Naïm Ouldali1,2,3,4, Corinne Levy1,2,5,6, Philippe Minodier2,7, Laurence Morin2,8, Sandra Biscardi2,5,6,9, Marie Aurel2,8, François Dubos2,10, Marie Alliette Dommergues2,11, Ellia Mezgueldi2,12, Karine Levieux2,13, Fouad Madhi2,5,14, Laure Hees2,15, Irina Craiu2,16, Chrystèle Gras Le Guen2,13, Elise Launay2,13, Ferielle Zenkhri2,16, Mathie Lorrot2,17, Yves Gillet2,15, Stéphane Béchet1,5, Isabelle Hau2,5,14, Alain Martinot2,10, Emmanuelle Varon2,18, François Angoulvant2,3,4, Robert Cohen1,2,5,6,19. 1. Association Clinique et Thérapeutique Infantile du Val-de-Marne, St Maur-des-Fossés, France. 2. Groupe de Pathologie Infectieuse Pédiatrique, Paris, France. 3. Unité d'Épidémiologie Clinique, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Unité Mixte de Recherche 1123-Epidémiologie Clinique et Évaluation Économique Appliquées aux Populations Vulnérables, Institut National de la Santé et de la Recherche Médicale, Paris, France. 4. Urgences Pédiatriques, Hôpital Necker Enfants Malades, Université Paris Descartes, Paris, France. 5. Université Paris Est, L'Institut Mondor de Recherche Biomédicale Groupement de Recherche Clinique Groupe d'Etude de Maladies Infectieuses Néonatales et Infantiles, Créteil, France. 6. Clinical Research Center, Centre Hospitalier Intercommunal de Créteil, Créteil, France. 7. Department of Pediatric Emergency, Centre Hospitalier Universitaire Nord, Marseille, France. 8. Department of General Pediatrics, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Université Paris Diderot, Sorbonne Paris Cité, Paris, France. 9. Department of Pediatric Emergency, Hôpital Intercommunal, Créteil, France. 10. Pediatric Emergency Unit and Infectious Diseases, Université de Lille, Centre Hospitalier Universitaire Lille, Lille, France. 11. Department of General Pediatrics, Centre Hospitalier de Versailles, Le Chesnay, France. 12. Pediatric Nephrology, Rheumatology, Dermatology Unit, Femme Mère Enfant Hospital, Hospices Civils de Lyon, University Lyon 1 Lyon, Lyon, France. 13. Department of Pediatrics, Centre Hospitalier Universitaire Nantes, Nantes, France. 14. Department of General Pediatrics, Hôpital Intercommunal, Créteil, France. 15. Department of Pediatric Emergency, L'Hôpital Femme Mère Enfant Lyon, Lyon, France. 16. Department of Pediatric Emergency, Assistance Publique-Hôpitaux de Paris, Hôpital Le Kremlin-Bicêtre, Université Paris, Paris, France. 17. Department of General Pediatrics, Assistance Publique-Hôpitaux de Paris, Hôpital Armand Trousseau, Université Sorbonne Paris Cité, Paris, France. 18. National Reference Center for Pneumococci, Laboratoire de Microbiologie, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Paris, France. 19. Unité Court Séjour, Petits Nourrissons, Service de Néonatologie, Centre Hospitalier Intercommunal de Créteil, Créteil, France.
Abstract
Importance: In several countries, 5 years after 13-valent pneumococcal conjugate vaccine (PCV13) implementation, serotype replacement has been reported for invasive pneumococcal disease, which raises concerns about the long-term outcome of PCV13 implementation. The long-term effect of vaccination on community-acquired pneumonia (CAP) remains unknown. Objective: To assess the long-term outcome of PCV13 implementation on CAP in children. Design, Setting, and Participants: This quasi-experimental, population-based, interrupted time-series analysis was based on a prospective multicenter study conducted from June 2009 to May 2017 in 8 French pediatric emergency departments. All patients 15 years and younger with chest radiography-confirmed CAP were included. Exposures: Community-acquired pneumonia. Main Outcomes and Measures: The number of CAP cases per 1000 pediatric emergency department visits over time, analyzed using a segmented regression model, adjusted for influenza-like illness syndromes. Results: We enrolled 12 587 children with CAP, including 673 cases of CAP with pleural effusion (5.3%), 4273 cases of CAP requiring hospitalization (33.9%), 2379 cases of CAP with high inflammatory biomarkers (18.9%), and 221 cases of proven pneumococcal CAP (1.8%). The implementation of PCV13 in 2010 was followed by a sharp decrease in the frequency of CAP (-0.8% per month [95% CI, -1.0% to -0.5% per month]), from 6.3 to 3.5 cases of CAP per 1000 pediatric emergency department visits until May 2014, then a slight increase since June 2014 (0.9% per month [95% CI, 0.4%-1.4% per month]), until 3.8 cases of CAP per 1000 pediatric emergency department visits in May 2017. There were marked immediate decreases in cases of CAP with pleural effusion (-48% [95% CI, -84% to -12%]), CAP requiring hospitalization (-30% [95% CI, -56% to -5%]), and CAP with high inflammatory biomarkers (-30% [95% CI, -54% to -6%]), without any rebound thereafter. Conclusions and Relevance: The changes associated with PCV13 use 7 years after implementation remain substantial, especially for CAP with pleural effusion, CAP requiring hospitalization, and CAP with high inflammatory biomarkers. Emerging non-PCV13 serotypes may be less likely involved in severe CAP than invasive pneumococcal disease.
Importance: In several countries, 5 years after 13-valent pneumococcal conjugate vaccine (PCV13) implementation, serotype replacement has been reported for invasive pneumococcal disease, which raises concerns about the long-term outcome of PCV13 implementation. The long-term effect of vaccination on community-acquired pneumonia (CAP) remains unknown. Objective: To assess the long-term outcome of PCV13 implementation on CAP in children. Design, Setting, and Participants: This quasi-experimental, population-based, interrupted time-series analysis was based on a prospective multicenter study conducted from June 2009 to May 2017 in 8 French pediatric emergency departments. All patients 15 years and younger with chest radiography-confirmed CAP were included. Exposures: Community-acquired pneumonia. Main Outcomes and Measures: The number of CAP cases per 1000 pediatric emergency department visits over time, analyzed using a segmented regression model, adjusted for influenza-like illness syndromes. Results: We enrolled 12 587 children with CAP, including 673 cases of CAP with pleural effusion (5.3%), 4273 cases of CAP requiring hospitalization (33.9%), 2379 cases of CAP with high inflammatory biomarkers (18.9%), and 221 cases of proven pneumococcal CAP (1.8%). The implementation of PCV13 in 2010 was followed by a sharp decrease in the frequency of CAP (-0.8% per month [95% CI, -1.0% to -0.5% per month]), from 6.3 to 3.5 cases of CAP per 1000 pediatric emergency department visits until May 2014, then a slight increase since June 2014 (0.9% per month [95% CI, 0.4%-1.4% per month]), until 3.8 cases of CAP per 1000 pediatric emergency department visits in May 2017. There were marked immediate decreases in cases of CAP with pleural effusion (-48% [95% CI, -84% to -12%]), CAP requiring hospitalization (-30% [95% CI, -56% to -5%]), and CAP with high inflammatory biomarkers (-30% [95% CI, -54% to -6%]), without any rebound thereafter. Conclusions and Relevance: The changes associated with PCV13 use 7 years after implementation remain substantial, especially for CAP with pleural effusion, CAP requiring hospitalization, and CAP with high inflammatory biomarkers. Emerging non-PCV13 serotypes may be less likely involved in severe CAP than invasive pneumococcal disease.
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