Metagenomic Next-Generation Sequencing for the Diagnosis of Infectious Uveitis: A Comprehensive Systematic Review

<b>Background</b>: Infectious uveitis is a potentially sight-threatening condition that requires timely and accurate pathogen identification to guide effective therapy. However, conventional microbiological tests (CMTs) often lack sensitivity and the inclusiveness of pathogen detection....

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Main Authors: Isabele Pardo, Luciana P. S. Finamor, Pedro S. Marra, Julia Messina G. Ferreira, Maria Celidonio Gutfreund, Mariana Kim Hsieh, Yimeng Li, João Renato Rebello Pinho, Luiz Vicente Rizzo, Takaaki Kobayashi, Daniel J. Diekema, Michael B. Edmond, Paulo J. M. Bispo, Alexandre R. Marra
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/17/6/757
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author Isabele Pardo
Luciana P. S. Finamor
Pedro S. Marra
Julia Messina G. Ferreira
Maria Celidonio Gutfreund
Mariana Kim Hsieh
Yimeng Li
João Renato Rebello Pinho
Luiz Vicente Rizzo
Takaaki Kobayashi
Daniel J. Diekema
Michael B. Edmond
Paulo J. M. Bispo
Alexandre R. Marra
author_facet Isabele Pardo
Luciana P. S. Finamor
Pedro S. Marra
Julia Messina G. Ferreira
Maria Celidonio Gutfreund
Mariana Kim Hsieh
Yimeng Li
João Renato Rebello Pinho
Luiz Vicente Rizzo
Takaaki Kobayashi
Daniel J. Diekema
Michael B. Edmond
Paulo J. M. Bispo
Alexandre R. Marra
author_sort Isabele Pardo
collection DOAJ
description <b>Background</b>: Infectious uveitis is a potentially sight-threatening condition that requires timely and accurate pathogen identification to guide effective therapy. However, conventional microbiological tests (CMTs) often lack sensitivity and the inclusiveness of pathogen detection. Metagenomic next-generation sequencing (mNGS) offers an unbiased approach to detecting a broad range of pathogens. This review evaluates its diagnostic performance in detecting infectious uveitis. <b>Methods</b>: A systematic search across multiple databases identified studies assessing the use of mNGS for diagnosing infectious uveitis. The included studies compared mNGS to CMTs, including polymerase chain reaction (PCR), culture, serology, and the IGRA (Interferon-Gamma Release Assay). The study characteristics; the detection rates; and the sensitivity, specificity, and predictive values were extracted. The sensitivity and specificity of mNGS were calculated using CMTs as a reference. <b>Results</b>: Twelve studies comprising 859 patients were included. The sensitivity of mNGS compared to that of CMTs ranged from 38.4% to 100%, while specificity varied between 15.8% and 100%. The commonly detected pathogens included varicella-zoster virus, cytomegalovirus, <i>Toxoplasma gondii</i>, and herpes simplex virus. In some cases, mNGS outperformed PCR in viral detection, aiding diagnosis when the standard methods failed. However, contamination risks and inconsistent diagnostic thresholds were noted. <b>Conclusions</b>: mNGS enables the diagnosis of infectious uveitis, particularly for viral causes, but its variable performance and standardization challenges warrant further investigation.
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spelling doaj-art-1a43232efdd240d7adf11abfa6fddd482025-08-20T03:29:49ZengMDPI AGViruses1999-49152025-05-0117675710.3390/v17060757Metagenomic Next-Generation Sequencing for the Diagnosis of Infectious Uveitis: A Comprehensive Systematic ReviewIsabele Pardo0Luciana P. S. Finamor1Pedro S. Marra2Julia Messina G. Ferreira3Maria Celidonio Gutfreund4Mariana Kim Hsieh5Yimeng Li6João Renato Rebello Pinho7Luiz Vicente Rizzo8Takaaki Kobayashi9Daniel J. Diekema10Michael B. Edmond11Paulo J. M. Bispo12Alexandre R. Marra13Faculdade Israelita de Ciências da Saúde Albert Einstein, Hospital Israelita Albert Einstein, São Paulo 05652-900, SP, BrazilDepartment of Ophthalmology, Universidade Federal de São Paulo, São Paulo 05508-090, SP, BrazilUniversity of California San Francisco, San Francisco, CA 94143, USAHospital Israelita Albert Einstein, Instituto Israelita de Ensino e Pesquisa Albert Einstein, São Paulo 05652-900, SP, BrazilFaculdade Israelita de Ciências da Saúde Albert Einstein, Hospital Israelita Albert Einstein, São Paulo 05652-900, SP, BrazilThe Program of Hospital Epidemiology, University of Iowa Health Care, Iowa City, IA 52242, USAUniversity of California San Francisco, San Francisco, CA 94143, USAFaculdade Israelita de Ciências da Saúde Albert Einstein, Hospital Israelita Albert Einstein, São Paulo 05652-900, SP, BrazilHospital Israelita Albert Einstein, Instituto Israelita de Ensino e Pesquisa Albert Einstein, São Paulo 05652-900, SP, BrazilDepartment of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADepartment of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADepartment of Medicine, School of Medicine, West Virginia University, Morgantown, WV 26506-9111, USADepartment of Ophthalmology, Harvard Medical School, Infectious Disease Institute, Massachusetts Eye and Ear, Boston, MA 02114, USAFaculdade Israelita de Ciências da Saúde Albert Einstein, Hospital Israelita Albert Einstein, São Paulo 05652-900, SP, Brazil<b>Background</b>: Infectious uveitis is a potentially sight-threatening condition that requires timely and accurate pathogen identification to guide effective therapy. However, conventional microbiological tests (CMTs) often lack sensitivity and the inclusiveness of pathogen detection. Metagenomic next-generation sequencing (mNGS) offers an unbiased approach to detecting a broad range of pathogens. This review evaluates its diagnostic performance in detecting infectious uveitis. <b>Methods</b>: A systematic search across multiple databases identified studies assessing the use of mNGS for diagnosing infectious uveitis. The included studies compared mNGS to CMTs, including polymerase chain reaction (PCR), culture, serology, and the IGRA (Interferon-Gamma Release Assay). The study characteristics; the detection rates; and the sensitivity, specificity, and predictive values were extracted. The sensitivity and specificity of mNGS were calculated using CMTs as a reference. <b>Results</b>: Twelve studies comprising 859 patients were included. The sensitivity of mNGS compared to that of CMTs ranged from 38.4% to 100%, while specificity varied between 15.8% and 100%. The commonly detected pathogens included varicella-zoster virus, cytomegalovirus, <i>Toxoplasma gondii</i>, and herpes simplex virus. In some cases, mNGS outperformed PCR in viral detection, aiding diagnosis when the standard methods failed. However, contamination risks and inconsistent diagnostic thresholds were noted. <b>Conclusions</b>: mNGS enables the diagnosis of infectious uveitis, particularly for viral causes, but its variable performance and standardization challenges warrant further investigation.https://www.mdpi.com/1999-4915/17/6/757systematic literature reviewmetagenomic NGSinfectious uveitisdiagnostic methods
spellingShingle Isabele Pardo
Luciana P. S. Finamor
Pedro S. Marra
Julia Messina G. Ferreira
Maria Celidonio Gutfreund
Mariana Kim Hsieh
Yimeng Li
João Renato Rebello Pinho
Luiz Vicente Rizzo
Takaaki Kobayashi
Daniel J. Diekema
Michael B. Edmond
Paulo J. M. Bispo
Alexandre R. Marra
Metagenomic Next-Generation Sequencing for the Diagnosis of Infectious Uveitis: A Comprehensive Systematic Review
Viruses
systematic literature review
metagenomic NGS
infectious uveitis
diagnostic methods
title Metagenomic Next-Generation Sequencing for the Diagnosis of Infectious Uveitis: A Comprehensive Systematic Review
title_full Metagenomic Next-Generation Sequencing for the Diagnosis of Infectious Uveitis: A Comprehensive Systematic Review
title_fullStr Metagenomic Next-Generation Sequencing for the Diagnosis of Infectious Uveitis: A Comprehensive Systematic Review
title_full_unstemmed Metagenomic Next-Generation Sequencing for the Diagnosis of Infectious Uveitis: A Comprehensive Systematic Review
title_short Metagenomic Next-Generation Sequencing for the Diagnosis of Infectious Uveitis: A Comprehensive Systematic Review
title_sort metagenomic next generation sequencing for the diagnosis of infectious uveitis a comprehensive systematic review
topic systematic literature review
metagenomic NGS
infectious uveitis
diagnostic methods
url https://www.mdpi.com/1999-4915/17/6/757
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