Comparison between Diagnostic Yield of Pleural Fluid ELISPOT and Thoracoscopic Guided Pleural Biopsy in Undiagnosed Pleural Effusion

ABSTRACT

Context Despite recent advances in the available diagnostic modalities, diagnosis of pleural tuberculosis remains a challenge because of the low yield of conventional methods. Pleural biopsy is the gold standard for confirmation of diagnosis, which is invasive and cumbersome. The concentration of mycobacterial peptide-specific activated lymphocytes at the site of infection can be utilized as the basis for using IGRA (interferon-gamma release assays) based evaluation of undiagnosed exudative pleural effusions.  Aim: To evaluate the performance of IGRA (Enzyme-linked Immunospot (ELISPOT) in pleural fluid for the diagnosis of pleural tuberculosis in histopathologically confirmed cases. Settings and Design: A prospective observational study compared the utility of ELISPOT with thoracoscopy guided pleural biopsies for the diagnosis of tubercular pleural effusions. Methods and Material: Forty-two consecutive cases of undiagnosed pleural effusions were enrolled and subjected to thoracoscopy guided pleural biopsy. Thirteen patients were confirmed to have tuberculosis, 27 had malignancy, and 2 had normal pleura. A total of 1x103 pleural fluid mononuclear cells (PFMCs) were cultured in the presence of early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) for 24 hours. The individual spots were then counted using an automated analyzer ELISPOT reader system.  Results: The number of spots developed in the pleural fluid was significantly higher in tubercular pleural effusions as compared to non-tubercular effusions (CFP-10154.76±14.61 vs 49.24±8.9; ESAT-6 150.3±17.27 v/s 45.34±8.23, p<0.001). At a cut-off value of more than 67 spots taken as positive for tuberculosis, the sensitivity of the test was 100% (95% CI 75.29% to 100.00%), specificity was 96.5% (95 % CI 82.24% to 99.91%), positive predictive value was 92.86% (95 % CI 65.45% to 98.89%) and negative predictive value was 100%.  Conclusions: ELISPOT can be a useful non-invasive test for the evaluation of undiagnosed pleural effusions and making a diagnosis of pleural tuberculosis with confidence.