Streptococcus pyogenes emm-types in northern Spain; population dynamics over a 7-year period
Introduction
Streptococcus pyogenes is a human restricted pathogen that can colonize the skin and pharyngeal epithelium. This bacterium is the main causative agent of bacterial pharyngitis in school-aged children and also causes a wide variety of infections ranging from mild to severe, life-threatening diseases. S. pyogenes invasive disease is a well-known and highly severe re-emerging disease but infections with less serious consequences also cause significant morbidity, consuming substantial economic and health resources.1 Little or no funding for studies of non-invasive S. pyogenes infection, which frequently are the source of the most severe streptococcal life-threatening diseases, has led to major knowledge gaps in this significant public health problem.
The M protein, which is exposed to the bacterial surface, comprises one of the main virulence factors of S. pyogenes, participating in adhesion to the epithelium and conferring protection against macrophage killing.2 This protein is encoded by the emm gene, which harbours a hyper-variable region with the antigen that evokes the human type-specific antibody response.2 The serologic method to characterize the M protein described by Rebbeca Lancefield has been replaced by sequencing the 180 residues of the variable region of the emm gene, which closely correlates with the homologous serologic M-type.3 Currently, emm-typing is the most widely used technique to characterize S. pyogenes strains.
Several efforts are being made to develop a vaccine to prevent S. pyogenes infections. To date, only one vaccine, based on the M protein and including 26 different subunit M peptides (26-valent M vaccine), has been demonstrated to be immunogenic and safe in human trials.4 The potential efficacy of this vaccine is limited to its suitability to local epidemiologic situations. Recently, this vaccine has been improved by replacing some emm-types and by increasing their number to up to 30,5 although type specificity continues to be a major challenge.
The aim of this study was to determine the clinical presentations of S. pyogenes infection and the prevalence and dynamic changes of the different emm-types within the community in a regional population over a 7-year period. The potential coverage of 26- and 30-valent vaccines and the relationship between specific emm-types with disease presentation were also analyzed.
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Materials and methods
This study included all episodes of infection with isolation of S. pyogenes between January 2005 and December 2011 at the Hospital Universitario Donostia, located in the city of San Sebastian, Basque Country, northern Spain, which attends a child and adult population of 405,745 inhabitants (2006 census). Only one isolate per episode was included. For some analysis patients were divided into four age groups: 0–4; 5–14; 15–64; and >64 years old.
Samples were cultured on sheep blood agar plates and
Clinical presentation of S. pyogenes infection. Relative incidence
Between 2005 and 2011, 11,342 episodes of S. pyogenes infection were recorded: 4323 (38.1%) in children 0–4 years old, 4697 (41.4%) in children 5–14 years old, 1911 (16.9%) in adults 15–64 years old and 218 (1.9%) in adults older than 64 years old (Table 1). In 193 (1.7%) adult patients, the age was unknown.
Considering the global period of study, the incidence of all S. pyogenes infections was higher between November and June (41.7/100,000 inhabitants) than between July and October
Discussion
The occurrence of severe invasive S. pyogenes (group A streptococci) infection is closely monitored in most parts of the world (Active Bacterial Core Surveillance http://www.cdc.gov/abcs/reports-findings/surv-reports.html, European Invasive Bacterial Diseases Surveillance Network (EU-IBIS) http://www.ecdc.europa.eu), but there is very little information on the overall (severe and non-severe) incidence of S. pyogenes clinical infections in the community. Because this was a laboratory-based
Acknowledgements
This study was supported in part by grant PI08/0808 from Fondo de Investigación Sanitaria, Ministerio de Sanidad y Política Social, Spain and by grant IT656-13 from the Education Department of the Basque Country Government, UPV/EHU.
We thank Julio Barado M.D. for his help with statistic analysis.
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These authors contributed equally to this work.