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

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.