A longitudinal study of streptococcus pneumoniae carriage in healthy children in the 13-valent pneumococcal conjugate vaccine era

Abstract

Few epidemiological data are available after the introduction of the 13-valent pneumococcal vaccine (PCV13) in 2010. We performed repeat nasopharyngeal swabs and evaluated the serotype distribution of Streptococcus pneumoniae (SP) and its association with PCV13 vaccine status in healthy Italian children aged 3–59 months. SP serotypes were assessed by the Quellung reaction. 618 children appropriately (28%) or incompletely (72%) vaccinated for age with PCV13 were available at baseline (T0). 515 were re-evaluated at 6 months from baseline (T6) and 436 at 12 months from baseline (T12). The percentage of appropriately vaccinated subjects at T0, T6 and T12 was 28%, 67% and 92%, respectively. Random effects logistic regression models with robust 95% confidence intervals was used to estimate the time-related changes in SP and PCV13 carriage and marginal probabilities were obtained from such models. The age-corrected probability of SP carriage was 0.31 (95% CI 0.22 - 0.41) at T0, 0.32 (0.24 - 0.40) at T6 and 0.28 (0.20 - 0.35) at T12. The probability of PCV13 serotypes carriage was 0.025 (0.001 - 0.050) at T0, 0.018 (0.001 - 0.039) at T6 and 0.010 (0.001 - 0.023) at T12. A decrease in PCV13 serotypes and a shift in non-PCV13 serotypes colonization was observed. In particular, the 15A serotype accounted for 4%, 8% and 23% of SP isolates at T0, T6 and T12, respectively. In conclusion, the benefits of the PCV13 vaccination on SP carriage increase with increasing coverage rates. The shift of SP isolates toward non-PCV13 serotypes needs to be studied further.

Keywords:

• cohort study
• children
• epidemiology
• nasopharyngeal carriage
• Streptococcus pneumoniae
• 13-valent pneumococcal conjugate vaccine

Abbreviations:

• CI, confidence interval
• IPD, invasive pneumococcal disease
• N, number
• OR, odds ratio
• MAR, missing at random
• PCV7, pneumococcal 7-valent vaccine
• PCV13, pneumococcal 13-valent vaccine
• SP, Streptococcus pneumoniae
• VT, vaccine type

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Funding

PNEUmi was supported by a research grant by the Italian Ministry of Health (“Ricerca finalizzata 2009”) and by an unrestricted grant from Pfizer Italia s.r.l. The sponsors had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Authors' Contributions

Prof Zuccotti and Dr Mameli had full access to the data and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Zuccotti, Mameli, Torresani. Acquisition of data: Mameli, Daprai, Fabiano, Penagini. Analysis and interpretation of data: Zuccotti, Mameli, Bedogni, Torresani, Daprai Garlaschi. Drafting of the manuscript: Zuccotti, Mameli, Bedogni, Daprai. Critical revision of the manuscript for important intellectual content: Zuccotti, Gramegna, Faccini, Torresani. Statistical analysis: Bedogni Study supervision: Zuccotti, Mameli, Torresani, Dilillo. All authors read and approved the final manuscript.

Note

PNEUmi Study Group (PMSG): Emanuela Ballerini, Benincaso, Milena Bonvissuto, Dorella Bricalli, Manuela Brioschi, Cinzia Simona Calloni, Marina Irene Camiletti, Giacomo Colella, Laura De Angelis, Silvia Decarlis, Francesca Di Nello, Massimiliano Dozzi, Erica Galli, Vera Gandini, Maria Grazia Giuliani, Franca Laviola, Barbara Loda, Maddalena Macedoni, Elisabetta Mazzucchi, Maria Gabriella Metta, Anna Moscatiello, Pilar Nannini, Mariangela Petruzzi, Damiano Picicco, Michela Picciotti, Stefania Pisanelli, Norberto Porta, Giulia Ramponi, Francesca Redaelli, Riccardo Rubini, Natascia Sala, Vincenzo Saitta, Rosa Maria Tiso, Mariangela Tomasetto, Matteo Torcoletti, Marta Travaini, Maurizio Valentini.