Skip to main content

Abstract

This chapter will review the basic biology of Mycobacterium tuberculosis and then focus on the epidemiology, clinical manifestations, and diagnosis in transplant patients. Prevention and treatment will be considered elsewhere. Tuberculosis (TB) remains a leading cause of human mortality in resource-limited settings, in part because it is still a diagnostic and treatment challenge. These challenges are compounded in immunocompromised hosts such as transplant patients because the performance of diagnostic tests is poor, the clinical presentation is often atypical, and treatment is complicated by toxicity and drug-drug interactions. While there have been significant recent advances in our understanding of bacterial pathogenesis and host responses, the picture remains incomplete. Conventional tuberculin skin testing, acid-fast bacilli smear, mycobacterial culture, and antibiotic sensitivity testing are imperfect tools. New molecular techniques improve the speed and certainty with which a diagnosis can be made, but little data exist on their use in the transplant patient. The prevalence of TB is low in the countries that have historically had access to organ transplantation. However, immigration to such countries and the expansion of transplants to countries with higher incidences of TB have made tuberculosis an increasingly important posttransplant complication. When tuberculosis does happen in transplant patients, the morbidity and mortality are substantial.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Wolf AJ, Linas B, Trevejo-Nuñez GJ, Kincaid E, Tamura T, Takatsu K, et al. Mycobacterium tuberculosis infects dendritic cells with high frequency and impairs their function in vivo. J Immunol. 2007;179(4):2509–19.

    Article  CAS  PubMed  Google Scholar 

  2. Schäfer G, Jacobs M, Wilkinson RJ, Brown GD. Non-opsonic recognition of Mycobacterium tuberculosis by phagocytes. J Innate Immun. 2009;1(3):231–43.

    Article  PubMed  CAS  Google Scholar 

  3. Ishikawa E, Ishikawa T, Morita YS, Toyonaga K, Yamada H, Takeuchi O, et al. Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. J Exp Med. 2009;206(13):2879–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Schoenen H, Bodendorfer B, Hitchens K, Manzanero S, Werninghaus K, Nimmerjahn F, et al. Cutting edge: mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate. J Immunol. 2010;184(6):2756–60.

    Article  CAS  PubMed  Google Scholar 

  5. Armstrong JA, Hart PD. Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. J Exp Med. 1971;134(3 Pt 1):713–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sturgill-Koszycki S, Schlesinger PH, Chakraborty P, Haddix PL, Collins HL, Fok AK, et al. Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase. Science. 1994;263(5147):678–81.

    Article  CAS  PubMed  Google Scholar 

  7. Russell DG. Mycobacterium tuberculosis: here today, and here tomorrow. Nat Rev Mol Cell Biol. 2001;2(8):569–77.

    Article  CAS  PubMed  Google Scholar 

  8. van der Wel N, Hava D, Houben D, Fluitsma D, van Zon M, Pierson J, et al. M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells. Cell. 2007;129(7):1287–98.

    Article  PubMed  CAS  Google Scholar 

  9. McDonough KA, Kress Y, Bloom BR. Pathogenesis of tuberculosis: interaction of Mycobacterium tuberculosis with macrophages. Infect Immun. 1993;61(7):2763–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Watson RO, Manzanillo PS, Cox JS. Extracellular M. tuberculosis DNA targets bacteria for autophagy by activating the host DNA-sensing pathway. Cell. 2012;150(4):803–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Manzanillo PS, Shiloh MU, Portnoy DA, Cox JS. Mycobacterium tuberculosis activates the DNA-dependent cytosolic surveillance pathway within macrophages. Cell Host Microbe. 2012;11(5):469–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sakowski ET, Koster S, Portal Celhay C, Park HS, Shrestha E, Hetzenecker SE, et al. Ubiquilin 1 promotes IFN-gamma-induced xenophagy of Mycobacterium tuberculosis. PLoS Pathog. 2015;11(7):e1005076.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Davis JM, Clay H, Lewis JL, Ghori N, Herbomel P, Ramakrishnan L. Real-time visualization of mycobacterium-macrophage interactions leading to initiation of granuloma formation in zebrafish embryos. Immunity. 2002;17(6):693–702.

    Article  CAS  PubMed  Google Scholar 

  14. Davis JM, Ramakrishnan L. The role of the granuloma in expansion and dissemination of early tuberculous infection. Cell. 2009;136(1):37–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wolf AJ, Desvignes L, Linas B, Banaiee N, Tamura T, Takatsu K, et al. Initiation of the adaptive immune response to Mycobacterium tuberculosis depends on antigen production in the local lymph node, not the lungs. J Exp Med. 2008;205(1):105–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chan J, Xing Y, Magliozzo RS, Bloom BR. Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages. J Exp Med. 1992;175(4):1111–22.

    Article  CAS  PubMed  Google Scholar 

  17. MacMicking JD, Taylor GA, McKinney JD. Immune control of tuberculosis by IFN-gamma-inducible LRG-47. Science. 2003;302(5645):654–9.

    Article  CAS  PubMed  Google Scholar 

  18. Kim BH, Shenoy AR, Kumar P, Das R, Tiwari S, MacMicking JD. A family of IFN-γ-inducible 65-kD GTPases protects against bacterial infection. Science. 2011;332(6030):717–21.

    Article  CAS  PubMed  Google Scholar 

  19. Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI, Deretic V. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell. 2004;119(6):753–66.

    Article  CAS  PubMed  Google Scholar 

  20. Levine B, Mizushima N, Virgin HW. Autophagy in immunity and inflammation. Nature. 2011;469(7330):323–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Egen JG, Rothfuchs AG, Feng CG, Horwitz MA, Sher A, Germain RN. Intravital imaging reveals limited antigen presentation and T cell effector function in mycobacterial granulomas. Immunity. 2011;34(5):807–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bold TD, Banaei N, Wolf AJ, Ernst JD. Suboptimal activation of antigen-specific CD4+ effector cells enables persistence of M. tuberculosis in vivo. PLoS Pathog. 2011;7(5):e1002063.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Srivastava S, Grace PS, Ernst JD. Antigen export reduces antigen presentation and limits T cell control of M. tuberculosis. Cell Host Microbe. 2016;19(1):44–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Banaiee N, Kincaid EZ, Buchwald U, Jacobs WR, Ernst JD. Potent inhibition of macrophage responses to IFN-gamma by live virulent Mycobacterium tuberculosis is independent of mature mycobacterial lipoproteins but dependent on TLR2. J Immunol. 2006;176(5):3019–27.

    Article  CAS  PubMed  Google Scholar 

  25. Harding CV, Boom WH. Regulation of antigen presentation by Mycobacterium tuberculosis: a role for Toll-like receptors. Nat Rev Microbiol. 2010;8(4):296–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Torrado E, Cooper AM. IL-17 and Th17 cells in tuberculosis. Cytokine Growth Factor Rev. 2010;21(6):455–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Seiler P, Aichele P, Bandermann S, Hauser AE, Lu B, Gerard NP, et al. Early granuloma formation after aerosol Mycobacterium tuberculosis infection is regulated by neutrophils via CXCR3-signaling chemokines. Eur J Immunol. 2003;33(10):2676–86.

    Article  CAS  PubMed  Google Scholar 

  28. Blomgran R, Desvignes L, Briken V, Ernst JD. Mycobacterium tuberculosis inhibits neutrophil apoptosis, leading to delayed activation of naive CD4 T cells. Cell Host Microbe. 2012;11(1):81–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Velmurugan K, Chen B, Miller JL, Azogue S, Gurses S, Hsu T, et al. Mycobacterium tuberculosis nuoG is a virulence gene that inhibits apoptosis of infected host cells. PLoS Pathog. 2007;3(7):e110.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  30. Hinchey J, Lee S, Jeon BY, Basaraba RJ, Venkataswamy MM, Chen B, et al. Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis. J Clin Invest. 2007;117(8):2279–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Keane J, Remold HG, Kornfeld H. Virulent Mycobacterium tuberculosis strains evade apoptosis of infected alveolar macrophages. J Immunol. 2000;164(4):2016–20.

    Article  CAS  PubMed  Google Scholar 

  32. Nandi B, Behar SM. Regulation of neutrophils by interferon-γ limits lung inflammation during tuberculosis infection. J Exp Med. 2011;208(11):2251–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Adams DO. The granulomatous inflammatory response. A review. Am J Pathol. 1976;84(1):164–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Ernst JD. The immunological life cycle of tuberculosis. Nat Rev Immunol. 2012;12(8):581–91.

    Article  CAS  PubMed  Google Scholar 

  36. Mogues T, Goodrich ME, Ryan L, LaCourse R, North RJ. The relative importance of T cell subsets in immunity and immunopathology of airborne Mycobacterium tuberculosis infection in mice. J Exp Med. 2001;193(3):271–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Caruso AM, Serbina N, Klein E, Triebold K, Bloom BR, Flynn JL. Mice deficient in CD4 T cells have only transiently diminished levels of IFN-gamma, yet succumb to tuberculosis. J Immunol. 1999;162(9):5407–16.

    CAS  PubMed  Google Scholar 

  38. Havlir DV, Barnes PF. Tuberculosis in patients with human immunodeficiency virus infection. N Engl J Med. 1999;340(5):367–73.

    Article  CAS  PubMed  Google Scholar 

  39. Kwan CK, Ernst JD. HIV and tuberculosis: a deadly human syndemic. Clin Microbiol Rev. 2011;24(2):351–76.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Silva FA, Matos JO, de Q Mello FC, Nucci M. Risk factors for and attributable mortality from tuberculosis in patients with hematologic malignances. Haematologica. 2005;90(8):1110–5.

    PubMed  Google Scholar 

  41. Flynn JL, Chan J, Triebold KJ, Dalton DK, Stewart TA, Bloom BR. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med. 1993;178(6):2249–54.

    Article  CAS  PubMed  Google Scholar 

  42. Alcaïs A, Abel L, Casanova JL. Human genetics of infectious diseases: between proof of principle and paradigm. J Clin Invest. 2009;119(9):2506–14.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  43. Bustamante J, Arias AA, Vogt G, Picard C, Galicia LB, Prando C, et al. Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease. Nat Immunol. 2011;12(3):213–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hambleton S, Salem S, Bustamante J, Bigley V, Boisson-Dupuis S, Azevedo J, et al. IRF8 mutations and human dendritic-cell immunodeficiency. N Engl J Med. 2011;365(2):127–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bogunovic D, Byun M, Durfee LA, Abhyankar A, Sanal O, Mansouri D, et al. Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency. Science. 2012;337(6102):1684–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Browne SK, Burbelo PD, Chetchotisakd P, Suputtamongkol Y, Kiertiburanakul S, Shaw PA, et al. Adult-onset immunodeficiency in Thailand and Taiwan. N Engl J Med. 2012;367(8):725–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Fabri M, Stenger S, Shin DM, Yuk JM, Liu PT, Realegeno S, et al. Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. Sci Transl Med. 2011;3(104):104ra2.

    Article  CAS  Google Scholar 

  48. Wilkinson RJ, Llewelyn M, Toossi Z, Patel P, Pasvol G, Lalvani A, et al. Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study. Lancet. 2000;355(9204):618–21.

    Article  CAS  PubMed  Google Scholar 

  49. Grange JM, Davies PD, Brown RC, Woodhead JS, Kardjito T. A study of vitamin D levels in Indonesian patients with untreated pulmonary tuberculosis. Tubercle. 1985;66(3):187–91.

    Article  CAS  PubMed  Google Scholar 

  50. Talat N, Perry S, Parsonnet J, Dawood G, Hussain R. Vitamin d deficiency and tuberculosis progression. Emerg Infect Dis. 2010;16(5):853–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Martineau AR, Leandro AC, Anderson ST, Newton SM, Wilkinson KA, Nicol MP, et al. Association between Gc genotype and susceptibility to TB is dependent on vitamin D status. Eur Respir J. 2010;35(5):1106–12.

    Article  CAS  PubMed  Google Scholar 

  52. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311(5768):1770–3.

    Article  CAS  PubMed  Google Scholar 

  53. Flynn JL, Goldstein MM, Chan J, Triebold KJ, Pfeffer K, Lowenstein CJ, et al. Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity. 1995;2(6):561–72.

    Article  CAS  PubMed  Google Scholar 

  54. Balcewicz-Sablinska MK, Keane J, Kornfeld H, Remold HG. Pathogenic Mycobacterium tuberculosis evades apoptosis of host macrophages by release of TNF-R2, resulting in inactivation of TNF-alpha. J Immunol. 1998;161(5):2636–41.

    CAS  PubMed  Google Scholar 

  55. Clay H, Volkman HE, Ramakrishnan L. Tumor necrosis factor signaling mediates resistance to mycobacteria by inhibiting bacterial growth and macrophage death. Immunity. 2008;29(2):283–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Bekker LG, Moreira AL, Bergtold A, Freeman S, Ryffel B, Kaplan G. Immunopathologic effects of tumor necrosis factor alpha in murine mycobacterial infection are dose dependent. Infect Immun. 2000;68(12):6954–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Tobin DM, Vary JC Jr, Ray JP, Walsh GS, Dunstan SJ, Bang ND, et al. The lta4h locus modulates susceptibility to mycobacterial infection in zebrafish and humans. Cell. 2010;140(5):717–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Agarwal N, Lamichhane G, Gupta R, Nolan S, Bishai WR. Cyclic AMP intoxication of macrophages by a Mycobacterium tuberculosis adenylate cyclase. Nature. 2009;460(7251):98–102.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  60. Solovic I, Sester M, Gomez-Reino JJ, Rieder HL, Ehlers S, Milburn HJ, et al. The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement. Eur Respir J. 2010;36(5):1185–206.

    Article  CAS  PubMed  Google Scholar 

  61. Wallis RS, Broder MS, Wong JY, Hanson ME, Beenhouwer DO. Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis. 2004;38(9):1261–5.

    Article  CAS  PubMed  Google Scholar 

  62. Bruns H, Meinken C, Schauenberg P, Harter G, Kern P, Modlin RL, et al. Anti-TNF immunotherapy reduces CD8+ T cell-mediated antimicrobial activity against Mycobacterium tuberculosis in humans. J Clin Invest. 2009;119(5):1167–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Mayer-Barber KD, Barber DL, Shenderov K, White SD, Wilson MS, Cheever A, et al. Caspase-1 independent IL-1beta production is critical for host resistance to mycobacterium tuberculosis and does not require TLR signaling in vivo. J Immunol. 2010;184(7):3326–30.

    Article  CAS  PubMed  Google Scholar 

  64. Cox JS, Chen B, McNeil M, Jacobs WR Jr. Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice. Nature. 1999;402(6757):79–83.

    Article  CAS  PubMed  Google Scholar 

  65. Camacho LR, Ensergueix D, Perez E, Gicquel B, Guilhot C. Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature-tagged transposon mutagenesis. Mol Microbiol. 1999;34(2):257–67.

    Article  CAS  PubMed  Google Scholar 

  66. Briken V, Porcelli SA, Besra GS, Kremer L. Mycobacterial lipoarabinomannan and related lipoglycans: from biogenesis to modulation of the immune response. Mol Microbiol. 2004;53(2):391–403.

    Article  CAS  PubMed  Google Scholar 

  67. Matsunaga I, Moody DB. Mincle is a long sought receptor for mycobacterial cord factor. J Exp Med. 2009;206(13):2865–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Puissegur MP, Botanch C, Duteyrat JL, Delsol G, Caratero C, Altare F. An in vitro dual model of mycobacterial granulomas to investigate the molecular interactions between mycobacteria and human host cells. Cell Microbiol. 2004;6(5):423–33.

    Article  CAS  PubMed  Google Scholar 

  69. Abdallah AM, Gey van Pittius NC, Champion PA, Cox J, Luirink J, Vandenbroucke-Grauls CM, et al. Type VII secretion--mycobacteria show the way. Nat Rev Microbiol. 2007;5(11):883–91.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Gordon SV, Brosch R, Billault A, Garnier T, Eiglmeier K, ST C. Identification of variable regions in the genomes of tubercle bacilli using bacterial artificial chromosome arrays. Mol Microbiol. 1999;32(3):643–55.

    Article  CAS  PubMed  Google Scholar 

  72. Brodin P, Rosenkrands I, Andersen P, Cole ST, Brosch R. ESAT-6 proteins: protective antigens and virulence factors? Trends Microbiol. 2004;12(11):500–8.

    Article  CAS  PubMed  Google Scholar 

  73. Guinn KM, Hickey MJ, Mathur SK, Zakel KL, Grotzke JE, Lewinsohn DM, et al. Individual RD1-region genes are required for export of ESAT-6/CFP-10 and for virulence of Mycobacterium tuberculosis. Mol Microbiol. 2004;51(2):359–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Hsu T, Hingley-Wilson SM, Chen B, Chen M, Dai AZ, Morin PM, et al. The primary mechanism of attenuation of bacillus Calmette-Guerin is a loss of secreted lytic function required for invasion of lung interstitial tissue. Proc Natl Acad Sci U S A. 2003;100(21):12420–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Pym AS, Brodin P, Brosch R, Huerre M, Cole ST. Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti. Mol Microbiol. 2002;46(3):709–17.

    Article  CAS  PubMed  Google Scholar 

  76. Abdallah AM, Verboom T, Weerdenburg EM, Gey van Pittius NC, Mahasha PW, Jimenez C, et al. PPE and PE_PGRS proteins of Mycobacterium marinum are transported via the type VII secretion system ESX-5. Mol Microbiol. 2009;73(3):329–40.

    Article  CAS  PubMed  Google Scholar 

  77. Philips JA. Mycobacterial manipulation of vacuolar sorting. Cell Microbiol. 2008;10(12):2408–15.

    Article  CAS  PubMed  Google Scholar 

  78. Wong D, Bach H, Sun J, Hmama Z, Av-Gay Y. Mycobacterium tuberculosis protein tyrosine phosphatase (PtpA) excludes host vacuolar-H+-ATPase to inhibit phagosome acidification. Proc Natl Acad Sci U S A. 2011;108(48):19371–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Sun J, Wang X, Lau A, Liao TY, Bucci C, Hmama Z. Mycobacterial nucleoside diphosphate kinase blocks phagosome maturation in murine RAW 264.7 macrophages. PLoS One. 2010;5(1):e8769.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  80. Fortune SM, Solache A, Jaeger A, Hill PJ, Belisle JT, Bloom BR, et al. Mycobacterium tuberculosis inhibits macrophage responses to IFN-gamma through myeloid differentiation factor 88-dependent and -independent mechanisms. J Immunol. 2004;172(10):6272–80.

    Article  CAS  PubMed  Google Scholar 

  81. Singh N, Paterson DL. Mycobacterium tuberculosis infection in solid-organ transplant recipients: impact and implications for management. Clin Infect Dis. 1998;27(5):1266–77.

    Article  CAS  PubMed  Google Scholar 

  82. Bucher JN, Schoenberg MB. Donor-derived tuberculosis after solid organ transplantation in two patients and a staff member. Infection. 2016;44(3):365–70.

    Article  CAS  PubMed  Google Scholar 

  83. Aguado JM, Herrero JA, Gavaldá J, Torre-Cisneros J, Blanes M, Rufí G, et al. Clinical presentation and outcome of tuberculosis in kidney, liver, and heart transplant recipients in Spain. Spanish Transplantation Infection Study Group, GESITRA. Transplantation. 1997;63(9):1278–86.

    Article  CAS  PubMed  Google Scholar 

  84. Torre-Cisneros J, Doblas A, Aguado JM, San Juan R, Blanes M, Montejo M, et al. Tuberculosis after solid-organ transplant: incidence, risk factors, and clinical characteristics in the RESITRA (Spanish Network of Infection in Transplantation) cohort. Clin Infect Dis. 2009;48(12):1657–65.

    Article  PubMed  Google Scholar 

  85. Yoo JW, Jo KW, Kim SH, Lee SO, Kim JJ, Park SK, et al. Incidence, characteristics, and treatment outcomes of mycobacterial diseases in transplant recipients. Transpl Int. 2016;29(5):549–58.

    Article  PubMed  Google Scholar 

  86. Naqvi A, Rizvi A, Hussain Z, Hafeez S, Hashmi A, Akhtar F, et al. Developing world perspective of posttransplant tuberculosis: morbidity, mortality, and cost implications. Transplant Proc. 2001;33(1-2):1787–8.

    Article  CAS  PubMed  Google Scholar 

  87. Sakhuja V, Jha V, Varma PP, Joshi K, Chugh KS. The high incidence of tuberculosis among renal transplant recipients in India. Transplantation. 1996;61(2):211–5.

    Article  CAS  PubMed  Google Scholar 

  88. Yuen KY, Woo PC. Tuberculosis in blood and marrow transplant recipients. Hematol Oncol. 2002;20(2):51–62.

    Article  CAS  PubMed  Google Scholar 

  89. Cordonnier C, Martino R, Trabasso P, Held TK, Akan H, Ward MS, et al. Mycobacterial infection: a difficult and late diagnosis in stem cell transplant recipients. Clin Infect Dis. 2004;38(9):1229–36.

    Article  CAS  PubMed  Google Scholar 

  90. Russo RL, Dulley FL, Suganuma L, França IL, Yasuda MA, Costa SF. Tuberculosis in hematopoietic stem cell transplant patients: case report and review of the literature. Int J Infect Dis. 2010;14(Suppl 3):e187–91.

    Article  PubMed  Google Scholar 

  91. Ip MS, Yuen KY, Woo PC, Luk WK, Tsang KW, Lam WK, et al. Risk factors for pulmonary tuberculosis in bone marrow transplant recipients. Am J Respir Crit Care Med. 1998;158(4):1173–7.

    Article  CAS  PubMed  Google Scholar 

  92. Ku SC, Tang JL, Hsueh PR, Luh KT, Yu CJ, Yang PC. Pulmonary tuberculosis in allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2001;27(12):1293–7.

    Article  CAS  PubMed  Google Scholar 

  93. Lopez de Castilla D, Schluger NW. Tuberculosis following solid organ transplantation. Transpl Infect Dis. 2010;12(2):106–12.

    Article  CAS  PubMed  Google Scholar 

  94. Chen CH, Shu KH, Ho HC, Cheng SB, Lin CC, Wei HJ, et al. A nationwide population-based study of the risk of tuberculosis in different solid organ transplantations in Taiwan. Transplant Proc. 2014;46(4):1032–5.

    Article  PubMed  Google Scholar 

  95. Muñoz P, Rodríguez C, Bouza E. Mycobacterium tuberculosis infection in recipients of solid organ transplants. Clin Infect Dis. 2005;40(4):581–7.

    Article  PubMed  Google Scholar 

  96. Ulubay G, Kupeli E, Duvenci Birben O, Seyfettin EP, Dogrul MI, Ozsancak Ugurlu A, et al. A 10-year experience of tuberculosis in solid-organ transplant recipients. Exp Clin Transplant. 2015;13(Suppl 1):214–8.

    PubMed  Google Scholar 

  97. Hsu MS, Wang JL, Ko WJ, Lee PH, Chou NK, Wang SS, et al. Clinical features and outcome of tuberculosis in solid organ transplant recipients. Am J Med Sci. 2007;334(2):106–10.

    Article  PubMed  Google Scholar 

  98. Jereb JA, Burwen DR, Dooley SW, Haas WH, Crawford JT, Geiter LJ, et al. Nosocomial outbreak of tuberculosis in a renal transplant unit: application of a new technique for restriction fragment length polymorphism analysis of Mycobacterium tuberculosis isolates. J Infect Dis. 1993;168(5):1219–24.

    Article  CAS  PubMed  Google Scholar 

  99. el-Agroudy AE, Refaie AF, Moussa OM, Ghoneim MA. Tuberculosis in Egyptian kidney transplant recipients: study of clinical course and outcome. J Nephrol. 2003;16(3):404–11.

    PubMed  Google Scholar 

  100. Atasever A, Bacakoglu F, Toz H, Basoglu OK, Duman S, Basak K, et al. Tuberculosis in renal transplant recipients on various immunosuppressive regimens. Nephrol Dial Transplant. 2005;20(4):797–802.

    Article  CAS  PubMed  Google Scholar 

  101. Bodro M, Sabe N, Santin M, Cruzado JM, Llado L, Gonzalez-Costello J, et al. Clinical features and outcomes of tuberculosis in solid organ transplant recipients. Transplant Proc. 2012;44(9):2686–9.

    Article  CAS  PubMed  Google Scholar 

  102. Olithselvan A, Rajagopala S, Vij M, Shanmugam V, Shanmugam N, Rela M. Tuberculosis in liver transplant recipients: experience of a South Indian liver transplant center. Liver Transpl. 2014;20(8):960–6.

    Article  PubMed  Google Scholar 

  103. Lou XF, Wu RH, Xu SZ, Lin XJ. Spinal tuberculosis in post-liver transplantation patients: case reports. Transpl Infect Dis. 2010;12(2):132–7.

    Article  CAS  PubMed  Google Scholar 

  104. Nelson CA, Zunt JR. Tuberculosis of the central nervous system in immunocompromised patients: HIV infection and solid organ transplant recipients. Clin Infect Dis. 2011;53(9):915–26.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Winthrop KL, Kubak BM, Pegues DA, Hufana C, Costamagna P, Desmond E, et al. Transmission of mycobacterium tuberculosis via lung transplantation. Am J Transplant. 2004;4(9):1529–33.

    Article  PubMed  Google Scholar 

  106. Kiuchi T, Inomata Y, Uemoto S, Satomura K, Egawa H, Okajima H, et al. A hepatic graft tuberculosis transmitted from a living-related donor. Transplantation. 1997;63(6):905–7.

    Article  CAS  PubMed  Google Scholar 

  107. Graham JC, Kearns AM, Magee JG, El-Sheikh MF, Hudson M, Manas D, et al. Tuberculosis transmitted through transplantation. J Infect. 2001;43(4):251–4.

    Article  CAS  PubMed  Google Scholar 

  108. Schulman LL, Scully B, McGregor CC, Austin JH. Pulmonary tuberculosis after lung transplantation. Chest. 1997;111(5):1459–62.

    Article  CAS  PubMed  Google Scholar 

  109. Aguado JM, Torre-Cisneros J, Fortún J, Benito N, Meije Y, Doblas A, et al. Tuberculosis in solid-organ transplant recipients: consensus statement of the group for the study of infection in transplant recipients (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology. Clin Infect Dis. 2009;48(9):1276–84.

    Article  PubMed  Google Scholar 

  110. Morris MI, Daly JS, Blumberg E, Kumar D, Sester M, Schluger N, et al. Diagnosis and management of tuberculosis in transplant donors: a donor-derived infections consensus conference report(†). Am J Transplant. 2012;12:2288–300.

    Article  CAS  PubMed  Google Scholar 

  111. Bumbacea D, Arend SM, Eyuboglu F, Fishman JA, Goletti D, Ison MG, et al. The risk of tuberculosis in transplant candidates and recipients: a TBNET consensus statement. Eur Respir J. 2012;40(4):990–1013.

    Article  PubMed  Google Scholar 

  112. Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, et al. Guidelines for preventing infectious complications among hematopoietic cell transplant recipients: a global perspective. Preface. Bone Marrow Transplant. 2009;44(8):453–5.

    Article  CAS  PubMed  Google Scholar 

  113. Pai M, Denkinger CM, Kik SV, Rangaka MX, Zwerling A, Oxlade O, et al. Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev. 2014;27(1):3–20.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  114. Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society. MMWR Recomm Rep. 2000;49(RR-6):1–51.

    Google Scholar 

  115. Mazurek GH, Jereb J, Vernon A, LoBue P, Goldberg S, Castro K, et al. Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection - United States, 2010. MMWR Recomm Rep. 2010;59(RR-5):1–25.

    PubMed  Google Scholar 

  116. Red book: 2009 report of the Committee on Infectious Disease. 28th ed ed. Pickering LK BC, Kimberlin DW, Long SS, eds, editor. Elk Grove Villiage, IL: American Academy of Pediatrics; 2009.

    Google Scholar 

  117. Lindemann M, Dioury Y, Beckebaum S, Cicinnati VR, Gerken G, Broelsch CE, et al. Diagnosis of tuberculosis infection in patients awaiting liver transplantation. Hum Immunol. 2009;70(1):24–8.

    Article  PubMed  Google Scholar 

  118. Manuel O, Humar A, Preiksaitis J, Doucette K, Shokoples S, Peleg AY, et al. Comparison of quantiferon-TB gold with tuberculin skin test for detecting latent tuberculosis infection prior to liver transplantation. Am J Transplant. 2007;7(12):2797–801.

    Article  CAS  PubMed  Google Scholar 

  119. Kim SY, Jung GS, Kim SK, Chang J, Kim MS, Kim YS, et al. Comparison of the tuberculin skin test and interferon-γ release assay for the diagnosis of latent tuberculosis infection before kidney transplantation. Infection. 2013;41(1):103–10.

    Article  CAS  PubMed  Google Scholar 

  120. Theodoropoulos N, Lanternier F, Rassiwala J, McNatt G, Preczewski L, DeMayo E, et al. Use of the QuantiFERON-TB Gold interferon-gamma release assay for screening transplant candidates: a single-center retrospective study. Transpl Infect Dis. 2012;14(1):1–8.

    Article  CAS  PubMed  Google Scholar 

  121. Sester M, van Leth F, Bruchfeld J, Bumbacea D, Cirillo DM, Dilektasli AG, et al. Risk assessment of tuberculosis in immunocompromised patients. A TBNET study. Am J Respir Crit Care Med. 2014;190(10):1168–76.

    Article  PubMed  Google Scholar 

  122. Hadaya K, Bridevaux PO, Roux-Lombard P, Delort A, Saudan P, Martin PY, et al. Contribution of interferon-gamma release assays (IGRAs) to the diagnosis of latent tuberculosis infection after renal transplantation. Transplantation. 2013;95(12):1485–90.

    Article  CAS  PubMed  Google Scholar 

  123. Moon SM, Lee SO, Choi SH, Kim YS, Woo JH, Yoon DH, et al. Comparison of the QuantiFERON-TB Gold In-Tube test with the tuberculin skin test for detecting latent tuberculosis infection prior to hematopoietic stem cell transplantation. Transpl Infect Dis. 2013;15(1):104–9.

    Article  CAS  PubMed  Google Scholar 

  124. Qin LL, Wang QR, Wang Q, Yao H, Wen LJ, Wu LL, et al. T-SPOT.TB for detection of tuberculosis infection among hematological malignancy patients and hematopoietic stem cell transplant recipients. Asian Pac J Cancer Prev. 2013;14(12):7415–9.

    Article  PubMed  Google Scholar 

  125. Horne DJ, Narita M, Spitters CL, Parimi S, Dodson S, Limaye AP. Challenging issues in tuberculosis in solid organ transplantation. Clin Infect Dis. 2013;57(10):1473–82.

    Article  PubMed  PubMed Central  Google Scholar 

  126. Kim SH, Lee SO, Park JB, Park IA, Park SJ, Yun SC, et al. A prospective longitudinal study evaluating the usefulness of a T-cell-based assay for latent tuberculosis infection in kidney transplant recipients. Am J Transplant. 2011;11(9):1927–35.

    Article  PubMed  Google Scholar 

  127. Huebner RE, Schein MF, Bass JB. The tuberculin skin test. Clin Infect Dis. 1993;17(6):968–75.

    Article  CAS  PubMed  Google Scholar 

  128. (CDC) CfDCaP. Updated guidelines for the use of nucleic acid amplification tests in the diagnosis of tuberculosis. MMWR Morb Mortal Wkly Rep. 2009;58(1):7–10.

    Google Scholar 

  129. Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010;363(11):1005–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Tortoli E, Russo C, Piersimoni C, Mazzola E, Dal Monte P, Pascarella M, et al. Clinical validation of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis. Eur Respir J. 2012;40(2):442–7.

    Article  PubMed  Google Scholar 

  131. Ao W, Aldous S, Woodruff E, Hicke B, Rea L, Kreiswirth B, et al. Rapid detection of rpoB gene mutations conferring rifampin resistance in Mycobacterium tuberculosis. J Clin Microbiol. 2012;50(7):2433–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Lin SY, Rodwell TC, Victor TC, Rider EC, Pham L, Catanzaro A, et al. Pyrosequencing for rapid detection of extensively drug-resistant Mycobacterium tuberculosis in clinical isolates and clinical specimens. J Clin Microbiol. 2014;52(2):475–82.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  133. Ocheretina O, Shen L, Escuyer VE, Mabou MM, Royal-Mardi G, Collins SE, et al. Whole genome sequencing investigation of a tuberculosis outbreak in Port-au-Prince, Haiti caused by a strain with a “low-level” rpoB mutation L511P - insights into a mechanism of resistance escalation. PLoS One. 2015;10(6):e0129207.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  134. Daum LT, Rodriguez JD, Worthy SA, Ismail NA, Omar SV, Dreyer AW, et al. Next-generation ion torrent sequencing of drug resistance mutations in Mycobacterium tuberculosis strains. J Clin Microbiol. 2012;50(12):3831–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Koser CU, Bryant JM, Becq J, Torok ME, Ellington MJ, Marti-Renom MA, et al. Whole-genome sequencing for rapid susceptibility testing of M. tuberculosis. N Engl J Med. 2013;369(3):290–2.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jennifer A. Philips .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Portal-Celhay, C., Philips, J.A. (2019). Tuberculosis. In: Safdar, A. (eds) Principles and Practice of Transplant Infectious Diseases. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-9034-4_29

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-9034-4_29

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-9032-0

  • Online ISBN: 978-1-4939-9034-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics