Skip to main content

Advertisement

Log in

Recent advances in tuberculosis diagnostics in resource-limited settings

  • Review
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Smear-negative and drug-resistant cases of tuberculosis (TB) disease necessitate the development of new diagnostic methods, especially in resource-limited settings. To improve the current TB situations, sensitive and specific TB point-of-care tests (POCTs) should be developed. This review addresses the current status of TB, novel diagnostic methodologies for TB, and the impact of those new diagnostics on TB control in such situations. Moreover, the perspective of TB management based on laboratory examinations is described. Smear microscopy with sputum samples is the only laboratory examination available in many resource-limited settings and is still used globally. Several nucleic acid amplification tests (NATs) have been developed. The World Health Organization (WHO) endorsed novel diagnostics based on NATs and updated their definition of a bacteriologically confirmed case requiring the biological specimen to be positive by smear microscopy, culture, or the WHO-recommended rapid diagnostic protocols. The use of new diagnostics increased the number of bacteriologically confirmed TB cases. Novel diagnostics are now available, but their sensitivity is still lower than that of conventional liquid culture method. To address the increasing incidence of TB, more resources including novel diagnostics as POCTs with higher sensitivity must be allocated to healthcare systems.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. WHO (2017) Global tuberculosis report 2017. WHO, Geneva

    Google Scholar 

  2. WHO (2012) Assessing tuberculosis under-reporting through inventory studies. In: WHO (ed)

  3. Uplekar M, Weil D, Lonnroth K, Jaramillo E, Lienhardt C, Dias HM, Falzon D, Floyd K, Gargioni G, Getahun H, Gilpin C, Glaziou P, Grzemska M, Mirzayev F, Nakatani H, Raviglione M, Programme WHGT (2015) WHO’s new end TB strategy. Lancet 385(9979):1799–1801. https://doi.org/10.1016/S0140-6736(15)60570-0

    Article  PubMed  Google Scholar 

  4. WHO (2016) Global tuberculosis report 2016. WHO, Geneva

    Google Scholar 

  5. CLSI (2008) Laboratory detection and identification of mycobacteria; approved guideline. CLSI document M48-A., vol 28. Clinical and Laboratory Standards Institute, Wayne

  6. Steingart KR, Henry M, Ng V, Hopewell PC, Ramsay A, Cunningham J, Urbanczik R, Perkins M, Aziz MA, Pai M (2006) Fluorescence versus conventional sputum smear microscopy for tuberculosis: a systematic review. Lancet Infect Dis 6(9):570–581. https://doi.org/10.1016/S1473-3099(06)70578-3

    Article  PubMed  Google Scholar 

  7. WHO (2011) Fluorescent light-emitting diode (LED) microscopy for diagnosis of tuberculosis: policy statement, Geneva

  8. Ridderhof JC, van Deun A, Kam KM, Narayanan PR, Aziz MA (2007) Roles of laboratories and laboratory systems in effective tuberculosis programmes. Bull World Health Organ 85(5):354–359

    Article  PubMed  PubMed Central  Google Scholar 

  9. Hall L, Jude KP, Clark SL, Wengenack NL (2011) Antimicrobial susceptibility testing of Mycobacterium tuberculosis complex for first and second line drugs by broth dilution in a microtiter plate format. J Vis Exp (52). https://doi.org/10.3791/3094

  10. Ratnam S, March SB (1986) Effect of relative centrifugal force and centrifugation time on sedimentation of mycobacteria in clinical specimens. J Clin Microbiol 23(3):582–585

    PubMed  PubMed Central  CAS  Google Scholar 

  11. Horita N, Yamamoto M, Sato T, Tsukahara T, Nagakura H, Tashiro K, Shibata Y, Watanabe H, Nagai K, Nakashima K, Ushio R, Ikeda M, Sakamaki K, Yoshiyama T, Kaneko T (2015) Sensitivity and specificity of Cobas TaqMan MTB real-time polymerase chain reaction for culture-proven Mycobacterium tuberculosis: meta-analysis of 26999 specimens from 17 studies. Sci Rep 5:18113. https://doi.org/10.1038/srep18113

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Steingart KR, Sohn H, Schiller I, Kloda LA, Boehme CC, Pai M, Dendukuri N (2013) Xpert(R) MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev 1:CD009593. https://doi.org/10.1002/14651858.CD009593.pub2

    Article  Google Scholar 

  13. WHO (2015) Global tuberculosis report 2015. WHO, Geneva

    Google Scholar 

  14. WHO (2014) Global tuberculosis report 2014. WHO, Geneva

    Google Scholar 

  15. WHO (2013) Global tuberculosis report 2013. WHO, Geneva

    Google Scholar 

  16. Initiative GL (2017) GLI planning for country transition to Xpert MTB/RIF Ultra cartridges

  17. FIND (2017) Report for WHO: a multicentre non-inferiority diagnostic accuracy study of the Ultra assay compared to the Xpert MTB/RIF assay, Geneva

  18. WHO (2016) The use of loop-mediated isothermal amplification ( TB-LAMP) for the diagnosis of pulmonary tuberculosis: policy guidance. In: WHO (ed)

  19. Nagai K, Horita N, Yamamoto M, Tsukahara T, Nagakura H, Tashiro K, Shibata Y, Watanabe H, Nakashima K, Ushio R, Ikeda M, Narita A, Kanai A, Sato T, Kaneko T (2016) Diagnostic test accuracy of loop-mediated isothermal amplification assay for Mycobacterium tuberculosis: systematic review and meta-analysis. Sci Rep 6:39090. https://doi.org/10.1038/srep39090

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. WHO (2015) The use of lateral flow urine lipoarabinomannan assay (LF-LAM) for the diagnosis and screening of active tuberculosis in people living with HIV. Policy guidance. In: WHO (ed)

  21. Flores LL, Steingart KR, Dendukuri N, Schiller I, Minion J, Pai M, Ramsay A, Henry M, Laal S (2011) Systematic review and meta-analysis of antigen detection tests for the diagnosis of tuberculosis. Clin Vaccine Immunol 18(10):1616–1627. https://doi.org/10.1128/CVI.05205-11

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Shah M, Hanrahan C, Wang ZY, Dendukuri N, Lawn SD, Denkinger CM, Steingart KR (2016) Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in HIV-positive adults. Cochrane Database Syst Rev 5:CD011420. https://doi.org/10.1002/14651858.CD011420.pub2

    Article  Google Scholar 

  23. Phillips M, Basa-Dalay V, Blais J, Bothamley G, Chaturvedi A, Modi KD, Pandya M, Natividad MP, Patel U, Ramraje NN, Schmitt P, Udwadia ZF (2012) Point-of-care breath test for biomarkers of active pulmonary tuberculosis. Tuberculosis (Edinb) 92(4):314–320. https://doi.org/10.1016/j.tube.2012.04.002

    Article  Google Scholar 

  24. Yi L, Sasaki Y, Nagai H, Ishikawa S, Takamori M, Sakashita K, Saito T, Fukushima K, Igarashi Y, Aono A, Chikamatsu K, Yamada H, Takaki A, Mori T, Mitarai S (2016) Evaluation of QuantiFERON-TB gold plus for detection of Mycobacterium tuberculosis infection in Japan. Sci Rep 6:30617. https://doi.org/10.1038/srep30617

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Kaur D, Berg S, Dinadayala P, Gicquel B, Chatterjee D, McNeil MR, Vissa VD, Crick DC, Jackson M, Brennan PJ (2006) Biosynthesis of mycobacterial lipoarabinomannan: role of a branching mannosyltransferase. Proc Natl Acad Sci U S A 103(37):13664–13669. https://doi.org/10.1073/pnas.0603049103

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Zhang X, Guo J, Fan S, Li Y, Wei L, Yang X, Jiang T, Chen Z, Wang C, Liu J, Ping Z, Xu D, Wang J, Li Z, Qiu Y, Li JC (2013) Screening and identification of six serum microRNAs as novel potential combination biomarkers for pulmonary tuberculosis diagnosis. PLoS One 8(12):e81076. https://doi.org/10.1371/journal.pone.0081076

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. McNerney R, Zumla A (2015) Impact of the Xpert MTB/RIF diagnostic test for tuberculosis in countries with a high burden of disease. Curr Opin Pulm Med 21(3):304–308. https://doi.org/10.1097/MCP.0000000000000161

    Article  PubMed  CAS  Google Scholar 

  28. Cox HS, Mbhele S, Mohess N, Whitelaw A, Muller O, Zemanay W, Little F, Azevedo V, Simpson J, Boehme CC, Nicol MP (2014) Impact of Xpert MTB/RIF for TB diagnosis in a primary care clinic with high TB and HIV prevalence in South Africa: a pragmatic randomised trial. PLoS Med 11(11):e1001760. https://doi.org/10.1371/journal.pmed.1001760

    Article  PubMed  PubMed Central  Google Scholar 

  29. Theron G, Zijenah L, Chanda D, Clowes P, Rachow A, Lesosky M, Bara W, Mungofa S, Pai M, Hoelscher M, Dowdy D, Pym A, Mwaba P, Mason P, Peter J, Dheda K, team T-N (2014) Feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing for tuberculosis in primary-care settings in Africa: a multicentre, randomised, controlled trial. Lancet 383(9915):424–435. https://doi.org/10.1016/S0140-6736(13)62073-5

    Article  PubMed  CAS  Google Scholar 

  30. Durovni B, Saraceni V, van den Hof S, Trajman A, Cordeiro-Santos M, Cavalcante S, Menezes A, Cobelens F (2014) Impact of replacing smear microscopy with Xpert MTB/RIF for diagnosing tuberculosis in Brazil: a stepped-wedge cluster-randomized trial. PLoS Med 11(12):e1001766. https://doi.org/10.1371/journal.pmed.1001766

    Article  PubMed  PubMed Central  Google Scholar 

  31. WHO (2003) Treatment of tuberculosis: guidelines for national programmes. In: WHO (ed)

  32. WHO (2016) WHO treatment guidelines for drug-resistant tuberculosis—2016 update. In: WHO (ed)

  33. Van Deun A, Maug AK, Salim MA, Das PK, Sarker MR, Daru P, Rieder HL (2010) Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis. Am J Respir Crit Care Med 182(5):684–692. https://doi.org/10.1164/rccm.201001-0077OC

    Article  PubMed  Google Scholar 

  34. Kent PT, Kubica GP (1985) A guide for level III In: Laboratory public health mycobacteriology. Centers for Disease Control, US Dept of Public Health and Human Services, Atlanta, Ga, pp 31–56

  35. Yoshimatsu S, Kato-Matsumaru T, Aono A, Chikamatsu K, Yamada H, Mitarai S (2015) Factors contribute to efficiency of specimen concentration of Mycobacterium tuberculosis by centrifugation and magnetic beads. Int J Mycobacteriol 4(3):245–249. https://doi.org/10.1016/j.ijmyco.2015.05.014

    Article  PubMed  Google Scholar 

  36. Starks AM, Aviles E, Cirillo DM, Denkinger CM, Dolinger DL, Emerson C, Gallarda J, Hanna D, Kim PS, Liwski R, Miotto P, Schito M, Zignol M (2015) Collaborative effort for a centralized worldwide tuberculosis relational sequencing data platform. Clin Infect Dis 61(Suppl 3):S141–S146. https://doi.org/10.1093/cid/civ610

    Article  PubMed Central  Google Scholar 

  37. Coll F, Mallard K, Preston MD, Bentley S, Parkhill J, McNerney R, Martin N, Clark TG (2012) SpolPred: rapid and accurate prediction of Mycobacterium tuberculosis spoligotypes from short genomic sequences. Bioinformatics 28(22):2991–2993. https://doi.org/10.1093/bioinformatics/bts544

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Funding

This project was supported by the Japan Society for the Promotion of Science (JSPS) Bilateral Open Partnership Joint Research Projects (MS).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Mitsuko Seki or Satoshi Mitarai.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

For this type of paper, formal consent does not apply.

Informed consent

For this type of paper, informed consent does not apply.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Seki, M., Kim, CK., Hayakawa, S. et al. Recent advances in tuberculosis diagnostics in resource-limited settings. Eur J Clin Microbiol Infect Dis 37, 1405–1410 (2018). https://doi.org/10.1007/s10096-018-3258-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-018-3258-y

Keywords

Navigation