Invasive Infections Caused by Lancefield Groups C/G and A Streptococcus, Western Australia, Australia, 2000–2018

Abstract

I nvasive, β-hemolytic Streptococcus disease is associated with high rates of illness and death and substantial financial cost (1-3). Human pathogenic β-hemolytic Streptococcus include Lancefield groups A (GAS, Streptococcus pyogenes), B (GBS, S. agalactiae), and C and G (GCGS, multiple species) ( 4). An understanding of the population-level disease burden is essential for planning preventive and management strategies (2). For GCGS, the major subspecies causing human infection is S. dysgalactiae subspecies equisimilis, which shares virulence factors with GAS, including the M protein (2). Evidence from epidemiologic studies and animal models also link GCGS infection to postinfectious immunologic complications such as rheumatic heart disease (5,6). For these reasons, GCGS and GAS have overlapping clinical manifestations and, from a prevention perspective, development efforts toward a vaccine for GAS may have off-target effects in preventing GCGS infection (7).Compared with knowledge about invasive GAS infections, much less is known about the epidemiology of invasive GCGS (iGCGS) disease or how clinical features and outcomes differ between them. Unlike GAS, which is notifiable in many jurisdictions, such as the United Kingdom (8) and Canada (9), iGCGS is not considered a notifiable disease in any jurisdiction. For the few settings where comparative epidemiologic data are available, the incidence of iGCGS infection is similar or higher than for invasive GAS (10,11). Also shared in common with invasive GAS infections, iGCGS has a death rate of 5%-10%, and its incidence appears to be increasing in recent years in some countries (10,(12)(13)(14).In a recent study, we demonstrated an increasing incidence of invasive GAS infection that disproportionately affects Indigenous Australians (15). By using this same methodology, we sought to describe the epidemiology of iGCGS infection in terms of incidence, median length of hospital stay, and all-cause deaths and to compare these metrics with those in patients with invasive GAS infections.

Inter-species gene flow drives ongoing evolution ofStreptococcus pyogenesandStreptococcus dysgalactiaesubsp.equisimilis

“…With increasing disease control efforts for S. pyogenes including vaccine development 26,27,42 and reports of high disease burden associated with invasive SDSE infection [1][2][3][4][5][6][7][8] , an improved understanding of the SDSE genomic population structure and overlap between these closely related pathogens provides a new framework for understanding the evolution and prevention of disease associated with infection by these human pathogens.…”

“…Streptococcus dysgalactiae subspecies equisimilis (SDSE), a beta-hemolytic Streptococcus normally possessing the Lancefield group C/G antigen, is an emerging cause of human disease with recently reported incidences of invasive disease comparable to or surpassing that of the closely related and historically important pathogen, Streptococcus pyogenes (group A Streptococcus) [1][2][3][4][5][6][7][8] . SDSE and S. pyogenes occupy the same ecological niche and possess overlapping disease manifestations including pharyngitis, skin and soft tissue infections, necrotising fasciitis, streptococcal toxic shock syndrome and osteoarticular infections 9,10 .…”

Overlapping Streptococcus pyogenes and Streptococcus dysgalactiae subspecies equisimilis household transmission and mobile genetic element exchange

“…SDSE is increasingly being recognised as an important cause of invasive human disease with recent studies suggesting incidence and mortality comparable to S. pyogenes 6 , 9 , 10 . While not traditionally considered as a cause of acute rheumatic fever/rheumatic heart disease (ARF/RHD), reports from northern Australia suggest that at least in high-incidence areas of ARF/RHD, SDSE throat carriage may have the potential to induce cardiac myosin cross-reactive antibodies mimicking that seen with S. pyogenes 7 , 8 .…”

“…The burden of disease caused by SDSE in these communities is not clearly defined. However, invasive SDSE disease also appears to disproportionately affect Aboriginal Australians 6 . In regions with a high burden of beta-haemolytic streptococcal disease and post-infectious sequelae, there has been evidence that superficial SDSE infection may trigger immune responses which cross-react with cardiac myosin 7 , 8 .…”

“…These findings raise the possibility that SDSE may contribute to immune priming and the burden of rheumatic heart disease in those regions 7 . In high-income regions, emerging evidence has also described crude rates of invasive SDSE disease comparable to, and in some jurisdictions, greater than S. pyogenes , particularly in the elderly 6 , 9 , 10 .…”