Title: Diagnostic Role of Cartridge Based Nucleic Acid Amplification Test in Diagnosing Tuberculosis in Patients Co-infected with Human Immunodeficiency Virus

Authors: Prem Parkash Gupta, Adarsh B Mynalli, Aparna Yadav

 DOI:  https://dx.doi.org/10.18535/jmscr/v5i5.100

Abstract

Background: During recent years, disease caused by human immunodeficiency virus (HIV) and tuberculosis (TB) have been the two leading infectious diseases associated with mortality worldwide. The delays in diagnosis and initiation of anti-tubercular treatment often lead to increased transmission of TB in the community and spread to extrapulmonary sites within the patient. Our study aimed at to assess the role of CBNAAT in early diagnosis of TB in HIV patients and detection of M. tuberculosis in sputum by CBNAAT compared to conventional sputum microscopy in pulmonary TB

Methods: The study screened 211 patients with clinical symptoms suggestive of pulmonary tuberculosis. 30 subjects were found to be seropositive for HIV. Out of 30 HIV-TB patients, 20 were male. Direct microscopic sputum examination was done using Light Emitting Diode based Fluorescent Microscopy (LED-FM) method. All patients also submitted sputum sample for GeneXpert MTB/Rif test, a cartridge based nucleic acid amplification test (CBNAAT), analysed using GX4 system. 

Results: LED-Fluorescent Microscopy sputum examination was positive for acid fast bacilli in 8/30 HIV seropositive patients and 131/181 subjects who were seronegative for HIV. The data suggested patients who were HIV positive were less likely to have sputum smear positive results. CBNAAT detected M. tuberculosis in 17/30 HIV-seropositive patients and in 133/181 HIV-seronegative subjects. 56.7% of the patients who were positive for HIV were also positive for MTB and two of them had rifampicin resistance detected by CBNAAT.  

Conclusions: CBNAAT significantly increased the conclusive diagnosis of tuberculosis in patients co-infected with HIV, and additionally detected rifampicin resistance, thus providing huge leap in management of tuberculosis in HIV setting.

Keywords: Cartridge based nucleic acid amplification test, HIV, Tuberculosis, GeneXpert MTB/Rif test, Rifampicin resistance.

References

1.     1.      Global Tuberculosis Control 2016, WHO, Geneva, 2016, www.who.int/tb/publications/global_report/en/. Accessed on 2 May 2017.

2.      Steingart KR, Ng V, Henry M, Hopewell PC, Ramsay A, Cunningham J, et al. Sputum processing methods to improve the sensitivity of smear microscopy for tuberculosis: a systematic review. Lancet Infect Dis 2006; 6: 664–74.

3.      Pandey P, Pant ND, Rijal KR, Shrestha B, Kattel S, Banjara MR, Maharjan B, Kc R. 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.

4.      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.

5.      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: 2495-2501.

6.      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: 229-237.

7.      Kranzer K, Houben RM, Glynn JR et al. Yield of HIV-associated tuberculosis during intensified case finding in resource-limited settings: a systematic review and meta-analysis. Lancet Infect Dis 2010; 93-102. 

8.      Hopewell PC, Pai M, Maher D, Uplekar M, Raviglione MC. International standards for tuberculosis care. Lancet Infect Dis. 2006; 6: 710-25.

9.      Cattamanchi A, Dowdy DW, Davis JL, Worodria W, Yoo S, Joloba M, et al. Sensitivity of direct versus concentrated sputum smear microscopy in HIV-infected patients suspected of having pulmonary tuberculosis. BMC Infect Dis 2009; 9: 53.

10.  Matee M, Mtei L, Lounasvaara T, Wieland-Alter W, Waddell R, Lyimo J, et al.. Sputum microscopy for the diagnosis of HIV-associated pulmonary tuberculosis in Tanzania. BMC Public Health 2008; 8: 68.

11.  Corbett EL, Watt CJ, Walker N, Maher D, Williams BG, Raviglione MC, et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med 2003; 163:1009-21.

12.  Steingart KR, Schiller I, Horne DJ, Pai M, Boehme CC, Dendukuri N. Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No.: CD009593.

13.  Chauhan LS. Drug resistant TB-RNTCP response. Indian J Tuberc 2008; 55: 5-8.

14.  Van Rie A, Page-Shipp L, Scott L et al. Xpert(®) MTB/RIF for point-of care diagnosis of TB in high-HIV burden, resource-limited countries: hype or hope? Expert Rev Mol Diagn 2010; 10: 937-46.

15.  Carriquiry G, Otero L, González-Lagos E, Zamudio C, Sánchez E, Nabeta P, et al. A Diagnostic Accuracy Study of Xpert®MTB/RIF in HIV-Positive Patients with high Clinical Suspicion of Pulmonary Tuberculosis in Lima, Peru. PLoS ONE2012;  7:  e44626. https://doi.org/10.1371/journal.pone.0044626.

16.  Alvarez-Uria G, 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; p4 article ID 932862, doi;10.1155/2012.

17.  Boehme CC1, 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: 1005-15.

18.  Experience with implementation of Xpert MTB/RIF in India; Report by Dr KS Sachdeva, Addl DDG (TB), Govt of india. Available at www.stoptb.org. Accessed on Accessed on 2 May 2017.

19.  WHO Policy statement: automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB/RIF system 2011. Available at: http://www.who.int/tb/ laboratory/en/. Accessed on 1 May 2017.

Corresponding Author

Prem Parkash Gupta

Professor, Department of Respiratory Medicine

PGIMS, Rohtak, India

Email: This email address is being protected from spambots. You need JavaScript enabled to view it.