What question did this study set out to answer?

The aim is to identify and evaluate host blood biomarkers for diagnosing childhood tuberculosis and assess their diagnostic accuracy.

March 10, 2026Open Access

Host blood biomarkers for the diagnosis of childhood tuberculosis disease: A systematic review and meta-analysis

Puntos clave

The aim is to identify and evaluate host blood biomarkers for diagnosing childhood tuberculosis and assess their diagnostic accuracy.
Conducted a systematic review and meta-analysis
Included original studies reporting biomarker concentration and accuracy
Assessed risk of bias using Quality Assessment of Diagnostic Accuracy Studies-2
Used hierarchical bivariate model for data synthesis
Identified 55 studies, with 42 at high risk of bias
Reported biomarker classes: 39 cytokine/protein, 10 mRNA, 4 miRNA
Twelve biosignatures and two individual biomarkers met WHO TPP for TB diagnosis
IP-10 showed sensitivity of 85.2% and specificity of 59.3%, not meeting WHO TPP

Resumen

ABSTRACTBackground Current tuberculosis (TB) diagnostics have limited sensitivity in children, resulting in undiagnosed and untreated cases; host blood biomarkers have the potential to narrow this diagnostic gap. Objectives To conduct a systematic review to identify host blood biomarkers which diagnose childhood TB and to summarize biomarker accuracy. Methods Data sources: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, SCOPUS, ClinicalTrials.gov, and World Health Organization (WHO) Global Index Medicus.Study eligibility criteria: Original studies that reported biomarker concentration and/or diagnostic accuracy for childhood TB.Participants: Children Tests: Any host blood biomarker measured prior to anti-TB therapy.Reference standards: Mycobacterial culture, nucleic acid amplification tests, and/or clinical diagnosis.Assessment of risk of bias: Quality Assessment of Diagnostic Accuracy Studies-2.Methods of data synthesis: A hierarchical bivariate model was used for meta-analysis. Results Fifty-five studies were included, of which 42 (76.4%) studies were at high risk of bias and/or had applicability concerns. The following biomarker classes were reported: cytokine/protein (n=39 studies), mRNA (n=10 studies), miRNA (n=4 studies), and other (n=11 studies). Twelve biosignatures (seven cytokine, four metalloproteinase, one miRNA) and two individual biomarkers (one cytokine, one metalloproteinase) met the WHO target product profile (TPP) for TB disease diagnosis (sensitivity ≥95%, specificity >98%). Meta-analysis was conducted for the cytokine interferon-γ-inducible protein 10 (IP-10) from seven studies; summary estimates of sensitivity (85.2%, 95% CI, 71.1-93.1%) and specificity (59.3%, 95% CI, 44.7-72.5%) did not meet WHO TPP. Discussion Host blood biomarkers were identified that met WHO targets for childhood TB disease diagnosis, however, most were reported from a single centre. Meta-analysis did not support IP-10 as an accurate stand-alone biomarker. High-quality studies are needed to validate host blood biomarkers in larger cohorts, and future work should focus on the development of point-of-care tests suitable for low resource settings.

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