Impact of the pneumococcal conjugate vaccines on invasive pneumococcal disease in France, 2001–2012
Introduction
In the early 2000s, Streptococcus pneumoniae was the most frequent cause of bacterial invasive disease in France affecting mainly children under two years of age and elderly. This situation justified the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the French immunization schedule in 2003. The vaccine was first recommended for children under two years of age at risk of pneumococcal invasive disease (IPD), in relation to medical or living conditions, i.e. children cared for more than 4 h/weeks with at least two other children, belonging to a family with more than 2 children, being breast-fed for less than 2 months, representing about 80% of each birth cohort [1]. Then the vaccine was recommended as a universal vaccination for all children under two years of age in June 2006 [2]. The 3 + 1 vaccination schedule (2, 3, 4 months, and a booster at 12–15 months) was changed in 2008 to a 2 + 1 schedule (2, 4 and 12 months). Analysis of surveillance data for the 2001–2006 period had shown a 71% decrease in vaccine-type (VT) IPD incidence in children under two years of age, but only a 21% decrease of overall IPD incidence in this age group. The impact of PCV7 on VT-IPD was partially offset by an increase in non-VT IPD incidence (+85%), related to serotype replacement. In older age groups, no decline in IPD incidence was observed [2]. In 2010, as soon as the PCV13 vaccine was marketed in France, a recommendation was made to shift from PCV7 to PCV13 and the PCV7 was withdrawn from the market in July. We analyzed the French IPD surveillance data from the pre-PCV7 (2001–2002) period until two years after PCV13 introduction (2012), in order to assess the specific impact of PCV7 and PCV13 on the incidence of IPD and on the serotype distribution in French children (0–15 years) and adults (>15 years).
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Vaccination coverage
PCV vaccination coverage is monitored through the Permanent Sample of Beneficiaries, extracted from the National Health Insurance Scheme (NHIS) database which covers the whole French population. This random sample of 1/97th of health insurance beneficiaries includes more than 500,000 individuals and contains their reimbursement claims for all drugs, including vaccines [3], [4].
Surveillance of IPD
IPD surveillance relies upon data generated by two laboratory-based national surveillance networks, Epibac and the
Results
In the pre-vaccine years 2001–2002, 8241 IPD cases were reported, 771 (9%) were meningitis; in children aged of less than 2 years 675 IPD cases were reported and 181 (27%) were meningitis. The incidence of IPD was 9.3 cases/100,000 population 95% confidence interval, 95% CI, [9.1, 9.5], it was higher in children aged of less than 2 years (30.3/100,000) and in adults aged of 65 years and over (27.7/100,000).
The serotype was determined in 404 IPD cases in children aged of less than 2 years, 313
Discussion
The introduction of PCV7 was followed by a decline in the incidence of IPD due to PCV7 serotypes in all age-groups, but the increase of IPD due to non-vaccine serotypes partially compensated this decrease in children aged of less than 2 years and exceeded it in older, non-vaccinated age-groups. The situation in France and in some European countries such as Spain was characterized by an initial low uptake of PCV7 and an important and rapid increase of IPD due to non-vaccine serotypes, mainly
Conclusions
Considering the whole 2001–2012 period, the vaccination of young children with PCV7 and PCV13 resulted in a decline in the all-type incidence of IPD in children up to the age of 5 but not in older children and adults. Beyond the non-disputable impact of PCV vaccination, some other unmeasured factors may have contributed to this evolution, especially in adults. The early impact of PCV13 vaccination observed on IPD in children targeted for vaccination and, for the first time in France, in older
Conflict of interest
A. Lepoutre declares no potential conflicts of interest, E. Varon received fees from Pfizer and GlaxoSmithKline for participation in working groups on pneumococcal vaccines, S. Georges, F. Dorléans, C. Janoir, L. Gutmann and D. Lévy-Bruhl declare no potential conflicts of interest.
Funding
This research was funded by the French Institute for Public Health Surveillance.
Acknowledgments
The authors thank all the biologists of the Epibac network for their helpful participation (list available at: http://www.invs.sante.fr/Dossiers-thematiques/Maladies-infectieuses/Maladies-a-prevention-vaccinale/Infections-invasives-d-origine-bacterienne-Reseau-EPIBAC/Methodes-de-la-surveillance), the coordinators of the Observatoires régionaux des pneumocoques (list available at: //www.sante-limousin.fr/public/observatoires/observatoire-des-pneumocoques/presentation/16e5496f74fa6e0319d340496390862b
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