The progression of tb diagnosis in the hiv era: from microscopes to molecules and back to the bedside

South Africa suffers from dual epidemics of TB and HIV.

Jonathan Peter, MB ChB, FCP (SA)

Physician and PhD Fellow, Department of Medicine, University of Cape Town

Jonathan Peter completed his training as a specialist in internal medicine in 2009. Currently he is a full-time PhD student with the UCT Lung Infection and Immunity unit and an NIH Fogarty International Clinical Research Fellow. His PhD research is focused on the utility of sputum induction and novel emerging tools for the diagnosis of TB in high HIV-prevalent primary care settings. Additionally, he is the clinical co-ordinator and co-investigator for a number of ongoing multicentre TB diagnostic trials and a part-time lecturer in the Department of Medicine, University of Cape Town.

Grant Theron, BSc (Hons), MSc (UCL), PhD

Post-doctoral fellow, Lung Infection and Immunity Unit, University of Cape Town

Grant Theron completed his PhD in Molecular and Cell Biology in 2009. He is currently a European Union and National Research Foundation funded post-doctoral fellow in the UCT Lung Infection and Immunity Unit. His post-doctoral research is focused on developing and evaluating new tools for the diagnosis of TB. Recently this has included the evaluation of the Xpert MTB/RIF assay in Cape Town as well the ongoing development of new molecular-based diagnostics.

Correspondence to: Jonathan Peter (jonnyp@mweb.co.za)

References

1. WHO. Global Tuberculosis control 2010. Geneva: World Health Organisation,2010. WHO/HTM/TB/2010.7.

2. Kwan CK, Ernst JD. HIV and tuberculosis: a deadly human syndemic. Clin Microbiol Rev 2011;24(2):351-376.

3. Steingart KR, Ramsay A, Pai M. Optimizing sputum smear microscopy for the diagnosis of pulmonary tuberculosis. Expert Rev Anti Infect Ther 2007;5(3):327-331.

4. Wilson D, Nachega J, Morroni C, Chaisson R, Maartens G. Diagnosing smear-negative tuberculosis using case definitions and treatment response in HIV-infected adults. Int J Tuberc Lung Dis 2006;10(1):31-38.

5. Greco S, Girardi E, Navarra A, Saltini C. Current evidence on diagnostic accuracy of commercially based nucleic acid amplification tests for the diagnosis of pulmonary tuberculosis. Thorax 2006;61(9):783-790.

6. Boehme CC, Nicol MP, Nabeta P, et al. Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the GX test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study. Lancet 2011;377(9776):1495-1505.

7. WHO. Automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: GX SYSTEM. Geneva, Swizterland: World Health Organization 2011. ISBN 978 92 4 150154 5.

8. Theron G, Peter J, van Zyl-Smit R, et al. Evaluation of the Xpert(R) MTB/RIF assay for the diagnosis of pulmonary tuberculosis in a high HIV prevalence setting. Am J Respir Crit Care Med 2011;184:132-140.

9. Zar HJ, Workman L, Boehme C, Eley B, Nicol M. Cartridge-based automated nucleic acid amplification test (GX) for the diagnosis of pulmonary tuberculosis in HIV-Infected and uninfected children: A prospective study. Paper presented at: ATS conference, 2011, Denver, Colorado.

10. Vadwai V, Boehme C, Nabeta P, Shetty A, Alland D, Rodrigues C. GX, a new pillar in the diagnosis of extrapulmonary tuberculosis? J Clin Microbiol 2011;49:2540-2545.

11. Minion J, Leung E, Menzies D, Pai M. Microscopic-observation drug susceptibility and thin layer agar assays for the detection of drug resistant tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis 2010;10(10):688-698.

12. Barnard M, Albert H, Coetzee G, O’Brien R, Bosman ME. Rapid molecular screening for multidrug-resistant tuberculosis in a high-volume public health laboratory in South Africa. Am J Respir Crit Care Med. 2008;177(7):787-792.

13. Steingart KR, Henry M, Laal S, et al. Commercial serological antibody detection tests for the diagnosis of pulmonary tuberculosis: a systematic review. PLoS Med 2007;4(6):e202.

14. Sester M, Sotgiu G, Lange C, et al. Interferon-gamma release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis. Eur Respir J 2011;37(1):100-111.

15. Ling DI, Pai M, Davids V, et al. Are interferon-{gamma} release assays useful for active tuberculosis in a high-burden setting? Eur Respir J 2011;38:649-656.

16. Patel VB, Singh R, Connolly C, et al. Cerebrospinal T-cell responses aid in the diagnosis of tuberculous meningitis in a human immunodeficiency virus- and tuberculosis-endemic population. Am J Respir Crit Care Med 2010;182(4):569-577.

17. Mandalakas AM, Detjen AK, Hesseling AC, Benedetti A, Menzies D. Interferon-gamma release assays and childhood tuberculosis: systematic review and meta-analysis. Int J Tuberc Lung Dis 2011;15:1069-1076.

18. Peter J, Green C, Hoelscher M, Mwaba P, Zumla A, Dheda K. Urine for the diagnosis of tuberculosis: current approaches, clinical applicability, and new developments. Curr Opin Pulm Med 2010;16(3):262-270.

19. Dheda K, Van-Zyl Smit RN, Sechi LA, et al. Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting. PLoS One 2009;4(3):e4689.

20. Wilson D, Mbhele L, Badri M, et al. Evaluation of the World Health Organization algorithm for the diagnosis of HIV-associated sputum smear-negative tuberculosis. Int J Tuberc Lung Dis 2011;15(7):919-924.

21. Holtz TH, Kabera G, Mthiyane T, et al. Use of a WHO-recommended algorithm to reduce mortality in seriously ill patients with HIV infection and smear-negative pulmonary tuberculosis in South Africa: an observational cohort study. Lancet Infect Dis 2011;11:533-540.

22. Nicol MP, Zar HJ. New specimens and laboratory diagnostics for childhood pulmonary TB: progress and prospects. Paediatr Respir Rev 2011;12(1):16-21.