Age-Dependent Prevalence of Nasopharyngeal Carriage of Streptococcus pneumoniae before Conjugate Vaccine Introduction: A Prediction Model Based on a Meta-Analysis Olivier Le Polain de Waroux 1 *, Stefan Flasche 1 , David Prieto-Merino 2 , W. John Edmunds 1 1 Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom, 2 Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom Abstract Introduction: Data on the prevalence of nasopharyngeal carriage of S.pneumoniae in all age groups are important to help predict the impact of introducing pneumococcal conjugate vaccines (PCV) into routine infant immunization, given the important indirect effect of the vaccine. Yet most carriage studies are limited to children under five years of age. We here explore the association between carriage prevalence and serotype distribution in children aged $5 years and in adults compared to children. Methods: We conducted a systematic review of studies providing carriage estimates across age groups in healthy populations not previously exposed to PCV, using MEDLINE and Embase. We used Bayesian linear meta-regression models to predict the overall carriage prevalence as well as the prevalence and distribution of vaccine and nonvaccine type (VT and NVT) serotypes in older age groups as a function of that in ,5 y olds. Results: Twenty-nine studies compromising of 20,391 individuals were included in the analysis. In all studies nasopharyngeal carriage decreased with increasing age. We found a strong positive linear association between the carriage prevalence in pre-school childen (,5 y) and both that in school aged children (5–17 y olds) and in adults. The proportion of VT serotypes isolated from carriers was consistently lower in older age groups and on average about 73% that of children ,5 y among 5–17 y olds and adults respectively. We provide a prediction model to infer the carriage prevalence and serotype distribution in 5–17 y olds and adults as a function of that in children ,5 years of age. Conclusion: Such predictions are helpful for assessing the potential population-wide effects of vaccination programmes, e.g. via transmission models, and thus assist in the design of future pneumococcal conjugate vaccination strategies. Citation: Le Polain de Waroux O, Flasche S, Prieto-Merino D, Edmunds WJ (2014) Age-Dependent Prevalence of Nasopharyngeal Carriage of Streptococcus pneumoniae before Conjugate Vaccine Introduction: A Prediction Model Based on a Meta-Analysis. PLoS ONE 9(1): e86136. doi:10.1371/journal.pone.0086136 Editor: Hiroshi Nishiura, The University of Tokyo, Japan Received September 30, 2013; Accepted December 4, 2013; Published January 23, 2014 Copyright: ß 2014 Le Polain de Waroux et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Olivier Le Polain de Waroux was supported by a doctoral research fellowship from the AXA Research fund for this piece of work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: olivier.lepolain@lshtm.ac.uk Introduction Colonization of the nasopharynx by Streptococcus pneumoniae is the reservoir for S.pneumoniae transmission and a prerequisite for pneumococcal disease [1]. Pneumococcal conjugate vaccines (PCV) reduce nasopharyngeal carriage of serotypes included in the vaccine by conferring capsular-specific immunity. Experience from countries where conjugate vaccines have been introduced has shown rapid and sustained carriage reduction of vaccine serotypes (VT) following vaccination. Those trends have been observed not only among vaccinated children but more widely across all age groups through a strong herd immunity effect [2,3]. Despite evidence of almost complete serotype replacement in many settings, whereby non-vaccine serotypes (NVT) colonise the space left vacant by vaccine type (VT) serotypes [4], pneumococcal conjugate vaccination programmes have led to a substantial reduction in severe disease due to the lower propensity of replacing serotypes to cause disease [4,5]. Ten- and thirteen-valent pneumococcal conjugate vaccines (PCV10 and PCV13) are now being introduced into the routine immunization programmes of many developing countries (www. jhsph.edu/ivac/vims.html), where their impact is expected to be high, given the disproportionate burden of pneumococcal disease in such settings [6]. Estimates of the potential impact of routinely introducing pneumococcal conjugate vaccines (PCVs), however, crucially depend on the nasopharyngeal carriage prevalence in the population before the introduction of PCV, the distribution of serotypes (VT and NVT) within the population, including among older children, adults and the elderly, and the propensity of replacing serotypes to cause disease across age groups. PLOS ONE | www.plosone.org 1 January 2014 | Volume 9 | Issue 1 | e86136