Biochemical Markers in Pleural Fluid for the Diagnosis of Tuberculous Pleural Effusion: A Retrospective Study

Background/Objectives: The rapid diagnosis of tuberculous pleural effusion (TPE) presents significant challenges for clinicians due to its paucibacillary nature. Routine biochemical markers may complement microbiological and molecular tests, especially in resource-limited settings. The objective of this study was to evaluate the diagnostic performance of pleural fluid adenosine deaminase (ADA), lactate dehydrogenase (LDH), total protein (TP), and the ADA/LDH and ADA/TP ratios for tuberculous pleural effusion, using Löwenstein–Jensen culture and Xpert MTB/RIF as microbiological reference standards Methods: We conducted a retrospective study (2016–2024) including 325 consecutive patients investigated for suspected TPE in a tertiary hospital. ADA, TP and LDH were measured, and additional ratio-based indices (ADA/TP, ADA/LDH) were calculated for 325 pleural fluid (PF) samples. Löwenstein–Jensen (LJ) culture (with MPT64 confirmation) and GeneXpert MTB/RIF (Xpert MTB/RIF) were used as separate microbiological reference standards. Sensitivity (Se), specificity (Sp), and areas under the ROC curve (AUC) were estimated, and optimal thresholds were determined using the Youden index. Results: Among 325 pleural fluid samples, 23 (7.1%) were culture-positive. Xpert MTB/RIF was performed in 73/325 patients (22.5%), with Mycobacterium tuberculosis detected in 19/73 (26.0%) tested samples. In PF, ADA provided the best performance against culture, with Se of 100%. Correlation analysis in PF showed a moderate positive association between TP and LDH (p < 0.0001). Conclusions: Among routine biochemical markers, PF ADA shows high NPV. Integrating these rapid, low-cost tests alongside LJ culture and Xpert MTB/RIF may streamline the diagnostic pathway for TPE.