Biomarkers Correlated with Tuberculosis Preventive Treatment Response: A Systematic Review and Meta-Analysis

There is a need to identify alternative biomarkers to predict tuberculosis (TB) preventive treatment response because observing the incidence decline renders a long follow-up period.

We searched PubMed, Embase and Web of Science up to 9 February 2023. The biomarker levels during preventive treatment were quantitatively summarized by means of meta-analysis using the random-effect model.

Eleven eligible studies, published during 2006-2022, were included in the meta-analysis, with frequently heterogeneous results. Twenty-six biomarkers or testing methods were identified regarding TB preventive treatment monitoring. The summarized standard mean differences of interferon-γ (INF-γ) were -1.44 (95% CI: -1.85, -1.03) among those who completed preventive treatment (τ² = 0.21; I² = 95.2%, p < 0.001) and -0.49 (95% CI: -1.05, 0.06) for those without preventive treatment (τ² = 0.13; I² = 82.0%, p < 0.001), respectively. Subgroup analysis showed that the INF-γ level after treatment decreased significantly from baseline among studies with high TB burden (-0.98, 95% CI: -1.21, -0.75) and among those with a history of Bacillus Calmette-Guérin vaccination (-0.87, 95% CI: -1.10, -0.63).

Our results suggested that decreased INF-γ was observed among those who completed preventive treatment but not in those without preventive treatment. Further studies are warranted to explore its value in preventive treatment monitoring due to limited available data and extensive between-study heterogeneity.