Whole genome sequence-based characterization of group A Streptococci (GAS; *Streptococcus pyogenes*) isolates causing invasive disease in South Africa, 2019–2020

Abstract

Invasive group A streptococcus (iGAS) is a major cause of morbidity. Penicillin and erythromycin are recommended for treatment. A 30-valent M-protein-based vaccine is being developed. We describe the molecular epidemiology of iGAS disease in South Africa, 2019 - 2020. iGAS episodes (cultured from normally sterile sites or from necrotising fasciitis wounds, among all ages) were detected through active, national, laboratory-based surveillance. At the national reference laboratory, isolates were confirmed phenotypically based on colony morphology, β-haemolysis and sensitivity to bacitracin; antimicrobial susceptibility testing was done by disk diffusion and broth microdilution; and isolates were further characterized by whole-genome sequencing. A SNP-based phylogenetic analysis determined genetic clusters. Of 1487 iGAS cases that were reported, 618 were characterised phenotypically (viable isolates available) and 577 genotypically. Incidence was 1.7 cases/100,000 persons in 2019 and 0.9/100,000 in 2020, with peaks in the extremes of age. All isolates were susceptible to the β-lactam antibiotics. Resistance was detected against tetracycline (10.5%;65/618), erythromycin (3.6%; 22/618), chloramphenicol (0.2%;1/618) and levofloxacin (0.2%;1/618). tetM and mef genes were present among isolates resistant to tetracycline and erythromycin, respectively. Overall, 56 emm types were identified. emm76 (33/577,5.7%), emm92 (30/577,5.2%) and emm82 (29/577,5.0%) were the most prevalent. Globally, emm1 is the most frequently occurring emm type in high-income countries, yet it was only detected in 3.7% of the isolates in the present study. emm76 and emm95 types accounted for most of the tetracycline- and erythromycin-resistant isolates, respectively. emm types in the 30-valent M-protein-based vaccine accounted for 44.6% (244/547) of isolates. Phylogenetically, identical emm types clustered together. Among genetic clusters, there was no geographical and temporal aggregation of cases. iGAS treatment with β- lactams remains appropriate. The 30-valent M-protein-based vaccine offers coverage to less than half of the isolates. No unidentified outbreaks were detected.