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    The Limitations of the Rheumatogenic Concept for Group A Streptococcus: Systematic Review and Genetic Analysis

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    Author
    de Crombrugghe, G; Baroux, N; Botteaux, A; Moreland, NJ; Williamson, DA; Steer, AC; Smeesters, PR
    Date
    2020-04-01
    Source Title
    Clinical Infectious Diseases
    Publisher
    OXFORD UNIV PRESS INC
    University of Melbourne Author/s
    Steer, Andrew; Smeesters, Pierre; Williamson, Deborah
    Affiliation
    Paediatrics (RCH)
    Microbiology and Immunology
    Metadata
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    Document Type
    Journal Article
    Citations
    de Crombrugghe, G., Baroux, N., Botteaux, A., Moreland, N. J., Williamson, D. A., Steer, A. C. & Smeesters, P. R. (2020). The Limitations of the Rheumatogenic Concept for Group A Streptococcus: Systematic Review and Genetic Analysis. CLINICAL INFECTIOUS DISEASES, 70 (7), pp.1453-1460. https://doi.org/10.1093/cid/ciz425.
    Access Status
    Access this item via the Open Access location
    URI
    http://hdl.handle.net/11343/253937
    DOI
    10.1093/cid/ciz425
    Open Access URL
    https://dipot.ulb.ac.be/dspace/bitstream/2013/309207/3/deCrombrugghe_CID_2019.pdf
    Abstract
    BACKGROUND: The concept that a minority of group A streptococcus (GAS) emm types are more "rheumatogenic" than others has been widely disseminated. We aimed to provide a comprehensive list of acute rheumatic fever-associated GAS isolates and assess the presence of associated rheumatogenic motifs. METHODS: Articles reporting GAS emm-type or emm-type-specific antibody responses associated with rheumatic fever were identified from 1 January 1944 to 31 July 2018. The revised Jones criteria were used to define rheumatic fever with a maximum period of 4 weeks between disease onset and microbiological characterization. A database of 175 representative M-protein sequences was used to analyze the protein diversity of rheumatic fever-associated strains in a phylogenetic tree and to identify the presence of 10 previously recognized rheumatogenic motifs. RESULTS: We included 411 cases of rheumatic fever, for which microbiological characterization identified 73 different emm types associated with the disease. The classic rheumatogenic emm types represented only 12.3% of the 73 emm types and were responsible for 31.6% of the 411 clinical cases. Rheumatic fever-associated emm types were disseminated throughout the phylogeny, suggesting they belong to various genetic backgrounds. Rheumatic fever-associated motifs were present in only 15.1% of the rheumatic fever-associated emm types and only 24.8% of clinical cases. CONCLUSIONS: The concept of rheumatogenicity should be extended to include strains other than those classically described. Our results highlight significant knowledge gaps in the understanding of rheumatic fever pathogenesis and suggest that a GAS vaccine candidate should offer broad coverage against a variety of GAS genetic variants in order to protect against this serious sequela.

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