Comparison Studies of GENXPERT versus MGIT Culture of Bronchial Lavage in Sputum Smear Negative Suspected Pulmonary Tuberculosis

Abhay Uppe^1, , Arti Sharma¹, Sayli Sawant¹, Deepak Gupta¹ and Girija Nair¹

¹Department of Pulmonary Medicine, D.Y.Medical College, Nerul Navi Mumbai, Maharashtra, India

Cite this paper:
Abhay Uppe, Arti Sharma, Sayli Sawant, Deepak Gupta and Girija Nair. Comparison Studies of GENXPERT versus MGIT Culture of Bronchial Lavage in Sputum Smear Negative Suspected Pulmonary Tuberculosis. American Journal of Infectious Diseases and Microbiology. 2018; 6(2):57-61. doi: 10.12691/ajidm-6-2-4

Abstract

Introduction: Xpert MTB/RIF (Cepheid, USA) is an automated real-time PCR system that simultaneously detects TB and resistance to rifampicin. The test has excellent accuracy when performed on sputum and is endorsed by the World Health Organisation (WHO) and the USA Federal Drug Administration. Aims: To measure the diagnostic yield of bronchoalveolar lavage gene Xpert and compare it with traditional mycobacterial cultures in smear-negative and sputum-scarce pulmonary tuberculosis. Methods: A prospective observational study at a tertiary care hospital in India was conducted. A total of 200 patients who were 18 years or older under evaluation for clinico‐radiological features of PTB with a history of a cough >2 weeks and a chest X‐ray with pulmonary parenchymal involvement were recruited after ensuring two consecutive sputum negative smears or inability to produce adequate sputum. A volume of one ml of BAL sample was used to detect mycobacterium tuberculosis by the G4 version of Xpert® MTB/RIF (Cepheid, USA) and by traditional mycobacterial cultures. cartridges without initial decontamination or centrifugation. Sensitivity, specificity and predictive values were calculated with 95% class intervals (CIs). McNemar’s test was used for comparison of sensitivities. Result: The results showed that the AFB smear test had 76.83% (95% CI: 66.20-85.44) sensitivity, 100.0% (95% CI: 96.92-100.0) specificity with 100.% PPV and 86.13% (95%CI: 80.72-90.21) NPV compared to culture report. The Gene Xpert test had better sensitivity 84.15% (95% CI: 74.42-91.28) and good specificity 97.52% (95% CI: 92.75-99.47) with 97.52% (95% CI: 92.75-99.47) PPV and 89.84% (95% CI: 84.30-93.58) NPV compared to AFB smear test. The Gene Xpert test to detect resistance against culture report had 89.47% (95% CI: 66.86-98.70) sensitivity, 90.61% (95% CI: 85.39-94.43) specificity with 50.0% (95% CI: 38.27-61.73) PPV and 98.90% (95% CI: 95.67-99.67) NPV. Conclusion: Xpert MTB/RIF has high sensitivity and specificity for diagnosis of both smear positive and smear negative PTB cases with high rates of detection of RIF resistance and greater concordance with gene sequencing for RIF resistance when com- pared with culture.

Keywords:
bronchalveolar lavage tuberculosis

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Raviglione M, Sulis G. Tuberculosis 2015: Burden, Challenges and Strategy for Control and Elimination. Infect Dis Rep 2016; 8: 6570.
[2]	Maartens G, Wilkinson RJ. Tuberculosis. Lancet 2007; 370: 2030-43.
[3]	World Health Organization. 2015 Global Tuberculosis Report. Geneva, Switzerland: WHO, 2015.
[4]	World Health Organization. Tuberculosis control in south east asia region: Annual TB report 2013. New Delhi, India: WHO 2013.
[5]	Chang C, Hong J, Yuan M, Chang M, Lee Y, Chang S, et al. Risk factors in patients with AFB smear-positive sputum who receive inappropriate antituberculous treatment. Drug Des Devel Ther 2013; 7:53-8.
[6]	Desta K, Asrat D, Lemma E, Gebeyehu M, Feleke B. Prevalence of smear-negative pulmonary tuberculosis among patients visiting St. Peter's Tuberculosis Specialized Hospital, Addis Ababa, Ethiopia. Ethiop Med J 2009; 47:17-24.
[7]	Theron G, Peter J, Meldau R, Khalfey H, Gina P, Matinyena B, et al. Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid. Thorax 2013; 68:1043-51.
[8]	Kheawon N, Chuang-Ngam S, Mitsoongneun S, Peam-Am J, Visalsawadi J. Role of routine bronchial washing culture for TB in Maharat Nakhon Ratchasima Hospital, Thailand. J Med Assoc Thai 2013; 96:558-63.
[9]	World Health Organization. Automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resitance: Xpert MTB/RIF SYSTEM. Publication number WHO/HTM/TB/ 2011.4. (2011). Available from http://whqlibdoc.who.int/publications/2011/9789241501545_eng.pdf (last accessed 7 June 2014).
[10]	World Health Organization. Automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB/RIF system for the diagnosis of pulmonary and extrapulmonary TB in adults and children. Publication number WHO/HTM/TB/ 2013.14. (2013) Available from http://apps.who.int/iris/bitstream/10665/112472/ 1/9789241506335_eng.pdf?ua51 (last accessed 7 June 2014).
[11]	Federal Drug Administration. Press release: FDA permits marketing of first U.S. test labeled for simultaneous detection of tuberculosis bacteria and resistance to the antibiotic rifampin. Available from http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm362602.htm (last accessed 13 January 2014).
[12]	Blakemore, R. et al. Evaluation of the analytical performance of the Xpert MTB/ RIF assay. J Clin Microbiol 48, 2495–2501 (2010).
[13]	Helb, D. et al. Rapid detection of Mycobacterium tuberculosis and rifampin resistance by use of on-demand, near-patient technology. J. Clin. Microbiol. 48, 229-237 (2010).
[14]	Mohan A, Sharma SK. Fibreoptic bronchoscopy in the diagnosis of sputum smear‐negative pulmonary tuberculosis: Current status. Indian J Chest Dis Allied Sci 2008; 50: 67‐78.
[15]	Central TB Division. Revised National Tuberculosis Control Programme Laboratory Network Guidelines for Quality Assurance of Smear Microscopy for Diagnosing Tuberculosis. New Delhi, India; 2005. Available from: http://www.tbcindia.nic.in/pdfs/RNTCP%20Lab%20Network%20Guidelines. [Last accessed on 2019 Sep 01].
[16]	Guenaoui K, Harir N, Ouardi A, Zeggai S, Sellam F, Bekri F, et al. Use of GeneXpert Mycobacterium tuberculosis/rifampicin for rapid detection of rifampicin resistant Mycobacterium tuberculosis strains of clinically suspected multi-drug resistance tuberculosis cases. Ann Transl Med 2016; 4(May (9)):168.
[17]	Steingart KR, Schiller I, Horne DJ, Pai M, Boehme CC, Dendukuri N. Xpert1 MTB/RIF assay for pulmo- nary tuberculosis and rifampicin resistance in adults (Review). Cochrane Database Syst. Rev. 1: CD009593.
[18]	Ullah I, Javaid A, Masud H, Ali M, Basit A, Ahmad W, et al. Rapid detection of Mycobacterium tuberculosis and rifampicin resistance in extrapulmonary tuberculosis and sputum smearnegative pulmonary suspects using Xpert MTB/RIF. J Med Microbiol 2017;66(April (4)):412-8.
[19]	Lee HY, Seong MW, Park SS, Hwang SS, Lee J, Park YS, et al. Diagnostic accuracy of Xpert1 MTB/RIF on bronchoscopy specimens in patients with suspected pulmonary tuberculosis. Int J Tuberc Lung Dis 2013; 17(July (7)): 917-21.
[20]	Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010; 363:1005-1015.
[21]	Steingart KR, Schiller I, Horne DJ, Pai M, Boehme CC, Dendukuri N. Xpert1 MTB/RIF assay for pulmo-nary tuberculosis and rifampicin resistance in adults (Review). Cochrane Database Syst. Rev. 1: CD009593.
[22]	Zeka AN, Tasbakan S and Cavusoglu C. Evaluation of the GeneXpert MTB/RIF Assay for the rapid diagnosis of tuberculosis and detection of RIF-resistance in pulmonary and extrapulmonary Speci- mens. J Clin Microbiol. 2011; 49: 4138-4141.
[23]	Ramaswamy S, Musser JM. Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. Tuber Lung Dis 1998;79(1): 3-29.
[24]	Lawn SD, Mwaba P, Bates M, Piatek A, Alexander H, Marais BJ, et al. Advances in tuberculosis diagnostics: the Xpert MTB/RIF assay and future prospects for a point-of-care test. Lancet Infect Dis 2013; 13(April (4)): 349-61.
[25]	Centers for Disease C and Prevention. Availability of an assay for detecting Mycobacterium tuberculosis, including rifampicin-resistant strains, and consid- erations for its use — United States, 2013. MMWR Morb Mortal Wkly Rep 2013;62:821-7.
[26]	Zhao Y, Xu S, Wang L, Chin DP, Wang S, Jiang G, et al. National survey of drug- resistant tuberculosis in China. N Engl J Med 2012; 366: 2161-70.
[27]	Vadwai V, Boehme C, Nabeta P, Shetty A, Rodrigue C. Need to confirm isoniazid susceptible cases in Xpert MTB/RIF rifampicin susceptible cases. Indian J Med Res. 2012; 135: 560-561. PMID: 22664508.