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1
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Muzanyi G, Bark CM. Severe Tuberculosis. Med Clin North Am 2025; 109:641-650. [PMID: 40185552 DOI: 10.1016/j.mcna.2024.12.001] [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] [Indexed: 04/07/2025]
Abstract
The global tuberculosis (TB) pandemic continues despite living in the era of the greatest advances in human medicine. Severe TB in the form of meningitis and miliary TB kills and disables people around the world every day. It disproportionately affects the most vulnerable populations, especially children. Diagnosis and treatment are challenging, and most have poor outcomes, often never receiving treatment at all. Dedicated TB researchers continue to make improvements in the management of severe TB, but the long-term success will require a global commitment to improving health care for poor people around the world.
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Affiliation(s)
- Grace Muzanyi
- Uganda-Case Western Reserve University Research Collaboration, PO Box 663, Kampala, Uganda
| | - Charles M Bark
- Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
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2
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Santoro-Lopes G, Clemente WT. Quantiferon Indeterminate Results: Understanding Their Impact on Tuberculosis Screening for SOT Candidates. Transplantation 2025; 109:584-585. [PMID: 39375896 DOI: 10.1097/tp.0000000000005238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/09/2024]
Affiliation(s)
- Guilherme Santoro-Lopes
- Infectious Diseases Department, Faculdade de Medicina, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Transplant Infections Consultant, Infectious Diseases Clinic, Hospital Universitário Clementino Fraga Filho, UFRJ, Rio de Janeiro, Brazil
| | - Wanessa Trindade Clemente
- Department of Laboratory Medicine, Faculdade de Medicina da Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
- Liver Transplant Program, Transplant Infectious Diseases, Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG/EBSERH), Belo Horizonte, Brazil
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3
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Kumar J, Nagaraju SP, Saravu K, Rangaswamy D. Report of renal allograft tuberculosis a decade after transplant: challenges in diagnosis and management. CEN Case Rep 2025; 14:61-64. [PMID: 38926296 PMCID: PMC11785852 DOI: 10.1007/s13730-024-00904-z] [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: 06/19/2023] [Accepted: 06/15/2024] [Indexed: 06/28/2024] Open
Abstract
Post-transplant infections constitute an important cause of morbidity and mortality in renal transplant recipients worldwide. Tuberculosis (TB) contributes significantly to this burden in endemic countries, such as India. We report a case of renal allograft TB, 10 years post-transplantation, diagnosed during a routine outpatient visit. An asymptomatic rise in serum creatinine level and a 6 month history of immunosuppressive drug non-compliance prompted evaluation of graft dysfunction. Biopsy of the renal allograft tissue suggested chronic active antibody mediated rejection with epithelioid granulomas in the interstitium. Guided by kidney biopsy, further testing with urine acid fast bacilli and urinary GeneXpert yielded positive results for TB. Treatment of TB was further complicated by the development of anti-tubercular therapy induced hepatitis and immune reconstitution inflammatory syndrome, which were managed with the reintroduction regimen and escalation of steroid dose, respectively. Our case highlights the atypical presentation and challenges in managing patients with TB in a post-renal transplant setting.
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Affiliation(s)
- Joy Kumar
- Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, India
| | - Shankar Prasad Nagaraju
- Department of Nephrology, Kasturba Hospital and Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, India
| | - Kavitha Saravu
- Department of Infectious Diseases, Kasturba Hospital and Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, India
| | - Dharshan Rangaswamy
- Department of Nephrology, Kasturba Hospital and Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, India.
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4
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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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5
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Loaiza-Oliva M, Gamarra S, Agusti J, Gaite L, Paladini JH, Martínez V, Arriola M, Gaite JA, Garcia-Effron G. High histoplasmosis incidence in kidney transplant recipients in Santa Fe city, Argentina. Med Mycol 2024; 62:myae099. [PMID: 39537196 DOI: 10.1093/mmy/myae099] [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: 08/09/2024] [Accepted: 11/12/2024] [Indexed: 11/16/2024] Open
Abstract
Histoplasmosis is endemic in the central/northeast region of Argentina. It is estimated that the incidence of this mycosis is low in solid organ transplant recipients. This work aims to describe the epidemiology, clinical forms, and evolution of kidney transplant recipients diagnosed with histoplasmosis in Santa Fe city, Argentina. A retrospective study was carried out between 2015 and 2020 on kidney transplant patients with symptoms associated with histoplasmosis in Santa Fe. Histoplasmosis diagnosis was performed through histopathology, recovery of Histoplasma spp., by culture, and/or positive nested Polimerase Chain Reaction (PCR) specific for the Histoplasma Hc100 gene. During the study period, 360 kidney transplantations were performed. Of these patients, 12 were diagnosed with histoplasmosis (3.3%). The patients' median age was 51 years, and 75% were male. Eleven patients (92%) presented the disseminated form of the disease. Thirty-three percent were diagnosed with histoplasmosis in their first year post-transplantation (mostly 6-12 months), while 42% received their diagnosis 3 years after transplantation. Laboratory diagnosis was performed by histopathology, culture, and PCR in four cases (33%), by culture and PCR in three cases (25%), and by PCR alone in three cases (25%). Thus, all 12 patients showed positive nested PCR results. All patients received amphotericin B as initial treatment. A good response was observed in 83% of patients. We found a high incidence of histoplasmosis in kidney transplant recipients (up to 10 times higher than reports from other endemic areas). Diagnosis by histopathology/culture showed 75% sensitivity, while nested PCR showed better sensitivity and diagnostic speed.
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Affiliation(s)
- Manuela Loaiza-Oliva
- Laboratorio de Micología y Diagnóstico Molecular - Cátedra de Parasitología y Micología - Facultad de Bioquímica - Universidad Nacional del Litoral, Santa Fe, C.P. 3000.Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Santa Fe, C.P. 3000.Argentina
| | - Soledad Gamarra
- Laboratorio de Micología y Diagnóstico Molecular - Cátedra de Parasitología y Micología - Facultad de Bioquímica - Universidad Nacional del Litoral, Santa Fe, C.P. 3000.Argentina
| | - Joaquín Agusti
- Clínica de Nefrología, Urología y Enfermedades Cardiovasculares - Grupo MIT, Santa Fe, Argentina. C.P. 3000
| | - Luis Gaite
- Clínica de Nefrología, Urología y Enfermedades Cardiovasculares - Grupo MIT, Santa Fe, Argentina. C.P. 3000
| | - José Hugo Paladini
- Clínica de Nefrología, Urología y Enfermedades Cardiovasculares - Grupo MIT, Santa Fe, Argentina. C.P. 3000
| | - Valeria Martínez
- Clínica de Nefrología, Urología y Enfermedades Cardiovasculares - Grupo MIT, Santa Fe, Argentina. C.P. 3000
| | - Mariano Arriola
- Clínica de Nefrología, Urología y Enfermedades Cardiovasculares - Grupo MIT, Santa Fe, Argentina. C.P. 3000
| | - Judith Ana Gaite
- Clínica de Nefrología, Urología y Enfermedades Cardiovasculares - Grupo MIT, Santa Fe, Argentina. C.P. 3000
| | - Guillermo Garcia-Effron
- Laboratorio de Micología y Diagnóstico Molecular - Cátedra de Parasitología y Micología - Facultad de Bioquímica - Universidad Nacional del Litoral, Santa Fe, C.P. 3000.Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Santa Fe, C.P. 3000.Argentina
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6
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Greenwald MA, Edwards N, Eastlund DT, Gurevich I, Ho APZ, Khalife G, Lin-Torre J, Thompson HW, Wilkins RM, Alrabaa SF. The American Association of Tissue Banks tissue donor screening for Mycobacterium tuberculosis-Recommended criteria and literature review. Transpl Infect Dis 2024; 26 Suppl 1:e14294. [PMID: 38852068 DOI: 10.1111/tid.14294] [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: 03/06/2024] [Revised: 04/12/2024] [Accepted: 04/25/2024] [Indexed: 06/10/2024]
Abstract
After two multistate outbreaks of allograft tissue-transmitted tuberculosis (TB) due to viable bone, evidence-based donor screening criteria were developed to decrease the risk of transmission to recipients. Exclusionary criteria, commentary, and references supporting the criteria are provided, based on literature search and expert opinion. Both exposure and reactivation risk factors were considered, either for absolute exclusion or for exclusion in combination with multiple risk factors. A criteria subset was devised for tissues containing viable cells. Risk factors for consideration included exposure (e.g., geographic birth and residence, travel, homelessness, incarceration, healthcare, and workplace) and reactivation (e.g., kidney disease, liver disease, history of transplantation, immunosuppressive medications, and age). Additional donor considerations include the possibility of sepsis and chronic illness. Donor screening criteria represent minimal criteria for exclusion and do not completely exclude all possible donor TB risks. Additional measures to reduce transmission risk, such as donor and product testing, are discussed but not included in the recommendations. Careful donor evaluation is critical to tissue safety.
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Affiliation(s)
- Melissa A Greenwald
- American Association of Tissue Banks, McLean, Virginia, USA
- Uniformed Services University, Bethesda, Maryland, USA
- Donor Alliance, Denver, Colorado, USA
| | | | | | | | | | - Ghada Khalife
- Solvita, Dayton, Ohio, USA
- Wright State University, Dayton, Ohio, USA
| | - Janet Lin-Torre
- MTF Biologics, Edison, New Jersey, USA
- Department of Medicine, Cooperman Barnabas Medical Center, Livingston, New Jersey, USA
| | | | | | - Sally F Alrabaa
- University of South Florida, Morsani College of Medicine, Tampa, Florida, USA
- LifeLink Tissue Bank, Tampa, Florida, USA
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7
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Tan SSX, Phoompoung P, Okamoto K, Chayakulkeeree M, Koh XX, Tan CK, Kong SNM, Tan TT, Chung SJ, Tan BH. Donor-derived infections-Insights from Singapore, Japan, and Thailand. Transpl Infect Dis 2024; 26 Suppl 1:e14370. [PMID: 39226139 DOI: 10.1111/tid.14370] [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: 06/08/2024] [Revised: 08/15/2024] [Accepted: 08/20/2024] [Indexed: 09/05/2024]
Abstract
BACKGROUND Solid organ transplantation (SOT) has expanded significantly in Asia over past few decades. Donor-derived infections (DDIs) remain a significant concern as they may adversely impact transplant outcomes. We aim to review the existing regulatory frameworks, screening protocols, and management practices for DDIs in Asia. METHODS We reached out to transplant infectious diseases experts in Asia to provide standardized data on annual SOT numbers, incidence of DDIs, regulatory frameworks, donor and recipient screening protocols, and DDI surveillance measures. We present the data from Singapore, Japan, and Thailand. RESULTS Donor screening for HIV, hepatitis B, hepatitis C, and syphilis is mandatory in all countries. Additionally, Japan screens for HTLV-1 antibody due to its endemicity. We also reviewed the protocols for screening and prevention of endemic infections in Asia. Singapore is the only country implementing universal screening for all donors for dengue, Zika, and chikungunya via blood and urine RT-PCR. Strongyloidiasis screening is not routinely done, although some transplant centers empirically give ivermectin prophylaxis to organ recipients. Tuberculosis screening with a donor questionnaire and chest radiograph is common for deceased donors, and some centers do Interferon Gamma Release Assay test for living donors. We also found a significant gap in the surveillance and reporting of potential DDIs in Asia and the overall incidence of DDIs in Asia is unknown and likely underreported. CONCLUSION The experiences of Singapore, Japan, and Thailand offer valuable insights into current practices and the unmet needs regarding a DDI registry and call for coordinated efforts to address this critical issue in the region.
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Affiliation(s)
- Sophie Seine Xuan Tan
- Department of Infectious Diseases, Singapore General Hospital, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
| | - Pakpoom Phoompoung
- Department of Medicine, Division of Infectious Disease and Tropical Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Koh Okamoto
- Department of Infectious Diseases, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Japan
| | - Methee Chayakulkeeree
- Department of Medicine, Division of Infectious Disease and Tropical Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Xiu Xian Koh
- National Organ Transplant Unit, Ministry of Health, Singapore, Singapore
| | - Chee-Kiat Tan
- Duke-NUS Medical School, Singapore, Singapore
- National Organ Transplant Unit, Ministry of Health, Singapore, Singapore
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore
| | | | - Thuan Tong Tan
- Department of Infectious Diseases, Singapore General Hospital, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
- Singhealth Duke Transplant Centre, Singapore, Singapore
| | - Shimin Jasmine Chung
- Department of Infectious Diseases, Singapore General Hospital, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
- Singhealth Duke Transplant Centre, Singapore, Singapore
| | - Ban Hock Tan
- Department of Infectious Diseases, Singapore General Hospital, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
- Singhealth Duke Transplant Centre, Singapore, Singapore
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8
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Prasad P, Sharma S, Mohanasundaram S, Agarwal A, Verma H. Tuberculosis in kidney transplant candidates and recipients. World J Transplant 2024; 14:96225. [PMID: 39295970 PMCID: PMC11317863 DOI: 10.5500/wjt.v14.i3.96225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 06/06/2024] [Accepted: 07/04/2024] [Indexed: 07/31/2024] Open
Abstract
Tuberculosis (TB) is the leading cause of infectious mortality and morbidity in the world, second only to coronavirus disease 2019. Patients with chronic kidney disease and kidney transplant recipients are at a higher risk of developing TB than the general population. Active TB is difficult to diagnose in this population due to close mimics. All transplant candidates should be screened for latent TB infection and given TB prophylaxis. Patients who develop active TB pre- or post-transplantation should receive multidrug combination therapy of antitubercular therapy for the recommended duration with optimal dose modification as per glomerular filtration rate.
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Affiliation(s)
- Pallavi Prasad
- Department of Nephrology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi 110029, Delhi, India
| | - Sourabh Sharma
- Department of Nephrology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi 110029, Delhi, India
| | | | - Anupam Agarwal
- Department of Nephrology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi 110029, Delhi, India
| | - Himanshu Verma
- Department of Nephrology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi 110029, Delhi, India
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9
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Righi I, Barone I, Rosso L, Morlacchi LC, Rossetti V, Caffarena G, Limanaqi F, Palleschi A, Clerici M, Trabattoni D. Immunopathology of lung transplantation: from infection to rejection and vice versa. Front Immunol 2024; 15:1433469. [PMID: 39286256 PMCID: PMC11402714 DOI: 10.3389/fimmu.2024.1433469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 08/14/2024] [Indexed: 09/19/2024] Open
Abstract
Lung transplantation offers a lifesaving option for patients with end-stage lung disease, but it is marred by a high risk of post-transplant infections, particularly involving multidrug-resistant bacteria, Cytomegalovirus, and fungal pathogens. This elevated infection rate, the highest among solid organ transplants, poses a significant challenge for clinicians, particularly within the first year post-transplantation, where infections are the leading cause of mortality. The direct exposure of lung allografts to the external environment exacerbates this vulnerability leading to constant immune stimulation and consequently to an elevated risk of triggering alloimmune responses to the lung allograft. The necessity of prolonged immunosuppression to prevent allograft rejection further complicates patient management by increasing susceptibility to infections and neoplasms, and complicating the differentiation between rejection and infection, which require diametrically opposed management strategies. This review explores the intricate balance between preventing allograft rejection and managing the heightened infection risk in lung transplant recipients.
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Affiliation(s)
- Ilaria Righi
- Thoracic Surgery and Lung Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Ivan Barone
- Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Lorenzo Rosso
- Thoracic Surgery and Lung Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Letizia Corinna Morlacchi
- Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Valeria Rossetti
- Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giovanni Caffarena
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
- Department of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Fiona Limanaqi
- Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, Milan, Italy
| | - Alessandro Palleschi
- Thoracic Surgery and Lung Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Mario Clerici
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
- Fondazione Don C. Gnocchi IRCCS, Milan, Italy
| | - Daria Trabattoni
- Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, Milan, Italy
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10
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Chacko B, Chaudhry D, Peter JV, Khilnani GC, Saxena P, Sehgal IS, Ahuja K, Rodrigues C, Modi M, Jaiswal A, Jasiel GJ, Sahasrabudhe S, Bose P, Ahuja A, Suprapaneni V, Prajapat B, Manesh A, Chawla R, Guleria R. ISCCM Position Statement on the Approach to and Management of Critically Ill Patients with Tuberculosis. Indian J Crit Care Med 2024; 28:S67-S91. [PMID: 39234233 PMCID: PMC11369919 DOI: 10.5005/jp-journals-10071-24783] [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: 07/02/2024] [Accepted: 07/24/2024] [Indexed: 09/06/2024] Open
Abstract
Tuberculosis (TB) is an important cause of morbidity and mortality globally. About 3-4% of hospitalized TB patients require admission to the intensive care unit (ICU); the mortality in these patients is around 50-60%. There is limited literature on the evaluation and management of patients with TB who required ICU admission. The Indian Society of Critical Care Medicine (ISCCM) constituted a working group to develop a position paper that provides recommendations on the various aspects of TB in the ICU setting based on available evidence. Seven domains were identified including the categorization of TB in the critically ill, diagnostic workup, drug therapy, TB in the immunocompromised host, organ support, infection control, and post-TB sequelae. Forty-one questions pertaining to these domains were identified and evidence-based position statements were generated, where available, keeping in focus the critical care aspects. Where evidence was not available, the recommendations were based on consensus. This position paper guides the approach to and management of critically ill patients with TB. How to cite this article Chacko B, Chaudhry D, Peter JV, Khilnani G, Saxena P, Sehgal IS, et al. isccm Position Statement on the Approach to and Management of Critically Ill Patients with Tuberculosis. Indian J Crit Care Med 2024;28(S2):S67-S91.
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Affiliation(s)
- Binila Chacko
- Medical Intensive Care Unit, Christian Medical College, Vellore, Tamil Nadu, India
| | - Dhruva Chaudhry
- Department of Pulmonary and Critical Care Medicine, Pt BDS Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India
| | - John V Peter
- Medical Intensive Care Unit, Christian Medical College, Vellore, Tamil Nadu, India
| | - Gopi C Khilnani
- Department of Pulmonary, Critical Care and Sleep Medicine, PSRI Hospital, New Delhi, India
| | - Prashant Saxena
- Department of Pulmonary, Critical Care and Sleep Medicine, Fortis Hospital, Vasant Kung, New Delhi, India
| | - Inderpaul S Sehgal
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, Punjab, India
| | - Kunal Ahuja
- Department of Pulmonary, Critical Care and Sleep Medicine, PSRI Hospital, New Delhi, India
| | - Camilla Rodrigues
- Department of Lab Medicine, Hinduja Hospital, Mumbai, Maharashtra, India
| | - Manish Modi
- Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, Punjab, India
| | - Anand Jaiswal
- Deparment of Respiratory Diseases, Medanta Medicity, Gurugram, Haryana, India
| | - G Joel Jasiel
- Medical Intensive Care Unit, Christian Medical College, Vellore, Tamil Nadu, India
| | - Shrikant Sahasrabudhe
- Department of Critical Care Medicine and Pulmonology, KIMS Manavata Hospital, Nashik, Maharashtra, India
| | - Prithviraj Bose
- Medical Intensive Care Unit, Christian Medical College, Vellore, Tamil Nadu, India
| | - Aman Ahuja
- Department of Pulmonary and Critical Care Medicine, PGIMS, Rohtak, Haryana, India
| | - Vineela Suprapaneni
- Department of Pulmonary and Critical Care Medicine, PGIMS, Rohtak, Haryana, India
| | - Brijesh Prajapat
- Department of Pulmonary and Critical Care Medicine, Yashoda Group of Hospitals, Ghaziabad, Uttar Pradesh, India
| | - Abi Manesh
- Department of Infectious Diseases, Christian Medical College, Vellore, Tamil Nadu, India
| | - Rajesh Chawla
- Department of Respiratory Medicine, Critical Care and Sleep Medicine, Indraprastha Apollo Hospitals, New Delhi, India
| | - Randeep Guleria
- Institute of Internal Medicine and Respiratory and Sleep Medicine, Medanta Medical School, Gurugram, Haryana, India
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11
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Khilnani GC, Tiwari P, Mittal S, Kulkarni AP, Chaudhry D, Zirpe KG, Todi SK, Mohan A, Hegde A, Jagiasi BG, Krishna B, Rodrigues C, Govil D, Pal D, Divatia JV, Sengar M, Gupta M, Desai M, Rungta N, Prayag PS, Bhattacharya PK, Samavedam S, Dixit SB, Sharma S, Bandopadhyay S, Kola VR, Deswal V, Mehta Y, Singh YP, Myatra SN. Guidelines for Antibiotics Prescription in Critically Ill Patients. Indian J Crit Care Med 2024; 28:S104-S216. [PMID: 39234229 PMCID: PMC11369928 DOI: 10.5005/jp-journals-10071-24677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 03/20/2024] [Indexed: 09/06/2024] Open
Abstract
How to cite this article: Khilnani GC, Tiwari P, Mittal S, Kulkarni AP, Chaudhry D, Zirpe KG, et al. Guidelines for Antibiotics Prescription in Critically Ill Patients. Indian J Crit Care Med 2024;28(S2):S104-S216.
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Affiliation(s)
- Gopi C Khilnani
- Department of Pulmonary, Critical Care and Sleep Medicine, PSRI Hospital, New Delhi, India
| | - Pawan Tiwari
- Department of Pulmonary, Critical Care and Sleep Medicine, AIIMS, New Delhi, India
| | - Saurabh Mittal
- Department of Pulmonary, Critical Care and Sleep Medicine, AIIMS, New Delhi, India
| | - Atul P Kulkarni
- Division of Critical Care Medicine, Department of Anaesthesia, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Dhruva Chaudhry
- Department of Pulmonary and Critical Care Medicine, University of Health Sciences, Rohtak, Haryana, India
| | - Kapil G Zirpe
- Department of Neuro Trauma Unit, Grant Medical Foundation, Pune, Maharashtra, India
| | - Subhash K Todi
- Department of Critical Care, AMRI Hospital, Kolkata, West Bengal, India
| | - Anant Mohan
- Department of Pulmonary, Critical Care and Sleep Medicine, AIIMS, New Delhi, India
| | - Ashit Hegde
- Department of Medicine & Critical Care, P D Hinduja National Hospital, Mumbai, India
| | - Bharat G Jagiasi
- Department of Critical Care, Kokilaben Dhirubhai Ambani Hospital, Navi Mumbai, Maharashtra, India
| | - Bhuvana Krishna
- Department of Critical Care Medicine, St John's Medical College and Hospital, Bengaluru, India
| | - Camila Rodrigues
- Department of Microbiology, P D Hinduja National Hospital, Mumbai, India
| | - Deepak Govil
- Department of Critical Care and Anesthesia, Medanta – The Medicity, GuruGram, Haryana, India
| | - Divya Pal
- Department of Critical Care and Anesthesia, Medanta – The Medicity, GuruGram, Haryana, India
| | - Jigeeshu V Divatia
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Manju Sengar
- Department of Medical Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Mansi Gupta
- Department of Pulmonary Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Mukesh Desai
- Department of Immunology, Pediatric Hematology and Oncology Bai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra, India
| | - Narendra Rungta
- Department of Critical Care & Anaesthesiology, Rajasthan Hospital, Jaipur, India
| | - Parikshit S Prayag
- Department of Transplant Infectious Diseases, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India
| | - Pradip K Bhattacharya
- Department of Critical Care Medicine, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India
| | - Srinivas Samavedam
- Department of Critical Care, Ramdev Rao Hospital, Hyderabad, Telangana, India
| | - Subhal B Dixit
- Department of Critical Care, Sanjeevan and MJM Hospital, Pune, Maharashtra, India
| | - Sudivya Sharma
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Susruta Bandopadhyay
- Department of Critical Care, AMRI Hospitals Salt Lake, Kolkata, West Bengal, India
| | - Venkat R Kola
- Department of Critical Care Medicine, Yashoda Hospitals, Hyderabad, Telangana, India
| | - Vikas Deswal
- Consultant, Infectious Diseases, Medanta - The Medicity, Gurugram, Haryana, India
| | - Yatin Mehta
- Department of Critical Care and Anesthesia, Medanta – The Medicity, GuruGram, Haryana, India
| | - Yogendra P Singh
- Department of Critical Care, Max Super Speciality Hospital, Patparganj, New Delhi, India
| | - Sheila N Myatra
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
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12
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Chiu CY, Mahmood M, Brumble LM, Vikram HR, Theel ES, Beam E. The Cascade of Care in Management of Solid Organ Transplant Candidates With Latent Tuberculosis Infection. Transplant Direct 2024; 10:e1672. [PMID: 38911278 PMCID: PMC11191954 DOI: 10.1097/txd.0000000000001672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 05/06/2024] [Accepted: 04/13/2024] [Indexed: 06/25/2024] Open
Abstract
Background Solid organ transplant (SOT) candidates should be screened and treated for latent tuberculosis infection (LTBI) to prevent tuberculosis (TB) reactivation after transplantation. We aimed to assess the steps from positive QuantiFERON (QFT) through LTBI treatment (cascade of care) in the SOT population. Methods We conducted a retrospective study of SOT recipients older than 18 y with a positive QFT during pretransplant evaluation at the Mayo Clinic from January 2010 to June 2023. We analyzed each cascade step to determine associated drop-out factors for LTBI management. Results Of 629 patients who had positive QFT results, 587 (93%) were evaluated by an infectious disease (ID) specialist, 478 (76%) were recommended to start LTBI treatment, 473 (75%) initiated LTBI treatment, and 457 (73%) completed LTBI treatment. LTBI treatment was not recommended in 109 patients evaluated by infectious disease, most of whom had previously received either LTBI (n = 72) or TB (n = 14) treatment. LTBI treatment was initiated before or after transplantation for 45% and 55% of patients, respectively. Isoniazid monotherapy was the most common regimen (92%), and adverse events were rare (7%). Seven patients developed active TB infection posttransplantation under various circumstances (3 without LTBI treatment, 1 during LTBI treatment, and 3 after completing LTBI treatment). Conclusions Our findings demonstrate the variability of LTBI management in SOT recipients with positive QFT. When recommended, most patients completed LTBI treatment successfully. Nonetheless, active TB was noted regardless of whether patients received LTBI treatment. This study highlights the importance of optimizing LTBI management in this population.
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Affiliation(s)
- Chia-Yu Chiu
- Division of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, MN
| | - Maryam Mahmood
- Division of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, MN
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN
| | - Lisa M. Brumble
- Division of Infectious Diseases, Mayo Clinic, Jacksonville, FL
| | | | - Elitza S. Theel
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Elena Beam
- Division of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, MN
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN
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Shinde AS, Kapoor D. Infections After Liver Transplant -Timeline, Management and Prevention. J Clin Exp Hepatol 2024; 14:101316. [PMID: 38264574 PMCID: PMC10801311 DOI: 10.1016/j.jceh.2023.101316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Accepted: 12/06/2023] [Indexed: 01/25/2024] Open
Abstract
Liver transplantation (LT) is the standard treatment for end- stage liver disease. Patient and graft survival have improved significantly in the last three decades owing to improvement in surgical technique, better perioperative management and better immunosuppressive regimens. However, LT recipients are at increased risk of infections, particularly in the first year after transplantation. The risk of infection is directly proportional to immunosuppressive regimen and graft function. In this review, we will briefly discuss the timeline of infections after liver transplant, preventive strategies and management of infectious complications.
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Affiliation(s)
- Ajay S. Shinde
- Consultant Gastroenterologist and Hepatologist, Yashoda Hospitals, Secunderabad, Telangana, India
| | - Dharmesh Kapoor
- Consultant Hepatologist, Yashoda Hospitals, Secunderabad, Telangana, India
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14
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Storoniak H, Dębska-Ślizień A. Miliary Tuberculosis as Postmortem Diagnosis in Solid Organ Transplant Recipient: Case Report and Review of the Literature. Transplant Proc 2024; 56:968-971. [PMID: 38388293 DOI: 10.1016/j.transproceed.2024.01.057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Accepted: 01/23/2024] [Indexed: 02/24/2024]
Abstract
BACKGROUND The diagnosis of tuberculosis (TB) in solid organ transplant (SOT) recipients presents challenges that may lead to treatment delay. These include atypical clinical presentations, increased likelihood of negative tuberculin skin test or/and interferon-gamma release assays, and negative sputum smear results despite active disease. The treatment poses challenges due to pharmacokinetic interactions, allograft-related toxicity, and inadequate immune response. CASE REPORT We report the case of a 70-year-old man after kidney transplantation in 2012. The patient was transferred from the urology unit with deteriorating renal function and presumed urosepsis. His pulmonary chest X-ray showed hilar pulmonary infiltrates. Computed tomography of the chest/abdomen/pelvis revealed mediastinal lymphadenopathy, pulmonary infiltrates, pulmonary effusion, and splenomegaly. His blood results showed pancytopenia and high inflammatory and renal markers. He was treated with broad-spectrum antibiotics covering bacterial, fungal, and viral infections. Despite initial clinical improvement, his kidney function deteriorated, and he required hemodialysis. His temperature continued to spike. On physical examination, he was confused and lethargic. He was scheduled to have a mediastinoscopy with lymph node biopsy, but he died the day before. The postmortem examination revealed miliary tuberculosis with tuberculosis of many organs: kidney transplant, native kidney, bone marrow, mediastinal lymph nodes, lungs, and spleen. CONCLUSIONS The diagnosis of active TB in transplant recipients requires a high index of suspicion and invasive procedures. The majority of all cases of active TB after SOT are disseminated or occur at extrapulmonary sites. Only a small minority of patients have classic cavitary changes on pulmonary imaging.
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Affiliation(s)
- Hanna Storoniak
- Department of Nephrology, Transplantology and Internal Medicine, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland.
| | - Alicja Dębska-Ślizień
- Department of Nephrology, Transplantology and Internal Medicine, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland
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15
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Nguyen Van R, Houssel-Debry P, Erard D, Dumortier J, Pouvaret A, Bergez G, Danion F, Surgers L, Le Moing V, Kamar N, Lanternier F, Tattevin P. Characteristics, management, and outcome of tuberculosis after liver transplant: A case series and literature review. Infect Dis Now 2024; 54:104869. [PMID: 38401760 DOI: 10.1016/j.idnow.2024.104869] [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: 11/11/2023] [Revised: 02/10/2024] [Accepted: 02/15/2024] [Indexed: 02/26/2024]
Abstract
BACKGROUND Liver transplant recipients are at risk of tuberculosis, which is particularly difficult-to diagnose and to treat in this population. METHODS Retrospective study of all cases of tuberculosis diagnosed from 2007 to 2022 in the French network of liver transplant sites. RESULTS Twenty-three liver transplant recipients were diagnosed with tuberculosis (six females, median age 59 years [interquartile range, 54-62]), with a median time lapse of 10 months [5-40.5] after transplant, and 38 days [26-60] after symptoms onset. Primary modes of pathogenesis were latent tuberculosis reactivation (n = 15) and transplant-related transmission (n = 3). Even though most patients with pre-transplant data had risk factors for tuberculosis (11/20), IFN-gamma release assay was performed in only three. Most cases involved extra-pulmonary tuberculosis (20/23, 87 %). With median follow-up of 63 months [24-108], five patients died (22 %), including four tuberculosis-related deaths. CONCLUSIONS Extrapulmonary tuberculosis is a severe disease in liver transplant recipients. Systematic pre-transplant screening of latent tuberculosis may prevent most of them.
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Affiliation(s)
- Rémi Nguyen Van
- Infectious Disease and Intensive Care Unit, Pontchaillou University Hospital, Rennes, France; Infectious Diseases, Centre Hospitalier Bretagne-Atlantique, Vannes, France
| | - Pauline Houssel-Debry
- Hepatology and Liver Transplantation, Pontchaillou University Hospital, Rennes, France
| | - Domitille Erard
- Hepatology and Liver Transplantation, La Croix Rousse University Hospital, Lyon, France
| | - Jérôme Dumortier
- Hepato-Gastroenterology, Edouard Herriot University Hospital, and University Lyon-1, Lyon, France
| | - Anne Pouvaret
- Infectious Diseases, University Hospital, Saint-Etienne, France
| | - Guillaume Bergez
- Infectious Disease, Beaujon Hospital, AP-HP, University Hospital, Paris, France
| | - François Danion
- Infectious Disease, University Hospital, Inserm UMR_S 1109 Immuno-rhumatologie Moléculaire, Université de Strasbourg, Strasbourg, France
| | - Laure Surgers
- Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, F75012 Paris, France; GHU APHP, Sorbonne Université, Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, F75012 Paris, France
| | - Vincent Le Moing
- Infectious Diseases, University Hospital, University of Montpellier, Montpellier, France
| | - Nassim Kamar
- Department of Nephrology and Organ Transplantation, Toulouse Rangueil University Hospital, INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University Paul Sabatier, Toulouse, France
| | - Fanny Lanternier
- Infectious Diseases, Necker-Enfants Malades Hospital, AP-HP, Université Paris-Cité, Paris, France
| | - Pierre Tattevin
- Infectious Disease and Intensive Care Unit, Pontchaillou University Hospital, Rennes, France.
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16
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Magda G. Opportunistic Infections Post-Lung Transplantation: Viral, Fungal, and Mycobacterial. Infect Dis Clin North Am 2024; 38:121-147. [PMID: 38280760 DOI: 10.1016/j.idc.2023.12.001] [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] [Indexed: 01/29/2024]
Abstract
Opportunistic infections are a leading cause of lung transplant recipient morbidity and mortality. Risk factors for infection include continuous exposure of the lung allograft to the external environment, high levels of immunosuppression, impaired mucociliary clearance and decreased cough reflex, and impact of the native lung microbiome in single lung transplant recipients. Infection risk is mitigated through careful pretransplant screening of recipients and donors, implementation of antimicrobial prophylaxis strategies, and routine surveillance posttransplant. This review describes common viral, fungal, and mycobacterial infectious after lung transplant and provides recommendations on prevention and treatment.
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Affiliation(s)
- Gabriela Magda
- Columbia University Lung Transplant Program, Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Irving Medical Center, Columbia University Vagelos College of Physicians and Surgeons, 622 West 168th Street PH-14, New York, NY 10032, USA.
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17
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Hyun J, Lee M, Jung I, Kim E, Hahn SM, Kim YR, Lim S, Ihn K, Kim MY, Ahn JG, Yeom JS, Jeong SJ, Kang JM. Changes in tuberculosis risk after transplantation in the setting of decreased community tuberculosis incidence: a national population-based study, 2008-2020. Ann Clin Microbiol Antimicrob 2024; 23:1. [PMID: 38172897 PMCID: PMC10765802 DOI: 10.1186/s12941-023-00661-4] [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: 08/31/2023] [Accepted: 12/10/2023] [Indexed: 01/05/2024] Open
Abstract
BACKGROUND Transplant recipients are immunocompromised and vulnerable to developing tuberculosis. However, active tuberculosis incidence is rapidly declining in South Korea, but the trend of tuberculosis infection among transplant recipients has not been elucidated. This study aimed to evaluate the risk of active tuberculosis after transplantation, including risk factors for tuberculosis and standardized incidence ratios, compared with that in the general population. METHODS This retrospective study was conducted based on the South Korean health insurance review and assessment database among those who underwent transplantation (62,484 recipients) between 2008 and 2020. Tuberculosis incidence was compared in recipients treated during higher- (2010-2012) and lower-disease burden (2016-2018) periods. Standardized incidence ratios were analyzed using the Korean Tuberculosis Surveillance System. The primary outcome was the number of new tuberculosis cases after transplantation. RESULTS Of 57,103 recipients analyzed, the overall cumulative incidence rate 1 year after transplantation was 0.8% (95% confidence interval [CI]: 0.7-0.8), significantly higher in the higher-burden period than in the lower-burden period (1.7% vs. 1.0% 3 years after transplantation, P < 0.001). Individuals who underwent allogeneic hematopoietic stem cell transplantation had the highest tuberculosis incidence, followed by those who underwent solid organ transplantation and autologous hematopoietic stem cell transplantation (P < 0.001). The overall standardized incidence ratio was 3.9 (95% CI 3.7-4.2) and was the highest in children aged 0-19 years, at 9.0 (95% CI 5.7-13.5). Male sex, older age, tuberculosis history, liver transplantation, and allogeneic hematopoietic stem cell transplantation were risk factors for tuberculosis. CONCLUSIONS Transplant recipients are vulnerable to developing tuberculosis, possibly influenced by their immunocompromised status, solid organ transplant type, age, and community prevalence of tuberculosis. Tuberculosis prevalence by country, transplant type, and age should be considered to establish an appropriate tuberculosis prevention strategy for high-risk groups.
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Affiliation(s)
- JongHoon Hyun
- Division of Infectious Diseases, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Republic of Korea
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Myeongjee Lee
- Department of Biomedical Systems Informatics, Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Inkyung Jung
- Division of Biostatistics, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Eunhwa Kim
- Department of Biomedical Systems Informatics, Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seung Min Hahn
- Department of Pediatric Hematology-Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yu Ri Kim
- Division of Hematology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sungmin Lim
- Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea
| | - Kyong Ihn
- Department of Pediatric Surgery, Department of Surgery, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Min Young Kim
- Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea
- Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jong Gyun Ahn
- Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea
- Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Joon-Sup Yeom
- Division of Infectious Disease, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro Seodaemun-Gu, Seoul, 03722, Republic of Korea
| | - Su Jin Jeong
- Division of Infectious Disease, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro Seodaemun-Gu, Seoul, 03722, Republic of Korea.
| | - Ji-Man Kang
- Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea.
- Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea.
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18
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Oliveira VDA, Almeida RAMDB, Cavalcante RDS, de Andrade LGM, Ribeiro SM. Radiological presentation of active pulmonary tuberculosis in kidney transplant recipients: a retrospective study of four cases and a review of the literature. Radiol Bras 2024; 57:e20230124. [PMID: 38993963 PMCID: PMC11235070 DOI: 10.1590/0100-3984.2023.0124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 12/06/2023] [Accepted: 01/24/2024] [Indexed: 07/13/2024] Open
Abstract
Although kidney transplantation is the best therapeutic option for patients with chronic kidney disease, the immunosuppression required greatly increases susceptibility to infections that are responsible for high post-transplant mortality. Pulmonary tuberculosis (TB) represents a major cause of such infections, and its early diagnosis is therefore quite important. In view of that, we researched the manifestations of active pulmonary TB in kidney transplant recipients, through chest X-ray and computed tomography (CT), as well as determining the number of cases of active pulmonary TB occurring over a 3.5-year period at our institution. We identified four cases of active pulmonary TB in kidney transplant recipients. The CT scans provided information complementary to the chest X-ray findings in all four of those cases. We compared our CT findings with those reported in the literature. We analyzed our experience in conjunction with an extensive review of the literature that was nevertheless limited because few studies have been carried out in lowand middle-income countries, where the incidence of TB is higher.
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Affiliation(s)
- Virgilio de Araujo Oliveira
- Faculdade de Medicina de Botucatu, Universidade Estadual Paulista
“Júlio de Mesquita Filho” (UNESP). Botucatu, SP, Brazil
| | | | - Ricardo de Souza Cavalcante
- Faculdade de Medicina de Botucatu, Universidade Estadual Paulista
“Júlio de Mesquita Filho” (UNESP). Botucatu, SP, Brazil
| | | | - Sergio Marrone Ribeiro
- Faculdade de Medicina de Botucatu, Universidade Estadual Paulista
“Júlio de Mesquita Filho” (UNESP). Botucatu, SP, Brazil
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19
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Chiang CY, Chen CH, Feng JY, Chiang YJ, Huang WC, Lin YJ, Huang YW, Wu HH, Lee PH, Lee MC, Shu CC, Wang HH, Wang JY, Wu MY, Lee CY, Wu MS. Prevention and management of tuberculosis in solid organ transplantation: A consensus statement of the transplantation society of Taiwan. J Formos Med Assoc 2023; 122:976-985. [PMID: 37183074 DOI: 10.1016/j.jfma.2023.04.025] [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: 01/09/2023] [Revised: 02/08/2023] [Accepted: 04/26/2023] [Indexed: 05/16/2023] Open
Abstract
Solid organ transplant recipients have an increased risk of tuberculosis (TB). Due to the use of immunosuppressants, the incidence of TB among solid organ transplant recipients has been consistently reported to be higher than that among the general population. TB frequently develops within the first year after transplantation when a high level of immunosuppression is maintained. Extrapulmonary TB and disseminated TB account for a substantial proportion of TB among solid organ transplant recipients. Treatment of TB among recipients is complicated by the drug-drug interactions between anti-TB drugs and immunosuppressants. TB is associated with an increased risk of graft rejection, graft failure and mortality. Detection and management of latent TB infection among solid organ transplant candidates and recipients have been recommended. However, strategy to mitigate the risk of TB among solid organ transplant recipients has not yet been established in Taiwan. To address the challenges of TB among solid organ transplant recipients, a working group of the Transplantation Society of Taiwan was established. The working group searched literatures on TB among solid organ transplant recipients as well as guidelines and recommendations, and proposed interventions to strengthen TB prevention and care among solid organ transplant recipients.
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Affiliation(s)
- Chen-Yuan Chiang
- Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Cheng-Hsu Chen
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Life Science, Tunghai University, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan
| | - Jia-Yih Feng
- Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yang-Jen Chiang
- Department of Urology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Organ Transplantation Institute, Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wei-Chang Huang
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Mycobacteria Center of Excellence, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan
| | - Yih-Jyh Lin
- Division of General and Transplant Surgery, Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan; College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yi-Wen Huang
- Pulmonary and Critical Care Unit, Changhua Hospital, Ministry of Health and Welfare, Changhua, Taiwan
| | - Hsin-Hsu Wu
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Pin-Hui Lee
- Taiwan Centers for Disease Control, Taipei, Taiwan
| | - Ming-Che Lee
- Division of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; TMU Research Center for Organ Transplantation, Taipei Medical University, Taipei, Taiwan
| | - Chin-Chung Shu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Hsu-Han Wang
- Department of Urology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Organ Transplantation Institute, Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jann-Yuan Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Mei-Yi Wu
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
| | - Chih-Yuan Lee
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Mai-Szu Wu
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan.
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20
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Feuth T, Rajalahti I, Vasankari T, Gissler M, Rimhanen-Finne R, Finne P, Helanterä I. Tuberculosis in Kidney Transplant Recipients: A Nationwide Cohort in a Low Tuberculosis Incidence Country. Transplant Direct 2023; 9:e1527. [PMID: 37636485 PMCID: PMC10455224 DOI: 10.1097/txd.0000000000001527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 07/14/2023] [Indexed: 08/29/2023] Open
Abstract
Background World Health Organization recommends tuberculosis (TB) preventive treatment for risk groups such as patients preparing for organ transplantation. Pretransplant screening or treatment of latent TB infection has not been routine practice in Finland. Methods In this nationwide registry study, we assessed the risk of TB among kidney transplant recipients compared to the general population. TB cases were identified by data linkage of the national infectious disease and the national transplant registries between 1995 and 2019. Standardized incidence ratios were calculated with adjustment for age, sex, and annual TB dynamics. Results A total of 4101 kidney transplants in 3900 recipients with a follow-up of 37 652 patient-years were included. Eighteen TB cases were detected. Patients diagnosed with TB were older (median age 64 y, interquartile range 56-66) at transplantation than those without TB (median 51 y, interquartile range 41-60, P < 0.001). The standardized incidence ratio of TB was 6.9 among kidney transplant recipients compared to general population during the whole study period 1995-2019 but decreased from 12.5 in 1995-2007 to 3.2 in 2008-2019. The standardized incidence ratio was 44.2 during the first year after transplantation. Significant differences in 5-y graft losses were not detected between TB patients and those without TB. Conclusions The standardized incidence ratio of TB in kidney transplant recipients has decreased over the years, but these patients remain at risk of TB, especially during the first posttransplant year. Cost-benefit analysis is required to address feasibility of latent TB infection screening among transplant candidates in countries with low incidence of TB.
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Affiliation(s)
- Thijs Feuth
- Department of Pulmonary Diseases and Allergology, Turku University Hospital, Turku, Finland
- Department of Pulmonary Medicine and Allergology, Faculty of Medicine, University of Turku, Turku, Finland
| | - Iiris Rajalahti
- Department of Pulmonary Diseases, Tampere University Hospital, Tampere, Finland
- Finnish Lung Health Association (Filha ry), Helsinki, Finland
| | - Tuula Vasankari
- Department of Pulmonary Medicine and Allergology, Faculty of Medicine, University of Turku, Turku, Finland
- Finnish Lung Health Association (Filha ry), Helsinki, Finland
| | - Mika Gissler
- Region Stockholm, Academic Primary Health Care Center, Stockholm, Sweden
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Ruska Rimhanen-Finne
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Patrik Finne
- Nephrology, Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Ilkka Helanterä
- Transplantation and Liver Surgery, Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
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21
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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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22
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Lino R, Amorim S, Silva C, Neves N, Araújo P, Pinto R, Pinheiro-Torres J, Pinho P, Macedo F, Santos L. Cutaneous Tuberculosis in Heart Transplant. Transplant Proc 2023; 55:1444-1448. [PMID: 37142508 DOI: 10.1016/j.transproceed.2023.03.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 03/06/2023] [Accepted: 03/27/2023] [Indexed: 05/06/2023]
Abstract
Tuberculosis is a disease with a significant global burden in terms of morbidity and mortality. It usually presents as a pulmonary disease but can occasionally have extrapulmonary presentations. Immunosuppressed people are at an increased risk of tuberculosis and more frequently have atypical manifestations of the disease. Cutaneous involvement is estimated to occur in only 2% of extrapulmonary presentations. We report a case of a heart transplant recipient with disseminated tuberculosis who initially presented with cutaneous manifestations in the form of multiple abscesses that were mistaken for a community-acquired bacterial infection. The diagnosis was made after positive nucleic acid amplification testing and cultures for Mycobacterium tuberculosis from the drainage of the abscesses. After initiating antituberculous treatment, the patient had 2 instances of immune reconstitution inflammatory syndrome. A combination of diminished immunosuppression due to discontinuation of mycophenolate mofetil in the setting of acute infection, rifampin drug interactions with cyclosporine, and the beginning of treatment of tuberculosis all contributed to this paradoxical worsening. The patient responded favorably to increased glucocorticoid therapy and showed no signs of treatment failure after 6 months of antituberculous therapy.
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Affiliation(s)
- Rita Lino
- Infectious Diseases Department, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal.
| | - Sandra Amorim
- Cardiology Department, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal
| | - Cláudio Silva
- Infectious Diseases Department, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal
| | - Nélia Neves
- Infectious Diseases Department, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal
| | - Paulo Araújo
- Cardiology Department, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal
| | - Roberto Pinto
- Cardiology Department, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal
| | - José Pinheiro-Torres
- Cardiothoracic Surgery Department, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal
| | - Paulo Pinho
- Cardiothoracic Surgery Department, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal
| | - Filipe Macedo
- Cardiology Department, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal
| | - Lurdes Santos
- Infectious Diseases Department, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal; ESCMID Study Group for Infections in Compromised Hosts, European Society of Clinical Microbiology and Infectious Diseases
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23
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Narsana N, Alejandra Pérez M, Subramanian A. Mycobacteria in Organ Transplant Recipients. Infect Dis Clin North Am 2023:S0891-5520(23)00040-5. [PMID: 37268476 DOI: 10.1016/j.idc.2023.04.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
This review describes the epidemiology and risk factors of tuberculosis (TB) in solid organ transplant recipients. We discuss the pre-transplant screening for risk of TB and management of latent TB in this population. We also discuss the challenges of management of TB and other difficult to treat mycobacteria such as Mycobacterium abscessus and Mycobacterium avium complex. The drugs for the management of these infections include rifamycins which have significant drug interactions with immunosuppressants and must be monitored closely.
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Affiliation(s)
- Niyati Narsana
- UC Davis School of Medicine, 4150 V Street, G500, Sacramento, CA 95817, USA.
| | | | - Aruna Subramanian
- Stanford University School of Medicine, 300 Pasteur Drive, Lane Building Suite 134, Stanford, CA 94305, USA
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24
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Yuan Z, Chao S, Xu Y, Niu Y. Chemoprophylaxis for the prevention of tuberculosis in kidney transplant recipients: A systematic review and meta-analysis. Front Pharmacol 2023; 14:1022579. [PMID: 37007009 PMCID: PMC10060851 DOI: 10.3389/fphar.2023.1022579] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 02/23/2023] [Indexed: 03/18/2023] Open
Abstract
Background: A systematic review and meta-analysis was performed to investigate the efficacy and safety of isoniazid (INH) prophylaxis to prevent tuberculosis (TB) infection in kidney transplant recipients (KTRs). Methods: Web of Science, SCOPUS, and PubMed were searched to identify relevant studies that compared the effects among patients who received INH prophylaxis after transplantation. Results: A total of 13 studies (involving 6,547 KTRs) were included in our analysis. We found that the risk of active TB infection (RR: 0.35, 95%CI 0.27-0.45, p < 0.01) for KTRs was lower in the INH treatment group than in those without prophylaxis. However, there was no significant difference between the two groups in mortality (RR: 0.93, 95%CI 0.67-1.28, p = 0.64), acute rejection (RR: 0.82, 95%CI 0.44-1.51, p = 0.52), and hepatotoxicity (RR: 1.25, 95%CI 0.94-1.65, p = 0.12). Conclusion: Isoniazid prophylaxis is a safe and effective for KTRs on reactivation of latent TB infection.
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Affiliation(s)
| | | | | | - Yulin Niu
- Department of Transplantation Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
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25
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Katrak S, Han E, Readhead A, Fung M, Keh C, Flood J, Barry P. Solid organ transplant recipients with tuberculosis disease in California, 2010 to 2020. Am J Transplant 2023; 23:401-407. [PMID: 36695700 DOI: 10.1016/j.ajt.2022.11.019] [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: 07/20/2022] [Revised: 11/07/2022] [Accepted: 11/29/2022] [Indexed: 01/13/2023]
Abstract
Using California Tuberculosis (TB) Registry data from 2010-2020, we compared the presentation and outcomes of patients with TB aged >15 years with and without solid organ transplantation (SOT). We matched to the United Network for Organ Sharing registry for 1987-2020 and the estimated time from transplantation to the diagnosis of TB, the incidence of posttransplant TB, and the probability of death and graft failure in SOT recipients with TB, compared to those without TB. From 2010-2020, there were 148 posttransplant TB cases. Patients with posttransplant TB were more likely to have extrapulmonary disease and more than twice as likely to die as TB patients without SOT (relative risk [RR], 2.2; 95% confidence interval [CI], 1.6-2.9). The median time from transplantation to TB diagnosis was 1.2 years, with the shortest time among lung transplant recipients. The incidence of TB disease among Californians with SOT was 56.0 per 100 000 person-years. The risk of death was higher among SOT recipients with posttransplant TB than those without (adjusted hazard ratio, 2.8; 95% CI, 2.0-4.1); the risk of graft failure was higher among kidney transplant recipients with posttransplant TB than those without (adjusted hazard ratio, 3.4; 95% CI, 1.7-6.9). An increased risk of death and graft failure in SOT recipients with posttransplant TB highlights the need for enhanced pretransplant TB prevention.
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Affiliation(s)
- Shereen Katrak
- Tuberculosis Control Branch, California Department of Public Health, Richmond, California, USA; Division of Infectious Diseases, University of California, San Francisco, California, USA.
| | - Emily Han
- Tuberculosis Control Branch, California Department of Public Health, Richmond, California, USA
| | - Adam Readhead
- Tuberculosis Control Branch, California Department of Public Health, Richmond, California, USA
| | - Monica Fung
- Division of Infectious Diseases, University of California, San Francisco, California, USA
| | - Chris Keh
- Tuberculosis Control Branch, California Department of Public Health, Richmond, California, USA; Division of Infectious Diseases, University of California, San Francisco, California, USA
| | - Jennifer Flood
- Tuberculosis Control Branch, California Department of Public Health, Richmond, California, USA
| | - Pennan Barry
- Tuberculosis Control Branch, California Department of Public Health, Richmond, California, USA; Division of Infectious Diseases, University of California, San Francisco, California, USA
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26
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Opportunistic Infections Post-Lung Transplantation: Viral, Fungal, and Mycobacterial. Clin Chest Med 2023; 44:159-177. [PMID: 36774162 DOI: 10.1016/j.ccm.2022.10.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2023]
Abstract
Opportunistic infections are a leading cause of lung transplant recipient morbidity and mortality. Risk factors for infection include continuous exposure of the lung allograft to the external environment, high levels of immunosuppression, impaired mucociliary clearance and decreased cough reflex, and impact of the native lung microbiome in single lung transplant recipients. Infection risk is mitigated through careful pretransplant screening of recipients and donors, implementation of antimicrobial prophylaxis strategies, and routine surveillance posttransplant. This review describes common viral, fungal, and mycobacterial infectious after lung transplant and provides recommendations on prevention and treatment.
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27
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Foppiano Palacios C, Medvedeva N, Cheung H, Cohen E, Azar MM, Malinis M. The cascade of care in testing and treatment of latent tuberculosis infection in liver transplant candidates. Transpl Infect Dis 2023; 25:e13999. [PMID: 36484433 DOI: 10.1111/tid.13999] [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: 08/25/2022] [Revised: 11/03/2022] [Accepted: 11/16/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND Testing and treatment for latent tuberculosis infection (LTBI) can mitigate risk of active tuberculosis (TB) post-liver transplant (LT). Testing and treatment completion rates have been reported low in this population. Our study aims to quantify the proportion of LT candidates who completed LTBI care cascade in our center. METHODS A retrospective chart review was conducted on LT candidates from 2012 to 2021. Primary outcome was the proportion of patients who completed each cascade stage. Secondary outcome was an analysis of factors associated with positive and indeterminate LTBI testing. RESULTS Of the 273 LT candidates, 265 (97.1%) were referred to transplant infectious disease (TID), 264 (96.7%) had orders for interferon-gamma release assay (IGRA), 262 (96%) underwent TID evaluation, and 259 (94.9%) completed IGRA. Twenty had LTBI, and 18 were treatment naïve and recommended for treatment. Of the 18, 15 (83.3%) agreed to therapy, 14 (77.8%) initiated treatment, and 12 (66.7%) completed treatment. No posttransplant TB reactivation occurred. Patients born in Asia, previous incarceration, past military service, and granuloma findings on chest imaging were likely to have positive IGRA (p < .05). Older age and travel to TB-endemic countries were likely to have indeterminate IGRA (p < .05). Indeterminate IGRAs were more common in QuantiFERON (QTF)-Gold Plus TB (15.3%) versus QTF-Gold TB (9.3%, p < .001). CONCLUSIONS High rates of LTBI testing and treatment initiation and completion can be attributed to a standardized process that includes TID evaluation. Future studies in larger cohort are needed to better understand factors that can optimize the completion rates of LTBI treatment in LT candidates.
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Affiliation(s)
- Carlo Foppiano Palacios
- Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Natalia Medvedeva
- Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Harry Cheung
- Yale University School of Medicine, New Haven, Connecticut, USA
| | - Elizabeth Cohen
- Department of Pharmacy Services, Yale New Haven Hospital, New Haven, Connecticut, USA
| | - Marwan M Azar
- Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.,Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Maricar Malinis
- Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.,Department of Surgery (Transplant), Yale University School of Medicine, New Haven, Connecticut, USA
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28
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Doblas A, Torre-Cisneros J. The role of alternative regimens in the management of tuberculosis in transplant recipients: From past challenges to future opportunities. Transpl Infect Dis 2022; 24:e13958. [PMID: 36468202 DOI: 10.1111/tid.13958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 08/12/2022] [Accepted: 08/18/2022] [Indexed: 12/07/2022]
Affiliation(s)
- Antonio Doblas
- Hospital Universitario Reina Sofia-Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
| | - Julian Torre-Cisneros
- Hospital Universitario Reina Sofia-Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain.,Universidad de Córdoba, Córdoba, Spain.,Center for Biomedical Research in Infectious Diseases Network (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
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29
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Radisic MV, Pujato NR, Bravo PM, Del Grosso RC, Hunter M, Beltramino S, Linares González L, Cornet ML, Del Carmen Rial M, Franzini RL, Dotta AC, León LR, Walther J, Uva PD, Werber G. Tuberculosis treatment without rifampin in kidney/kidney-pancreas transplantation: A case series report. Transpl Infect Dis 2022; 24:e13949. [PMID: 36515463 DOI: 10.1111/tid.13949] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 07/24/2022] [Accepted: 08/01/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND The best approach to tuberculosis (TB) treatment in transplanted patients is still unknown. Current guidelines are based on evidence either extrapolated from other populations or observational. Rifampin-containing regimens have strong pharmacokinetic interactions with immunosuppressive regimens, with high rates of organ dysfunction and ∼20% mortality. This report describes the results obtained using non-rifampin-containing regimens to treat confirmed TB in adult patients with kidney/kidney-pancreas transplantation. METHODS Retrospective data analysis from confirmed TB cases in adult kidney/kidney-pancreas transplant recipients (2006-2019), treated "de novo" with non-rifampin-containing regimens. RESULTS Fifty-seven patients had confirmed TB. Thirty patients were treated "de novo" with non-rifampin-containing regimens. These patients' mean age was 49.24 (±11.50) years. Induction immunosuppression was used in 22 patients. Maintenance immunosuppression was tacrolimus-mycophenolate-steroids in 13 (43%), sirolimus-mycophenolate-steroids in 6 (20%), and other immunosuppressive regimens in 11 (36%). Belatacept was used in four patients. TB localizations: pulmonary 43%; disseminated 23%; extrapulmonary 33%. Twenty-seven (90%) patients completed treatment with isoniazid, ethambutol, and levofloxacin (12 months, 23; 9 months, 3; 6 months, 1); 12 of these patients also received pyrazinamide for the first 2 months and were cured with functioning grafts. One patient (3%) lost the graft while on treatment. Two patients (7%) died while on TB treatment. Median (range) follow-up after completion of TB treatment was 32 (8-150) months. No TB relapses were observed. CONCLUSIONS Results with non-rifampin-containing TB treatments in this case series were better (in terms of mortality and graft dysfunction) than those previously described with rifampin-containing regimens in transplanted patients.
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Affiliation(s)
- Marcelo Victor Radisic
- Infectious, Diseases Department, Instituto de Trasplante y Alta Complejidad (ITAC), Autonomous City of Buenos Aires, Argentina
| | - Natalia Rosana Pujato
- Infectious, Diseases Department, Instituto de Trasplante y Alta Complejidad (ITAC), Autonomous City of Buenos Aires, Argentina
| | - Pablo Martin Bravo
- Infectious, Diseases Department, Instituto de Trasplante y Alta Complejidad (ITAC), Autonomous City of Buenos Aires, Argentina
| | - Roxana Constanza Del Grosso
- Internal Medicine Department, Instituto de Trasplante y Alta Complejidad (ITAC), Autonomous City of Buenos Aires, Argentina
| | - Martin Hunter
- Internal Medicine Department, Instituto de Trasplante y Alta Complejidad (ITAC), Autonomous City of Buenos Aires, Argentina
| | - Santiago Beltramino
- Critical Care Unit, Instituto de Trasplante y Alta Complejidad (ITAC), Autonomous City of Buenos Aires, Argentina
| | - Laura Linares González
- Infectious, Diseases Department, Instituto de Trasplante y Alta Complejidad (ITAC), Autonomous City of Buenos Aires, Argentina
| | - María Lucía Cornet
- Infectious, Diseases Department, Instituto de Trasplante y Alta Complejidad (ITAC), Autonomous City of Buenos Aires, Argentina
| | - Maria Del Carmen Rial
- Kidney Transplantation Unit, Instituto de Trasplante y Alta Complejidad (ITAC), Autonomous City of Buenos Aires, Argentina
| | - Rosa Livia Franzini
- Kidney Transplantation Unit, Instituto de Trasplante y Alta Complejidad (ITAC), Autonomous City of Buenos Aires, Argentina
| | - Ana C Dotta
- Kidney Transplantation Unit, Instituto de Trasplante y Alta Complejidad (ITAC), Autonomous City of Buenos Aires, Argentina
| | - Luis Roberto León
- Kidney Transplantation Unit, Instituto de Trasplante y Alta Complejidad (ITAC), Autonomous City of Buenos Aires, Argentina
| | - Javier Walther
- Kidney Transplantation Unit, Instituto de Trasplante y Alta Complejidad (ITAC), Autonomous City of Buenos Aires, Argentina
| | - Pablo Daniel Uva
- Kidney-Pancreas Transplantation Unit, Instituto de Trasplante y Alta Complejidad (ITAC), Autonomous City of Buenos Aires, Argentina
| | - Gustavo Werber
- Critical Care Unit, Instituto de Trasplante y Alta Complejidad (ITAC), Autonomous City of Buenos Aires, Argentina
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30
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Schaberg T, Brinkmann F, Feiterna-Sperling C, Geerdes-Fenge H, Hartmann P, Häcker B, Hauer B, Haas W, Heyckendorf J, Lange C, Maurer FP, Nienhaus A, Otto-Knapp R, Priwitzer M, Richter E, Salzer HJ, Schoch O, Schönfeld N, Stahlmann R, Bauer T. Tuberkulose im Erwachsenenalter. Pneumologie 2022; 76:727-819. [DOI: 10.1055/a-1934-8303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
ZusammenfassungDie Tuberkulose ist in Deutschland eine seltene, überwiegend gut behandelbare Erkrankung. Weltweit ist sie eine der häufigsten Infektionserkrankungen mit ca. 10 Millionen Neuerkrankungen/Jahr. Auch bei einer niedrigen Inzidenz in Deutschland bleibt Tuberkulose insbesondere aufgrund der internationalen Entwicklungen und Migrationsbewegungen eine wichtige Differenzialdiagnose. In Deutschland besteht, aufgrund der niedrigen Prävalenz der Erkrankung und der damit verbundenen abnehmenden klinischen Erfahrung, ein Informationsbedarf zu allen Aspekten der Tuberkulose und ihrer Kontrolle. Diese Leitlinie umfasst die mikrobiologische Diagnostik, die Grundprinzipien der Standardtherapie, die Behandlung verschiedener Organmanifestationen, den Umgang mit typischen unerwünschten Arzneimittelwirkungen, die Besonderheiten in der Diagnostik und Therapie resistenter Tuberkulose sowie die Behandlung bei TB-HIV-Koinfektion. Sie geht darüber hinaus auf Versorgungsaspekte und gesetzliche Regelungen wie auch auf die Diagnosestellung und präventive Therapie einer latenten tuberkulösen Infektion ein. Es wird ausgeführt, wann es der Behandlung durch spezialisierte Zentren bedarf.Die Aktualisierung der S2k-Leitlinie „Tuberkulose im Erwachsenenalter“ soll allen in der Tuberkuloseversorgung Tätigen als Richtschnur für die Prävention, die Diagnose und die Therapie der Tuberkulose dienen und helfen, den heutigen Herausforderungen im Umgang mit Tuberkulose in Deutschland gewachsen zu sein.
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Affiliation(s)
- Tom Schaberg
- Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose e. V. (DZK), Berlin
| | - Folke Brinkmann
- Abteilung für pädiatrische Pneumologie/CF-Zentrum, Universitätskinderklinik der Ruhr-Universität Bochum, Bochum
| | - Cornelia Feiterna-Sperling
- Klinik für Pädiatrie mit Schwerpunkt Pneumologie, Immunologie und Intensivmedizin, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin und Humboldt-Universität zu Berlin, Berlin
| | | | - Pia Hartmann
- Labor Dr. Wisplinghoff Köln, Klinische Infektiologie, Köln
- Department für Klinische Infektiologie, St. Vinzenz-Hospital, Köln
| | - Brit Häcker
- Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose e. V. (DZK), Berlin
| | | | | | - Jan Heyckendorf
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig-Holstein, Campus Kiel
| | - Christoph Lange
- Klinische Infektiologie, Forschungszentrum Borstel
- Deutsches Zentrum für Infektionsforschung (DZIF), Standort Hamburg-Lübeck-Borstel-Riems
- Respiratory Medicine and International Health, Universität zu Lübeck, Lübeck
- Baylor College of Medicine and Texas Childrenʼs Hospital, Global TB Program, Houston, TX, USA
| | - Florian P. Maurer
- Nationales Referenzzentrum für Mykobakterien, Forschungszentrum Borstel, Borstel
- Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Hamburg
| | - Albert Nienhaus
- Institut für Versorgungsforschung in der Dermatologie und bei Pflegeberufen (IVDP), Universitätsklinikum Hamburg Eppendorf (UKE), Hamburg
| | - Ralf Otto-Knapp
- Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose e. V. (DZK), Berlin
| | | | | | | | | | | | - Ralf Stahlmann
- Institut für klinische Pharmakologie und Toxikologie, Charité Universitätsmedizin, Berlin
| | - Torsten Bauer
- Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose e. V. (DZK), Berlin
- Lungenklinik Heckeshorn, Helios Klinikum Emil von Behring, Berlin
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Vargas Barahona L, Henao-Cordero J, Smith J, Gray A, Marshall CB, Scherger S, Bajrovic V, Koullias Y. Disseminated tuberculosis in a lung transplant recipient presenting as tenosynovitis, subcutaneous nodules, and liver abscesses. Ther Adv Infect Dis 2022; 9:20499361221132153. [PMID: 36311553 PMCID: PMC9597014 DOI: 10.1177/20499361221132153] [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: 08/12/2022] [Accepted: 09/23/2022] [Indexed: 11/09/2022] Open
Abstract
Tuberculosis is of particular concern in lung transplant recipients. We present the case of a patient who received a double lung transplant from a deceased donor from Mexico and developed disseminated tuberculosis 60 days post-transplant manifested as tenosynovitis, liver abscesses, and subcutaneous nodules with no definitive lung allograft involvement. The recipient did not have evidence of tuberculosis on explanted lungs, had a negative interferon gamma release assay pre-transplant, and did not have risk factors for this infection. Mycobacterium tuberculosis should remain in the differential diagnosis of early post-transplant infections with atypical presentations, evidence of dissemination, or lack of improvement with appropriate antimicrobial coverage, even in the absence of typical lung findings.
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Affiliation(s)
| | - José Henao-Cordero
- Division of Infectious Diseases, University of
Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Joshua Smith
- Division of Pulmonary Sciences and Critical
Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO,
USA
| | - Alice Gray
- Division of Pulmonary Sciences and Critical
Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO,
USA
| | - Carrie B. Marshall
- Department of Pathology, University of Colorado
Anschutz Medical Campus, Aurora, CO, USA
| | - Sias Scherger
- Division of Infectious Diseases, University of
Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Valida Bajrovic
- Division of Infectious Diseases, University of
Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Yiannis Koullias
- Division of Infectious Diseases, University of
Colorado Anschutz Medical Campus, Aurora, CO, USA,Gilead Sciences, Inc., Foster City, CA,
USA
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Sorohan BM, Ismail G, Tacu D, Obrișcă B, Ciolan G, Gîngu C, Sinescu I, Baston C. Mycobacterium Tuberculosis Infection after Kidney Transplantation: A Comprehensive Review. Pathogens 2022; 11:pathogens11091041. [PMID: 36145473 PMCID: PMC9505385 DOI: 10.3390/pathogens11091041] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 09/10/2022] [Accepted: 09/12/2022] [Indexed: 11/18/2022] Open
Abstract
Tuberculosis (TB) in kidney transplant (KT) recipients is an important opportunistic infection with higher incidence and prevalence than in the general population and is associated with important morbidity and mortality. We performed an extensive literature review of articles published between 1 January 2000 and 15 June 2022 to provide an evidence-based review of epidemiology, pathogenesis, diagnosis, treatment and outcomes of TB in KT recipients. We included all studies which reported epidemiological and/or outcome data regarding active TB in KT, and we approached the diagnostic and treatment challenges according to the current guidelines. Prevalence of active TB in KT recipients ranges between 0.3–15.2%. KT recipients with active TB could have a rejection rate up to 55.6%, a rate of graft loss that varies from 2.2% to 66.6% and a mortality rate up to 60%. Understanding the epidemiological risk, risk factors, transmission modalities, diagnosis and treatment challenges is critical for clinicians in providing an appropriate management for KT with TB. Among diagnostic challenges, which are at the same time associated with delay in management, the following should be considered: atypical clinical presentation, association with co-infections, decreased predictive values of screening tests, diverse radiological aspects and particular diagnostic methods. Regarding treatment challenges in KT recipients with TB, drug interactions, drug toxicities and therapeutical adherence must be considered.
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Affiliation(s)
- Bogdan Marian Sorohan
- Department of Kidney Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Department of General Medicine, Carol Davila University of Medicine and Pharmacy, 020022 Bucharest, Romania
- Correspondence: ; Tel.: +40-740156198
| | - Gener Ismail
- Department of General Medicine, Carol Davila University of Medicine and Pharmacy, 020022 Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Dorina Tacu
- Department of Kidney Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Bogdan Obrișcă
- Department of General Medicine, Carol Davila University of Medicine and Pharmacy, 020022 Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Gina Ciolan
- Department of Pneumology, Marius Nasta National Institute of Pneumology, 050159 Bucharest, Romania
| | - Costin Gîngu
- Department of Kidney Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Department of General Medicine, Carol Davila University of Medicine and Pharmacy, 020022 Bucharest, Romania
| | - Ioanel Sinescu
- Department of Kidney Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Department of General Medicine, Carol Davila University of Medicine and Pharmacy, 020022 Bucharest, Romania
| | - Cătălin Baston
- Department of Kidney Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Department of General Medicine, Carol Davila University of Medicine and Pharmacy, 020022 Bucharest, Romania
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Disseminated Histoplasmosis, Pulmonary Tuberculosis, and Cytomegalovirus Disease in a Renal Transplant Recipient after Infection with SARS-CoV-2. Case Rep Transplant 2022; 2022:8042168. [PMID: 36071914 PMCID: PMC9441404 DOI: 10.1155/2022/8042168] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 07/11/2022] [Accepted: 08/20/2022] [Indexed: 12/02/2022] Open
Abstract
Introduction Infection with SARS-CoV-2 increases the risk of acute graft dysfunction (AGD) in renal transplant recipients (RTR), and the risk of concurrently presenting with opportunistic infections is also increased. There is no current consensus on the management of immunosuppression during SARS-CoV-2 infection in RTR. Case Presentation. A 35-year-old male RTR from a living related donor presented with SARS-CoV-2 infection (January 2021). Two months later, despite alterations to his immunosuppression regimen (tacrolimus (TAC) was reduced by 50%, and the mycophenolic acid (MMF) was suspended with the remission of symptoms), the patient presented with pulmonary tuberculosis, pneumonia due to respiratory syncytial virus (RSV), cytomegalovirus (CMV) pneumonitis, and histoplasmosis (HP). Management was initiated with antituberculosis medications, ganciclovir, antibiotics, and liposomal amphotericin B, and the immunosuppressants were suspended, yet the patient's evolution was catastrophic and the outcome fatal. Conclusion We recommend that in RTR post-COVID-19, the immunosuppression regimen should be gradually reinstated along with strict vigilance in observing for highly prevalent coinfections (TB, HP, and CMV).
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Waller KMJ, De La Mata NL, Wyburn KR, Hedley JA, Rosales BM, Kelly PJ, Ramachandran V, Shah KK, Morton RL, Rawlinson WD, Webster AC. Notifiable Infectious Diseases Among Organ Transplant Recipients: A Data-Linked Cohort Study, 2000–2015. Open Forum Infect Dis 2022; 9:ofac337. [PMID: 35937651 PMCID: PMC9348761 DOI: 10.1093/ofid/ofac337] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Indexed: 11/12/2022] Open
Abstract
Background Infections, including common communicable infections such as influenza, frequently cause disease after organ transplantation, although the quantitative extent of infection and disease remains uncertain. Methods A cohort study was conducted to define the burden of notifiable infectious diseases among all solid organ recipients transplanted in New South Wales, Australia, 2000–2015. Data linkage was used to connect transplant registers to hospital admissions, notifiable diseases, and the death register. Standardized incidence ratios (SIRs) were calculated relative to general population notification rates, accounting for age, sex, and calendar year. Infection-related hospitalizations and deaths were identified. Results Among 4858 solid organ recipients followed for 39 183 person-years (PY), there were 792 notifications. Influenza was the most common infection (532 cases; incidence, 1358 [95% CI, 1247–1478] per 100 000 PY), highest within 3 months posttransplant. Next most common was salmonellosis (46 cases; incidence, 117 [95% CI, 87–156] per 100 000 PY), then pertussis (38 cases; incidence, 97 [95% CI, 71–133] per 100 000 PY). Influenza and invasive pneumococcal disease (IPD) showed significant excess cases compared with the general population (influenza SIR, 8.5 [95% CI, 7.8–9.2]; IPD SIR, 9.8 [95% CI, 6.9–13.9]), with high hospitalization rates (47% influenza cases, 68% IPD cases) and some mortality (4 influenza and 1 IPD deaths). By 10 years posttransplant, cumulative incidence of any vaccine-preventable disease was 12%, generally similar by transplanted organ, except higher among lung recipients. Gastrointestinal diseases, tuberculosis, and legionellosis had excess cases among transplant recipients, although there were few sexually transmitted infections and vector-borne diseases. Conclusions There is potential to avoid preventable infections among transplant recipients with improved vaccination programs, health education, and pretransplant donor and recipient screening.
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Affiliation(s)
- Karen M J Waller
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Health and Medicine, University of Sydney , Sydney , Australia
| | - Nicole L De La Mata
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Health and Medicine, University of Sydney , Sydney , Australia
| | - Kate R Wyburn
- Department of Renal Medicine, Royal Prince Alfred Hospital , Camperdown , Australia
- Sydney Medical School, Faculty of Health and Medicine, University of Sydney , Sydney , Australia
| | - James A Hedley
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Health and Medicine, University of Sydney , Sydney , Australia
| | - Brenda M Rosales
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Health and Medicine, University of Sydney , Sydney , Australia
| | - Patrick J Kelly
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Health and Medicine, University of Sydney , Sydney , Australia
| | - Vidiya Ramachandran
- Serology and Virology Division, New South Wales Health Pathology Randwick Prince of Wales Hospital , Randwick , Australia
| | - Karan K Shah
- Clinical Trials Centre, University of Sydney National Health and Medical Research Council , Camperdown , Australia
| | - Rachael L Morton
- Clinical Trials Centre, University of Sydney National Health and Medical Research Council , Camperdown , Australia
| | - William D Rawlinson
- Serology and Virology Division, New South Wales Health Pathology Randwick Prince of Wales Hospital , Randwick , Australia
- School of Medical Sciences, School of Biotechnology and Biomolecular Sciences, and School of Women’s and Children’s Health, University of New South Wales , Sydney , Australia
| | - Angela C Webster
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Health and Medicine, University of Sydney , Sydney , Australia
- Clinical Trials Centre, University of Sydney National Health and Medical Research Council , Camperdown , Australia
- Centre for Transplant and Renal Research, Westmead Hospital , Sydney , Australia
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Kim OH, Shim TS, Jo KW. Drug-level change and optimal dose adjustment of tacrolimus with the use of rifabutin for treating mycobacterial disease in solid organ transplant recipients. Transpl Infect Dis 2022; 24:e13893. [PMID: 35822673 DOI: 10.1111/tid.13893] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 05/24/2022] [Accepted: 06/14/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND Little is known about the change in drug level and the need for dose adjustment of calcineurin inhibitor when it is used with rifabutin in solid organ transplant (SOT) recipients. We aimed to analyze whether the drug level of tacrolimus significantly reduced after the use of rifabutin and to assess optimal adjustment of tacrolimus dose in SOT recipients. METHODS Of the SOT recipients in a tertiary referral center in South Korea in 2000-2019, 50 patients who maintained an unchanged dose of tacrolimus after the use of rifabutin for treating mycobacterial disease were enrolled. Their medical records were reviewed retrospectively. RESULTS The mean age of the patients was 53.9 ± 11.5 years. The most commonly transplanted organ was the liver (66.0%). The most common indication of rifabutin use was for treating active tuberculosis (78.0%). After rifabutin initiation, the trough level of tacrolimus decreased significantly to the subtherapeutic range in 38 (76.0%) patients. The drug levels of these 38 patients dropped from 7.2 to 3.8 ng/mL (p < 0.001) after rifabutin treatment. In these patients, the median 1.5-fold increase in the tacrolimus dose was required to restore the drug level to the within-therapeutic range. CONCLUSIONS These findings indicate that careful tacrolimus drug-level monitoring and dose adjustment are necessary for most SOT recipients when rifabutin is administered for the treatment of mycobacterial disease. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Ock-Hwa Kim
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Chungnam National University Sejong Hospital, Sejong, Republic of Korea
| | - Tae Sun Shim
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Kyung-Wook Jo
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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36
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Tuberculosis incidence in patients with chronic kidney disease: a systematic review and meta-analysis. Int J Infect Dis 2022; 122:188-201. [PMID: 35609860 DOI: 10.1016/j.ijid.2022.05.046] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 04/04/2022] [Accepted: 05/19/2022] [Indexed: 01/01/2023] Open
Abstract
OBJECTIVE The aim of this study was to estimate global TB incidence in patients with CKD. METHODS The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was followed to perform the study. Electronic and gray literature sources were investigated for studies published between 2000 and 2021. The Joanna Briggs Institute critical appraisal checklist was used to assess the quality of the studies, and STATA version 16 was used for analysis. The I2 heterogeneity test was employed to assess heterogeneity. To examine publication bias, funnel plots and Egger's regression tests were performed. RESULTS A total of 104 studies with a sample size of 1,548,774 were included. TB incidence in patients with CKD ranges from 60 per 100,000 in the UK to 19,270 per 100,000 in China. The pooled TB incidence was estimated as 3718 per 100,000 (95%CI; 3024, 4411). Higher pooled TB incidence was found in the African region (9952/100,000, 95%CI; 6854, 13,051), followed by the South-East Asian (7200/100,000, 95%CI; 4537, 9863) and Eastern Mediterranean (5508/100,000, 95%CI; 3470, 7547) regions. In particular, patients on hemodialysis (5611/100,000) and on peritoneal dialysis (3533/100,000) had higher incidence of TB than did renal transplantation patients (2700/100,000) and patients with predialysis CKD (913/100,000). Furthermore, extrapulmonary TB (2227/100,000) was more common than pulmonary TB (1786/100,000). CONCLUSION This study identifies high TB incidence in patients with CKD with regional disparities. Thus, the authors recommend active TB screening in this group of individuals.
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Malinis M, LaHoz RM, Vece G, Annambhotla P, Aslam S, Basavaraju SV, Bucio J, Danziger-Isakov L, Florescu DF, Jones JM, Rana M, Wolfe CR, Michaels MG. Donor-derived tuberculosis among solid organ transplant recipients in the United States - 2008-2018. Transpl Infect Dis 2022; 24:e13800. [PMID: 35064737 DOI: 10.1111/tid.13800] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 01/04/2022] [Accepted: 01/07/2022] [Indexed: 11/28/2022]
Abstract
Mycobacterium tuberculosis can be transmitted via organ donation and result in severe outcomes. To better understand donor-derived tuberculosis (DDTB), all potential transmissions reported to the Organ Procurement and Transplantation Network (OPTN) Ad Hoc Disease Transmission Advisory Committee between 2008-2018 were analyzed. Among 51 total reports, nine (17%) (9 donors/35 recipients) had ≥1 recipient with proven/probable disease transmission. Of these, eight were reported due to recipient disease, and one was reported due to a positive donor result. Proven/probable DDTB transmissions were reported in six lung and five non-lung recipients. The median time to diagnosis was 104 days post-transplant (range 0-165 days). Pulmonary TB, extrapulmonary TB, pulmonary plus extrapulmonary TB, and asymptomatic TB infection with positive interferon-gamma release assay were present in five, three, one, and two recipients, respectively. All recipients received treatment and survived except for one whose death was not attributed to TB. All donors associated with proven/probable DDTB had ≥1 TB risk factor. Six were born in a TB-endemic country, five had traveled to a TB-endemic country, 3 had been incarcerated, and 3 had latent TB infection. These cases highlight the importance of evaluating donors for TB based on risk factors. Early post-transplant TB in organ recipients of donors with TB risk factors requires prompt reporting to OPTN to identify other potential affected recipients and implement timely treatment interventions. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Maricar Malinis
- Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Ricardo M LaHoz
- Division of Infectious Disease and Geographic Medicine, University of Texas Southwestern, Dallas, TX
| | | | | | - Saima Aslam
- Division of Infectious Diseases and Global Public Health, University of California San Diego, San Diego, CA
| | | | | | - Lara Danziger-Isakov
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH
| | - Diana F Florescu
- Division of Infectious Diseases, Department of Internal Medicine University of Nebraska Medical Center, Lincoln, NE
| | | | - Meenakshi Rana
- Division of Infectious Diseases, Mount Sinai School of Medicine, New York, NY
| | | | - Marian G Michaels
- Department of Pediatrics, UPMC Children's Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, PA
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Varughese S, Sahay M, Shah D, Nagvekar V, Jha V. Evaluation and management of tuberculosis in solid organ transplant recipients: South Asian expert group opinion. INDIAN JOURNAL OF TRANSPLANTATION 2022. [DOI: 10.4103/ijot.ijot_18_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
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Rashid HU, Begum NAS, Kashem TS. Mycobacterial infections in solid organ transplant recipients. KOREAN JOURNAL OF TRANSPLANTATION 2021; 35:208-217. [PMID: 35769848 PMCID: PMC9235462 DOI: 10.4285/kjt.21.0033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 12/25/2021] [Indexed: 11/25/2022] Open
Abstract
Mycobacterium tuberculosis (MTB) infection in solid organ transplant (SOT) recipients remains a major challenge for physicians and surgeons. Active tuberculosis (TB) is associated with increased morbidity and mortality in SOT recipients. MTB usually develops after transplantation in a recipient with latent TB infection (LTBI) before transplantation and may also be transmitted from the donor or acquired from the community. Therefore, screening for LTBI in donors and recipients before transplantation is very important in preventing active disease after transplantation. This review article is based on recently published data, case series, and expert recommendations. We reviewed updated information about the epidemiology, diagnosis, and treatment of latent and active TB before and after transplantation. We also reviewed recent treatments for multidrug-resistant TB.
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Affiliation(s)
- Harun Ur Rashid
- Department of Nephrology, Kidney Foundation Hospital and Research Institute, Dhaka, Bangladesh
| | - Nura Afza Salma Begum
- Department of Nephrology, Kidney Foundation Hospital and Research Institute, Dhaka, Bangladesh
| | - Tasnuva Sarah Kashem
- Department of Nephrology, Kidney Foundation Hospital and Research Institute, Dhaka, Bangladesh
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40
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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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Park S, Park S, Kim JE, Yu MY, Kim YC, Kim DK, Joo KW, Kim YS, Han K, Lee H. Risk of active tuberculosis infection in kidney transplantation recipients: A matched comparative nationwide cohort study. Am J Transplant 2021; 21:3629-3639. [PMID: 33938138 DOI: 10.1111/ajt.16627] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 04/01/2021] [Accepted: 04/21/2021] [Indexed: 01/25/2023]
Abstract
Large-scale evidence comparing the risk of Mycobacterium tuberculosis (TB) between kidney transplant (KT) recipients and dialysis patients is warranted. This is a nationwide retrospective cohort study based on the claims database of South Korea where a moderate prevalence of TB is reported. We included incident KT recipients from 2011 to 2015 and compared their active TB risks with 1:1 matched dialysis and general population control groups, respectively. The risk of incident active TB was assessed by multivariable Cox regression. Associations between active TB and posttransplant death or death-censored graft failure were investigated. The number of matched subjects included in each of the study groups was 7462. The KT group showed a significantly higher risk of active TB than the general population group (hazard ratio [HR] 3.39 [1.88-6.10]), whereas it showed a similar risk to that of the dialysis group (HR 0.98 [0.73-1.31]). In KT patients, active TB was a significant risk factor for both death (HR 2.33 [1.24-4.39]) and death-censored graft failure (HR 2.26 [1.39-3.67]). Although KT recipients may not have to burden the additional risk of active TB when compared with dialysis patients in recent medicine, active TB should not be overlooked as it is associated with a worse prognosis in posttransplant patients.
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Affiliation(s)
- Sehoon Park
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.,Department of Internal Medicine, Armed Forces Capital Hospital, Seoul, Korea
| | - Sanghyun Park
- Department of Medical Statistics, College of Medicine, Catholic University of Korea, Seoul, Korea
| | - Ji Eun Kim
- Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
| | - Mi-Yeon Yu
- Department of Internal Medicine, Hanyang University Guri Hospital, Gyeonggi-do, Korea
| | - Yong Chul Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Dong Ki Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.,Kidney Research Institute, Seoul National University, Seoul, Korea
| | - Kwon Wook Joo
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.,Kidney Research Institute, Seoul National University, Seoul, Korea
| | - Yon Su Kim
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.,Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.,Kidney Research Institute, Seoul National University, Seoul, Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea
| | - Hajeong Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
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Joean O, Welte T, Gottlieb J. Chest Infections after Lung Transplantation. Chest 2021; 161:937-948. [PMID: 34673023 DOI: 10.1016/j.chest.2021.10.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 09/21/2021] [Accepted: 10/12/2021] [Indexed: 10/20/2022] Open
Abstract
Despite substantial progress in the long-term follow-up strategies for lung transplant recipients, morbidity and mortality remain high mostly due to the elevated infectious risk and to the development of chronic lung allograft dysfunction. The high immunosuppressive levels necessary to prevent acute rejection and the graft's constant exposure to the environment come at the high price of frequent infectious complications. Moreover, some infectious agents have been shown to trigger acute rejection or chronic allograft dysfunction. A rapid diagnostic approach followed by an early treatment and follow-up strategy are of paramount importance. They are, however, challenging endeavors due to the vast spectrum of possible pathogens and to the discrete clinical features as a consequence of transplant recipients' impaired immune response. This review proposes a stratified diagnostic strategy, discusses the most relevant pathogens and the corresponding therapeutic approaches while also offering an insight in the infection prevention strategies: vaccination, prophylaxis, preemptive therapy, antibiotic stewardship.
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Affiliation(s)
- Oana Joean
- Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany
| | - Tobias Welte
- Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease, Member of the German Center for Lung Research, Hannover, Germany.
| | - Jens Gottlieb
- Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease, Member of the German Center for Lung Research, Hannover, Germany
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DeFreitas MR, McAdams HP, Azfar Ali H, Iranmanesh AM, Chalian H. Complications of Lung Transplantation: Update on Imaging Manifestations and Management. Radiol Cardiothorac Imaging 2021; 3:e190252. [PMID: 34505059 DOI: 10.1148/ryct.2021190252] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Revised: 04/02/2021] [Accepted: 07/12/2021] [Indexed: 12/23/2022]
Abstract
As lung transplantation has become the most effective definitive treatment option for end-stage chronic respiratory diseases, yearly rates of this surgery have been steadily increasing. Despite improvement in surgical techniques and medical management of transplant recipients, complications from lung transplantation are a major cause of morbidity and mortality. Some of these complications can be classified on the basis of the time they typically occur after lung transplantation, while others may occur at any time. Imaging studies, in conjunction with clinical and laboratory evaluation, are key components in diagnosing and monitoring these conditions. Therefore, radiologists play a critical role in recognizing and communicating findings suggestive of lung transplantation complications. A description of imaging features of the most common lung transplantation complications, including surgical, medical, immunologic, and infectious complications, as well as an update on their management, will be reviewed here. Keywords: Pulmonary, Thorax, Surgery, Transplantation Supplemental material is available for this article. © RSNA, 2021.
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Affiliation(s)
- Mariana R DeFreitas
- Department of Radiology, Division of Cardiothoracic Imaging (M.R.D., H.P.M., A.M.I., H.C.), and Department of Medicine, Division of Pulmonary, Allergy and Critical Care (H.A.A.), Duke University Medical Center, Durham, NC
| | - Holman Page McAdams
- Department of Radiology, Division of Cardiothoracic Imaging (M.R.D., H.P.M., A.M.I., H.C.), and Department of Medicine, Division of Pulmonary, Allergy and Critical Care (H.A.A.), Duke University Medical Center, Durham, NC
| | - Hakim Azfar Ali
- Department of Radiology, Division of Cardiothoracic Imaging (M.R.D., H.P.M., A.M.I., H.C.), and Department of Medicine, Division of Pulmonary, Allergy and Critical Care (H.A.A.), Duke University Medical Center, Durham, NC
| | - Arya M Iranmanesh
- Department of Radiology, Division of Cardiothoracic Imaging (M.R.D., H.P.M., A.M.I., H.C.), and Department of Medicine, Division of Pulmonary, Allergy and Critical Care (H.A.A.), Duke University Medical Center, Durham, NC
| | - Hamid Chalian
- Department of Radiology, Division of Cardiothoracic Imaging (M.R.D., H.P.M., A.M.I., H.C.), and Department of Medicine, Division of Pulmonary, Allergy and Critical Care (H.A.A.), Duke University Medical Center, Durham, NC
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Kwon DE, Han SH, Han KD, La Y, Lee KH. Incidence rate of active tuberculosis in solid organ transplant recipients: Data from a nationwide population cohort in a high-endemic country. Transpl Infect Dis 2021; 23:e13729. [PMID: 34505751 DOI: 10.1111/tid.13729] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 09/01/2021] [Accepted: 09/02/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND The management of active tuberculosis (TB) in solid organ transplantation (SOT) recipients is challenging given the pharmacological interaction and the potential delays in diagnosis due to atypical presentation. The incidence rates (IRs) of post-SOT TB from the whole recipients' cohort in a high-endemic country have not been evaluated. METHODS We established a SOT cohort (n = 15 598) and confirmed cases of TB between 2011 and 2015 from the Korean National Health Insurance Database using ICD-10 codes. After excluding 1302 and 180 SOT-recipients due to age (<18 years) and presence of pre-SOT TB and/or treatment for latent TB during wash-out period between 2006 and cohort entry, we analyzed 14 116 SOT recipients and 70 580 individuals with no history of SOT matched by age and sex. The hazard ratios (HRs) of IRs were adjusted for age, sex, low-income status, diabetes mellitus, chronic co-morbidities, and anti-TNF-α therapy. RESULTS The IR of TB was significantly higher (adjusted HR [aHR]: 6.1, 95% confidence interval [CI]: 4.5-7.6) in SOT recipients (4.9/1000 person-years) than in non-SOT individuals (0.8/1000 person-years). Of the transplanted organs, the pancreas (pancreas alone and simultaneous pancreas-kidney) and lung had the highest IR (aHR: 16.3 [6.1-42.2] and 16.1 [5.9-43.8], respectively). The use of anti-thymocyte globulin and azathioprine was associated with a higher IR (aHR: 1.53 [1.01-2.43] and 3.92 [1.21-12.47], respectively), but basiliximab was associated with a lower IR (aHR: 0.67 [0.48-0.98]). CONCLUSION The IR of TB in SOT recipients, especially in the pancreas and lung, was significantly higher than that in the non-SOT population.
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Affiliation(s)
- Da Eun Kwon
- Department of Internal Medicine, Division of Infectious Disease, Yonsei University College of Medicine, Yonsei University, Seoul, Republic of Korea
| | - Sang Hoon Han
- Department of Internal Medicine, Division of Infectious Disease, Yonsei University College of Medicine, Yonsei University, Seoul, Republic of Korea
| | - Kyung Do Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Yeonju La
- Department of Internal Medicine, Division of Infectious Disease, Yonsei University College of Medicine, Yonsei University, Seoul, Republic of Korea
| | - Kyoung Hwa Lee
- Department of Internal Medicine, Division of Infectious Disease, Yonsei University College of Medicine, Yonsei University, Seoul, Republic of Korea
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Malinis M, Koff A. Mycobacterium tuberculosis in solid organ transplant donors and recipients. Curr Opin Organ Transplant 2021; 26:432-439. [PMID: 34074939 DOI: 10.1097/mot.0000000000000885] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
PURPOSE OF REVIEW Due to impaired immune response, solid organ transplant (SOT) recipients are susceptible to tuberculosis (TB) and its subsequent morbidity and mortality. Current prevention strategies, diagnostic and treatment approach to TB infection in donors and recipients were reviewed in this article. RECENT FINDINGS Screening of latent tuberculosis infection (LTBI) in donors and recipients is the cornerstone of TB-preventive strategy in recipients and requires an assessment of TB risk factors, TB-specific immunity testing, and radiographic evaluation. Interferon-gamma release assay has superseded the tuberculin skin test in LTBI evaluation despite its recognized limitations. LTBI treatment should be offered to transplant candidates and living donors before transplantation and donation, respectively. Diagnosis of TB disease can be challenging because of nonspecific clinical presentation in the recipient and is limited by the sensitivity of current diagnostics. The approach to LTBI and TB disease treatment is similar to the general population, but can be challenging because of potential drug interactions and toxicities. SUMMARY The appropriate evaluation of donors and recipients for TB can mitigate posttransplant TB disease. Current approaches to diagnosis and treatment parallels that of immunocompetent hosts. Future research evaluating existing and novel diagnostics and treatment in transplant recipients is needed.
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Affiliation(s)
- Maricar Malinis
- Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
| | - Alan Koff
- Division of Infectious Diseases, Department of Internal Medicine, UC Davis School of Medicine, Sacramento, California, USA
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Anand P. Neurologic Infections in Patients on Immunomodulatory and Immunosuppressive Therapies. ACTA ACUST UNITED AC 2021; 27:1066-1104. [PMID: 34623105 DOI: 10.1212/con.0000000000000985] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW Both broadly immunosuppressive medications and selective immunomodulatory agents that act on particular components of the immune system are increasingly used in the treatment of neurologic and non-neurologic diseases. These therapies predispose patients to particular infections, some of which may affect the nervous system. Therefore, familiarity with the clinical and radiologic features of neurologic infections associated with specific immunomodulatory therapies is of importance for the practicing neurologist. This article reviews these neuroinfectious conditions, as well as other neurologic complications unique to transplant recipients and other patients who are immunocompromised. RECENT FINDINGS Diagnosis of infectious pathogens in patients who are immunocompromised may be particularly challenging because a decreased immune response can lead to atypical imaging or laboratory findings. Next-generation sequencing and other novel diagnostic modalities may improve the rate of early identification of neurologic infections in patients who are immunocompromised and ultimately ameliorate outcomes in this vulnerable population. SUMMARY A broad range of bacterial, viral, fungal, and parasitic infections of the nervous system can complicate solid organ and hematopoietic cell transplantation as well as other forms of immunocompromise. In addition to neurologic infections, such patients are at risk of neurotoxic and neuroinflammatory complications related to immunomodulatory and immunosuppressive therapies. Early recognition of infectious and noninfectious complications of immunocompromise is essential to guide appropriate treatment, which can include antimicrobial therapy and, in some cases, withdrawal of the predisposing medication with a transition to an alternative regimen.
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Nasir N, Sarfaraz S, Khanum I, Ansari T, Nasim A, Dodani SK, Luxmi S. Tuberculosis in Solid Organ Transplantation: Insights from TB Endemic Areas. Curr Infect Dis Rep 2021. [DOI: 10.1007/s11908-021-00756-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Babar ZU, Nasim A, Kumar S, Nazmi J, Badlani S, Nadeem A, Aziz T. A case series of multidrug-resistant tuberculosis in renal transplant recipients: Challenges in management from a TB endemic country. Transpl Infect Dis 2021; 23:e13659. [PMID: 34057810 DOI: 10.1111/tid.13659] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 02/15/2021] [Accepted: 03/07/2021] [Indexed: 11/28/2022]
Abstract
Multidrug-resistant tuberculosis (MDR-TB) is caused by Mycobacterium tuberculosis that is resistant to isoniazid and rifampicin (Rif). The use of immunosuppressive drugs in solid organ transplant recipients can increase the risk of TB. Management of MDR-TB is quite challenging in the general population with poor compliance owing to lengthy treatment duration and drug toxicities. New drugs as well as shorter regimen have been used to increase the likelihood of adherence. The experience of treating MDR-TB in the transplant recipients is limited. New drugs like bedaquiline, linezolid, clofazimine, and delamanid have rarely been used in transplant recipients. To the best of our knowledge, only 14 cases of MDR-TB in transplant population have been reported in the literature and no case from Pakistan, a high TB burden country. We are reporting our experience of treating 4 renal transplant recipients. We used new drug regimen and found many side effects. Treatment outcome was successful with complete cure in 3 of our patients, however one died of severe drug toxicity. The most worrisome drug interaction was between azathioprine and linezolid, with life-threatening thrombocytopenia. There was no graft dysfunction noted at the end of the therapy. The management of MDR-TB in transplant recipients is challenging; excellent coordination between transplant team and Infectious Diseases Physician for close monitoring and follow-up is needed.
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Affiliation(s)
- Zaheer Udin Babar
- Infectious Diseases Department, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan
| | - Asma Nasim
- Infectious Diseases Department, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan
| | - Sunil Kumar
- Infectious Diseases Department, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan
| | - Jawwad Nazmi
- Department of Pulmonology, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan
| | - Sanjay Badlani
- Infectious Diseases Department, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan
| | - Ali Nadeem
- Department of Microbiology, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan
| | - Tahir Aziz
- Department of Transplantation, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan
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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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50
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Meinerz G, Silva CKD, Dorsdt DMB, Adames JB, Andrade JP, Ventura PE, Monteiro ADA, Pasqualotto AC, Garcia VD, Keitel E. Latent tuberculosis screening before kidney transplantation in the South of Brazil. J Bras Nefrol 2021; 43:520-529. [PMID: 33999988 PMCID: PMC8940112 DOI: 10.1590/2175-8239-jbn-2020-0189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Accepted: 02/25/2021] [Indexed: 11/22/2022] Open
Abstract
Background: Tuberculosis (TB) is a prevalent infection after kidney transplantation (KT) in high-burden countries. Latent tuberculosis infection (LTBI) screening includes previous TB history, chest radiograph findings, and tuberculin test (TST) and/or interferon-gamma release assays (IGRAs) results. We aimed to compare our routine LTBI screening of KT candidates and living donors (LD) with their IGRA results, and evaluate if this would improve isoniazid (INH) treatment referral. Methods: We evaluated adult KT candidates and LD with complete routine LTBI screening and QuantiFERON-TB® Gold In-Tube (QFT) testing. Blood samples were collected from April 4th, 2014 to October 31st, 2018, with follow-up until October 31st, 2019. Results: There were 116 KT recipients, with 30% QFT-positive results. Positive QFT was associated with past TB history (p=0.007), positive TST (p<0.0001), residual radiographic lesions (p=0.003), and diabetes (p=0.035). There were 25 LD, 40% had positive QFT. Positive QFT was associated with a positive TST (p=0.002). Positive QFT results increased INH referral in 80%. Post-transplant TB incidence was 2.6% in a median follow-up of 2 (1-33) months. No variables were associated with post-transplant TB. TB patients had inferior, although non-significant, 5-year graft survival (66.7% vs. 76.5%) (p = 0.402). Conclusion: In the present study, the association of QFT to our routine LTBI screening incremented INH treatment referral, but there was still a high incidence of post-transplant TB, possibly related to other forms of infection, such as new exposure and donor transmission.
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Affiliation(s)
- Gisele Meinerz
- Santa Casa de Misericórdia de Porto Alegre, Departamento de Nefrologia e Transplante de Rim e Pâncreas, Porto Alegre, RS, Brasil.,Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Patologia, Porto Alegre, RS, Brasil
| | - Cynthia Keitel da Silva
- Santa Casa de Misericórdia de Porto Alegre, Departamento de Nefrologia e Transplante de Rim e Pâncreas, Porto Alegre, RS, Brasil.,Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Patologia, Porto Alegre, RS, Brasil
| | | | - Julia Bertoni Adames
- Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brasil
| | | | - Pedro Enrico Ventura
- Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brasil
| | | | - Alessandro Comarú Pasqualotto
- Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brasil.,Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brasil
| | - Valter Duro Garcia
- Santa Casa de Misericórdia de Porto Alegre, Departamento de Nefrologia e Transplante de Rim e Pâncreas, Porto Alegre, RS, Brasil
| | - Elizete Keitel
- Santa Casa de Misericórdia de Porto Alegre, Departamento de Nefrologia e Transplante de Rim e Pâncreas, Porto Alegre, RS, Brasil.,Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Patologia, Porto Alegre, RS, Brasil
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