Diagnostic Accuracy of Pleural Fluid Biomarkers and Nucleic Acid Amplification Tests in Tuberculous Pleural Effusion: An Umbrella Review.

INTRODUCTION/

OBJECTIVE

Tuberculous Pleural Effusion (TPE) is a common but diagnostically challenging form of extrapulmonary tuberculosis. Many overlapping systematic reviews have evaluated pleural-fluid biomarkers and Nucleic Acid Amplification Tests (NAATs). This umbrella review aimed to synthesise and compare the diagnostic accuracy of pleural-fluid tests for TPE within a single appraised framework.

METHODS

We conducted an umbrella review (JBI methodology; PRISMA 2020 reporting) of 20 systematic reviews with meta-analysis, appraised them using AMSTAR 2, quantified primary-study overlap with the Corrected Covered Area (CCA), and summarised the certainty of evidence reported by the source reviews (GRADE).

RESULTS

Cytokine markers showed the highest accuracy (IFN-γ sensitivity 0.93, specificity 0.96; IL-27 0.94/0.97). ADA was a robust rule-out test (0.92/0.90). NAATs were highly specific but insensitive (Xpert MTB/RIF 0.52/0.99; Xpert Ultra 0.68/0.97).

DISCUSSION: The overlap among reviews was high to very high, and the apparent hierarchy was found to be influenced by reference-standard heterogeneity, indicating that the observed ranking should not be interpreted as free of methodological bias.

CONCLUSION

No single test is optimal; pleural-fluid biomarkers and NAATs play complementary roles that depend on pre-test probability.