Xie, Ouli

Chisholm, Rebecca H

Featherstone, Leo

Nguyen, An N T

Hayes, Andrew J

Jespersen, Magnus G

Zachreson, Cameron

Tellioglu, Nefel

Tonkin-Hill, Gerry

Dotel, Ravindra

Spring, Stephanie

Liu, Alice

Rofe, Alexander

Duchene, Sebastian

Sherry, Norelle L

Baird, Robert

Krause, Vicki

Holt, Deborah C

Coin, Lachlan J M

Rai, Neela Joshi

O'Sullivan, Matthew V N

Bond, Katherine

Corander, Jukka

Howden, Benjamin P

Korman, Tony M

Currie, Bart

Tong, Steven Y C

Davies, Mark R

2025-04-04

Defining the temporal dynamics of invasive Streptococcus pyogenes (group A Streptococcus) and differences between hyperendemic and lower-incidence regions provides crucial insights into pathogen evolution and, in turn, informs preventive measures. We aimed to examine the clinical and temporal lineage dynamics of S pyogenes across different disease settings in Australia to improve understanding of drivers of pathogen diversity.In this retrospective, multicentre, clinical and genomic epidemiology study, we identified cases of invasive S pyogenes infection from normally sterile sites between Jan 1, 2011, and Feb 28, 2023. Data were collected from five hospital networks across low-incidence regions in temperate southeast Australia and the hyperendemic, tropical, and largely remote Top End of the Northern Territory of Australia. The crude incidence rate ratio (IRR) of bloodstream S pyogenes infection comparing the Top End and southeast Australia and in First Nations people compared with non-First Nations people was estimated by quasi-Poisson regression. We estimated odds ratios (ORs) of intensive care unit (ICU) admission, in-hospital mortality, and 30-day mortality for the Top End versus southeast Australia using logistic regression. Retrieved and successfully sequenced isolates were assigned lineages at whole-genome resolution. Temporal trends in the composition of co-circulating lineages were compared between the two regions. We used an S pyogenes-specific multistrain simulated transmission model to examine the relationship between host population-specific parameters and observed pathogen lineage dynamics. The prevalence of accessory genes (those present in 5-95% of all genomes) was compared across geographies and temporal periods to investigate genomic drivers of diversity.We identified 500 cases of invasive S pyogenes infection in patients in the Top End and 495 cases in patients in southeast Australia. The crude IRR of bloodstream infection for the Top End compared with southeast Australia was 5·97 (95% CI 4·61-7·73) across the entire study period; in the Top End, infection disproportionately affected First Nations people compared with non-First Nations people (5·41, 4·28-6·89). The odds of in-hospital mortality (OR 0·43, 95% CI 0·26-0·70), 30-day mortality (0·38, 0·23-0·63), and ICU admission (0·42, 0·30-0·59) were lower in the Top End than in southeast Australia. Longitudinal lineage analysis of 642 S pyogenes genomes identified waves of replacement with distinct lineages in the Top End, whereas southeast Australia had a small number of dominant lineages that persisted and cycled in frequency. The transmission model qualitatively reproduced a similar pattern of replacement with distinct lineages when using a high transmission rate, small population size, and high levels of human movement-characteristics similar to those of communities in the hyperendemic Top End. Using a lower transmission rate, larger population size, and lower levels of migration similar to those of communities in urbanised southeast Australia, the transmission model qualitatively reproduced a pattern of dominant lineages that cycled in frequency. Despite distinct circulating lineages, the prevalence of accessory genes in the bacterial population was maintained across geographies and temporal periods.In a hyperendemic setting, the replacement of distinct S pyogenes lineages occurred in waves, which could be linked to the disproportionate burden of disease and sparse human population in this setting. The maintenance of bacterial gene frequency could be consistent with multilocus selection. These findings suggest that lineage-specific interventions-such as vaccines under development-should consider disease setting and, without broad cross-protection, might lead to lineage replacement.National Health and Medical Research Council, and Leducq Foundation.

Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Monash Infectious Diseases, Monash Health, Melbourne, VIC, Australia; Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia.

Department of Mathematical and Physical Sciences, La Trobe University, Melbourne, VIC, Australia; Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia.

Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia.

Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia.

Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

School of Computing and Information Systems, University of Melbourne, Melbourne, VIC, Australia.

Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; School of Computing and Information Systems, University of Melbourne, Melbourne, VIC, Australia.

Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Department of Biostatistics, Faculty of Medicine, University of Oslo, Oslo, Norway.

Department of Infectious Diseases, Blacktown Hospital, Sydney, NSW, Australia.

Monash Infectious Diseases, Monash Health, Melbourne, VIC, Australia; Infectious Diseases Department, Royal Darwin Hospital, Darwin, NT, Australia.

Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Victorian Infectious Diseases Service, The Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

Victorian Infectious Diseases Service, The Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Department of Microbiology, The Royal Melbourne Hospital, Melbourne, VIC, Australia.

Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Department of Computational Biology, Institut Pasteur, Paris, France.

Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Microbiological Diagnostic Unit Public Health Laboratory, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Department of Infectious Diseases & Immunology, Austin Health, Melbourne, VIC, Australia.

Territory Pathology, Northern Territory Department of Health, Royal Darwin Hospital, Darwin, NT, Australia.

Northern Territory Centre for Disease Control, Northern Territory Department of Health, Darwin, NT, Australia.

Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia; Faculty of Health, Charles Darwin University, Darwin, NT, Australia.

Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

Department of Infectious Diseases, Westmead Hospital, Sydney, NSW, Australia.

Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Infectious Diseases, Westmead Hospital, Sydney, NSW, Australia; NSW Health Pathology, Westmead Hospital, Sydney, NSW, Australia.

Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Victorian Infectious Diseases Service, The Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Department of Microbiology, The Royal Melbourne Hospital, Melbourne, VIC, Australia.

Department of Biostatistics, Faculty of Medicine, University of Oslo, Oslo, Norway; Parasites and Microbes, Wellcome Sanger Institute, Cambridge, UK; Helsinki Institute for Information Technology, Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland.

Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Microbiological Diagnostic Unit Public Health Laboratory, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Department of Infectious Diseases & Immunology, Austin Health, Melbourne, VIC, Australia.

Monash Infectious Diseases, Monash Health, Melbourne, VIC, Australia; Centre for Inflammatory Diseases, Monash University, Melbourne, VIC, Australia.

Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia; Infectious Diseases Department, Royal Darwin Hospital, Darwin, NT, Australia.

Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Victorian Infectious Diseases Service, The Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia. Electronic address: mark.davies1@unimelb.edu.au.

Lancet Microbe . 2025 Apr 4:101053. doi: 10.1016/j.lanmic.2024.101053. Online ahead of print.

2666-5247

https://pubmed.ncbi.nlm.nih.gov/40194534/?otool=iaurydwlib

https://hdl.handle.net/10137/14238

Temporal and geographical lineage dynamics of invasive Streptococcus pyogenes in Australia from 2011 to 2023: a retrospective, multicentre, clinical and genomic epidemiology study.

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