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      Assessment of the accuracy of 11 different diagnostic tests for the detection of Schistosomiasis mansoni in individuals from a Brazilian area of low endemicity using latent class analysis

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          Abstract

          Background

          Schistosomiasis is a parasitic disease associated with poverty. It is estimated that 7.1 million people are infected with Schistosoma mansoni in Latin America, with 95% of them living in Brazil. Accurate diagnosis and timely treatment are important measures to control and eliminate schistosomiasis, but diagnostic improvements are needed to detect infections, especially in areas of low endemicity.

          Methodology

          This research aimed to evaluate the performance of 11 diagnostic tests using latent class analysis (LCA). A cross-sectional survey was undertaken in a low endemicity area of the municipality of Malacacheta, Minas Gerais, Brazil. Feces, urine, and blood samples were collected from 400 residents older than 6 years of age, who had not been treated with praziquantel in the 12 months previous to the collection of their samples. The collected samples were examined using parasitological (Helm Test ® kit Kato-Katz), nucleic acid amplification tests -NAATs (PCR, qPCR and LAMP on urine; PCR-ELISA, qPCR and LAMP on stool), and immunological (POC-CCA, the commercial anti- Schistosoma mansoni IgG ELISA kit from Euroimmun, and two in-house ELISA assays using either the recombinant antigen PPE or the synthetic peptide Smp150390.1) tests.

          Results

          The positivity rate of the 11 tests evaluated ranged from 5% (qPCR on urine) to 40.8% (commercial ELISA kit). The estimated prevalence of schistosomiasis was 12% (95% CI: 9–15%) according to the LCA. Among all tests assessed, the commercial ELISA kit had the highest estimated sensitivity (100%), while the Kato-Katz had the highest estimated specificity (99%). Based on the accuracy measures observed, we proposed three 2-step diagnostic approaches for the active search of infected people in endemic settings. The approaches proposed consist of combinations of commercial ELISA kit and NAATs tests performed on stool. All the approaches had higher sensitivity and specificity than the mean values observed for the 11 tests (70.4 and 89.5%, respectively).

          Conclusion

          We showed that it is possible to achieve high specificity and sensitivity rates with lower costs by combining serological and NAATs tests, which would assist in the decision-making process for appropriate allocation of public funding aiming to achieve the WHO target of eliminating schistosomiasis as a public health problem by 2030.

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          How to perform a meta-analysis with R: a practical tutorial

          Meta-analysis is of fundamental importance to obtain an unbiased assessment of the available evidence. In general, the use of meta-analysis has been increasing over the last three decades with mental health as a major research topic. It is then essential to well understand its methodology and interpret its results. In this publication, we describe how to perform a meta-analysis with the freely available statistical software environment R, using a working example taken from the field of mental health. R package meta is used to conduct standard meta-analysis. Sensitivity analyses for missing binary outcome data and potential selection bias are conducted with R package metasens. All essential R commands are provided and clearly described to conduct and report analyses. The working example considers a binary outcome: we show how to conduct a fixed effect and random effects meta-analysis and subgroup analysis, produce a forest and funnel plot and to test and adjust for funnel plot asymmetry. All these steps work similar for other outcome types. R represents a powerful and flexible tool to conduct meta-analyses. This publication gives a brief glimpse into the topic and provides directions to more advanced meta-analysis methods available in R.
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            There are two popular statistical models for meta-analysis, the fixed-effect model and the random-effects model. The fact that these two models employ similar sets of formulas to compute statistics, and sometimes yield similar estimates for the various parameters, may lead people to believe that the models are interchangeable. In fact, though, the models represent fundamentally different assumptions about the data. The selection of the appropriate model is important to ensure that the various statistics are estimated correctly. Additionally, and more fundamentally, the model serves to place the analysis in context. It provides a framework for the goals of the analysis as well as for the interpretation of the statistics. In this paper we explain the key assumptions of each model, and then outline the differences between the models. We conclude with a discussion of factors to consider when choosing between the two models. Copyright © 2010 John Wiley & Sons, Ltd. Copyright © 2010 John Wiley & Sons, Ltd.
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              Loop-mediated isothermal amplification of DNA.

              T. Notomi (2000)
              We have developed a novel method, termed loop-mediated isothermal amplification (LAMP), that amplifies DNA with high specificity, efficiency and rapidity under isothermal conditions. This method employs a DNA polymerase and a set of four specially designed primers that recognize a total of six distinct sequences on the target DNA. An inner primer containing sequences of the sense and antisense strands of the target DNA initiates LAMP. The following strand displacement DNA synthesis primed by an outer primer releases a single-stranded DNA. This serves as template for DNA synthesis primed by the second inner and outer primers that hybridize to the other end of the target, which produces a stem-loop DNA structure. In subsequent LAMP cycling one inner primer hybridizes to the loop on the product and initiates displacement DNA synthesis, yielding the original stem-loop DNA and a new stem-loop DNA with a stem twice as long. The cycling reaction continues with accumulation of 10(9) copies of target in less than an hour. The final products are stem-loop DNAs with several inverted repeats of the target and cauliflower-like structures with multiple loops formed by annealing between alternately inverted repeats of the target in the same strand. Because LAMP recognizes the target by six distinct sequences initially and by four distinct sequences afterwards, it is expected to amplify the target sequence with high selectivity.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                15 December 2022
                2022
                : 13
                : 1048457
                Affiliations
                [1] 1Grupo de Pesquisa em Helmintologia e Malacologia Médica, Instituto René Rachou, Fundação Oswaldo Cruz , Belo Horizonte, Minas Gerais, Brazil
                [2] 2Laboratório de Educação em Ambiente e Saúde, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz , Rio de Janeiro, Brazil
                [3] 3Núcleo de Estudos em Saúde Pública e Envelhecimento, Instituto René Rachou, Fundação Oswaldo Cruz , Belo Horizonte, Minas Gerais, Brazil
                [4] 4Grupo de Pesquisa em Biologia e Imunologia de Doenças Infecciosas e Parasitárias, Instituto René Rachou, Fundação Oswaldo Cruz , Belo Horizonte, Minas Gerais, Brazil
                [5] 5Grupo de Pesquisa em Genômica Funcional de Parasitos, Instituto René Rachou, Fundação Oswaldo Cruz , Belo Horizonte, Minas Gerais, Brazil
                Author notes

                Edited by: Leonard Peruski, Centers for Disease Control and Prevention (CDC), United States

                Reviewed by: Jean Tenena Coulibaly, Félix Houphouët-Boigny University, Côte d'Ivoire; Georgette B. Salieb-Beugelaar, Münster University of Applied Sciences, Germany

                *Correspondence: Cristina Toscano Fonseca, cristina.toscano@ 123456fiocruz.br

                This article was submitted to Infectious Agents and Disease, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2022.1048457
                9797737
                36590409
                e2213672-0e6e-47d2-b504-91cd18d72e88
                Copyright © 2022 Mesquita, Caldeira, Favre, Massara, Beck, Simões, Carvalho, Neves, de Oliveira, Lacerda, de Almeida, Carvalho, Mourão, Oliveira, Silva-Pereira and Fonseca.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 19 September 2022
                : 04 November 2022
                Page count
                Figures: 4, Tables: 3, Equations: 3, References: 81, Pages: 20, Words: 14985
                Funding
                Funded by: Conselho Nacional de Desenvolvimento Científico/Programa de Excelência em Pesquisa—Pesquisa e Ensaios Clínicos
                Award ID: 420685/2017-0
                Funded by: Fundação de Amparo à Pesquisa do Estado de Minas Gerais , doi 10.13039/501100004901;
                Award ID: APQ-01596-16 e APQ-00875-18
                Funded by: CAPES Print-Fiocruz Program, and Vice-Presidência de Educação, Informação e Comunicação (VPEIC-Fiocruz)
                Award ID: CTF-303131/2018-7
                Award ID: EO-313471/2019-3
                Award ID: 317389/2021-1
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                schistosomiasis,schistosoma mansoni,diagnostic tests,diagnosis,latent class analysis,clinical research,sensitivity,specificity

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