Schistosomiasis is a parasitic infection caused by worms of the genus Schistosoma. It is a neglected tropical disease, affecting mainly populations living in poverty without adequate sanitation.... Show moreSchistosomiasis is a parasitic infection caused by worms of the genus Schistosoma. It is a neglected tropical disease, affecting mainly populations living in poverty without adequate sanitation. Treatment relies on one drug mainly, praziquantel, and its efficacy is dependent on the diagnostic tool used.Due to the parasite’s intravascular localisation, it is difficult to directly quantify them in infected humans. Thus, methods of detection like worm-derived circulating cathodic antigen (CCA) in urine or circulating anodic antigen (CAA) in urine and serum, have gained more attention. This thesis aims to explore and shed light on how to interpret schistosome-related circulating antigens CCA and CAA. We have addressed the interpretation of schistosome related assays in endemic and non-endemic regions, supported by data obtained from an animal study. Different diagnostic value can be attributed to different assays within different contexts. The results highlight the importance of a better understanding of antigen excretion patterns by different species to support optimalisation of antigen-based diagnostics of schistosomiasis. Show less
BackgroundSchistosomiasis control relies mainly on mass drug administration of Praziquantel (PZQ) to school aged children (SAC). Although precision mapping has recently guided decision making, the... Show moreBackgroundSchistosomiasis control relies mainly on mass drug administration of Praziquantel (PZQ) to school aged children (SAC). Although precision mapping has recently guided decision making, the sub-districts and the epidemiological differences existing between bio-ecological settings in which infected children come from were not taken into consideration. This study was designed to fill this gap by using POC-CCA and KK to comparatively determine the prevalence and infection intensities of Schistosoma mansoni (S. mansoni) and to perform fine-scale mapping of S. mansoni infections and its infection intensities with the overarching goal of identifying sub-districts presenting high transmission risk where control operations must be boosted to achieve schistosomiasis elimination.MethodologyDuring a cross- sectional study conducted in Makenene, 1773 stool and 2253 urine samples were collected from SAC of ten primary schools. S. mansoni infections were identified using the point of care circulating cathodic antigen (POC-CCA) and Kato-Katz (KK) test respectively on urine and stool samples. Geographical coordinates of houses of infected SAC were recorded using a global position system device. Schistosome infections and infection intensities were map using QGIS software.ResultsThe prevalence of S. mansoni inferred from POC-CCA and KK were 51.3% and 7.3% respectively. Most infected SAC and those bearing heavy infections intensities were clustered in sub-districts of Baloua, Mock-sud and Carriere. Houses with heavily-infected SAC were close to risky biotopes.ConclusionThis study confirms the low sensitivity of KK test compared to POC-CCA to accurately identify children with schistosome infection and bearing different schistosome burden. Fine-scale mapping of schistosome infections and infection intensities enabled to identify high transmission sub-districts where control measures must be boosted to reach schistosomiasis elimination. Show less
Casacuberta Partal, M.; Beenakker, M.; Dood, C. de; Hoekstra, P.; Kroon, L.; Kornelis, D.; ... ; Lieshout, L. van 2021
ABSTRACTThe point-of-care urine based strip test for the detection of circulating cathodic antigen (POC-CCA) in schistosome infections is a frequently used tool for diagnosis and mapping of... Show moreABSTRACTThe point-of-care urine based strip test for the detection of circulating cathodic antigen (POC-CCA) in schistosome infections is a frequently used tool for diagnosis and mapping of Schistosoma mansoni in school-aged children. Because of its ease of use, the test is increasingly applied to adults and preschool-aged children (PSAC), but its performance has not been specifically evaluated in these target groups. Recent observations have raised concerns about possible reduced specificity, in particular in pregnant women (PW) and PSAC. We thus explored specificity of the POC-CCA urine strip test (Rapid Medical Diagnostics, Pretoria, South Africa) in a non-endemic, nonexposed population of 47 healthy nonpregnant adults (NPAs), 52 PW, and 58 PSAC. A total of 157 urines were tested with POC-CCA, of which five (10.6%) NPAs, 17 (32.7%) PW, and 27 (46.5%) PSAC were positive. The highest scores were found in the youngest babies, with an infant of 9 months being the oldest positive case. On measuring pH, it appeared that all POC-CCA strongly positive urines were acidic (pH range 5–5.5), whereas addition of pH-neutral buffer to a subsample reversed the false positivity. We conclude that the POC-CCA test has reduced specificity in PW and infants younger than 9 months, but that the false positivity might be eliminated by modifications in the buffers used in the test. Show less
Amoah, A.S.; Hoekstra, P.T.; Casacuberta Partal, M.; Coffeng, L.E.; Corstjens, P.L.A.M.; Greco, B.; ... ; Dam, G.J. van 2020
Although preventive chemotherapy has been instrumental in reducing schistosomiasis incidence worldwide, serious challenges remain. These problems include the omission of certain groups from... Show moreAlthough preventive chemotherapy has been instrumental in reducing schistosomiasis incidence worldwide, serious challenges remain. These problems include the omission of certain groups from campaigns of mass drug administration, the existence of persistent disease hotspots, and the risk of recrudescent infections. Central to these challenges is the fact that the diagnostic tools currently used to establish the burden of infection are not sensitive enough, especially in low-endemic settings, which results in underestimation of the true prevalence of active Schistosoma spp infections. This central issue necessitates that the current schistosomiasis control strategies recommended by WHO are re-evaluated and, possibly, adapted. More targeted interventions and novel approaches have been used to estimate the prevalence of schistosomiasis, such as establishing infection burden by use of precision mapping, which provides high resolution spatial information that delineates variations in prevalence within a defined geographical area. Such information is instrumental in guiding targeted intervention campaigns. However, the need for highly accurate diagnostic tools in such strategies is a crucial factor that is often neglected. The availability of highly sensitive diagnostic tests also opens up the possibility of applying strategies of sample pooling to reduce the cost of control programmes. To interrupt the transmission of, and eventually eliminate, schistosomiasis, better local targeting of preventive chemotherapy, in combination with highly sensitive diagnostic tools, is crucial. Show less
Casacuberta Partal, M.; Janse, J.J.; Schuijlenburg, R. van; Vries, J.J.C. de; Erkens, M.A.A.; Suijk, K.; ... ; Roestenberg, M. 2020
Background: Travellers infected with Schistosoma spp. might be pauci- or even asymptomatic on first presentation. Therefore, schistosomiasis may remain undiagnosed in this population. Active... Show moreBackground: Travellers infected with Schistosoma spp. might be pauci- or even asymptomatic on first presentation. Therefore, schistosomiasis may remain undiagnosed in this population. Active infection, as evidenced by the presence of the tissue-dwelling worm, can be demonstrated via the detection of adult worm-derived circulating anodic antigen (CAA) utilising a robust well-described lateral flow-(LF) based test applying background-free up-converting reporter particles (UCP). In this prospective study, we assessed the diagnostic value of serum and urine UCP-LF CAA test in comparison with two Schistosoma-specific serological assays detecting antibodies against adult worm antigen-immuno fluorescence assay (AWA-IFA) and against soluble egg antigen-enzyme-linked immunosorbent assay (SEA-ELISA) antigens in travellers.Methods: Samples were collected from 106 Dutch travellers who reported freshwater contact in sub-Saharan Africa and who were recruited up to 2 years after return. Subjects were asked to complete a detailed questionnaire on travel history, water contact, signs and symptoms compatible with schistosomiasis.Results: Two travellers were positive by serum CAA and an additional one by urine CAA. A total of 22/106 (21%) samples were antibody positive by AWA-IFA and 9/106 (9%) by SEA-ELISA. At follow-up 6 weeks and 6 months after praziquantel treatment, all seropositives remained antibody positive whereas CAA was cleared. Seropositivity could not be predicted by the type of fresh water-related activity, country visited or symptoms reported.Conclusion: The low number of UCP-LF CAA positives suggests that in travellers, active infections often do not establish or have very low worm burden. Based on our high seroconversion rates, we conclude that the AWA-IFA assay is the most sensitive test to detect schistosome exposure. Given the lack of predictive symptoms or risk factors, we recommend schistosomiasis screening at least by serology in all travellers with reported freshwater contact in high-endemic areas. Show less
Hoekstra, P.T.; Casacuberta Partal, M.; Lieshout, L. van; Corstjens, P.L.A.M.; Tsonaka, R.; Assare, R.K.; ... ; Dam, G.J. van 2020
BackgroundPreventive chemotherapy with praziquantel (PZQ) is the cornerstone of schistosomiasis control. However, a single dose of PZQ (40 mg/kg) does not cure all infections. Repeated doses of PZQ... Show moreBackgroundPreventive chemotherapy with praziquantel (PZQ) is the cornerstone of schistosomiasis control. However, a single dose of PZQ (40 mg/kg) does not cure all infections. Repeated doses of PZQ at short intervals might increase efficacy in terms of cure rate (CR) and intensity reduction rate (IRR). Here, we determined the efficacy of a single versus four repeated treatments with PZQ on Schistosoma mansoni infection in school-aged children from Cote d'Ivoire, using two different diagnostic tests.MethodsAn open-label, randomized controlled trial was conducted from October 2018 to January 2019. School-aged children with a confirmed S. mansoni infection based on Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA) urine cassette test were randomly assigned to receive either a single or four repeated doses of PZQ, administered at two-week intervals. The primary outcome was the difference in CR between the two treatment arms, measured by triplicate KK thick smears 10 weeks after the first treatment. Secondary outcomes included CR estimated by POC-CCA, IRR by KK and POC-CCA, and safety of repeated PZQ administration.Principal findingsDuring baseline screening, 1,022 children were assessed for eligibility of whom 153 (15%) had a detectable S. mansoni infection, and hence, were randomized to the standard treatment group (N = 70) and the intense treatment group (N = 83). Based on KK, the CR was 42% (95% confidence interval (CI) 31-52%) in the standard treatment group and 86% (95% CI 75-92%) in the intense treatment group. Observed IRR was 72% (95% CI 55-83%) in the standard treatment group and 95% (95% CI 85-98%) in the intense treatment group. The CR estimated by POC-CCA was 18% (95% CI 11-27%) and 36% (95% CI 26-46%) in the standard and intense treatment group, respectively. Repeated PZQ treatment did not result in a higher number of adverse events.Author summaryThe previously established efficacy of the widely used drug praziquantel (PZQ) against schistosomiasis might have been overestimated due to the use of inaccurate diagnostic methods. Repeated PZQ treatment at short intervals in areas with ongoing transmission could more effectively target non-susceptible schistosomula as they will have matured into drug susceptible worms within a few weeks. In the current study, we aimed to determine the cure rate (CR) of repeated PZQ, measured by the Kato-Katz (KK) technique and the point-of-care circulating cathodic antigen (POC-CCA) test, respectively. An open-label, randomized controlled trial was conducted assigning 153 school-aged children with a confirmed Schistosoma mansoni infection to two groups, one receiving a single PZQ treatment, while the second group received four repeated PZQ treatments, given at two-week intervals. Based on the KK test, the CR was significantly higher after four repeated treatments compared to a single treatment. When using POC-CCA, a diagnostic method that has not been utilized before in studies assessing the efficacy of four repeated PZQ treatments, the CR was much lower, even after four repeated PZQ treatments. Our results indicate that worms are still present after multiple PZQ treatments and that PZQ might be less efficacious than previously published. Show less
Casacuberta Partal, M.; Hoekstra, P.T.; Kornelis, D.; Lieshout, L. van; Dam, G.J. van 2019
The point-of-care strip assay for the detection of the schistosome Circulating Cathodic Antigen (POC-CCA) in urine has shown to be a user-friendly and sensitive alternative to stool microscopy for... Show moreThe point-of-care strip assay for the detection of the schistosome Circulating Cathodic Antigen (POC-CCA) in urine has shown to be a user-friendly and sensitive alternative to stool microscopy for the diagnosis of Schistosoma mansoni infections. However, visual scoring of the test is by definition observer dependent and leads to discussion about the qualitative interpretation, in particular in low intensity infections when test lines tend to be weak. In order to standardise visual scoring, an innovative approach for semi-quantitative interpretation of the POC-CCA cassettes, called G-scores, was developed and evaluated. Urines (n = 110) from a S. mansoni endemic area were used to evaluate this new approach. Test lines of the POC-CCA were visually compared against the G-scores, i.e. a series of artificial cassettes containing inkjet-printed strips of different intensities in order to grade the POC-CCA test line on a scale of 1 to 10. A significant positive correlation (Spearman 0.660, p < 0.001) was observed between G-scores and eggs per gram of faeces. This proof-of-concept study demonstrates the usefulness of the G-scores for standardising the visual scoring of the POC-CCA urine strip assay. Several research groups have already indicated an interest in the G-scores for their field work. Further distribution of the cassettes, in particular when provided in combination with reference standards, will assist the wider schistosomiasis community in dealing with issues like batch-to-batch differences and interpretation of trace readings. Show less
Casacuberta Partal, M.; Hoekstra, P.T.; Kornelis, D.; Lieshout, L. van; Dam, G.J. van 2019
The point-of-care strip assay for the detection of the schistosome Circulating Cathodic Antigen (POC-CCA) in urine has shown to be a user-friendly and sensitive alternative to stool microscopy for... Show moreThe point-of-care strip assay for the detection of the schistosome Circulating Cathodic Antigen (POC-CCA) in urine has shown to be a user-friendly and sensitive alternative to stool microscopy for the diagnosis of Schistosoma mansoni infections. However, visual scoring of the test is by definition observer dependent and leads to discussion about the qualitative interpretation, in particular in low intensity infections when test lines tend to be weak. In order to standardise visual scoring, an innovative approach for semi-quantitative interpretation of the POC-CCA cassettes, called G-scores, was developed and evaluated. Urines (n = 110) from a S. mansoni endemic area were used to evaluate this new approach. Test lines of the POC-CCA were visually compared against the G-scores, i.e. a series of artificial cassettes containing inkjet-printed strips of different intensities in order to grade the POC-CCA test line on a scale of 1 to 10. A significant positive correlation (Spearman 0.660, p < 0.001) was observed between G-scores and eggs per gram of faeces. This proof-of-concept study demonstrates the usefulness of the G-scores for standardising the visual scoring of the POC-CCA urine strip assay. Several research groups have already indicated an interest in the G-scores for their field work. Further distribution of the cassettes, in particular when provided in combination with reference standards, will assist the wider schistosomiasis community in dealing with issues like batch-to-batch differences and interpretation of trace readings. Show less
