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      Group A streptococci clones associated with invasive infections and pharyngitis in Portugal present differences in emm types, superantigen gene content and antimicrobial resistance

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          Abstract

          Background

          A few lineages of Group A streptococci (GAS) have been associated with a reemergence of severe invasive streptococcal disease in developed countries. However, the majority of the comparisons between invasive and non-invasive GAS isolates have been performed for collections of reduced genetic diversity or relied on limited typing information to distinguish clones. We characterized by several typing methods and compared a collection of 160 isolates recovered from normally sterile sites with 320 isolates associated with pharyngitis and recovered in the same time period in Portugal.

          Results

          Although most of the isolates belonged to clones that were equally prevalent in invasive infections and pharyngitis, we identified markers of invasiveness, namely the emm types 1 and 64, and the presence of the speA and speJ genes. In contrast, emm4, emm75, and the ssa and speL/M genes were significantly associated with pharyngitis. There was a strong agreement between the emm type, the superantigen (SAg) genes and the clusters defined by pulsed-field gel electrophoresis (PFGE) profiling. Therefore, combinations of particular emm types and SAg genes frequently co-occurred in the same PFGE cluster, but there was no synergistic or antagonistic interaction between them in determining invasiveness. Only macrolide-susceptible PFGE clones were significantly associated with invasive infections or pharyngitis, while the clones of resistant isolates sharing all other molecular properties analyzed were equally prevalent in the two groups of isolates.

          Conclusions

          This study confirmed the importance of the widely disseminated emm1-T1-ST28 clone in invasive infections but also identified other clones linked to either invasive infections ( emm64-ST164) or pharyngitis ( emm4-T4-ST39), which may be more limited in their temporal and geographical spread. Clonal properties like some emm types or SAg genes were associated with disease presentation, highlighting the importance of bacterial genetic factors to the outcome of GAS infections, although other, yet unidentified factors may also play an important role.

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          Most cited references38

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          The global burden of group A streptococcal diseases.

          The global burden of disease caused by group A streptococcus (GAS) is not known. We review recent population-based data to estimate the burden of GAS diseases and highlight deficiencies in the available data. We estimate that there are at least 517,000 deaths each year due to severe GAS diseases (eg, acute rheumatic fever, rheumatic heart disease, post-streptococcal glomerulonephritis, and invasive infections). The prevalence of severe GAS disease is at least 18.1 million cases, with 1.78 million new cases each year. The greatest burden is due to rheumatic heart disease, with a prevalence of at least 15.6 million cases, with 282,000 new cases and 233,000 deaths each year. The burden of invasive GAS diseases is unexpectedly high, with at least 663,000 new cases and 163,000 deaths each year. In addition, there are more than 111 million prevalent cases of GAS pyoderma, and over 616 million incident cases per year of GAS pharyngitis. Epidemiological data from developing countries for most diseases is poor. On a global scale, GAS is an important cause of morbidity and mortality. These data emphasise the need to reinforce current control strategies, develop new primary prevention strategies, and collect better data from developing countries.
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            PHYLOViZ: phylogenetic inference and data visualization for sequence based typing methods

            Background With the decrease of DNA sequencing costs, sequence-based typing methods are rapidly becoming the gold standard for epidemiological surveillance. These methods provide reproducible and comparable results needed for a global scale bacterial population analysis, while retaining their usefulness for local epidemiological surveys. Online databases that collect the generated allelic profiles and associated epidemiological data are available but this wealth of data remains underused and are frequently poorly annotated since no user-friendly tool exists to analyze and explore it. Results PHYLOViZ is platform independent Java software that allows the integrated analysis of sequence-based typing methods, including SNP data generated from whole genome sequence approaches, and associated epidemiological data. goeBURST and its Minimum Spanning Tree expansion are used for visualizing the possible evolutionary relationships between isolates. The results can be displayed as an annotated graph overlaying the query results of any other epidemiological data available. Conclusions PHYLOViZ is a user-friendly software that allows the combined analysis of multiple data sources for microbial epidemiological and population studies. It is freely available at http://www.phyloviz.net.
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              The epidemiology of invasive group A streptococcal infection and potential vaccine implications: United States, 2000-2004.

              Invasive group A Streptococcus (GAS) infection causes significant morbidity and mortality in the United States. We report the current epidemiologic characteristics of invasive GAS infections and estimate the potential impact of a multivalent GAS vaccine. From January 2000 through December 2004, we collected data from Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs), a population-based system operating at 10 US sites (2004 population, 29.7 million). We defined a case of invasive GAS disease as isolation of GAS from a normally sterile site or from a wound specimen obtained from a patient with necrotizing fasciitis or streptococcal toxic shock syndrome in a surveillance area resident. All available isolates were emm typed. We used US census data to calculate rates and to make age- and race-adjusted national projections. We identified 5400 cases of invasive GAS infection (3.5 cases per 100,000 persons), with 735 deaths (case-fatality rate, 13.7%). Case-fatality rates for streptococcal toxic shock syndrome and necrotizing fasciitis were 36% and 24%, respectively. Incidences were highest among elderly persons (9.4 cases per 100,000 persons), infants (5.3 cases per 100,000 persons), and black persons (4.7 cases per 100,000 persons) and were stable over time. We estimate that 8950-11,500 cases of invasive GAS infection occur in the United States annually, resulting in 1050-1850 deaths. The emm types in a proposed 26-valent vaccine accounted for 79% of all cases and deaths. Independent factors associated with death include increasing age; having streptococcal toxic shock syndrome, meningitis, necrotizing fasciitis, pneumonia, or bacteremia; and having emm types 1, 3, or 12. GAS remains an important cause of severe disease in the United States. The introduction of a vaccine could significantly reduce morbidity and mortality due to these infections.
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                Author and article information

                Journal
                BMC Microbiol
                BMC Microbiol
                BMC Microbiology
                BioMed Central
                1471-2180
                2012
                27 November 2012
                : 12
                : 280
                Affiliations
                [1 ]Instituto de Microbiologia, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
                [2 ]Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal
                Article
                1471-2180-12-280
                10.1186/1471-2180-12-280
                3543706
                23181337
                825d7412-7066-401c-8bf7-dfa90a5da7c0
                Copyright ©2012 Friães et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 February 2012
                : 23 November 2012
                Categories
                Research Article

                Microbiology & Virology
                streptococcus pyogenes,exotoxins,streptococcal m protein,pharyngitis,invasive infection

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