{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T19:21:19Z","timestamp":1791660079514,"version":"4.3.4"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["206724\/Z\/17\/Z"],"award-info":[{"award-number":["206724\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["106680\/B\/14\/Z"],"award-info":[{"award-number":["106680\/B\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["214560\/Z\/18\/Z"],"award-info":[{"award-number":["214560\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Clin Microbiol"],"published-print":{"date-parts":[[2024,4,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Mortality from tuberculous meningitis (TBM) remains around 30%, with most deaths occurring within 2 months of starting treatment. Mortality from drug-resistant strains is higher still, making early detection of drug resistance (DR) essential. Targeted next-generation sequencing (tNGS) produces high read depths, allowing the detection of DR-associated alleles with low frequencies. We applied Deeplex Myc-TB\u2014a tNGS assay\u2014to cerebrospinal fluid (CSF) samples from 72 adults with microbiologically confirmed TBM and compared its genomic drug susceptibility predictions to a composite reference standard of phenotypic susceptibility testing (pDST) and whole genome sequencing, as well as to clinical outcomes. Deeplex detected\n              <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n              complex DNA in 24\/72 (33.3%) CSF samples and generated full DR reports for 22\/24 (91.7%). The read depth generated by Deeplex correlated with semi-quantitative results from MTB\/RIF Xpert. Alleles with &lt;20% frequency were seen at canonical loci associated with first-line DR. Disregarding these low-frequency alleles, Deeplex had 100% concordance with the composite reference standard for all drugs except pyrazinamide and streptomycin. Three patients had positive CSF cultures after 30 days of treatment; reference tests and Deeplex identified isoniazid resistance in two, and Deeplex alone identified low-frequency rifampin resistance alleles in one. Five patients died, of whom one had pDST-identified pyrazinamide resistance. tNGS on CSF can rapidly and accurately detect drug-resistant TBM, but its application is limited to those with higher bacterial loads. In those with lower bacterial burdens, alternative approaches need to be developed for both diagnosis and resistance detection.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jcm.01287-23","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T14:00:57Z","timestamp":1710165657000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Targeted sequencing from cerebrospinal fluid for rapid identification of drug-resistant tuberculous meningitis"],"prefix":"10.1128","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0116-4870","authenticated-orcid":false,"given":"Trinh Thi Bich","family":"Tram","sequence":"first","affiliation":[{"name":"Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le Pham Tien","family":"Trieu","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le Thanh Hoang","family":"Nhat","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do Dang Anh","family":"Thu","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Le","family":"Quang","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Duc","family":"Bang","sequence":"additional","affiliation":[{"name":"Pham Ngoc Thach Hospital for Tuberculosis and Lung Disease, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tran Thi Hong","family":"Chau","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy E.","family":"Thwaites","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy M.","family":"Walker","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vu Thi Ngoc","family":"Ha","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8733-692X","authenticated-orcid":false,"given":"Nguyen Thuy Thuong","family":"Thuong","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgph.0000069"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00435-X"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix849"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/14787210.2018.1540930"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2011.07.005"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-021-06705-4"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix230"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw763"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/498220"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02338-2020"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2021.102051"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1507062"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2021.102084"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2014.02.013"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.707244"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01796-2020"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jctube.2018.04.002"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.03073-14"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.1303.3997"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_3_5_25_2","volume-title":"R: A language and environment for statistical computing","author":"R Core Team","year":"2016","unstructured":"R Core Team. 2016. 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