{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:37:23Z","timestamp":1780472243371,"version":"3.54.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:00:00Z","timestamp":1563840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Belgian Fonds National de la Recherche Scientifique","award":["FNRS PDR N\u00b0 T.0255.16F"],"award-info":[{"award-number":["FNRS PDR N\u00b0 T.0255.16F"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The concept that a minority of group A streptococcus (GAS) emm types are more \u201crheumatogenic\u201d than others has been widely disseminated. We aimed to provide a comprehensive list of acute rheumatic fever\u2013associated GAS isolates and assess the presence of associated rheumatogenic motifs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Articles reporting GAS emm-type or emm-type\u2013specific 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\u2013associated strains in a phylogenetic tree and to identify the presence of 10 previously recognized rheumatogenic motifs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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\u2013associated emm types were disseminated throughout the phylogeny, suggesting they belong to various genetic backgrounds. Rheumatic fever\u2013associated motifs were present in only 15.1% of the rheumatic fever\u2013associated emm types and only 24.8% of clinical cases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciz425","type":"journal-article","created":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T19:18:13Z","timestamp":1558379893000},"page":"1453-1460","source":"Crossref","is-referenced-by-count":34,"title":["The Limitations of the Rheumatogenic Concept for Group A Streptococcus: Systematic Review and Genetic Analysis"],"prefix":"10.1093","volume":"70","author":[{"given":"Gabrielle","family":"de Crombrugghe","sequence":"first","affiliation":[{"name":"Academic Children Hospital Queen Fabiola, Universit\u00e9 libre de Bruxelles, Brussels, Belgium"},{"name":"Molecular Bacteriology Laboratory, Universit\u00e9 libre de Bruxelles, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noemie","family":"Baroux","sequence":"first","affiliation":[{"name":"Tropical Diseases Research Group, Murdoch Children\u2019s Research Institute, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Botteaux","sequence":"first","affiliation":[{"name":"Molecular Bacteriology Laboratory, Universit\u00e9 libre de Bruxelles, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole J","family":"Moreland","sequence":"first","affiliation":[{"name":"Faculty of Medical and Health Sciences, The University of Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A","family":"Williamson","sequence":"first","affiliation":[{"name":"Microbiological Diagnostic Unit Public Health Laboratory, University of Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C","family":"Steer","sequence":"first","affiliation":[{"name":"Tropical Diseases Research Group, Murdoch Children\u2019s Research Institute, Melbourne, Australia"},{"name":"Centre for International Child Health, University of Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre R","family":"Smeesters","sequence":"first","affiliation":[{"name":"Academic Children Hospital Queen Fabiola, Universit\u00e9 libre de Bruxelles, Brussels, Belgium"},{"name":"Molecular Bacteriology Laboratory, Universit\u00e9 libre de Bruxelles, Brussels, Belgium"},{"name":"Tropical Diseases Research Group, Murdoch Children\u2019s Research Institute, Melbourne, Australia"},{"name":"Centre for International Child Health, University of Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,23]]},"reference":[{"key":"2020052904195826400_CIT0001","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1056\/NEJMoa1603693","article-title":"Global, regional, and national burden of rheumatic heart disease, 1990\u20132015","volume":"377","author":"Watkins","year":"2017","journal-title":"N Engl J Med"},{"key":"2020052904195826400_CIT0002","doi-asserted-by":"crossref","first-page":"15084","DOI":"10.1038\/nrdp.2015.84","article-title":"Acute rheumatic fever and rheumatic heart disease","volume":"2","author":"Carapetis","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"2020052904195826400_CIT0003","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.meegid.2018.03.006","article-title":"Streptococcal pharyngitis and rheumatic heart disease: the superantigen hypothesis 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