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.