Skip to main content

Advertisement

SpringerLink
Log in

Tuberculosis in Transplantation: Diagnosis, Prevention, and Treatment

  • Transplant and Oncology (MG Ison, Section Editor)
  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

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.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

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

  1. WHO: Global Tuberculosis Control report. WHO report 2011. In. Geneva, Switzerland, 2011.

  2. Munoz P, Rodriguez C, Bouza E. Mycobacterium tuberculosis infection in recipients of solid organ transplants. Clin Infect Dis. 2005;40:581–7.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  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. Subramanian A, Dorman S. Practice ASTIDCo: Mycobacterium tuberculosis in solid organ transplant recipients. Am J Transplant. 2009;9 Suppl 4:S57–62.

    Article  PubMed  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

  14. Andersen P, Munk ME, Pollock JM, et al. Specific immune-based diagnosis of tuberculosis. Lancet. 2000;356:1099–104.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  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;149:177–84.

    PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

  35. Field M, Clarke A, Kelleher M, et al. Anti-tuberculosis prophylaxis following renal transplantation: acceptable variations? Transpl Infect Dis. 2012.

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  39. Currie AC, Knight SR, Morris PJ. Tuberculosis in renal transplant recipients: the evidence for prophylaxis. Transplantation. 2010;90:695–704.

    Article  PubMed  Google Scholar 

  40. Schluger LK, Sheiner PA, Jonas M, et al. Isoniazid hepatotoxicity after orthotopic liver transplantation. Mt Sinai J Med. 1996;63:364–9.

    PubMed  CAS  Google Scholar 

  41. Higgins RM, Cahn AP, Porter D, et al. Mycobacterial infections after renal transplantation. Q J Med. 1991;78:145–53.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  43. Ram R, Swarnalatha G, Prasad N, et al. Tuberculosis in renal transplant recipients. Transpl Infect Dis. 2007;9:97–101.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  52. Sterling KA, Eftekhari P, Girndt M, et al.: The immunoregulatory function of vitamin D: implications in chronic kidney disease. Nat Rev Nephrol. 2012.

Download references

Disclosure

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

Author information

Authors and Affiliations

  1. Department of Internal Medicine IV, Saarland University, Homburg, Germany

    Sarah Kirsch

  2. Department of Transplant and Infection Immunology, Institute of Virology, Saarland University, 66421, Homburg, Germany

    Martina Sester

Authors
  1. Sarah Kirsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martina Sester
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martina Sester.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kirsch, S., Sester, M. Tuberculosis in Transplantation: Diagnosis, Prevention, and Treatment. Curr Infect Dis Rep 14, 650–657 (2012). https://doi.org/10.1007/s11908-012-0293-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11908-012-0293-1

Keywords

Search

Navigation