Challenges in Management: Solid Organ Transplantation & Tuberculosis Michele I Morris, M.D., FACP, FIDSA Director, Immunocompromised Host Section Associate Professor of Clinical Medicine Division of Infectious Diseases University of Miami Miller School of Medicine Miami, FL, USA
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Challenges in Management:
Solid Organ Transplantation &
Tuberculosis
Michele I Morris, M.D., FACP, FIDSA Director, Immunocompromised Host Section
Associate Professor of Clinical Medicine Division of Infectious Diseases
University of Miami Miller School of Medicine Miami, FL, USA
The Nightmare Scenario
• 45 year old female nurse mother of 2 develops active pulmonary TB after work related exposure
• Treated with RIPE, develops hepatic failure 12 weeks into therapy
• Is she a candidate for liver transplant?
• If so, how do you manage her TB post-transplant?
Expert Clinical Opinion
TB in Solid Organ Transplant
(SOT)
• Epidemiology
• Interventions to prevent TB post-transplant
– Screening deceased & living donors
– Screening transplant candidates
– Management of Latent TB in SOT
• Worse Case Scenario – Treating TB post-transplant – How TB providers can help
TB Epidemiology in SOT
• SOT recipients 36-74 fold higher risk for TB than general population
• TB incidence 1.2-6.4%, up to 15% in highly endemic countries
• Drug-drug interactions with transplant immunosuppressants allograft rejection organ loss
– Transplant experts with little TB experience
– TB experts with little transplant experience
Sources of TB in Transplant
Recipients
• Reactivation in recipients with untreated or unrecognized latent or active TB
• Post-transplant exposure – Likely more common in high TB incidence countries – Nosocomial outbreaks – Travel
• Donor-derived – transmitted through organ allograft – ~4% post-transplant TB – Likely more common in lung recipients
• Relapse – history of previously treated active TB with persistent viable bacilli despite clinical cure – 3.5% relapse rate at 2 years with 4 drug/6 month TB therapy
• Only 20-25% of post-transplant TB patients had +TST pre-transplant – End stage organ failure TST anergy/IGRA
indeterminate results
• No gold standard to diagnose LTBI • Sensitivity of IGRAs may be better than TST • Both tests specific, any + should be considered as
evidence of TB infection • Neither TST nor IGRA can distinguish latent from
active TB
TST & IGRA Performance in
Transplant Candidates
QuantiFERON-TB Assay in
Hemodialysis Patients
High rate of indeterminates but none with active TB
Inoue T, Nakamura T, Katsuma A. Nephrol Dial Transplant 2009.
Predictive Value of T-SPOT TB Test
in Kidney Transplant Candidates
Kim S-H, Lee S-O, Park JB. Amer J Transpl 2011.
Rate difference 3.3/100 + vs -/indeterminate P<0.001
Theodoropoulos N, Lanternier F, Rassiwala J. Transpl Inf Dis 2011.
Quantiferon-TB Assay in Liver
Candidates • TST and QFT diagnose latent TB infection at
similar rates pre-liver transplant – consider IGRA followed by TST, esp in high risk
• Candidates with advanced liver disease – Indeterminate results more likely
– QFT performs better than TST
• Approach to indeterminate QFT – Repeat when patient healthier
– Alternative test – T-SPOT TB or TST
Manuel O, Humar A, Preiksaitis J. Amer J Transpl 2007. Casas S, Munoz L, Moure R. Liver Transpl 2011. Theodoropoulos N, Lanternier F, Rassiwala J. Transpl Inf Dis 2011.
Pre-transplant Latent TB
Evaluation: CT vs. CXR
Lyu J, Lee S-G, Hwang S. Liver Transpl 2011.
2549 liver transplant recipients in South Korea – 36 developed TB Matched 4:1 with controls without post-transplant TB
Aguado JM, Torre-Cisneros J. Clin Infect Dis 2009.
TB Screening Algorithm for Transplant Candidates
Testing Post-Transplant:
TST vs. IGRA
Hadaya K, Bridevaux P-O, Roux-Lombard P. Transplantation 2013.
205 Swiss renal transplant recipients Comparison of 2 IGRAs with TST All show poor sensitivity T-SPOT TB most sensitive
TB Screening of Deceased Donors
Detailed History is Key, but Complex
End Stage Organ Failure +/- ICU Care
Required Screening for
Multiple Infectious Diseases
Reliance on Diagnostic Tests with Variable
Sensitivity
Brain death Consent
6-48 hours
Surgical organ recovery
Meds, Stabilize, Labs, Echo, Bronch Place organs
Referral pt. on ventilator
Aortic cross-clamp
Donor Management
Eval
Slide provided by Susan Ganz, M.D.
TB Screening of Deceased Donors
• TST not feasible • IGRAs often indeterminant
– Head injury patients known to have cellular immunity
– Screening cattle for M. bovis pre/post mortem demonstrated ~50% decrease in gamma interferon after slaughter
– 1997 - Treatment < 9 months associated with mortality
Meije Y, Piersimoni C, Torre-Cisneros J. Clin Microbiol Infect 2014. Aguado JM, Herrera JA, Gavalda J. Transplantation 1997. Park YS, Choi JY, Cho CH. Yonsei Med J 2004.
Treatment of TB post-SOT
• Do NOT treat alone – need transplant team clinician involvement – Complex drug-drug interactions
– Potential loss of organ allograft
• Do NOT use standard DOT – Daily dosing strongly preferred due to impact on other
medications (and medication levels)
• Do NOT give up on the organ allograft or the patient – Frequent visits with both transplant clinician managing TB
and TB provider essential for successful outcome
Immune Reconstitution Syndrome
(IRS) in Post-SOT TB • Increased inflammatory response seen in HIV patients • Occurs in 14% of TB post-transplant • Risk Factors
• Complicates monitoring of clinical response to treatment – Need to distinguish from progressive infection – Median onset 47 days after starting anti-TB therapy
• Increased 1 year Mortality (33% IRIS vs 17% no IRIS)
Sun HY. Prog Transplant 2014;24:37-43.
Take Home Messages • Transplant recipients are at high risk for TB related
morbidity and mortality
• Available diagnostics do not work optimally in deceased donors & critically ill transplant candidates
• Diagnose & treat LTBI pre-transplant if possible
• Post-transplant TB treatment requires close teamwork