Presence of Group A streptococcus frequently assayed virulence genes in invasive disease: a systematic review and meta-analysis.

Introduction: It is currently unclear what the role of Group A streptococcus (GAS) virulence factors (VFs) is in contributing to the invasive potential of GAS. This work investigated the evidence for the association of GAS VFs with invasive disease.

Methods: We employed a broad search strategy for studies reporting the presence of GAS VFs in invasive and non-invasive GAS disease. Data were independently extracted by two reviewers, quality assessed, and meta-analyzed using Stata®.

Results: A total of 32 studies reported on 45 putative virulence factors [invasive (n = 3,236); non-invasive (n = 5,218)], characterized by polymerase chain reaction (PCR) (n = 30) and whole-genome sequencing (WGS) (n = 2). The risk of bias was rated as low and moderate, in 23 and 9 studies, respectively. Meta-,analyses of high-quality studies (n = 23) revealed a significant association of [OR, 1.64 (95%CI, 1.06; 2.52)] with invasive infection. Meta-analysis of WGS studies demonstrated a significant association of [OR, 1.91 (95%CI, 1.36; 2.67)] and [OR, 2.83 (95%CI, 1.63; 4.92)] with invasive GAS (iGAS). Meta-analysis of PCR studies indicated a significant association of [OR, 1.59 (95%CI, 1.10; 2.30)] and [OR, 2.95 (95%CI, 1.81; 4.80)] with invasive infection. A significant inverse association was observed between [OR, 0.42 (95%CI, 0.20; 0.87)] and invasive infection.

Conclusion: This systematic review and genomic meta-analysis provides evidence of a statistically significant association with invasive infection for the gene, while , , , , , and show statistically significantly inverse associations with invasive infection. , , and are associated with GAS virulence; however, it is unclear if they are markers of invasive infection. This work could possibly aid in developing preventative strategies.