{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T11:52:35Z","timestamp":1783511555548,"version":"3.55.0"},"reference-count":26,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"unspecified","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100031697","name":"South African Medical Association","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100031697","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004513","name":"Harry Crossley Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100004513","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000061","name":"Fogarty International Center","doi-asserted-by":"publisher","award":["D43 TW010559"],"award-info":[{"award-number":["D43 TW010559"]}],"id":[{"id":"10.13039\/100000061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2021,7,14]]},"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Current tuberculosis triage and predictive tools offer poor accuracy and are ineffective for detecting asymptomatic disease in people living with HIV (PLHIV). Host tuberculosis transcriptomic biomarkers hold promise for diagnosing prevalent and predicting progression to incident tuberculosis and guiding further investigation, preventive therapy and follow-up. We aim to conduct a systematic review of performance of transcriptomic signatures of tuberculosis in PLHIV.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>We will search MEDLINE (PubMed), WOS Core Collection, Biological Abstracts, and SciELO Citation Index (Web of Science), Africa-Wide Information and General Science Abstracts (EBSCOhost), Scopus, and Cochrane Central Register of Controlled Trials databases for articles published in English between 1990 and 2020. Case\u2013control, cross-sectional, cohort and randomised controlled studies evaluating performance of diagnostic and prognostic host-response transcriptomic signatures in PLHIV of all ages and settings will be included. Eligible studies will include PLHIV in signature test or validation cohorts, and use microbiological, clinical, or composite reference standards for pulmonary or extrapulmonary tuberculosis diagnosis. Study quality will be evaluated using the \u2018Quality Assessment of Diagnostic Accuracy Studies-2\u2019 tool and cumulative review evidence assessed using the \u2018Grading of Recommendations Assessment, Development and Evaluation\u2019 approach. Study selection, quality appraisal and data extraction will be performed independently by two reviewers. Study, cohort and signature characteristics of included studies will be tabulated, and a narrative synthesis of findings presented. Primary outcomes of interest, biomarker sensitivity and specificity with estimate precision, will be summarised in forest plots. Expected heterogeneity in signature characteristics, study settings, and study designs precludes meta-analysis and pooling of results. Review reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Formal ethics approval is not required as primary human participant data will not be collected. Results will be disseminated through peer-reviewed publication and conference presentation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD42021224155.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2021-048623","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T12:52:06Z","timestamp":1628167926000},"page":"e048623","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Host blood transcriptomic biomarkers of tuberculosis disease in people living with HIV: a systematic review protocol"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4054-2766","authenticated-orcid":false,"given":"Simon C","family":"Mendelsohn","sequence":"first","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town Faculty of Health Sciences, Cape Town, Western Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2030-0751","authenticated-orcid":false,"given":"Humphrey","family":"Mulenga","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town Faculty of Health Sciences, Cape Town, Western Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6121-9039","authenticated-orcid":false,"given":"Stanley Kimbung","family":"Mbandi","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town Faculty of Health Sciences, Cape Town, Western Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatoumatta","family":"Darboe","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town Faculty of Health Sciences, Cape Town, Western Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Shelton","sequence":"additional","affiliation":[{"name":"Bongani Mayosi Health Sciences Library, University of Cape Town, Cape Town, Western Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0641-1359","authenticated-orcid":false,"given":"Thomas J","family":"Scriba","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town Faculty of Health Sciences, Cape Town, Western Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Hatherill","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town Faculty of Health Sciences, Cape Town, Western Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2021,8,5]]},"reference":[{"key":"2025120518504653000_11.8.e048623.1","unstructured":"WHO . Global tuberculosis report 2020. Geneva: World Health Organization, 2020. https:\/\/www.who.int\/tb\/publications\/global_report\/en"},{"key":"2025120518504653000_11.8.e048623.2","doi-asserted-by":"crossref","first-page":"e515","DOI":"10.1016\/S2352-3018(18)30137-1","article-title":"Sensitivity and specificity of WHO\u2019s recommended four-symptom screening rule for tuberculosis in people living with HIV: a systematic review and meta-analysis","volume":"5","author":"Hamada","year":"2018","journal-title":"Lancet HIV"},{"key":"2025120518504653000_11.8.e048623.3","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2236"},{"key":"2025120518504653000_11.8.e048623.4","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0017984","article-title":"The tuberculin skin test versus quantiferon TB Gold\u00ae in predicting tuberculosis disease in an adolescent cohort study in South Africa","volume":"6","author":"Mahomed","year":"2011","journal-title":"PLoS One"},{"key":"2025120518504653000_11.8.e048623.5","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir410"},{"key":"2025120518504653000_11.8.e048623.6","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1002786","article-title":"Host-response-based gene signatures for tuberculosis diagnosis: a systematic comparison of 16 signatures","volume":"16","author":"Warsinske","year":"2019","journal-title":"PLoS Med"},{"key":"2025120518504653000_11.8.e048623.7","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(19)30469-2"},{"key":"2025120518504653000_11.8.e048623.8","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(19)30282-6"},{"key":"2025120518504653000_11.8.e048623.9","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0237574","article-title":"Performance of diagnostic and predictive host blood transcriptomic signatures for tuberculosis disease: a systematic review and meta-analysisPerformance of diagnostic and predictive host blood transcriptomic signatures for Tuberculosis disease: A systematic review and meta-analysis","volume":"15","author":"Mulenga","year":"2020","journal-title":"PLoS ONE"},{"key":"2025120518504653000_11.8.e048623.10","unstructured":"WHO . High-priority target product profiles for new tuberculosis diagnostics: report of a consensus meeting. Geneva: World Health Organization, 2014. https:\/\/apps.who.int\/iris\/handle\/10665\/135617"},{"key":"2025120518504653000_11.8.e048623.11","doi-asserted-by":"crossref","first-page":"e183779","DOI":"10.1001\/jamanetworkopen.2018.3779","article-title":"Assessment of validity of a blood-based 3-gene signature score for progression and diagnosis of tuberculosis, disease severity, and treatment response","volume":"1","author":"Warsinske","year":"2018","journal-title":"JAMA Netw Open"},{"key":"2025120518504653000_11.8.e048623.12","unstructured":"WHO . Consensus meeting report: Development of a target product profile (TPP) and a framework for evaluation for a test for predicting progression from tuberculosis infection to active disease. Geneva: World Health Organization, 2017. http:\/\/apps.who.int\/iris\/handle\/10665\/259176"},{"key":"2025120518504653000_11.8.e048623.13","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2019.01441","article-title":"Detection of tuberculosis recurrence, diagnosis and treatment response by a blood transcriptomic risk signature in hiv-infected persons on antiretroviral therapy","volume":"10","author":"Darboe","year":"2019","journal-title":"Front Microbiol"},{"key":"2025120518504653000_11.8.e048623.14","doi-asserted-by":"crossref","DOI":"10.1186\/2046-4053-4-1","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement","volume":"4","author":"Moher","year":"2015","journal-title":"Syst Rev"},{"key":"2025120518504653000_11.8.e048623.15","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.g7647","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation","volume":"350","author":"Shamseer","year":"2015","journal-title":"BMJ"},{"key":"2025120518504653000_11.8.e048623.16","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.19163"},{"key":"2025120518504653000_11.8.e048623.17","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.38636.593461.68"},{"key":"2025120518504653000_11.8.e048623.18","doi-asserted-by":"publisher","DOI":"10.1080\/02763869.2017.1259891"},{"key":"2025120518504653000_11.8.e048623.19","doi-asserted-by":"publisher","DOI":"10.1059\/0003-4819-155-8-201110180-00009"},{"key":"2025120518504653000_11.8.e048623.20","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39489.470347.AD"},{"key":"2025120518504653000_11.8.e048623.21","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39500.677199.AE"},{"key":"2025120518504653000_11.8.e048623.22","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/S2213-2600(19)30355-8","article-title":"Headway made towards biosignatures for incipient tuberculosis","volume":"8","author":"Scriba","year":"2020","journal-title":"The Lancet Respir Med"},{"key":"2025120518504653000_11.8.e048623.23","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/S2213-2600(20)30045-X","article-title":"Blood transcriptional signatures for tuberculosis testing","volume":"8","author":"Mendelsohn","year":"2020","journal-title":"Lancet Respir Med"},{"key":"2025120518504653000_11.8.e048623.24","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0204029","article-title":"Biomarkers for diagnosis of childhood tuberculosis: a systematic review","volume":"13","author":"Togun","year":"2018","journal-title":"PLoS One"},{"key":"2025120518504653000_11.8.e048623.25","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/s41564-019-0380-2","article-title":"A systematic review of biomarkers to detect active tuberculosis","volume":"4","author":"MacLean","year":"2019","journal-title":"Nat Microbiol"},{"key":"2025120518504653000_11.8.e048623.26","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1097\/COH.0000000000000512","article-title":"Diagnosing active tuberculosis in people living with HIV: an ongoing challenge","volume":"14","author":"MacLean","year":"2019","journal-title":"Curr Opin HIV AIDS"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2021-048623","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T02:50:55Z","timestamp":1764989455000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2021-048623"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8]]},"references-count":26,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8,5]]},"published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1136\/bmjopen-2021-048623"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2021-048623","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8]]}}}