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      Diagnostic performance of ELISA, IFAT and Western blot for the detection of anti- Leishmania infantum antibodies in cats using a Bayesian analysis without a gold standard

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          Abstract

          Background

          Anti- Leishmania antibodies are increasingly investigated in cats for epidemiological studies or for the diagnosis of clinical feline leishmaniosis. The immunofluorescent antibody test (IFAT), the enzyme-linked immunosorbent assay (ELISA) and western blot (WB) are the serological tests more frequently used. The aim of the present study was to assess diagnostic performance of IFAT, ELISA and WB to detect anti- L. infantum antibodies in feline serum samples obtained from endemic ( n = 76) and non-endemic ( n = 64) areas and from cats affected by feline leishmaniosis ( n = 21) by a Bayesian approach without a gold standard.

          Methods

          Cut-offs were set at 80 titre for IFAT and 40 ELISA units for ELISA. WB was considered positive in presence of at least a 18 KDa band. Statistical analysis was performed through a written routine with MATLAB software in the Bayesian framework. The latent data and observations from the joint posterior were simulated in the Bayesian approach by an iterative Markov Chain Monte Carlo technique using the Gibbs sampler for estimating sensitivity and specificity of the three tests.

          Results

          The median seroprevalence in the sample used for evaluating the performance of tests was estimated at 0.27 [credible interval (CI) = 0.20–0.34]. The median sensitivity of the three different methods was 0.97 (CI: 0.86–1.00), 0.75 (CI: 0.61–0.87) and 0.70 (CI: 0.56–0.83) for WB, IFAT and ELISA, respectively. Median specificity reached 0.99 (CI: 0.96–1.00) with WB, 0.97 (CI: 0.93–0.99) with IFAT and 0.98 (CI: 0.94–1.00) with ELISA. IFAT was more sensitive than ELISA (75 vs 70%) for the detection of subclinical infection while ELISA was better for diagnosing clinical leishmaniosis when compared with IFAT (98 vs 97%).

          Conclusions

          The overall performance of all serological techniques was good and the most accurate test for anti- Leishmania antibody detection in feline serum samples was WB.

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          Most cited references26

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          Measuring the accuracy of diagnostic systems.

          J Swets (1988)
          Diagnostic systems of several kinds are used to distinguish between two classes of events, essentially "signals" and "noise". For them, analysis in terms of the "relative operating characteristic" of signal detection theory provides a precise and valid measure of diagnostic accuracy. It is the only measure available that is uninfluenced by decision biases and prior probabilities, and it places the performances of diverse systems on a common, easily interpreted scale. Representative values of this measure are reported here for systems in medical imaging, materials testing, weather forecasting, information retrieval, polygraph lie detection, and aptitude testing. Though the measure itself is sound, the values obtained from tests of diagnostic systems often require qualification because the test data on which they are based are of unsure quality. A common set of problems in testing is faced in all fields. How well these problems are handled, or can be handled in a given field, determines the degree of confidence that can be placed in a measured value of accuracy. Some fields fare much better than others.
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            LeishVet guidelines for the practical management of canine leishmaniosis

            The LeishVet group has formed recommendations designed primarily to help the veterinary clinician in the management of canine leishmaniosis. The complexity of this zoonotic infection and the wide range of its clinical manifestations, from inapparent infection to severe disease, make the management of canine leishmaniosis challenging. The recommendations were constructed by combining a comprehensive review of evidence-based studies, extensive clinical experience and critical consensus opinion discussions. The guidelines presented here in a short version with graphical topic displays suggest standardized and rational approaches to the diagnosis, treatment, follow-up, control and prevention of canine leishmaniosis. A staging system that divides the disease into four stages is aimed at assisting the clinician in determining the appropriate therapy, forecasting prognosis, and implementing follow-up steps required for the management of the leishmaniosis patient.
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              Epidemiologic issues in the validation of veterinary diagnostic tests.

              In this review, we critically discuss the objectives, methods and limitations of different approaches for the validation of diagnostic tests. We show (based on published data and our own experiences) that estimates for the diagnostic sensitivity and specificity may vary among populations and/or subpopulations of animals, conditional on the distribution of influential covariates. Additional variability in those parameter estimates may be attributable to the sampling strategy. The uncertainty about diagnostic parameters is of concern for the decision-maker in the context of clinical diagnosis or quantitative risk assessment as well as for the epidemiologist who uses test data for prevalence estimation or risk-factor studies. Examples for the calculation of diagnostic parameters are presented together with bias-avoidance strategies. We suggest guidelines for an epidemiologic approach to test validation of veterinary diagnostic tests.
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                Author and article information

                Contributors
                mfpersichetti@gmail.com
                laia.solano@uab.cat
                angela.vullo@izssicilia.it
                marisa.masucci@unime.it
                marty.p@chu-nice.fr
                delaunay.p@chu-nice.fr
                fabrizio.vitale@izssicilia.it
                mariagrazia.pennisi@unime.it
                Journal
                Parasit Vectors
                Parasit Vectors
                Parasites & Vectors
                BioMed Central (London )
                1756-3305
                13 March 2017
                13 March 2017
                2017
                : 10
                : 119
                Affiliations
                [1 ]ISNI 0000 0004 1758 1905, GRID grid.466852.b, , Istituto Zooprofilattico Sperimentale della Sicilia, ; A. Mirri, Via G. Marinuzzi 3, Palermo, 90129 Italy
                [2 ]GRID grid.7080.f, Departament de Medicina i Cirurgia Animals. Facultat de Veterinària, , Universitat Autònoma de Barcelona, ; Bellaterra, Cerdanyola, 08193 Barcelona Spain
                [3 ]ISNI 0000 0001 2178 8421, GRID grid.10438.3e, Dipartimento di Scienze Veterinarie, , Università degli Studi di Messina , ; Polo Universitario Annunziata, Messina, 98168 Italy
                [4 ]Centre Hospitalier Universitaire de Nice, Faculté de Médecine, Université de Nice-Sophia Antipolis, Inserm U 1065, Hôpital de l’Archet, 151, route de Saint Antoine de Ginestière, CS 23079 06202 Nice Cedex 3, France
                [5 ]Parasitologie-Mycologie, Hôpital de l’Archet, Centre Hospitalier Universitaire de Nice, France-MIVEGEC, UMR IRD224 - CNRS 5290 - Université de Montpellier, Montpellier Cedex 5, France
                [6 ]ISNI 0000 0004 1758 1905, GRID grid.466852.b, , Centro di Referenza Nazionale per le Leishmaniosi (C.Re.Na.L), Istituto Zooprofilattico Sperimentale della Sicilia, ; A. Mirri, Via G. Marinuzzi 3, Palermo, 90129 Italy
                Article
                2046
                10.1186/s13071-017-2046-3
                5346856
                28285598
                12e47a52-1a95-4ccd-ac2c-db99951a72fd
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 20 January 2017
                : 17 February 2017
                Categories
                Research
                Custom metadata
                © The Author(s) 2017

                Parasitology
                bayesian analysis,cat,diagnostic performance,elisa,gold standard,ifat,leishmania,leishmaniosis,serological diagnosis,western blot

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