A recent update of the diagnostic methods for tuberculosis and their applicability in Indonesia: a narrative review

  • Tri Nugraha Susilawati Department of Microbiology, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia
  • Riska Larasati Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia https://orcid.org/0000-0003-4328-670X
Keywords: diagnosis, infection, tuberculosis
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Tuberculosis (TB) is a major global problem, especially with the high prevalence of HIV-TB co-infection. Delayed diagnosis and continual transmission contribute to high mortality in Indonesia, which has the third highest incidence of TB in the world, after China and India. Therefore, early diagnosis is needed to reduce the number of cases and to administer therapy to prevent the transmission of bacteria. The diagnosis of TB remains a challenge in clinical practice due to poor sensitivity and the requirement of skilled staff in microscopic tests, the slow growth Mycobacterium in culture, and the low number of bacilli present in extrapulmonary TB. Despite being the golden standard for TB diagnosis, cultures require 2–8 weeks to grow. Other methods for diagnosing TB include interferon-gamma release assays and serologic tests such as the tuberculin skin test. Recently, the World Health Organization recommended the GeneXpert MTB/RIF assay for diagnosing TB. This review presents the current state of TB epidemiology and various methods for TB diagnosis. In particular, the paper provides an in-depth discussion about the GeneXpert MTB/RIF assay that has been made available recently in selected tertiary hospitals in Indonesia.


  1. World Health Organization [Internet]. Global Tuberculosis Report 2018. Geneva: World Health Organization; 2018 [cited 2019 Apr 5]. Available from: https://www.who.int/tb/publications/global_report/en/

  2. Indonesian Ministry of Health. National Guidelines for Tuberculosis Control (Pedoman Nasional Pengendalian Tuberkulosis) 2014. Jakarta; 2014. p. 1-210.

  3. Collins D, Hafidz F, Mustikawati D. The economic burden of tuberculosis in Indonesia. Int J Tuberc Lung Dis. 2017;21(9):1041-48. https://doi.org/10.5588/ijtld.16.0898

  4. Molicotti P, Bua A, Zanetti S. Cost-effectiveness in the diagnosis of tuberculosis: choices in developing countries. J Infect Dev Ctries. 2014;8(1):24-38. https://doi.org/10.3855/jidc.3295

  5. 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(1):229-37. https://doi.org/10.1128/JCM.01463-09

  6. Lawn SD, Nicol MP. Xpert® MTB/RIF assay: development, evaluation and implementation of a new rapid molecular diagnostic for tuberculosis and rifampicin resistance. Future Microbiol. 2011;6(9):1067-82. https://doi.org/10.2217/fmb.11.84

  7. Nikam C, Kazi M, Nair C, Jaggannath M, Manoj MM, Vinaya RV, et al. Evaluation of the Indian TrueNAT micro RT-PCR device with GeneXpert for case detection of pulmonary tuberculosis. Int J Mycobacteriol. 2014;3(3):205-10. https://doi.org/10.1016/j.ijmyco.2014.04.003

  8. Yruela I, Contreras-Moreira B, Magalhães C, Osório NS, Gonzalo-Asensio J. Mycobacterium tuberculosis complex exhibits lineage-specific variations affecting protein ductility and epitope recognition. Genome Biol Evol. 2016;8(12):3751-64. https://doi.org/10.1093/gbe/evw279

  9. Goldman E, Green LH. Practical Handbook of Microbiology. Second Edition. Boca Raton: CRC Press; 2009. pp. 109-1.1

  10. Centers for Disease Control and Prevention; National Center for HIV/AIDS, Viral Hepatitis, STD, TB Prevention - Division of Tuberculosis Elimination [Internet]. Core Curriculum on Tuberculosis: What the Clinician Should Know. Atlanta: Centers for Disease Control and Prevention; 2013 [cited 2018 Jan 15]. Available from: https://www.cdc.gov/tb/education/corecurr/pdf/corecurr_all.pdf

  11. Lewinsohn DM, Leonard MK, LoBue PA, Cohn DL, Daley CL, Desmond E, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017;64(2:)111-5. https://doi.org/10.1093/cid/ciw778

  12. Nunes-Alves C, Booty MG, Carpenter SM, Jayaraman P, Rothchild AC, Behar SM. In search of a new paradigm for protective immunity to TB. Nat Rev Microbiol. 2014;12(4):289-99. https://doi.org/10.1038/nrmicro3230

  13. Pravin KN, Chourasia E. Use of GeneXpert assay for diagnosis of tuberculosis from body fluid specimens, a 2 years study. J Microbiol Biotechnol. 2016;1(1):000105. https://doi.org/10.23880/OAJMB-16000105

  14. Indonesian Ministry of Health. Indonesian Health Profile (Profil Kesehatan Indonesia) 2015. 2016. p. 403.

  15. Garcia de Viedma D, Lorenzo G, Cardona PJ, Rodriguez NA, Gordillo S, Serrano MJ, et al. Association between the infectivity of Mycobacterium tuberculosis strains and their efficiency for extrarespiratory infection. J Infect Dis. 2005;192(12):2059-65. https://doi.org/10.1086/498245

  16. Piatek AS, Van Cleeff M, Alexander H, Coggin WL, Rehr M, Van Kampen S, et al. GeneXpert for TB diagnosis: planned and purposeful implementation. Glob Health Sci Pract. 2013;1(1):18-23. https://doi.org/10.9745/GHSP-D-12-00004

  17. Dharan NJ, Amisano D, Mboowa G, Ssengooba W, Blakemore R, Kubiak RW, et al. Improving the sensitivity of the Xpert MTB/RIF assay on sputum pellets by decreasing the amount of added sample reagent: a laboratory and clinical evaluation. J Clin Microbiol. 2015;53(4):1258-63. https://doi.org/10.1128/JCM.03619-14

  18. 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 Syst Rev. 2014;(1):CD009593. https://doi.org/10.1002/14651858.CD009593.pub3

  19. Lawn SD, Zumla AI. Diagnosis of extrapulmonary tuberculosis using the Xpert® MTB/RIF assay. Expert Rev Anti Infect Ther. 2012;10(6):631-5. https://doi.org/10.1586/eri.12.43

  20. Agrawal M, Bajaj A, Bhatia V, Dutt S. Comparative study of GeneXpert with ZN stain and culture in samples of suspected pulmonary tuberculosis. J Clin Diagn Res. 2016;10(5):DC09-12. https://doi.org/10.7860/JCDR/2016/18837.7755

  21. 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(9):168. https://doi.org/10.21037/atm.2016.05.09

  22. Zeka AN, Tasbakan S, Cavusoglu C. Evaluation of the GeneXpert MTB/RIF assay for rapid diagnosis of tuberculosis and detection of rifampin resistance in pulmonary and extrapulmonary specimens. J Clin Microbiol. 2011;49(12):4138-41. https://doi.org/10.1128/JCM.05434-11

  23. Ghariani A, Jaouadi T, Smaoui S, Mehiri E, Marouane C, Kammoun S, et al. Diagnosis of lymph node tuberculosis using the GeneXpert MTB/RIF in Tunisia. Int J Mycobacteriol. 2015;4(4):270-5. https://doi.org/10.1016/j.ijmyco.2015.05.011

  24. Pang Y, Su B, Zheng H, Zhang Z, Ma A, Wang Y, et al. Factors associated with missed detection of Mycobacterium tuberculosis by automated BACTEC MGIT 960 system. Biomed Res Int. 2016;2016:5972021. https://doi.org/10.1155/2016/5972021

  25. Maynard-Smith L, Larke N, Peters JA, Lawn SD. Diagnostic accuracy of the Xpert MTB/RIF assay for extrapulmonary and pulmonary tuberculosis when testing non-respiratory samples: a systematic review. BMC Infect Dis. 2014;14:709. https://doi.org/10.1186/s12879-014-0709-7

  26. Duman N, Ersoy-Evans S, Karadağ O, Așçioğlu S, Sener B, Kiraz S, et al. Screening for latent tuberculosis infection in psoriasis and psoriatic arthritis patients in tuberculosis-endemic country: a comparison of the QuantiFERON®-TB Gold In-Tube test and tuberculin skin test. Int J Dermatol. 2014;53(10):1286-92. https://doi.org/10.1111/ijd.12522

  27. Niguse S, Desta K, Gebremichael G, Gebrezgeaxier A, Getahun M, Kassa D. GuantiFERON-TB Gold In-tube test for the diagnosis of active and latent tuberculosis in selected health facilities of Addis Ababa, Ethiopia. BMC Res Notes. 2018;11(1):293. https://doi.org/10.1186/s13104-018-3410-x

  28. Pandey S, Congdon J, McInnes B, Pop A, Coulter C. Evaluation of the GeneXpert MTB/RIF assay on extrapulmonary and respiratory samples other than sputum: a low burden country experience. Pathology. 2017;49(1):70-4. https://doi.org/10.1016/j.pathol.2016.10.004

  29. Nurwidya F, Handayani D, Burhan E, Yunus F. Molecular diagnosis of tuberculosis. Chonnam Med J. 2018;54(1):1-9. https://doi.org/10.4068/cmj.2018.54.1.1

  30. Denkinger CM, Schumacher SG, Boehme CC, Dendukuri N, Pai M, Steingart KR. Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2014;44(2):435-46. https://doi.org/10.1183/09031936.00007814

  31. Kokuto H, Sasaki Y, Yoshimatsu S, Mizuno K, Yi L, Mitrai S. Detection of Mycobacterium tuberculosis (MTB) in fecal specimens from adults diagnosed with pulmonary tuberculosis using the Xpert MTB/rifampicin test. Open Forum Infect Dis. 2015;2(2):ofv074. https://doi.org/10.1093/ofid/ofv074

  32. Indonesian Minister of Health. The Minister of Health rules no. 67 the year 2016 about management of tuberculosis (Peraturan Menteri Kesehatan nomor 67 tahun 2016 tentang penanggulangan tuberkulosis). Jakarta [Indonesia]; 2016. 163 p. Indonesian.

  33. Indonesian Ministry of Health. National guidelines of medical service for management of tuberculosis (pedoman nasional pelayanan kedokteran tata laksana tuberkulosis). Jakarta [Indonesia]; 2013. 210 p. Indonesian.

  34. Indonesian Ministry of Health. Technical guidelines about management of tuberculosis in children (petunjuk teknis manajemen dan tatalaksana TB anak). Jakarta [Indonesia]; 2016. 98 p. Indonesian.

How to Cite
Susilawati TN, Larasati R. A recent update of the diagnostic methods for tuberculosis and their applicability in Indonesia: a narrative review. Med J Indones [Internet]. 2019Oct.4 [cited 2020Jul.6];28(3):284-91. Available from: http://mji.ui.ac.id/journal/index.php/mji/article/view/2589
Review Article