In multiple surveillance studies, serotype 19A strains have been identified as major replacement strains in pneumococcal disease (invasive disease and AOM) reflecting both their greater predominance in carriage and their disease potential. However, the importance of 19A as a replacement serotype in invasive diseases, AOM and NP carriage varies across countries where PCV7 has been implemented, for reasons that are not fully understood [5, 17, 18]. Previous studies have identified two important factors affecting serotype 19A carriage, namely the prevalence prior to PCV7 implementation, and the level of antibiotic use (a large proportion of 19A strains were non susceptible prior to vaccine implementation) . However, non susceptible strains predominated among other serotypes that have expanded to a lesser extent . Here we investigated other potential risk factors for 19A carriage.
In our population of children aged from 6 to 24 months with a high rate of PCV7 vaccine coverage, we confirmed the importance of antibiotic exposure, and also found a role of DCC attendance and AOM.
Several studies have shown that DCC attendance increases the risk of pneumococcal carriage [8, 20]. However, this is the first time that DCC attendance has been specifically linked to increased 19A carriage (OR = 1.85, 95% CI [1.46-;2.35]). The explanation is not only that DCC attendance increased the overall risk of pneumococcal colonization, and 19A was the most frequently carried serotype in this population of highly PCV7-vaccinated children. In addition, 19A was the most prevalent serotype in the subpopulation of DCC attendees carrying pneumococci (OR = 1.56, 95% CI [1.21-;2.02]). The fact that 19A is frequently resistant to antibiotics and that DCC attendees have higher antibiotic exposure does not fully explain our observations. Indeed, 19A carriage was also the most prevalent serotype among carriers of resistant strains (OR = 1.39, 95% CI [1.01-;1.89]). The proportion of children attending DCC in a given country may thus influence the observed increase in 19A disease.
Children with AOM were also more likely to carry serotype 19A. As 19A has already shown to be the most frequent middle-ear-fluid isolate in PCV7-vaccinated children, this result might have been expected. However, our results also support the hypothesis that 19A has higher AOM disease potential than other non vaccine serotypes .
The main limitation of our study is the homogeneity of our population (children aged 6 to 24 months, PCV7-vaccinated, without antibiotics exposure within 7 days before enrolment, and with no severe underlying health disorders) making it more difficult to extrapolate our findings to other populations. Furthermore, our study is based on nasopharyngeal carriage results and cannot be directly extrapolated to invasive pneumococcal disease or middle-ear infections. Future implementation of a pneumococcal conjugate vaccine that includes a 19A conjugate may resolve the problems posed by serotype 19A, provided such a vaccine has a significant impact on 19A carriage. Ongoing surveillance of carriage is therefore necessary, because the primary pneumococcal reservoir is the nasopharynx of children. Hence, early insight into post-vaccine effects can be obtained by monitoring changes in pediatric carriage.