{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T06:51:19Z","timestamp":1787899879575,"version":"build-2784847793"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Early diagnosis of tuberculosis meningitis (TBM) remains a great challenge during clinical practice. The diagnostic efficacies of cerebrospinal fluid (CSF)\u2010based mycobacterial growth indicator tube (MGIT) culture, modified Ziehl\u2013Neelsen (ZN) staining, Xpert MTB\/RIF, and\u00a0metagenomic next\u2010generation sequencing (mNGS) for TBM remained elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 216 adult patients with suspicious TBM were retrospectively enrolled in this multi\u2010cohort study. The diagnostic performances for MGIT, modified ZN staining, Xpert MTB\/RIF, and mNGS using CSF samples were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Uniform clinical case definition classified 88 (40.7%) out of 216 patients as the\u00a0definite TBM, 5 (2.3%) patients as probable TBM cases, and 24 (11.1%) patients as possible TBM cases. The sensitivities of\u00a0MGIT, modified ZN staining, Xpert MTB\/RIF, and mNGS\u00a0for TBM diagnosis against consensus uniform case definition for definite TBM were 25.0%, 76.1%, 73.9%, and 84.1%, respectively. Negative predictive values (NPVs) were 66.0%, 85.9%, 84.8%, and 90.1%, respectively.\u00a0The sensitivities of\u00a0MGIT, modified ZN staining, Xpert MTB\/RIF, and mNGS\u00a0for TBM diagnosis against consensus uniform case definition for definite, probable, and possible TBM were 18.8%, 57.3%, 55.5%, and 63.2%, respectively. Negative predictive values (NPVs) were 51.0%, 66.4%, 65.6%, and 69.7%, respectively. mNGS combined with modified ZN stain and Xpert could cover TBM cases against a composite microbiological reference standard, yielding 100% specificity and 100% NPV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Metagenomic next\u2010generation sequencing detected TBM with higher sensitivity than Xpert, ZN staining and MGIT culture, but mNGS cannot be used as a rule\u2010out test. mNGS combined with Xpert or modified ZN staining could enhance the sensitivity of diagnostic tests for TBM.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24307","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T20:38:09Z","timestamp":1645735089000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Comparative diagnostic utility of metagenomic next\u2010generation sequencing, GeneXpert, modified Ziehl\u2013Neelsen staining, and culture using cerebrospinal fluid for tuberculous meningitis: A\u00a0multi\u2010center, retrospective study in China"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5955-687X","authenticated-orcid":false,"given":"Yuxin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Nanjing Drum Tower Hospital Nanjing University Medical School  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine No. 4 People\u2019s Hospital of Qinghai Province  Xining China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1077-8847","authenticated-orcid":false,"given":"Xiaojin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Hebei Chest Hospital  Hebei 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