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Incidence, Outcomes, and Long-term Immune Response to Tuberculosis in Organ Transplant Recipients

Natori, Yoichiro, MD1; Ferreira, Victor H., PhD1; Nellimarla, Srinivas, PhD1; Husain, Shahid, MD1; Rotstein, Coleman, MD1; Humar, Atul, MD1; Kumar, Deepali, MD1

doi: 10.1097/TP.0000000000002340
Original Clinical Science—General

Background Tuberculosis (TB) is a significant opportunistic infection in solid organ transplant recipients (SOTR). There are limited data on TB incidence in transplantation from low prevalence countries as well as on long-term TB-specific immune responses.

Methods We performed a single-center retrospective review of SOTR diagnosed with active TB between 2000 and 2015 and further contacted the available patients for a study of long-term T-cell responses using an interferon-gamma (IFN-γ) release assay and a flow cytometry-based assay.

Results We identified 31 SOTR with active TB for an incidence of 62 cases/100 000 patient-years. Nineteen (61.3%) of 31 patients were diagnosed within the first year after transplant. Nineteen (61.3%) were born in countries with high TB prevalence and disseminated disease occurred in 22.6%. No patient had been screened for latent TB infection pretransplant. The majority of patients received isoniazid and a rifamycin as part of multidrug regimen. In addition, 13 (44.8%) of 29 patients received quinolones. One-year mortality in this population was 19.4%. Eight patients were available for long-term immune responses. Of these, all had detectable IFN-γ response by IFN-γ release assay testing and 7 of 8 had detectable TB-specific T cells, primarily central and effector T-cell responses in the CD4+ compartment and terminally differentiated T cells in the CD8+ compartment.

Conclusions TB has high incidence in SOTR even in low-prevalence regions but especially targets patients who originated from TB-endemic countries. Long-term TB-specific T-cell responses were found in the majority of patients.

1 Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.

Received 26 March 2018. Revision received 22 May 2018.

Accepted 16 June 2018.

A.H. and D.K. have joint senior authorship.

D.K. has received research funding from Qiagen, and Oxford Immunotec as well as consultancy fees from Qiagen and Oxford Immunotec. A.H. has received research funding from Qiagen. The remaining authors declare no conflicts of interest.

The authors declare no funding for this study.

Y.N., A.H., and D.K. participated in research design, the writing of the article, performance of the research, and data analysis. V.H.F. and S.N. participated in the data analysis and interpretation. S.H. and C.R. participated in the writing of the article.

Correspondence: Deepali Kumar MD, Transplant Infectious Diseases & Multi Organ Transplant Program, University Health Network, 585 University Ave., 11-PMB-174, Toronto, ON, Canada M5G 2N2. (deepali.kumar@uhn.ca).

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

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