Antoni Noguera-Julian1,2,3,4, Joan Calzada-Hernández1, Folke Brinkmann5, Robindra Basu Roy6,7, Olga Bilogortseva8, Michael Buettcher9, Isabel Carvalho10, Vira Chechenyeva8,11, Lola Falcón12, Florian Goetzinger13, Carmelo Guerrero-Laleona14, Peter Hoffmann15, Marija Jelusic16, Tim Niehues17, Iveta Ozere18,19, Fiona Shackley20, Elena Suciliene21, Steven B Welch22, Elisabeth H Schölvinck23, Nicole Ritz24,25,26, Marc Tebruegge26,27,28. 1. Malalties Infeccioses i Resposta Inflamatòria Sistèmica en Pediatria, Unitat d´Infeccions, Servei de Pediatria, Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona, Spain. 2. Departament de Pediatria, Universitat de Barcelona, Barcelona, Spain. 3. CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. 4. Red de Investigación Translacional en Infectología Pediátrica (RITIP), Madrid, Spain. 5. Department of Pulmonology, University Children's Hospital, Ruhr University, Bochum, Germany. 6. Department of Paediatrics, Oxford University, Oxford, United Kingdom. 7. Children's Hospital, John Radcliffe Hospital, Oxford, United Kingdom. 8. Department of Child Phthisiology, National Institute of Phthisiology and Pulmonology, National Academy of Medical Sciences of Ukraine, Kiev, Ukraine. 9. Lucerne Children's Hospital, Lucerne Cantonal Hospital, Lucerne, Switzerland. 10. Department of Pediatrics, Vila Nova de Gaia Hospital Centre, Vila Nova de Gaia, Portugal. 11. Center of Infectious Diseases, "Clinic for Children With HIV/AIDS", National Specialized Children's Hospital (Okhmatdyt), Kiev, Ukraine. 12. Department of Paediatric Infectious Diseases, Rheumatology and Immunodeficiency, Hospital Virgen del Rocío, Seville, Spain. 13. Department of Pediatrics and Adolescent Medicine, Wilhelminenspital, Vienna, Austria. 14. Infectious Diseases Unit, Pediatric Department, Miguel Servet University Hospital-University of Zaragoza, Zaragoza, Spain. 15. Department of Internal Medicine, Gastroenterology, and Diabetology, Evang. Kliniken Essen-Mitte, Essen, Germany. 16. Department of Pediatrics, University of Zagreb, School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia. 17. Immunodeficiency and Rheumatology Center, Helios Klinikum Krefeld, Krefeld, Germany. 18. Department of Infectious Diseases and Dermatology, Riga Stradinš University, Riga, Latvia. 19. Center of Tuberculosis and Lung Diseases, Riga East University Hospital, Riga, Latvia. 20. Department of Paediatrics, Sheffield Children's National Health Service Foundation Trust, Sheffield, United Kingdom. 21. Children Hospital, Affiliate of Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania. 22. Birmingham Chest Clinic and Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom. 23. University of Groningen, University Medical Center Groningen/Beatrix Children's Hospital, Groningen, the Netherlands. 24. Paediatric Infectious Diseases and Vaccinology Unit, University of Basel Children's Hospital, Basel, Switzerland. 25. Faculty of Medicine, University of Basel, Basel, Switzerland. 26. Department of Paediatrics, University of Melbourne, Parkville, Australia. 27. Department of Paediatric Infectious Diseases and Immunology, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. 28. Department of Infection, Immunity, and Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Abstract
BACKGROUND: In adults, anti-tumor necrosis factor-α (TNF-α) therapy is associated with progression of latent tuberculosis (TB) infection (LTBI) to TB disease, but pediatric data are limited. METHODS: Retrospective multicenter study within the Paediatric Tuberculosis Network European Trials Group, capturing patients <18 years who developed TB disease during anti-TNF-α therapy. RESULTS: Sixty-six tertiary healthcare institutions providing care for children with TB participated. Nineteen cases were identified: Crohn's disease (n = 8; 42%) and juvenile idiopathic arthritis (n = 6; 32%) were the commonest underlying conditions. Immune-based TB screening (tuberculin skin test and/or interferon-γ release assay) was performed in 15 patients before commencing anti-TNF-α therapy but only identified 1 LTBI case; 13 patients were already receiving immunosuppressants at the time of screening. The median interval between starting anti-TNF-α therapy and TB diagnosis was 13.1 (IQR, 7.1-20.3) months. All cases presented with severe disease, predominantly miliary TB (n = 14; 78%). One case was diagnosed postmortem. TB was microbiologically confirmed in 15 cases (79%). The median duration of anti-TB treatment was 50 (IQR, 46-66) weeks. Five of 15 (33%) cases who had completed TB treatment had long-term sequelae. CONCLUSIONS: LTBI screening is frequently false-negative in this patient population, likely due to immunosuppressants impairing test performance. Therefore, patients with immune-mediated diseases should be screened for LTBI at the point of diagnosis, before commencing immunosuppressive medication. Children on anti-TNF-α therapy are prone to severe TB disease and significant long-term morbidity. Those observations underscore the need for robust LTBI screening programs in this high-risk patient population, even in low-TB-prevalence settings.
BACKGROUND: In adults, anti-tumor necrosis factor-α (TNF-α) therapy is associated with progression of latent tuberculosis (TB) infection (LTBI) to TB disease, but pediatric data are limited. METHODS: Retrospective multicenter study within the Paediatric Tuberculosis Network European Trials Group, capturing patients <18 years who developed TB disease during anti-TNF-α therapy. RESULTS: Sixty-six tertiary healthcare institutions providing care for children with TB participated. Nineteen cases were identified: Crohn's disease (n = 8; 42%) and juvenile idiopathic arthritis (n = 6; 32%) were the commonest underlying conditions. Immune-based TB screening (tuberculin skin test and/or interferon-γ release assay) was performed in 15 patients before commencing anti-TNF-α therapy but only identified 1 LTBI case; 13 patients were already receiving immunosuppressants at the time of screening. The median interval between starting anti-TNF-α therapy and TB diagnosis was 13.1 (IQR, 7.1-20.3) months. All cases presented with severe disease, predominantly miliary TB (n = 14; 78%). One case was diagnosed postmortem. TB was microbiologically confirmed in 15 cases (79%). The median duration of anti-TB treatment was 50 (IQR, 46-66) weeks. Five of 15 (33%) cases who had completed TB treatment had long-term sequelae. CONCLUSIONS:LTBI screening is frequently false-negative in this patient population, likely due to immunosuppressants impairing test performance. Therefore, patients with immune-mediated diseases should be screened for LTBI at the point of diagnosis, before commencing immunosuppressive medication. Children on anti-TNF-α therapy are prone to severe TB disease and significant long-term morbidity. Those observations underscore the need for robust LTBI screening programs in this high-risk patient population, even in low-TB-prevalence settings.
Authors: Jon C Emery; Alexandra S Richards; Katie D Dale; C Finn McQuaid; Richard G White; Justin T Denholm; Rein M G J Houben Journal: Proc Biol Sci Date: 2021-01-20 Impact factor: 5.349
Authors: Sara Parigi; Amelia Licari; Sara Manti; Gian Luigi Marseglia; Maria Angela Tosca; Michele Miraglia Del Giudice; Carlo Caffarelli; Mauro Calvani; Alberto Martelli; Fabio Cardinale; Claudio Cravidi; Marzia Duse; Elena Chiappini Journal: Acta Biomed Date: 2020-09-15