Introduction: Group A streptococcus (GAS) gives rise to various clinical presentations in humans, from benign to severe invasive infections. This ubiquitous bacterial pathogen possesses a wide range of virulence factors and displays genomic diversity. M protein and Streptococcal pyrogenic exotoxins (spes) are among the major factors associated with the pathogenesis of GAS. This work sought to provide evidence, from published studies, for the association of GAS virulence factors with invasive disease in an effort to contribute to understanding GAS pathobiology for vaccine development efforts.
Methods: Using a broad search strategy carried out independently by two reviewers across a number of databases, we sought out molecular studies reporting on the association of genetic elements with invasive and non-invasive disease. Data were extracted and subjected to quality assessment and meta-analysis using Stata®.
Results: The search strategy yielded 592 studies, from which 16 reported on 32 virulence factors in invasive (n=2339) vs non-invasive infections (n=2768). Methods of detection included PCR (n=11), Multiplex PCR (n=4) and WGS (n=1). Associations of GAS elements with invasive disease were unremarkable, except for speA [Odds Ratio, 1.72 (95%CI, 1.17;2.53), 10 studies, PCR method]. There was trend of association of speG [OR, 1.94 (95%CI, 0.99;3.78), 5 studies, PCR method] and speM [OR, 1.44 (95%CI, 0.99;3.78), 6 studies, PCR method] with invasive disease. The negative association of speH and speI with invasive disease was not statistically significant.
Conclusion: This study, assessing the involvement of streptococcal pyrogenic exotoxins and superantigens with invasive disease, found weak evidence of an association for three GAS elements. Further studies are needed to investigate this observation.