Gabrielle de Crombrugghe1,2, Noemie Baroux3, Anne Botteaux2, Nicole J Moreland4, Deborah A Williamson5, Andrew C Steer3,6, Pierre R Smeesters1,2,3,6. 1. Academic Children Hospital Queen Fabiola, Université libre de Bruxelles, Brussels, Belgium. 2. Molecular Bacteriology Laboratory, Université libre de Bruxelles, Brussels, Belgium. 3. Tropical Diseases Research Group, Murdoch Children's Research Institute, Melbourne, Australia. 4. Faculty of Medical and Health Sciences, The University of Auckland, New Zealand. 5. Microbiological Diagnostic Unit Public Health Laboratory, University of Melbourne, Australia. 6. Centre for International Child Health, University of Melbourne, Australia.
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.
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.
Authors: Alana L Whitcombe; Reuben McGregor; Julie Bennett; Jason K Gurney; Deborah A Williamson; Michael G Baker; Nicole J Moreland Journal: J Infect Dis Date: 2022-08-12 Impact factor: 7.759
Authors: Rukshan Am Rafeek; Adam S Hamlin; Nicholas M Andronicos; Craig S Lawlor; David J McMillan; Kadaba S Sriprakash; Natkunam Ketheesan Journal: Immunol Cell Biol Date: 2022-07-20 Impact factor: 5.853
Authors: Devaki H Pilapitiya; Paul W R Harris; Paulina Hanson-Manful; Reuben McGregor; Renata Kowalczyk; Jeremy M Raynes; Lauren H Carlton; Renwick C J Dobson; Michael G Baker; Margaret Brimble; Slawomir Lukomski; Nicole J Moreland Journal: Pathog Dis Date: 2021-07-09 Impact factor: 3.166