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Skouvig Pedersen O, Sperling S, Koch A, Lillebaek T, Dahl VN, Fløe A. Evaluating stratified T-SPOT.TB results for diagnostic accuracy in tuberculosis disease: a retrospective cohort study with sensitivities, specificities, and predictive values. Clin Microbiol Infect 2025; 31:808-817. [PMID: 39793964 DOI: 10.1016/j.cmi.2025.01.002] [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: 10/30/2024] [Revised: 12/29/2024] [Accepted: 01/04/2025] [Indexed: 01/13/2025]
Abstract
OBJECTIVES The study aimed to investigate the association between quantitative T-SPOT.TB values and the risk of incident and prevalent tuberculosis disease (TBD), identify risk factors, and evaluate test accuracy. METHODS This retrospective cohort study followed patients tested consecutively with T-SPOT.TB at Aarhus University Hospital from 2010 to 2017, with follow-up for incident TBD through 2022. Data on demographics, comorbidities, medications, and TB status were collected from patient records and national registries. Cox proportional hazard models with restricted cubic splines assessed the risk of incident TBD (occurring ≥3 months post-test) by quantitative spot counts. Cox and log-binomial regressions identified risk factors for incident and prevalent TBD (occurring between 3 months before and after the test). Sensitivity, specificity, and predictive values assessed test accuracy. T-SPOT.TB was the index test, and microbiologically and/or clinically confirmed TBD was the reference standard. RESULTS Among 8542 individuals with complete follow-up, 59 developed incident TBD over 67 456 person-years. Among 9014 individuals tested once, 162 had prevalent TBD at the time of testing. The risk of incident TBD increased with higher spot counts, plateauing for tests with more than ten spots. The strongest risk factors for both incident and prevalent TBD were categorical T-SPOT.TB results: compared with negative tests (≤4 spots), adjusted hazard ratios for incident TBD were 5.0 (95% CI: 1.9-13.1) for borderline (5-7 spots) and 8.0 (95% CI: 4.0-15.7) for positive tests (≥8 spots). Adjusted risk ratios for prevalent TBD were 14.9 (95% CI: 7.7-28.9) for borderline and 35.6 (95% CI: 21.4-59.2) for positive tests. Sensitivities for incident and prevalent TBD were 54.0% (95% CI: 39.3-68.2%) and 78.4% (95% CI: 71.3-84.5%), respectively. Specificities were 84.8 (84.0-85.4) and 83.7 (82.9-84.4), respectively. DISCUSSION Incident TBD risk increases with T-SPOT.TB values but plateaus beyond 10 spots. Borderline and positive T-SPOT.TB results are strongly linked to TBD risk.
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Affiliation(s)
- Ole Skouvig Pedersen
- Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
| | - Søren Sperling
- Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark; Department of Respiratory Diseases, Gødstrup Hospital, Gødstrup, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Anders Koch
- Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark; Department of Infectious Diseases, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark
| | - Troels Lillebaek
- Global Health Section, Department of Public Health, University of Copenhagen, Copenhagen, Denmark; International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark
| | - Victor Naestholt Dahl
- International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
| | - Andreas Fløe
- Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Virdee AK, Knudtzen FC, Llibre JM, Omland LH, Obel N, Stærke NB, Åhsberg J, Ørsted I, Kronborg G, Mohey R, Montejo MDPF, Johansen IS, Martin-Iguacel R. Risk of Tuberculosis After Achieving HIV Virological Suppression on Antiretroviral Therapy: A Danish Nationwide Prospective Cohort Study. Clin Infect Dis 2025; 80:854-863. [PMID: 39378332 DOI: 10.1093/cid/ciae499] [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: 07/17/2024] [Revised: 09/24/2024] [Accepted: 10/05/2024] [Indexed: 10/10/2024] Open
Abstract
BACKGROUND In countries with low tuberculosis burden, the risk of tuberculosis in people with human immunodeficiency virus (HIV; PWH) once HIV virological suppression is achieved is not fully understood. METHODS In a nationwide cohort, we included all adult PWH from the Danish HIV Cohort initiating antiretroviral therapy (ART) (1995-2017) without prior tuberculosis disease. We used Kaplan-Meier estimation and Poisson regression to calculate the tuberculosis incidence rate (IR) after 6 months of ART, along with associated risk factors and mortality rates. RESULTS Among 6849 PWH initiating ART (median follow-up, 7.4 years), 84 developed tuberculosis (IR, 1.4/1000 person-years [PY]), 54 of them >6 months after ART initiation (IR, 0.97/1000 PY [95% confidence interval [CI]: 1.17-1.79); 1.95/1000 PY [1.34-2.76] in non-Danish born, 0.36/1000 PY [.21-.62] in Danish born without injection drug use (IDU), and 2.95/1000 PY [1.53-5.66] in Danish born with IDU). Danish-born individuals with suppressed viremia and no IDU or known tuberculosis exposures had the lowest risk (IR, 0.05/1000 PY). In the adjusted analysis, being non-Danish born (adjusted IR ratio, 4.27 [95% CI: 2.36-7.72]), IDU (4.95 [2.55-9.62]), and previous AIDS-defining events (2.05 [1.06-3.94]) raised the tuberculosis risk, while suppressed HIV RNA levels (0.58 [.34-.99]) reduced it. The overall mortality rate for HIV/tuberculosis coinfected after ART was high, at 48.9/1000 PY (95% CI: 30.4-78.7). CONCLUSIONS The tuberculosis risk remains elevated in PWH beyond 6 months after ART initiation, especially among migrants, those with IDU, those without suppressed HIV RNA, and those exposed to areas highly endemic for tuberculosis or with social risk determinants of health. Conversely, PWH without these risk factors have a tuberculosis risk similar to the general population and would not require targeted tuberculosis screening strategies.
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Affiliation(s)
- Amrit Kaur Virdee
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark
- Research Unit for Infectious Diseases, University of Southern Denmark, Odense, Denmark
| | - Fredrikke Christie Knudtzen
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark
- Research Unit for Infectious Diseases, University of Southern Denmark, Odense, Denmark
| | - Josep M Llibre
- Infectious Diseases Department and Fight Infections Foundation, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain
| | - Lars Haukali Omland
- Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Niels Obel
- Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | | | - Johanna Åhsberg
- Research Unit for Infectious Diseases, University of Southern Denmark, Odense, Denmark
- Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Mycobacterial Centre for Research Southern Denmark-MyCRESD, Odense, Denmark
| | - Iben Ørsted
- Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark
| | - Gitte Kronborg
- Department of Infectious Diseases, Copenhagen University Hospital, Amager Hvidovre Hospital, Hvidovre, Denmark
| | - Rajesh Mohey
- Department of Infectious Diseases, Viborg Hospital, Viborg, Denmark
| | | | - Isik Somuncu Johansen
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark
- Research Unit for Infectious Diseases, University of Southern Denmark, Odense, Denmark
- Mycobacterial Centre for Research Southern Denmark-MyCRESD, Odense, Denmark
| | - Raquel Martin-Iguacel
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark
- Research Unit for Infectious Diseases, University of Southern Denmark, Odense, Denmark
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Sadeghi MH, Radmehr S, Mohagheghzadeh N, Fathi J, Malekzadegan Y, Moghadam HZ. Innovative electrochemical biosensors for tuberculosis detection. Clin Chim Acta 2025; 574:120327. [PMID: 40286897 DOI: 10.1016/j.cca.2025.120327] [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: 03/22/2025] [Revised: 04/19/2025] [Accepted: 04/21/2025] [Indexed: 04/29/2025]
Abstract
Tuberculosis (TB) continues to pose a significant global health threat, highlighting the urgent need for the development of rapid, precise, and accessible diagnostic tools to effectively manage its transmission. Conventional diagnostic techniques, such as sputum microscopy and culture-based assays, face several drawbacks, including lengthy processing times, limited sensitivity, and the requirement for specialized laboratory facilities. In this landscape, electrochemical biosensors have emerged as promising alternatives, offering improved sensitivity, specificity, and rapid detection capabilities. This review presents a thorough overview of recent advancements in the development and application of innovative electrochemical biosensors for TB detection. It explores the integration of nanomaterials such as graphene, gold nanoparticles, and carbon nanotubes, focusing on their contributions to enhanced sensor performance in terms of signal amplification and biorecognition efficacy. By synthesizing current research and technological developments, this review emphasizes the considerable potential of electrochemical biosensors to transform TB diagnostics, ultimately assisting in better disease management and control strategies worldwide.
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Affiliation(s)
- Mohammad Hassan Sadeghi
- Medical Student, School of Medicine,Zahedan University of Medical Science, Sistanbaluchestan, Iran
| | - Safa Radmehr
- Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Neda Mohagheghzadeh
- Department of Bacteriology & Virology, School of Medicine, Shiraz University of Medical Sciences, Iran
| | - Javad Fathi
- Department of Bacteriology & Virology, School of Medicine, Shiraz University of Medical Sciences, Iran
| | - Yalda Malekzadegan
- Department of Microbiology and Parasitology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran.
| | - Hesam Zendehdel Moghadam
- Research and Technology Department, Iranian Academic Center for Education Culture and Research Kerman Branch, Iran.
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Ahmad I, Sead FF, Kanjariya P, Kumar A, Rajivm A, Shankhyan A, Jaidka S, Kumar H, Aminov Z. Nanomaterial sensors for enhanced detection of serotonin. Clin Chim Acta 2025; 569:120160. [PMID: 39892692 DOI: 10.1016/j.cca.2025.120160] [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: 01/04/2025] [Revised: 01/23/2025] [Accepted: 01/23/2025] [Indexed: 02/04/2025]
Abstract
The detection of serotonin (5-HT), a critical neurotransmitter, has garnered significant attention in biosensor research because of its pivotal role in neurological and physiological processes. This narrative review highlights advancements in nanomaterial-based sensors designed to increase the sensitivity, specificity, and functionality of serotonin detection. Carbon-based nanomaterials, including carbon nanotubes (CNTs), graphene derivatives, and carbon nanofibers (CNFs), have demonstrated remarkable potential owing to their large surface area, superior electrical conductivity, and biocompatibility. These materials enable rapid electron transfer and selective serotonin adsorption, making them integral to electrochemical and wearable sensor technologies. Emerging technologies, including field-effect transistors (FETs), magnetoelastic biosensors, and molecularly imprinted polymers (MIPs), have demonstrated ultralow detection limits and real-time monitoring capabilities, suggesting promising applications for clinical diagnostics and personalized healthcare. Metal-based sensors, which utilize nanoparticles of gold, silver, and other metals, have also shown exceptional performance in serotonin detection through enhanced electrocatalysis and optical properties. This review underscores the transformative potential of nanomaterial-based sensors in serotonin detection, emphasizing their role in advancing neuroscience research, disease diagnostics, and therapeutic monitoring.
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Affiliation(s)
- Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia; Health and Medical Research Center, King Khalid University, AlQura'a, Abha, P.O. Box 960, Saudi Arabia.
| | - Fadhel F Sead
- Department of Dentistry, College of Dentistry, the Islamic University, Najaf, Iraq; Department of Medical Analysis, Medical Laboratory Technique College, the Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq; Department of Medical Analysis, Medical Laboratory Technique College, the Islamic University of Babylon, Babylon, Iraq
| | - Prakash Kanjariya
- Marwadi University Research Center, Department of Physics, Faculty of Science, Marwadi University, Rajkot 360003, Gujarat, India
| | - Anjan Kumar
- Department of Electronics and Communication Engineering, GLA University, Mathura 281406, India
| | - Asha Rajivm
- Department of Physics & Electronics, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - Aman Shankhyan
- Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura 140401, Punjab, India
| | - Sachin Jaidka
- Department of Physics, Department of Applied Sciences, Chandigarh Engineering College, Chandigarh Group of Colleges-Jhanjeri, Mohali140307, Punjab, India
| | - Harish Kumar
- Department of Applied Sciences-Physics, NIMS Institute of Engineering & Technology, NIMS University Rajasthan, Jaipur, India
| | - Zafar Aminov
- Department of Public Health and Healthcare Management, Samarkand State Medical University, 18 Amir Temur Street, Samarkand, Uzbekistan
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Johansen IS, Roen A, Kraef C, Martín-Iguacel R, Nemeth J, Fenner L, Zangerle R, Llibre JM, Miller RF, Suarez I, de Wit S, Wit F, Mussini C, Saracino A, Canetti D, Volny-Anne A, Jaschinski N, Neesgaard B, Ryom L, Peters L, Garges HP, Rooney JF, Podlekareva D, Mocroft A, Kirk O. Risk of tuberculosis after initiation of antiretroviral therapy among persons with HIV in Europe. Int J Infect Dis 2024; 147:107199. [PMID: 39142437 DOI: 10.1016/j.ijid.2024.107199] [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: 05/07/2024] [Revised: 07/27/2024] [Accepted: 07/31/2024] [Indexed: 08/16/2024] Open
Abstract
OBJECTIVES Tuberculosis (TB) risk after initiation of antiretroviral treatment (ART) is not well described in a European setting, with an average TB incidence of 25/105 in the background population. METHODS We included all adult persons with HIV starting ART in the RESPOND cohort between 2012 and 2020. TB incidence rates (IR) were assessed for consecutive time intervals post-ART initiation. Risk factors for TB within 6 months from ART initiation were evaluated using Poisson regression models. RESULTS Among 8441 persons with HIV, who started ART, 66 developed TB during 34,239 person-years of follow-up (PYFU), corresponding to 1.87/1000 PYFU (95% confidence interval [CI]: 1.47-2.37). TB IR was highest in the first 3 months after ART initiation (14.41/1000 PY (95%CI 10.08-20.61]) and declined at 3-6, 6-12, and >12 months post-ART initiation (5.89 [95%CI 3.35-10.37], 2.54 [95%CI 1.36-4.73] and 0.51 [95%CI 0.30-0.86]), respectively. Independent risk factors for TB within the first 6 months after ART initiation included follow-up in Northern or Eastern Europe region, African origin, baseline CD4 count <200 cells/mm3, HIV RNA >100,000 copies/mL, injecting drug use and heterosexual transmission. CONCLUSIONS TB IR was highest in the first 3 months post-ART initiation and was associated with baseline risk factors, highlighting the importance of thorough TB risk assessment at ART initiation.
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Affiliation(s)
- Isik S Johansen
- Department of Infectious Diseases, Odense University Hospital, University of Southern Denmark, Odense, Denmark; Research Unit of Infectious Diseases, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
| | - Ashley Roen
- Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, UK; CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Christian Kraef
- CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Raquel Martín-Iguacel
- Department of Infectious Diseases, Odense University Hospital, University of Southern Denmark, Odense, Denmark; Research Unit of Infectious Diseases, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Johannes Nemeth
- Swiss HIV Cohort Study (SHCS), University of Zurich, Zurich, Switzerland
| | - Lukas Fenner
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | - Robert Zangerle
- Austrian HIV Cohort Study (AHIVCOS), Medizinische Universität Innsbruck, Innsbruck, Austria
| | - Josep M Llibre
- Infectious Diseases Division, University Hospital Germans Trias, Badalona, Spain; Fight Infections Foundation, Badalona, Spain
| | - Robert F Miller
- The Royal Free HIV Cohort Study, Royal Free Hospital, University College London, London, UK
| | - Isabelle Suarez
- Department of Internal Medicine, Medical Faculty and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Stephane de Wit
- CHU Saint-Pierre, Centre de Recherche en Maladies Infectieuses a.s.b.l., Brussels, Belgium
| | - Ferdinand Wit
- AIDS Therapy Evaluation in the Netherlands (ATHENA) Cohort, HIV Monitoring Foundation, Amsterdam, the Netherlands
| | | | - Annalisa Saracino
- Italian Cohort Naive Antiretrovirals (ICONA), ASST Santi Paolo e Carlo, Milano, Italy
| | - Diana Canetti
- San Raffaele Scientific Institute, Università Vita-Salute San Raffaele, Milano, Italy
| | | | - Nadine Jaschinski
- CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Bastian Neesgaard
- CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Lene Ryom
- CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Dept of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Lars Peters
- CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | | | | | - Daria Podlekareva
- CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Department of Respiratory Medicine and Infectious Disease, Copenhagen University Hospital, Bispebjerg, Denmark; Gilead Sciences, Foster City, CA, USA
| | - Amanda Mocroft
- Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, UK; CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Ole Kirk
- Research Unit of Infectious Diseases, Department of Clinical Research, University of Southern Denmark, Odense, Denmark; CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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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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Perez RL, Chase J, Tanner R. Shared challenges to the control of complex intracellular neglected pathogens. Front Public Health 2024; 12:1423420. [PMID: 39324165 PMCID: PMC11422159 DOI: 10.3389/fpubh.2024.1423420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 08/13/2024] [Indexed: 09/27/2024] Open
Abstract
The complex intracellular pathogens Mycobacterium tuberculosis, Mycobacterium leprae, Leishmania spp., and Burkholderia pseudomallei, which cause tuberculosis, leprosy, leishmaniasis, and melioidosis respectively, represent major health threats with a significant global burden concentrated in low- and middle-income countries. While these diseases vary in their aetiology, pathology and epidemiology, they share key similarities in the biological and sociodemographic factors influencing their incidence and impact worldwide. In particular, their occurrence in resource-limited settings has important implications for research and development, disease prevalence and associated risk factors, as well as access to diagnostics and therapeutics. In accordance with the vision of the VALIDATE (VAccine deveLopment for complex Intracellular neglecteD pAThogeEns) Network, we consider shared challenges to the effective prevention, diagnosis and treatment of these diseases as shaped by both biological and social factors, illustrating the importance of taking an interdisciplinary approach. We further highlight how a cross-pathogen perspective may provide valuable insights for understanding and addressing challenges to the control of all four pathogens.
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Affiliation(s)
- Rebecca Lynn Perez
- Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
- Wadham College, University of Oxford, Oxford, United Kingdom
| | - Jemima Chase
- Wadham College, University of Oxford, Oxford, United Kingdom
| | - Rachel Tanner
- Wadham College, University of Oxford, Oxford, United Kingdom
- Department of Biology, University of Oxford, Oxford, United Kingdom
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Vasiliu A, Martinez L, Gupta RK, Hamada Y, Ness T, Kay A, Bonnet M, Sester M, Kaufmann SHE, Lange C, Mandalakas AM. Tuberculosis prevention: current strategies and future directions. Clin Microbiol Infect 2024; 30:1123-1130. [PMID: 37918510 PMCID: PMC11524220 DOI: 10.1016/j.cmi.2023.10.023] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 10/20/2023] [Accepted: 10/22/2023] [Indexed: 11/04/2023]
Abstract
BACKGROUND An estimated one fourth of the world's population is infected with Mycobacterium tuberculosis, and 5-10% of those infected develop tuberculosis in their lifetime. Preventing tuberculosis is one of the most underutilized but essential components of curtailing the tuberculosis epidemic. Moreover, current evidence illustrates that tuberculosis manifestations occur along a dynamic spectrum from infection to disease rather than a binary state as historically conceptualized. Elucidating determinants of transition between these states is crucial to decreasing the tuberculosis burden and reaching the END-TB Strategy goals as defined by the WHO. Vaccination, detection of infection, and provision of preventive treatment are key elements of tuberculosis prevention. OBJECTIVES This review provides a comprehensive summary of recent evidence and state-of-the-art updates on advancements to prevent tuberculosis in various settings and high-risk populations. SOURCES We identified relevant studies in the literature and synthesized the findings to provide an overview of the current state of tuberculosis prevention strategies and latest research developments. CONTENT We present the current knowledge and recommendations regarding tuberculosis prevention, with a focus on M. bovis Bacille-Calmette-Guérin vaccination and novel vaccine candidates, tests for latent infection with M. tuberculosis, regimens available for tuberculosis preventive treatment and recommendations in low- and high-burden settings. IMPLICATIONS Effective tuberculosis prevention worldwide requires a multipronged approach that addresses social determinants, and improves access to tuberculosis detection and to new short tuberculosis preventive treatment regimens. Robust collaboration and innovative research are needed to reduce the global burden of tuberculosis and develop new detection tools, vaccines, and preventive treatments that serve all populations and ages.
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Affiliation(s)
- Anca Vasiliu
- Department of Pediatrics, Baylor College of Medicine, Global TB Program, Houston, TX, USA.
| | - Leonardo Martinez
- Department of Epidemiology, School of Public Health, Boston University, Boston, MA, USA
| | - Rishi K Gupta
- Institute of Health Informatics, University College London, London, United Kingdom
| | - Yohhei Hamada
- Institute for Global Health, University College London, London, United Kingdom
| | - Tara Ness
- Department of Pediatrics, Baylor College of Medicine, Global TB Program, Houston, TX, USA
| | - Alexander Kay
- Department of Pediatrics, Baylor College of Medicine, Global TB Program, Houston, TX, USA
| | - Maryline Bonnet
- University of Montpellier, TransVIHMI, IRD, INSERM, Montpellier, France
| | - Martina Sester
- Department of Transplant and Infection Immunology, Saarland University, Homburg, Germany
| | - Stefan H E Kaufmann
- Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany; Systems Immunology (Emeritus Group), Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany; Hagler Institute for Advanced Study, Texas A&M University, College Station, TX, USA
| | - Christoph Lange
- Department of Pediatrics, Baylor College of Medicine, Global TB Program, Houston, TX, USA; Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany; Respiratory Medicine and International Health, University of Lübeck, Lübeck, Germany
| | - Anna M Mandalakas
- Department of Pediatrics, Baylor College of Medicine, Global TB Program, Houston, TX, USA; Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany
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9
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Headley CA, Gautam S, Olmo‐Fontanez A, Garcia‐Vilanova A, Dwivedi V, Schami A, Weintraub S, Tsao PS, Torrelles JB, Turner J. Mitochondrial Transplantation Promotes Protective Effector and Memory CD4 + T Cell Response During Mycobacterium Tuberculosis Infection and Diminishes Exhaustion and Senescence in Elderly CD4 + T cells. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2401077. [PMID: 39039808 PMCID: PMC11423092 DOI: 10.1002/advs.202401077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 05/16/2024] [Indexed: 07/24/2024]
Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), is a major global health concern, particularly affecting those with weakened immune systems, including the elderly. CD4+ T cell response is crucial for immunity against M.tb, but chronic infections and aging can lead to T cell exhaustion and senescence, worsening TB disease. Mitochondrial dysfunction, prevalent in aging and chronic diseases, disrupts cellular metabolism, increases oxidative stress, and impairs T-cell functions. This study investigates the effect of mitochondrial transplantation (mito-transfer) on CD4+ T cell differentiation and function in aged mouse models and human CD4+ T cells from elderly individuals. Mito-transfer in naïve CD4+ T cells is found to promote protective effector and memory T cell generation during M.tb infection in mice. Additionally, it improves elderly human T cell function by increasing mitochondrial mass and altering cytokine production, thereby reducing markers of exhaustion and senescence. These findings suggest mito-transfer as a novel approach to enhance aged CD4+ T cell functionality, potentially benefiting immune responses in the elderly and chronic TB patients. This has broader implications for diseases where mitochondrial dysfunction contributes to T-cell exhaustion and senescence.
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Affiliation(s)
- Colwyn A. Headley
- Host‐Pathogen Interactions ProgramTexas Biomedical Research InstituteSan AntonioTX78227USA
- Biomedical Sciences Graduate ProgramThe Ohio State UniversityColumbusOH43201USA
- Stanford Cardiovascular InstituteStanford University School of MedicineStanfordCA94305USA
| | - Shalini Gautam
- Host‐Pathogen Interactions ProgramTexas Biomedical Research InstituteSan AntonioTX78227USA
| | - Angelica Olmo‐Fontanez
- Population Health ProgramTexas Biomedical Research InstituteSan AntonioTX78227USA
- Southwest National Primate Research CenterTexas Biomedical Research InstituteSan AntonioTX78227USA
| | | | - Varun Dwivedi
- Host‐Pathogen Interactions ProgramTexas Biomedical Research InstituteSan AntonioTX78227USA
| | - Alyssa Schami
- Population Health ProgramTexas Biomedical Research InstituteSan AntonioTX78227USA
| | - Susan Weintraub
- Department of Biochemistry & Structural BiologyUT health San AntonioSan AntonioTX78229USA
| | - Philip S. Tsao
- Stanford Cardiovascular InstituteStanford University School of MedicineStanfordCA94305USA
| | - Jordi B. Torrelles
- Population Health ProgramTexas Biomedical Research InstituteSan AntonioTX78227USA
- Internaltional Center for the Advancement of Research & Education (I•CARE)Texas Biomedical Research InstituteSan AntonioTX78227USA
| | - Joanne Turner
- Host‐Pathogen Interactions ProgramTexas Biomedical Research InstituteSan AntonioTX78227USA
- Abigail Wexner Research Institute at Nationwide Children's HospitalColumbusOH43205USA
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10
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Isago H. The Association between Dyslipidemia and Pulmonary Diseases. J Atheroscler Thromb 2024; 31:1249-1259. [PMID: 39010219 PMCID: PMC11374539 DOI: 10.5551/jat.rv22021] [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: 07/17/2024] Open
Abstract
Dyslipidemia is one of the most common diseases worldwide. As a component of metabolic syndrome, the prevalence and mechanism by which dyslipidemia promotes cardiovascular diseases has been well studied, although the relationship between pulmonary diseases is not well understood. Because the lung is a respiratory organ with a large surface area and is exposed to the environment outside the body, it continuously inhales various substances. As a result, pulmonary diseases have a vast diversity, including chronic inflammatory diseases, allergic diseases, cancers, and infectious diseases. Recently, growing evidence has suggested that dyslipidemia plays a role in the pathogenesis and prognosis of various pulmonary diseases. We herein review the current understanding of the relationship between dyslipidemia and pulmonary diseases, including chronic obstructive pulmonary diseases, asthma, and lung cancer, and infectious pulmonary diseases, including community-acquired pneumonia, tuberculosis, nontuberculous mycobacterial pulmonary disease, and COVID-19. In addition, we focus on recent evidence of the utility of statins, specifically 3-hydroxy-3-methylglutaryl-coA reductase inhibitors, in the prevention and treatment of the various pulmonary diseases described above.
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Affiliation(s)
- Hideaki Isago
- Department of Clinical Laboratory, The University of Tokyo Hospital
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11
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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12
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Østergaard AA, Lillebaek T, Petersen I, Fløe A, Bøkan EHW, Hilberg O, Holden IK, Larsen L, Colic A, Wejse C, Ravn P, Nørgård BM, Bjerrum S, Johansen IS. Prevalence estimates of tuberculosis infection in adults in Denmark: a retrospective nationwide register-based cross-sectional study, 2010 to 2018. Euro Surveill 2024; 29:2300590. [PMID: 38516789 PMCID: PMC11063675 DOI: 10.2807/1560-7917.es.2024.29.12.2300590] [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: 10/26/2023] [Accepted: 01/12/2024] [Indexed: 03/23/2024] Open
Abstract
BackgroundTuberculosis (TB) elimination requires identifying and treating persons with TB infection (TBI).AimWe estimate the prevalence of positive interferon gamma release assay (IGRA) tests (including TB) and TBI (excluding TB) in Denmark based on TBI screening data from patients with inflammatory bowel disease (IBD) or inflammatory rheumatic disease (IRD).MethodsUsing nationwide Danish registries, we included all patients with IBD or IRD with an IGRA test performed between 2010 and 2018. We estimated the prevalence of TBI and positive IGRA with 95% confidence intervals (CI) in adolescents and adults aged 15-64 years after sample weighting adjusting for distortions in the sample from the background population of Denmark for sex, age group and TB incidence rates (IR) in country of birth.ResultsIn 13,574 patients with IBD or IRD, 12,892 IGRA tests (95.0%) were negative, 461 (3.4%) were positive and 221 (1.6%) were indeterminate, resulting in a weighted TBI prevalence of 3.2% (95% CI: 2.9-3.5) and weighted positive IGRA prevalence of 3.8% (95% CI: 3.5-4.2) among adults aged 15-64 years in the background population of Denmark. Unweighted TBI prevalence increased with age and birthplace in countries with a TB IR higher than 10/100,000 population.ConclusionEstimated TBI prevalence is low in Denmark. We estimate that 200,000 persons have TBI and thus are at risk of developing TB. Screening for TBI and preventive treatment, especially in persons born in high TB incidence countries or immunosuppressed, are crucial to reduce the risk of and eliminate TB.
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Affiliation(s)
- Anne Ahrens Østergaard
- Department of Infectious Diseases and Mycobacterial Centre for Research Southern Denmark, MyCRESD, Odense University Hospital, Denmark
- Research Unit of Infectious Diseases, Department of Clinical Research, University of Southern Denmark
| | - Troels Lillebaek
- International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Denmark
- Department of Public Health, University of Copenhagen, Denmark
| | - Inge Petersen
- Department of Infectious Diseases and Mycobacterial Centre for Research Southern Denmark, MyCRESD, Odense University Hospital, Denmark
| | - Andreas Fløe
- Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark
| | - Eliza H Worren Bøkan
- Department of Infectious Diseases and Mycobacterial Centre for Research Southern Denmark, MyCRESD, Odense University Hospital, Denmark
| | - Ole Hilberg
- Department of Medicine, Vejle Hospital, Hospital Lillebælt, Vejle, Denmark
| | - Inge K Holden
- Department of Infectious Diseases and Mycobacterial Centre for Research Southern Denmark, MyCRESD, Odense University Hospital, Denmark
- Research Unit of Infectious Diseases, Department of Clinical Research, University of Southern Denmark
| | - Lone Larsen
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Department of Clinical Medicine, The Faculty of Medicine, Aalborg University, Denmark
| | - Ada Colic
- Department of Rheumatology, Zealand University Hospital, Køge, Denmark
| | - Christian Wejse
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
- GloHAU, Center for Global Health, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Pernille Ravn
- Section for Infectious Diseases, Department of Medicine, Herlev and Gentofte Hospital, Copenhagen, University of Copenhagen, Gentofte, Denmark
| | - Bente Mertz Nørgård
- Center of Clinical Epidemiology, Odense University Hospital and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark
| | - Stephanie Bjerrum
- Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Research Unit of Infectious Diseases, Department of Clinical Research, University of Southern Denmark
| | - Isik Somuncu Johansen
- Department of Infectious Diseases and Mycobacterial Centre for Research Southern Denmark, MyCRESD, Odense University Hospital, Denmark
- Research Unit of Infectious Diseases, Department of Clinical Research, University of Southern Denmark
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13
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van Geuns D, Arts RJ, de Vries G, Wit FW, Degtyareva SY, Brown J, Pareek M, Lipman M, van Crevel R. Screening for tuberculosis infection and effectiveness of preventive treatment among people with HIV in low-incidence settings. AIDS 2024; 38:193-205. [PMID: 37991008 PMCID: PMC10734787 DOI: 10.1097/qad.0000000000003747] [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: 06/15/2023] [Revised: 09/29/2023] [Accepted: 10/03/2023] [Indexed: 11/23/2023]
Abstract
OBJECTIVE To determine the yield of screening for latent tuberculosis infection (LTBI) among people with HIV (PWH) in low tuberculosis (TB) incidence countries (<10 TB cases per 100 000 persons). DESIGN A systematic review and meta-analysis were performed to assess prevalence and predictive factors of LTBI, rate of TB progression, effect of TB preventive treatment (TPT), and numbers needed to screen (NNS). METHODS PubMed and Cochrane Library were searched for studies reporting primary data, excluding studies on active or paediatric TB. We extracted LTBI cases, odds ratios, and TB incidences; pooled estimates using a random-effects model; and used the Newcastle-Ottawa scale for bias. RESULTS In 51 studies with 65 930 PWH, 12% [95% confidence interval (CI) 10-14] had a positive LTBI test, which was strongly associated with origin from a TB-endemic country [odds ratio (OR) 4.7] and exposure to TB (OR 2.9). Without TPT (10 629 PWH), TB incidence was 28/1000 person-years (PY; 95% CI 12-45) for LTBI-test positive versus 4/1000 PY (95% CI 0-7) for LTBI-test-negative individuals. Among 625 PWH (1644 PY) receiving TPT, 15 developed TB (6/1000 PY). An estimated 20 LTBI-positive individuals would need TPT to prevent one case of TB, and numbers NNS to detect LTBI or prevent active TB varied according to a-priori risk of LTBI. CONCLUSION The relatively high prevalence of LTBI among PWH and the strong correlation with origin from a TB-endemic country support risk-stratified LTBI screening strategies for PWH in low-incidence countries and treating those who test positive.
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Affiliation(s)
- Dorine van Geuns
- Julius Centre for Health Sciences and Primary Care Medicine, University Medical Centre Utrecht, Utrecht
| | - Rob J.W. Arts
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen
| | - Gerard de Vries
- National Institute for Public Health and the Environment (RIVM), Bilthoven
| | - Ferdinand W.N.M. Wit
- Department of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, University of Amsterdam
- Stichting HIV Monitoring, Amsterdam, the Netherlands
| | - Svetlana Y. Degtyareva
- Department of Infectious Diseases, Epidemiology and Phthisiology, RUDN University, Moscow, Russia
| | - James Brown
- Department of Respiratory Medicine, Royal Free London NHS Foundation Trust, London
| | - Manish Pareek
- Department of Respiratory Sciences, University of Leicester
- Department of Infection and HIV medicine, Leicester Royal Infirmary, Leicester
| | - Marc Lipman
- Department of Respiratory Medicine, Royal Free London NHS Foundation Trust, London
- UCL Respiratory, University College London, London
| | - Reinout van Crevel
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
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14
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Headley CA, Gautam S, Olmo-Fontanez A, Garcia-Vilanova A, Dwivedi V, Schami A, Weintraub S, Tsao PS, Torrelles JB, Turner J. Mitochondrial Transplantation promotes protective effector and memory CD4 + T cell response during Mycobacterium tuberculosis infection and diminishes exhaustion and senescence in elderly CD4 + T cells. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.01.24.577036. [PMID: 38328206 PMCID: PMC10849707 DOI: 10.1101/2024.01.24.577036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2024]
Abstract
Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (M.tb), remains a significant health concern worldwide, especially in populations with weakened or compromised immune systems, such as the elderly. Proper adaptive immune function, particularly a CD4+ T cell response, is central to host immunity against M.tb. Chronic infections, such as M.tb, as well as aging promote T cell exhaustion and senescence, which can impair immune control and promote progression to TB disease. Mitochondrial dysfunction contributes to T cell dysfunction, both in aging and chronic infections and diseases. Mitochondrial perturbations can disrupt cellular metabolism, enhance oxidative stress, and impair T-cell signaling and effector functions. This study examined the impact of mitochondrial transplantation (mito-transfer) on CD4+ T cell differentiation and function using aged mouse models and human CD4+ T cells from elderly individuals. Our study revealed that mito-transfer in naïve CD4+ T cells promoted the generation of protective effector and memory CD4+ T cells during M.tb infection in mice. Further, mito-transfer enhanced the function of elderly human T cells by increasing their mitochondrial mass and modulating cytokine production, which in turn reduced exhaustion and senescence cell markers. Our results suggest that mito-transfer could be a novel strategy to reestablish aged CD4+ T cell function, potentially improving immune responses in the elderly and chronic TB patients, with a broader implication for other diseases where mitochondrial dysfunction is linked to T cell exhaustion and senescence.
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Affiliation(s)
- Colwyn A. Headley
- Host-Pathogen Interactions Program, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA
- Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH, 43201, USA
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305
| | - Shalini Gautam
- Host-Pathogen Interactions Program, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA
| | - Angelica Olmo-Fontanez
- Population Health Program, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA
- Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA
| | - Andreu Garcia-Vilanova
- Population Health Program, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA
| | - Varun Dwivedi
- Host-Pathogen Interactions Program, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA
| | - Alyssa Schami
- Population Health Program, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA
| | - Susan Weintraub
- Department of Biochemistry & Structural Biology, UT health San Antonio, TX, 78229, USA
| | - Philip S. Tsao
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305
| | - Jordi B. Torrelles
- Population Health Program, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA
- Internaltional Center for the Advancement of Research & Education (I•CARE), Texas Biomedical Research Institute, San Antonio, TX, 78227, USA
| | - Joanne Turner
- Host-Pathogen Interactions Program, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA
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15
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Zhou G, Luo S, He J, Chen N, Zhang Y, Cai S, Guo X, Song C. Risk of progression to active tuberculosis for indeterminate interferon-gamma release assay in immunocompromised individuals: a systematic review and meta-analysis. Clin Microbiol Infect 2023; 29:1375-1384. [PMID: 37422080 DOI: 10.1016/j.cmi.2023.07.003] [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: 02/17/2023] [Revised: 06/28/2023] [Accepted: 07/01/2023] [Indexed: 07/10/2023]
Abstract
BACKGROUND Limited data exist on assessing the risk of active tuberculosis (TB) in immunocompromised individuals during screening for latent tuberculosis infection (LTBI). OBJECTIVES To assess the risk of progression to active TB for indeterminate interferon-γ release assays (IGRA) results in immunocompromised individuals during screening for LTBI. DATA SOURCES PubMed, Embase, Web of Science, and the Cochrane Library were searched without start date or language restrictions on 18 April 2023. STUDY ELIGIBILITY CRITERIA Cohort study or randomized controlled trials that investigated the risk of progression to active TB for indeterminate IGRA during LTBI screening. PARTICIPANTS Immunocompromised individuals. TEST: IGRA (T-SPOT.TB and QuantiFERON). REFERENCE STANDARD None. ASSESSMENT OF RISK OF BIAS A modified version of the Newcastle-Ottawa Scale. METHODS OF DATA SYNTHESIS Fixed effects meta-analysis was used to obtain two pooled risk ratios (RRs). RR-ip represented disease progression rate in untreated individuals with indeterminate IGRA versus positive IGRA. RR-in represented disease progression rate in untreated individuals with indeterminate IGRA versus negative IGRA. RESULTS Among the 5102 identified studies, 28 (14 792 immunocompromised individuals) were included. The pooled RR-ip and RR-in for cumulative incidence were 0.51 (95% CI, 0.32-0.82; I2 = 0%) and 2.94 (95% CI, 1.78-4.85; I2 = 0%), respectively. In addition, 11 studies reporting person-year data were included to verify the reliability of cumulative incidence results. The pooled RR-ip and RR-in for person-year incidence were 0.40 (95% CI, 0.19-0.82; I2 = 13%) and 2.67 (95% CI, 1.24-5.79; I2 = 23%), respectively. DISCUSSION Indeterminate IGRA results in immunocompromised individuals may represent an intermediate risk of progression to active TB, with half the risk for positive results and three times for negative results. Proper follow-up and management of patients with indeterminate results are crucial for mitigating progression risk and improving patient outcomes.
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Affiliation(s)
- Guozhong Zhou
- Department of Science and Research, The Affiliated Anning First People's Hospital of Kunming University of Science and Technology, Kunming, Yunnan Province, China
| | - Shiqi Luo
- Department of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
| | - Jian He
- Department of Pulmonary and Critical Care Medicine, The Affiliated Anning First People's Hospital of Kunming University of Science and Technology, Kunming, Yunnan Province, China
| | - Nan Chen
- Department of Endocrinology, The Affiliated Anning First People's Hospital of Kunming University of Science and Technology, Kunming, Yunnan Province, China
| | - Yu Zhang
- Department of Endocrinology, The Affiliated Anning First People's Hospital of Kunming University of Science and Technology, Kunming, Yunnan Province, China
| | - Shunli Cai
- School of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan Province, China
| | - Xin Guo
- School of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan Province, China
| | - Chao Song
- Department of Medical Imaging, The Affiliated Anning First People's Hospital of Kunming University of Science and Technology, Kunming, Yunnan Province, China.
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16
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Havumaki J, Warren JL, Zelner J, Menzies NA, Calderon R, Contreras C, Lecca L, Becerra MC, Murray M, Cohen T. Spatially-targeted tuberculosis screening has limited impact beyond household contact tracing in Lima, Peru: A model-based analysis. PLoS One 2023; 18:e0293519. [PMID: 37903091 PMCID: PMC10615320 DOI: 10.1371/journal.pone.0293519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 10/15/2023] [Indexed: 11/01/2023] Open
Abstract
Mathematical models have suggested that spatially-targeted screening interventions for tuberculosis may efficiently accelerate disease control, but empirical data supporting these findings are limited. Previous models demonstrating substantial impacts of these interventions have typically simulated large-scale screening efforts and have not attempted to capture the spatial distribution of tuberculosis in households and communities at a high resolution. Here, we calibrate an individual-based model to the locations of case notifications in one district of Lima, Peru. We estimate the incremental efficiency and impact of a spatially-targeted interventions used in combination with household contact tracing (HHCT). Our analysis reveals that HHCT is relatively efficient with a median of 40 (Interquartile Range: 31.7 to 49.9) household contacts required to be screened to detect a single case of active tuberculosis. However, HHCT has limited population impact, producing a median incidence reduction of only 3.7% (Interquartile Range: 5.8% to 1.9%) over 5 years. In comparison, spatially targeted screening (which we modeled as active case finding within high tuberculosis prevalence areas 100 m2 grid cell) is far less efficient, requiring evaluation of ≈12 times the number of individuals as HHCT to find a single individual with active tuberculosis. Furthermore, the addition of the spatially targeted screening effort produced only modest additional reductions in tuberculosis incidence over the 5 year period (≈1.3%) in tuberculosis incidence. In summary, we found that HHCT is an efficient approach for tuberculosis case finding, but has limited population impact. Other screening approaches which target areas of high tuberculosis prevalence are less efficient, and may have limited impact unless very large numbers of individuals can be screened.
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Affiliation(s)
- Joshua Havumaki
- Department of Epidemiology of Microbial Diseases, Yale University, New Haven, CT, United States of America
| | - Joshua L. Warren
- Department of Biostatistics, Yale School of Public Health, New Haven, CT, United States of America
| | - Jon Zelner
- Department of Epidemiology, University of Michigan, Ann Arbor, MI, United States of America
- Center for Social Epidemiology and Population Health, University of Michigan School of Public Health, Ann Arbor, MI, United States of America
| | - Nicolas A. Menzies
- Department of Global Health and Population, Harvard T. H. Chan, School of Public Health, Boston, MA, United States of America
| | - Roger Calderon
- Socios en Salud Sucursal Peru, Lima, Peru
- Programa Acadêmico de Tuberculose, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | | | - Leonid Lecca
- Department of Global Health and Population, Harvard T. H. Chan, School of Public Health, Boston, MA, United States of America
- Socios en Salud Sucursal Peru, Lima, Peru
| | - Mercedes C. Becerra
- Department of Global Health and Population, Harvard T. H. Chan, School of Public Health, Boston, MA, United States of America
| | - Megan Murray
- Department of Global Health and Population, Harvard T. H. Chan, School of Public Health, Boston, MA, United States of America
| | - Ted Cohen
- Department of Epidemiology of Microbial Diseases, Yale University, New Haven, CT, United States of America
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Hase R, Suzuki D, de Luise C, Chen H, Nonnenmacher E, Higuchi T, Katayama K, Kinjo M, Jinno S, Morishima T, Sugiyama N, Tanaka Y, Setoguchi S. Validity of claims-based diagnoses for infectious diseases common among immunocompromised patients in Japan. BMC Infect Dis 2023; 23:653. [PMID: 37789253 PMCID: PMC10548573 DOI: 10.1186/s12879-023-08466-8] [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: 12/21/2022] [Accepted: 07/16/2023] [Indexed: 10/05/2023] Open
Abstract
BACKGROUND To validate Japanese claims-based disease-identifying algorithms for herpes zoster (HZ), Mycobacterium tuberculosis (MTB), nontuberculous mycobacteria infections (NTM), and Pneumocystis jirovecii pneumonia (PJP). METHODS VALIDATE-J, a multicenter, cross-sectional, retrospective study, reviewed the administrative claims data and medical records from two Japanese hospitals. Claims-based algorithms were developed by experts to identify HZ, MTB, NTM, and PJP cases among patients treated 2012-2016. Diagnosis was confirmed with three gold standard definitions; positive predictive values (PPVs) were calculated for prevalent (regardless of baseline disease-free period) and incident (preceded by a 12-month disease-free period for the target conditions) cases. RESULTS Of patients identified using claims-based algorithms, a random sample of 377 cases was included: HZ (n = 95 [55 incident cases]); MTB (n = 100 [58]); NTM (n = 82 [50]); and PJP (n = 100 [84]). PPVs ranged from 67.4-70.5% (HZ), 67.0-90.0% (MTB), 18.3-63.4% (NTM), and 20.0-45.0% (PJP) for prevalent cases, and 69.1-70.9% (HZ), 58.6-87.9% (MTB), 10.0-56.0% (NTM), and 22.6-51.2% (PJP) for incident cases, across definitions. Adding treatment to the algorithms increased PPVs for HZ, with a small increase observed for prevalent cases of NTM. CONCLUSIONS VALIDATE-J demonstrated moderate to high PPVs for disease-identifying algorithms for HZ and MTB using Japanese claims data.
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Affiliation(s)
- Ryota Hase
- Department of Infectious Diseases, Kameda Medical Center, 929 Higashi-cho, Kamogawa, 296-8602, Chiba, Japan
- Department of Infectious Diseases, Japanese Red Cross Narita Hospital, 90-1 Iidacho, Narita, 286-8523, Chiba, Japan
| | - Daisuke Suzuki
- Department of Infectious Diseases, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Aichi, Japan
- Department of Infectious Diseases, Anjo Kosei Hospital, Anjo, Aichi, Japan
| | - Cynthia de Luise
- Safety Surveillance Research, Pfizer Inc, 235 E 42nd Street, New York, NY, 10017, USA
| | - Haoqian Chen
- Center for Pharmacoepidemiology and Treatment Science, Rutgers Institute for Health, Health Care Policy and Aging Research, 112 Paterson Street, New Brunswick, NJ, 08901, USA
| | - Edward Nonnenmacher
- Center for Pharmacoepidemiology and Treatment Science, Rutgers Institute for Health, Health Care Policy and Aging Research, 112 Paterson Street, New Brunswick, NJ, 08901, USA
| | - Takakazu Higuchi
- Blood Transfusion Department, Dokkyo Medical University Saitama Medical Center, 2-1-50 Minamikoshigaya, Koshigaya, 343-8555, Saitama, Japan
| | - Kayoko Katayama
- Cancer Prevention and Cancer Control Division, Kanagawa Cancer Center Research Institute, 1-1-2 Nakao, Asahi-ku, Yokohama, 241-0815, Kanagawa, Japan
- Department of Informatics, Gunma University, Maebashi, Gunma, Japan
| | - Mitsuyo Kinjo
- Division of Rheumatology, Okinawa Chubu Hospital, 281 Miyazato, Uruma, 904-2293, Okinawa, Japan
| | - Sadao Jinno
- Section of Rheumatology, Kobe University School of Medicine, 7-5-2 Kusunoki-chou, Kobe-shi, 650-0017, Hyogo, Japan
| | - Toshitaka Morishima
- Cancer Control Center, Osaka International Cancer Institute, 3-1-69 Otemae, Chūō-ku, 541-8567, Osaka, Japan
| | - Naonobu Sugiyama
- Inflammation & Immunology, Medical Affairs, Pfizer Japan Inc, 3-22-7 Yoyogi, Shibuya-ku, 151-8589, Tokyo, Japan.
| | - Yoshiya Tanaka
- First Department of Internal Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Kitakyushu, 807-8555, Fukuoka, Japan
| | - Soko Setoguchi
- Center for Pharmacoepidemiology and Treatment Science, Rutgers Institute for Health, Health Care Policy and Aging Research, 112 Paterson Street, New Brunswick, NJ, 08901, USA.
- Department of Medicine, Rutgers Robert Wood Johnson Medical School and Institute for Health, Rutgers Biomedical and Health Science, 89 French Street, New Brunswick, NJ, 08901, USA.
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18
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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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19
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Bharati J, Anandh U, Kotton CN, Mueller T, Shingada AK, Ramachandran R. Diagnosis, Prevention, and Treatment of Infections in Kidney Transplantation. Semin Nephrol 2023; 43:151486. [PMID: 38378396 DOI: 10.1016/j.semnephrol.2023.151486] [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: 02/22/2024]
Abstract
Kidney transplant often is complicated by infections in the recipient from therapy-related and patient-related risk factors. Infections in kidney transplant recipients are associated with increased morbidity, mortality, and allograft dysfunction. There is a predictable timeline after kidney transplant regarding the types of pathogens causing infections, reflecting the net state of immunosuppression. In the early post-transplant period, bacterial infections comprise two thirds of all infections, followed by viral and fungal infections. Infections occurring early after kidney transplantation are generally the result of postoperative complications. In most cases, opportunistic infections occur within 6 months after kidney transplantation. They may be caused by a new infection, a donor-derived infection, or reactivation of a latent infection. Community-acquired pneumonia, upper respiratory tract infections, urinary tract infections, and gastrointestinal infections are the most common infections in the late period after transplantation when the net immunosuppression is minimal. It is crucial to seek information on the time after transplant, reflecting the net state of immunosuppression, previous history of exposure/infections, geography, and seasonal outbreaks. It is imperative that we develop regionally specific guidelines on screening, prevention, and management of infections after kidney transplantation.
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Affiliation(s)
- Joyita Bharati
- Section of Nephrology, Boston Medical Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA.
| | - Urmila Anandh
- Department of Nephrology, Amrita Hospitals, Faridabad, Delhi National Capital Region, India
| | - Camille N Kotton
- Infectious Diseases Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Thomas Mueller
- Renal Transplant Program, University Hospital of Zurich, Zurich, Switzerland
| | | | - Raja Ramachandran
- Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
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20
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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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21
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Matulyte E, Kancauskiene Z, Kausas A, Urboniene J, Lipnickiene V, Kopeykiniene J, Gudaitis T, Raudonis S, Danila E, Costagliola D, Matulionyte R. Latent Tuberculosis Infection and Associated Risk Factors among People Living with HIV and HIV-Uninfected Individuals in Lithuania. Pathogens 2023; 12:990. [PMID: 37623950 PMCID: PMC10459141 DOI: 10.3390/pathogens12080990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/20/2023] [Accepted: 07/26/2023] [Indexed: 08/26/2023] Open
Abstract
BACKGROUND People living with HIV (PLHIV) with latent tuberculosis infection (LTBI) are at increased risk of tuberculosis (TB) reactivation compared to the HIV-negative population. Lithuania belongs to the 18 high-priority TB countries in the European region. The aim of this study was to compare the prevalence of LTBI and LTBI-related risk factors between PLHIV and HIV-uninfected populations. METHODS A cross-sectional study was conducted in three Lithuanian Infectious Diseases centres from August 2018 to May 2022 using the interferon gamma release assay (IGRA) and tuberculin skin test (TST) in Vilnius, and IGRA only in Siauliai and Klaipeda. Cohen's kappa was used to assess IGRA and TST agreement. A structured questionnaire was completed by the study participants. LTBI-related risk factors were identified using a multivariable logistic regression model. RESULTS In total, 391 PLHIV and 443 HIV-uninfected individuals enrolled, with a median age of 41 (IQR 36-48) and 43 (IQR 36-50), consisting of 69.8% and 65.5% male, respectively. The prevalence of LTBI defined by positive IGRA and/or TST among PLHIV was higher compared to that in the HIV-uninfected population (20.5% vs. 15.3%; OR 1.42; 95% CI 1.02-2.03; p = 0.04). The concordance between IGRA and TST was fair: kappa = 0.23 (95% CI 0.09-0.34). In multivariable analyses, association with injecting drug use (IDU) (ORa 2.25, 95% CI 1.27-3.99, p = 0.01) and imprisonment (ORa 1.99, 95% CI 1.13-3.52, p = 0.02) in all participants, IDU (ORa 2.37, 95% CI 1.09-5.15; p = 0.029) in PLHIV and a history of contact with an active TB patient (ORa 3.33, 95% CI 1.53-7.24; p = 0.002) in HIV-uninfected individuals were significant associations evidenced by LTBI. CONCLUSIONS The prevalence of LTBI among PLHIV in Lithuania is higher compared to that in the HIV-uninfected population and the European average. The association with IDU in PLHIV emphasizes the need for integrated HIV, TB and substance abuse treatment to provide patient-centred care.
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Affiliation(s)
- Elzbieta Matulyte
- Department of Infectious Diseases and Dermatovenerology, Faculty of Medicine, Vilnius University Hospital Santaros Klinikos, Vilnius University, LT-08410 Vilnius, Lithuania;
| | - Zavinta Kancauskiene
- Department of Infectious Diseases, University Hospital of Klaipeda, LT-92888 Klaipeda, Lithuania;
| | - Aidas Kausas
- Adult Infectious Diseases Unit, Clinic of Conservative Medicine, Republican Siauliai County Hospital, LT-76231 Siauliai, Lithuania;
| | - Jurgita Urboniene
- Centre of Infectious Diseases, Vilnius University Hospital Santaros Klinikos, LT-08410 Vilnius, Lithuania;
| | - Vilnele Lipnickiene
- National Public Health Surveillance Laboratory, LT-10210 Vilnius, Lithuania;
| | - Jelena Kopeykiniene
- Department of Diagnostics, University Hospital of Klaipeda, LT-92888 Klaipeda, Lithuania;
| | - Tomas Gudaitis
- Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania; (T.G.); (S.R.)
| | - Sarunas Raudonis
- Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania; (T.G.); (S.R.)
| | - Edvardas Danila
- Faculty of Medicine, Institute of Clinical Medicine, Clinic of Chest Diseases, Immunology, and Allergology, Vilnius University, LT-03101 Vilnius, Lithuania;
- Centre of Pulmonology and Allergology, Vilnius University Hospital Santaros Klinikos, LT-08661 Vilnius, Lithuania
| | - Dominique Costagliola
- Institut Pierre Louis Épidémiologie de Santé Publique, Sorbonne Université, INSERM, F75013 Paris, France;
| | - Raimonda Matulionyte
- Department of Infectious Diseases and Dermatovenerology, Faculty of Medicine, Vilnius University Hospital Santaros Klinikos, Vilnius University, LT-08410 Vilnius, Lithuania;
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22
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Njagi LN, Nduba V, Mureithi MW, Mecha JO. Prevalence and predictors of tuberculosis infection among people living with HIV in a high tuberculosis burden context. BMJ Open Respir Res 2023; 10:10/1/e001581. [PMID: 37197794 DOI: 10.1136/bmjresp-2022-001581] [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: 12/06/2022] [Accepted: 04/28/2023] [Indexed: 05/19/2023] Open
Abstract
BACKGROUND Tuberculosis (TB) disease is the leading cause of mortality among people living with HIV (PLHIV). Interferon-gamma release assays (IGRAs) are approved for TB infection ascertainment. However, current IGRA data on the prevalence of TB infection in the context of near-universal access to antiretroviral therapy (ART) and TB preventive therapy (TPT) are lacking. We estimated the prevalence and determinants of TB infection among PLHIV within a high TB and HIV burden context. METHODS This cross-sectional study included data from adult PLHIV age ≥18 years in whom QuantiFERON-TB Gold Plus (QFT-Plus) assay, an IGRA, was performed. TB infection was defined as a positive or indeterminate QFT-Plus test. Participants with TB and those who had previously used TPT were excluded. Regression analysis was performed to identify independent predictors of TB infection. RESULTS Of 121 PLHIV with QFT-Plus test results, females were 74.4% (90/121), and the mean age was 38.4 (SD 10.8) years. Overall, 47.9% (58/121) were classified as TB infection (QFT-Plus test positive and indeterminate results were 39.7% (48/121) and 8.3% (10/121), respectively). Being obese/overweight (body mass index ≥25 kg/m2; p=0.013, adjusted OR (aOR) 2.90, 95% CI 1.25 to 6.74) and ART usage for >3 years (p=0.013, aOR 3.99, 95% CI 1.55 to 10.28) were independently associated with TB infection. CONCLUSION There was a high TB infection prevalence among PLHIV. A longer period of ART and obesity were independently associated with TB infection. The relationship between obesity/overweight and TB infection may be related to ART use and immune reconstitution and requires further investigation. Given the known benefit of test-directed TPT among PLHIV never exposed to TPT, its clinical and cost implications for low and middle-income countries should be explored further.
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Affiliation(s)
- Lilian Nkirote Njagi
- Center for Respiratory Disease Research, Kenya Medical Research Institute, Nairobi, Kenya
- Department of Medical Microbiology & Immunology, University of Nairobi Faculty of Health Sciences, Nairobi, Kenya
| | - Videlis Nduba
- Center for Respiratory Disease Research, Kenya Medical Research Institute, Nairobi, Kenya
| | - Marianne Wanjiru Mureithi
- Department of Medical Microbiology & Immunology, University of Nairobi Faculty of Health Sciences, Nairobi, Kenya
| | - Jared Ongechi Mecha
- Department of Clinical Medicine and Therapeutics, University of Nairobi Faculty of Health Sciences, Nairobi, Kenya
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23
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Hamada Y, Gupta RK, Quartagno M, Izzard A, Acuna-Villaorduna C, Altet N, Diel R, Dominguez J, Floyd S, Gupta A, Huerga H, Jones-López EC, Kinikar A, Lange C, van Leth F, Liu Q, Lu W, Lu P, Rueda IL, Martinez L, Mbandi SK, Muñoz L, Padilla ES, Paradkar M, Scriba T, Sester M, Shanaube K, Sharma SK, Sloot R, Sotgiu G, Thiruvengadam K, Vashishtha R, Abubakar I, Rangaka MX. Predictive performance of interferon-gamma release assays and the tuberculin skin test for incident tuberculosis: an individual participant data meta-analysis. EClinicalMedicine 2023; 56:101815. [PMID: 36636295 PMCID: PMC9829704 DOI: 10.1016/j.eclinm.2022.101815] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 12/14/2022] [Accepted: 12/19/2022] [Indexed: 01/06/2023] Open
Abstract
Background Evidence on the comparative performance of purified protein derivative tuberculin skin tests (TST) and interferon-gamma release assays (IGRA) for predicting incident active tuberculosis (TB) remains conflicting. We conducted an individual participant data meta-analysis to directly compare the predictive performance for incident TB disease between TST and IGRA to inform policy. Methods We searched Medline and Embase from 1 January 2002 to 4 September 2020, and studies that were included in previous systematic reviews. We included prospective longitudinal studies in which participants received both TST and IGRA and estimated performance as hazard ratios (HR) for the development of all diagnoses of TB in participants with dichotomised positive test results compared to negative results, using different thresholds of positivity for TST. Secondary analyses included an evaluation of the impact of background TB incidence. We also estimated the sensitivity and specificity for predicting TB. We explored heterogeneity through pre-defined sub-group analyses (e.g. country-level TB incidence). Publication bias was assessed using funnel plots and Egger's test. This review is registered with PROSPERO, CRD42020205667. Findings We obtained data from 13 studies out of 40 that were considered eligible (N = 32,034 participants: 36% from countries with TB incidence rate ≥100 per 100,000 population). All reported data on TST and QuantiFERON Gold in-Tube (QFT-GIT). The point estimate for the TST was highest with higher cut-offs for positivity and particularly when stratified by bacillus Calmette-Guérin vaccine (BCG) status (15 mm if BCG vaccinated and 5 mm if not [TST5/15 mm]) at 2.88 (95% CI 1.69-4.90). The pooled HR for QFT-GIT was higher than for TST at 4.15 (95% CI 1.97-8.75). The difference was large in countries with TB incidence rate <100 per 100,000 population (HR 10.38, 95% CI 4.17-25.87 for QFT-GIT VS. HR 5.36, 95% CI 3.82-7.51 for TST5/15 mm) but much of this difference was driven by a single study (HR 5.13, 95% CI 3.58-7.35 for TST5/15 mm VS. 7.18, 95% CI 4.48-11.51 for QFT-GIT, when excluding the study, in which all 19 TB cases had positive QFT-GIT results). The comparative performance was similar in the higher burden countries (HR 1.61, 95% CI 1.23-2.10 for QFT-GIT VS. HR 1.72, 95% CI 0.98-3.01 for TST5/15 mm). The predictive performance of both tests was higher in countries with TB incidence rate <100 per 100,000 population. In the lower TB incidence countries, the specificity of TST (76% for TST5/15 mm) and QFT-GIT (74%) for predicting active TB approached the minimum World Health Organization target (≥75%), but the sensitivity was below the target of ≥75% (63% for TST5/15 mm and 65% for QFT-GIT). The absolute differences in positive and negative predictive values between TST15 mm and QFT-GIT were small (positive predictive values 2.74% VS. 2.46%; negative predictive values 99.42% VS. 99.52% in low-incidence countries). Egger's test did not show evidence of publication bias (0.74 for TST15 mm and p = 0.68 for QFT-GIT). Interpretation IGRA appears to have higher predictive performance than the TST in low TB incidence countries, but the difference was driven by a single study. Any advantage in clinical performance may be small, given the numerically similar positive and negative predictive values. Both IGRA and TST had lower performance in countries with high TB incidence. Test choice should be contextual and made considering operational and likely clinical impact of test results. Funding YH, IA, and MXR were supported by the National Institute for Health and Care Research (NIHR), United Kingdom (RP-PG-0217-20009). MQ was supported by the Medical Research Council [MC_UU_00004/07].
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Affiliation(s)
- Yohhei Hamada
- Institute for Global Health, University College London, London, United Kingdom
| | - Rishi K. Gupta
- Institute for Global Health, University College London, London, United Kingdom
| | - Matteo Quartagno
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, United Kingdom
| | - Abbie Izzard
- Institute for Global Health, University College London, London, United Kingdom
| | | | - Neus Altet
- Unitat de Tuberculosis, Hospital Universitari Vall d’Hebron-Drassanes, Barcelona, Spain
- Unitat de TDO de la Tuberculosis ‘Servicios Clínicos’, Barcelona, Spain
| | - Roland Diel
- Institute for Epidemiology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Jose Dominguez
- Institut d'Investigació Germans Trias i Pujol, CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Sian Floyd
- Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom
| | - Amita Gupta
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Edward C. Jones-López
- Division of Infectious Diseases, Department of Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA
| | - Aarti Kinikar
- Byramjee Jeejeebhoy Government Medical College and Sassoon General Hospital, Pune, Maharashtra, India
| | - Christoph Lange
- Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany
- German Center for Infection Research (DZIF), Clinical Tuberculosis Unit, Borstel, Germany
- Respiratory Medicine & International Health, University of Lübeck, Lübeck, Germany
- Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA
- Tuberculosis Network European Trials Group (TBnet), Borstel, Germany
| | - Frank van Leth
- Tuberculosis Network European Trials Group (TBnet), Borstel, Germany
- Department of Health Sciences, VU University, Amsterdam, the Netherlands
- Amsterdam Public Health research institute, Amsterdam, the Netherlands
| | - Qiao Liu
- Department of Chronic Communicable Disease, Center for Disease Control and Prevention of Jiangsu Province, Nanjing, Jiangsu Province, PR China
| | - Wei Lu
- Department of Chronic Communicable Disease, Center for Disease Control and Prevention of Jiangsu Province, Nanjing, Jiangsu Province, PR China
| | - Peng Lu
- Department of Chronic Communicable Disease, Center for Disease Control and Prevention of Jiangsu Province, Nanjing, Jiangsu Province, PR China
| | - Irene Latorre Rueda
- Institut d'Investigació Germans Trias i Pujol, CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Leonardo Martinez
- Department of Epidemiology, School of Public Health, Boston University, Boston, MA, USA
| | - Stanley Kimbung Mbandi
- South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and Division of Immunology, Department of Pathology, University of Cape Town, South Africa, Western Cape, South Africa
| | - Laura Muñoz
- Department of Clinical Sciences, University of Barcelona, Barcelona, Spain
| | | | - Mandar Paradkar
- Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune, Maharashtra, India
- Johns Hopkins India, Pune, Maharashtra, India
| | - Thomas Scriba
- South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and Division of Immunology, Department of Pathology, University of Cape Town, South Africa, Western Cape, South Africa
| | - Martina Sester
- Tuberculosis Network European Trials Group (TBnet), Borstel, Germany
- Department of Transplant and Infection Immunology, Saarland University, Homburg, Germany
| | | | - Surendra K. Sharma
- Department of Internal Medicine, All India Institute of Medical Sciences, New Delhi, India
- Department of Molecular Medicine, Jamia Hamdard Institute of Molecular Medicine, Hamdard University, Delhi, India
- Departments of General Medicine & Pulmonary Medicine, JNMC, Datta Meghe Institute of Medical Sciences, Maharashtra, India
| | - Rosa Sloot
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Giovanni Sotgiu
- Tuberculosis Network European Trials Group (TBnet), Borstel, Germany
- Clinical Epidemiology and Medical Statistics Unit, Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy
| | - Kannan Thiruvengadam
- National Institute for Research in Tuberculosis, Indian Council of Medical Research, Chennai, Tamil Nadu, India
| | - Richa Vashishtha
- Department of Internal Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Ibrahim Abubakar
- Institute for Global Health, University College London, London, United Kingdom
| | - Molebogeng X. Rangaka
- Institute for Global Health, University College London, London, United Kingdom
- School of Public Health, and Clinical Infectious Disease Research Institute-Africa, University of Cape Town, Cape Town, South Africa
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Kawatsu L, Kaneko N, Imahashi M, Kamada K, Uchimura K. Practices and attitudes towards tuberculosis and latent tuberculosis infection screening in people living with HIV/AIDS among HIV physicians in Japan. AIDS Res Ther 2022; 19:60. [PMID: 36463211 PMCID: PMC9719667 DOI: 10.1186/s12981-022-00487-8] [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: 09/14/2022] [Accepted: 11/28/2022] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND Tuberculosis (TB) continues to be the leading cause of death for people living with HIV/AIDS (PLHIV), and HIV is the strongest known risk factor for progression to active TB disease for persons with latent TB infection (LTBI). Screening for active TB and LTBI, and TB preventive therapy (TPT) is recommended, however, clinical practices regarding LTBI screening for HIV positive population have not been uniform, resulting in low rates of LTBI screening and TPT uptake, in both low and high TB-burden countries. We sought to explore the practices and attitudes towards TB and LTBI screening in PLHIV among HIV physicians in Japan. METHODS We conducted a cross-sectional survey whereby an on-line questionnaire was administered to physicians who are currently, or have the experience of, providing care and treatment for PLHIV in Japan. RESULTS The questionnaire was sent to a total of 83 physicians, of which 59 responded (response rate; 71.1%). 52.5% (31/59) conducted routine screening and 44.0% (26/59) conducted selectively screening for active TB among HIV/AIDS patients. As for LTBI, 54.2% (32/59) conducted routine screening and 35.6% (21/59) conducted selective screening for LTBI among PLHIV. "T-SPOT only" was the most frequently used method of screening (n = 33), followed by "QFT only" (n = 11). Criteria for LTBI screening included TB burden in the country of birth of the patient, previous contact with a TB patient, and CD4+ cell count. 83.1% (49/59) either "always" or "selectively" offered TPT to PLHIV diagnosed with LTBI, and among the 49 respondents who did provide TPT, 77.6% (38/49) chose 9-months isoniazid as their first choice. None chose regimen including rifampicin. CONCLUSIONS Our study revealed that practices regarding TB and LTBI screening and treatment for PLHIV among HIV physicians were mixed and not necessarily in accordance with the various published guidelines. Building and disseminating scientific evidence that takes into consideration the local epidemiology of TB and HIV in Japan is urgently needed to assist physicians make decisions.
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Affiliation(s)
- Lisa Kawatsu
- Department of Epidemiology and Clinical Research, The Research Institute of Tuberculosis, 3-1-24, Matsuyama, Kiyose City, Tokyo, Japan
| | - Noriyo Kaneko
- Graduate School of Nursing, Nagoya City University, 1 Kawasumi, Mizuho-Machi, Mizuho, Nagoya, Aichi Japan
| | - Mayumi Imahashi
- Laboratory of Infectious Diseases, Department of Infectious Diseases and Immunology, National Hospital Organization Nagoya Medical Center, 4-1-1 Sannomaru, Naka-Ku, Nagoya City, Aichi Japan
| | - Keisuke Kamada
- Department of Epidemiology and Clinical Research, The Research Institute of Tuberculosis, 3-1-24, Matsuyama, Kiyose City, Tokyo, Japan
| | - Kazuhiro Uchimura
- Department of Epidemiology and Clinical Research, The Research Institute of Tuberculosis, 3-1-24, Matsuyama, Kiyose City, Tokyo, Japan
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Bergeron A, Mikulska M, De Greef J, Bondeelle L, Franquet T, Herrmann JL, Lange C, Spriet I, Akova M, Donnelly JP, Maertens J, Maschmeyer G, Rovira M, Goletti D, de la Camara R, Maertens J, De Greef J, Slavin M, Spriet I, Hubacek P, Bergeron A, Cordonnier C, Kanerva J, Herbrecht R, Herrmann JL, Lanternier F, Bondeelle L, Robin C, Einsele H, Lehrnbecher T, Groll A, Maschmeyer G, Lange C, von Lilienfeld-Toal M, Pana D, Roilides E, Kassa C, Averbuch D, Engelhard D, Cesaro S, Mikulska M, Pagano L, Castagnola E, Compagno F, Goletti D, Mesini A, Donnelly PJ, Styczynski J, Botelho de Sousa A, Aljurf M, de la Camara R, Navarro D, Rovira M, Franquet T, Garcia-Vidal C, Ljungman P, Paukssen K, Ammann R, Lamoth F, Hirsch H, Ritz N, Akova M, Ceesay M, Warris A, Chemaly R. Mycobacterial infections in adults with haematological malignancies and haematopoietic stem cell transplants: guidelines from the 8th European Conference on Infections in Leukaemia. THE LANCET. INFECTIOUS DISEASES 2022; 22:e359-e369. [PMID: 35636446 DOI: 10.1016/s1473-3099(22)00227-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 03/27/2022] [Accepted: 03/29/2022] [Indexed: 10/18/2022]
Abstract
Mycobacterial infections, both tuberculosis and nontuberculous, are more common in patients with haematological malignancies and haematopoietic stem cell transplant recipients than in the general population-although these infections remain rare. Mycobacterial infections pose both diagnostic and therapeutic challenges. The management of mycobacterial infections is particularly complicated for patients in haematology because of the many drug-drug interactions between antimycobacterial drugs and haematological and immunosuppressive treatments. The management of mycobacterial infections must also consider the effect of delaying haematological management. We surveyed the management practices for latent tuberculosis infection (LTBI) in haematology centres in Europe. We then conducted a meticulous review of the literature on the epidemiology, diagnosis, and management of LTBI, tuberculosis, and nontuberculous mycobacterial infections among patients in haematology, and we formulated clinical guidelines according to standardised European Conference on Infections in Leukaemia (ECIL) methods. In this Review, we summarise the available literature and the recommendations of ECIL 8 for managing mycobacterial infections in patients with haematological malignancies.
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Affiliation(s)
- Anne Bergeron
- Division of Pulmonology, Geneva University Hospitals, Geneva, Switzerland; University of Paris, ECSTRRA Team, Inserm, Paris, France.
| | - Malgorzata Mikulska
- Division of Infectious Diseases, Department of Health Sciences, University of Genoa, Genoa, Italy; San Martino Polyclinic Hospital, Genoa, Italy
| | - Julien De Greef
- Division of Internal Medicine and Infectious Diseases, Saint-Luc University Clinics, Catholic University of Louvain, Brussels, Belgium
| | - Louise Bondeelle
- Division of Pulmonology, Saint Louis Hospital, APHP, University of Paris, Paris, France
| | - Tomas Franquet
- Department of Radiology, Sant Pau Hospital, Autonomous University of Barcelona, Barcelona, Spain
| | - Jean-Louis Herrmann
- Microbiology Department, Raymond Poincaré Hospital, GHU Paris-Saclay, Paris, France; Division of Infection and Inflammation, Paris-Saclay University, UVSQ, Inserm, Paris, France
| | - Christoph Lange
- Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany; German Center for Infection Research (DZIF), TTU Tuberculosis, Borstel, Germany; Respiratory Medicine and International Health, University of Lübeck, Lübeck, Germany; Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA
| | - Isabel Spriet
- Department of Pharmaceutical and Pharmacological Sciences, University Hospitals Leuven, University of Leuven, Leuven, Belgium
| | - Murat Akova
- Department of Medicine, Section of Infectious Diseases, Hacettepe University Medical School, Ankara, Turkey
| | | | - Johan Maertens
- Department of Haematology, University Hospitals Leuven, University of Leuven, Leuven, Belgium
| | - Georg Maschmeyer
- Department of Haematology, Oncology, and Palliative Care, Ernst von Bergmann Clinic, Potsdam, Germany
| | - Montserrat Rovira
- BMT Unit, Haematology Department, Hospital Clinic, IDIBAPS and Josep Carreras Foundation, Barcelona, Spain
| | - Delia Goletti
- Translational Research Unit, Department of Epidemiology and Preclinical Research, Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy
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Mert D, Ozer M, Merdin A, İskender G, Uncu Ulu B, Kizil Çakar M, Dal MS, Altuntaş F, Ertek M. Latent tuberculosis in adult hematopoietic stem cell transplantation recipients: Clinical experience from a previously endemic population. Medicine (Baltimore) 2022; 101:e31786. [PMID: 36401428 PMCID: PMC9678539 DOI: 10.1097/md.0000000000031786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/05/2022] Open
Abstract
Hematopoietic stem cell transplantation (HSCT) recipients may be at an elevated risk of developing active tuberculosis infection due to suppression in the cellular immune system. Herein, we aimed to evaluate the prevalence of latent tuberculosis and active tuberculosis in patients with allogeneic and autologous HSCT. In this cohort, data were obtained retrospectively from patients' records. The patients who were followed up in the bone marrow transplantation unit of the University of Health Sciences Dr Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital between January 2016 and December 2019 were screened for the study. And the HSCT recipients who had tuberculin skin test and/or QuantiFERON-TB gold (QFT-GIT) test results were included in the study. A total of 361 patients were included in the study, 227 patients had autologous HSCT, and 134 patients had allogeneic HSCT. QFT-GIT was performed in 10 patients with allogeneic HSCT, and it was found positive in only 1 patient. Tuberculin skin test ≥5 mm was accepted as positive and was accepted to have latent tuberculosis, and it was positive in 18.2% (41) of the patients with autologous HSCT and was positive in 21.6% (29) of the patients with allogeneic HSCT. There was no significant difference between the 2 groups (P = .429). Isoniazid (INH) prophylaxis was started in 16.7% of patients with autologous HSCT and 22.4% of patients with allogeneic HSCT. During follow-up, active tuberculosis did not develop in any patients in both groups. There was no statistically significant difference found between allogeneic and autologous HSCT recipients regarding the prevalence of latent tuberculosis. Active tuberculosis infection did not develop in any of the patients who started INH prophylaxis. INH prophylaxis seems to be very efficient in preventing the reactivation of latent tuberculosis in patients going through allogeneic HSCT and/or autologous HSCT.
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Affiliation(s)
- Duygu Mert
- University of Health Sciences Dr Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, Ankara, Turkey
- *Correspondence: Duygu Mert, University of Health Sciences Dr Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, Mehmet Akif Ersoy mah, Vatan cad., No: 91, Yenimahalle/Ankara 06200, Turkey (e-mail: )
| | - Muhammet Ozer
- Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Alparslan Merdin
- University of Health Sciences Ankara Gülhane Education and Research Hospital, Department of Hematology, Ankara, Turkey
| | - Gülşen İskender
- University of Health Sciences Dr Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, Ankara, Turkey
| | - Bahar Uncu Ulu
- University of Health Sciences Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, Department of Hematology & Bone Marrow Transplantation, Ankara, Turkey
| | - Merih Kizil Çakar
- University of Health Sciences Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, Department of Hematology & Bone Marrow Transplantation, Ankara, Turkey
| | - Mehmet Sinan Dal
- University of Health Sciences Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, Department of Hematology & Bone Marrow Transplantation, Ankara, Turkey
| | - Fevzi Altuntaş
- University of Health Sciences Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, Department of Hematology & Bone Marrow Transplantation, Ankara, Turkey
| | - Mustafa Ertek
- University of Health Sciences Dr Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, Ankara, Turkey
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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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28
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Wu S, Ding X, Yang Q, Wang M, He JQ. Association of Three SNPs Loci of Kelch-Like-ECH-Associated Protein 1 (Human) with Tuberculosis in Chinese Han Population. Int J Gen Med 2022; 15:6365-6372. [PMID: 35935100 PMCID: PMC9355661 DOI: 10.2147/ijgm.s373555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 07/27/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose Progression from latent tuberculosis infection (LTBI) to pulmonary TB (PTB) was associated with genetic polymorphisms, but there were limited genetic polymorphism data on LTBI and PTB. We aimed at examining the association of KEAP1 gene polymorphisms with PTB and LTBI. Patients and Methods PTB patients and close contacts of PTB patients were recruited from West China Hospital of Sichuan University. After obtaining the patient’s consent, we draw 2–5mL of blood from the patient’s peripheral vein. Tag-SNPs of KEAP1 were chosen according to previous studies. The genotyping was done by improved multiplex ligase detection reaction (iMLDR). We used logistic regression to assess the association of SNPs with LTBI/PTB, with sex and age as covariates. Results A total of 209 PTB patients, 201 LTBI, and 204 HCS were included in the present study. Three Tag-SNPs were included in this study. Significant association was found for KEAP1 rs1048290 between LTBI and HCS. Compared with the KEAP1 rs1048290 CC genotype, genotype GC had an 38% decreased risk for development LTBI (P = 0.043, OR = 0.62, 95% CI: 0.039–0.98). We also found that SNPs in KEAP1 were significantly related to PTB compared to LTBI. Compared with the rs11545829G allele, allele A had an 30% decreased risk for development PTB (P = 0.034, OR = 0.70, 95% CI: 0.51–0.97). We also found the rs11668429 polymorphism was related to PTB. Compared with TT, GT had a significantly increased risk of LTBI developing into PTB (P = 0.041, OR = 1.68, 95% CI: 1.02–2.77). Conclusion Our study suggested that KEAP1 polymorphisms were significantly related to susceptibility to PTB and LTBI subjects.
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Affiliation(s)
- Shouquan Wu
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Xiaojuan Ding
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Qianlan Yang
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Minggui Wang
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Jian-Qing He
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
- Correspondence: Jian-Qing He, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, 37, Guo Xue Alley, Chengdu, 610041, People’s Republic of China, Tel +86-18980602293, Fax +86-028-85422571, Email
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29
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Zhao L, Cho WC, Luo JL. Exploring the patient-microbiome interaction patterns for pan-cancer. Comput Struct Biotechnol J 2022; 20:3068-3079. [PMID: 35782745 PMCID: PMC9233187 DOI: 10.1016/j.csbj.2022.06.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 06/06/2022] [Accepted: 06/06/2022] [Indexed: 11/03/2022] Open
Abstract
Microbes play important roles in human health and disease. Immunocompromised cancer patients are more vulnerable to getting microbial infections. Regions of hypoxia and acidic tumor microenvironment shape the microbial community diversity and abundance. Each cancer has its own microbiome, making cancer-specific sets of microbiomes. High-throughput profiling technologies provide a culture-free approach for microbial profiling in tumor samples. Microbial compositional data was extracted and examined from the TCGA unmapped transcriptome data. Biclustering, correlation, and statistical analyses were performed to determine the seven patient-microbe interaction patterns. These two-dimensional patterns consist of a group of microbial species that show significant over-representation over the 7 pan-cancer subtypes (S1-S7), respectively. Approximately 60% of the untreated cancer patients have experienced tissue microbial composition and functional changes between subtypes and normal controls. Among these changes, subtype S5 had loss of microbial diversity as well as impaired immune functions. S1, S2, and S3 had been enriched with microbial signatures derived from the Gammaproteobacteria, Actinobacteria and Betaproteobacteria, respectively. Colorectal cancer (CRC) was largely composed of two subtypes, namely S4 and S6, driven by different microbial profiles. S4 patients had increased microbial load, and were enriched with CRC-related oncogenic pathways. S6 CRC together with other cancer patients, making up almost 40% of all cases were classified into the S6 subtype, which not only resembled the normal control's microbiota but also retained their original "normal-like" functions. Lastly, the S7 was a rare and understudied subtype. Our study investigated the pan-cancer heterogeneity at the microbial level. The identified seven pan-cancer subtypes with 424 subtype-specific microbial signatures will help us find new therapeutic targets and better treatment strategies for cancer patients.
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Affiliation(s)
- Lan Zhao
- Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, United States
| | - William C.S. Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China
| | - Jun-Li Luo
- The Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
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Fernández-Blázquez A, Argüelles Menéndez P, Sabater-Cabrera C, García-García JM, Asensi Álvarez V, Palacios Gutiérrez JJ. [Translated article] Diagnosis of tuberculous infection in immunosuppressed patients and/or candidates for biologics using a combination of 2 IGRA tests: T-SPOT.TB/QuantiFERON TB Gold In-Tube vs. T-SPOT.TB/QuantiFERON TB Gold Plus. Arch Bronconeumol 2022. [PMID: 35525572 DOI: 10.1016/j.arbres.2020.04.026] [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: 11/02/2022]
Abstract
INTRODUCTION The diagnosis of latent tuberculous infection (LTI) by IGRA continues to generate debate. Experience in the simultaneous use of 2 IGRA tests is scant. The aim of this study was to compare the results of 2 versions of QuantiFERON-TB Gold (In-Tube/Plus) with those of T-SPOT.TB, and to analyse the effectiveness of a dual strategy (T-SPOT.TB + QTF) for the diagnosis of LTI in an immunosuppressed population. METHODS We conducted a prospective study (May 2015-June 2017) that included 2999 immunosuppressed patients and/or candidates for biologics, in whom 2 simultaneous IGRA tests were performed: Group 1 (1535 patients): T-SPOT.TB + QuantiFERON-TB Gold-In-Tube (QTF-GIT); Group 2 (1464 patients): T-SPOT.TB + QuantiFERON-TB Gold Plus (QTF-Plus. RESULTS The concordance between QTF-GIT and T-SPOT.TB was 83.19% (κ = 0.532). The percentage of positive, negative, and indeterminate results were, respectively: 14.33% vs. 17.06%; 82.41% vs. 74.46%; and 3.25% vs. 8.46%. The concordance between QTF-Plus and T-SPOT.TB was 87.56% (κ = 0.609). The percentage of positive, negative, and indeterminate results were, respectively: 15.02% vs. 15.36%; 82.92% vs. 79.37%; and 2.04% vs. 5.25%. Discrepancies between T-SPOT.TB and QTF-Plus were 12.43%, suggesting that 103 patients were positive and another 79 were negative due exclusively to 1 of the 2 IGRAs. CONCLUSIONS Greater concordance was found between QTF-Plus and T-SPOT.TB than between QTF-GIT and T-SPOT.TB. However, we believe that the proportion of discrepancies between T-SPOT.TB and QTF-Plus is sufficiently important from a clinical point of view to justify the simultaneous use of 2 IGRA in this specific patient group.
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Affiliation(s)
- Ana Fernández-Blázquez
- Unidad de Referencia Regional de Micobacterias, Servicio de Microbiología, Hospital Universitario Central de Asturias, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Spain.
| | - Pablo Argüelles Menéndez
- Unidad de Referencia Regional de Micobacterias, Servicio de Microbiología, Hospital Universitario Central de Asturias, Spain
| | - Christian Sabater-Cabrera
- Unidad de Referencia Regional de Micobacterias, Servicio de Microbiología, Hospital Universitario Central de Asturias, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Spain
| | | | - Víctor Asensi Álvarez
- Unidad de Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Universitario Central de Asturias, Facultad de Medicina, Universidad de Oviedo, Spain
| | - Juan José Palacios Gutiérrez
- Unidad de Referencia Regional de Micobacterias, Servicio de Microbiología, Hospital Universitario Central de Asturias, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Spain
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Comparison of QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold-Plus in the Diagnosis of Mycobacterium tuberculosis Infections in Immunocompromised Patients: a Real-World Study. Microbiol Spectr 2022; 10:e0187021. [PMID: 35234509 PMCID: PMC9045206 DOI: 10.1128/spectrum.01870-21] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
QuantiFERON-TB Gold Plus (QFT-Plus) is an emerging QuantiFERON test after QuantiFERON-TB Gold In-Tube (QFT-GIT) for tuberculosis infection detection; it is an IFN-γ release assay. We compared QFTPlus, which has an additional TB antigen 2 (TB2) tube to induce cell-mediated (CD8+ T cell) immune responses, with QFT-GIT. We conducted this study to assess the agreement of the QFT-GIT and QFT-Plus assays in immunocompromised patients in a clinical setting. A total of 278 immunocompromised patients and 175 immunocompetent patients from different departments were continuously enrolled from August 2020 to March 2021, and each patient underwent both tests. Correlations between QFT-GIT and QFT-Plus assays showed good agreement (κ value = 0.859). Patients receiving long-term immunosuppressant therapy had the lowest concordance between QFT-GIT and QFT-Plus assays; 9 out of 11 positive latent tuberculosis infection (LTBI) cases were diagnosed by the QFT-Plus assay, implying that QFT-Plus may detect more LTBI than QFT-GIT does in these patients. Indeterminate results were associated with lower lymphocyte, CD4+ T cell, and CD8+ T cell absolute counts, and with lower CD4/CD8 ratios. In conclusion, we found that the QFT-GIT and QFT-Plus assays had high agreement not only in immunocompetent patients but also in immunocompromised patients. QFT-Plus may detect more LTBI than QFT-GIT in patients receiving long-term immunosuppressant therapy. Thresholds were established for lymphocyte absolute counts of >1.15 × 109 cells, and for CD4+ T cell absolute counts of >467.7 × 106 to 478.5 × 106 cells, which may lessen the incidence of indeterminate results. IMPORTANCE This study evaluated the performance of QFT-GIT and QFT-Plus in the diagnosis of M. tuberculosis infection in immunocompromised patients and found that QFT-Plus may detect more LTBI than QFT-GIT does in patients receiving long-term immunosuppressant therapy. We believe that our study makes a significant contribution to the literature because it highlights the different diagnostic accuracies of QFT-GIT and QFT-Plus in different subpopulations of immunocompromised and immunocompetent patients. Selecting a test with better performance, particularly in patients with a high risk of developing active TB, may assist the health sector in better managing TB. Furthermore, we believe that this study will be of significance to the diagnosis of LTBI.
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Yang Y, Wang HJ, Hu WL, Bai GN, Hua CZ. Diagnostic Value of Interferon-Gamma Release Assays for Tuberculosis in the Immunocompromised Population. Diagnostics (Basel) 2022; 12:diagnostics12020453. [PMID: 35204544 PMCID: PMC8871457 DOI: 10.3390/diagnostics12020453] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 02/04/2022] [Accepted: 02/07/2022] [Indexed: 02/04/2023] Open
Abstract
Interferon-gamma release assays (IGRAs) are widely used in the diagnosis of Mycobacterium tuberculosis (M. tuberculosis) infection by detecting interferon-γ released by previously sensitized T-cells in-vitro. Currently, there are two assays based on either enzyme-linked immunosorbent assay (ELISA) or enzyme-linked immunospot (ELISPOT) technology, with several generations of products available. The diagnostic value of IGRAs in the immunocompromised population is significantly different from that in the immunocompetent population because their results are strongly affected by the host immune function. Both physiological and pathological factors can lead to an immunocompromised situation. We summarized the diagnostic value and clinical recommendations of IGRAs for different immunocompromised populations, including peoplewith physiological factors (pregnant and puerperal women, children, and older people), as well as people with pathological factors (solid organ transplantation recipients, combination with human immunodeficiency virus infection, diabetes mellitus, end-stage renal disease, end-stage liver disease, and chronic immune-mediated inflammatory diseases). Though the performance of IGRAs is not perfect and often requires a combination with other diagnostic strategies, it still has some value in the immunocompromised population. Hopefully, the newly developed IGRAs could better target this population.
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Affiliation(s)
- Ying Yang
- Department of Infectious Diseases, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China; (Y.Y.); (H.-J.W.); (W.-L.H.); (G.-N.B.)
| | - Hong-Jiao Wang
- Department of Infectious Diseases, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China; (Y.Y.); (H.-J.W.); (W.-L.H.); (G.-N.B.)
| | - Wei-Lin Hu
- Department of Infectious Diseases, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China; (Y.Y.); (H.-J.W.); (W.-L.H.); (G.-N.B.)
- Department of Medical Microbiology, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China
| | - Guan-Nan Bai
- Department of Infectious Diseases, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China; (Y.Y.); (H.-J.W.); (W.-L.H.); (G.-N.B.)
| | - Chun-Zhen Hua
- Department of Infectious Diseases, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China; (Y.Y.); (H.-J.W.); (W.-L.H.); (G.-N.B.)
- Correspondence: ; Tel.: +86-136-0580-2618
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Auguste PE, Mistry H, McCarthy ND, Sutcliffe PA, Clarke AE. Cost-effectiveness of testing for latent tuberculosis infection in people with HIV. AIDS 2022; 36:1-9. [PMID: 34873091 DOI: 10.1097/qad.0000000000003060] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
OBJECTIVE The aim of this study was to estimate the cost-effectiveness of screening strategies for predicting LTBI that progresses to active tuberculosis (TB) in people with HIV. DESIGN We developed a decision-analytical model that constituted a decision tree covering diagnosis of LTBI and a Markov model covering progression to active TB. The model represents the lifetime experience following testing for LTBI, and discounting costs, and benefits at 3.5% per annum in line with UK standards. We undertook probabilistic and one-way sensitivity analyses. SETTING UK National Health Service and Personal Social Service perspective in a primary care setting. PARTICIPANTS Hypothetical cohort of adults recently diagnosed with HIV. INTERVENTIONS Interferon-gamma release assays and tuberculin skin test. MAIN OUTCOME MEASURE Cost per quality-adjusted life year (QALY). RESULTS All strategies except T-SPOT.TB were cost-effective at identifying LTBI, with the QFT-GIT-negative followed by TST5mm strategy being the most costly and effective. Results indicated that there was little preference between strategies at a willingness-to-pay threshold of £20 000. At thresholds above £40 000 per QALY, there was a clear preference for the QFT-GIT-negative followed by TST5mm, with a probability of 0.41 of being cost-effective. Results showed that specificity for QFT-GIT and TST5mm were the main drivers of the economic model. CONCLUSION Screening for LTBI has important public health and clinical benefits. Most of the strategies are cost-effective. These results should be interpreted with caution because of the paucity of studies included in the meta-analysis of test accuracy studies. Additional high-quality primary studies are needed to have a definitive answer about, which strategy is the most effective.
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Affiliation(s)
| | | | - Noel D McCarthy
- Evidence in Communicable Disease Epidemiology and Control, Warwick Medical School, University of Warwick, Coventry, UK
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Alsukait S, Alsaad A, Alotaibi G, Alsaif F, Alotaibi H. Conversion rate of tuberculosis screening tests among dermatology patients treated with tumor necrosis factor inhibitors. Indian J Dermatol 2022; 67:1-4. [PMID: 35656235 PMCID: PMC9154160 DOI: 10.4103/ijd.ijd_201_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Background: The use of tumor necrosis factor-α inhibitors (TNFi) has been associated with an increased risk latent tuberculosis (TB) reactivation. The role of TB screening assays in monitoring patients during TNFi therapy remains uncertain. Spontaneous conversions and reversions have been described. Aims: This study aims to determine the conversion and reversion rate of TB screening tests among dermatology patients receiving TNFi in a country with moderate TB incidence. Subjects and Methods: A retrospective single-center study conducted on all patients in whom treatment with TNFi was initiated in our dermatology clinic in a tertiary university hospital, Riyadh, Saudi Arabia, until September 2018. Data were collected from the hospital electronic patient information system. Results: One hundred and eighteen patients were included. Majority (79.9%) of patients used adalimumab. Psoriasis was the most common indication (90%). Among patients with negative baseline TB screening who had been retested during TNFi therapy (n = 65; 55%), conversion to positive was observed in nine patients (13.8%) with a mean duration of exposure of 39.7 months, whereas among patients with positive TB testing result (n = 18), 10 (55.5%) reverted to negative. Conclusions: This study emphasizes the need for prospective large-scale multispecialty studies assessing the significance of TB retesting, which should be considered when designing rescreening protocols.
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White HA, Okhai H, Kirwan P, Rafeeq SH, Dillon H, Hefford P, Wiselka MJ, Pareek M. Tuberculosis incidence in country of origin is a key determinant of the risk of active tuberculosis in people living with HIV: Data from a 30-year observational cohort study. HIV Med 2021; 23:650-660. [PMID: 34939299 DOI: 10.1111/hiv.13222] [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: 07/02/2021] [Revised: 11/04/2021] [Accepted: 12/06/2021] [Indexed: 11/28/2022]
Abstract
INTRODUCTION People living with HIV (PLWH) are at high risk of active tuberculosis (TB) but this risk in the era of antiretroviral treatment (ART) remains unclear. It is critical to identify the groups who should be prioritised for latent TB (LTBI) screening. In this study we identified the risk factors associated with developing incident TB disease, by analysing a 30-year observational cohort. METHODS We evaluated PLWH in Leicester, UK, between 1983 and 2017 to ascertain those who developed active TB and the timing of this in relation to HIV diagnosis; whether before, concurrently with, or more than 3 months after the diagnosis of HIV (incident TB). Predictors of incident TB were ascertained using Cox proportional hazards models. RESULTS In all, 325 out of 2158 (15.1%) PLWH under care had had active TB; 64/325 (19.7%) prior to HIV diagnosis, 161/325 (49.5%) concurrently with/within 3 months of HIV diagnosis and 100/325 (30.8%) had incident TB. Incident TB risk was 4.57/1000 person-years. Increased TB incidence in the country of birth was associated with an increased risk of developing incident TB [50-149/100 000 population, adjusted hazard ratio (AHR) = 3.10, 95% CI: 0.94-10.20; 150-249/100 000 population, AHR = 7.14, 95% CI: 3.46-14.74; 250-349/100 000 population, AHR = 5.90, 95% CI: 2.32-14.99; ≥ 350/100 000 population, AHR = 3.96, 95% CI: 1.39-11.26]. CONCLUSIONS Tuberculosis risk remains high among PLWH and is related to TB incidence in the country of birth. Further work is required to determine whether specific groups of PLWH should be targeted for programmatic LTBI screening, and whether it will result in high uptake and completion of chemoprophylaxis and is cost-effective for widespread implementation.
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Affiliation(s)
- Helena A White
- Department of Respiratory Sciences, University of Leicester, Leicester, UK.,Department of Infection and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Hajra Okhai
- Institute for Global Health, University College London, London, UK
| | - Peter Kirwan
- Blood Safety, Hepatitis, Sexually Transmitted Infections and HIV Service, Public Health England, London, UK
| | - Sonia H Rafeeq
- Blood Safety, Hepatitis, Sexually Transmitted Infections and HIV Service, Public Health England, London, UK
| | - Helen Dillon
- Department of Infection and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Phillip Hefford
- Department of Infection and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Martin J Wiselka
- Department of Infection and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Manish Pareek
- Department of Respiratory Sciences, University of Leicester, Leicester, UK.,Department of Infection and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK
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Hanafiah M, Mukhari SAM, Mustapha AM, Mumin NA. Intraventricular tuberculosis abscess in an immunocompromised patient: clinical vignette. ASIAN BIOMED 2021; 15:293-297. [PMID: 37551366 PMCID: PMC10321223 DOI: 10.2478/abm-2021-0036] [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: 11/20/2022]
Abstract
Tuberculosis is caused by Mycobacterium tuberculosis. Tuberculosis of the central nervous system is common and manifestations include meningeal and intraparenchymal diseases. However, intraventricular tuberculous abscess is a rare manifestation of intracranial tuberculous infection. We present a case of an immunocompromised female patient with high-grade fever and signs of meningism. The computed tomography and magnetic resonance imaging (MRI) of the brain showed hydrocephalus with rim-enhancing lesion in the right lateral ventricle. The MRI demonstrated a hypointense signal on T1-weighted imaging, hyperintense signal on T2-weighted imaging, and mild restricted diffusion in diffusion-weighted imaging. She underwent emergency external ventricular drainage and frank pus was drained. Diagnosis of tuberculosis was made via polymerase chain reaction analysis and culture. Understanding the intracranial manifestation of neurotuberculosis is imperative to arrive at the diagnosis correctly and ensure prompt treatment.
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Affiliation(s)
- Mohamad Hanafiah
- Department of Radiology, Sunway Medical Centre,Jalan Lagoon Selatan, Bandar Sunway, 47500Petaling Jaya, Selangor, Malaysia
| | - Shahizon A Mohamed Mukhari
- Department of Radiology, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000Cheras, Kuala Lumpur, Malaysia
| | - Aida M Mustapha
- Department of Radiology, Hospital Shah Alam,Persiaran Kayangan 7, 40000Shah Alam, Selangor, Malaysia
| | - Nazimah Ab Mumin
- Department of Radiology, Faculty of Medicine, University Teknologi Mara, 40450Shah Alam, Selangor, Malaysia
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Lee CS, Shu CC, Chen YC, Liao KM, Ho CH. Tuberculosis treatment incompletion in patients with lung cancer: occurrence and predictors. Int J Infect Dis 2021; 113:200-206. [PMID: 34600134 DOI: 10.1016/j.ijid.2021.09.072] [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: 08/06/2021] [Revised: 09/23/2021] [Accepted: 09/27/2021] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Lung cancer patients are high-risk for active tuberculosis (TB); however, fragility and drug-drug interaction might lead to TB treatment interruption. TB treatment incompletion occurrence and predictors among lung cancer patients remain unclear. METHODS We recruited lung cancer patients with new-onset TB from Taiwan Cancer Registry and Taiwanese National Health Insurance 2007-2015 databases. TB treatment incompletion was the identified primary outcome, and associated risk factors were analyzed. RESULTS A total of 1155 lung cancer patients with new-onset TB were identified and classified as treatment incompletion (n=706, 61.13%) or completion (n=449). Gender and age distribution was similar in both groups. Under multivariable logistic regression, advanced cancer (stage III and IV) and no first-line TB drugs use were independent factors for treatment incompletion; but older age was not significant. For patients surviving >1 year since TB diagnosis, independent factors for treatment incompletion included no first-line TB drugs use (except pyrazinamide) and absence of hypertension. Cancer stage had borderline significance. CONCLUSIONS TB treatment incompletion occurred in 61.13% of lung cancer patients. Clinicians should carefully titrate anti-TB medications and monitor side effects in lung cancer patients, especially those with treatment incompletion risk factors, to avoid treatment interruption due to fragility and/or drug intolerance.
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Affiliation(s)
- Chung-Shu Lee
- Department of Pulmonary and Critical Care Medicine, New Taipei Municipal Tu Cheng Hospital, New Taipei City, Taiwan; Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University, School of Medicine, Taipei, Taiwan
| | - Chin-Chung Shu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Chen Chen
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
| | - Kuang-Ming Liao
- Department of Internal Medicine, Chi Mei Medical Center, Chiali, Tainan, Taiwan.
| | - Chung-Han Ho
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Information Management, Southern Taiwan University of Science and Technology.
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Tuon FF. Latent tuberculosis infection and kidney transplantation. J Bras Nefrol 2021; 43:455-456. [PMID: 34543376 PMCID: PMC8940120 DOI: 10.1590/2175-8239-jbn-2021-e008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 07/28/2021] [Indexed: 11/22/2022] Open
Affiliation(s)
- Felipe Francisco Tuon
- Pontifícia Universidade Católica do Paraná, Faculdade de Medicina, Laboratório de Doenças Infecciosas Emergentes, Curitiba, PR, Brasil
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Abstract
Increasing numbers of head and neck cancer patients are placed on immune checkpoint inhibitors for indications such as recurrent and metastatic disease. There is a theoretical increased risk of contracting and reactivation of tuberculosis (TB) with programmed cell death-1 blockade due to potentiation of type 1 T helper response and increased production of interferon-gamma. This is a potentially life-threatening complication of therapy and requires expedient diagnosis and treatment. We present a case of a patient with metastatic nasopharyngeal carcinoma treated with avelumab, a programmed cell death-ligand 1 inhibitor with resulting laryngeal TB as the presenting symptom of reactivated TB. The patient required quadruple anti-TB therapy, but developed ongoing sequelae of laryngeal TB, including dysphagia and laryngeal stenosis. Ongoing trials are examining the use of avelumab in head and neck cancer patients with locally advanced disease, recurrent, or metastatic disease. Awareness of the risk of new and reactivated TB is crucial.
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Tuberculosis in allogeneic haematopoietic stem cell transplantation: so many unresolved questions! Bone Marrow Transplant 2021; 56:2050-2051. [PMID: 34145415 DOI: 10.1038/s41409-021-01381-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 05/25/2021] [Accepted: 06/10/2021] [Indexed: 02/05/2023]
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The latent tuberculosis cascade-of-care among people living with HIV: A systematic review and meta-analysis. PLoS Med 2021; 18:e1003703. [PMID: 34492003 PMCID: PMC8439450 DOI: 10.1371/journal.pmed.1003703] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 09/14/2021] [Accepted: 06/20/2021] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Tuberculosis preventive therapy (TPT) reduces TB-related morbidity and mortality in people living with HIV (PLHIV). Cascade-of-care analyses help identify gaps and barriers in care and develop targeted solutions. A previous latent tuberculosis infection (LTBI) cascade-of-care analysis showed only 18% of persons in at-risk populations complete TPT, but a similar analysis for TPT among PLHIV has not been completed. We conducted a meta-analysis to provide this evidence. METHODS AND FINDINGS We first screened potential articles from a LTBI cascade-of-care systematic review published in 2016. From this study, we included cohorts that reported a minimum of 25 PLHIV. To identify new cohorts, we used a similar search strategy restricted to PLHIV. The search was conducted in Medline, Embase, Health Star, and LILACS, from January 2014 to February 2021. Two authors independently screened titles and full text and assessed risk of bias using the Newcastle-Ottawa Scale for cohorts and Cochrane Risk of Bias for cluster randomized trials. We meta-analyzed the proportion of PLHIV completing each step of the LTBI cascade-of-care and estimated the cumulative proportion retained. These results were stratified based on cascades-of-care that used or did not use LTBI testing to determine eligibility for TPT. We also performed a narrative synthesis of enablers and barriers of the cascade-of-care identified at different steps of the cascade. A total of 71 cohorts were included, and 70 were meta-analyzed, comprising 94,011 PLHIV. Among the PLHIV included, 35.3% (33,139/94,011) were from the Americas and 29.2% (27,460/94,011) from Africa. Overall, 49.9% (46,903/94,011) from low- and middle-income countries, median age was 38.0 [interquartile range (IQR) 34.0;43.6], and 65.9% (46,328/70,297) were men, 43.6% (29,629/67,947) were treated with antiretroviral therapy (ART), and the median CD4 count was 390 cell/mm3 (IQR 312;458). Among the cohorts that did not use LTBI tests, the cumulative proportion of PLHIV starting and completing TPT were 40.9% (95% CI: 39.3% to 42.7%) and 33.2% (95% CI: 31.6% to 34.9%). Among cohorts that used LTBI tests, the cumulative proportions of PLHIV starting and completing TPT were 60.4% (95% CI: 58.1% to 62.6%) and 41.9% (95% CI:39.6% to 44.2%), respectively. Completion of TPT was not significantly different in high- compared to low- and middle-income countries. Regardless of LTBI test use, substantial losses in the cascade-of-care occurred before treatment initiation. The integration of HIV and TB care was considered an enabler of the cascade-of-care in multiple cohorts. Key limitations of this systematic review are the observational nature of the included studies, potential selection bias in the population selection, only 14 cohorts reported all steps of the cascade-of-care, and barriers/facilitators were not systematically reported in all cohorts. CONCLUSIONS Although substantial losses were seen in multiple stages of the cascade-of-care, the cumulative proportion of PLHIV completing TPT was higher than previously reported among other at-risk populations. The use of LTBI testing in PLHIV in low- and middle-income countries was associated with higher proportion of the cohorts initiating TPT and with similar rates of completion of TPT.
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Martin-Iguacel R, Llibre JM, Pedersen C, Obel N, Stærke NB, Åhsberg J, Ørsted I, Holden I, Kronborg G, Mohey R, Rasmussen LD, Johansen IS. Tuberculosis incidence and mortality in people living with human immunodeficiency virus: a Danish nationwide cohort study. Clin Microbiol Infect 2021; 28:570-579. [PMID: 34438070 DOI: 10.1016/j.cmi.2021.07.036] [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: 05/02/2021] [Revised: 07/15/2021] [Accepted: 07/26/2021] [Indexed: 01/30/2023]
Abstract
OBJECTIVES To explore changes over time in the epidemiology of tuberculosis (TB) in Denmark in people living with human immunodeficiency virus (HIV) (PLWH). METHODS In this nationwide, population-based cohort study we included all adult PLWH from the Danish HIV Cohort Study (1995-2017) without previous TB. We estimated TB incidence rate (IR), all-cause mortality rate (MR), associated risk and prognostic factors using Poisson regression. RESULTS Among 6982 PLWH (73 596 person-years (PY)), we observed 217 TB events (IR 2.9/1000 PY, 95% CI 2.6-3.4: IR 6.7, 95% CI 5.7-7.9 among migrants and IR 1.4, 95% CI 1.1-1.7 among Danish-born individuals; p < 0.001). The IR of concomitant HIV/TB remained high and unchanged over time. The IR of TB diagnosed >3 months after HIV diagnosis declined with calendar time, longer time from HIV diagnosis, and CD4 cell recovery. Independent TB risk factors were African/Asian/Greenland origin (adjusted incidence rate ratio (aIRR) 5.2, 95% CI 3.5-7.6, aIRR 6.5, 95% CI 4.2-10.0, aIRR 7.0, 95% CI 3.4-14.6, respectively), illicit drug use (aIRR 6.9, 95% CI 4.2-11.2), CD4 <200 cells/μL (aIRR 2.7, 95% CI 2.0-3.6) and not receiving antiretroviral therapy (aIRR 3.7, 95% CI 2.5-5.3). Fifty-five patients died (MR 27.9/1000 PY, 95% CI 21.4-36.3), with no improvement in mortality over time. Mortality prognostic factors were Danish-origin (adjusted mortality rate ratio (aMRR) 2.3, 95% CI 1.3-4.3), social burden (aMRR 3.9, 95% CI 2.2-7.0), CD4 <100 cells/μL at TB diagnosis (aMRR 2.6, 95% CI 1.3-4.9), TB diagnosed >3 months after HIV versus concomitant diagnosis (aMRR 4.3, 95% CI 2.2-8.7) and disseminated TB (aMRR 3.3, 95% CI 1.1-9.9). CONCLUSION Late HIV presentation with concomitant TB remains a challenge. Declining TB rates in PLWH were observed over time and with CD4 recovery, highlighting the importance of early and successful antiretroviral therapy. However, MR remained high. Our findings highlight the importance of HIV and TB screening strategies and treatment of latent TB in high-risk groups.
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Affiliation(s)
- Raquel Martin-Iguacel
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark; Research Unit for Infectious Diseases, University of Southern Denmark, Denmark.
| | - Josep M Llibre
- Infectious Diseases Department and Fight AIDS and Infectious Diseases Foundation, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain
| | - Court Pedersen
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark; Research Unit for Infectious Diseases, University of Southern Denmark, Denmark
| | - Niels Obel
- Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | | | - Johanna Åhsberg
- Research Unit for Infectious Diseases, University of Southern Denmark, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Mycobacterial Centre for Research Southern Denmark, MyCRESD, Odense, Denmark
| | - Iben Ørsted
- Department of Infectious Diseases, Hvidovre Hospital, Hvidovre, Denmark
| | - Inge Holden
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark; Research Unit for Infectious Diseases, University of Southern Denmark, Denmark; Mycobacterial Centre for Research Southern Denmark, MyCRESD, Odense, Denmark
| | - Gitte Kronborg
- Department of Infectious Diseases, Herning Hospital, Herning, Denmark
| | - Rajesh Mohey
- Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark
| | - Line Dahlerup Rasmussen
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark; Research Unit for Infectious Diseases, University of Southern Denmark, Denmark
| | - Isik Somuncu Johansen
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark; Research Unit for Infectious Diseases, University of Southern Denmark, Denmark; Mycobacterial Centre for Research Southern Denmark, MyCRESD, Odense, Denmark.
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Ronge L, Sloot R, Preez KD, Kay AW, Lester Kirchner H, Grewal HMS, Mandalakas AM, Hesseling AC. The Magnitude of Interferon Gamma Release Assay Responses in Children With Household Tuberculosis Contact Is Associated With Tuberculosis Exposure and Disease Status. Pediatr Infect Dis J 2021; 40:763-770. [PMID: 34050092 PMCID: PMC8277676 DOI: 10.1097/inf.0000000000003196] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
BACKGROUND The clinical utility of the magnitude of interferon gamma (IFNγ) in response to mycobacterial antigens is unknown. We assessed the association between quantitative IFNγ response and degree of Mycobacterium tuberculosis exposure, infection and tuberculosis (TB) disease status in children. METHODS We completed cross-sectional analysis of children (≤15 years) exposed to an adult with bacteriologically confirmed TB, 2007-2012 in Cape Town, South Africa. IFNγ values were reported as concentrations and spot forming units for the QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB, respectively. Random-effects linear regression was used to investigate the relation between the M. tuberculosis contact score, clinical phenotype (TB diseased, infected, uninfected) and IFNγ▪response as outcome, adjusted for relevant covariates. RESULTS We analyzed data from 669 children (median age, 63 months; interquartile range, 33-108 months). A 1-unit increase in M. tuberculosis contact score was associated with an increase of IFNγ 0.60 international unit/mL (95% confidence interval [CI], 0.44-0.76 international unit/mL), and IFNγ spot forming unit 2 counts (95% CI, 1-3). IFNγ response was significantly lower among children with M. tuberculosis infection compared with children with TB disease (β = -1.42; 95% CI, -2.80 to -0.03) for the QFT-GIT, but not for the T-SPOT.TB. This association was strongest among children 2-5 years (β = -2.35 years; 95% CI, -4.28 to -0.42 years) and absent if <2 years. CONCLUSIONS The magnitude of IFNγ response correlated with the degree of recent M. tuberculosis exposure, measured by QFT-GIT and T-SPOT.TB, and was correlated with clinically relevant TB phenotypes using the QFT-GIT. IFNγ values are not only useful in estimating the risk of M. tuberculosis infection but may also support the diagnosis of TB disease in children. DISCUSSION The magnitude of IFNγ response correlated with the degree of recent M. tuberculosis exposure, measured by QFT-GIT and T-SPOT.TB, and was correlated with clinically relevant TB phenotypes using the QFT-GIT. IFNγ values are not only useful in estimating the risk of M. tuberculosis infection but may also support the diagnosis of TB disease in children.
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Affiliation(s)
- Lena Ronge
- Desmond Tutu TB Centre, Department of Paediatrics and Child
Health, Stellenbosch University, Cape Town, South Africa
| | - Rosa Sloot
- Desmond Tutu TB Centre, Department of Paediatrics and Child
Health, Stellenbosch University, Cape Town, South Africa
| | - Karen Du Preez
- Desmond Tutu TB Centre, Department of Paediatrics and Child
Health, Stellenbosch University, Cape Town, South Africa
| | - Alexander W. Kay
- The Global Tuberculosis Program, Texas
Children’s Hospital, Department of Pediatrics, Baylor College of Medicine,
Houston, Texas, USA
| | - H. Lester Kirchner
- Department of Population Health Sciences, Geisinger
Clinic, Danville, Pennsylvania, USA
| | - Harleen M. S. Grewal
- Department of Clinical Science, BIDS group, Faculty
of Medicine, University of Bergen, Bergen, Norway
- Department of Microbiology, Haukeland University
Hospital, Bergen, Norway
| | - Anna M. Mandalakas
- The Global Tuberculosis Program, Texas
Children’s Hospital, Department of Pediatrics, Baylor College of Medicine,
Houston, Texas, USA
| | - Anneke C. Hesseling
- Desmond Tutu TB Centre, Department of Paediatrics and Child
Health, Stellenbosch University, Cape Town, South Africa
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Borekci S, Karakas FG, Sirekbasan S, Kubat B, Karaali R, Can G, Kocazeybek BS, Gemicioglu B. The Relationship between Pre-Pandemic Interferon Gamma Release Assay Test Results and COVID-19 Infection: Potential Prognostic Value of Indeterminate IFN- γ Release Assay Results. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2021; 2021:1989277. [PMID: 34367385 PMCID: PMC8342180 DOI: 10.1155/2021/1989277] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 07/23/2021] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To reveal the relationship between interferon-gamma release assay (IGRA) test (Standard ETB-Feron ELISA (TBF)) results performed within 12 months before the COVID-19 pandemic and the frequency of COVID-19 infections and the severity of COVID-19. METHODS The retrospective TBF test results and contact information of 684 patients aged over 18 years who underwent TBF testing between March 11th, 2019, and March 10th, 2020, were obtained. Of the 684 patients contacted by phone, 365 agreed to participate in the study and were enrolled. The patients were divided into three groups (TBF test positive, negative, and indeterminate). The data obtained from the questionnaire were compared statistically. RESULTS According to the TBF test results, positive (n = 51, 14%), negative (n = 286, 78.3%), and indeterminate (n = 28, 7.7%) groups were compared. The frequency of COVID-19 infections in the indeterminate group was found significantly higher than that in the positive and negative groups (p=0.005). When the group with COVID-19 (n = 46, 12.6%) was compared with the group without (n = 319, 87.4%), no difference was found in terms of age, sex, body mass index, smoking history and number of cigarettes smoked, TB history, diabetes mellitus, hypertension, coronary artery disease, and biologic and corticosteroid therapy use. Only the frequency of obstructive pulmonary disease was significantly higher in the group without COVID-19 (p=0.033). CONCLUSION The frequency of COVID-19 infection was increased in patients with indeterminate TBF test results. Indeterminate TBF test results may be a guide in terms of risk stratification in groups at risk for COVID-19.
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Affiliation(s)
- Sermin Borekci
- Department of Pulmonary Diseases, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Fatma Gulsum Karakas
- Department of Pulmonary Diseases, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Serhat Sirekbasan
- Department of Medical Laboratory Techniques, Eldivan Vocational School of Health Services, Cankırı Karatekin University, Cankırı, Turkey
| | - Bahar Kubat
- Department of Pulmonary Diseases, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Rıdvan Karaali
- Department of Infectious Diseases, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Gunay Can
- Department of Public Health, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Bekir Sami Kocazeybek
- Department of Medical Microbiology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Bilun Gemicioglu
- Department of Pulmonary Diseases, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
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45
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Ledesma JR, Ma J, Zheng P, Ross JM, Vos T, Kyu HH. Interferon-gamma release assay levels and risk of progression to active tuberculosis: a systematic review and dose-response meta-regression analysis. BMC Infect Dis 2021; 21:467. [PMID: 34022827 PMCID: PMC8141158 DOI: 10.1186/s12879-021-06141-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 05/05/2021] [Indexed: 12/26/2022] Open
Abstract
Background Identifying and treating individuals with high risk of progression from latent tuberculosis infection to active tuberculosis (TB) disease is critical for eliminating the disease. We aimed to conduct a systematic review and meta-regression analysis to quantify the dose-response relationship between interferon-gamma release assay (IGRA) levels and the risk of progression to active TB. Methods We searched PubMed and Embase from 1 January 2001 to 10 May 2020 for longitudinal studies that reported the risk of progression from latent to active TB as a function of baseline IGRA values. We used a novel Bayesian meta-regression method to pool effect sizes from included studies and generate a continuous dose-response risk curve. Our modeling framework enabled us to incorporate random effects across studies, and include data with different IGRA ranges across studies. The quality of included studies were assessed using the Newcastle-Ottawa scale (NOS). Results We included 34 studies representing 581,956 person-years of follow-up with a total of 788 incident cases of TB in the meta-regression analysis. Higher levels of interferon-gamma were associated with increased risk of progression to active tuberculosis. In the dose-response curve, the risk increased sharply between interferon-gamma levels 0 and 5 IU/ml, after which the risk continued to increase moderately but at a slower pace until reaching about 15 IU/ml where the risk levels off. Compared to 0 IU/ml, the relative risk of progression to active TB among those with interferon-gamma levels of 0.35, 1, 5, 10, 15, and 20 IU/ml were: 1.64 (1.28–2.08), 2.90 (2.02–3.88), 11.38 (6.64–16.38), 19.00 (13.08–26.90), 21.82 (14.65–32.57), and 22.31 (15.43–33.00), respectively. The dose-response relationship remains consistent when limiting the analysis to studies that scored highest in the NOS. Conclusion The current practice of dichotomizing IGRA test results simplifies the TB infection disease continuum. Evaluating IGRA test results over a continuous scale could enable the identification of individuals at greatest risk of progression to active TB. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06141-4.
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Affiliation(s)
- Jorge R Ledesma
- Institute for Health Metrics and Evaluation, University of Washington, 3980 15th Ave. NE, Seattle, WA, 98195, USA
| | - Jianing Ma
- Institute for Health Metrics and Evaluation, University of Washington, 3980 15th Ave. NE, Seattle, WA, 98195, USA
| | - Peng Zheng
- Institute for Health Metrics and Evaluation, University of Washington, 3980 15th Ave. NE, Seattle, WA, 98195, USA.,Department of Health Metrics Sciences, University of Washington, 3980 15th Ave. NE, Seattle, WA, 98195, USA
| | - Jennifer M Ross
- Department of Global Health, University of Washington, 325 9th Avenue, Box 359931, Seattle, WA, 98104, USA.,Department of Medicine, University of Washington, 1959 NE Pacific Street, Box 356420, Seattle, WA, 98195, USA
| | - Theo Vos
- Institute for Health Metrics and Evaluation, University of Washington, 3980 15th Ave. NE, Seattle, WA, 98195, USA.,Department of Health Metrics Sciences, University of Washington, 3980 15th Ave. NE, Seattle, WA, 98195, USA
| | - Hmwe H Kyu
- Institute for Health Metrics and Evaluation, University of Washington, 3980 15th Ave. NE, Seattle, WA, 98195, USA. .,Department of Health Metrics Sciences, University of Washington, 3980 15th Ave. NE, Seattle, WA, 98195, USA.
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46
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Denissen JK, Reyneke B, Waso M, Khan S, Khan W. Human Pathogenic Bacteria Detected in Rainwater: Risk Assessment and Correlation to Microbial Source Tracking Markers and Traditional Indicators. Front Microbiol 2021; 12:659784. [PMID: 34025613 PMCID: PMC8138566 DOI: 10.3389/fmicb.2021.659784] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 04/09/2021] [Indexed: 11/22/2022] Open
Abstract
Roof-harvested rainwater (RHRW) was investigated for the presence of the human pathogenic bacteria Mycobacterium tuberculosis (M. tuberculosis), Yersinia spp. and Listeria monocytogenes (L. monocytogenes). While Yersinia spp. were detected in 92% (n = 25) of the RHRW samples, and L. monocytogenes and M. tuberculosis were detected in 100% (n = 25) of the samples, a significantly higher mean concentration (1.4 × 103 cells/100 mL) was recorded for L. monocytogenes over the sampling period. As the identification of appropriate water quality indicators is crucial to ensure access to safe water sources, correlation of the pathogens to traditional indicator organisms [Escherichia coli (E. coli) and Enterococcus spp.] and microbial source tracking (MST) markers (Bacteroides HF183, adenovirus and Lachnospiraceae) was conducted. A significant positive correlation was then recorded for E. coli versus L. monocytogenes (r = 0.6738; p = 0.000), and Enterococcus spp. versus the Bacteroides HF183 marker (r = 0.4071; p = 0.043), while a significant negative correlation was observed for M. tuberculosis versus the Bacteroides HF183 marker (r = −0.4558; p = 0.022). Quantitative microbial risk assessment indicated that the mean annual risk of infection posed by L. monocytogenes in the RHRW samples exceeded the annual infection risk benchmark limit (1 × 10–4 infections per person per year) for intentional drinking (∼10–4). In comparison, the mean annual risk of infection posed by E. coli was exceeded for intentional drinking (∼10–1), accidental consumption (∼10–3) and cleaning of the home (∼10–3). However, while the risk posed by M. tuberculosis for the two relevant exposure scenarios [garden hosing (∼10–5) and washing laundry by hand (∼10–5)] was below the benchmark limit, the risk posed by adenovirus for garden hosing (∼10–3) and washing laundry by hand (∼10–3) exceeded the benchmark limit. Thus, while the correlation analysis confirms that traditional indicators and MST markers should be used in combination to accurately monitor the pathogen-associated risk linked to the utilisation of RHRW, the integration of QMRA offers a more site-specific approach to monitor and estimate the human health risks associated with the use of RHRW.
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Affiliation(s)
- Julia K Denissen
- Department of Microbiology, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa
| | - Brandon Reyneke
- Department of Microbiology, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa
| | - Monique Waso
- Faculty of Health Sciences, University of Johannesburg, Doornfontein, South Africa
| | - Sehaam Khan
- Faculty of Health Sciences, University of Johannesburg, Doornfontein, South Africa
| | - Wesaal Khan
- Department of Microbiology, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa
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47
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Patel V, Foster A, Salem A, Kumar A, Kumar V, Biswas B, Mirsaeidi M, Kumar N. Long-term exposure to indoor air pollution and risk of tuberculosis. INDOOR AIR 2021; 31:628-638. [PMID: 33016379 PMCID: PMC9580027 DOI: 10.1111/ina.12756] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 09/13/2020] [Accepted: 09/25/2020] [Indexed: 05/09/2023]
Abstract
Indoor air pollution (IAP) is a recognized risk factor for various diseases. This paper examines the role of indoor solid fuel exposure in the risk of mycobacterium tuberculosis (TB) in Delhi Metropolitan, India. Using a cross-sectional design, subjects were screened for a history of active TB and lifelong exposure to IAP sources, such as solid fuel burning and kerosene. The TB prevalence rate in the study area was 1117 per 100 000 population. Every year, increase in solid fuel exposure was associated with a three percent higher likelihood of a history of active TB. Subjects exposed to solid fuel and kerosene use for both heating home and cooking showed significant associations with TB. Age, household expenditure (a proxy of income), lung function, and smoking also showed significant associations with TB. Smokers and solid fuel-exposed subjects were four times more likely to have a history of active TB than non-smoker and unexposed subjects. These finding calls strategies to mitigate solid fuel exposure, such as use of clean cookstove and ventilation, to mitigate the risk of TB which aligns with the United Nations' goal of "End TB by 2030."
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Affiliation(s)
- Vidhiben Patel
- Department of Public Health Sciences, Environmental Health Division, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Andrew Foster
- Department of Economics, Brown University, Providence, RI, USA
| | - Alison Salem
- Department of Public Health Sciences, Environmental Health Division, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Amit Kumar
- Society for Environmental Health, New Delhi, India
| | - Vineet Kumar
- Society for Environmental Health, New Delhi, India
| | - Biplab Biswas
- Department of Geography, Burdwan University, Burdwan, West Bengal 713104, India
| | - Mehdi Mirsaeidi
- Department of Public Health Sciences, Environmental Health Division, University of Miami Miller School of Medicine, Miami, FL, USA
- Department of Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, Miller School of Medicine, Miami VA Healthcare System, University of Miami, Miami, FL, USA
| | - Naresh Kumar
- Department of Public Health Sciences, Environmental Health Division, University of Miami Miller School of Medicine, Miami, FL, USA
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48
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Park JH, Choi EJ, Park HS, Choi SH, Lee SO, Kim YS, Woo JH, Lee JH, Lee JH, Lee KH, Shim TS, Kim SH. Treatment of Latent Tuberculosis Infection Based on the Interferon-γ Release Assay in Allogeneic Stem Cell Transplant Recipients. Clin Infect Dis 2021; 71:1977-1979. [PMID: 31930297 DOI: 10.1093/cid/ciaa030] [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: 11/20/2019] [Accepted: 01/11/2020] [Indexed: 12/15/2022] Open
Abstract
In hematopoietic stem cell transplant recipients, the incidence of tuberculosis in positive interferon-γ release assay (IGRA) without isoniazid prophylaxis (3.58/100 person-years) was higher than in negative or indeterminate IGRA (1.15/100 person-years; P = .01) and in positive IGRA with isoniazid prophylaxis (0/100 person-years; P = .09). The number needed to treat was 22 (95% confidence interval, 12-99) with positive IGRA results.
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Affiliation(s)
- Joung Ha Park
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Eun-Ji Choi
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Han-Seung Park
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sang-Ho Choi
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sang-Oh Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yang Soo Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jun Hee Woo
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jung-Hee Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Je-Hwan Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Kyoo-Hyung Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Tae Sun Shim
- Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sung-Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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Haranahalli K, Tong S, Kim S, Awwa M, Chen L, Knudson SE, Slayden RA, Singleton E, Russo R, Connell N, Ojima I. Structure-activity relationship studies on 2,5,6-trisubstituted benzimidazoles targeting Mtb-FtsZ as antitubercular agents. RSC Med Chem 2021; 12:78-94. [PMID: 34046600 PMCID: PMC8132993 DOI: 10.1039/d0md00256a] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 09/14/2020] [Indexed: 11/21/2022] Open
Abstract
Filamenting temperature sensitive protein Z (FtsZ) is an essential bacterial cell division protein and a promising target for the development of new antibacterial therapeutics. As a part of our ongoing SAR studies on 2,5,6-trisubstituted benzimidazoles as antitubercular agents targeting Mtb-FtsZ, a new library of compounds with modifications at the 2 position was designed, synthesized and evaluated for their activity against Mtb-H37Rv. This new library of trisubstituted benzimidazoles exhibited MIC values in the range of 0.004-50 μg mL-1. Compounds 6b, 6c, 20f and 20g showed excellent growth inhibitory activities ranging from 0.004-0.08 μg mL-1. This SAR study has led to the discovery of a remarkably potent compound 20g (MIC 0.0039 μg mL-1; normalized MIC 0.015 μg mL-1). Our 3DQSAR model predicted 20g as the most potent compound in the library.
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Affiliation(s)
- Krupanandan Haranahalli
- Institute of Chemical Biology and Drug Discovery, Stony Brook University Stony Brook NY USA
- Department of Chemistry, Stony Brook University Stony Brook NY USA
| | - Simon Tong
- Department of Chemistry, Stony Brook University Stony Brook NY USA
| | - Saerom Kim
- Department of Chemistry, Stony Brook University Stony Brook NY USA
| | - Monaf Awwa
- Department of Chemistry, Stony Brook University Stony Brook NY USA
| | - Lei Chen
- Department of Chemistry, Stony Brook University Stony Brook NY USA
| | - Susan E Knudson
- Department of Microbiology, Immunology and Pathology, Colorado State University Fort Collins Colorado 80523-1682 USA
| | - Richard A Slayden
- Department of Microbiology, Immunology and Pathology, Colorado State University Fort Collins Colorado 80523-1682 USA
| | - Eric Singleton
- Department of Medicine, Center for Emerging and Re-emerging Pathogens, Rutgers University Newark New Jersey 07103 USA
| | - Riccardo Russo
- Department of Medicine, Center for Emerging and Re-emerging Pathogens, Rutgers University Newark New Jersey 07103 USA
| | - Nancy Connell
- Department of Medicine, Center for Emerging and Re-emerging Pathogens, Rutgers University Newark New Jersey 07103 USA
- Department of Physiology, Rutgers University Newark New Jersey 07103 USA
| | - Iwao Ojima
- Institute of Chemical Biology and Drug Discovery, Stony Brook University Stony Brook NY USA
- Department of Chemistry, Stony Brook University Stony Brook NY USA
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50
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Wang PH, Lin SY, Lee SSJ, Lin SW, Lee CY, Wei YF, Shu CC, Wang JY, Yu CJ. CD4 response of QuantiFERON-TB Gold Plus for positive consistency of latent tuberculosis infection in patients on dialysis. Sci Rep 2020; 10:21367. [PMID: 33288814 PMCID: PMC7721715 DOI: 10.1038/s41598-020-78374-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 11/12/2020] [Indexed: 11/09/2022] Open
Abstract
A significantly negative reversion in the QuantiFERON-TB Gold In-tube (QFT-GIT) test is reported in patients on dialysis, which makes the results unreliable. The CD4 and CD8 responses of the QFT-Gold plus (QFT-Plus) may have better positive consistency, but this needs to be investigated. We enrolled dialysis patients with baseline positive QFT-GIT0 results and conducted two rounds of follow-up paired QFT-GIT1&2 and QFT-Plus1&2 tests at an interval of 6 months. The positive consistency, concordance, and discordance of the QFT results were analyzed. A total of 236 patients on dialysis were screened, and 73 participants with positive QFT-GIT0 results were enrolled. The baseline QFT-GIT0 response was higher in the 1st QFT-Plus1(+) group than in the QFT-Plus1(-) group, but insignificantly different between the 1st QFT-GIT1(+) and QFT-GIT1(-) groups. The two assays had good correlation when concurrently tested. Fifty-three subjects completed a second round of the QFT-GIT2 and QFT-Plus2. Persistent positivity was higher with the QFT-Plus2 (81.8%) than with the QFT-GIT2 (58.8%, p = 0.040). The QFT-GIT1 and QFT-Plus1 CD4 responses were higher in patients with persistent positivity than in those with negative reversion, whereas the difference of the QFT-Plus TB1 and TB2 data, representative of the CD8 response, were similar between positive persistence and negative reversion. In conclusion, the QFT-Plus provides more reliable positive consistency than does the QFT-GIT. The CD4 interferon-γ response might play a role in maintaining positivity of LTBI.
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Affiliation(s)
- Ping-Huai Wang
- Division of Pulmonology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.,Department of Nursing, Oriental Institute of Technology, New Taipei City, Taiwan
| | - Shu-Yung Lin
- Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung Shan South Road, Taipei, Taiwan.,College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Susan Shih-Jung Lee
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Shu-Wen Lin
- Graduate Institute of Clinical Pharmacy, National Taiwan University, Taipei, Taiwan
| | - Chih-Yuan Lee
- College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Yu-Feng Wei
- Division of Chest Medicine, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
| | - Chin-Chung Shu
- Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung Shan South Road, Taipei, Taiwan. .,College of Medicine, National Taiwan University, Taipei, Taiwan.
| | - Jann-Yuan Wang
- Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung Shan South Road, Taipei, Taiwan.,College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chong-Jen Yu
- Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung Shan South Road, Taipei, Taiwan.,College of Medicine, National Taiwan University, Taipei, Taiwan
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