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-10:154.76±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.
Downloads
References
2. Zhai K, Lu Y, Shi HZ. Tuberculous pleural effusion. J Thorac Dis 2016;8:E486-94.
3. Porcel JM, Esquerda A, Vives M, Bielsa S. Etiology of pleural effusions: analysis of more than 3,000 consecutive thoracenteses. Arch Bronconeumol 2014;50:161-5.
4. Porcel JM, Light RW. Pleural effusions. Dis Mon 2013;59:29-57.
5. Conde MB, Loivos AC, Rezende VM, et al. Yield of sputum induction in the diagnosis of pleural tuberculosis. American journal of respiratory and critical care medicine 2003;167:723-5.
6. Diacon AH, Van de Wal BW, Wyser C, et al. Diagnostic tools in tuberculous pleurisy: a direct comparative study. The European respiratory journal 2003;22:589-91.
7. Ferreiro L, San Jose E, Valdes L. Tuberculous pleural effusion. Arch Bronconeumol 2014;50:435-43.
8. Li D, Shen Y, Fu X, Li M, Wang T, Wen F. Combined detections of interleukin-33 and adenosine deaminase for diagnosis of tuberculous pleural effusion. Int J Clin Exp Pathol 2015;8:888-93.
9. da Silva CT, Jr., Behrsin RF, Cardoso GP, de Araujo EG. Evaluation of adenosine deaminase activity for the diagnosis of pleural TB in lymphocytic pleural effusions. Biomark Med 2013;7:113-8.
10. Suleman A, Kamal M, Abbasi MA. Diagnostic Utility Of Pleural Fluid Adenosine Deaminase Level In Tuberculous Pleural Effusion. J Ayub Med Coll Abbottabad 2016;28:245-8.
11. Tang Y, Zhang J, Huang H, et al. Pleural IFN-gamma release assay combined with biomarkers distinguished effectively tuberculosis from malignant pleural effusion. BMC Infect Dis 2019;19:55.
12. Li M, Wang H, Wang X, Huang J, Wang J, Xi X. Diagnostic accuracy of tumor necrosis factor-alpha, interferon-gamma, interleukin-10 and adenosine deaminase 2 in differential diagnosis between tuberculous pleural effusion and malignant pleural effusion. J Cardiothorac Surg 2014;9:118.
13. Theron G, Zijenah L, Chanda D, et al. Feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing for tuberculosis in primary-care settings in Africa: a multicentre, randomised, controlled trial. Lancet (London, England) 2014;383:424-35.
14. Lusiba JK, Nakiyingi L, Kirenga BJ, et al. Evaluation of Cepheid's Xpert MTB/Rif test on pleural fluid in the diagnosis of pleural tuberculosis in a high prevalence HIV/TB setting. PloS one 2014;9:e102702.
15. Sehgal IS, Dhooria S, Aggarwal AN, Behera D, Agarwal R. Diagnostic Performance of Xpert MTB/RIF in Tuberculous Pleural Effusion: Systematic Review and Meta-analysis. Journal of clinical microbiology 2016;54:1133-6.
16. Christopher DJ, Dinakaran S, Gupta R, James P, Isaac B, Thangakunam B. Thoracoscopic pleural biopsy improves yield of Xpert MTB/RIF for diagnosis of pleural tuberculosis. Respirology (Carlton, Vic) 2018;23:714-7.
17. Lalvani A, Pareek M. Interferon gamma release assays: principles and practice. Enfermedades infecciosas y microbiologia clinica 2010;28:245-52.
18. Jafari C, Ernst M, Strassburg A, et al. Local immunodiagnosis of pulmonary tuberculosis by enzyme-linked immunospot. The European respiratory journal 2008;31:261-5.
19. Tang Y, Zhang J, Huang H, et al. Pleural IFN-gamma release assay combined with biomarkers distinguished effectively tuberculosis from malignant pleural effusion. BMC Infect Dis 2019;19:55.
20. Chen KY, Feng PH, Chang CC, et al. Novel biomarker analysis of pleural effusion enhances differentiation of tuberculous from malignant pleural effusion. Int J Gen Med 2016;9:183-9.
21. Vorster MJ, Allwood BW, Diacon AH, Koegelenberg CF. Tuberculous pleural effusions: advances and controversies. J Thorac Dis 2015;7:981-91.
22. Chang KC, Chan MC, Leung WM, et al. Optimising the utility of pleural fluid adenosine deaminase for the diagnosis of adult tuberculous pleural effusion in Hong Kong. Hong Kong Med J 2018;24:38-47.
23. Wu YH, Zhao GW, Wang XF, Wang MS. Pleural effusion adenosine deaminase is not accurate in diagnosis of pediatric tuberculous pleural effusion: a retrospective study. Eur Rev Med Pharmacol Sci 2015;19:1706-10.
24. Du F, Xie L, Zhang Y, et al. Prospective Comparison of QFT-GIT and T-SPOT.TB Assays for Diagnosis of Active Tuberculosis. Scientific reports 2018;8:5882.
25. Liao M, Yang Q, Zhang J, et al. Gamma interferon immunospot assay of pleural effusion mononuclear cells for diagnosis of tuberculous pleurisy. Clin Vaccine Immunol 2014;21:347-53.
26. Adilistya T, Astrawinata DA, Nasir UZ. Use of Pleural Fluid Interferon-gamma Enzyme-linked Immunospot Assay in the Diagnosis of Pleural Tuberculosis. Acta medica Indonesiana 2016;48:41-7.
27. Kim MC, Kim SM, Lee SO, et al. A diagnostic algorithm for tuberculous pleurisy using the ELISPOT assay on peripheral blood and pleural effusion. Infectious diseases (London, England) 2016;48:688-94.

Copyright (c) 2019 Zia Hashim, Mansi Gupta, Alok Nath, Ajmal Khan, Ravi Mishra, Harshit Singh, Vikas Agarwal

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.