Efficacy of cartridge based nucleic acid amplification test to diagnose tubercular pleural effusion
Keywords:Cartridge based nucleic acid amplification test, GeneXpert MTB/Rif test, Extrapulmonary tuberculosis, Pleural effusion, Rifampicin resistance
Background: Tuberculosis (TB) remains a major health concern worldwide. Extra pulmonary tuberculosis (EPTB) in India accounts up to 20% of all tuberculosis cases. EPTB often remains undetected and untreated due to variable clinical presentation and lack of diagnostic means. Early detection of TB and drug resistance is important in the management of TB. The aim of present study was to assess the role of cartridge based nucleic acid amplification test in rapid diagnosis of tubercular pleural effusion.
Methods: The study screened 211 symptomatic patients. The patients with clinical and radiological presentations suggestive of pleural effusion were analyzed using light’s criteria to make a diagnosis of tubercular pleural effusion; these patients submitted pleural fluid sample for smear microscopy after concentration for presence of acid fast bacilli under light emitting diode based fluorescent microscopy (LED-FM), and for cartridge based nucleic acid amplification test (CBNAAT) using GX4 GeneXpert MTB/Rif test system. The results were statistically analyzed.
Results: Out of patients who had pleural effusion without any pulmonary tuberculosis, pleural fluid biochemistry analyses using light’s criteria detected 20 tubercular pleural effusions (11 male and 9 female). Seven patients had history of extrapulmonary tuberculosis in past, all of them received treatment with effective treatment compliance in past. Pleural fluid microscopic examination for detection of acid-fast bacilli was not able to detect acid-fast bacilli in any of these 20 patients diagnosed with tubercular pleural effusion. CBNAAT could authentically detect M. tuberculosis in 5/20 patients diagnosed with tubercular pleural effusion. There was no impact of gender, previous history of tuberculosis, history of anti-tuberculosis treatment (ATT) intake, or compliance to ATT on CBNAAT status in this study.
Conclusions: CBNAAT has the potential to significantly authenticate tubercular etiology in some of smear-negative pleural fluid specimens with rapid test results. It has an added advantage to assess the rifampicin drug sensitivity. All this contribute hugely in diagnosis and management of tubercular pleural effusion.
World Health Organization. Global tuberculosis report 2015. Available at www.who.int/tb/publications/global_report/en/. Accessed on 16th May 2017.
TB India 2015. Revised national TB control programme: annual status report central TB division. Directorate general of health services, Ministry of Health and Family Welfare, Nirman Bhavan, New Delhi. Available at www.tbcindia.nic.in. Accessed on 12th May 2017.
Lange C, Mori T. Advances in the diagnosis of tuberculosis. Respirol. 2010;15:220-40.
Pai M, Ling DI. Rapid diagnosis of extra pulmonary tuberculosis using nucleic acid amplification tests: what is the evidence? Future Microbiol. 2008;3:1-4.
Pandey P, Pant ND, Rijal KR, Shrestha B, Kattel S, Banjara MR, et al. Diagnostic accuracy of GeneXpert MTB/RIF assay in comparison to conventional drug susceptibility testing method for the diagnosis of multidrug-resistant tuberculosis. PLoS One. 2017;12:e0169798.
Pai M, Nathavitharana R. Extrapulmonary tuberculosis: new diagnostics and new policies. Indian J Chest Dis Allied Sci. 2014;56:71-3.
Light RW. Update on tuberculous pleural effusion. Respirol. 2010;15:451-8.
Light RW. The light criteria: the beginning and why they are useful 40 years later. Clin Chest Med. 2013;34:21-6.
WHO Policy Xpert MTB/RIF. World Health Organization. Policy statement: automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB/RIF system. WHO/HTM/TB/2011.4 Geneva; 2011. Available at http://apps.who.int/iris/bitstream/10665/44586/1/9789241501545_eng.pdf
Blakemore R, Story E, Helb D, Kop J, Banada P, Owens MR, et al. Evaluation of the analytical performance of the Xpert MTB/RIF assay. J Clin Microbiol. 2010;48:2495-501.
Helb D, Jones M, Story E, Boehme C, Wallace E, Ho K, et al. Rapid detection of Mycobacterium tuberculosis and rifampin resistance by use of on-demand, near-patient technology. J Clin Microbiol. 2010;48:229-37.
Kranzer K, Houben RM, Glynn JR, Bekker LG, Wood R, Lawn SD. Yield of HIV-associated tuberculosis during intensified case finding in resource-limited settings: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10(2):93-102.
Porcel JM. Tuberculous pleural effusion. Lung. 2009;187:263-70.
Leibowitz S, Kennedy L, Lessof MH. The tuberculin reaction in the pleural cavity and its suppression by antilymphocyte serum. Br J Exp Pathol. 1973;54:152-62.
eibert AF, Haynes J, Middleton R, Bass JB. Tuberculous pleural effusion. Twenty-years’ experience. Chest. 1991;99:883-6.
Mitra DK, Sharma SK, Dinda AK, Bindra MS, Madan B, Ghosh B. Polarized helper T cells in tubercular pleural effusion: phenotypic identity and selective recruitment. Eur J Immunol. 2005;35:2367-75.
Antony VB, Repine JE, Harada RN, Good JT Jr, Sahn SA. Inflammatory responses in experimental tuberculosis pleurisy. Acta Cytol. 1983;27:355-61.
Sharma SK, Mitra DK, Balamurugan A, Pandey RM, Mehra NK. Cytokine polarization in miliary and pleural tuberculosis. J Clin Immunol. 2002;22:345-52.
Gopi A, Madhavan SM, Sharma SK, Sahn SA. Diagnosis and treatment of tuberculous pleural effusion in 2006. Chest. 2007;131:880-9.
Ruan SY, Chuang YC, Wang JY, Lin JW, Chien JY, Huang CT. Revisiting tuberculous pleurisy: pleural fluid characteristics and diagnostic yield of mycobacterial culture in an endemic area. Thorax. 2012;67:822-7.
Chauhan LS. Drug resistant TB-RNTCP response. Indian J Tuberc. 2008;55:5-8.
Uria GA, Azcona JM, Midde M, Naik PK, Reddy S, Reddy R. Rapid diagnosis of pulmonary and extrapulmonary tuberculosis in HIV-Infected patients. Comparison of LED fluorescent microscopy and the GeneXpert MTB/RIF assay in a district hospital in India. Tuberc Res Treat. 2012;2012:932862.
Sajed AN, Khan S, Butt AS, Srwar A, Akhtar R. Rapid detection of mycobacterium tuberculosis and Rifampicin resistance in extrapulmonary samples using GeneXpert MTB/RIF assay. IOSR J Den Med Sci. 2014;13:50-3.
Hillemann D, Rusch Gerdes S, Boehme C, Richter E. Rapid molecular detection of extrapulmonary tuberculosis by the automated GeneXpert MTB/RIF system. J Clin Microbiol. 2011;49:1202-5.