Supplementary materials: Systematic review and meta-analysis of the prevalence of group A streptococcal emm clusters in Africa to inform vaccine development.

Background An emm-cluster based system was proposed as a standard typing scheme to facilitate and enhance future studies of Group A Streptococcus (Strep A) epidemiological surveillance, M protein function and vaccine development strategies. We provide an evidence-based distribution of Strep A emm clusters in Africa and assess the potential coverage of the new 30-valent vaccine in terms of an emm cluster-based approach.

Method Two reviewers independently assessed studies retrieved from a comprehensive search and extracted relevant data. Meta-analyses were performed (random effects model) to aggregate emm cluster prevalence estimates.

Results Eight studies (n=1,595 isolates) revealed the predominant emm clusters as E6 (18%, 95% confidence interval (CI), 12.6; 24.0%), followed by E3 (14%, 95%CI, 11.2; 17.4%) and E4 (13%, 95%CI, 9.5; 16.0%). There is negligible variation in emm clusters as regards regions, age and socio-economic status across the continent. Considering an emm cluster-based vaccine strategy, which assumes cross-protection within clusters, the 30-valent vaccine currently in clinical development, would provide hypothetical coverage to 80.3% of isolates in Africa.

Conclusion This systematic review indicates the most predominant Strep A emm cluster in Africa is E6 followed by E3, E4 and D4. The current 30-valent vaccine would provide considerable coverage across the diversity of emm cluster types in Africa. Future efforts could be directed toward estimating the overall potential coverage of the new 30-valent vaccine based on cross-opsonization studies with representative panels of Strep A isolates from populations at highest risk for Strep A diseases.

Importance Low vaccine coverage is of grave public health concern, particularly in developing countries where epidemiological data are often absent. To inform vaccine development for group A streptococcus (Strep A), we report on the epidemiology of the M Protein emm clusters from Strep A infections in Africa, where Strep A-related illnesses and their sequalae including rheumatic fever and rheumatic heart disease, are of a high burden. This first report of emm clusters across the continent indicate a high probably of coverage by the M Protein-based vaccine currently undergoing testing, were an emm-cluster based approach to be used.