title: Impact of pneumococcal conjugate vaccines on pneumococcal meningitis cases in France between 2001 and 2014: a time series analysis.
abstract: BACKGROUND
  Pneumococcal meningitis (PM) is a major invasive pneumococcal disease. Two pneumococcal conjugate vaccines (PCVs) have been introduced in France: PCV7 was recommended in 2003 and replaced in 2010 by PCV13, which has six additional serotypes. The impact of introducing those vaccines on the evolution of PM case numbers and serotype distributions in France from 2001 to 2014 is assessed herein.
  
  
  METHODS
  Data on 5166 Streptococcus pneumoniae strains isolated from cerebrospinal fluid between 2001 and 2014 in the 22 regions of France were obtained from the National Reference Center for Pneumococci. The effects of the different vaccination campaigns were estimated using time series analyses through autoregressive moving-average models with exogenous variables ("flu-like" syndromes incidence) and intervention functions. Intervention functions used 11 dummy variables representing each post vaccine epidemiological period. The evolution of serotype distributions was assessed for the entire population and the two most exposed age groups (<5 and > 64 years old).
  
  
  RESULTS
  For the first time since PCV7 introduction in 2003, total PM cases decreased significantly after starting PCV13 use: -7.1 (95% CI, -10.85 to -3.35) cases per month during 2013-2014, and was confirmed in children < 5 years old (-3.5; 95% CI, -4.81 to -2.13) and adults > 64 years old (-2.0; 95% CI, -3.36 to -0.57). During 2012-2014, different non-vaccine serotypes emerged: 12F, 24F in the entire population and children, 6C in the elderly; serotypes 3 and 19F persisted in the entire population.
  
  
  CONCLUSIONS
  Unlike other European countries, the total PM cases in France declined only after introduction of PCV13. This suggests that vaccine pressure alone does not explain pneumococcal epidemiological changes and that other factors could play a role. Serotype distribution had changed substantially compared to the pre-vaccine era, as in other European countries, but very differently from the US. A highly reactive surveillance system is thus necessary not only to monitor evolutions due to vaccine pressure and to verify the local serotypic appropriateness of new higher-valent pneumococcal vaccines, but also to recognise and prevent unexpected changes due to other internal or external factors.
authors.affiliation: Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases (B2PHI), Inserm, UVSQ, Institut Pasteur, Université Paris-Saclay, Paris, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Alari
authors.affiliation: Service de Médecine Interne et Maladies Infectieuses, Hôpital Bretonneau CHRU de Tours, Tours, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Chaussade
authors.affiliation: Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases (B2PHI), Inserm, UVSQ, Institut Pasteur, Université Paris-Saclay, Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Domenech De Cellès
authors.affiliation: Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases (B2PHI), Inserm, UVSQ, Institut Pasteur, Université Paris-Saclay, Paris, France.
authors.forename: Lénaig
authors.initials: L
authors.lastname: Le Fouler
authors.affiliation: National Reference Center for Pneumococci, APHP, Paris, France.|Hôpital Européen Georges-Pompidou, Laboratoire de Microbiologie Clinique, APHP, Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Varon
authors.affiliation: Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases (B2PHI), Inserm, UVSQ, Institut Pasteur, Université Paris-Saclay, Paris, France.
authors.forename: Lulla
authors.initials: L
authors.lastname: Opatowski
authors.affiliation: Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases (B2PHI), Inserm, UVSQ, Institut Pasteur, Université Paris-Saclay, Paris, France.|APHP, Hôpital Raymond-Poincaré, Unité Fonctionnelle de Santé Publique (D.G.), Garches, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Guillemot
authors.affiliation: Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases (B2PHI), Inserm, UVSQ, Institut Pasteur, Université Paris-Saclay, Paris, France. laurence.watier@inserm.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Watier
mesh_terms: D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007223:Infant; D008586:Meningitis, Pneumococcal / Q000453:epidemiology*; D022242:Pneumococcal Vaccines / Q000627:therapeutic use*; D065288:Serogroup; D013296:Streptococcus pneumoniae / Q000235:genetics; D018074:Vaccines, Conjugate / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate
keywords: Pneumococcal conjugate vaccine; Pneumococcal meningitis; Serotype replacement; Surveillance data; Times series modelling