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Fayos M, Silva JT, Fernández-Ruiz M, Ruiz-Merlo T, Visentin A, Loinaz C, Manrique-Municio A, Caso JM, González-Olmedo J, Rodríguez-Góncer I, López-Medrano F, Lumbreras C, Aguado JM, San-Juan R. Efficacy and safety of a preventive strategy against tuberculosis in liver transplantation recipients including the treatment of latent infection with moxifloxacin. Transpl Infect Dis 2024; 26:e14382. [PMID: 39340395 DOI: 10.1111/tid.14382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 08/20/2024] [Accepted: 09/11/2024] [Indexed: 09/30/2024]
Abstract
BACKGROUND Preventive management of tuberculosis in liver transplantation (LT) is challenging due to difficulties in detecting and treating latent tuberculosis infection (LTBI). The aim of this study was to analyze the safety and efficacy of a screening strategy for LTBI with the inclusion of moxifloxacin as treatment. METHODS We performed a retrospective single-center study of all LTs performed between 2016 and 2019 with a minimum 4-year follow-up and a standardized protocol for the evaluation of LTBI. RESULTS Pretransplant LTBI screening was performed in 191/218 (87.6%) patients, and LTBI was diagnosed in 27.2% of them. Treatment for LTBI was administered to 71.2% of the patients and included moxifloxacin in 75.6% of the cases. After a median follow-up of 1628 days, no cases of active tuberculosis occurred among moxifloxacin-treated patients. The incidence of Clostridioides difficile (0.46 vs. 0.38 episodes/1000 transplant-days; p = .8) and multidrug-resistant gram-negative bacilli infection (0 vs. 0.7 episodes per 1000 transplant-days; p = .08) were not significantly higher in comparison to patients who did not receive moxifloxacin. CONCLUSION A preventive strategy based on systematic LTBI screening and moxifloxacin treatment before LT in positive cases appears safe and effective in preventing the development of tuberculosis in LT recipients. However, our findings are limited by a small sample size; thus, larger studies are required to validate our observations.
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Affiliation(s)
- Marina Fayos
- Unit of Infectious Diseases, University Hospital "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Jose Tiago Silva
- Unit of Infectious Diseases, University Hospital "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
- Antimicrobial Stewardship Team in Hospitalized Patients (PROA-HU12O), University Hospital "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
- School of Medicine, Universidad Complutense, Madrid, Spain
| | - Mario Fernández-Ruiz
- Unit of Infectious Diseases, University Hospital "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
- School of Medicine, Universidad Complutense, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Tamara Ruiz-Merlo
- Unit of Infectious Diseases, University Hospital "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Alessandro Visentin
- Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Carmelo Loinaz
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation University Hospital "12 de Octubre", Madrid, Spain
| | - Alejandro Manrique-Municio
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation University Hospital "12 de Octubre", Madrid, Spain
| | - José María Caso
- Unit of Infectious Diseases, University Hospital "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Jesús González-Olmedo
- Unit of Infectious Diseases, University Hospital "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Isabel Rodríguez-Góncer
- Unit of Infectious Diseases, University Hospital "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Francisco López-Medrano
- Unit of Infectious Diseases, University Hospital "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
- School of Medicine, Universidad Complutense, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Carlos Lumbreras
- School of Medicine, Universidad Complutense, Madrid, Spain
- Department of Internal Medicine, University Hospital "12 de Octubre", Madrid, Spain
| | - José María Aguado
- Unit of Infectious Diseases, University Hospital "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
- School of Medicine, Universidad Complutense, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Rafael San-Juan
- Unit of Infectious Diseases, University Hospital "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
- School of Medicine, Universidad Complutense, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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Zhang H, Zeng J, Zhu T, Lin T, Song T. Isoniazid prophylaxis based on tuberculosis risk factors in living kidney transplantation recipients: A retrospective cohort study. Int J Antimicrob Agents 2024; 64:107375. [PMID: 39486467 DOI: 10.1016/j.ijantimicag.2024.107375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 10/20/2024] [Accepted: 10/24/2024] [Indexed: 11/04/2024]
Abstract
BACKGROUND Tuberculosis (TB) is a major and severe opportunistic infection among solid organ transplant recipients. Chemoprophylaxis is advised for those with latent tuberculosis infection. However, the effectiveness of an isoniazid (INH) prophylactic approach based on TB risk factors remains uncertain. METHODS This study included all living-donor kidney transplant recipients between January 2016 and December 2022. The recipients were categorized into three groups: the risk group with INH (R-INH), the risk group without INH (R-NINH), and the non-risk group (NR), based on the presence of TB risk factors and INH usage. The R-INH group received a 6-month INH prophylactic regimen to prevent post-transplant TB infection. The incidence of active TB among the groups was assessed. RESULTS A total of 1348 patients were divided into R-INH (n = 108), R-NINH (n = 371), and NR (n = 869). Forty-seven patients (3.49%) developed TB with an incidence rate of 16.0 per 1000 person-years. Compared to NR, the TB incidence in R-INH was not statistically different (hazard ratios, 0.55, 95% confidence interval, 0.07-4.21, P = 0.564), whereas it was significantly higher in R-NINH (hazard ratios, 5.04, 95% confidence interval, 2.64-9.62, P < 0.001). The median time from transplantation to TB was 19 months (interquartile range: 6-39), and 18 patients (38.3%) were diagnosed within 1 year of transplantation. Ninety-four patients (87.0%) completed INH prophylaxis, with adverse events including two cases of hepatotoxicity (1.85%) and one case of peripheral neuritis (0.93%). CONCLUSIONS A 6-month INH regimen based on TB risk factors is effective and well-tolerated for preventing post-transplant TB in kidney transplant recipients.
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Affiliation(s)
- Hao Zhang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Organ Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jun Zeng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Organ Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Tingting Zhu
- Nephrology and Urology Ward, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Tao Lin
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Organ Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Turun Song
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Organ Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
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Lee YW, Chung H, Kim SH, Sung H, Ha SM, Jwa EK, Jung DH, Moon DB, Lee SG, Lee SO. Safety and outcome of treatment of latent tuberculosis infection in liver transplant recipients. Infection 2024; 52:1055-1061. [PMID: 38347366 DOI: 10.1007/s15010-023-02161-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 12/14/2023] [Indexed: 06/02/2024]
Abstract
PURPOSE Liver transplant (LT) recipients have an increased risk of tuberculosis (TB), which is associated with higher mortality rates. This retrospective cohort study assessed the outcome and tolerability of screening and treatment of latent tuberculosis infection (LTBI) in LT recipients. METHODS Between March 2020 and February 2022, all adult LT candidates at our institution were screened for LTBI. The candidates who tested positive for interferon-γ-releasing assay or met epidemiological or clinical-radiological criteria for LTBI were treated and monitored. RESULTS Among the 857 LT recipients, 199 (23.2%) were diagnosed with LTBI, of which 171 (85.9%) initiated LTBI treatment. The median duration of follow-up was 677 days. Adequate LTBI treatment occurred in 141/171 (82.5%) patients and was discontinued prematurely in 30/171 (17.5%) patients. The most common reason for discontinuation was liver enzyme elevation (11/30, 36.7%), although only five discontinued treatment due to suspicion of isoniazid-associated hepatotoxicity. None of the LTBI-treated patients developed active TB during the follow-up period, while 3.6% (1/28) of untreated LTBI patients and 0.6% (4/658) of patients without LTBI developed TB. CONCLUSION These findings demonstrate that LTBI screening and treatment is a safe and effective strategy to prevent TB in LT recipients. However, monitoring for adverse events and liver enzyme elevation is recommended.
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Affiliation(s)
- Yun Woo Lee
- Division of Infectious Diseases, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea
| | - Hyemin Chung
- Division of Infectious Diseases, Department of Internal Medicine, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Republic of Korea
| | - Sung-Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Heungsup Sung
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Su-Min Ha
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Eun-Kyoung Jwa
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Dong-Hwan Jung
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Deok-Bog Moon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sung-Gyu Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang-Oh Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
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Meregildo-Rodriguez ED, Yuptón-Chávez V, Asmat-Rubio MG, Vásquez-Tirado GA. Latent tuberculosis infection (LTBI) in health-care workers: a cross-sectional study at a northern Peruvian hospital. Front Med (Lausanne) 2023; 10:1295299. [PMID: 38098842 PMCID: PMC10720426 DOI: 10.3389/fmed.2023.1295299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2023] [Accepted: 11/13/2023] [Indexed: 12/17/2023] Open
Abstract
Background Healthcare workers (HCWs) have a higher risk of latent tuberculosis infection (LTBI) and active tuberculosis than the general population. In HCWs, the risk of tuberculosis infection depends on the local tuberculosis prevalence, HCWs' characteristics, the healthcare facility, and prevention and control measures. We aimed to estimate the prevalence and risk factors for LTBI in HCWs at a northern Peruvian hospital. Methods This study had two phases: (1) a cross-sectional phase involving recruitment, history taking, and sampling for the Interferon-Gamma Release Assays (IGRA test), and (2) a prospective follow-up of IGRA-positive participants. We enrolled direct and non-direct patient caregivers among HCWs. We defined an LTBI case if the IGRA test was positive and clinical, laboratory, and radiological evaluations for active tuberculosis were negative. Results We recruited 308 participants between November 2022 and May 2023. The mean age was 38.6 ± 8.3 years. Over 75% of the participants were female. The most common job category was technicians (30.5%), physicians (22.7%), nurses (20.5%), and other HCWs groups (17.5%). Most participants worked in hospital wards (28.2%), diagnostics departments (16.9%), and critical care departments (15.6%). The LTBI prevalence among HCWs was 17.86% (95% CI 13.84-22.70). In multivariate analysis, after adjusting for age, time working in our hospital, and family history of tuberculosis, males had a higher risk of LTBI (aPR 1.69, 95% CI 1.01-2.77) than females. Working for more than 10 years increased the risk of LBTI (aPR 2.4, 95% CI 1.44-3.97) compared to working for ≤10 years. Even further, participants who had worked for more than 20 years had an aPR of 4.31 (95% CI 1.09-13.65) compared to those with ≤10 years. Similarly, occupational exposure increased the risk of LTBI (aPR 2.21, 95% CI 1.27-4.08) compared to those HCWs not occupationally exposed. Conclusion The LTBI prevalence in HCWs at a northern Peruvian hospital was lower compared to other Peruvian cities. Males, more experienced, and occupational exposed HCWs are at higher risk of LTBI. LTBI prevalence in Peruvian HCWs is still high. More studies are needed to address some aspects this study has not examined.
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Yahav D, Gitman MR, Margalit I, Avni T, Leeflang MMG, Husain S. Screening for Latent Tuberculosis Infection in Solid Organ Transplant Recipients to Predict Active Disease: A Systematic Review and Meta-Analysis of Diagnostic Studies. Open Forum Infect Dis 2023; 10:ofad324. [PMID: 37559757 PMCID: PMC10407303 DOI: 10.1093/ofid/ofad324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 06/26/2023] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND This is a systematic review and meta-analysis of diagnostic test accuracy studies to assess the predictive value of both tuberculin skin test (TST) and interferon-gamma release assays (IGRA) for active tuberculosis (TB) among solid organ transplantation (SOT) recipients. METHODS Medline, Embase, and the CENTRAL databases were searched from 1946 until June 30, 2022. Two independent assessors extracted data from studies. Sensitivity analyses were performed to investigate the effect of studies with high or low risk of bias. Methodological quality of each publication was assessed using QUADAS-2. RESULTS A total of 43 studies (36 403 patients) with patients who were screened for latent TB infection (LTBI) and who underwent SOT were included: 18 were comparative and 25 noncomparative (19 TST, 6 QuantiFERON-TB Gold In-Tube [QFT-GIT]). For IGRA tests taken together, positive predictive value (PPV) and negative predictive value (NPV) were 1.2% and 99.6%, respectively. For TST, PPV was 2.13% and NPV was 95.5%. Overall, PPV is higher when TB burden is higher, regardless of test type, although still low in absolute terms. Incidence of active TB was similar between studies using LTBI prophylaxis (mean incidence 1.22%; 95% confidence interval [CI], .2179-2.221) and those not using prophylaxis (mean incidence 1.045%; 95% CI, 0.2731-1.817; P = .7717). Strengths of this study include the large number of studies available from multiple different countries; limitations include absence of gold standard for diagnosis of latent TB and low incidence of active TB. CONCLUSIONS We found both TST and IGRA had a low PPV and high NPV for the development of active TB posttransplant. Further studies are needed to better understand how to prevent active TB in the SOT population.
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Affiliation(s)
- Dafna Yahav
- Infectious Diseases Unit, Sheba Medical Center, Ramat-Gan, Israel
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Melissa R Gitman
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Ili Margalit
- Infectious Diseases Unit, Sheba Medical Center, Ramat-Gan, Israel
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Tomer Avni
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Medicine A, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel
| | - Mariska M G Leeflang
- Department of Epidemiology and Data Science, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Shahid Husain
- Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Canada
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Pediatric Tuberculosis Management: A Global Challenge or Breakthrough? CHILDREN 2022; 9:children9081120. [PMID: 36010011 PMCID: PMC9406656 DOI: 10.3390/children9081120] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 07/19/2022] [Accepted: 07/23/2022] [Indexed: 12/17/2022]
Abstract
Managing pediatric tuberculosis (TB) remains a public health problem requiring urgent and long-lasting solutions as TB is one of the top ten causes of ill health and death in children as well as adolescents universally. Minors are particularly susceptible to this severe illness that can be fatal post-infection or even serve as reservoirs for future disease outbreaks. However, pediatric TB is the least prioritized in most health programs and optimal infection/disease control has been quite neglected for this specialized patient category, as most scientific and clinical research efforts focus on developing novel management strategies for adults. Moreover, the ongoing coronavirus pandemic has meaningfully hindered the gains and progress achieved with TB prophylaxis, therapy, diagnosis, and global eradication goals for all affected persons of varying age bands. Thus, the opening of novel research activities and opportunities that can provide more insight and create new knowledge specifically geared towards managing TB disease in this specialized group will significantly improve their well-being and longevity.
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Lauar ID, Faria LC, Romanelli RMDC, Clemente WT. Latent tuberculosis: Risk factors, screening and treatment in liver transplantation recipients from an endemic area. World J Transplant 2021; 11:512-522. [PMID: 35070787 PMCID: PMC8713304 DOI: 10.5500/wjt.v11.i12.512] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 09/25/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Patients undergoing solid organ transplantation, particularly those who live or have lived in tuberculosis (TB) endemic areas, are at a high risk of developing TB. The majority of post-transplantation TB cases are associated with reactivation of latent TB infection (LTBI). Brazil is in a single position with overlapping areas of high TB endemicity and high transplant activity. In liver transplant (LT), one should be aware of the potential hepatotoxicity associated with the treatment regimens for LTBI.
AIM To evaluate the frequency of LTBI in LT patients and treatment-related issues.
METHODS This was a retrospective analysis of a cohort of cirrhotic patients aged ≥ 18 years, who underwent LT at a high-complexity teaching hospital from January 2005 to December 2012.
RESULTS Overall, 429 patients underwent LT during the study period. Of these, 213 (49.7%) underwent the tuberculin skin test (TST) during the pre-transplant period, and 35 (16.4%) of them had a positive result. The treatment for LTBI was initiated after LT in 12 (34.3%) of the TST-positive patients; in 3 (25.0%), treatment was maintained for at least 6 mo.
CONCLUSION The prevalence of LTBI was lower than expected. Initiation and completion of LTBI treatment was limited by difficulties in the management of these special patients.
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Affiliation(s)
- Isabela Dias Lauar
- Medicine Department, Universidade José do Rosário Vellano, Belo Horizonte 31710030, Minas Gerais, Brazil
| | - Luciana Costa Faria
- Internal Medicine Department, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Roberta Maia de Castro Romanelli
- Pediatrics Department, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Wanessa Trindade Clemente
- Department of Laboratory Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 30130100, Minas Gerais, Brazil
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Friedman DZP, Doucette K. Mycobacteria: Selection of Transplant Candidates and Post-lung Transplant Outcomes. Semin Respir Crit Care Med 2021; 42:460-470. [PMID: 34030207 DOI: 10.1055/s-0041-1727250] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Mycobacterium is a large, clinically relevant bacterial genus made up of the agents of tuberculosis and leprosy and hundreds of species of saprophytic nontuberculous mycobacteria (NTM). Pathogenicity, clinical presentation, epidemiology, and antimicrobial susceptibilities are exceptionally diverse between species. Patients with end-stage lung disease and recipients of lung transplants are at a higher risk of developing NTM colonization and disease and of severe manifestations and outcomes of tuberculosis. Data from the past three decades have increased our knowledge of these infections in lung transplant recipients. Still, there are knowledge gaps to be addressed to further our understanding of risk factors and optimal treatments for mycobacterial infections in this population.
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Affiliation(s)
- Daniel Z P Friedman
- Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.,Division of Infectious Disease, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Karen Doucette
- Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
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Kareem AI, Malan SF, Joubert J. Radical Releasing Anti-Tuberculosis Agents and the Treatment of Mycobacterial Tuberculosis Infections - An Overview. Mini Rev Med Chem 2021; 22:387-407. [PMID: 33605858 DOI: 10.2174/1389557521666210219161045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 01/19/2021] [Accepted: 01/19/2021] [Indexed: 11/22/2022]
Abstract
The treatment and management of tuberculosis (TB) is a major global concern. Approved drugs for the treatment of TB to date displayed various modes of action which can be grouped into radical releasing and non-radical releasing anti TB agents. Radical releasing agents are of special interest because they diffuse directly into the mycobacterium cell wall, interact with the host cell DNA causing DNA strand breakages and fatal destabilization of the DNA helix inhibiting nucleic acid synthase. As a therapeutic agent with aforementioned activity, nitroimidazoles and most especially bicyclic nitroimidazoles are currently in clinical use for the treatment of tuberculosis. However, the approved drugs, pretomanid (PR) and delamanid (DE) are limited in their nitric oxide radical (NO•) releasing abilities to cause effective bactericidity. It is believed that their bactericidal activity can be improved by harnessing alternative strategies to increase NO• release. The last decade has witness the strategic inclusion of NO-donors into native drugs to improve their activities and/or reverse resistance. The rationale behind this strategy is the targeting of NO• release at specific therapeutic sites. This review therefore aims to highlight various radical releasing agents that may be effective in the treatment of TB. The review also investigates various structural modification to PR and DE and suggests alternative strategies to improve NO• release as well as some applications where NO-donor hybrid drugs have been used with good therapeutic effect.
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Affiliation(s)
- Afeez I Kareem
- Department of Pharmaceutical Chemistry, Faculty of Natural Sciences, University of the Western Cape, Private Bag X17, Bellville 7535. South Africa
| | - Sarel F Malan
- Department of Pharmaceutical Chemistry, Faculty of Natural Sciences, University of the Western Cape, Private Bag X17, Bellville 7535. South Africa
| | - Jacques Joubert
- Department of Pharmaceutical Chemistry, Faculty of Natural Sciences, University of the Western Cape, Private Bag X17, Bellville 7535. South Africa
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Shu CC, Tsai MK, Lin SW, Wang JY, Yu CJ, Lee CY. Latent Tuberculosis Infection Increases in Kidney Transplantation Recipients Compared With Transplantation Candidates: A Neglected Perspective in Tuberculosis Control. Clin Infect Dis 2020; 71:914-923. [PMID: 32620949 PMCID: PMC7428385 DOI: 10.1093/cid/ciz851] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2019] [Accepted: 06/30/2020] [Indexed: 01/18/2023] Open
Abstract
Background The prevalence and incidence of latent tuberculosis infection (LTBI) in patients with kidney transplantation remain unclear. Methods In this prospective study, we enrolled kidney transplantation candidates (KTCs) and recipients (KTRs) from 2014 to 2018. We defined LTBI as a positive result of QuantiFERON-TB Gold In-tube (QFT). We analyzed the predictors for LTBI acquisition and followed up on QFT assay test for 2 years among those initially without LTBI. Results Of 425 patients enrolled, 305 (71.8%) patients belonged to the KTC group and 120 (28.2%) to the KTR group. The initial QFT showed positive results in 32 (10.5%) and 24 (20.0%) patients in the KTC and KTR groups, respectively (P = .009). The QFT response value in patients with LTBI was higher in the KTR group than in the KTC group (1.85 vs 1.06 IU/mL, P = .046). Multivariate logistic regression showed that old age, absence of bacillus Calmette–Guérin (BCG) scar, presence of donor-specific antibody, and KTR group were independent factors for positive LTBI. For participants with initial negative QFT, positive QFT conversion within a 2-year follow-up was higher after kidney transplantation (20%) than in KTCs (5.5%) (P = .034). Conclusions This study is the first cohort to follow up LTBI status in patients with kidney transplantation and shows its higher prevalence and incidence in KTRs. It indicates that surveillance of LTBI after renal transplantation is important. In addition to status of kidney transplantation, old age, no BCG vaccination, and positive donor-specific antibody are also positive predictors for LTBI.
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Affiliation(s)
- Chin-Chung Shu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Meng-Kun Tsai
- College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Surgery, National Taiwan University Hospital, Taipei
| | - Shu-Wen Lin
- Graduate Institute of Clinical Pharmacy, National Taiwan University, Taipei, Taiwan
| | - Jann-Yuan Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chong-Jen Yu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chih-Yuan Lee
- College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Surgery, National Taiwan University Hospital, Taipei.,Center of Precision Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
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Yang A, Shi J, Luo Y, Ye Y, Tan Y, Huang H, Zhao Y. Allo-HSCT recipients with invasive fungal disease and ongoing immunosuppression have a high risk for developing tuberculosis. Sci Rep 2019; 9:20402. [PMID: 31892702 PMCID: PMC6938515 DOI: 10.1038/s41598-019-56013-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Accepted: 12/05/2019] [Indexed: 12/24/2022] Open
Abstract
Patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at high risk of acquiring tuberculosis (TB) due to a status of immunosuppression. We conducted a nested case control study to investigate the incidence and risk factors for TB after allo-HSCT. Between 2012 and 2017, 730 consecutive allo-HSCT recipients were enrolled, and 14 patients (1.92%) were diagnosed with TB. Relatively, 54 allo-HSCT recipients were selected as control. Patients who suffered TB had a significantly higher 3-year non-relapse mortality rate than the control group (30.36% vs 5.39%, P < 0.01). In multivariate analysis, invasive fungal disease (HR 4.87, 95% CI 1.39–17.09), treatment with a relatively high dose of prednisone (HR 10.34, 95% CI 1.12–95.47) and treatment with tacrolimus (HR 4.79, 95% CI 1.18–19.44) were identified independent risk factors for TB occurrence post allo-HSCT (P < 0.05). Meanwhile, donor type, dose and type of anti-thymocyte globulin (ATG) administrated, as well as treatment intensity, did not alter the incidence of TB. Therefore, allo-HSCT recipients with unexplained fever, especially those who suffer from invasive fungal disease and ongoing immunosuppression with a relatively high dose of prednisone or tacrolimus, are at a high-risk of developing active TB. Closely Monitoring TB occurrence, making a timely diagnosis and administering the proper treatment may be beneficial to those high-risk patients.
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Affiliation(s)
- Apeng Yang
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, 310003, China.,Department of Hematology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China
| | - Jimin Shi
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, 310003, China
| | - Yi Luo
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, 310003, China
| | - Yishan Ye
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, 310003, China
| | - Yamin Tan
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, 310003, China
| | - He Huang
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China. .,Institute of Hematology, Zhejiang University, Hangzhou, 310003, China.
| | - Yanmin Zhao
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China. .,Institute of Hematology, Zhejiang University, Hangzhou, 310003, China.
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12
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Abad CL, Razonable RR. Prevention and treatment of tuberculosis in solid organ transplant recipients. Expert Rev Anti Infect Ther 2019; 18:63-73. [PMID: 31826668 DOI: 10.1080/14787210.2020.1704255] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Introduction: Tuberculosis (TB) in solid organ transplant (SOT) recipients is associated with significant morbidity and mortality. Its management in transplant recipients is difficult and highly complex, given the underlying immunosuppression and the risks of drug-drug interactions imposed by immunosuppressive drugs that are needed to maintain the transplant allograft.Areas covered: We provide a brief review of TB in SOT and discuss the clinical indications, mechanisms of action and drug resistance, drug-drug interactions, and adverse effects of anti-TB drugs. We provide a summary of recent clinical trials, which serve as the foundation for current recommendations. We further include relevant updates on new agents being evaluated for clinical use in TB management.Expert commentary: TB causes significant morbidity in SOT recipients. The drugs used in the treatment for latent TB and active disease in SOT are similar to the regimens used in the general population. However, TB disease in transplant recipients is more difficult to manage because of the potential for hepatotoxicity and the complex drug-drug interactions with immunosuppressive drugs. We believe that alternative regimens suited for the vulnerable transplant population, and more therapeutic drug options are needed given the adverse toxicities associated with currently approved anti-TB drugs.
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Affiliation(s)
- Cybele L Abad
- Section of Infectious Diseases, University of the Philippines-Manila, Philippine General Hospital, Manila, Philippines
| | - Raymund R Razonable
- Division of Infectious Diseases, Department of Medicine, The William J. Von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, USA
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13
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Harries AD, Kumar AMV, Satyanarayana S, Takarinda KC, Timire C, Dlodlo RA. Treatment for latent tuberculosis infection in low- and middle-income countries: progress and challenges with implementation and scale-up. Expert Rev Respir Med 2019; 14:195-208. [PMID: 31760848 DOI: 10.1080/17476348.2020.1694907] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Introduction: Treatment of latent tuberculosis infection (LTBI) is a crucial but neglected component of global tuberculosis control. The 2018 United Nations High-Level Meeting committed world leaders to provide LTBI treatment to at least 30 million people, including 4 million children<5 years, 20 million other household contacts and 6 million HIV-infected people by 2022.Areas covered: This review searched MEDLINE between 1990 and 2019 and discussed: i) high-risk groups to be prioritized for diagnosis and treatment of LTBI; ii) challenges with diagnosing LTBI in programmatic settings; iii) LTBI treatment options including isoniazid monotherapy, shorter regimens (rifampicin-monotherapy, rifampicin-isoniazid and rifapentine-isoniazid) and treatments for contacts of drug-resistant patients; iv) issues with programmatic scale-up of treatment including policy considerations, ruling out active TB, time to start treatment, safety, uninterrupted drug supplies and treatment adherence; and v) recording and reporting.Expert opinion: In 2017, <1.5 million persons were reported to be treated for LTBI. This must rapidly increase to 6 million persons annually. If HIV programs focus on HIV-infected people already accessing or about to start antiretroviral therapy and TB programs focus on household contacts, these targets could be achieved. Isoniazid remains the current treatment of choice although shorter courses of rifapentine-isoniazid are possible alternatives.
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Affiliation(s)
- Anthony D Harries
- The Centre for Operational Research, International Union Against Tuberculosis and Lung Disease, Paris, France.,Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
| | - Ajay M V Kumar
- The Centre for Operational Research, International Union Against Tuberculosis and Lung Disease, Paris, France.,South-East Asia Office, International Union Against Tuberculosis and Lung Disease, New Delhi, India.,Yenepoya Medical College, Yenepoya (Deemed to be University), Mangalore, India
| | - Srinath Satyanarayana
- The Centre for Operational Research, International Union Against Tuberculosis and Lung Disease, Paris, France.,South-East Asia Office, International Union Against Tuberculosis and Lung Disease, New Delhi, India
| | - Kudakwashe C Takarinda
- The Centre for Operational Research, International Union Against Tuberculosis and Lung Disease, Paris, France.,AIDS and TB Department, Ministry of Health and Child Care, Harare, Zimbabwe
| | - Collins Timire
- The Centre for Operational Research, International Union Against Tuberculosis and Lung Disease, Paris, France.,AIDS and TB Department, Ministry of Health and Child Care, Harare, Zimbabwe
| | - Riitta A Dlodlo
- TB Department, International Union Against Tuberculosis and Lung Disease, Paris, France
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14
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Abad CLR, Deziel PJ, Razonable RR. Treatment of latent TB Infection and the risk of tuberculosis after solid organ transplantation: Comprehensive review. Transpl Infect Dis 2019; 21:e13178. [PMID: 31541575 DOI: 10.1111/tid.13178] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Revised: 08/27/2019] [Accepted: 09/14/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND Mycobacterium tuberculosis disease may occur after treatment of latent TB infection (LTBI). Prompted by a case of reactivation TB disease in a solid organ transplant (SOT) recipient who received LTBI treatment, we reviewed the literature to examine outcomes, adverse effects, resistance, and treatment choices of tuberculosis after LTBI therapy. METHODS MEDLINE and Web of Science from inception to 5/2019 were reviewed using key words "latent tuberculosis infection" and "SOT" or "transplantation." The search yielded nine cases, 41 cohort studies and six randomized controlled trials (RCT). RESULTS Cohort and RCT demonstrated significant reduction in TB disease among transplanted patients who received LTBI therapy; only 56/2651 (2.1%) SOT patients developed TB after LTBI therapy. Adverse drug reactions occurred in 149/1148 (12.9%) and 73/641 (11.4%) of cohort and RCT patients, respectively. Among liver recipients, 56/266 (21%) developed side effects, of which half (29/56, 51.8%) was INH-related. There was no reported INH resistance. CONCLUSIONS Latent TB infection treatment is efficacious in SOT recipients at risk of TB disease. However, tuberculosis may still occur despite LTBI treatment. Hepatotoxicity associated with LTBI therapy is infrequent, although more commonly observed among liver recipients.
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Affiliation(s)
- Cybele Lara R Abad
- Section of Infectious Diseases, Department of Medicine, Philippine General Hospital, University of the Philippines, Manila, Philippines
| | - Paul J Deziel
- Division of Infectious Diseases, Department of Medicine, The William J Von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic College of Medicine and Sciences, Rochester, MN, USA
| | - Raymund R Razonable
- Division of Infectious Diseases, Department of Medicine, The William J Von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic College of Medicine and Sciences, Rochester, MN, USA
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15
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Silva JT, San-Juan R, Fernández-Ruiz M, Aguado JM. Fluoroquinolones for the treatment of latent Mycobacterium tuberculosis infection in liver transplantation. World J Gastroenterol 2019; 25:3291-3298. [PMID: 31341356 PMCID: PMC6639553 DOI: 10.3748/wjg.v25.i26.3291] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 05/30/2019] [Accepted: 06/08/2019] [Indexed: 02/06/2023] Open
Abstract
Solid organ transplantation (SOT) is the best treatment option for end-stage organ disease. Newer immunosuppressive agents have reduced the incidence of graft rejection but have increased the risk of infection, particularly due to the reactivation of latent infections due to opportunistic agents such as Mycobacterium tuberculosis. Active tuberculosis (TB) after SOT is a significant cause of morbidity and mortality. Most cases of posttransplant TB are secondary to reactivation of latent tuberculosis infection (LTBI) due to the effects of long-term immunosuppressive therapy. Risk minimization strategies have been developed to diagnose LTBI and initiate treatment prior to transplantation. Isoniazid with vitamin B6 supplementation is the treatment of choice. However, liver transplantation (LT) candidates and recipients have an increased risk of isoniazid-induced liver toxicity, leading to lower treatment completion rates than in other SOT populations. Fluoroquinolones (FQs) exhibit good in vitro antimycobacterial activity and a lower risk of drug-induced liver injury than isoniazid. In the present review, we highlight the disease burden posed by posttransplant TB and summarize the emerging clinical evidence supporting the use of FQs for the treatment of LTBI in LT recipients and candidates.
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Affiliation(s)
- Jose Tiago Silva
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Hospital “12 de Octubre” (imas12), School of Medicine, Universidad Complutense, Madrid 28041, Spain
| | - Rafael San-Juan
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Hospital “12 de Octubre” (imas12), School of Medicine, Universidad Complutense, Madrid 28041, Spain
| | - Mario Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Hospital “12 de Octubre” (imas12), School of Medicine, Universidad Complutense, Madrid 28041, Spain
| | - José María Aguado
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Hospital “12 de Octubre” (imas12), School of Medicine, Universidad Complutense, Madrid 28041, Spain
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16
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Incidence, Outcomes, and Long-term Immune Response to Tuberculosis in Organ Transplant Recipients. Transplantation 2019; 103:210-215. [PMID: 29944616 DOI: 10.1097/tp.0000000000002340] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
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.
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17
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Latent Tuberculosis Infection among Healthcare Workers in Duhok Province: From Screening to Prophylactic Treatment. Trop Med Infect Dis 2019; 4:tropicalmed4020085. [PMID: 31126022 PMCID: PMC6631700 DOI: 10.3390/tropicalmed4020085] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 05/17/2019] [Accepted: 05/20/2019] [Indexed: 11/16/2022] Open
Abstract
Healthcare workers (HCWs) are at increased risk of infection with Mycobacterium tuberculosis (Mtb) and, hence, of developing tuberculosis (TB) disease. The aims of this study are to identify the prevalence and determinants of latent TB infection (LTBI) among HCWs in Duhok Province. This is a cross-sectional prospective study conducted during April–July 2018 in different health care facilities of Duhok province. HCWs at multiple levels were selected by a non-systematic random sampling method. Information on demographic and associated risk factors of LTBI were collected by using a standardized questionnaire. Thereafter, all HCWs underwent QuantiFERON Gold Plus (QFT-Plus) assay. HCWs with indeterminate QFT-Plus underwent a Tuberculin Skin Test. HCWs with positive results were further evaluated by smear microscopy investigation and chest X-ray examination. Three hundred ninety-five HCWs were enrolled; 49 (12%) tested positive for LTBI. The mean age of the HCWs was 33.4 ± 9.25 with a female predominance (51.1%). According to the univariate analysis, LTBI was significantly higher among HCWs with the following: age groups ≥ 30 years, alcohol intake, ≥ 11 years of employment, high risk stratification workplaces, and medical doctors. In the multivariate analysis, the age group of 30–39 years (OR = 0.288, 95% CI: 0.105–0.794, p value = 0.016) was the only risk factor associated with LTBI. Further medical investigations did not reveal active TB cases among HCWs with LTBI. With regards to prophylactic treatment, 31 (63.3%) LTBI HCWs accepted the treatment, whereas 18 (36.7%) declined the chemoprophylaxis. Of these 31 HCWs on chemoprophylaxis, 12 (38.7%) received isoniazid (INH) for six months, 17 (54.8%) received INH in combination with rifampicin (RMP) for three months, and two (6.5%) received alternative therapy because of anti-TB drug intolerance. In conclusions, although Iraq is a relatively high TB burden country, the prevalence of LTBI among Duhok HCWs is relatively low. It is important to screen HCWs in Duhok for LTBI, particularly medical doctors, young adults, alcoholics, and those whom had a long duration of employment in high-risk workplaces. The acceptance rate of HCWs with LTBI to chemoprophylaxis was low. Therefore, ensuring medical efforts to educate the healthcare staff particularly, non-professionals are a priority to encourage chemoprophylaxis acceptance.
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18
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Interferon-gamma release assay for tuberculosis screening of solid-organ transplant recipients is cost-effective. J Infect 2019; 78:58-65. [DOI: 10.1016/j.jinf.2018.07.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2018] [Revised: 05/12/2018] [Accepted: 07/06/2018] [Indexed: 01/28/2023]
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19
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Obeid KM, Hassan MA, Chinnakotla S, Young JH. Genitourinary Tract Infection Due to Mycobacterium avium intracellulare Complex Infection in Pretransplant Setting With Recurrence Following Transplant: A Case Report. Transplant Proc 2018; 50:3937-3939. [PMID: 30577290 DOI: 10.1016/j.transproceed.2018.09.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 09/05/2018] [Indexed: 11/26/2022]
Abstract
Genitourinary (GU) tract infection with Mycobacterium avium intracellulare complex (MAI) is very rare and, to our knowledge, has never been reported in the solid organ transplant literature. CASE DESCRIPTION: A 61-year-old Somali-born woman had a history of liver cirrhosis due to chronic hepatitis C infection. She was diagnosed as having and treated for latent tuberculosis infection and GU tract infection due to MAI. She received a total of 17 months antimycobacterial therapy consisting of azithromycin, ethambutol, and moxifloxacin. Within 5 months of the initiation of antimicrobial therapy, there was documented sterilization of urine mycobacterial cultures. Liver and kidney transplant was performed 3 months after finishing the treatment course. One year following transplant, GU tract infection due to MAI recurred. She declined further diagnostic testing as well as mycobacterial therapy. She died 15 months following transplant for reasons not related to infections. CONCLUSION: The treatment of MAI infection in solid organ transplant candidates and recipients is challenging, and the duration of therapy in this population is not known. The recurrence of infection following transplant in this case may argue in favor of a duration that extends beyond the date of transplant. The combination of a fluoroquinolone and ethambutol may successfully prevent reactivation of tuberculosis in patients with history of latent tuberculosis infection and deserves further evaluation.
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Affiliation(s)
- K M Obeid
- Program in Adult Transplant Infectious Disease, Division of Infectious Disease and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
| | - M A Hassan
- Division of Gastroenterology, Department of Medicine, University of Minnesota, Minneapolis, Minnesota
| | - S Chinnakotla
- Division of Transplantation, Department of Surgery, University of Minnesota, Minneapolis, Minnesota
| | - J H Young
- Program in Adult Transplant Infectious Disease, Division of Infectious Disease and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota
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20
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Jung BH, Park JI, Lee SG. Urgent Living-Donor Liver Transplantation in a Patient With Concurrent Active Tuberculosis: A Case Report. Transplant Proc 2018; 50:910-914. [PMID: 29661461 DOI: 10.1016/j.transproceed.2018.02.013] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Revised: 01/30/2018] [Accepted: 02/01/2018] [Indexed: 12/26/2022]
Abstract
BACKGROUND Although active tuberculosis (TB) is considered a contraindication for liver transplantation (LT), this is the only treatment in patients with liver failure and concurrent active TB. We report a case with successful urgent living-donor LT for irreversible liver failure in the presence of active TB. CASE PRESENTATION A 48-year-old man, with a history of decompensated alcoholic liver cirrhosis, was presented with stupor. At admission, his consciousness had deteriorated to semi-coma, and his renal function also rapidly deteriorated to hepatorenal syndrome. A preoperative computed tomography scan of the chest revealed several small cavitary lesions in both upper lobes, and acid-fast bacillus stain from his sputum was graded 2+. Adenosine deaminase levels from ascites were elevated, suggesting TB peritonitis. A first-line anti-TB drug regimen was started immediately (rifampin, isoniazid, levofloxacin, and amikacin). An urgent living-donor LT was performed 2 days later. After LT, the regimen was changed to second-line anti-TB drugs (amikacin, levofloxacin, cycloserine, and pyridoxine). The sputum acid-fast bacillus stain tested negative on postoperative day 10. His liver function remained well preserved, even after the reversion to first-line anti-TB treatment. The patient recovered without any anti-TB medication-related complications and was discharged. CONCLUSIONS LT can be prudently performed as a life-saving option, particularly for patients with liver failure and concurrent active TB.
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Affiliation(s)
- B-H Jung
- Department of Surgery, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea
| | - J-I Park
- Department of Surgery, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.
| | - S-G Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, Ulsan University College of Medicine, Seoul, Republic of Korea
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21
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The gastroenterologist's guide to management of the post-liver transplant patient. Am J Gastroenterol 2018; 113:819-828. [PMID: 29748558 DOI: 10.1038/s41395-018-0049-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 02/11/2018] [Indexed: 12/11/2022]
Abstract
The management of the post-liver transplant patient is complex and involves a large interdisciplinary team. After referral to a transplant center, evaluation and listing, and eventual transplantation, the patient is cared for closely by the transplant center. Once deemed ready for discharge, the patient returns to the primary care provider for ongoing management of the various issues that increase in incidence post transplant such as osteoporosis, cardiovascular, and renal diseases, as well as metabolic syndrome. The role of the gastroenterologist is not well defined, but certainly, he or she may be called upon for the initial evaluation and ongoing management of gastrointestinal as well as hepatobiliary issues. This includes but is not limited to the investigation of abnormal liver tests, non-specific gastrointestinal complaints such as nausea, vomiting, or diarrhea, biliary complications, and even recurrent hepatic disease. Having familiarity with post-transplant immunosuppressive agents, drug interactions, and potential infectious and malignancy-related complications of transplant is essential, as the primary gastroenterologist may be expected in some situations to field the initial work-up, if patient access to the transplant center is limited. The aim of this review is to summarize the gastroenterologist's role in the management of the post-liver transplant patient.
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22
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Pennington KM, Kennedy CC, Chandra S, Lauzardo M, Brito MO, Griffith DE, Seaworth BJ, Escalante P. Management and diagnosis of tuberculosis in solid organ transplant candidates and recipients: Expert survey and updated review . J Clin Tuberc Other Mycobact Dis 2018;11:37-46. [PMID: 31720390 PMCID: PMC6830179 DOI: 10.1016/j.jctube.2018.04.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Revised: 04/02/2018] [Accepted: 04/09/2018] [Indexed: 01/07/2023] Open
Abstract
Background : Optimal screening and management of latent tuberculosis infection (LTBI) and active tuberculosis (TB) in solid organ transplant (SOT) candidates and recipients is necessary to prevent morbidity and mortality. Methods : We conducted a cross-sectional survey of TB and transplant experts across the United States reviewing the clinical practice preferences on key management issues related to LTBI and TB in SOT candidates and recipients. Results : Thirty TB and 13 SOT experts were surveyed (response rate = 53.8%). Both groups agreed that tuberculin skin test (TST) and chest x-ray screening in SOT candidates was useful (78.6% and 84.6%, respectively). TST after SOT was not useful for most transplant experts and TB experts (0% vs. 32.1%, respectively), but both groups were split on usefulness of interferon gamma release assays (IGRA) in SOT recipients (42.9% TB experts vs. 46.2% SOT experts). Most experts recommend LTBI treatment prior to SOT if close monitoring is assured (82.1% TB experts vs. 76.9% transplant experts). LTBI treatment with isoniazid was preferred for patients on calcineurin inhibitors. Evaluation for suspected TB in SOT recipients varied, but most TB experts favored sputum testing (88.9%) whereas most transplant experts favored bronchoscopic testing (69.2%). Preferred TB treatment regimens in SOT recipients were similar to regimens recommended for immunocompetent patients. Conclusions : Most TB and transplant experts recommend evaluation and treatment for LTBI in SOT candidates. Liver transplant candidates, however, should only be treated if close monitoring can be assured and after consulting with a hepatologist. Practice preferences varied regarding the initial diagnostic approach for suspected TB in SOT recipients; however, most experts agreed that SOT recipients should receive similar treatments as immunocompetent patients.
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Affiliation(s)
- Kelly M Pennington
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic Rochester, MN, USA.,Robert D. and Patricia E. Center for the Science of Healthcare Delivery, Mayo Clinic Rochester, MN USA
| | - Cassie C Kennedy
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic Rochester, MN, USA.,William J. von Liebig Transplant Center, Mayo Clinic Rochester, MN, USA.,Robert D. and Patricia E. Center for the Science of Healthcare Delivery, Mayo Clinic Rochester, MN USA
| | - Subhash Chandra
- Gastroenterology Section, CHI Health Creighton University Medical Center, Omaha, NE, USA
| | - Michael Lauzardo
- Southeastern National Tuberculosis Center and the Division of Infectious Diseases, University of Florida Health Science Center, Gainesville, FL, USA
| | - Maximo O Brito
- Southeastern National Tuberculosis Center and the Division of Infectious Diseases, University of Florida Health Science Center, Gainesville, FL, USA
| | - David E Griffith
- Section of Infectious Diseases, University of Illinois at Chicago, Chicago, IL, USA
| | - Barbara J Seaworth
- Heartland National TB Center, University of Texas Health Science Center at Tyler, Tyler, TX, USA
| | - Patricio Escalante
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic Rochester, MN, USA.,Mayo Clinic Center for Tuberculosis, Mayo Clinic, Rochester, MN
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23
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Moyses-Neto M, Drumond D, Morgantetti G, Garcia TMP, Bolella VR, Romao EA. Cutaneous and articular tuberculosis in a renal transplant recipient. Rev Soc Bras Med Trop 2017; 50:565-567. [DOI: 10.1590/0037-8682-0090-2016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2016] [Accepted: 04/07/2017] [Indexed: 02/04/2023] Open
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24
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Basera TJ, Ncayiyana J, Engel ME. Prevalence and risk factors of latent tuberculosis infection in Africa: a systematic review and meta-analysis protocol. BMJ Open 2017; 7:e012636. [PMID: 28720611 PMCID: PMC5541490 DOI: 10.1136/bmjopen-2016-012636] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Revised: 08/24/2016] [Accepted: 01/03/2017] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION Latent tuberculosis infection (LTBI) remains a major public health problem and one of the major contributors to the pool of active tuberculosis cases. The true burden of LTBI in Africa is not known. Early modelling studies estimate that over 33% of the world's population is infected with latent tuberculosis. We propose conducting a systematic review and a meta-analysis to evaluate the burden and risk factors of LTBI in Africa reported in studies from 2000 to 2017. METHODS AND ANALYSIS We will include cross-sectional studies, cohort studies and case-control studies estimating either tuberculin skin test (TST) or interferon-gamma release assay (IGRA) confirmed prevalence of LTBI and associated risk factors among people in African countries. A comprehensive search of relevant literature will be conducted on electronic databases using common and medical subject heading (MeSH) terms for LTBI, and an African search filter. Risk of bias will be evaluated by assessing all qualifying full-text articles for quality and eligibility using a quality score assessment tool. Standardised data extraction will be carried out after which prevalence estimates will be pooled using random-effects models in Stata V.13. Where there is sufficient data , subgroup meta-analyses will be conducted by risk factors including participant's age group, occupation, location and HIV status. This systematic review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocols 2015 Statement. ETHICS AND DISSEMINATION No ethical issues were foreseen given that this was a protocol for a systematic review of published studies. The results of this study will be published in a peer-reviewed journal and presented at conferences. TRIAL REGISTRATION NUMBER Systematic review registration: PROSPERO CRD42016037997.
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Affiliation(s)
- Tariro J Basera
- Department of Epidemiology & Biostatistics, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Jabulani Ncayiyana
- Department of Epidemiology & Biostatistics, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Mark E Engel
- Department of Medicine, Faculty of Health Sciences University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa
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McCulloch M, Lin PL. Globalization of pediatric transplantation: The risk of tuberculosis or not tuberculosis. Pediatr Transplant 2017; 21. [PMID: 28160362 DOI: 10.1111/petr.12891] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/04/2017] [Indexed: 12/15/2022]
Abstract
The risk of TB among pediatric SOT recipients increases as the globalization of medical care continues to broaden. Unlike adults, children and especially infants are more susceptible to TB as a complication after transplantation. Little data exist regarding the true incidence of TB and the optimal risk-based management of this very vulnerable population. Here, we highlight the theoretical and practical issues that complicate the management of these patients and pose some questions that should be addressed when managing these patients. More data are needed to provide optimal guidance of the best diagnostic and management practices to this unique population.
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Affiliation(s)
- Mignon McCulloch
- Red Cross War Memorial Children's Hospital, School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa
| | - Philana Ling Lin
- Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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Knoll BM, Nog R, Wu Y, Dhand A. Three months of weekly rifapentine plus isoniazid for latent tuberculosis treatment in solid organ transplant candidates. Infection 2017; 45:335-339. [PMID: 28276008 DOI: 10.1007/s15010-017-1004-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Accepted: 02/28/2017] [Indexed: 01/19/2023]
Abstract
BACKGROUND Isoniazid daily for 9 months is the recommended regimen for latent tuberculosis infection (LTBI) in solid organ transplant (SOT) candidates, but its use is controversial, due to reports of hepatotoxicity and low treatment completion rates. A 12-week course of once weekly directly observed therapy (DOT) with isoniazid plus rifapentine (3HP) is a new LTBI treatment regimen. Tolerability and safety data of 3HP LTBI treatment in SOT candidates are limited. METHODS Twelve consecutive SOT candidates who underwent DOT with 3HP for LTBI at Westchester Medical Center, Valhalla, New York, USA, between January 2013 and August 2016 were prospectively evaluated for tolerability and safety of 3HP. The diagnosis of LTBI was made in a person with a positive interferon-gamma release test, without a history of previously treated active or latent tuberculosis infection, and without signs, symptoms, or radiographic evidence of active tuberculosis. Patients were followed up 1 month after treatment completion and at routine follow-up visits with their transplant providers. RESULTS Eleven patients were men, and the median age was 60 years (range 44-72). Eight patients were liver, and four kidney transplant candidates. The median Model for End-Stage Liver Disease (MELD score) was 17 (range 10-31). All patients completed treatment. Only a single patient developed transaminitis greater than twice the baseline value. Three patients underwent liver transplantation. None of them developed tuberculosis at 9, 22, or 40 months following transplantation. CONCLUSION Directly observed 3HP LTBI treatment was not associated with hepatotoxicity, even in patients with higher MELD scores. Further studies are needed to confirm the safety and efficacy of this LTBI treatment regimen in the SOT population.
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Affiliation(s)
- B M Knoll
- Transplant Infectious Diseases, Westchester Medical Center, 100 Woods Road, BHC-A-Wing LL, Valhalla, NY, 10595, USA. .,New York Medical College, Valhalla, NY, USA.
| | - R Nog
- Transplant Infectious Diseases, Westchester Medical Center, 100 Woods Road, BHC-A-Wing LL, Valhalla, NY, 10595, USA.,New York Medical College, Valhalla, NY, USA
| | - Y Wu
- New York Medical College, Valhalla, NY, USA
| | - A Dhand
- Transplant Infectious Diseases, Westchester Medical Center, 100 Woods Road, BHC-A-Wing LL, Valhalla, NY, 10595, USA.,New York Medical College, Valhalla, NY, USA
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Matteelli A, Sulis G, Capone S, D'Ambrosio L, Migliori GB, Getahun H. Tuberculosis elimination and the challenge of latent tuberculosis. Presse Med 2017; 46:e13-e21. [PMID: 28279508 DOI: 10.1016/j.lpm.2017.01.015] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Accepted: 01/17/2017] [Indexed: 12/18/2022] Open
Abstract
Latent tuberculosis infection (LTBI) affects one third to one fourth of the human population and is the reservoir for a significant proportion of emerging active tuberculosis (TB) cases, especially in low incidence countries. The World Health Organization launched in 2015 the END-TB strategy that aims at TB elimination and promotes, for the first time ever, the management of LTBI. The preventive package, basically consisting of testing and treatment for LTBI in groups at high risk of reactivation, is a mainstay of the first pillar of the strategy, alongside prompt diagnosis and early treatment of both drug-susceptible and drug-resistant TB disease. Testing and treatment for LTBI should be pursued with a programmatic perspective. This implies strong political commitment, adequate funding and an effective monitoring and evaluation system. People living with HIV and children under five years of age who are household contact of a contagious TB cases are primarily targeted in all epidemiological setting. In high resource and low incidence setting, additional at risk populations should also be the target for systematic LTBI testing and treatment. Research is urgently needed to develop diagnostic tests with higher predictive value to identify individuals that progress from infection to disease. Similarly, shorter and safer treatment regimens are needed to make the trade-off between potential benefits and harms more favourable for an increasing proportion of infected individuals.
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Affiliation(s)
- Alberto Matteelli
- University of Brescia, WHO Collaborating Centre for TB/HIV co-infection and TB Elimination, Department of Infectious and Tropical Diseases, Brescia, Italy.
| | - Giorgia Sulis
- University of Brescia, WHO Collaborating Centre for TB/HIV co-infection and TB Elimination, Department of Infectious and Tropical Diseases, Brescia, Italy
| | - Susanna Capone
- University of Brescia, WHO Collaborating Centre for TB/HIV co-infection and TB Elimination, Department of Infectious and Tropical Diseases, Brescia, Italy
| | - Lia D'Ambrosio
- Maugeri Care and Research Institute, WHO Collaborating Centre for Tuberculosis and Lung Diseases, Tradate, Italy; Public Health Consulting Group, Lugano, Switzerland
| | - Giovanni Battista Migliori
- Maugeri Care and Research Institute, WHO Collaborating Centre for Tuberculosis and Lung Diseases, Tradate, Italy
| | - Haileyesus Getahun
- World Health Organization, Global Tuberculosis Programme, Geneva, Switzerland
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Kiazyk S, Ball TB. Latent tuberculosis infection: An overview. CANADA COMMUNICABLE DISEASE REPORT = RELEVE DES MALADIES TRANSMISSIBLES AU CANADA 2017; 43:62-66. [PMID: 29770066 PMCID: PMC5764738 DOI: 10.14745/ccdr.v43i34a01] [Citation(s) in RCA: 110] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Latent tuberculosis infection (LTBI) is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens without evidence of clinically manifested active tuberculosis (TB) disease. Individuals with LTBI represent a reservoir for active TB cases. The detection and management of LTBI is now a key component of the World Health Organization's End TB Strategy and the Government of Canada's federal framework for action on TB prevention and control. This is because people with LTBI can progress to active TB or undergo reactivation, a risk that is greatly increased in those with immunocompromising conditions. This overview provides a summary of LTBI and reactivation risk, as well as the recent advances in the diagnosis and treatment of LTBI.
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Affiliation(s)
- S Kiazyk
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB
- Department of Medical Microbiology, University of Manitoba, Winnipeg, MB
| | - TB Ball
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB
- Department of Medical Microbiology, University of Manitoba, Winnipeg, MB
- Department of Immunology, University of Manitoba, Winnipeg, MB
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Guirao-Arrabal E, Santos F, Redel-Montero J, Vaquero JM, Cantisán S, Vidal E, Torre-Giménez Á, Rivero A, Torre-Cisneros J. Risk of tuberculosis after lung transplantation: the value of pretransplant chest computed tomography and the impact of mTOR inhibitors and azathioprine use. Transpl Infect Dis 2016; 18:512-9. [PMID: 27224905 DOI: 10.1111/tid.12555] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Revised: 01/16/2016] [Accepted: 02/29/2016] [Indexed: 01/24/2023]
Abstract
BACKGROUND It is necessary to determine the incidence and risk factors for tuberculosis (TB), as well as strategies to assess and treat latent tuberculosis infection (LTBI) in lung transplant recipients. METHODS A retrospective cohort study of 398 lung transplant recipients was performed. Episodes of TB were studied and the incidence rate was calculated. Logistic regression analysis was used to analyze specific variables as potential risk factors for TB. RESULTS Median follow-up was 558 days (range 1-6636). Six cases (1.5%) of TB were documented in 398 transplant patients. The incidence density of TB was 406.3 cases/10(5) patient-years (95% confidence interval [CI] 164.7-845), which is higher than in the general population (13.10 cases/10(5) person-years). All cases occurred in the period 1993-2006, when the tuberculin skin test (TST) and treatment of LTBI in positive TST patients were not part of the protocol. Pretransplant computed tomography (CT) showed residual lesions in 50% of patients who developed TB, although the TST was negative and the chest radiograph was inconclusive. Multivariate analysis identified the presence of residual lesions in the pretransplant chest CT (odds ratio [OR] 11.5, 95% CI 1.9-69.1, P = 0.008), use of azathioprine (OR 10.6, 95% CI 1.1-99.1, P = 0.038), and use of everolimus (OR 6.7, 95% CI 1.1-39.8, P = 0.036) as independent risk factors for TB. CONCLUSIONS Residual lesions in the pretransplant chest CTs and the use of azathioprine and mTOR inhibitors are associated with the risk of TB.
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Affiliation(s)
- E Guirao-Arrabal
- Infectious Diseases Unit, Hospital Universitario Reina Sofía, Córdoba, Spain.,Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Córdoba, Spain
| | - F Santos
- Thoracic Surgery and Lung Transplantation Unit, Hospital Universitario Reina Sofía, Córdoba, Spain
| | - J Redel-Montero
- Thoracic Surgery and Lung Transplantation Unit, Hospital Universitario Reina Sofía, Córdoba, Spain
| | - J M Vaquero
- Thoracic Surgery and Lung Transplantation Unit, Hospital Universitario Reina Sofía, Córdoba, Spain
| | - S Cantisán
- Infectious Diseases Unit, Hospital Universitario Reina Sofía, Córdoba, Spain.,Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Córdoba, Spain
| | - E Vidal
- Infectious Diseases Unit, Hospital Universitario Reina Sofía, Córdoba, Spain.,Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Córdoba, Spain
| | - Á Torre-Giménez
- Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Córdoba, Spain
| | - A Rivero
- Infectious Diseases Unit, Hospital Universitario Reina Sofía, Córdoba, Spain.,Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Córdoba, Spain
| | - J Torre-Cisneros
- Infectious Diseases Unit, Hospital Universitario Reina Sofía, Córdoba, Spain.,Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Córdoba, Spain
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Infectious Considerations in the Pre-Transplant Evaluation of Cirrhotic Patients Awaiting Orthotopic Liver Transplantation. Curr Infect Dis Rep 2016; 18:4. [PMID: 26743200 DOI: 10.1007/s11908-015-0514-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The incidence of end-stage liver disease (ESLD) is increasing and many of these patients may be considered for orthotopic liver transplantation. As patients with ESLD are at risk of a number of infections, infectious disease physicians should be aware of the management of these infections in order to provide optimal patient care and ensure transplantation success. We present a review of the literature pertaining to infectious disease considerations in the liver transplant candidate. It highlights several topics with recent developments including the management of hepatitis C virus infection prior to transplantation, treatment of hepatitis B virus infection, colonization and infection with multidrug resistant organisms, and management of spontaneous bacterial peritonitis.
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Grim SA, Layden JE, Roth P, Gallitano S, Adams W, Clark NM. Latent tuberculosis in kidney and liver transplant patients: a review of treatment practices and outcomes. Transpl Infect Dis 2015; 17:768-77. [PMID: 26263530 DOI: 10.1111/tid.12436] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2015] [Revised: 04/20/2015] [Accepted: 07/26/2015] [Indexed: 12/17/2022]
Abstract
BACKGROUND The standard treatment of latent tuberculosis infection (LTBI) is associated with toxicities and data are limited on tolerability among patients with advanced organ disease listed for transplant. Alternate options are available, but they have yet to be studied in this population. METHODS A retrospective review of the treatment of LTBI among kidney and/or liver transplant candidates was conducted to assess factors impacting therapy initiation, tolerability, and completion of therapy. RESULTS Of 174 eligible patients, treatment of LTBI was initiated in 129, of which 91 were listed for kidney transplant and 38 were listed for liver or liver/kidney transplant. Infectious Diseases consultation was independently associated with treatment initiation when controlling for waitlisted organ and receipt of hemodialysis (odds ratio [OR] 81.14, 95% confidence interval [CI] 23.94-274.94, P < 0.001). Documented completion of first-line therapy was 47% overall, and 49% and 39%, respectively, among kidney and liver/kidney candidates (P = not significant). On multivariable analysis, controlling for baseline aspartate aminotransferase and waitlisted organ, first-line receipt of rifampin was associated with lower rates of treatment completion (OR 0.19, 95% CI 0.05-0.77, P = 0.02). CONCLUSION Based on medical record documentation, completion of first-line therapy was <50% in this cohort, although this is likely an underestimate, as 34% of patients had no chart documentation that therapy was completed. Approximately 20% of patients did not complete first-line therapy because of adverse effects.
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Affiliation(s)
- S A Grim
- Department of Medicine, Loyola University Medical Center, Maywood, Illinois, USA.,Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, Illinois, USA
| | - J E Layden
- Department of Medicine, Loyola University Medical Center, Maywood, Illinois, USA.,Department of Public Health Sciences, Loyola University Chicago, Maywood, Illinois, USA
| | - P Roth
- Department of Medicine, Greenville Health System, Greenville, South Carolina, USA
| | - S Gallitano
- SUNY Downstate Medical Center, Brooklyn, New York, USA
| | - W Adams
- Department of Public Health Sciences, Loyola University Chicago, Maywood, Illinois, USA
| | - N M Clark
- Department of Medicine, Loyola University Medical Center, Maywood, Illinois, USA
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Liu J, Yan J, Wan Q, Ye Q, Huang Y. The risk factors for tuberculosis in liver or kidney transplant recipients. BMC Infect Dis 2014; 14:387. [PMID: 25015108 PMCID: PMC4227141 DOI: 10.1186/1471-2334-14-387] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Accepted: 07/03/2014] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Liver or kidney transplant recipients are at a higher risk of developing tuberculosis (TB) than general population. We aimed to clarify the incidence density of and risk factors for TB in liver or kidney transplant recipients in the present study. METHODS All patients with TB following liver or kidney transplantation were investigated retrospectively at the Third Xiangya Hospital, Central South University, Changsha, China. The incidence density of TB was calculated. We performed a nested case-control study (1:1) to investigate by univariate and multivariate logistic regression analysis the potential risk factors for TB. RESULTS From January 2000 to August 2013, 1748 kidney and 166 liver transplant recipients were performed at a university teaching hospital. Among the 1914 recipients, 45 cases (2.4%) of TB were reported. The incidence density was 506 cases per 105 patient-years in kidney or liver transplant recipients, which was 7 times higher than in the general Chinese population (around 70 cases per 105 person-years). The median time to develop TB was 20.0 months (interquartile ratio: 5.0-70.0). The receipt of a graft from a cadaveric donor (odds ratio [OR] = 3.7; 95% confidence interval [CI] = 1.4-10.0; P = 0.010) and the preoperative evidence of latent TB (OR = 6.8; 95% CI = 2.0-22.7; P = 0.002) were identified as two risk factors for developing TB in liver or kidney transplant recipients. CONCLUSIONS The incidence density of TB among liver or kidney transplant recipients was much higher than in the general Chinese population. Recipients receiving a graft from a cadaveric donor and the preoperative evidence of latent TB were two major risk factors for developing TB in liver or kidney transplant recipients.
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Affiliation(s)
| | | | - Qiquan Wan
- Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
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