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ORIGINAL RESEARCH article

Front. Tuberc.
Sec. Diagnosis of Tuberculosis
Volume 2 - 2024 | doi: 10.3389/ftubr.2024.1377540
This article is part of the Research Topic Tuberculosis diagnosis, drug resistance, and drug target discovery View all 18 articles

Analyses of blood-derived host biomarkers for pulmonary tuberculosis diagnosis in human immunodeficiency virus coinfected individuals in Sub-Saharan Africa: a systematic review and meta-analysis

Provisionally accepted
Antony Morwamoche Rapulana Antony Morwamoche Rapulana 1,2,3Thabo Mpotje Thabo Mpotje 1,2Nondumiso Mthiyane Nondumiso Mthiyane 2,4Theresa K Smit Theresa K Smit 1,2Timothy McHugh Timothy McHugh 3Mohlopheni Jackson Marakalala Mohlopheni Jackson Marakalala 1,2,3*
  • 1 School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Mayville, KwaZulu-Natal, South Africa
  • 2 Africa Health Research Institute (AHRI), Durban, South Africa
  • 3 Centre for Clinical Microbiology, Division of Infection and Immunity, Faculty of Medical Sciences, University College London, London, England, United Kingdom
  • 4 Institute for Global Health, Faculty of Population Health Sciences, University College London, London, England, United Kingdom

The final, formatted version of the article will be published soon.

    Objective: Our objective was to conduct a review of host blood-derived biomarkers as potential diagnostic targets for pulmonary TB and as alternative tests to identify active tuberculosis in HIV co-infected individuals. Methods: A systematic review and meta-analysis of host blood-derived biomarkers with potential for diagnosis of active tuberculosis in HIV co-infected individuals was conducted. Cochrane Library, Embase, MEDLINE, PubMed and Web of Science databases were searched up to 7 November 2023. A hierarchical summary receiver operating characteristic (HSROC) model was used to evaluate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) of the following potential biomarkers: C-reactive protein (CRP), Interferon gamma induced protein-10 (IP-10), Neopterin, IGRA, Kynurenine to tryptophan (K/T) ratio and use of different panels of combined biomarkers; including 5 biomarker panel (IL-6, INF-y, MIG, CRP, and IL-18), 4 biomarker panel (IL-6, IL-21, INF-y, IL-1a), 6 biomarker panel (APO-ACIII, CXCL1, CXCL9, CCL8, CCL-1, and CD56), and 9 biomarker panel (Alpha-2-macroglobulin, fibrinogen, CRP, MMP-a, transthyretin, complement factor H, INF-y, IP-10, and TNF-α). Results: Twenty-three studies were included. The pooled sensitivity of CRP, IP-10, Neopterin, combined biomarker signatures, IGRA and K/T ratio were 77% (60 – 88), 79% (72 - 84), 82% (43 – 96), 78% (64 - 88), 71% (65 – 76), 95% (90 – 98), respectively and the pooled specificity were 90% (80 – 96), 82% (59 – 93), 42% (22 – 66), 85% (73 – 92), 33% (18 – 54), and 95% (82 – 99), respectively. Conclusion: CRP, IP-10, K/T ratio and the panels of multiple combined biomarkers that include the following cytokines, chemokines, and acute phase proteins IL-6, INF-y, MIG, CRP, IL-18, IL-21, IL-1a, APO-ACIII, CXCL1, CXCL9, CCL8, CCL-1, CD56, Alpha-2-macroglobulin, fibrinogen, MMP-a, transthyretin, complement factor H, IP-10, and TNF-α are potential blood biomarkers that can aid TB diagnosis in HIV co-infected individuals.

    Keywords: Cytokines, chemokine, Systematic review, TB diagnosis, biomarkers, HIV/TB co-infection

    Received: 27 Jan 2024; Accepted: 06 Dec 2024.

    Copyright: © 2024 Rapulana, Mpotje, Mthiyane, Smit, McHugh and Marakalala. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Mohlopheni Jackson Marakalala, School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Mayville, 4058, KwaZulu-Natal, South Africa

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.