Pathogenesis, epidemiology and control of Group A <i>Streptococcus</i> infection

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Abstract

Streptococcus pyogenes (Group A Streptococcus; GAS) is exquisitely adapted to the human host, resulting in asymptomatic infection, pharyngitis, pyoderma, scarlet fever or invasive diseases, with potential for triggering post-infection immune sequelae. GAS deploys a range of virulence determinants to allow colonization, dissemination within the host and transmission, disrupting both innate and adaptive immune responses to infection. Fluctuating global GAS epidemiology is characterized by the emergence of new GAS clones, often associated with the acquisition of new virulence or antimicrobial determinants that are better adapted to the infection niche or averting host immunity. The recent identification of clinical GAS isolates with reduced penicillin sensitivity and increasing macrolide resistance threatens both frontline and penicillin-adjunctive antibiotic treatment. The World Health Organization (WHO) has developed a GAS research and technology road map and has outlined preferred vaccine characteristics, stimulating renewed interest in the development of safe and effective GAS vaccines.

Abstract

In this Review, Brouwer et al. summarize recent developments in our understanding of Group A Streptococcus (GAS), focusing on the epidemiologic and clinical features of GAS infection and the molecular mechanisms associated with GAS virulence and drug resistance.

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The global burden of group A streptococcal diseases.

Jonathan Carapetis, Andrew Steer, E. Mulholland … (2005)

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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Disease manifestations and pathogenic mechanisms of group a Streptococcus.

Mark Walker, Timothy C Barnett, Jason McArthur … (2014)

Streptococcus pyogenes, also known as group A Streptococcus (GAS), causes mild human infections such as pharyngitis and impetigo and serious infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, repeated GAS infections may trigger autoimmune diseases, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease. Combined, these diseases account for over half a million deaths per year globally. Genomic and molecular analyses have now characterized a large number of GAS virulence determinants, many of which exhibit overlap and redundancy in the processes of adhesion and colonization, innate immune resistance, and the capacity to facilitate tissue barrier degradation and spread within the human host. This improved understanding of the contribution of individual virulence determinants to the disease process has led to the formulation of models of GAS disease progression, which may lead to better treatment and intervention strategies. While GAS remains sensitive to all penicillins and cephalosporins, rising resistance to other antibiotics used in disease treatment is an increasing worldwide concern. Several GAS vaccine formulations that elicit protective immunity in animal models have shown promise in nonhuman primate and early-stage human trials. The development of a safe and efficacious commercial human vaccine for the prophylaxis of GAS disease remains a high priority.

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Global emm type distribution of group A streptococci: systematic review and implications for vaccine development.

Andrew Steer, Irwin Law, Laisiana Matatolu … (2009)

emm sequence typing is the most widely used method for defining group A streptococcal (GAS) strains, and has been applied to isolates in all regions of the world. We did a systematic review of the global distribution of GAS emm types. 102 articles and reports were included (38 081 isolates). Epidemiological data from high-income countries were predominant, with sparse data from low-income countries. The epidemiology of GAS disease in Africa and the Pacific region seems to be different from that in other regions, particularly high-income countries. In Africa and the Pacific, there were no dominant emm types, a higher diversity of emm types, and many of the common emm types in other parts of the world were less common (including emm 1, 4, 6, and 12). Our data have implications for the development of GAS vaccines. On the basis of the available data, the current formulation of the experimental multivalent emm vaccine would provide good coverage in high-income countries, particularly USA, Canada, and Europe, but poor coverage in Africa and the Pacific, and only average coverage in Asia and the Middle East.

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Author and article information

Contributors

Mark J. Walker:

ORCID: http://orcid.org/0000-0001-7423-2769

mark.walker@uq.edu.au

Journal

Journal ID (nlm-ta): Nat Rev Microbiol

Journal ID (iso-abbrev): Nat Rev Microbiol

Title: Nature Reviews. Microbiology

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 1740-1526

ISSN (Electronic): 1740-1534

Publication date (Electronic): 9 March 2023

Pages: 1-17

Affiliations

[1 ]GRID grid.1003.2, ISNI 0000 0000 9320 7537, School of Chemistry and Molecular Biosciences, , The University of Queensland, ; Brisbane, Queensland Australia

[2 ]GRID grid.1003.2, ISNI 0000 0000 9320 7537, Australian Infectious Diseases Research Centre, , The University of Queensland, ; Brisbane, Queensland Australia

[3 ]GRID grid.1003.2, ISNI 0000 0000 9320 7537, Institute for Molecular Bioscience, , The University of Queensland, ; Brisbane, Queensland Australia

[4 ]Instituto Mexicano del Seguro Social, CONACYT, Mexico City, Mexico

[5 ]GRID grid.1008.9, ISNI 0000 0001 2179 088X, Department of Microbiology and Immunology, , The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, ; Melbourne, Victoria Australia

Author information

Stephan Brouwer http://orcid.org/0000-0002-9777-2992

Bodie F. Curren http://orcid.org/0000-0002-1165-6406

Nichaela Harbison-Price http://orcid.org/0000-0002-5794-1923

David M. P. De Oliveira http://orcid.org/0000-0002-5085-7163

Mark R. Davies http://orcid.org/0000-0001-6141-5179

Mark J. Walker http://orcid.org/0000-0001-7423-2769

Article

Publisher ID: 865

DOI: 10.1038/s41579-023-00865-7

PMC ID: 9998027

PubMed ID: 36894668

SO-VID: fdd6f03b-b52a-4d98-8a2a-a10d47b2df77

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Pathogenesis, epidemiology and control of Group A Streptococcus infection

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Vaccines

Most cited references 215

The global burden of group A streptococcal diseases.

Disease manifestations and pathogenic mechanisms of group a Streptococcus.

Global emm type distribution of group A streptococci: systematic review and implications for vaccine development.

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