Reactivation Infections in Solid Organ Transplant Recipients

Ellie S. Walker

Michael G. Ison

INTRODUCTION

Infection is one of the leading causes of morbidity and mortality in solid organ transplant recipients despite advances in preoperative screening, infection prophylaxis, and immunosuppressive regimens.¹ Posttransplant infection may be the result of an infection acquired from the organ donor, of de novo acquisition of a typical or opportunistic pathogen posttransplant, or of reactivation of infection latently infecting the recipient at the time of transplantation.¹ Pretransplant screening of transplant candidates is directed at identifying patients at risk of such reactivation infections posttransplant.² When latent infection is identified, patients may be managed through application of pretransplant treatment, posttransplant prophylaxis, or careful monitoring for reactivation coupled with early therapy posttransplant.² Although a range of pathogens may lie dormant in a patient and reactivate posttransplant to cause infection, viruses and mycobacteria are associated with the most frequent morbidity and mortality.¹^,³ Herpes viruses, hepatitis viruses, and polyoma viruses are the most common viral infections that may reactivate in the recipient posttransplant.¹ Extensive reviews of the epidemiology and prevention of hepatitis and BK virus infection have been published recently.⁴^,⁵ Here, we focus on the current state-of-the-art of screening for and preventing cytomegalovirus (CMV) and tuberculosis in the posttransplant period.

CASE PRESENTATION: PART A

The patient is a 60-year-old Hispanic man who was originally born in rural Mexico with end-stage renal disease on hemodialysis. He had a history of hyperlipidemia, type II diabetes, heart failure, pulmonary hypertension, and anemia. During pretransplant screening for renal transplant, he was found to have a positive interferon-γ release assay (IGRA) (QuantiFERON-TB Gold) and was diagnosed with latent TB infection (LTBI). Isoniazid (INH) and vitamin B₆ were initiated to complete a 9-month course. The patient followed up regularly and reported compliance with INH and completed treatment.

Latent Mycobacterium tuberculosis Infection

The incidence of reactivation of latent M. tuberculosis is 20- to 74-fold higher among transplant recipients than in the general population.⁶ In the United States, the majority of posttransplant tuberculosis occurs as the result of reactivation of latent TB, and screening of candidates is associated with a reduction in the rate of posttransplant infection.⁷^,⁸ As a result, current guidelines recommend the screening of all transplant candidates for tuberculosis.² The American Society of Transplantation Infectious Diseases Community of Practice guidelines recommend screening for LTBI and treatment
of LTBI in all transplant candidates.²^,⁹ Screening consists of a detailed patient history, chest x-ray, and either tuberculin skin testing (TST) or an IGRA. The three currently approved IGRAs in the United States are the QuantiFERON-TB gold, QuantiFERON-TB Gold In-Tube, and TB. Studies comparing TST with the approved IGRA assays have shown similar sensitivity and specificity, and the Centers for Disease Control (CDC) and American Society of Transplantation (AST) recommend that the tests may be used interchangeably.¹⁰ Studies comparing pretransplant screening with TST and the QuantiFERON-TB gold IGRA show comparable, low rates of posttransplant TB infections.¹¹ However, IGRAs have benefits over TST, in some settings. IGRAs may increase the proportion of patients who complete pretransplant LTBI screening as patients do not need to return for TST reading.¹⁰ IGRAs also have a lower rate of false-positive results, have less cross-reactivity with other Mycobacteria, and may be used for patients who have previously received bacillus calmette-guerin (BCG) vaccination.¹¹ In addition, IGRAs may yield fewer false-negative results than TST in patients with immunosuppression as these patients may have cutaneous anergy.⁹^,¹⁰

Current recommendations state that patients diagnosed with LTBI should be treated with either 9 months of isoniazid with supplemental vitamin B₆ or 4 months of rifampin.¹² An alternative regimen of 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) was recently found to be equally effective but with a higher treatment completion rate than 9 months of isoniazid.¹³ Ideally, LTBI treatment is initiated prior to organ transplantation. Typically, isoniazid/B₆ regimens are utilized in the pretransplant period since rifampin may induce cytochrome P450 enzymes and effect posttransplant immunosuppressive levels; if rifampin is utilized (typically because of isoniazid intolerance), the patient should be placed on medical hold until approximately 1 month after completing therapy. Although there is a concern about hepatotoxicity, particularly with isoniazid-containing regimens, isoniazid is generally well tolerated by patients with end-organ failure awaiting transplant as long as liver function testing is performed regularly.¹⁴ Patients with end-stage liver disease and baseline liver function test abnormalities greater than three to five times the upper limits of normal should typically have LTBI delayed until posttransplant.¹⁵

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