 × 2 contingency tables and compared using the McNemar’s chi-square test.ResultsA total of 1899 and 1878 children were surveyed at pre- and post-treatment respectively. S. mansoni infection prevalence was 26.5 and 21.4% during pre- and post-treatment respectively using POC-CCA test, and 4.9 and 1.5% for pre- and post-treatment respectively using Kato-Katz technique. Taking POC-CCA as the gold standard, Kato-Katz was found to have significantly lower sensitivity both at pre- and post-treatment, Sn = 12.5% and Sn = 5.2% respectively, McNemar test χ2m = 782.0, p < 0.001. In overall, the results showed a slight/poor agreement between the two methods, kappa index (k) = 0.11, p < 0.001, inter-rater agreement = 77.1%.ConclusionsResults showed POC-CCA technique as an effective, sensitive and accurate screening tool for Schistosoma mansoni infection in areas of low prevalence. It was up to 14-fold accurate than Kato-Katz which had extremely inadequate sensitivity. We recommend usage of POC-CCA alongside Kato-Katz examinations by Schistosomiasis control programs in low prevalence areas.

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