Chapter 49 : Tuberculosis

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Tuberculosis, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816872/9781555815141_Chap49-1.gif /docserver/preview/fulltext/10.1128/9781555816872/9781555815141_Chap49-2.gif


Approximately one-third of the world’s population is thought to harbor latent forms of tuberculosis and the resultant huge reservoir for future disease. The recent increase in multidrug resistant disease and a dangerous interplay between tuberculosis and human immunodeficiency virus (HIV) infection continues to pose serious challenges for health care in the years to come. is transmitted by the inhalation of small droplet nuclei, which are aerosolized infectious particles generated by coughing, talking, and sneezing. A minority of patients with tuberculosis, who are started on highly active antiretroviral therapy (HAART) experience immune reconstitution disease (IRD) due to rapid restoration of the immune system with an increased response to mycobacterial antigens. To be valuable as a surrogate endpoint, a biomarker should measure an event that is directly involved in pathogenesis or protection and should change early during treatment. Early bactericidal activity (EBA) is used in the early evaluation of new tuberculosis drugs and is based on the rate of fall of colony-forming unit counts of (logcfu/day) in overnight sputum samples that are collected before and on alternate days of treatment, up to day 14. A host of nonspecific markers have been described that appear promising as biomarkers for tuberculosis. The extent of the tuberculosis problem that exists today represents an affront to modern society. New tools are urgently needed and only multidisciplinary approaches that include all sectors of healthcare providers and researchers stand a chance to address the problem effectively.

Citation: Walzl G, Helden P, Botha P. 2011. Tuberculosis, p 623-631. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch49
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Anteroposterior chest radiograph of an adult female with sputum culture confirmed tuberculosis with HIV coinfection (i.e., CD4 T-cell count of 274 × 10/L and not on antiretroviral treatment). There are bilateral infiltrates, right upper lobe cavitation, and right-sided pleural involvement. Courtesy of the Division of Radiology, Tygerberg Academic Hospital.

Citation: Walzl G, Helden P, Botha P. 2011. Tuberculosis, p 623-631. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch49
Permissions and Reprints Request Permissions
Download as Powerpoint


1. American Thoracic Society. 1992. Control of tuberculosis in the United States. Am. J. Respir. Dis. 146: 16231633.
2. Andrews, J. R.,, N. S. Shah,, N. Gandhi,, T. Moll,, and G. Friedland, Tugela Ferry Care and Research (TF CARES) Collaboration. 2007. Multidrug-resistant and extensively drug-resistant tuberculosis: implications for the HIV epidemic and antiretroviral therapy rollout in South Africa. J. Infect. Dis. 196: S482S490.
3. Basua,, S.,, G. H. Friedland,, J. Medlock,, J. R Andrews,, N. S. Shah,, N. R. Gandhi,, A. Moll,, P. Moodley,, A. W. Sturm, and, A. P. Galvania. 2009. Averting epidemics of extensively drug-resistant tuberculosis. Proc. Natl. Acad. Sci. USA 106: 76727677.
4. Bates, J. H.,, and W. W. Stead. 1993. The history of tuberculosis as a global epidemic. Med. Clin. N. Am. 77: 12051217.
5. Biomarkers Working Group. 2001. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin. Pharmacol. Ther. 69: 8995.
6. Bock,, N. N.,, P. A. Jensen,, B. Miller, and, E. Nardell. 2007. Tuberculosis infection control in resource-limited settings in the era of expanding HIV care and treatment. J. Infect. Dis. 196:S108–S113.
7. Carroll, N. M.,, P. Uys,, A. Hesseling,, K. Lawrence,, C. Pheiffer,, F. Salker,, K. Duncan,, N. Beyers,, and P. D. van Helden. 2008. Prediction of delayed treatment response in pulmonary tuberculosis: use of time to positivity values of Bactec cultures. Tuberculosis 88: 624630.
8. Charalambous, S.,, A. D. Grant,, V. Moloi,, R. Warren,, J. H. Day,, P. van Helden,, R. J. Hayes,, K. L. Fielding,, K. M. De Cock,, R. E. E,, and G. J. Churchyard. 2008. Contribution of reinfection to recurrent tuberculosis in South African gold miners. Int. J. Tuberc. Lung Dis. 8: 942948.
9. Daley, C. L., P. M. Small, and, G. F. Schecter. 1992. An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus. N. Engl. J. Med. 36: 231235.
10. Davies, P. D. O., and M. Pai. 2008. The diagnosis and misdiagnosis of tuberculosis. Int. J. Tuberc. Lung Dis. 12: 12261234.
11. Dheda, K.,, R. van Zyl Smit,, M. Badri,, and M. Pai. 2009. T-cell interferon-γ release assays for the rapid immunodiagnosis of tuberculosis: clinical utility in high-burden versus low-burden settings. Curr. Opin. Pulm. Med. 15: 188200.
12. Doherty, T. M.,, R. S. Wallis, and, A. Zumla. 2009. Biomarkers for tuberculosis disease status and diagnosis. Curr. Opin. Pulm. Med. 15: 181187.
13. Donald, P. R., and, P. D. van Helden. 2009. The global burden of tuberculosis—combating drug resistance in difficult times. N. Engl. J. Med. 360: 23932395.
14. Fitzgerald, D., and, D. W. Haas. 2005. Mycobacterium tuberculosis, p. 2852- 2886. In G. L. Mandell,, J. E. Bennet,, and R. Dolin R (ed.). Principles and Practice of Infectious Diseases, 6th ed. Elsevier/Churchill Livingstone, Philadelphia.
15. Fletcher, H. A. 2007. Correlates of immune protection from tuberculosis. Curr. Mol. Med. 7: 319325.
16. Flynn, J. L., and, J. Chan. 2003. Immune evasion by Mycobacterium tuberculosis: living with the enemy. Curr. Opin. Immunol. 4: 450455.
17. Graham, M. N. 1996. The role of immunologic and viral markers in predicting clinical outcome in HIV infection. AIDS 10:S21–S25.
18. Greco, S.,, E. Girardi,, A. Navarra,, and C. Saltini. 2006. Current evidence on diagnostic accuracy of commercially based nucleic acid amplification tests for the diagnosis of pulmonary tuberculosis. Thorax 61: 783790.
19. Gandhi,, N. R.,, A. Moll,, A. W Sturm,, R. Pawinski,, T. Govender,, U. Lalloo,, K. Zeller,, J. Andrews, and, G. Friedland. 2006. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet 368: 15541556.
20. Gruman, J., and, M. Follick. 1998. Putting evidence into practice: the OBSSR report of the working group on the integration of effective behavioral treatments into clinical care. Office of Behavioral and Social Sciences Research, National Institutes of Health, Bethesda, MD. http://obssr.od.nih.gov/pdf/everpt3.pdf. Accessed 10 August 2009.
21. Hussey, G., T. Chisholm, and, M. Kibel. 1991. Miliary tuberculosis in children: a review of 94 cases. Pediatr. Infect. Dis. J. 10: 832836.
22. Jacobsen, M.,, J. Mattow,, D. Repsilber,, and S. H. E. Kaufmann. 2008. Novel strategies to identify biomarkers in tuberculosis. Biol, Chem. 389: 487495.
23. Jassal, M., and, W. R. Bishai. 2009. Extensively drug-resistant tuberculosis. Lancet Infect, Dis. 1: 1930.
24. Johnson, R.,, E. M. Streicher,, G. E. Louw,, R. M. Warren,, P. D. van Helden,, and T. C. Victor. 2006. Drug resistance in Mycobacterium tuberculosis. Curr. Issues Mol. Biol. 8: 97112.
25. Klausner,, J. D.,, R. W. Ryder,, E. Baende,, U. Lelo, J. C. Wil-liame,, K. Ngamboli,, J. H. Perriens,, M. Kaboto, and, J. Prignot. 1993. Mycobacterium tuberculosis in household contacts of human immunodeficiency virus type 1-seropositive patients with active pulmonary tuberculosis in Kinshasa, Zaire. J. Infect. Dis. 168: 106111.
26. Lawn, S. D., S. T. Butera, and, T. M. Shinnick. 2002. Tuberculosis unleashed: the impact of human immunodeficiency virus infection on the host granulomatous response to Mycobacterium tuberculosis. Microbes Infect. 4: 635646.
27. Lawn,, S. D.,, L. G. Bekker,, K. Middelkoop,, L. Myer, and, R. Wood. 2006. Impact of HIV infection on the epidemiology of tuberculosis in a peri-urban community in South Africa: the need for age-specific interventions. Clin. Infect. Dis. 42: 10401047.
28. Lawn, S. D.,, L. Myer,, L. G. Bekker,, and R. Wood. 2007. Tuberculosis-associated immune reconstitution disease: incidence, risk factors and impact in an antiretroviral treatment service in South Africa. AIDS 21: 335341.
29. Lawn, S. D., and, G. Churchyard. 2009. Epidemiology of HIV-associated tuberculosis. Curr. Opin. HIV AIDS 4: 325333.
30. Middelkoop, K.,, L. G. Bekker,, L. Myer,, R. Dawson,, and R. Wood. 2008. Rates of tuberculosis transmission to children and adolescents in a community with a high prevalence of HIV infection among adults. Clin. Infect. Dis. 47: 349355.
31. Moore, D. A.,, C. A. Evans,, R. H. Gilman,, L. Caviedes,, J. Coronel,, A. Vivar,, E. Sanchez,, Y. Pinedo,, J. C. Saravia,, C. Salazar,, R. Oberhelman,, M. G. Hollm-Delgado,, D. La-Chira,, A. R. Escombe, and, J. S. Friedland. 2006. Microscopic-observation drug susceptibility assay for the diagnosis of TB. N. Engl. J. Med. 355: 15391550.
32. Morrison, J., M. Pai, and, P. C. Hopewell. 2008. Tuberculosis and latent tuberculosis infections in close contacts of people with pulmonary tuberculosis in low-income and middleincome countries: a systematic review and meta-analysis. Lancet Infect. Dis. 8: 359368.
33. Muga, R.,, I. Ferreros,, K. Langohr,, P. G. de Olalla,, J. Del Romero,, M. Quintana,, I. Alastrue,, J. Belda,, J. Tor,, S. Perez-Hoyos,, and J. Del Amo. 2007. Changes in the incidence of tuberculosis in a cohort of HIV-seroconverters before and after the introduction of HAART AIDS 21: 25212527.
34. Nash, D. R., and, J. E. Douglass. 1980. Anergy in active pulmonary tuberculosis: a comparison between positive and negative reactors and an evaluation of 5 TU and 250 TU skin test doses. Chest 77: 3237.
35. Nissen, S. E., and, K. Wolski. 2007. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N. Engl. J. Med. 356: 24572471.
36. Ottenhoff,, T. H.,, F. A. Verreck,, M. A. Hoeve, and, E. van de Vosse. 2005. Control of human host immunity to mycobacteria. Tuberculosis 85: 5364.
37. Pai, M.,, L. L. Flores,, A. Hubbard,, L. W. Riley,, and J. M. Colford, Jr. 2004. Nucleic acid amplification tests in the diagnosis of tuberculous pleuritis: a systematic review and meta-analysis. BMC Infect. Dis. 4:6.
38. Pepper,, T., P. Joseph,, C. Mwenya,, G. S McKee,, A. Haushalter,, A. Carter,, J. Warkentin,, D. W. Haas, and, T. R. Sterling. 2008. Normal chest radiography in pulmonary tuberculosis: implications for obtaining respiratory specimen cultures. Int. J. Tuberc. Lung Dis. 12: 397403.
39. Perkins, M. D., and, J. Cunningham. 2007. Facing the crisis: improving the diagnosis of tuberculosis in the HIV era. J. Infect. Dis. 196: S15S27.
40. Perrin,, F. M. R.,, M. C. I. Lipman,, T. D. McHugh,, and S. H. Gillespie. 2007. Biomarkers of treatment response in clinical trials of novel antituberculosis agents. Lancet Infect. Dis. 7: 481490.
41. Seder, R. A.,, P. A. Darrah, and, M. Roederer. 2008. T-cell quality in memory and protection: implications for vaccine design. Nat. Rev. Immunol. 8: 247258.
42. Sharma, K. S.,, A. Mohan,, A. Sharma,, and D. K. Mitra. 2005. Miliary tuberculosis: new insights into an old disease. Lancet Infect. Dis. 5: 415430.
43. Stead, W. W. 1989. Pathogenesis of tuberculosis: clinical and epidemiologic perspective. Rev. Infect. Dis. 11: S366S368.
44. Stop TB Partnership and World Health Organization. 2006. Global plan to stop TB 2006-2015. The World Health Organization, Geneva, Switzerland. www.stoptb.org/global/plan
45. Van Rie, A.,, R. M. Warren,, M. Richardson,, T. C Victor,, R. P. Gie,, D. A. Enarson,, N. Beyers,, and P.D. van Helden. 1999. Exogenous reinfection is a common cause of tuberculosis recurrence after cure. N. Eng. J. Med. 341: 11741179.
46. Veenstra,, H., I. Crous,, S. Brahmbhatt,, P. Lukey,, N. Beyers, P. D. van Helden, and, G. Walzl. 2007. Changes in the kinetics of intracellular IFN-γ production in TB patients during treatment. Clin. Immunol. 124: 336344.
47. Walzl, G.,, K. Ronacher,, J. F. Djoba Siawaya,, and H. M. Dockrell. 2008. Biomarkers for TB treatment response: challenges and future strategies. J. Infect. 57: 103109.
48. Wallis,, R. S.,, T. M. Doherty,, P. Onyebujoh,, M. Vahedi,, H. Lang,, O. Olesen,, S. Parida, and, A. Zumla. 2009. Biomarkers for tuberculosis disease activity, cure, and relapse. Lancet Infect. Dis. 9: 162172.
49. Watkins, R. E., R. Brennan, and, A. J. Plant. 2000. Tuberculin reactivity and the risk of tuberculosis: a review. Int. J. Tuberc. Lung Dis. 4: 895903.
50. Wayne, L. G., and, K. Y. Lin. 1982. Glyoxylate metabolism and adaptation of Mycobacterium tuberculosis to survival under anaerobic conditions. Infect. Immun. 37: 10421049.
51. Woldehanna, S., and, J. Volmink. 2004. Treatment of latent tuberculosis infection in HIV infected persons. Cochrane Database Syst. Rev. CD000171.
52. World Health Organization. 2009. Global tuberculosis control: surveillance, planning, financing. World Health Organization, Geneva, Switzerland, http://www.who.int/tb/publications/global_report/2009/pdf/full_report.pdf
53. Young D. B., H. P. Gideon, and, R. J. Wilkinson. 2009. Eliminating latent tuberculosis. Trends Microbiol. 17: 183188.
54. Zumla, A.,, R. S. Wallis,, T. M. Doherty,, N. Klein,, S. Parida,, O. Olesen,, H. Lång,, M. Vahedi,, and P. Onyebujoh. 2008. Joint TDR/EC expert consultation on biomarkers in tuberculosis: report of the joint TDR/EC expert consultation to evaluate the potential roles of biomarkers in the management of HIV-infected and HIV-uninfected patients with tuberculosis. World Health Organization, Geneva, Switzerland. http://apps.who.int/tdr/svc/publications/tdrresearch-publications/biomarkers

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error