Global landscape of Streptococcus pneumoniae serotypes colonising healthy individuals worldwide before vaccine introduction; a systematic review and meta-analysis

BackgroundMonitoring pneumococcal carriage prevalence and serotype distribution is critical to understanding pneumococcal transmission dynamics and vaccine impact, particularly where routine disease surveillance is limited. This study aimed to describe and interpret heterogeneity in serotype-specific carriage globally before widespread use of pneumococcal conjugate vaccines (PCVs). MethodsA systematic literature review was undertaken to summarise all pneumococcal carriage studies across continents and age groups before PCV introduction. Serotype distributions were assessed via Bayesian nested meta-regression and hierarchical clustering. FindingsIn total 237 studies from 74 countries were included, comprising 492 age-specific datasets that contained 47,769 serotyped isolates.The modelled carriage prevalence differed substantially across regions, ranging in <5y from 35% (95%CrI 34%-35%) in Europe to 69% (95%CrI 69-70%) in Africa. Serotypes 19F, 6B, 6A, 23F, and 14 were the five most prevalent in children <5 years. The modelled proportion of Synflorix-10 (PCV10) serotypes carried by <5y ranged from 45% (95% CrI: 44% to 46%) in Asia to 59% (58% to 60%) in Europe, and that of Prevenar-13 (PCV13) from 60% (59% to 61%) in Asia to 76% (75% to 77%) in Europe. The diversity of carried serotypes increased with age, and so did the prevalence of vaccine-type serotypes. However, variation in serotype distribution did not cluster by age, ethnicity, region, or overall carriage prevalence. InterpretationGlobally, pre-PCV pneumococcal carriage was dominated by a few serotypes. Serotype distribution variability was not easily attributable to a single discriminatory factor. FundingThe review was funded by a grant to OlPdW from the World Health Organisation (grant number: SPHQ14-APW-2639) and by a Fellowship to SF jointly funded by the Wellcome Trust and the Royal Society (grant number: 208812/Z/17/Z).