Advances in the laboratory diagnosis of tuberculosis

Main Article Content

Guadalupe García Elorriaga, PhD Guillermo del Rey Pineda, PhD


Despite the advances made in the past 30 years in the laboratory diagnosis of tuberculosis (TB), only a small portion of the overall world population has benefitted. The World Health Organization (WHO) has recommended the use of nucleic acid amplification tests (NAAT) to detect TB instead of smear microscopy, since they can detect TB with greater precision, particularly in patients with paucibacillary disease and in individuals living with HIV. A broad range of molecular TB detection tests are currently being developed and evaluated, some for use in reference laboratories and others for peripheral medical care settings and point-of-care. There has been a surge of molecular tests designed, manufactured, and implemented in countries with a high TB load, and some are specifically meant for use in locations that are close to the patient. In terms of drug susceptibility testing, NAAT and next-generation sequencing may provide faster results than traditional phenotype culture. Further, the results of tests that detect or quantify cytokines released in the inflammatory process in latent tuberculosis infection (LTBI), such as the Interferon-Gamma Release Assay (IGRA), or that quantify IL-6 or other cytokines, depend, as in the tuberculin skin tests (TST), on the prevalence of TB in the tested population. We herein review the recent advances in TB detection tests and resistance to anti-TB drugs.

Article Details

How to Cite
ELORRIAGA, Guadalupe García; PINEDA, Guillermo del Rey. Advances in the laboratory diagnosis of tuberculosis. Medical Research Archives, [S.l.], v. 9, n. 1, jan. 2021. ISSN 2375-1924. Available at: <>. Date accessed: 14 aug. 2022. doi:
Research Articles


World Health Organization. 2020. Global tuberculosis report 2020. Geneva: World Health Organization, WHO Press, Geneva

2. García-Elorriaga G, del Rey-Pineda G. Practical and laboratory diagnosis of tuberculosis: From sputum smear to molecular biology. Switzerland: Springer, 2015. ISBN 978-3-319-20478-9

3. García-Elorriaga G, del Rey-Pineda G. Current Research in the Laboratory Diagnosis of Tuberculosis. SMGroup, 2016. ISBN: 978-1-944685-00-3

4. Fennelly KP, Acuna-Villaorduna C, Jones-Lopez E, Lindsley WG, Milton DK. Microbial Aerosols: New Diagnostic Specimens for Pulmonary Infections.Chest. 2020; 157:540-546. doi: 10.1016/j.chest.2019.10.012

5. Costa RRD, Silva SFD, Fochat RC, Macedo RL, Pereira TV, Silva MR et al. Comparison between Ogawa-Kudoh and modified Petroff techniques for mycobacteria cultivation in the diagnosis of pulmonary tuberculosis. Einstein (Sao Paulo). 2018; 16:eAO4214. doi: 10.1590/S1679-45082018AO4214

6. Asmar S, Drancourt M. Rapid culture-based diagnosis of pulmonary tuberculosis in developed and developing countries. Front Microbiol. 2015; 6:1184. doi: 10.3389/fmicb.2015.01184

7. Alva A, Aquino F, Gilman RH, Olivares C, Requena D, Gutiérrez AH et al. Morphological Characterization of Mycobacterium tuberculosis in a MODS Culture for an Automatic Diagnostics through Pattern Recognition. PLoS One. 2013; 8::e82809. doi: 10.1371/journal.pone.0082809

8. Barr DA, Kerkhoff AD, Schutz C, Ward AM, Davies GR, Wilkinson RJ et al. HIV-associated M. tuberculosis blood stream infection is under-diagnosed by a single blood culture. J Clin Microbiol. 2018; 56:e01914-17. doi: 10.1128/JCM.01914-17

9. Liu HC, Gao YL, Li DF, Zao XY, Pan YQ, Chang-Tai Zhu CT. Value of Xpert MTB/RIF using bronchoalveolar lavage fluid for the diagnosis of pulmonary tuberculosis: A systematic review and meta-analysis. J Clin Microbiol. 2020; pii: JCM.02170-20. doi: 10.1128/JCM.02170

10. Chakravorty S, Simmons AM, Rowneki M, Parmar H, Cao Y, Ryan J et al. The New Xpert MTB/RIF Ultra: improving detection of mycobacterium tuberculosis and resistance to rifampin in an assay suitable for point-of-care testing. MBio. 2017; 8:e00812–e00817

11. Nicol MP, Workman L, Prins M, Bateman L, Ghebrekristos Y, Mbhele S et al. Accuracy of Xpert MTB/RIF Ultra for the diagnosis of pulmonary tuberculosis in children. Pediatr Infect Dis J. 2018 ; 37:e261-e263. doi: 10.1097/INF.0000000000001960

12. Meldau R, Randall P, Pooran A, Limberis J, Makambwa E, Dhansay M et al. Same day tools, including Xpert Ultra and unstimulated IFN-1 γ, for the rapid diagnosis of pleural tuberculosis – a prospective observational study. J Clin Microbiol. 2019; 26; 57:e00614-19. doi: 10.1128/JCM.00614-19

13. World Health Organization. 2017. Next-generation Xpert® MTB/RIF Ultra assay
recommended by WHO. World Health Organization, Geneva.

14. Pai M. 2020. Global health technologies: time to re-think the ‘trickle down’ model. Forbes.

15. World Health Organization. 2020. Molecular assays intended as initial tests for the
diagnosis of pulmonary and extrapulmonary TB and rifampicin resistance in adults and
children: rapid communication. Policy update. World Health Organization, Geneva

16. Xie YL, Chakravorty S, Armstrong DT, Hall SL, Via LE, Song T et al. Evaluation of a Rapid Molecular Drug-Susceptibility Test for Tuberculosis. N Engl J Med. 2017; 377:1043-1054

17. Treatment Action Group. 2019. 2019 Pipeline Report: Tuberculosis Diagnostics.Treatment Action Group, Group TA, New York.

18. Ortega C, Wood R, Murton H, Andama A, Cattamanchi A, Dixon R et al. Diagnosis of pulmonary tuberculosis by oral swab analysis (OSA): optimisation and development of non-sputum, point-of-care methods. Int J Tuberc Lung Dis. 2019; 23:S211

19. Deng S, Sun Y, Xia H, Liu Z, Gao L, Yang J et al. Accuracy of Commercial Molecular Diagnostics for the Detection of Pulmonary Tuberculosis in China: A Systematic Review. Sci Rep. 2019; 9:4553

20. Sun Y, Gao L, Xia H, Yang Z, Deng S, Yang J. Accuracy of molecular diagnostic tests for drug-resistant tuberculosis detection in China: a systematic review. Int J Tuberc Lung Dis. 2019; 23:931-942

21. Kohli M, MacLean E, Schumacher SG, Pai M, Denkinger CM. Under review. Diagnostic accuracy of centralized assays for TB detection and detection of resistance to rifampicin and isoniazid: A systematic review and meta-analysis. Eur Respir J. 2020; doi: 10.1183/13993003.00747-2020

22. Roche Molecular Systems I. 2018. Cobas(R) MTB: Nucleic acid test for use on the
Cobas(R) 6800/8800 systems. Roche Molecular Systems, Basel

23. Rocchetti TT, Silbert S, Gostnell A, Kubasek C, Widen R. Validation of a Multiplex
Real-Time PCR Assay for Detection of Mycobacterium spp., Mycobacterium tuberculosis
Complex, and Mycobacterium avium Complex Directly from Clinical Samples by Use of
the BD Max Open System. J Clin Microbiol. 2016; 54:1644-7

24. FIND. 2020. Diagnostics Pipeline Tracker: Tuberculosis, on FIND. Accessed

25. World Health Organization. 2018. Technical guide on next-generation sequencing
technologies for the detection of mutations associated with drug resistance in Mycobacterium tuberculosis complex. World Health Organization, Organization WH,

26. Organization WH. 2019. Relational sequencing TB data platform [website]. World Health Organization, Geneva.

27. Zignol M, Cabibbe AM, Dean AS, Glaziou P, Alikhanova N, Ama Cet al. Genetic sequencing for surveillance of drug resistance in tuberculosis in highly endemic countries: a multi-country population-based surveillance study. Lancet Infect Dis. 2018; 18:675-683.

28. Meehan CJ, Goig GA, Kohl TA, Verboven L, Dippenaar A, Ezewudo M et al. Whole genome sequencing of Mycobacterium tuberculosis: current standards and open issues. Nat Rev Microbiol. 2019; 17:533-545

29. National Institute for Communicable Diseases. 2018. National Institute for Communicable Diseases Annual Overview 2018/2019. National Institute for Communicable Diseases, Capetown.

30. Venkatesan P. COVID-19 diagnostics- not at the expense of other diseases. Lancet Microbe. 2020; 1:e64 doi: 10.1016/S2666-5247(20)30041-0

31. Stop TB Partnership. 2020. The potential impact of the COVID-19 response on tuberculosis in high-burden countries: a modelling analysis. Stop TB Partnership, Geneva

32. United States Food and Drug Administration. 2020. Coronavirus (COVID-19) Update: FDA Issues first Emergency Use Authorization for Point of Care Diagnostic. United States Food and Drug Administration, Atlanta

33. Estévez O, Anibarro L, Garet E, Martínez A, Pena A, Barcia L et al. Multi-parameter Flow cytometry immunophenotyping distinguishes different stages of tuberculosis infection. J Infect. 2020; 81:57-71. DOI: 10.1016/j.jinf.2020.03.064

34. Lu LL, Smith MT, Yu KKQ, Luedemann C, Suscovich TJ, Grace PS et al. IFN-γ independent immune markers of Mycobacterium tuberculosis exposure. Nat Med. 2019, 25:977-987. doi: 10.1038/s41591-019-0441-3

35. Adankwah E, Nausch N, Minadzi D, Abass MK, Franken KLMC, Ottenhoff THM et al. Interleukin-6 and Mycobacterium tuberculosis dormancy antigens improve diagnosis of tuberculosis. J Infect. 2020; 0163-4453(20)30729-5. doi: 10.1016/j.jinf.2020.11.032.

36. Lesosky M, Rangaka MX, Pienaar C, Coussens AK, Goliath R, Mathee S et al. Plasma biomarkers to detect prevalent or predict progressive tuberculosis associated with Human Immunodeficiency Virus–1. Clin Infect Dis. 2019; 69:295-305. doi: 10.1093/cid/ciy823