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Latent tuberculosis: what the host “sees”?

  • UNIVERSITY OF PITTSBURGH IMMUNOLOGY 2011
  • Published:
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Abstract

Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB), is the most successful pathogen of mankind and remains a major threat to global health as the leading cause of death due to a bacterial pathogen. Yet 90–95% of those who are infected with MTB remain otherwise healthy. These people are classified as “latently infected,” but remain a reservoir from which active TB cases will continue to develop (“reactivation tuberculosis”). Latent infection is defined by the absence of clinical symptoms of TB in addition to a delayed hypersensitivity reaction to the purified protein derivative of MTB used in tuberculin skin test or a T-cell response to MTB-specific antigens. In the absence of reliable control measures for tuberculosis, understanding latent MTB infection and subsequent reactivation is a research priority. This review aims to summarize the recent findings in human and non-human primate models of tuberculosis that have led to new concepts of latent tuberculosis.

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References

  1. WHO. Global tuberculosis control: key findings from the December 2009 WHO report. Wkly Epidemiol Rec. 2010;85(9):69–80.

    Google Scholar 

  2. Daniel TM. The history of tuberculosis. Respir Med. 2006;100(11):1862–70.

    PubMed  Google Scholar 

  3. Trunz BB, Fine P, Dye C. Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness. Lancet. 2006;367(9517):1173–80.

    PubMed  Google Scholar 

  4. Walker V, Selby G, Wacogne I. Does neonatal BCG vaccination protect against tuberculous meningitis? Arch Dis Child. 2006;91(9):789–91.

    PubMed  CAS  Google Scholar 

  5. Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, Mosteller F. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA. 1994;271(9):698–702.

    PubMed  CAS  Google Scholar 

  6. Brewer TF. Preventing tuberculosis with bacillus Calmette-Guerin vaccine: a meta-analysis of the literature. Clin Infect Dis. 2000;31(Suppl 3):S64–7.

    PubMed  Google Scholar 

  7. Behr MA, Small PM. Has BCG attenuated to impotence? Nature. 1997;389(6647):133–4.

    PubMed  CAS  Google Scholar 

  8. Behr MA, Wilson MA, Gill WP, Salamon H, Schoolnik GK, Rane S, Small PM. Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science. 1999;284(5419):1520–3.

    PubMed  CAS  Google Scholar 

  9. Gordon SV, Eiglmeier K, Garnier T, Brosch R, Parkhill J, Barrell B, Cole ST, Hewinson RG. Genomics of Mycobacterium bovis. Tuberculosis (Edinb). 2001;81(1–2):157–63.

    CAS  Google Scholar 

  10. Mahairas GG, Sabo PJ, Hickey MJ, Singh DC, Stover CK. Molecular analysis of genetic differences between Mycobacterium bovis BCG, virulent M. bovis. J Bacteriol. 1996;178(5):1274–82.

    PubMed  CAS  Google Scholar 

  11. Brosch R, Gordon SV, Marmiesse M, et al. A new evolutionary scenario for the Mycobacterium tuberculosis complex. Proc Natl Acad Sci U S A. 2002;99(6):3684–9.

    PubMed  CAS  Google Scholar 

  12. Knezevic I, Corbel MJ. WHO discussion on the improvement of the quality control of BCG vaccines. Vaccine. 2006;24(18):3874–7.

    PubMed  CAS  Google Scholar 

  13. Ritz N, Hanekom WA, Robins-Browne R, Britton WJ, Curtis N. Influence of BCG vaccine strain on the immune response and protection against tuberculosis. FEMS Microbiol Rev. 2008;32(5):821–41.

    PubMed  CAS  Google Scholar 

  14. Maartens G, Wilkinson RJ. Tuberculosis. Lancet. 2007;370(9604):2030–43.

    PubMed  Google Scholar 

  15. Russell DG, Barry CE 3rd, Flynn JL. Tuberculosis: what we don’t know can, and does, hurt us. Science. 2010;328(5980):852–6.

    PubMed  CAS  Google Scholar 

  16. Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med. 2008;149(3):177–84.

    PubMed  Google Scholar 

  17. Pai M, Minion J, Sohn H, Zwerling A, Perkins MD. Novel and improved technologies for tuberculosis diagnosis: progress and challenges. Clin Chest Med. 2009;30(4):701–16. viii.

    PubMed  Google Scholar 

  18. Lalvani A, Pareek M. A 100 year update on diagnosis of tuberculosis infection. Br Med Bull. 2009;93:69–84.

    PubMed  Google Scholar 

  19. Lange C, Mori T. Advances in the diagnosis of tuberculosis. Respirology. 2010;15(2):220–40.

    PubMed  Google Scholar 

  20. Rangaka MX, Wilkinson KA, Seldon R, et al. Effect of HIV-1 infection on T-Cell-based and skin test detection of tuberculosis infection. Am J Respir Crit Care Med. 2007;175(5):514–20.

    PubMed  Google Scholar 

  21. Lalvani A, Pareek M. Interferon gamma release assays: principles and practice. Enferm Infecc Microbiol Clin. 2009;28:245–52.

    PubMed  Google Scholar 

  22. Herzog H. History of tuberculosis. Respiration. 1998;65(1):5–15.

    PubMed  CAS  Google Scholar 

  23. Barry CE 3rd, Boshoff HI, Dartois V, et al. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat Rev Microbiol. 2009;7(12):845–55.

    PubMed  CAS  Google Scholar 

  24. Lin PL, Flynn JL. Understanding latent tuberculosis: a moving target. J Immunol. 2010;185(1):15–22.

    PubMed  CAS  Google Scholar 

  25. Young DB, Gideon HP, Wilkinson RJ. Eliminating latent tuberculosis. Trends Microbiol. 2009;17(5):183–8.

    PubMed  CAS  Google Scholar 

  26. Mtei L, Matee M, Herfort O, et al. High rates of clinical and subclinical tuberculosis among HIV-infected ambulatory subjects in Tanzania. Clin Infect Dis. 2005;40(10):1500–7.

    PubMed  Google Scholar 

  27. Flynn JL, Chan J, Lin PL. Macrophages and control of granulomatous inflammation in tuberculosis. Mucosal Immunol 2011.

  28. Lin PL, Rodgers M, Smith L, et al. Quantitative comparison of active and latent tuberculosis in the cynomolgus macaque model. Infect Immun. 2009;77(10):4631–42.

    PubMed  CAS  Google Scholar 

  29. Lin PL, Pawar S, Myers A, et al. Early events in Mycobacterium tuberculosis infection in cynomolgus macaques. Infect Immun. 2006;74(7):3790–803.

    PubMed  CAS  Google Scholar 

  30. Capuano SV 3rd, Croix DA, Pawar S, et al. Experimental Mycobacterium tuberculosis infection of cynomolgus macaques closely resembles the various manifestations of human M. tuberculosis infection. Infect Immun. 2003;71(10):5831–44.

    PubMed  CAS  Google Scholar 

  31. Via LE, Lin PL, Ray SM, et al. Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman primates. Infect Immun. 2008;76(6):2333–40.

    PubMed  CAS  Google Scholar 

  32. Canetti G. The Tubercule bacillus. Inc, New York: Springer Publishing Co; 1955.

    Google Scholar 

  33. Loomis HM. Some facts in the etiology of tuberculosis, evidenced by thirty autopsies and experiments upon animals. Medical Record. 1890;38:689–98.

    Google Scholar 

  34. Opie EaA J. Tubercle bacilli in latent tuberculous lesions and lung tissue without tuberculous lesions. Arch Pathol. 1927;4:1–21.

    Google Scholar 

  35. Griffith AD. Types of tubercle bacilli in human tuberculosis. J Pathol Bacteriol. 1929;32:813–40.

    Google Scholar 

  36. Vandiviere HM. The treated pulmonary lesion and its tubercle bacillus II. The death and resurrection. Am J Med Sci. 1956;232:30–7.

    PubMed  CAS  Google Scholar 

  37. Cardona PJ. New insights on the nature of latent tuberculosis infection and its treatment. Inflamm Allergy Drug Targets. 2007;6(1):27–39.

    PubMed  CAS  Google Scholar 

  38. Wayne LG, Sohaskey CD. Nonreplicating persistence of mycobacterium tuberculosis. Annu Rev Microbiol. 2001;55:139–63.

    PubMed  CAS  Google Scholar 

  39. Stewart GR, Robertson BD, Young DB. Tuberculosis: a problem with persistence. Nat Rev Microbiol. 2003;1(2):97–105.

    PubMed  CAS  Google Scholar 

  40. Gomez JE, McKinney JD M. tuberculosis persistence, latency, and drug tolerance. Tuberculosis (Edinb). 2004;84(1–2):29–44.

    Google Scholar 

  41. Zhang Y. Persistent and dormant tubercle bacilli and latent tuberculosis. Front Biosci. 2004;9:1136–56.

    PubMed  CAS  Google Scholar 

  42. Boshoff HI, Barry CE 3rd. Tuberculosis - metabolism and respiration in the absence of growth. Nat Rev Microbiol. 2005;3(1):70–80.

    PubMed  CAS  Google Scholar 

  43. Ehlers S. Lazy, dynamic or minimally recrudescent? On the elusive nature and location of the mycobacterium responsible for latent tuberculosis. Infection. 2009;37(2):87–95.

    PubMed  CAS  Google Scholar 

  44. Cosma CL, Sherman DR, Ramakrishnan L. The secret lives of the pathogenic mycobacteria. Annu Rev Microbiol. 2003;57:641–76.

    PubMed  CAS  Google Scholar 

  45. Betts JC, Lukey PT, Robb LC, McAdam RA, Duncan K. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol Microbiol. 2002;43(3):717–31.

    PubMed  CAS  Google Scholar 

  46. Roxas BA, Li Q. Acid stress response of a mycobacterial proteome: insight from a gene ontology analysis. Int J Clin Exp Med. 2009;2(4):309–28.

    PubMed  CAS  Google Scholar 

  47. Rustad TR, Harrell MI, Liao R, Sherman DR. The enduring hypoxic response of Mycobacterium tuberculosis. PLoS One. 2008;3(1):e1502.

    PubMed  Google Scholar 

  48. Stewart GR, Wernisch L, Stabler R, Mangan JA, Hinds J, Laing KG, Young DB, Butcher PD. Dissection of the heat-shock response in Mycobacterium tuberculosis using mutants and microarrays. Microbiology. 2002;148(Pt 10):3129–38.

    PubMed  CAS  Google Scholar 

  49. Rustad TR, Sherrid AM, Minch KJ, Sherman DR. Hypoxia: a window into Mycobacterium tuberculosis latency. Cell Microbiol. 2009;11(8):1151–9.

    PubMed  CAS  Google Scholar 

  50. Rao PK, Rodriguez GM, Smith I, Li Q. Protein dynamics in iron-starved Mycobacterium tuberculosis revealed by turnover and abundance measurement using hybrid-linear ion trap-Fourier transform mass spectrometry. Anal Chem. 2008;80(18):6860–9.

    PubMed  CAS  Google Scholar 

  51. Kesavan AK, Brooks M, Tufariello J, Chan J, Manabe YC. Tuberculosis genes expressed during persistence and reactivation in the resistant rabbit model. Tuberculosis (Edinb). 2009;89(1):17–21.

    CAS  Google Scholar 

  52. Lin MY, Ottenhoff TH. Not to wake a sleeping giant: new insights into host-pathogen interactions identify new targets for vaccination against latent Mycobacterium tuberculosis infection. Biol Chem. 2008;389(5):497–511.

    PubMed  CAS  Google Scholar 

  53. Black GF, Thiel BA, Ota MO, et al. Immunogenicity of novel DosR regulon-encoded candidate antigens of Mycobacterium tuberculosis in three high-burden populations in Africa. Clin Vaccine Immunol. 2009;16(8):1203–12.

    PubMed  CAS  Google Scholar 

  54. Demissie A, Leyten EM, Abebe M, et al. Recognition of stage-specific mycobacterial antigens differentiates between acute and latent infections with Mycobacterium tuberculosis. Clin Vaccine Immunol. 2006;13(2):179–86.

    PubMed  CAS  Google Scholar 

  55. Leyten EM, Lin MY, Franken KL, et al. Human T-cell responses to 25 novel antigens encoded by genes of the dormancy regulon of Mycobacterium tuberculosis. Microbes Infect. 2006;8(8):2052–60.

    PubMed  CAS  Google Scholar 

  56. Roupie V, Romano M, Zhang L, et al. Immunogenicity of eight dormancy regulon-encoded proteins of Mycobacterium tuberculosis in DNA-vaccinated and tuberculosis-infected mice. Infect Immun. 2007;75(2):941–9.

    PubMed  CAS  Google Scholar 

  57. Wilkinson RJ, Wilkinson KA, De Smet KA, Haslov K, Pasvol G, Singh M, Svarcova I, Ivanyi J. Human T- and B-cell reactivity to the 16 kDa alpha-crystallin protein of Mycobacterium tuberculosis. Scand J Immunol. 1998;48(4):403–9.

    PubMed  CAS  Google Scholar 

  58. Geluk A, Lin MY, van Meijgaarden KE, Leyten EM, Franken KL, Ottenhoff TH, Klein MR T. cell recognition of the HspX protein of Mycobacterium tuberculosis correlates with latent M. tuberculosis infection but not BCG vaccination. Infect Immun. 2007;75:2914–21.

    PubMed  CAS  Google Scholar 

  59. Wilkinson KA, Stewart GR, Newton SM, et al. Infection biology of a novel alpha-crystallin of Mycobacterium tuberculosis: Acr2. J Immunol. 2005;174(7):4237–43.

    PubMed  CAS  Google Scholar 

  60. Gideon HP, Wilkinson KA, Rustad TR, et al. Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines. PLoS Pathog. 2010;6(12):e1001237.

    PubMed  CAS  Google Scholar 

  61. Smieja MJ, Marchetti CA, Cook DJ, Smaill FM. Isoniazid for preventing tuberculosis in non-HIV infected persons. Cochrane Database Syst Rev. 2000;2:CD001363.

    PubMed  Google Scholar 

  62. Houk VN, Kent DC, Sorensen K, Baker JH. The eradication of tuberculosis infection by isoniazid chemoprophylaxis. Arch Environ Health. 1968;16(1):46–50.

    PubMed  CAS  Google Scholar 

  63. Mount FW, Ferebee SH. The effect of isoniazid prophylaxis on tuberculosis morbidity among household contacts of previously known cases of tuberculosis. Am Rev Respir Dis. 1962;85:821–7.

    PubMed  CAS  Google Scholar 

  64. Ferebee SH, Mount FW. Tuberculosis morbidity in a controlled trial of the prophylactic use of isoniazid among household contacts. Am Rev Respir Dis. 1962;85:490–510.

    PubMed  CAS  Google Scholar 

  65. Veening GJ. Long term isoniazid prophylaxis. Controlled trial on INH prophylaxis after recent tuberculin conversion in young adults. Bull Int Union Tuberc. 1968;41:169–71.

    PubMed  CAS  Google Scholar 

  66. Ford CB, Lin PL, Chase MR, et al. Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection. Nat Genet. 2011.

  67. Yang CM, Hsu CH, Lee CM, Wang FC. Intense uptake of [F-18]-fluoro-2 deoxy-d-glucose in active pulmonary tuberculosis. Ann Nucl Med. 2003;17(5):407–10.

    PubMed  Google Scholar 

  68. Hara T, Kosaka N, Suzuki T, Kudo K, Niino H. Uptake rates of 18F-fluorodeoxyglucose and 11C-choline in lung cancer and pulmonary tuberculosis: a positron emission tomography study. Chest. 2003;124(3):893–901.

    PubMed  CAS  Google Scholar 

  69. Goo JM, Im JG, Do KH, Yeo JS, Seo JB, Kim HY, Chung JK. Pulmonary tuberculoma evaluated by means of FDG PET: findings in 10 cases. Radiology. 2000;216(1):117–21.

    PubMed  CAS  Google Scholar 

  70. Cooper AM. Cell-mediated immune responses in tuberculosis. Annu Rev Immunol. 2009;27:393–422.

    PubMed  CAS  Google Scholar 

  71. Cooper AM, Khader SA. The role of cytokines in the initiation, expansion, and control of cellular immunity to tuberculosis. Immunol Rev. 2008;226:191–204.

    PubMed  CAS  Google Scholar 

  72. Mattila JT, Diedrich CR, Lin PL, Phuah J, Flynn JL. Simian immunodeficiency virus-induced changes in T cell cytokine responses in cynomolgus macaques with latent Mycobacterium tuberculosis infection are associated with timing of reactivation. J Immunol. 2011;186(6):3527–37.

    PubMed  CAS  Google Scholar 

  73. Hanekom WA, Abel B, Scriba TJ. Immunological protection against tuberculosis. S Afr Med J. 2007;97(10 Pt 2):973–7.

    PubMed  Google Scholar 

  74. Newport MJ, Huxley CM, Huston S, Hawrylowicz CM, Oostra BA, Williamson R, Levin M. A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N Engl J Med. 1996;335(26):1941–9.

    PubMed  CAS  Google Scholar 

  75. Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, Siegel JN, Braun MM. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001;345(15):1098–104.

    PubMed  CAS  Google Scholar 

  76. Millington KA, Innes JA, Hackforth S, et al. Dynamic relationship between IFN-gamma and IL-2 profile of Mycobacterium tuberculosis-specific T cells and antigen load. J Immunol. 2007;178(8):5217–26.

    PubMed  CAS  Google Scholar 

  77. Caccamo N, Guggino G, Joosten SA, et al. Multifunctional CD4(+) T cells correlate with active Mycobacterium tuberculosis infection. Eur J Immunol. 2010;40(8):2211–20.

    PubMed  CAS  Google Scholar 

  78. Sutherland JS, Adetifa IM, Hill PC, Adegbola RA, Ota MO. Pattern and diversity of cytokine production differentiates between Mycobacterium tuberculosis infection and disease. Eur J Immunol. 2009;39(3):723–9.

    PubMed  CAS  Google Scholar 

  79. Day CL, Mkhwanazi N, Reddy S, Mncube Z, van der Stok M, Klenerman P, Walker BD. Detection of polyfunctional Mycobacterium tuberculosis-specific T cells and association with viral load in HIV-1-infected persons. J Infect Dis. 2008;197(7):990–9.

    PubMed  CAS  Google Scholar 

  80. Wilkinson KA, Seldon R, Meintjes G, Rangaka MX, Hanekom WA, Maartens G, Wilkinson RJ. Dissection of regenerating T-Cell responses against tuberculosis in HIV-infected adults sensitized by Mycobacterium tuberculosis. Am J Respir Crit Care Med. 2009;180(7):674–83.

    PubMed  CAS  Google Scholar 

  81. Seder RA, Darrah PA, Roederer M. T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol. 2008;8(4):247–58.

    PubMed  CAS  Google Scholar 

  82. Khader SA, Cooper AM. IL-23 and IL-17 in tuberculosis. Cytokine. 2008;41(2):79–83.

    PubMed  CAS  Google Scholar 

  83. Cooper AM. Editorial: be careful what you ask for: is the presence of IL-17 indicative of immunity? J Leukoc Biol. 2010;88(2):221–3.

    PubMed  CAS  Google Scholar 

  84. Berry MP, Graham CM, McNab FW, et al. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature. 2010;466(7309):973–7.

    PubMed  CAS  Google Scholar 

  85. Green AM, Mattila JT, Bigbee CL, Bongers KS, Lin PL, Flynn JL. CD4(+) regulatory T cells in a cynomolgus macaque model of Mycobacterium tuberculosis infection. J Infect Dis. 2010;202(4):533–41.

    PubMed  CAS  Google Scholar 

  86. Burl S, Hill PC, Jeffries DJ, et al. FOXP3 gene expression in a tuberculosis case contact study. Clin Exp Immunol. 2007;149(1):117–22.

    PubMed  CAS  Google Scholar 

  87. Kaufmann SH. How can immunology contribute to the control of tuberculosis? Nat Rev Immunol. 2001;1(1):20–30.

    PubMed  CAS  Google Scholar 

  88. Tsai MC, Chakravarty S, Zhu G, et al. Characterization of the tuberculous granuloma in murine and human lungs: cellular composition and relative tissue oxygen tension. Cell Microbiol. 2006;8(2):218–32.

    PubMed  CAS  Google Scholar 

  89. Maglione PJ, Chan J. How B cells shape the immune response against Mycobacterium tuberculosis. Eur J Immunol. 2009;39(3):676–86.

    PubMed  CAS  Google Scholar 

  90. Maertzdorf J, Repsilber D, Parida SK, Stanley K, Roberts T, Black G, Walzl G, Kaufmann SH. Human gene expression profiles of susceptibility and resistance in tuberculosis. Genes Immun. 2011;12(1):15–22.

    PubMed  CAS  Google Scholar 

  91. Jacobsen M, Repsilber D, Gutschmidt A, Neher A, Feldmann K, Mollenkopf HJ, Ziegler A, Kaufmann SH. Candidate biomarkers for discrimination between infection and disease caused by Mycobacterium tuberculosis. J Mol Med. 2007;85(6):613–21.

    PubMed  CAS  Google Scholar 

  92. Walzl G, Ronacher K, Hanekom W, Scriba TJ, Zumla A. Immunological biomarkers of tuberculosis. Nat Rev Immunol. 2011;11(5):343–54.

    PubMed  CAS  Google Scholar 

  93. Keane J. Tumor necrosis factor blockers and reactivation of latent tuberculosis. Clin Infect Dis. 2004;39(3):300–2.

    PubMed  CAS  Google Scholar 

  94. Wallis RS. Infectious complications of tumor necrosis factor blockade. Curr Opin Infect Dis. 2009;22(4):403–9.

    PubMed  CAS  Google Scholar 

  95. Lin PL, Myers A, Smith L, et al. Tumor necrosis factor neutralization results in disseminated disease in acute and latent Mycobacterium tuberculosis infection with normal granuloma structure in a cynomolgus macaque model. Arthritis Rheum. 2010;62(2):340–50.

    PubMed  CAS  Google Scholar 

  96. Corbett EL, Bandason T, Cheung YB, et al. Epidemiology of tuberculosis in a high HIV prevalence population provided with enhanced diagnosis of symptomatic disease. PLoS Med. 2007;4(1):e22.

    PubMed  Google Scholar 

  97. Lawn SD, Wood R, Wilkinson RJ. Changing concepts of “latent tuberculosis infection” in patients living with HIV infection. Clin Dev Immunol. 2011.

  98. Kalsdorf B, Scriba TJ, Wood K, et al. HIV-1 infection impairs the bronchoalveolar T-cell response to mycobacteria. Am J Respir Crit Care Med. 2009;180(12):1262–70.

    PubMed  CAS  Google Scholar 

  99. Diedrich CR, Mattila JT, Klein E, et al. Reactivation of latent tuberculosis in cynomolgus macaques infected with SIV is associated with early peripheral T cell depletion and not virus load. PLoS One. 2010;5(3):e9611.

    PubMed  Google Scholar 

  100. Kagina BM, Abel B, Bowmaker M, et al. Delaying BCG vaccination from birth to 10 weeks of age may result in an enhanced memory CD4 T cell response. Vaccine. 2009;27(40):5488–95.

    PubMed  CAS  Google Scholar 

  101. Hesseling AC, Marais BJ, Gie RP, Schaaf HS, Fine PE, Godfrey-Faussett P, Beyers N. The risk of disseminated Bacille Calmette-Guerin (BCG) disease in HIV-infected children. Vaccine. 2007;25(1):14–8.

    PubMed  Google Scholar 

  102. Hesseling AC, Rabie H, Marais BJ, et al. Bacille Calmette-Guerin vaccine-induced disease in HIV-infected and HIV-uninfected children. Clin Infect Dis. 2006;42(4):548–58.

    PubMed  CAS  Google Scholar 

  103. WHO. Revised BCG vaccination guidelines for infants at risk for HIV infection. Wkly Epidemiol Rec. 2007;82(21):193–6.

    Google Scholar 

  104. Delogu G, Fadda G. The quest for a new vaccine against tuberculosis. J Infect Dev Ctries. 2009;3(1):5–15.

    PubMed  Google Scholar 

  105. Lambert PH, Hawkridge T, Hanekom WA. New vaccines against tuberculosis. Clin Chest Med. 2009;30(4):811–26. x.

    PubMed  Google Scholar 

  106. Hanekom WA, Lawn SD, Dheda K, Whitelaw A. Tuberculosis research update. Trop Med Int Health. 2010;15(8):981–9.

    PubMed  CAS  Google Scholar 

  107. Aagaard C, Hoang T, Dietrich J, et al. A multistage tuberculosis vaccine that confers efficient protection before and after exposure. Nat Med. 2011;17(2):189–94.

    PubMed  CAS  Google Scholar 

  108. Akolo C, Adetifa I, Shepperd S, Volmink J. Treatment of latent tuberculosis infection in HIV infected persons. Cochrane Database Syst Rev. 2010;1:CD000171.

    PubMed  Google Scholar 

  109. Menzies D, Al Jahdali H, Al Otaibi B. Recent developments in treatment of latent tuberculosis infection. Indian J Med Res. 2011;133(3):257–66.

    PubMed  CAS  Google Scholar 

  110. Lobue P, Menzies D. Treatment of latent tuberculosis infection: an update. Respirology. 2010;15(4):603–22.

    PubMed  Google Scholar 

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Acknowledgments

We are grateful to support from the NIH (HL106804, HL092883, and AI50732 to JLF) and the Bill and Melinda Gates Foundation. We are also grateful to the members of the Flynn laboratory and our colleagues, particularly Drs. Douglas Young, Clifton Barry, III, John Chan, Robert Wilkinson and Denise Kirschner for intellectual discussions.

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Correspondence to JoAnne L. Flynn.

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Gideon, H.P., Flynn, J.L. Latent tuberculosis: what the host “sees”?. Immunol Res 50, 202–212 (2011). https://doi.org/10.1007/s12026-011-8229-7

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