{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:01:15Z","timestamp":1787022075218,"version":"build-2736575974"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tuberculous meningitis (TBM) is a severe form of extrapulmonary tuberculosis and its early diagnosis is very difficult leading to present with severe disability or die. The current study aimed to assess the accuracy of metagenomic next generation sequencing (mNGS) for TBM, and to identify a new test for the early diagnosis of TBM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched for articles published in Embase, PubMed, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data up to June 30, 2020 for studies that assessed the efficacy of mNGS for the diagnosis of TBM. Then, the accuracy between mNGS and a composite reference standard (CRS) in these articles was compared using the meta-analysis approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Four independent studies with 342 samples comparing mNGS and a CRS were included in this study. The sensitivity of mNGS for TBM diagnosis ranged from 27% to 84%. The combined sensitivity of mNGS was 61%, and the I\n                      <jats:sup>2<\/jats:sup>\n                      value was 92%. Moreover, the specificity of mNGS for TBM diagnosis ranged from 96% to 100%. The combined specificity of mNGS was 98%, and the I\n                      <jats:sup>2<\/jats:sup>\n                      value was 74%. The heterogeneity between studies in terms of sensitivity and specificity was significant. The area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) of mNGS for TBM was 0.98.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The sensitivity of mNGS for TBM diagnosis was moderate. Furthermore, the specificity was extremely high, and the AUC of the SROC indicated a very good diagnostic efficacy. mNGS could be used as an early diagnostic method for TBM, however, the results should be treated with caution for the heterogeneity between studies was extremely significant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>INPLASY202070100.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0243161","type":"journal-article","created":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T16:06:43Z","timestamp":1606838803000},"page":"e0243161","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":34,"title":["Metagenomic next generation sequencing for the diagnosis of tuberculosis meningitis: A systematic review and meta-analysis"],"prefix":"10.1371","volume":"15","author":[{"given":"Guocan","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuchen","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqin","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8121-5932","authenticated-orcid":true,"given":"Hong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,12,1]]},"reference":[{"key":"pone.0243161.ref001","unstructured":"World Health Organization. Global tuberculosis report 2019. Geneva, Switzerland; 2019."},{"issue":"3","key":"pone.0243161.ref002","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S1473-3099(19)30649-8","article-title":"Xpert MTB\/RIF Ultra versus Xpert MTB\/RIF for the diagnosis of tuberculous meningitis: a prospective, randomised, diagnostic accuracy study","volume":"20","author":"J Donovan","year":"2020","journal-title":"Lancet Infect Dis."},{"key":"pone.0243161.ref003","first-page":"4878240","article-title":"Diagnostic Accuracy of the Xpert MTB\/RIF Assay for Lymph Node Tuberculosis: A Systematic Review and Meta-Analysis","volume":"2019","author":"G Yu","year":"2019","journal-title":"Biomed Res Int"},{"issue":"3","key":"pone.0243161.ref004","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/S1473-3099(19)30550-X","article-title":"Xpert MTB\/RIF Ultra for the diagnosis of HIV-associated tuberculous meningitis: a prospective validation study","volume":"20","author":"FV Cresswell","journal-title":"Lancet Infect Dis. 2020"},{"key":"pone.0243161.ref005","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1097\/MAJ.0b013e3181a590f1","article-title":"Predictors for outcome and treatment delay in patients with tuberculous meningitis","volume":"338","author":"JJ Sheu","year":"2009","journal-title":"Am J Med Sci"},{"key":"pone.0243161.ref006","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.2217\/bmm.14.67","article-title":"Methods of rapid diagnosis for the etiology of meningitis in adults","volume":"8","author":"NC Bahr","year":"2014","journal-title":"Biomark Med"},{"issue":"1","key":"pone.0243161.ref007","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/S1473-3099(17)30474-7","article-title":"Diagnostic accuracy of Xpert MTB\/RIF Ultra for tuberculous meningitis in HIV-infected adults: a prospective cohort study","volume":"18","author":"NC Bahr","year":"2018","journal-title":"Lancet Infect Dis"},{"key":"pone.0243161.ref008","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.2217\/fmb-2017-0028","article-title":"Challenges in pleural tuberculosis diagnosis: existing reference standards and nucleic acid tests","volume":"12","author":"S Tyagi","year":"2017","journal-title":"Future Microbiol"},{"issue":"8","key":"pone.0243161.ref009","first-page":"CD012768","article-title":"Xpert\u00ae MTB\/RIF assay for extrapulmonary tuberculosis and rifampicin resistance.","volume":"8","author":"M Kohli","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"issue":"9","key":"pone.0243161.ref010","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1093\/cid\/ciw083","article-title":"Tuberculous Meningitis International Research Consortium. GeneXpert MTB\/Rif to Diagnose Tuberculous Meningitis: Perhaps the First Test but not the Last","volume":"62","author":"NC Bahr","year":"2016","journal-title":"Clin Infect Dis"},{"issue":"suppl_2","key":"pone.0243161.ref011","doi-asserted-by":"crossref","first-page":"S231","DOI":"10.1093\/cid\/ciy693","article-title":"Microbiological Diagnostic Performance of Metagenomic Next-generation Sequencing When Applied to Clinical Practice","volume":"67","author":"Q Miao","year":"2018","journal-title":"Clin Infect Dis"},{"issue":"5","key":"pone.0243161.ref012","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s12031-019-01472-z","article-title":"Reduction of Human DNA Contamination in Clinical Cerebrospinal Fluid Specimens Improves the Sensitivity of Metagenomic Next-Generation Sequencing","volume":"70","author":"XC Ji","year":"2020","journal-title":"J Mol Neurosci"},{"issue":"3","key":"pone.0243161.ref013","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.clinre.2018.04.007","article-title":"Diagnosis of local hepatic tuberculosis through next-generation sequencing: Smarter, faster and better","volume":"42","author":"JW Ai","year":"2018","journal-title":"Clin Res Hepatol Gastroenterol"},{"issue":"8","key":"pone.0243161.ref014","doi-asserted-by":"crossref","first-page":"574.e1","DOI":"10.1016\/j.cmi.2017.02.006","article-title":"Untargeted next-generation sequencing-based first-line diagnosis of infection in immunocompromised adults: a multicentre, blinded, prospective study","volume":"23","author":"P Parize","year":"2017","journal-title":"Clin Microbiol Infect"},{"key":"pone.0243161.ref015","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.3389\/fmicb.2019.01993","article-title":"The Feasibility of Metagenomic Next-Generation Sequencing to Identify Pathogens Causing Tuberculous Meningitis in Cerebrospinal Fluid","volume":"10","author":"S Wang","year":"2019","journal-title":"Front Microbiol"},{"key":"pone.0243161.ref016","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3389\/fcimb.2020.00088","article-title":"Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Encephalitis and Meningitis: A Large, Prospective Case Series of 213 Patients","volume":"10","author":"XW Xing","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"key":"pone.0243161.ref017","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.ijid.2020.04.048","article-title":"Metagenomic Next-Generation Sequencing (mNGS) in cerebrospinal fluid for rapid diagnosis of Tuberculosis meningitis in HIV-negative population","volume":"96","author":"L Yan","year":"2020","journal-title":"Int J Infect Dis"},{"key":"pone.0243161.ref018","article-title":"Metatagenomic NextGeneration Sequencing for diagnosis of tuberculosis meningitis: A protocol of systematic review and meta-analysis.","author":"G Yu","journal-title":"Inplasy protocol"},{"issue":"7","key":"pone.0243161.ref019","doi-asserted-by":"crossref","first-page":"e1000097","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.","volume":"6","author":"PRISMA Group","year":"2009","journal-title":"PLoS Med"},{"issue":"8","key":"pone.0243161.ref020","doi-asserted-by":"crossref","first-page":"529","DOI":"10.7326\/0003-4819-155-8-201110180-00009","article-title":"QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies","volume":"155","author":"PF Whiting","year":"2011","journal-title":"Ann Intern Med"},{"issue":"8","key":"pone.0243161.ref021","doi-asserted-by":"crossref","first-page":"e0221427","DOI":"10.1371\/journal.pone.0221427","article-title":"Diagnostic accuracy of the Xpert MTB\/RIF assay for bone and joint tuberculosis: A meta-analysis","volume":"14","author":"Y Shen","year":"2019","journal-title":"PLoS One"},{"key":"pone.0243161.ref022","volume-title":"Statistical Software Components S456880","author":"Ben Dwamena","year":"2007"},{"key":"pone.0243161.ref023","doi-asserted-by":"crossref","first-page":"351","DOI":"10.3389\/fcimb.2019.00351","article-title":"Clinical Evaluation of Diagnosis Efficacy of Active Mycobacterium tuberculosis Complex Infection via Metagenomic Next-Generation Sequencing of Direct Clinical Samples","volume":"9","author":"X Zhou","year":"2019","journal-title":"Front Cell Infect Microbiol"},{"key":"pone.0243161.ref024","first-page":"19","article-title":"The significance of second-generation sequencing in the early diagnosis of tuberculous meningitis","volume":"40","author":"H Ma","year":"2019","journal-title":"J Med Forum"},{"key":"pone.0243161.ref025","article-title":"Diagnostic value of high-throughput sequencing of metagenome in infectious diseases of central nervous system","author":"X Xing","year":"2019","journal-title":"Chinese People's Liberation Army medical college"},{"issue":"11","key":"pone.0243161.ref026","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s11910-017-0796-0","article-title":"Tuberculous Meningitis in Children and Adults: New Insights for an Ancient Foe","volume":"17","author":"A Mezochow","year":"2017","journal-title":"Curr Neurol Neurosci Rep"},{"key":"pone.0243161.ref027","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/S1474-4422(13)70168-6","article-title":"Tuberculous meningitis: more questions, still too few answers","volume":"12","author":"GE Thwaites","year":"2013","journal-title":"Lancet Neurol"},{"key":"pone.0243161.ref028","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1097\/QCO.0000000000000331","article-title":"Recent advances in the diagnosis and management of tuberculous meningitis","volume":"30","author":"NT Mai","year":"2017","journal-title":"Curr Opin Infect Dis"},{"key":"pone.0243161.ref029","doi-asserted-by":"crossref","first-page":"e0199290","DOI":"10.1371\/journal.pone.0199290","article-title":"Diagnostic accuracy of the loop-mediated isothermal amplification assay for extrapulmonary tuberculosis: A meta-analysis","volume":"13","author":"G Yu","year":"2018","journal-title":"PLOS ONE"},{"key":"pone.0243161.ref030","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijid.2020.06.042","article-title":"CapitalBio Mycobacterium real-time polymerase chain reaction detection test: Rapid diagnosis of Mycobacterium tuberculosis and nontuberculous mycobacterial infection","volume":"98","author":"Y Shen","year":"2020","journal-title":"Int J Infect Dis"},{"key":"pone.0243161.ref031","first-page":"1166","article-title":"Nucleic acid amplification tests for the diagnosis of tuberculous lymphadenitis: a systematic review","volume":"11","author":"P Daley","year":"2007","journal-title":"Int J Tuberc Lung Dis"},{"key":"pone.0243161.ref032","doi-asserted-by":"crossref","first-page":"105752","DOI":"10.1016\/j.clineuro.2020.105752","article-title":"Next-generation sequencing of cerebrospinal fluid for the diagnosis of neurocysticercosis","volume":"193","author":"X Fei","year":"2020","journal-title":"Clin Neurol Neurosurg."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0243161","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T23:23:32Z","timestamp":1618529012000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0243161"}},"subtitle":[],"editor":[{"given":"Frederick","family":"Quinn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,12,1]]},"references-count":32,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0243161","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,1]]}}}