Naïm Ouldali1, Emmanuelle Varon2, Corinne Levy3, François Angoulvant4, Scarlett Georges5, Marie-Cécile Ploy6, Marie Kempf7, Julie Cremniter8, Robert Cohen9, Daniel Levy Bruhl5, Kostas Danis5. 1. Public health France, the French National Public Health agency, Saint Maurice, France; Association Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France; Groupe de Pathologie Infectieuse Pédiatrique, Paris, France; Department of General Paediatrics, Infectious Diseases and Internal Medicine, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France; Unité d'épidémiologie clinique, Épidémiologie clinique, évaluation économique appliquées aux populations vulnérables, unité mixte de recherche 1123, Assistance publique des hôpitaux de Paris, Hôpital Robert Debré, Institut National de la Santé et de la Recherche Médicale, Paris, France. Electronic address: naim.ouldali@activ-france.fr. 2. National Reference Centre for Pneumococci, Centre Hospitalier Intercommunal de Créteil, Créteil, France. 3. Association Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France; Groupe de Pathologie Infectieuse Pédiatrique, Paris, France; Clinical Research Centre, Centre Hospitalier Intercommunal de Créteil, Créteil, France; Université Paris Est, Mondor Institute of Biomedical Research-Groupement de Recherche Clinique Groupe d'étude de Maladies Infectieuses Néonatales et Infantiles, Créteil, France. 4. Groupe de Pathologie Infectieuse Pédiatrique, Paris, France; Centre de recherche des cordeliers, unité mixte de recherche 1138, Institut National de la Santé et de la Recherche Médicale, Paris, France; Paediatric Emergency Department, Necker Enfants Malades Hospital, Université Paris Descartes, Paris, France. 5. Public health France, the French National Public Health agency, Saint Maurice, France. 6. University Hospital Centre Limoges, Regional Observatories for Pneumococci, Limoges, France; Limoges University, Institut national de la santé et de la recherche médicale, Le centre hospitalier et universitaire de Limoges, France. 7. University Hospital Centre Limoges, Regional Observatories for Pneumococci, Limoges, France; Laboratory of Bacteriology-Hygiene, Health Biology Institute, Angers University Hospital, Angers, France; Centre de Recherche en Cancérologie et Immunologie Nantes Angers, Institut national de la santé et de la recherche médicale, Nantes University, Angers University, Angers, France. 8. University Hospital Centre Limoges, Regional Observatories for Pneumococci, Limoges, France; Department of Bacteriology, Poitiers University Hospital, Poitiers, France. 9. Association Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France; Groupe de Pathologie Infectieuse Pédiatrique, Paris, France; Clinical Research Centre, Centre Hospitalier Intercommunal de Créteil, Créteil, France; Université Paris Est, Mondor Institute of Biomedical Research-Groupement de Recherche Clinique Groupe d'étude de Maladies Infectieuses Néonatales et Infantiles, Créteil, France; Unité Court Séjour, Petits Nourrissons, Service de Néonatologie, Centre Hospitalier Intercommunal de Créteil, Créteil, France.
Abstract
BACKGROUND: The long-term benefits of pneumococcal conjugate vaccines (PCVs) remain unknown because of serotype replacement. We aimed to estimate the effect of PCV implementation on invasive pneumococcal disease incidence in France. METHODS: We did a quasi-experimental interrupted time-series analysis using data from a French national prospective surveillance system. We included all invasive pneumococcal disease cases in children and adults from more than 250 participating hospitals between Jan 1, 2001, and Dec 31, 2017. The primary outcome was incidence of invasive pneumococcal disease (meningitis and non-meningitis) over time, analysed by segmented regression with autoregressive error. Isolates were serotyped by latex agglutination with antiserum samples. FINDINGS: We included 75 903 patients with invasive pneumococcal disease, including 4302 (5·7%) children younger than 2 years and 37 534 (49·4%) adults aged 65 years or older. Before PCV7 implementation, the estimated monthly incidence of invasive pneumococcal disease was 0·78 cases per 100 000 inhabitants, which did not change significantly up to May, 2010. PCV13 implementation in 2010 was followed by a significant decrease in the incidence of invasive pneumococcal disease (-1·5% per month, 95% CI -2·2 to -0·8), reaching an estimated monthly incidence of 0·52 cases per 100 000 inhabitants in December, 2014. From January, 2015, the incidence rebounded (1·8% per month, 95% CI 1·0 to 2·6), reaching an estimated monthly incidence of 0·73 cases per 100 000 inhabitants in December, 2017. The estimated monthly incidence increased from 0·93 cases per 100 000 in December, 2014, to 1·73 cases per 100 000 in December, 2017, for children younger than 2 years, and from 1·54 cases per 100 000 in December, 2014, to 2·08 cases per 100 000 in December, 2017, for adults aged 65 years or older. The main non-PCV13 serotypes involved in the increase were 24F in young children and 12F, 22F, 9N, and 8 in adults aged 65 years or older. INTERPRETATION: PCV13 implementation led to a major reduction in the incidence of invasive pneumococcal disease. However, a rebound in cases among children and adults since 2015, driven by several emerging non-PCV13 serotypes, jeopardises the long-term PCV benefits. These findings, if confirmed in the coming years, should be considered in the development of next-generation PCVs and might guide policy makers in the selection of future pneumococcal vaccines. FUNDING: Foundation for Medical Research; Pfizer, BioMérieux, Sanofi for the Regional Observatory of Pneumococci.
BACKGROUND: The long-term benefits of pneumococcal conjugate vaccines (PCVs) remain unknown because of serotype replacement. We aimed to estimate the effect of PCV implementation on invasive pneumococcal disease incidence in France. METHODS: We did a quasi-experimental interrupted time-series analysis using data from a French national prospective surveillance system. We included all invasive pneumococcal disease cases in children and adults from more than 250 participating hospitals between Jan 1, 2001, and Dec 31, 2017. The primary outcome was incidence of invasive pneumococcal disease (meningitis and non-meningitis) over time, analysed by segmented regression with autoregressive error. Isolates were serotyped by latex agglutination with antiserum samples. FINDINGS: We included 75 903 patients with invasive pneumococcal disease, including 4302 (5·7%) children younger than 2 years and 37 534 (49·4%) adults aged 65 years or older. Before PCV7 implementation, the estimated monthly incidence of invasive pneumococcal disease was 0·78 cases per 100 000 inhabitants, which did not change significantly up to May, 2010. PCV13 implementation in 2010 was followed by a significant decrease in the incidence of invasive pneumococcal disease (-1·5% per month, 95% CI -2·2 to -0·8), reaching an estimated monthly incidence of 0·52 cases per 100 000 inhabitants in December, 2014. From January, 2015, the incidence rebounded (1·8% per month, 95% CI 1·0 to 2·6), reaching an estimated monthly incidence of 0·73 cases per 100 000 inhabitants in December, 2017. The estimated monthly incidence increased from 0·93 cases per 100 000 in December, 2014, to 1·73 cases per 100 000 in December, 2017, for children younger than 2 years, and from 1·54 cases per 100 000 in December, 2014, to 2·08 cases per 100 000 in December, 2017, for adults aged 65 years or older. The main non-PCV13 serotypes involved in the increase were 24F in young children and 12F, 22F, 9N, and 8 in adults aged 65 years or older. INTERPRETATION: PCV13 implementation led to a major reduction in the incidence of invasive pneumococcal disease. However, a rebound in cases among children and adults since 2015, driven by several emerging non-PCV13 serotypes, jeopardises the long-term PCV benefits. These findings, if confirmed in the coming years, should be considered in the development of next-generation PCVs and might guide policy makers in the selection of future pneumococcal vaccines. FUNDING: Foundation for Medical Research; Pfizer, BioMérieux, Sanofi for the Regional Observatory of Pneumococci.
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