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

Background Monitoring 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). Methods A 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. Findings In 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. Interpretation Globally, pre-PCV pneumococcal carriage was dominated by a few serotypes. Serotype distribution variability was not easily attributable to a single discriminatory factor. Funding The 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). ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The 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). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This systematic review used published data. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors