Abstract
Streptococcus pyogenes or group A Streptococcus (GAS) causes diseases ranging from uncomplicated pharyngitis to life-threatening infections. It has complex epidemiology driven by the diversity, the temporal and geographical fluctuations of the circulating strains. Despite the global burden of GAS diseases, there is currently no available vaccination strategy against GAS infections. This study, based on a longitudinal population survey, aimed to understand the dynamic of GAS emm types and to give leads to better recognition of underlying mechanisms for the emergence of successful clones. From 2009 to 2017, we conducted a systematic culture-based diagnosis of GAS infections in a French Brittany population with a prospective recovery of clinical data. The epidemiological analysis was performed using emm typing combined with the structural and functional cluster-typing system for all the recovered strains. Risk factors for the invasiveness, identified by univariate analysis, were computed in a multiple logistic regression analysis, and the only independent risk factor remaining in the model was the age (OR for the entire range [CI95%] = 6.35 [3.63, 11.10]; p<0.0001). Among the 61 different emm types identified, the most prevalent were emm28 (16%), emm89 (15%), emm1 (14%), and emm4 (8%), which accounted for more than 50% of circulating strains. During the study period, five genotypes identified as emm44, 66, 75, 83, 87 emerged successively and belonged to clusters D4, E2, E3, and E6 that were different from those gathering "Prevalent" emm types (clusters A-C3 to 5, E1 and E4). We previously reported significant genetic modifications for emm44, 66, 83 and 75 types resulting possibly from a short adaptive evolution. Herein we additionally observed that the emergence of a new genotype could occur in a susceptible population having specific risk factors or probably lacking a naturally-acquired cluster-specific immune cross-protection. Among emergent emm types, emm75 and emm87 tend to become prevalent with a stable annual incidence and the risk of a clonal expansion have to be considered.
Highlights
Streptococcus pyogenes or Group A Streptococcus (GAS) are Gram-positive cocci that usually colonize the human skin and throat and cause a wide variety of diseases ranging in severity from uncomplicated pharyngitis to severe and life-threatening infections [1]
The diagnosis of GAS infections was mainly performed within the University Hospital Centre (UHC) of Rennes, and explain that, over the 21 regions of French Brittany, the majority of GAS isolates was recovered from patients residing in Rennes and the neighbouring areas (S1 Fig)
GAS infections were categorized as non-invasive (350/942, 37%), and invasive infections (539/942; 57%) that were subcategorized in probable invasive (171/942; 18%), and definite invasive infections (368/942; 39%)
Summary
Streptococcus pyogenes or Group A Streptococcus (GAS) are Gram-positive cocci that usually colonize the human skin and throat and cause a wide variety of diseases ranging in severity from uncomplicated pharyngitis to severe and life-threatening infections [1]. Lancefield’s pioneering work demonstrated that GAS infections elicit a robust immune response by producing opsonizing antibodies against the cell surface M protein encoded by the emm gene [3]. For an epidemiological survey of GAS infections, emm genotyping based on the sequence of the 5’ hypervariable end of the emm gene, is a worldwide-accepted marker [4]. Many trials are in progress (CANVAS Group: Coalition to Accelerate New Vaccines Against Streptococcus) [5], there is currently no available vaccination against GAS infections. Its unavailability is mainly explained by the epidemiological complexity of circulating strains stressed by their geographical diversity and temporal variability [6,7,8,9,10]
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