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

Aims Natriuretic peptides are extensively studied biomarkers for atrial fibrillation (AF) and heart failure (HF). Their role in the pathogenesis of both diseases is not entirely understood and previous studies several single-nucleotide polymorphisms (SNPs) at the NPPA-NPPB locus associated with natriuretic peptides have been identified. We investigated the causal relationship between natriuretic peptides and AF as well as HF using a Mendelian randomization approach. Methods and results N-terminal pro B-type natriuretic peptide (NT-proBNP) (N = 6669), B-type natriuretic peptide (BNP) (N = 6674), and mid-regional pro atrial natriuretic peptide (MR-proANP) (N = 6813) were measured in the FINRISK 1997 cohort. N = 30 common SNPs related to NT-proBNP, BNP, and MR-proANP were selected from studies. We performed six Mendelian randomizations for all three natriuretic peptide biomarkers and for both outcomes, AF and HF, separately. Polygenic risk scores (PRSs) based on multiple SNPs were used as genetic instrumental variable in Mendelian randomizations. Polygenic risk scores were significantly associated with the three natriuretic peptides. Polygenic risk scores were not significantly associated with incident AF nor HF. Most cardiovascular risk factors showed significant confounding percentages, but no association with PRS. A causal relation except for small causal betas is unlikely. Conclusion In our Mendelian randomization approach, we confirmed an association between common genetic variation at the NPPA-NPPB locus and natriuretic peptides. A strong causal relationship between natriuretic peptides and incidence of AF as well as HF at the community-level was ruled out. Therapeutic approaches targeting natriuretic peptides will therefore very likely work through indirect mechanisms.

BackgroundSystemic sclerosis (SSc) is a rare autoimmune multisystemic disease with a significant disease burden and impact on life quality and survival. Disease specific, diagnostic and prognostic antibodies (ab) are known such as Scl70 and centromer (ACA) ab1 or recently endothelin or angiotensin receptors.2 Functional ab can bind G protein-coupled receptors (GPCR) regulating immune function and were reported in the pathogenesis of various inflammatory and non-inflammatory diseases.3 ObjectivesWe analysed 31 ab against GPCRs and growth factors in a retrospective cohort of 71 SSc patients compared to 196 sera from healthy controls (HC). Ab levels were related to disease manifestations such as sex, age, SSc phenotype in order to hypothesise functional ab and new pathogenic targets in SSc.MethodsThe retrospective clinical characterisation of 14 male and 57 female SSc patients (26–82 years) included mRSS, organ involvement assessed by laboratory tests, spirometry and imaging such as CT-scan or echocardiography. 30/71 had active disease (EUSTAR activity score). Ab were measured by ELISA and normalised to a standard serum. Median ab levels from SSc were compared to HC (Mann Whitney Test). Ab patterns were analysed using different statistical approaches (factor analysis, principal component analysis (PCA), linear discriminant analysis (LDA), cluster analysis and biserial correlation.ResultsClinical SSc subgroups (diffuse/limited cutaneous, male/female) differ in ab levels and form separate clusters (LDA method). Moreover, 5 resp. 7 latent factors group ab and clinical disease manifestations. Factor analysis reveals VEGFR2 and YBX1 ab to be more unique with the lowest communalities. The biserial correlation shows moderate associations between ab patterns and SSc specific symptoms such as Raynaud’s, calcinosis or akroosteolysis but also unspecific symptoms such as polyneuropathy. Compared to association of ETAR ab with Raynaud’s and skin sclerosis HGFR ab are inversely correlated. In HC most ab levels against GPCR and growth factors are higher than in SSc except for YBX1 which has the highest ab levels in SSc patients. In HC ab levels against YBX1 ab are associated with male sex and family history of rheumatic diseases. Yet, ADRB2 ab are linked to the absence of GI symptoms or depression and ab against ENG, ETAR, PAR2, PAR1 with normal troponine levels (absence of heart involvement).Abstract OP0005 – Figure 1(a) Projection of individuals (points) and variables (arrows), representing the measured proteins, in the space of the two principle components. The almost perfect separation between controls (cyan) and cases (orange) is explained by higher protein levels for almost all proteins in the HD groups against lower values in the SSc group. By contrast, only the YBI_P18 protein presents a tendance to be higher in the SSc group and lower in the other group. M1 and betaladr proteins have lowest contributions for separing HG from SSc participiants. (b) Dandelion plot displays 5 latent factors the cluster antibodies against GPCR...

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