Mycobacterium tuberculosis infection in immunocompromised hosts: A diagnostic challenge

Abstract

The number of cases of tuberculosis (TB) in the United States declined by 45% between 1993 and 2006. This decline occurred disproportionately among United States–born persons (66%) compared to foreign-born individuals, among whom the number of cases actually increased by 5%. In solid-organ transplant recipients, the incidence of Mycobacterium tuberculosis (MTB) infection worldwide ranges between 0.35% and 15%, depending on the level of endemicity. This rate can be 36to 74-fold greater than that in the general population. The majority of MTB cases after transplantation represent reactivation of latent tuberculosis infection (LTBI), although acquisition of primary TB infection posttransplant and transmission of MTB via the transplanted organ are infrequent possibilities. Active TB in the posttransplantation setting can pose a number of challenges: atypical presentation leading to a delay in diagnosis, therapy associated with drug interactions and toxicities, graft rejection, and formidable morbidity and mortality. This is of particular concern in both patients with end-stage liver disease awaiting liver transplantation and liver transplant recipients, given the hepatotoxicity of several anti-TB medications and their associated drug interactions with immunosuppressants. In this issue of Liver Transplantation, Holty et al. present a systematic review and meta-analysis of TB in liver transplant recipients. They included cases of active MTB infection following liver transplantation as well as transplant candidates or recipients who received 6 months of therapy for LTBI prior to transplantation. The prevalence of active TB in liver transplant recipients was 1.3%. Extrapulmonary infection was seen in 67%, multiorgan involvement was seen in 27%, and 31% died. Tuberculin skin test (TST) results were as follows: a) Among 38 cases of posttransplant active TB with known pretransplant TST status, 37% were TST-positive, 53% were negative, and 11% were anergic; among 17 of these patients who had a posttransplant TST, only 35% were positive. b) In 3 studies with 2972 patients who underwent liver transplantation, 31% of the patients had a pretransplant TST, and 13% of these were positive. None of the TST-positive patients who received isoniazid therapy for at least 6 months developed active TB, whereas 7 TST-positive patients developed active disease without such therapy (mean follow-up, 54 months). Short-term mortality in patients with active posttransplant TB was 31%, with 65% of deaths directly attributed to MTB infection. Because reactivation of LTBI represents the majority of posttransplant cases of active TB, it is prudent to screen and identify such patients before transplantation for consideration of appropriate therapy for LTBI. Until recently, TST was the only test available for LTBI diagnosis. As noted previously, TST was notoriously insensitive: 64% of patients with posttransplant active TB were either TST-negative or anergic prior to transplantation, and 65% of patients had a negative posttransplant TST in the setting of active TB. TST has