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1. Tuberculosis Disease in Children and Adolescents on Therapy With Antitumor Necrosis Factor-ɑ Agents: A Collaborative, Multicenter Paediatric Tuberculosis Network European Trials Group (ptbnet) Study

Author

Noguera-Julian A., Calzada-Hernandez J., Brinkmann F., Roy R. B., Bilogortseva O., Buettcher M., Carvalho I., Chechenyeva V., Falcon L., Goetzinger F., Guerrero-Laleona C., Hoffmann P., Jelusic M., Niehues T., Ozere I., Shackley F., Suciliene E., Welch S. B., Scholvinck E. H., Ritz N., Tebruegge M., Curtis N., Villanueva P., Marais B., Britton P., Clark J., Pichler J., Zschocke A., Bogyi M., Dreesman A., Mouchet F., Velizarova S., Pavic I., Nygaard U., Pulsen A., Kontturi A., Salo E., Chadelat K., Kruger R., Tee S., Ahrens F., Barker M., Zimmermann T., Schulze-Sturm U., Kaiser-Labusch P., Tsolia M., Ghanaie O. M., Buonsenso D., Lo Vecchio A., Ivaskeviciene I., Vilc V., Smyrnaios A., Arbore A. S., Starshinova A., Solovic I., Krivec U., Aldeco M., Espiau M., Soriano-Arandes A., Neth O., Santiago B., Gomez-Pastrana D., Blazquez D., Bustillo M., Perez-Porcuna T. M., Cilleruelo M. J., Kotz K., Bennet R., Relly C., Niederer-Loher A., Rochat I., Pavskyi S., Riordan A., Doherty C., Bamford A., Shingadia D., Emonts M., Ferreras-Antolin L., McMaster P., Moriarty P., Noguera-Julian, A., Calzada-Hernandez, J., Brinkmann, F., Roy, R. B., Bilogortseva, O., Buettcher, M., Carvalho, I., Chechenyeva, V., Falcon, L., Goetzinger, F., Guerrero-Laleona, C., Hoffmann, P., Jelusic, M., Niehues, T., Ozere, I., Shackley, F., Suciliene, E., Welch, S. B., Scholvinck, E. H., Ritz, N., Tebruegge, M., Curtis, N., Villanueva, P., Marais, B., Britton, P., Clark, J., Pichler, J., Zschocke, A., Bogyi, M., Dreesman, A., Mouchet, F., Velizarova, S., Pavic, I., Nygaard, U., Pulsen, A., Kontturi, A., Salo, E., Chadelat, K., Kruger, R., Tee, S., Ahrens, F., Barker, M., Zimmermann, T., Schulze-Sturm, U., Kaiser-Labusch, P., Tsolia, M., Ghanaie, O. M., Buonsenso, D., Lo Vecchio, A., Ivaskeviciene, I., Vilc, V., Smyrnaios, A., Arbore, A. S., Starshinova, A., Solovic, I., Krivec, U., Aldeco, M., Espiau, M., Soriano-Arandes, A., Neth, O., Santiago, B., Gomez-Pastrana, D., Blazquez, D., Bustillo, M., Perez-Porcuna, T. M., Cilleruelo, M. J., Kotz, K., Bennet, R., Relly, C., Niederer-Loher, A., Rochat, I., Pavskyi, S., Riordan, A., Doherty, C., Bamford, A., Shingadia, D., Emonts, M., Ferreras-Antolin, L., Mcmaster, P., and Moriarty, P.

Subjects
reactivation, Disease, anti-TNF-alpha, 0302 clinical medicine, Medicine, children, 030212 general & internal medicine, JUVENILE IDIOPATHIC ARTHRITIS, Child, Anti–TNF-alpha, RISK, Latent tuberculosis, GAMMA RELEASE ASSAYS, Miliary tuberculosi, SERIOUS INFECTION, Infectious Diseases, tuberculosis, anti–TNF-alpha, medicine.drug, miliary tuberculosis, Microbiology (medical), Adult, medicine.medical_specialty, Miliary tuberculosis, Tuberculosis, Adolescent, CORTICOSTEROIDS, Tuberculin, DIAGNOSIS, CLASSIFICATION, 03 medical and health sciences, Necrosis, Latent Tuberculosis, Internal medicine, SURVEILLANCE, INFLIXIMAB, Humans, Retrospective Studies, 030203 arthritis & rheumatology, business.industry, Tuberculin Test, Tumor Necrosis Factor-alpha, Retrospective cohort study, medicine.disease, FACTOR INHIBITORS, Infliximab, Clinical research, business, Interferon-gamma Release Tests
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 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.

Published
2019

2. Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV-1 infection 2015: optimizing health in preparation for adult life

Author

Bamford, A., Turkova, A., Lyall, H., Foster, C., Klein, N., Bastiaans, D., Burger, D., Bernadi, S., Butler, K., Chiappini, E., Clayden, P., Della Negra, M., Giacomet, V., Giaquinto, C., Gibb, D., Galli, L., Hainaut, M., Koros, M., Marques, L., Nastouli, E., Niehues, T., Noguera-Julian, A., Rojo, P., Rudin, C., Scherpbier, H. J., Tudor-Williams, G., Welch, S. B., AII - Amsterdam institute for Infection and Immunity, Paediatric Infectious Diseases / Rheumatology / Immunology, and AII - Infectious diseases

Subjects
Male, Science et gestion hospitalières, antiretroviral therapy, Adolescent, Pharmacologie, Santé publique, Humans, Pharmacology (medical), Preschool, Pathologie maladies infectieuses, child, Original Research, Acquired Immunodeficiency Syndrome, AIDS-Related Opportunistic Infections, HIV-1, Coinfection, Health Policy, HIV‐1, Anti-Retroviral Agents, Child, Child, Preschool, Europe, Female, Infant, Infant, Newborn, Infectious Diseases, Newborn
Abstract

The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV-1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short-term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long-term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first- and second-line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART ‘pipeline’ of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2018

3. COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study

Author

Benoît Bernar, Astrid Rojahn, Laura Jones, Elisabeth Schölvinck, Robin Kobbe, Laura Lancella, Delane Shingadia, Fiona Shackley, Lynne McFetridge, Conor Doherty, Cornelius Rau, Nicolaus Schwerk, Oksana Kozdoba, Koen Vanden Driessche, Arnaud G L'Huillier, Jasmin Pfefferle, Srini Bandi, R Song, Andreia Ribeiro, Ivan Solovic, Jonathan P. Glenthoej, Ulrich Heininger, Susana Melendo, Tine Boiy, Uros Krivec, An Bael, Luca Pierantoni, Edda Haberlandt, Miguel Lanaspa, Noémie Wagner, Andrea Lo Vecchio, Francesc Ripoll, Lise Heilmann Jensen, Piero Valentini, Anita Niederer, Roland Berger, Nicole Ritz, Aida M. Gutiérrez-Sánchez, Christelle Christiaens, Franziska Zucol, Katy Fidler, Jolanta Bernatoniene, Anna Starshinova, Volker Strenger, Claus Klingenberg, Ilona Lind, Clare S. Murray, Angela Zacharasiewicz, Ivan Pavic, Amanda Williams, Christina Thir, Vera Chechenyeva, Karsten Kötz, Stephanie Thee, Laura Buchtala, Danilo Buonsenso, Patrick Gavin, Rimvydas Ivaškevicius, Sara Debulpaep, Francesca Ippolita Calò Carducci, Marine Creuven, Beatriz Soto, Srđan Roglić, Lola Falcón, Yvonne Beuvink, Petra Zimmermann, Petra Schelstraete, Lynne Speirs, Daniela S. Kohlfürst, Antoni Noguera-Julian, Mihhail Tistsenko, Steven B. Welch, Hanna Schmid, Anastasios Smyrnaios, Laura Minguell, Andrew Riordan, Michael Buettcher, Angelika Berger, Isabel Carvalho, Daan Van Brusselen, Inga Ivaškeviciene, Matilde Bustillo, Valentina Vilc, Folke Brinkmann, Nina Krajcar, Olaf Neth, Alicia Demirjian, Matthias Bogyi, Ulle Uustalu, Maria Tsolia, Borja Ibanez, Elisabeth Whittaker, Ariane Biebl, Irini Eleftheriou, Burkhard Simma, Petra Prunk, Borbàla Zsigmond, Veronika Osterman, Zoe Oliver, Antoni Soriano-Arandes, Ulrikka Nygaard, Marcello Lanari, Marc Tebruegge, Olga Bilogortseva, Michael Barker, Svetlana Velizarova, Florian Götzinger, Natalia Gabrovska, Begoña Santiago-García, Benhur Şirvan Çetin, Paddy McMaster, Anna Zschocke, Frances Child, Nick Makwana, Mar Santos, Group, ptbnet COVID-19 Study, Gotzinger F., Santiago-Garcia B., Noguera-Julian A., Lanaspa M., Lancella L., Calo Carducci F.I., Gabrovska N., Velizarova S., Prunk P., Osterman V., Krivec U., Lo Vecchio A., Shingadia D., Soriano-Arandes A., Melendo S., Lanari M., Pierantoni L., Wagner N., L'Huillier A.G., Heininger U., Ritz N., Bandi S., Krajcar N., Roglic S., Santos M., Christiaens C., Creuven M., Buonsenso D., Welch S.B., Bogyi M., Brinkmann F., Tebruegge M., Pfefferle J., Zacharasiewicz A., Berger A., Berger R., Strenger V., Kohlfurst D.S., Zschocke A., Bernar B., Simma B., Haberlandt E., Thir C., Biebl A., Vanden Driessche K., Boiy T., Van Brusselen D., Bael A., Debulpaep S., Schelstraete P., Pavic I., Nygaard U., Glenthoej J.P., Heilmann Jensen L., Lind I., Tistsenko M., Uustalu U., Buchtala L., Thee S., Kobbe R., Rau C., Schwerk N., Barker M., Tsolia M., Eleftheriou I., Gavin P., Kozdoba O., Zsigmond B., Valentini P., Ivaskeviciene I., Ivaskevicius R., Vilc V., Scholvinck E., Rojahn A., Smyrnaios A., Klingenberg C., Carvalho I., Ribeiro A., Starshinova A., Solovic I., Falcon L., Neth O., Minguell L., Bustillo M., Gutierrez-Sanchez A.M., Guarch Ibanez B., Ripoll F., Soto B., Kotz K., Zimmermann P., Schmid H., Zucol F., Niederer A., Buettcher M., Cetin B.S., Bilogortseva O., Chechenyeva V., Demirjian A., Shackley F., McFetridge L., Speirs L., Doherty C., Jones L., McMaster P., Murray C., Child F., Beuvink Y., Makwana N., Whittaker E., Williams A., Fidler K., Bernatoniene J., Song R., Oliver Z., Riordan A., Gotzinger, F., Santiago-Garcia, B., Noguera-Julian, A., Lanaspa, M., Lancella, L., Calo Carducci, F. I., Gabrovska, N., Velizarova, S., Prunk, P., Osterman, V., Krivec, U., Lo Vecchio, A., Shingadia, D., Soriano-Arandes, A., Melendo, S., Lanari, M., Pierantoni, L., Wagner, N., L'Huillier, A. G., Heininger, U., Ritz, N., Bandi, S., Krajcar, N., Roglic, S., Santos, M., Christiaens, C., Creuven, M., Buonsenso, D., Welch, S. B., Bogyi, M., Brinkmann, F., Tebruegge, M., Pfefferle, J., Zacharasiewicz, A., Berger, A., Berger, R., Strenger, V., Kohlfurst, D. S., Zschocke, A., Bernar, B., Simma, B., Haberlandt, E., Thir, C., Biebl, A., Vanden Driessche, K., Boiy, T., Van Brusselen, D., Bael, A., Debulpaep, S., Schelstraete, P., Pavic, I., Nygaard, U., Glenthoej, J. P., Heilmann Jensen, L., Lind, I., Tistsenko, M., Uustalu, U., Buchtala, L., Thee, S., Kobbe, R., Rau, C., Schwerk, N., Barker, M., Tsolia, M., Eleftheriou, I., Gavin, P., Kozdoba, O., Zsigmond, B., Valentini, P., Ivaskeviciene, I., Ivaskevicius, R., Vilc, V., Scholvinck, E., Rojahn, A., Smyrnaios, A., Klingenberg, C., Carvalho, I., Ribeiro, A., Starshinova, A., Solovic, I., Falcon, L., Neth, O., Minguell, L., Bustillo, M., Gutierrez-Sanchez, A. M., Guarch Ibanez, B., Ripoll, F., Soto, B., Kotz, K., Zimmermann, P., Schmid, H., Zucol, F., Niederer, A., Buettcher, M., Cetin, B. S., Bilogortseva, O., Chechenyeva, V., Demirjian, A., Shackley, F., Mcfetridge, L., Speirs, L., Doherty, C., Jones, L., Mcmaster, P., Murray, C., Child, F., Beuvink, Y., Makwana, N., Whittaker, E., Williams, A., Fidler, K., Bernatoniene, J., Song, R., Oliver, Z., and Riordan, A.

Subjects
Male, Delivery of Health Care / organization & administration, medicine.medical_treatment, Coronavirus Infections / therapy, Coronavirus Infections / epidemiology, law.invention, Patient Admission, 0302 clinical medicine, law, Risk Factors, COVID-19, children, Europe, Developmental and Educational Psychology, 030212 general & internal medicine, Child, ddc:618, Intensive care unit, Coronavirus, SARS-CoV-2, child, treatment, intensive care, Intensive Care Units, N/A, Child, Preschool, Female, Europe / epidemiology, Coronavirus Infections, Human, Cohort study, medicine.medical_specialty, Pneumonia, Viral / epidemiology, Intensive Care Unit, Pneumonia, Viral, Patient Admission / trends, Intensive Care Units / organization & administration, Article, Follow-Up Studie, 03 medical and health sciences, Betacoronavirus, 030225 pediatrics, Internal medicine, Lower respiratory tract infection, medicine, Extracorporeal membrane oxygenation, Humans, Pediatrics, Perinatology, and Child Health, Pandemics, Pneumonia, Viral / therapy, Mechanical ventilation, Betacoronaviru, Coronavirus Infection, business.industry, Risk Factor, Infant, Newborn, Infant, Odds ratio, medicine.disease, ptbnet COVID-19 Study Group, Clinical research, El Niño, Pediatrics, Perinatology and Child Health, business, Delivery of Health Care, Follow-Up Studies
Abstract

Background To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. Methods This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. Findings 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one ( Interpretation COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. Funding ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.

Published
2020

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