Tuberculosis in solid organ transplant candidates and recipients
- Aruna Subramanian, MD
Aruna Subramanian, MD
- Clinical Associate Professor of Medicine
- Stanford University School of Medicine
The incidence of tuberculosis among solid organ transplant recipients is higher compared with the general population but varies by geographic location [1-3]. The diagnosis of TB in solid organ transplant recipients presents challenges that may lead to treatment delay. These include atypical clinical presentations, increased likelihood of negative tuberculin skin tests and/or interferon-gamma release assays, and negative sputum smear results despite active disease [4-9]. The treatment of tuberculosis in transplant recipients also has its own challenges, which include pharmacokinetic interactions between immunosuppressive and antituberculous medications, allograft-related drug toxicities, and inadequate immune responses to Mycobacterium tuberculosis due to exogenous immunosuppression [4-7].
This topic reviews M. tuberculosis infections in solid organ transplant recipients. Nontuberculous mycobacterial infections in solid organ transplant recipients; bacterial, viral, and fungal infections in lung transplant recipients; and the evaluation, treatment, and prophylaxis of infection in solid organ transplant recipients are reviewed separately. (See "Nontuberculous mycobacterial infections in solid organ transplant candidates and recipients" and "Bacterial infections following lung transplantation" and "Prevention of cytomegalovirus infection in lung transplant recipients" and "Clinical manifestations, diagnosis, and treatment of cytomegalovirus infection in lung transplant recipients" and "Fungal infections following lung transplantation" and "Evaluation for infection before solid organ transplantation" and "Infection in the solid organ transplant recipient" and "Prophylaxis of infections in solid organ transplantation".)
Overview — The prevalence of active tuberculosis (TB) among transplant recipients in developed countries has ranged from 1.2 to 6.4 percent but has been reported to be as high as 10 to 15 percent in endemic regions [4,5,7,10]. (See "Epidemiology of tuberculosis".)
The incidence of TB in solid organ transplant recipients is not well established and varies by geographic location, but the incidence has been shown to be significantly higher among transplant recipients compared with the general population [1-3]. In a prospective study of 4388 solid organ transplant recipients at 16 transplant centers in Spain, the incidence of TB was 512 cases per 100,000 patients per year compared with 19 cases per 100,000 inhabitants per year in the general population . Among solid organ transplant recipients, lung transplant recipients had the highest incidence of TB (2072 cases per 100,000 patients per year).
Transmission — TB occurs most commonly in transplant recipients as a result of reactivation of latent infection in the recipient but also may arise from unrecognized infection in the allograft or acquisition of new infection after transplantation [4,5,11]. There are several reports of TB transmission from the donor allograft to the recipient [5,11,12], especially when the donor country of origin is highly endemic for TB .
- 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.
- Morales P, Briones A, Torres JJ, et al. Pulmonary tuberculosis in lung and heart-lung transplantation: fifteen years of experience in a single center in Spain. Transplant Proc 2005; 37:4050.
- Lopez de Castilla D, Schluger NW. Tuberculosis following solid organ transplantation. Transpl Infect Dis 2010; 12:106.
- Singh N, Paterson DL. Mycobacterium tuberculosis infection in solid-organ transplant recipients: impact and implications for management. Clin Infect Dis 1998; 27:1266.
- Muñoz P, Rodríguez C, Bouza E. Mycobacterium tuberculosis infection in recipients of solid organ transplants. Clin Infect Dis 2005; 40:581.
- Subramanian AK, Nuermberger EL. Tuberculosis in transplant recipients: diagnostic and therapeutic dilemmas. Transpl Infect Dis 2008; 10:229.
- Subramanian AK, Morris MI, AST Infectious Diseases Community of Practice. Mycobacterium tuberculosis infections in solid organ transplantation. Am J Transplant 2013; 13 Suppl 4:68.
- Subramanian AK. Tuberculosis in solid organ transplant candidates and recipients: current and future challenges. Curr Opin Infect Dis 2014; 27:316.
- Horne DJ, Narita M, Spitters CL, et al. Challenging issues in tuberculosis in solid organ transplantation. Clin Infect Dis 2013; 57:1473.
- Aguado JM, Torre-Cisneros J, Fortún 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.
- Winthrop KL, Kubak BM, Pegues DA, et al. Transmission of mycobacterium tuberculosis via lung transplantation. Am J Transplant 2004; 4:1529.
- Peters TG, Reiter CG, Boswell RL. Transmission of tuberculosis by kidney transplantation. Transplantation 1984; 38:514.
- 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.
- Fiske CT, Griffin MR, Erin H, et al. Black race, sex, and extrapulmonary tuberculosis risk: an observational study. BMC Infect Dis 2010; 10:16.
- 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; 40:990.
- Meije Y, Piersimoni C, Torre-Cisneros J, et al. Mycobacterial infections in solid organ transplant recipients. Clin Microbiol Infect 2014; 20 Suppl 7:89.
- Nahid P, Dorman SE, Alipanah N, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. Clin Infect Dis 2016; 63:e147.
- Aguado JM, Herrero JA, Gavaldá 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.
- Zhang XF, Lv Y, Xue WJ, et al. Mycobacterium tuberculosis infection in solid organ transplant recipients: experience from a single center in China. Transplant Proc 2008; 40:1382.
- Schulman LL, Scully B, McGregor CC, Austin JH. Pulmonary tuberculosis after lung transplantation. Chest 1997; 111:1459.
- Chan AC, Lo CM, Ng KK, et al. Implications for management of Mycobacterium tuberculosis infection in adult-to-adult live donor liver transplantation. Liver Int 2007; 27:81.
- Vachharajani TJ, Oza UG, Phadke AG, Kirpalani AL. Tuberculosis in renal transplant recipients: rifampicin sparing treatment protocol. Int Urol Nephrol 2002-2003; 34:551.
- Sayiner A, Ece T, Duman S, et al. Tuberculosis in renal transplant recipients. Transplantation 1999; 68:1268.
- al-Sulaiman MH, Dhar JM, al-Khader AA. Successful use of rifampicin in the treatment of tuberculosis in renal transplant patients immunosuppressed with cyclosporine. Transplantation 1990; 50:597.
- Offermann G, Keller F, Molzahn M. Low cyclosporin A blood levels and acute graft rejection in a renal transplant recipient during rifampin treatment. Am J Nephrol 1985; 5:385.
- Escalante P. Mycobacterial infections in solid organ transplantation. Curr Opin Organ Transplant 2007; 12:585.
- Niemi M, Backman JT, Fromm MF, et al. Pharmacokinetic interactions with rifampicin : clinical relevance. Clin Pharmacokinet 2003; 42:819.
- López-Montes A, Gallego E, López E, et al. Treatment of tuberculosis with rifabutin in a renal transplant recipient. Am J Kidney Dis 2004; 44:e59.
- Lee J, Yew WW, Wong CF, et al. Multidrug-resistant tuberculosis in a lung transplant recipient. J Heart Lung Transplant 2003; 22:1168.
- Vandevelde C, Chang A, Andrews D, et al. Rifampin and ansamycin interactions with cyclosporine after renal transplantation. Pharmacotherapy 1991; 11:88.
- Sun HY, Munoz P, Torre-Cisneros J, et al. Mycobacterium tuberculosis-associated immune reconstitution syndrome in solid-organ transplant recipients. Transplantation 2013; 95:1173.
- Sun HY, Munoz P, Torre-Cisneros J, et al. Tuberculosis in solid-organ transplant recipients: disease characteristics and outcomes in the current era. Prog Transplant 2014; 24:37.
- 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.
- Mazurek GH, Jereb J, Vernon A, et al. Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection - United States, 2010. MMWR Recomm Rep 2010; 59:1.
- Pai M, Denkinger CM, Kik SV, et al. Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev 2014; 27:3.
- 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.
- Casas S, Muñoz 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.
- Ferguson TW, Tangri N, Macdonald K, et al. The diagnostic accuracy of tests for latent tuberculosis infection in hemodialysis patients: a systematic review and meta-analysis. Transplantation 2015; 99:1084.
- Rogerson TE, Chen S, Kok J, et al. Tests for latent tuberculosis in people with ESRD: a systematic review. Am J Kidney Dis 2013; 61:33.
- Pai M, Lewinsohn DM. Interferon-gamma assays for tuberculosis: is anergy the Achilles' heel? Am J Respir Crit Care Med 2005; 172:519.
- Menzies D, Gardiner G, Farhat M, et al. Thinking in three dimensions: a web-based algorithm to aid the interpretation of tuberculin skin test results. Int J Tuberc Lung Dis 2008; 12:498.
- Sester M, van Leth F, Bruchfeld J, et al. Risk assessment of tuberculosis in immunocompromised patients. A TBNET study. Am J Respir Crit Care Med 2014; 190:1168.
- Antony SJ, Ynares C, Dummer JS. Isoniazid hepatotoxicity in renal transplant recipients. Clin Transplant 1997; 11:34.
- Singh N, Wagener MM, Gayowski T. Safety and efficacy of isoniazid chemoprophylaxis administered during liver transplant candidacy for the prevention of posttransplant tuberculosis. Transplantation 2002; 74:892.
- Jahng AW, Tran T, Bui L, Joyner JL. Safety of treatment of latent tuberculosis infection in compensated cirrhotic patients during transplant candidacy period. Transplantation 2007; 83:1557.
- Schmidt T, Schub D, Wolf M, et al. Comparative analysis of assays for detection of cell-mediated immunity toward cytomegalovirus and M. tuberculosis in samples from deceased organ donors. Am J Transplant 2014; 14:2159.
- Centers for Disease Control and Prevention (CDC). Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent Mycobacterium tuberculosis infection. MMWR Morb Mortal Wkly Rep 2011; 60:1650.
- Sterling TR, Villarino ME, Borisov AS, et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med 2011; 365:2155.
- Centers for Disease Control and Prevention (CDC). 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.