Age-dependent prevalence of nasopharyngeal carriage of streptococcus pneumoniae before conjugate vaccine introduction: a prediction model based on a meta-analysis

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.

Figure 1. Flow chart of the study selection process.

Figure 2. Overall carriage prevalence in older age groups against <5 y olds: scatter plot and fitted model.

Each circle corresponds to one study, with the circle size proportional to the study size (i.e. number of individuals contributing to the x and y axis estimates). The lines correspond to the fitted Bayesian linear meta-regression model. The dashed black line shows the median posterior estimate and the grey shaded area the 95% credible interval around the median. The red dotted lines represent the 95% prediction interval.

Figure 3. VT proportion in carried serotypes among <5 y and older ages: scatter plot and fitted model.

Each circle corresponds to one study, with the circle size proportional to the study size (i.e. number of individuals contributing to the x and y axis estimates). The lines correspond to the fitted Bayesian linear meta-regression model. The dashed black line shows the median posterior estimate and the grey shaded area the 95% credible interval around the median. The red dotted lines represent the 95% prediction interval.

Figure 4. VT and NVT prevalence in 5–17 y olds against <5 y olds: scatter plot and fitted model.

Each circle corresponds to one study, with the circle size proportional to the study size (i.e. number of individuals contributing to the x and y axis estimates). The lines correspond to the fitted Bayesian linear meta-regression model. The dashed black line shows the median posterior estimate and the grey shaded area the 95% credible interval around the median. The red dotted lines represent the 95% prediction interval.

Figure 5. VT and NVT prevalence in adults against <5 y olds: scatter plot and fitted model.

Each circle corresponds to one study, with the circle size proportional to the study size (i.e. number of individuals contributing to the x and y axis estimates). The lines correspond to the fitted Bayesian linear meta-regression model. The dashed black line shows the median posterior estimate and the grey shaded area the 95% credible interval around the median. The red dotted lines represent the 95% prediction interval.