Donor derived <i>Mycobacterium tuberculosis</i> infection after solid‐organ transplantation: A comprehensive review

Abad, Cybele Lara; Razonable, Raymund R.

doi:10.1111/tid.12971

Cited by 44 publications

(26 citation statements)

References 28 publications

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“…During this time, 336 047 transplants were performed in the United States, indicating that donor-derived TB transmission is rare. 22 Among these cases, recipients developed symptoms within 6 months Eight of nine (89%) P/P DDTB were diagnosed early after transplant with a median time of 106 days, consistent with previous reports, 15 which suggested median onset of DDTB was two months (range 0.2-15 months). Intensified immunosuppression in the early period of SOT likely influences the timing of infection.…”

Section: Discussionsupporting

confidence: 84%

“…TB transmission through solid organ transplantation continues to occur, most likely attributed to travel or prior residence by donors in endemic countries. [10][11][12][13][14][15][16] In the United States, transplant centers or the organ procurement organization (OPO) are mandated to report potential donor-derived transmission events to the OPTN for investigation by the DTAC. These cases are reviewed and categorized by the likelihood of transmission from donor to recipient(s).…”

Section: Introductionmentioning

confidence: 99%

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Donor‐derived tuberculosis among solid organ transplant recipients in the United States—2008 to 2018

Malinis

Hoz

Vece³

et al. 2022

Transplant Infectious Dis

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Mycobacterium tuberculosis can be transmitted via organ donation and result in severe outcomes. To better understand donor-derived tuberculosis (DDTB), all potential transmissions reported to the Organ Procurement and Transplantation Network (OPTN) Ad Hoc Disease Transmission Advisory Committee between 2008 and 2018 were analyzed. Among 51 total reports, nine (17%) (9 donors/35 recipients) had ≥ 1 recipient with proven/probable disease transmission. Of these, eight were reported due to recipient disease, and one was reported due to a positive donor result.Proven/probable DDTB transmissions were reported in six lung and five nonlung recipients. The median time to diagnosis was 104 days posttransplant (range 0-165 days).Pulmonary TB, extrapulmonary TB, pulmonary plus extrapulmonary TB, and asymptomatic TB infection with positive interferon-gamma release assay were present in five, three, one, and two recipients, respectively. All recipients received treatment and survived except for one whose death was not attributed to TB. All donors associated with proven/probable DDTB had ≥ 1 TB risk factor. Six were born in a TB-endemic country, five had traveled to a TB-endemic country, three had been incarcerated, and three had latent TB infection. These cases highlight the importance of evaluating donors for TB based on risk factors. Early posttransplant TB in organ recipients of donors with TB risk factors requires prompt reporting to OPTN to identify other potential affected recipients and implement timely treatment interventions.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Donor‐derived tuberculosis among solid organ transplant recipients in the United States—2008 to 2018

Malinis

Hoz

Vece³

et al. 2022

Transplant Infectious Dis

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“…The current guidelines mainly recommend the tuberculin skin test (TST) for screening of LTBI in solid organ candidates and recipients and living donors. Nevertheless, this test has some disadvantages: interpretation bias; false-positive results related to previous exposure to others Mycobacteria or BCG vaccination; and cutaneous anergy on patients with CKD 2 , 4 , 6 , 7 . IFN-γ release assays (IGRAs) is a new diagnostic method and is probably more sensitive in candidates with chronic renal failure.…”

Section: Discussionmentioning

confidence: 99%

“…It most commonly presents as a fever that is usually treated as a sign of a non-TB infection. The suspicion of TB must be done when there is no response to empiric antibacterial treatment 7 , 8 .…”

Section: Discussionmentioning

confidence: 99%

Donor-derived TB after kidney transplantation: a case report

et al. 2022

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Introduction: Tuberculosis (TB) is a possible serious complication of solid organ transplantation, associated with high mortality and morbidity. Post-transplant TB has varied pathogenesis with many approaches to its prevention, which is the most important way to reduce its incidence. Treatment of TB in organ recipients is challenging because of drug toxicity and interaction with immunosuppressants. Case report: an 18-year-old woman that underwent kidney transplantation from a deceased donor and was discharged with fair renal function was readmitted at 37th postoperative day with fever. CT showed signs of miliary TB and fluid collection besides graft fistulization through the skin. The patient presented positive BAAR in the drained fluid and Koch's bacillus in the urine. She was treated with a four-drug regimen (rifampicin, isoniazid, pyrazinamide, and etambutol), with great response and preserved graft function. We were informed that the recipient of the contralateral kidney also presented post-transplant TB, implying in a donor-derived origin. Conclusion: TB is an important differential diagnosis for infectious complications in patients after solid-organ transplantation, especially in endemic regions. Its initial clinical presentation can be unspecific and it should be suspected in the presence of fever or formation of fluid collections. The suspicion of TB is the key to early diagnosis and satisfactory outcomes in post-transplant TB.

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“…Increased susceptibility to opportunistic infections is common in immunodeficient hosts, including individuals with primary immunodeficiency disorders (PID), transplant recipients, and patients receiving chemotherapy or immunosuppression for rheumatologic disease (5–7). It has been long appreciated that global T cell deficiency, such as occurs in severe combined immunodeficiency (SCID) and advanced HIV infection, is associated with risk of severe mycobacterial infections.…”

Section: Introductionmentioning

confidence: 99%

Mycobacteria-Specific T Cells May Be Expanded From Healthy Donors and Are Near Absent in Primary Immunodeficiency Disorders

et al. 2019

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Mycobacterial Infections can be severe in patients with T-cell deficiency or phagocyte disorders, and treatment is frequently complicated by antimicrobial resistance. Restoration of T-cell immunity via stem cell transplantation facilitates control of mycobacterial infections, but presence of active infections during transplantation is associated with a higher risk of mortality. Adoptive T cell immunotherapy has been successful in targeting viruses, but has not been attempted to treat mycobacterial infections. We sought to expand and characterize mycobacterial-specific T-cells derived from healthy donors in order to determine suitability for adoptive immunotherapy. Mycobacteria-specific T-cells (MSTs) were generated from 10 healthy donors using a rapid ex vivo expansion protocol targeting five known mycobacterial target proteins (AG85B, PPE68, ESXA, ESXB, and ADK). MSTs were compared to T-cells expanded from the same donors using lysate from M. tuberculosis or purified protein derivative from M. avium (sensitin). MST expansion from seven patients with primary immunodeficiency disorders (PID) and two patients with IFN-γ autoantibodies and invasive M. avium infections. MSTs expanded from healthy donors recognized a median of 3 of 5 antigens, with production of IFN-γ, TNF, and GM-CSF in CD4 + T cells. Comparison of donors who received BCG vaccine ( n = 6) to those who did not ( n = 4) showed differential responses to PPE68 ( p = 0.028) and ADK ( p = 0.015) by IFN-γ ELISpot. MSTs expanded from lysate or sensitin also recognized multiple mycobacterial antigens, with a statistically significant differences noted only in the response to PPE68 ( p = 0.016). MSTs expanded from patients with primary immunodeficiency (PID) and invasive mycobacterial infections showed activity against mycobacterial antigens in only two of seven subjects, whereas both patients with IFN-γ autoantibodies recognized mycobacterial antigens. Thus, MSTs can be generated from donors using a rapid expansion protocol regardless of history of BCG immunization. Most tested PID patients had no detectable T-cell immunity to mycobacteria despite history of infection. MSTs may have clinical utility for adoptive immunotherapy in T-cell deficient patients with invasive mycobacterial infections.

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Donor derived Mycobacterium tuberculosis infection after solid‐organ transplantation: A comprehensive review

Cited by 44 publications

References 28 publications

Donor‐derived tuberculosis among solid organ transplant recipients in the United States—2008 to 2018

Donor‐derived tuberculosis among solid organ transplant recipients in the United States—2008 to 2018

Donor-derived TB after kidney transplantation: a case report

Mycobacteria-Specific T Cells May Be Expanded From Healthy Donors and Are Near Absent in Primary Immunodeficiency Disorders

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