Impact of a Pneumococcal Conjugate Vaccination Program on Carriage among Children in Norway

In July 2006, the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in Norway with a reduced (2 doses + 1 boost) dose schedule. Post-PCV7 shifts in pneumococcal reservoirs were assessed by two point prevalence studies of nasopharyngeal colonization among children in day care centers, before (2006) and after (2008) widespread use of PCV7. Nasopharyngeal swabs were obtained from 1,213 children, 611 in 2006 and 602 in 2008. A total of 1,102 pneumococcal isolates were recovered. Serotyping, multilocus sequence typing, and antimicrobial drug susceptibility testing were performed on all isolates. Although carriage of PCV7 serotypes decreased among both vaccinated and unvaccinated children, the overall prevalence of pneumococcal carriage remained high (80.4%) after vaccine introduction. The pneumococcal populations were diverse, and in the shift toward non-PCV7 serotypes, expansion of a limited number of established clonal complexes was observed. While non-antimicrobial-susceptible clones persisted among PCV7 serotypes, antimicrobial resistance did not increase among non-PCV7 serotypes. Direct and indirect protection of PCV7 against nasopharyngeal colonization was inferred from an overall decrease in carriage of PCV7 serotypes. No preference was found for nonsusceptible clones among the replacing non-PCV7 serotypes.Streptococcus pneumoniae is a leading cause of otitis media, sinusitis, pneumonia, and meningitis worldwide (35). S. pneumoniae colonizes the nasopharynx and is considered a part of the normal flora in early childhood (1). Following the implementation of childhood vaccination with the seven-valent conjugated pneumococcal vaccine (PCV7), reports from several locations have described declines in carriage of the seven serotypes included in the vaccine, i.e., serotypes 4, 6B, 9V, 14, 18C, 19F and 23F (4, 6, 13, 19, 24). Due to reduced transmission of PCV7 serotypes, the incidence of invasive pneumococcal disease (IPD) declines also among the unvaccinated, which is an indirect effect of conjugate pneumococcal vaccination. However, the effect of PCV7 may in part be eroded over time as non-PCV7 serotypes emerge as a more frequent cause of IPD (11). In the United States, non-antimicrobial-susceptible clones seem to have an advantage among the emerging and expanding non-PCV7 serotypes, both in asymptomatic colonization and IPD (10, 20). This is primarily demonstrated by increasing incidence rates of drug-resistant clones of serotype 19A (23).PCV7 was introduced into the Norwegian childhood vaccination program in a dose schedule of two doses and one boost (2 + 1 dose schedule) in July 2006 and has been offered free of charge to all children born in 2006 and since. A high level of effectiveness of the vaccination program among children was demonstrated quickly after vaccine introduction, and the effect included a decline in IPD caused by erythromycin-resistant S. pneumoniae (34).As part of the Norwegian surveillance of PCV7 introduction, a cross-sectional study of nasopharyngeal carriage of Streptococcus pneumoniae among children attending day care centers (DCC) was performed in the early autumn of 2006. Data from this study, with exception of data regarding 38 vaccinated participants, have been reported previously (33). To assess the impact of the 2 + 1 dose schedule PCV7 vaccination program on carriage of S. pneumoniae, a follow-up was performed in 2008. Serotyping, antimicrobial susceptibility testing, and genotyping of the isolates from 2008 were performed, and the results were compared to those from analyses of the previous collection. Shifts in clonal compositions of the pneumococcal populations were analyzed and are reported here.Limited outpatient use of antimicrobial agents is recommended in Norway, and the levels of nonsusceptibility to antimicrobials among S. pneumoniae isolates from both local infections and IPD are low (25). Hence, emphasis has been put on post-PCV7 changes in nonsusceptibility to antimicrobials and nonsusceptible clones in a setting with limited antimicrobial use and resistance.