Mycobacterium tuberculosis (TB) is a common pathogen worldwide, and it may cause significant infection after solid organ transplantation (SOT). We reviewed all reported TB cases to provide an update on its epidemiology, clinical presentation, management, and outcome after SOT.

MEDLINE, EMBASE, and OVID were reviewed from January 1, 1998, to December 31, 2016, using keywords tuberculosis and solid organ transplant or transplantation.

There were 187 publications reporting 2082 cases of TB among kidney (n = 1719), liver (n = 253), heart (n = 77), lung (n = 25), and kidney-pancreas (n = 8) recipients. Among cohort studies, the median incidence was 2.37% (range, 0.05%-13.27%) overall. Most TB disease was considered reactivation of latent infection, occurring beyond the first year after SOT. Early-onset cases were seen among donor-derived TB cases. Fever was the most common symptom. Radiologic findings were highly variable. Extrapulmonary and disseminated TB occurred 29.84% and 15.96%, respectively. Multidrug-resistant TB was rare. Treatment using 4 or 5 drugs was commonly associated with hepatotoxicity and graft dysfunction. All-cause mortality was 18.84%.

This large review highlights the complexity of TB after SOT. Reactivation TB, donor-transmitted infection, extrapulmonary involvement, and disseminated disease are common occurrences. Treatment of TB is commonly associated with hepatotoxicity and graft dysfunction.

Liver transplantation for end-stage liver disease is increasingly being undertaken in India.(1) Routine tuberculin skin testing (TST) for latent Mycobacterium tuberculosis infection (LTBI) and isoniazid prophylaxis in TST-positive liver-transplant recipients (LTRs) is recommended(2,3) but seldom implemented worldwide.(4-7) The role of TST-testing and isoniazid prophylaxis in LTRs remains further undefined in high prevalence areas, including India. We describe the burden of LTBI in LTRs; the epidemiological aspects of M. tuberculosis infection in high prevalence areas; identifiable risk factors for M. tuberculosis infection; the limitations of current diagnostic techniques for LTBI in LTRs and the efficacy and toxicity of isoniazid prophylaxis in TST-positive LTRs and suggest directions for future investigations in this area.

The optimal means for detecting and managing liver transplantation (LT) patients with latent tuberculosis (TB) are not well defined. Our study aims were to (1) determine the frequency and risk factors of latent TB in a large cohort of consecutive adult LT candidates and (2) determine the safety and efficacy of isoniazid treatment in LT recipients with latent TB. A review of patients assessed for latent TB by skin testing using purified protein derivative (PPD; January 2004 to September 2008) or with the interferon-γ release assay QuantiFERON-TB Gold (QFT; March 2008 to October 2009) was undertaken. The baseline clinical features and outcomes of subjects with latent TB and subjects without latent TB were compared. Twenty-five of 420 subjects (6.0%) were positive for PPD. In comparison, 11 of 119 subjects (9.2%) had a positive QFT assay, and 15 others (13%) had indeterminate results. Both PPD-positive and QFT-positive subjects were less likely to be Caucasian than subjects without latent TB (p < 0.001). The 3-year survival rate of the 25 LT recipients with latent TB was similar to that of the 296 LT recipients without latent TB (78.7% versus 74.6%, P = 0.58). Fifteen of the 25 latent TB patients received isoniazid at a mean of 0.67 months after LT. Although isoniazid was discontinued in 8 subjects because of possible side effects, none of the 25 latent TB patients developed TB reactivation after transplantation with a mean follow-up of 33 months. In conclusion, both QFT testing and PPD testing demonstrate similar rates of detecting latent TB infection in American LT candidates, but QFT testing also leads to a moderate rate of indeterminate test results. Early isoniazid chemoprophylaxis after LT is poorly tolerated and is frequently discontinued.

A liver transplantation is the first choice of treatment for patients with hepatic insufficiency due to chronic diseases. Infections in the postoperative period represent one of the main causes of mortality in these cases. However, few articles have evaluated the predominance of certain infectious diseases and their influence on postoperative mortality.

We retrospectively evaluated the medical records of 236 patients who underwent liver transplantation from January 1997 to January 2007. In these records we checked the serological profiles for these diseases: toxoplasmosis, syphilis, human T lymphotropic virus (HTLV) I and II infection, Chagas disease, hepatitis A, hepatitis B, hepatitis C, paracoccidioidomycosis, tuberculosis, acquired immunodeficiency syndrome, cytomegalovirus (CMV), and mononucleosis (Epstein-Barr virus [EBV]). The statistical analysis was performed by table frequencies.

CMV showed positivity (CMV-IgG) in 94.7% of patients, 95.8% for EBV, 33.3% for toxoplasmosis, 47.9% for hepatitis C, and 5% for hepatitis B.

Our analysis showed the importance of serological investigations and diagnostic examinations before the transplantation procedure, seeking to minimize possible reactivation of the disease after the use of immunosuppression drugs, particularly in the first 6 months after transplantation, or even to avoid a primary infection.

Although advances in surgical technique, immunosuppressive regimens, and medical management have led to improved survival and quality of life after solid organ transplantation, infection continues to represent a major cause of morbidity and mortality in transplant recipients. Immunosuppressive therapy after transplantation compromises cell-mediated immunity in particular, leaving the patient at risk for opportunistic as well as routine community-acquired infections. Mycobacterial infection is a rare but important complication of solid organ transplantation, presenting significant risk to the patient and challenges in terms of treatment. The available literature consists predominantly of case reports and institutional experiences. This article examines both Mycobacterium tuberculosis and nontuberculous mycobacterial infection in the transplant setting.

To provide a better understanding and summarize recent advances in the diagnosis and treatment of Mycobacterium tuberculosis (MTB) infection in solid organ transplant (SOT) candidates and recipients.

Despite advances in SOT medicine, MTB causes substantial morbidity and mortality in SOT recipients, with reported prevalence rates of 0.4-6%. The primary source of posttransplant MTB is reactivation of pretransplant latent MTB infection. The short-term mortality rate in SOT recipients with drug-susceptible active MTB is 30%. In immunocompromised persons with extensively drug-resistant MTB, the mortality rate approaches 100%. Clinical presentation is often atypical with more than half of SOT recipients presenting with extrapulmonary or disseminated disease. Pretransplant latent MTB infection screening and treatment is the cornerstone for preventing reactivation and dissemination of active MTB posttransplant. Treatment of active MTB in SOT recipients is problematic, given significant drug toxicity and interaction with immunosuppressive agents.

A high degree of suspicion for latent and active MTB infection in SOT candidates and recipients is warranted to establish a timely diagnosis and initiate life-saving appropriate therapy.

Mycobacterium tuberculosis (MTB) causes substantial morbidity and mortality in liver transplant recipients. We examined the efficacy of isoniazid latent Mycobacterium tuberculosis infection (LTBI) treatment in liver transplant recipients and reviewed systematically all cases of active MTB infection in this population. We found 7 studies that evaluated LTBI treatment and 139 cases of active MTB infection in liver transplant recipients. Isoniazid LTBI treatment was associated with reduced MTB reactivation in transplant patients with latent MTB risk factors (0.0% versus 8.2%, P = 0.02), and isoniazid-related hepatotoxicity occurred in 6% of treated patients, with no reported deaths. The prevalence of active MTB infection in transplant recipients was 1.3%. Nearly half of all recipients with active MTB infection had an identifiable pretransplant MTB risk factor. Among recipients who developed active MTB infection, extrapulmonary involvement was common (67%), including multiorgan disease (27%). The short-term mortality rate was 31%. Surviving patients were more likely to have received 3 or more drugs for MTB induction therapy (P = 0.003) and to have been diagnosed within 1 month of symptom onset (P = 0.01) and were less likely to have multiorgan disease (P = 0.01) or to have experienced episodes of acute transplant rejection (P = 0.02). Compared with the general population, liver transplant recipients have an 18-fold increase in the prevalence of active MTB infection and a 4-fold increase in the case-fatality rate. For high-risk transplant candidates, isoniazid appears safe and is probably effective at reducing MTB reactivation. All liver transplant candidates should receive a tuberculin skin test, and isoniazid LTBI treatment should be given to patients with a positive skin test result or MTB pretransplant risk factors, barring a specific contraindication. Liver Transpl 15:894-906, 2009. (c) 2009 AASLD.

Four cases are presented, immunosuppressed by at least three different mechanisms: one HIV-positive patient with a CD4 count of 0.29 x 10(6)/ml, one malnourished patient, and two kidney-transplanted patients. All patients had a negative interferon (IFN)-gamma test for suspected tuberculosis (TB), but a positive culture. We conclude that a negative IFN-gamma test does not exclude TB disease in immunosuppressed patients.

The sensitivities of various gamma interferon release assays (IGRAs) for the detection of past latent Mycobacterium tuberculosis infection are not known. In this study, we aimed to assess the effects of various IGRA formats and in vitro incubation periods on test outcome. The results of the tuberculin skin test (TST) were compared with those of the QuantiFERON-TB Gold in-tube (QFT-GIT) test, an overnight enzyme-linked immunospot assay (ELISPOT), and a 6-day lymphocyte stimulation test (LST) by using the same M. tuberculosis-specific peptides and samples from 27 TST-positive persons with a history of exposure to M. tuberculosis, 4 patients cured of tuberculosis (TB), and 9 TST-negative controls. Among the TST-positive persons, the LST was more frequently positive (92%; P < 0.01) than either the QFT-GIT test (33%) or ELISPOT (46%). While good agreement was observed between the QFT-GIT test and ELISPOT (kappa = 0.71) and between TST and LST (kappa = 0.78), the agreement between TST or LST, on the one hand, and the QFT-GIT test or ELISPOT, on the other, was poor. These data indicate that the QFT-GIT test and overnight ELISPOT are less sensitive for the detection of past latent TB than the 6-day LST. The observed discrepancies between these IGRAs are most likely related to differences in incubation periods. Whether TST-positive persons with positive LST results but negative QFT-GIT and ELISPOT results are at risk for the development of TB needs to be elucidated before short-incubation IGRAs can be used for the screening of individuals for latent TB before immunosuppressive treatment.

Tuberculosis (TB) remains a major threat to global health. The recently launched Global Plan to Stop Tuberculosis 2006-2015 highlights the need for accurate, simple and low-cost diagnostic tests for the detection of TB infection. For the first time in decades, new diagnostic tools have emerged that may facilitate this goal. The discovery of Mycobacterium tuberculosis-specific immunodominant antigens has led to the development of interferon gamma-release assays that have been shown to have high sensitivity and specificity for TB disease. This review focuses on the QuantiFERON-TB Gold tests and addresses the potential strengths and limitations of the current assays, summarizes the available evidence for their use and identifies areas of future research and development. Although representing an advance in TB diagnostics, with the potential to have a significant impact on global TB control, many issues remain unanswered. The cost of the tests and laboratory requirements may limit their use in developing countries. Most importantly, additional studies are needed in TB-endemic regions, particularly in high-risk persons such as children and individuals who are also co-infected with HIV.