Getting to grips with invasive group A streptococcal infection surveillance in Australia: are we experiencing an epidemic?

Well publicised, rapid onset deaths in previously healthy children from invasive group A streptococcal disease (iGAS) in Australia in recent years have highlighted the emerging burden of iGAS.1,2,3 Here we explore the evidence and knowledge gaps to inform clinicians, public health units and the Australian public regarding iGAS definition and epidemiological trends in Australia.

iGAS is associated with high morbidity, mortality and substantial health expenditure.4,5 Clinical forms include sepsis, streptococcal toxic shock syndrome, necrotising fasciitis, pneumonia/empyema, bacteraemia and postpartum endometritis.6 Group A Streptococcus (GAS) infections are not currently vaccine preventable, but through the Australian Strep A Vaccine Initiative, the Australian Government and global philanthropic partners have invested heavily in accelerating the vaccine development.7,8 Although GAS remains susceptible to penicillin and most β‐lactam antibiotics, mortality rates as high as 70–80% have been reported for iGAS necrotising fasciitis, and overall case fatalities remain high (8–16%) for the other phenotypes.5,9

Global increase in incidence of iGAS, local epidemiology and possible explanations

In December 2022, the World Health Organization (WHO) released a statement noting increasing iGAS incidence including fatalities in at least five of its European member states during the latter half of 2022.10 France, Ireland, the Netherlands, Sweden and the United Kingdom reported an increase in cases of iGAS, predominantly affecting children under 10 years of age.10 The United States also reported an increase in iGAS in 2022, relative to case numbers during the pandemic years.11 In the UK, where iGAS surveillance has been occurring since 2010,12 29 paediatric deaths were recorded from October to December 2022 (an average of 116 annualised), compared with 27 annual deaths during the last comparably high season in 2017–2018.13 Excess deaths in children were also reported in Ireland,14 the US15 and the Netherlands.16

iGAS became nationally notifiable in Australia in July 2021, preceded by Queensland since 200517 and Northern Territory since 2011.18 The remaining jurisdictions commenced notification between August 2021 and September 2022. This potentially complicates our assessment of whether the WHO advisory on increased iGAS globally also applies in Australia. In December 2022, Victoria19 issued an advisory to clinicians in response to an increase in cases of iGAS being notified locally. New South Wales,20 Western Australia21 and Australian Capital Territory22 followed with similar advisories in January 2023. According to the National Communicable Disease Surveillance (NCDS) dashboard, there were 1180 cases of iGAS notified in 2022 with Queensland having the highest number (386 cases, 33%).23 The Australian total for the first two quarters of 2023 was 1185 cases (updated as of 20 July 2023), including 339 cases from NSW, 253 cases from Queensland (highest year‐to‐date total of 5‐year records available online) and 308 cases in Victoria, indicating that the higher numbers being observed are not yet slowing down (Box).

The incidence of iGAS has been steadily increasing over the past two decades worldwide.24 The drivers of widespread and sharp increases seen in iGAS incidence across the world in late 2022 are uncertain, although several hypotheses are plausible. First, the emergence of M1_UK, an emm1 strain of GAS, in many parts of the world including Australia has been implicated, at least temporally, with an increase in invasive infections.25 This lineage has acquired several bacteriophage‐encoded superantigens, and their relationship with virulence and pathogenicity in iGAS is being further elucidated.25 Second, some health authorities have suggested that non‐pharmaceutical interventions during the COVID‐19 pandemic response — such as hand hygiene practices, face masking, and social distancing — may have contributed to a temporary reduction in the rate of iGAS cases, which has since rebounded to pre‐pandemic levels with the easing of those restrictions.26 However, increases in some parts of the world have been well above a pre‐pandemic high season. Third, surges in respiratory viral infections were observed in Australia and internationally following the easing of COVID‐19 restrictions.27,28,29

Predisposition to iGAS following viral infections such as influenza and varicella zoster virus are well described.9 The reduction in all respiratory viruses that followed the pandemic non‐pharmaceutical interventions created the environment in which iGAS declined, but with the return of respiratory viruses as well as reduced population immunity during the 3 years when people were not exposed to viral or bacterial infections may have created this niche. Predisposition to iGAS following COVID‐19 infection is plausible, although the association is yet to be fully elucidated. A recently published time series analysis found that the increase in iGAS cases in late 2022 also coincided with a major outbreak of respiratory viruses (including SARS‐CoV‐2) in the paediatric population, suggesting a contributory predisposition towards the observed surge in iGAS cases.30

Imperfect surveillance data in its infancy

The Communicable Diseases Network Australia (CDNA) surveillance case definition for notification of iGAS is the detection of GAS from a normally sterile site by culture or nucleic acid detection.26 While this definition is well placed to capture GAS bacteraemia, empyema, bone and joint infections, or infections involving otherwise sterile sites, it does not currently capture many common forms of iGAS. For example, in necrotising skin and soft tissue infections and invasive peripartum infections, GAS may not be isolated from the bloodstream and may only be isolated from non‐sterile sites such as superficial skin tissue or the cervix. Global experts offer a broader iGAS case definition, which recommends capturing confirmed (isolation of GAS from a sterile site) as well as probable cases (clinically congruent with severe GAS illness with GAS isolated from a non‐sterile site; for example, maternal sepsis with GAS isolated from the cervix or the placenta). These definitions are intended to provide a comprehensive picture of the burden of iGAS that is consistent with traditional surveillance definitions.31

Given that the national CDNA case definition does not capture some forms of iGAS, and the relative infancy and the incompleteness of surveillance across all states and territories, the iGAS numbers reflected currently in the NCDS dashboard are likely to be a significant underestimate of the true burden of disease.

Lack of consensus in public health management of iGAS

iGAS was made nationally notifiable before the development of the CDNA Series of National Guidelines (SoNG; https://www.health.gov.au/resources/collections/cdna‐series‐of‐national‐guidelines‐songs) or surveillance plan for the disease. This has complicated the response to the current apparent increase in cases, requiring ongoing use of jurisdictional or institutional clinical guidelines, which vary in their case definitions and clinical recommendations. The risk of secondary iGAS cases among household contacts of a confirmed case is up to 2000 times higher in the 30 days following exposure compared with the general population,32,33 with the highest reported risk in mother–neonate pairs and older people.33,34 Currently, management of iGAS contacts and outbreaks is left to respective state public health units (PHUs), resulting in a wide variation in advice among PHUs. In guidelines for chemoprophylaxis for close contacts, the definition of iGAS can differ from that of the CDNA and from other PHUs, and variations can also occur in the definition of a close contact and the recommendation for prophylactic regimen (). The CDNA has convened a working group to develop a SoNG for iGAS. This work will be critical to a harmonised national response to iGAS, including addressing the variation in existing guidelines, particularly the definition of close contacts and indications for chemoprophylaxis.

Inequitable epidemics

The apparent increase in iGAS in southern jurisdictions has attracted media and public health attention. However, the burden of iGAS in Northern Australia is a longstanding epidemic, with a disproportionate incidence in Aboriginal and Torres Strait Islanders, who experience iGAS at 6–10 times the rate of non‐Indigenous people.18,35,36 This inequity is mirrored in the Kimberley region of Western Australia.37 The devastating impacts have attracted relatively little public attention or action. This slower moving epidemic is almost certainly driven by the high rates of skin infections, potentiated by household crowding and inadequate access to health hygiene infrastructure.38 It is essential that action to understand and address the iGAS burden focuses on the ongoing and unmet needs of Aboriginal and Torres Strait Islander people in Australia. Consideration should be given to collection of Indigenous status as part of the National Notifiable Disease Surveillance System to assess progress of this inequitable epidemic across Australia.

Urgent need to synthesise clinical, public health and preventive priorities

While evidence‐based guidelines are being formulated to inform the public health response, critical research and clinical gaps remain. There is an unmet need for more comprehensive surveillance data that reflect the true incidence of iGAS in Australia with the capacity for clinical data linkage, enabling PHUs to respond to cases and clusters of iGAS in real time. Surveillance at a microbiological level has enabled the global community to track emerging virulent lineages such as the M1_UK strain. Such surveillance distinguishes between locally and internationally acquired spread. The Australian Pathogen Genomics Program (https://www.auspathogen.org.au) is currently building Australia's molecular surveillance for iGAS nationally, to build on jurisdictional reports of local molecular epidemiology.

GAS causes a wide spectrum of disease from superficial infections through to invasive and post‐infectious conditions, such as acute rheumatic fever and rheumatic heart disease. Global concerted effort for a GAS vaccine is underway and its success is eagerly awaited; however, a successful candidate will historically take several years to pass late phase clinical trials and regulatory approvals.8 Detailed epidemiological understanding of iGAS is critical to facilitate planning for more definitive preventions such as a GAS vaccine rollout or chemoprophylaxis measures, while continuing to monitor their impacts on epidemiology and antimicrobial resistance.

To target iGAS when a GAS vaccine becomes available, current epidemiology suggests it should be preferentially provided as an infant series with a booster dose during pregnancy, to reduce the burden of puerperal and neonatal sepsis. This schedule would also be optimal to prevent iGAS in Northern Australia where the early onset and lifelong burden of skin infections drive iGAS incidence.38 An additional dose before school entry may be considered in this population for prevention of acute rheumatic fever as this post‐infectious condition predominantly affects 5–14‐year‐olds.39 Lastly, a booster dose for people over 60 years of age should also be considered given the propensity for iGAS in the extremes of age. Ultimately, the development and implementation of a GAS vaccine will require ongoing investment in discovery science, good baseline epidemiological understanding, and a clear economic argument for the investment, all of which rely on a representative disease burden provided by a well functioning iGAS surveillance system. Recent events provide further impetus for these needs to be urgently prioritised by the public health, clinical and research communities in Australia.