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      Accuracy of parasitological and immunological tests for the screening of human schistosomiasis in immigrants and refugees from African countries: An approach with Latent Class Analysis

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          Abstract

          Background

          Schistosomiasis is a neglected infection affecting millions of people, mostly living in sub-Saharan Africa. Morbidity and mortality due to chronic infection are relevant, although schistosomiasis is often clinically silent. Different diagnostic tests have been implemented in order to improve screening and diagnosis, that traditionally rely on parasitological tests with low sensitivity. Aim of this study was to evaluate the accuracy of different tests for the screening of schistosomiasis in African migrants, in a non endemic setting.

          Methodology/Principal findings

          A retrospective study was conducted on 373 patients screened at the Centre for Tropical Diseases (CTD) in Negrar, Verona, Italy. Biological samples were tested with: stool/urine microscopy, Circulating Cathodic Antigen (CCA) dipstick test, ELISA, Western blot, immune-chromatographic test (ICT). Test accuracy and predictive values of the immunological tests were assessed primarily on the basis of the results of microscopy (primary reference standard): ICT and WB resulted the test with highest sensitivity (94% and 92%, respectively), with a high NPV (98%). CCA showed the highest specificity (93%), but low sensitivity (48%). The analysis was conducted also using a composite reference standard, CRS (patients classified as infected in case of positive microscopy and/or at least 2 concordant positive immunological tests) and Latent Class Analysis (LCA). The latter two models demonstrated excellent agreement (Cohen’s kappa: 0.92) for the classification of the results. In fact, they both confirmed ICT as the test with the highest sensitivity (96%) and NPV (97%), moreover PPV was reasonably good (78% and 72% according to CRS and LCA, respectively). ELISA resulted the most specific immunological test (over 99%). The ICT appears to be a suitable screening test, even when used alone.

          Conclusions

          The rapid test ICT was the most sensitive test, with the potential of being used as a single screening test for African migrants.

          Author summary

          Schistosomiasis is probably the most important of the neglected tropical diseases (NTD) caused by helminthes (worms). It is acquired bathing in freshwater in endemic areas. The life cycle is complex and involves freshwater snails. Schistosomiasis, caused by Schistosoma mansoni, S. haematobium and less frequently by other species, affects more than 200 million people, mostly in Africa, and may chronically cause irreversible damage of the liver ( S. mansoni) or of the kidneys and the urinary tract, including cancer of the bladder ( S. haematobium). As in chronic infections eggs of both species are often missed by microscopy of faeces and urine, with this retrospective study we evaluate the accuracy of different, alternative diagnostic tests, for the screening of schistosomiasis in African migrants and asylum seekers, of whom many thousands reach the Italian coast every year proceding from the most endemic areas. The most interesting finding of our study is that a rapid diagnostic test for antibody detection in blood, easy to use as a point-of-care tool, resulted the most sensitive of the five tests evaluated, and thus is very promising as a screening tool even when used without any additional test.

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          Most cited references33

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          A review of solutions for diagnostic accuracy studies with an imperfect or missing reference standard.

          In diagnostic accuracy studies, the reference standard may be imperfect or not available in all patients. We systematically reviewed the proposed solutions for these situations and generated methodological guidance. Review of methodological articles. We categorized the solutions into four main groups. The first group includes methods that impute or adjust for missing data on the reference standard. The second group consists of methods that correct estimates of accuracy obtained with an imperfect reference standard. In the third group a reference standard is constructed by combining multiple test results through a predefined rule, based on a consensus procedure, or through statistical modeling. In the fourth group, the diagnostic accuracy paradigm is abandoned in favor of validation studies that relate index test results to relevant clinical data, such as history, future clinical events, and response to therapy. Most of the methods try to impute, adjust, or construct a reference standard. In situations that deviate only marginally from the classical diagnostic accuracy paradigm, these are valuable methods. In cases where an acceptable reference standard does not exist, the concept of clinical test validation may provide an alternative paradigm to evaluate a diagnostic test.
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            Advances in the Diagnosis of Human Schistosomiasis.

            Schistosomiasis is a major neglected tropical disease that afflicts more than 240 million people, including many children and young adults, in the tropics and subtropics. The disease is characterized by chronic infections with significant residual morbidity and is of considerable public health importance, with substantial socioeconomic impacts on impoverished communities. Morbidity reduction and eventual elimination through integrated intervention measures are the focuses of current schistosomiasis control programs. Precise diagnosis of schistosome infections, in both mammalian and snail intermediate hosts, will play a pivotal role in achieving these goals. Nevertheless, despite extensive efforts over several decades, the search for sensitive and specific diagnostics for schistosomiasis is ongoing. Here we review the area, paying attention to earlier approaches but emphasizing recent developments in the search for new diagnostics for schistosomiasis with practical applications in the research laboratory, the clinic, and the field. Careful and rigorous validation of these assays and their cost-effectiveness will be needed, however, prior to their adoption in support of policy decisions for national public health programs aimed at the control and elimination of schistosomiasis.
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              Outbreak of urogenital schistosomiasis in Corsica (France): an epidemiological case study.

              Schistosomiasis is a snail-borne parasitic disease endemic in several tropical and subtropical countries. However, in the summer of 2013, an unexpected outbreak of urogenital schistosomiasis occurred in Corsica, with more than 120 local people or tourists infected. We used a multidisciplinary approach to investigate the epidemiology of urogenital schistosomiasis in Corsica, aiming to elucidate the origin of the outbreak.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                5 June 2017
                June 2017
                : 11
                : 6
                : e0005593
                Affiliations
                [1 ]Centre for Tropical Diseases, Ospedale Sacro Cuore Don Calabria, Negrar, Verona, Italy
                [2 ]University of Verona, Department of Computer Science, Verona, Italy
                [3 ]Barcelona Institute for Global Health, ISGlobal-CRESIB, Universitat de Barcelona, Barcelona, Spain
                [4 ]Infectious and Tropical Diseases Department, Azienda Ospedaliera Universitaria Careggi, Florence, Italy
                Swiss Tropical and Public Health Institute, SWITZERLAND
                Author notes

                The authors have declared that no competing interests exist.

                • Conceptualization: ZB.

                • Data curation: AB AA FG FF FP.

                • Formal analysis: MG ZB.

                • Funding acquisition: AB.

                • Investigation: AB AA FG FF FP.

                • Methodology: ZB MG DB.

                • Project administration: AB FP ZB.

                • Resources: FP FF.

                • Supervision: DB ZB.

                • Visualization: MG ARM LZ.

                • Writing – original draft: AB ZB.

                • Writing – review & editing: MG ZB ARM DB LZ AA FG.

                Author information
                http://orcid.org/0000-0003-0108-6822
                Article
                PNTD-D-17-00211
                10.1371/journal.pntd.0005593
                5472324
                28582412
                27801556-96a1-4832-a89f-2cedcffa1def
                © 2017 Beltrame et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 February 2017
                : 24 April 2017
                Page count
                Figures: 2, Tables: 3, Pages: 15
                Funding
                LDBIO Diagnostics provided the Western blot and ICT kits. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Parasitic Diseases
                Helminth Infections
                Schistosomiasis
                Medicine and Health Sciences
                Tropical Diseases
                Neglected Tropical Diseases
                Schistosomiasis
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Urine
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Urine
                Biology and Life Sciences
                Physiology
                Body Fluids
                Urine
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Urine
                Biology and Life Sciences
                Organisms
                Animals
                Invertebrates
                Helminths
                Schistosoma
                Schistosoma Mansoni
                Biology and Life Sciences
                Organisms
                Animals
                Invertebrates
                Helminths
                Schistosoma
                Schistosoma Haematobium
                Research and Analysis Methods
                Immunologic Techniques
                Immunoassays
                Enzyme-Linked Immunoassays
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Serology
                Medicine and Health Sciences
                Parasitic Diseases
                Medicine and Health Sciences
                Diagnostic Medicine
                Custom metadata
                vor-update-to-uncorrected-proof
                2017-06-15
                The whole database is available in the Supporting information file.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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