Comparison of same day diagnostic tools including Gene Xpert and unstimulated IFN-γ for the evaluation of pleural tuberculosis: a prospective cohort study

Background: The accuracy of currently available same-day diagnostic tools (smear microscopy and conventional nucleic acid amplification tests) for pleural tuberculosis (TB) is sub-optimal. Newer technologies may offer improved detection. Methods: Smear-microscopy, adenosine deaminase (ADA), interferon gamma (IFN-gamma), and Xpert MTB/RIF [using an unprocessed (1 ml) and centrifuged (similar to 20 ml) sample] test accuracy was evaluated in pleural fluid from 103 consecutive patients with suspected pleural TB. Culture for M. tuberculosis and/or histopathology (pleural biopsy) served as the reference standard. Patients were followed prospectively to determine their diagnostic categorisation. Results: Of 93 evaluable participants, 40 had definite-TB (reference positive), 5 probable-TB (not definite but treated for TB) and 48 non-TB (culture and histology negative, and not treated for TB). Xpert MTB/RIF sensitivity and specificity (95% Cl) was 22.5% (12.4 -37.6) and 98% (89.2 -99.7), respectively, and centrifugation did not improve sensitivity (23.7%). The Xpert MTB/RIF internal positive control showed no evidence of inhibition. Biomarker specific sensitivity, specificity, PPV, and NPVs were: ADA (48.85 IU/L; rule-in cut-point) 55.3% (39.8 -69.9), 95.2% (83.9 -98.7), 91.4 (73.4 -95.4), 69.7% (56.7 -80.1); ADA (30 IU/L; clinically used cut-point) 79% (63.7 -89), 92.7% (80.6 -97.5), 91.0 (73.4 -95.4), 82.7% (69.3 -90.1); and IFN-. (107.7 pg/ml; rule-in cut-point) 92.5% (80.2 -97.5), 95.9% (86.1 -98.9), 94.9% (83.2 -98.6), 93.9% (83.5 -97.9), respectively (IFN-. sensitivity and NPV better than Xpert [p < 0.05] and rule-in ADA [p < 0.05]). Conclusion: The usefulness of Xpert MTB/RIF to diagnose pleural TB is limited by its poor sensitivity. IFN-gamma is an excellent rule-in test and, compared to ADA, has significantly better sensitivity and rule-out value in a TB-endemic setting.