Current Infectious Disease Reports

, Volume 14, Issue 6, pp 650–657 | Cite as

Tuberculosis in Transplantation: Diagnosis, Prevention, and Treatment

Transplant and Oncology (MG Ison, Section Editor)


Tuberculosis should always be taken into consideration as a possible infectious complication in transplant recipients. It is more frequent and fatal, and its diagnosis, prevention, and treatment are more challenging, in transplanted patients, as compared with the general population. Latent infection with M. tuberculosis is indirectly diagnosed by assessing the presence of a specific adaptive immune response, but depending on the assay used, the informative value of immunodiagnostic assays may be limited by the inhibitory action of immunosuppressive medication, and the positive predictive value for progression toward active tuberculosis is generally low. Diagnosis of active tuberculosis is challenging, since symptoms in immunocompromised patients are frequently less pronounced and atypical. Finally, treatment of tuberculosis is complicated by unpredictable drug interactions, drug-related organ toxicities, and development of drug resistance. This review provides an overview of the epidemiological characteristics of posttransplant tuberculosis and summarizes current knowledge on the prevention, diagnosis, and treatment of tuberculosis in transplant recipients.


Tuberculosis Mycobacterium tuberculosis Latent infection with M. tuberculosis IGRA Interferon-γ-release assay TST Skin testing Flow-cytometry ELISA ELISPOT Adaptive immune response Posttransplant infection Chemoprophylaxis Transplantation Solid organ transplant recipients Immunosuppression Infection Immunodeficiency Diagnosis Prevention Treatment Guidelines Management Screening 



No potential conflicts of interest relevant to this article were reported.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    WHO: Global Tuberculosis Control report. WHO report 2011. In. Geneva, Switzerland, 2011.Google Scholar
  2. 2.
    Munoz P, Rodriguez C, Bouza E. Mycobacterium tuberculosis infection in recipients of solid organ transplants. Clin Infect Dis. 2005;40:581–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Sester U, Wilkens H, van Bentum K, et al. Impaired detection of Mycobacterium tuberculosis immunity in patients using high levels of immunosuppressive drugs. Eur Respir J. 2009;34:702–10.PubMedCrossRefGoogle Scholar
  4. 4.
    Vandermarliere A, Van Audenhove A, Peetermans WE, et al. Mycobacterial infection after renal transplantation in a Western population. Transpl Infect Dis. 2003;5:9–15.PubMedCrossRefGoogle Scholar
  5. 5.
    Basiri A, Hosseini-Moghaddam SM, Simforoosh N, et al. The risk factors and laboratory diagnostics for post renal transplant tuberculosis: a case–control, country-wide study on definitive cases. Transpl Infect Dis. 2008;10:231–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Torre-Cisneros J, Doblas A, Aguado JM, 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;48:1657–65.PubMedCrossRefGoogle Scholar
  7. 7.
    Canet E, Dantal J, Blancho G, et al. Tuberculosis following kidney transplantation: clinical features and outcome. A French multicentre experience in the last 20 years. Nephrol Dial Transplant. 2011;26:3773–8.Google Scholar
  8. 8.
    Singh N, Paterson DL. Mycobacterium tuberculosis infection in solid-organ transplant recipients: impact and implications for management. Clin Infect Dis. 1998;27:1266–77.PubMedCrossRefGoogle Scholar
  9. 9.
    Morris MI, Daly JS, Blumberg E, et al. Diagnosis and management of tuberculosis in transplant donors: a donor-derived infections consensus conference report. Am J Transplant. 2012;12:2288–300.Google Scholar
  10. 10.
    Subramanian A, Dorman S. Practice ASTIDCo: Mycobacterium tuberculosis in solid organ transplant recipients. Am J Transplant. 2009;9 Suppl 4:S57–62.PubMedCrossRefGoogle Scholar
  11. 11.
    Aguado JM, Herrero JA, Gavalda J, 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; 63:1278–1286.Google Scholar
  12. 12.
    Queipo JA, Broseta E, Santos M, et al. Mycobacterial infection in a series of 1261 renal transplant recipients. Clin Microbiol Infect. 2003;9:518–25.PubMedCrossRefGoogle Scholar
  13. 13.
    •• Bumbacea D, Arend SM, Eyuboglu F, et al. The risk of tuberculosis in transplant candidates and recipients: A TBNET consensus statement. Eur Respir J. 2012; in press. This document provides an excellent consensus statement for tuberculosis in transplant recipients, including stem cell recipients. Google Scholar
  14. 14.
    Andersen P, Munk ME, Pollock JM, et al. Specific immune-based diagnosis of tuberculosis. Lancet. 2000;356:1099–104.PubMedCrossRefGoogle Scholar
  15. 15.
    Mack U, Migliori GB, Sester M, et al. LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement. Eur Respir J. 2009;33:956–73.PubMedCrossRefGoogle Scholar
  16. 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;149:177–84.PubMedGoogle Scholar
  17. 17.
    Sester M, Sotgiu G, Lange C, et al. Interferon-g release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2011;37:100–11.PubMedCrossRefGoogle Scholar
  18. 18.
    Sester M, Sester U, Clauer P, et al. Tuberculin skin testing underestimates a high prevalence of latent tuberculosis infection in hemodialysis patients. Kidney Int. 2004;65:1826–34.PubMedCrossRefGoogle Scholar
  19. 19.
    Dinser R, Fousse M, Sester U, et al. Evaluation of latent tuberculosis infection in patients with inflammatory arthropathies before treatment with TNF-alpha blocking drugs using a novel flow-cytometric interferon-gamma release assay. Rheumatology (Oxford). 2008;47:212–8.CrossRefGoogle Scholar
  20. 20.
    Sester U, Junker H, Hodapp T, et al. Improved efficiency in detecting cellular immunity towards M. tuberculosis in patients receiving immunosuppressive drug therapy. Nephrol Dial Transplant. 2006;21:3258–68.PubMedCrossRefGoogle Scholar
  21. 21.
    Manuel O, Humar A, Preiksaitis J, et al. Comparison of Quantiferon-TB Gold with tuberculin skin test for detecting latent tuberculosis infection prior to liver transplantation. Am J Transplant. 2007;7:2797–801.PubMedCrossRefGoogle Scholar
  22. 22.
    Casas S, Munoz L, Moure R, et al. Comparison of the 2-step tuberculin skin test and the quantiFERON-TB Gold In-Tube Test for the screening of tuberculosis infection before liver transplantation. Liver Transpl. 2011;17:1205–11.PubMedCrossRefGoogle Scholar
  23. 23.
    Kim SH, Lee SO, Park JB, 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;11:1927–35.PubMedCrossRefGoogle Scholar
  24. 24.
    van Zyl-Smit RN, Pai M, Peprah K, et al. Within-subject variability and boosting of T-cell interferon-gamma responses after tuberculin skin testing. Am J Respir Crit Care Med. 2009;180:49–58.PubMedCrossRefGoogle Scholar
  25. 25.
    Diel R, Loddenkemper R, Niemann S, et al. Negative and positive predictive value of a whole-blood interferon-{gamma} release assay for developing active tuberculosis: an update. Am J Respir Crit Care Med. 2011;183:88–95.PubMedCrossRefGoogle Scholar
  26. 26.
    • Rangaka MX, Wilkinson KA, Glynn JR, et al. Predictive value of interferon-gamma release assays for incident active tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12:45–55. This meta-analysis focuses on the positive predictive value of IGRAs for active tuberculosis in different patient cohorts. PubMedCrossRefGoogle Scholar
  27. 27.
    • Boehme CC, Nabeta P, Hillemann D, et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010;363:1005–15. The study demonstrated a sensitive and rapid detection of tuberculosis and rifampin resistance by molecular testing. PubMedCrossRefGoogle Scholar
  28. 28.
    Miotto P, Bigoni S, Migliori GB, et al. Early tuberculosis treatment monitoring by Xpert(R) MTB/RIF. Eur Respir J. 2012;39:1269–71.PubMedCrossRefGoogle Scholar
  29. 29.
    Theron G, Peter J, van Zyl-Smit R, et al. Evaluation of the Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in a high HIV prevalence setting. Am J Respir Crit Care Med. 2011;184:132–40.PubMedCrossRefGoogle Scholar
  30. 30.
    Sester U, Fousse M, Dirks J, et al. Whole-blood flow-cytometric analysis of antigen-specific CD4 T-cell cytokine profiles distinguishes active tuberculosis from non-active states. PLoS One. 2011;6:e17813.PubMedCrossRefGoogle Scholar
  31. 31.
    Streitz M, Tesfa L, Yildirim V, et al. Loss of receptor on tuberculin-reactive T-cells marks active pulmonary tuberculosis. PLoS One. 2007;2:e735.PubMedCrossRefGoogle Scholar
  32. 32.
    Harari A, Rozot V, Enders FB, et al. Dominant TNF-alpha + Mycobacterium tuberculosis-specific CD4+ T cell responses discriminate between latent infection and active disease. Nat Med. 2011;17:372–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Theron G, Peter J, Lenders L, et al. Correlation of mycobacterium tuberculosis specific and non-specific quantitative Th1 T-cell responses with bacillary load in a high burden setting. PLoS One. 2012;7:e37436.PubMedCrossRefGoogle Scholar
  34. 34.
    Sester M, van Leth F, Girardi E, et al. Head-to-head analysis of IGRAs and skin-testing in immunocompromised patients: Interim analysis of a multicenter TBNET study Eur Respir J. 2010; abstract.Google Scholar
  35. 35.
    Field M, Clarke A, Kelleher M, et al. Anti-tuberculosis prophylaxis following renal transplantation: acceptable variations? Transpl Infect Dis. 2012.Google Scholar
  36. 36.
    Page KR, Sifakis F. Montes de Oca R, et al.: Improved adherence and less toxicity with rifampin vs isoniazid for treatment of latent tuberculosis: a retrospective study. Arch Intern Med. 2006;166:1863–70.PubMedCrossRefGoogle Scholar
  37. 37.
    Centers for Disease C, Prevention. Severe isoniazid-associated liver injuries among persons being treated for latent tuberculosis infection - United States, 2004–2008. MMWR Morb Mortal Wkly Rep. 2010;59:224–9.Google Scholar
  38. 38.
    Vikrant S, Agarwal SK, Gupta S, et al. Prospective randomized control trial of isoniazid chemoprophylaxis during renal replacement therapy. Transpl Infect Dis. 2005;7:99–108.PubMedCrossRefGoogle Scholar
  39. 39.
    Currie AC, Knight SR, Morris PJ. Tuberculosis in renal transplant recipients: the evidence for prophylaxis. Transplantation. 2010;90:695–704.PubMedCrossRefGoogle Scholar
  40. 40.
    Schluger LK, Sheiner PA, Jonas M, et al. Isoniazid hepatotoxicity after orthotopic liver transplantation. Mt Sinai J Med. 1996;63:364–9.PubMedGoogle Scholar
  41. 41.
    Higgins RM, Cahn AP, Porter D, et al. Mycobacterial infections after renal transplantation. Q J Med. 1991;78:145–53.PubMedGoogle Scholar
  42. 42.
    Agarwal SK, Gupta S, Dash SC, et al. Prospective randomised trial of isoniazid prophylaxis in renal transplant recipient. Int Urol Nephrol. 2004;36:425–31.PubMedCrossRefGoogle Scholar
  43. 43.
    Ram R, Swarnalatha G, Prasad N, et al. Tuberculosis in renal transplant recipients. Transpl Infect Dis. 2007;9:97–101.PubMedCrossRefGoogle Scholar
  44. 44.
    Menzies D, Benedetti A, Paydar A, et al. Effect of duration and intermittency of rifampin on tuberculosis treatment outcomes: a systematic review and meta-analysis. PLoS Med. 2009;6:e1000146.PubMedCrossRefGoogle Scholar
  45. 45.
    Chang KC, Leung CC, Yew WW, et al. Dosing schedules of 6-month regimens and relapse for pulmonary tuberculosis. Am J Respir Crit Care Med. 2006;174:1153–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Aguado JM, Torre-Cisneros J, Fortun J, 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;48:1276–84.PubMedCrossRefGoogle Scholar
  47. 47.
    Horne DJ, Spitters C, Narita M. Experience with rifabutin replacing rifampin in the treatment of tuberculosis. Int J Tuberc Lung Dis. 2011;15:1485–1489, i.PubMedCrossRefGoogle Scholar
  48. 48.
    Narita M, Stambaugh JJ, Hollender ES, et al. Use of rifabutin with protease inhibitors for human immunodeficiency virus-infected patients with tuberculosis. Clin Infect Dis. 2000;30:779–83.PubMedCrossRefGoogle Scholar
  49. 49.
    Martineau AR, Nhamoyebonde S, Oni T, et al. Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in Cape Town, South Africa. Proc Natl Acad Sci U S A. 2011;108:19013–7.PubMedCrossRefGoogle Scholar
  50. 50.
    • Fabri M, Stenger S, Shin DM, et al. Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. Sci Transl Med. 2011;3:104ra102. This study elucidated a Vitamin D dependent mechanism of the adaptive immune system for defense of M. tuberculosis. PubMedCrossRefGoogle Scholar
  51. 51.
    •• Martineau AR, Timms PM, Bothamley GH, et al. High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet. 2011;377:242–50. This clinical trial assessed the effect of Vitamin D supplemtentation on sputum conversion of patients with active tuberculosis. PubMedCrossRefGoogle Scholar
  52. 52.
    Sterling KA, Eftekhari P, Girndt M, et al.: The immunoregulatory function of vitamin D: implications in chronic kidney disease. Nat Rev Nephrol. 2012.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Internal Medicine IVSaarland UniversityHomburgGermany
  2. 2.Department of Transplant and Infection Immunology, Institute of VirologySaarland UniversityHomburgGermany

Personalised recommendations