Living with rheumatic fever and rheumatic heart disease in Victoria, Australia: A qualitative study.

BACKGROUND: In Victoria, Australia, children with Pacific Islander ('Pacific') ethnicities are overrepresented in acute rheumatic fever (ARF) and rheumatic heart disease (RHD). In June 2023, ARF and RHD became notifiable in Victoria. To inform public health and clinical practice, we described young Pacific patients' and their caregivers' understandings and experiences of ARF/RHD, and identified possible ways to improve the delivery of clinical care. METHODS: We established a project reference group including local Pacific people to guide this research. Pacific patients who attended an ARF/RHD clinic at The Royal Children's Hospital, Melbourne, were invited to participate, as were their caregivers. A Samoan researcher conducted qualitative 'talanoa' (conversational) interviews with patients and caregivers. A second researcher conducted semi-structured interviews with treating clinicians and other stakeholders. Interview transcripts underwent thematic analysis guided by the Tuilaepa Youth Mentoring Services Pacific Youth Wellbeing Framework. RESULTS: We interviewed 27 participants. This included nine patients and nine caregivers, all of whom were Samoan. These 18 participants expressed a desire to learn more about ARF/RHD and connect with other affected people. While some shared their experiences of having well-liked and trusted healthcare providers, patients often struggled to have two-way clinical conversations. The need to support clinicians working with high-risk populations to improve their awareness of ARF was identified. Receiving treatment on time was a top priority for affected families, despite injection pain, inconvenience and financial costs. The need to support continuity of care for young adult patients was raised by participants. CONCLUSIONS: Pacific people living with ARF/RHD and their families require additional support to receive high quality management in Victoria. Introducing a patient register and a specialist RHD nurse would enhance access to treatment, as would removing cost barriers, improving clinical awareness of ARF/RHD and creating Victoria-specific patient resources.

What Lies Beneath? The Role of Community Engagement in Translating COVID-19 Research Findings to Policy-Makers.

BACKGROUND: Community engagement is key to developing local and context-specific strategies for the prevention and control of COVID-19. However, expedited research design and approval in the early days of the pandemic may have limited the opportunities for community members to influence pandemic-related research. In this study, we sought to understand how a Community Engagement Group (CEG) could impact a large longitudinal COVID-19 research project (Optimise), when involved solely in the interpretation and knowledge translation phases of the research. METHODS: Seven community members were recruited for the CEG, representing a diverse range of groups. Each month, Optimise data of topical importance were compiled into a draft report. The CEG discussed the draft report at their monthly meeting and members' contributions were incorporated into the final report for distribution to policy-makers. In this study, a document analysis was undertaken of ten consecutive reports produced between February and November 2021. Each report was compared pre- and post- the inclusion of CEG contributions, which were then analysed using thematic analysis. RESULTS: Community engagement in the interpretation and knowledge translation phases of Optimise had positive impacts on reports for policy-makers, including grounding the empirical findings in broader community perspectives, identifying policy issues affecting different groups and contributing unique insights beyond the empirical findings. Overall, the CEG contributions demonstrated the complexity of lived experience lying beneath the empirical data. CONCLUSION: Community engagement in the translation of the Optimise findings resulted in research reports to policy-makers that were reflective of a broader range of community perspectives, and that provided potential solutions to emerging policy issues related to COVID-19. This study adds to the evidence base about the impact of community engagement in the later interpretation and knowledge translation phases of research, particularly in the context of reporting to policy-makers during a public health emergency.

Overlooked, dismissed, and downplayed: reversion of Mycobacterium tuberculosis immunoreactivity.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb). Following infection, immune responses to Mtb antigens can be measured using the tuberculin skin test or an interferon-γ release assay. The gain of Mtb immunoreactivity, a change from a negative to a positive tuberculin skin test or interferon-γ release assay result, is called conversion and has long been used as a measure of Mtb exposure. However, the loss of immunoreactivity (reversion; a positive followed by a negative result) has often been overlooked. Instead, in clinical and epidemiological circles, Mtb immunoreactivity is commonly considered to persist lifelong and confer a lifetime of disease risk. We present a critical review, describing the evidence for reversion from cohort studies, ecological studies and studies of TB progression risk. We outline the inconsistent reasons why reversion has been dismissed from common understanding and present evidence demonstrating that, just as conversion predominantly indicates prior exposure to Mtb antigens, so its opposite, reversion, suggests the reduction or absence of exposure (endogenous or exogenous). Mtb immunoreactivity is dynamic in both individuals and populations and this is why it is useful for stratifying short-term TB progression risk. The neglect of reversion has shaped TB research and policy at all levels, influencing clinical management and skewing Mtb infection risk estimation and transmission modelling, leading to an underestimation of the contribution of re-exposure to the burden of TB, a serious oversight for an infectious disease. More than a century after it was first demonstrated, it is time to incorporate reversion into our understanding of the natural history of TB.

ATAGI targeted review 2023: Vaccination for preventing influenza in Australia.

Abstract: Annual seasonal influenza epidemics cause substantial disease and economic burden worldwide. During the coronavirus disease 2019 (COVID-19) pandemic in 2020 and 2021, influenza activity significantly declined. However, influenza resurged in Australia following the relaxation of non-pharmaceutical interventions, with increased influenza virus circulation in early 2022 coinciding with the SARS-CoV-2 Omicron BA.2 variant wave. Together with other respiratory virus diseases, these disease impacts on the Australian population and healthcare system have re-emphasised the importance of influenza vaccination and control. We aim to provide an overview of the current seasonal influenza vaccination program in Australia and summarise evidence and considerations underpinning potential future immunisation strategies. Influenza causes disproportionately higher morbidity and mortality in young children and older adults. Other populations at elevated risk from influenza include Aboriginal and Torres Strait Islander peoples, pregnant women, and people with certain underlying medical conditions. All Australians aged ≥ 6 months are recommended to receive influenza vaccine every year. The National Immunisation Program (NIP) provides free vaccine for eligible at-risk populations. While approximately 70% of older adults had received influenza vaccine in 2022, coverage in other age groups remains suboptimal. There are several key unmet needs and challenges, but also potential strategies for enhancing the influenza vaccination program in Australia. Improved monitoring and evaluation, including the use of relevant linked datasets for such purposes, is imperative to better understand variations in coverage and vaccination impact in specific populations. Adoption of evidence-based strategies, such as culturally appropriate resources that consider the characteristics of diverse Australian populations, may also help to achieve higher vaccine coverage rates. Additionally, greater vaccine uptake across the population could be facilitated by expanding the NIP-eligible population where cost-effective, and adopting the use of more effective and different types of vaccines when available.

Community health workers' dissemination of COVID-19 information and services in the early pandemic response: a systematic review.

BACKGROUND: Community health workers (CHWs) had important roles mitigating the impact of the COVID-19 pandemic in vulnerable communities. We described how CHWs supported the dissemination of COVID-19 information and services during the early pandemic response. METHODS: Online article searches were conducted across five scientific databases, with review article reference lists hand searched to identify grey/unpublished literature. Articles were included if they reported on a program that engaged CHWs and aimed to prevent/control COVID-19. RESULTS: Nineteen relevant programs were identified from 18 included articles. CHWs were widely engaged in the pandemic response, especially in low- and middle-income countries and in vulnerable communities. CHWs' ability to effectively disseminate COVID-19 information/services was enabled by community trust and understanding community needs. CHWs were often underfunded and required to work in difficult conditions. Pre-existing services incorporating CHWs rapidly adapted to the new challenges brought by the pandemic. CONCLUSIONS: We recommend establishing programs that employ CHWs to disseminate health information and services in communities at-risk of misinformation and poor health outcomes during non-pandemic times. CHWs are well-placed to deliver interventions should an infectious disease outbreak arise. Having pre-existing trusted relationships between CHWs and community members may help protect vulnerable groups, including when outbreaks occur.

The challenges of living with Debilitating Symptom Complexes Attributed to Ticks (DSCATT) - A qualitative study.

OBJECTIVE: We sought to explore the lived experience of people with Debilitating Symptom Complexes Attributed to Ticks (DSCATT) to inform the development of a potential treatment intervention. METHODS: We conducted one-to-one in-depth, semi-structured interviews with 13 people living in Australia affected by DSCATT. Interviews were transcribed and analysed using thematic analysis. RESULTS: Although participants attributed the origin of their illness to tick bites, not all were adamant they had Lyme disease. Negative experiences in conventional healthcare were marked and were reported to exacerbate the impact of the illness and affect mental health. Further, these negative experiences propelled participants to seek unapproved treatments (by Australian standards). The desire for the illness to be acknowledged and causative agents identified was pronounced among the participant group. CONCLUSIONS: Individuals with DSCATT experience significant challenges amid a contentious healthcare landscape surrounding chronic symptoms attributed to ticks in Australia. Our findings suggest the need for empathetic, supportive and patient-centred treatments for this cohort. IMPLICATIONS FOR PUBLIC HEALTH: DSCATT results in a considerable burden across multiple domains for those affected. Negative experiences with healthcare exacerbate the suffering of people with DSCATT in Australia. New approaches that acknowledge the illness experience of people with DSCATT, alongside evidence-based treatments that encompass biopsychosocial models of care, are needed to tackle this debilitating condition.

Antibiotics to eradicate Streptococcus pyogenes pharyngeal carriage in asymptomatic children and adults: A systematic review.

Streptococcus pyogenes (S. pyogenes) is a Gram-positive bacteria which causes a spectrum of diseases ranging from asymptomatic infection to life-threatening sepsis. Studies report up to 2000 times greater risk of invasive S. pyogenes disease in close contacts of index cases within 30-days of symptom onset. Despite this, there is variability in the management of asymptomatic carriage of S. pyogenes and those at risk of secondary cases of invasive S. pyogenes infection. OBJECTIVE: Our systematic review assessed the efficacy of different antibiotic regimens used for eradication of S. pyogenes from the pharynx in asymptomatic individuals. METHODS: We searched Pubmed, EMBASE (1974-), OVID Medline (1948-) and the Cochrane CENTRAL registry. We included randomised controlled trials (RCTs) with asymptomatic participants with >50% with pharyngeal cultures positive with S. pyogenes at baseline. Only studies with microbiological methods including culture (+/- polymerase chain reaction, PCR) were included. We included studies published in English. Each included study was assessed by two independent reviewers for data extraction and risk of bias. RESULTS: Of 1166 unique records identified, three RCTs were included in the review. Two of the three included RCTs found oral clindamycin for 10-days was the most efficacious regimen, compared to intramuscular benzathine penicillin G followed by 4 days of oral rifampicin, or monotherapy using benzathine penicillin, phenoxymethylpenicillin or erythromycin. Two RCTs were assessed as being at high risk of bias, with the third study demonstrating low/some risk of bias. CONCLUSIONS: Current available evidence for the optimal antibiotic in eradicating pharyngeal S. pyogenes carriage is limited. Future RCTs should include penicillin, first-generation cephalosporins, rifampicin, macrolides (such as azithromycin) and clindamycin.

Testing the intrinsic mechanisms driving the dynamics of Ross River Virus across Australia.

The mechanisms driving dynamics of many epidemiologically important mosquito-borne pathogens are complex, involving combinations of vector and host factors (e.g., species composition and life-history traits), and factors associated with transmission and reporting. Understanding which intrinsic mechanisms contribute most to observed disease dynamics is important, yet often poorly understood. Ross River virus (RRV) is Australia's most important mosquito-borne disease, with variable transmission dynamics across geographic regions. We used deterministic ordinary differential equation models to test mechanisms driving RRV dynamics across major epidemic centers in Brisbane, Darwin, Mandurah, Mildura, Gippsland, Renmark, Murray Bridge, and Coorong. We considered models with up to two vector species (Aedes vigilax, Culex annulirostris, Aedes camptorhynchus, Culex globocoxitus), two reservoir hosts (macropods, possums), seasonal transmission effects, and transmission parameters. We fit models against long-term RRV surveillance data (1991-2017) and used Akaike Information Criterion to select important mechanisms. The combination of two vector species, two reservoir hosts, and seasonal transmission effects explained RRV dynamics best across sites. Estimated vector-human transmission rate (average ß = 8.04x10-4per vector per day) was similar despite different dynamics. Models estimate 43% underreporting of RRV infections. Findings enhance understanding of RRV transmission mechanisms, provide disease parameter estimates which can be used to guide future research into public health improvements and offer a basis to evaluate mitigation practices.

The associations between invasive group A streptococcal disease and infection with influenza, varicella, or hepatitis C viruses: A data linkage study, Victoria, Australia.

OBJECTIVES: To quantify the associations between invasive group A streptococcal disease (iGAS) incidence and influenza, varicella, and chronic hepatitis C virus (HCV). METHODS: We used individual-level linked data of iGAS cases from Victoria, Australia (2007-2017) to assess associations between these viral infections and iGAS. A self-controlled case series method was used to estimate the relative incidence of iGAS following an influenza or varicella infection, while the relative incidence of iGAS among HCV cases, and HCV cases who inject drugs, was estimated using population-level data and a negative binomial regression model. RESULTS: Of the 1949 individuals with at least one iGAS diagnosis, 82 were diagnosed with influenza at least once, 30 with varicella, and 118 with HCV during the study period. The relative incidence of iGAS increased substantially following infection with influenza (incidence rate ratio [IRR]: 34.5, 95% confidence interval [CI]: 21.3-55.8) or varicella (IRR: 22.4, 95% CI: 10.3-48.8). iGAS incidence was higher among HCV cases (IRR: 5.7, 95% CI: 4.4-7.3) compared to individuals without HCV. iGAS incidence was also higher among HCV cases who inject drugs (IRR: 17.9, 95% CI: 13.0-24.4) compared to individuals without HCV who did not inject drugs. CONCLUSIONS: We found a significantly higher risk of iGAS following an influenza or varicella infection and for chronic HCV cases, particularly those who inject drugs. These findings are relevant to public health practice and support the timely identification of iGAS cases.

Evaluating a peer-to-peer health education program in Australian public housing communities during the COVID-19 pandemic.

BACKGROUND: The cohealth Health Concierge program operated in Melbourne, Australia from July 2020 to 30 June 2022. It provided peer-to-peer support to culturally and linguistically diverse residents of high-rise public housing. During this time, the COVID-19 public health response changed frequently and included movement restriction, testing and vaccination. We conducted a mixed-methods evaluation to determine the Health Concierge program's impact on residents' engagement with health services and public health activities. METHODS: The evaluation, informed by a Project Reference Group, used the RE-AIM framework. We analysed data from 20,901 routinely collected forms describing interactions between Concierges and residents from August 2021 to May 2022. Additional evaluation-specific data were collected between March and May 2022 in four housing estates; we surveyed 301 residents and conducted 32 interviews with residents, Concierges and program stakeholders. RESULTS: Concierges promoted COVID-safe behaviours; linked residents with support, testing and vaccination services; and disseminated up-to-date information. Of the 20,901 recorded interactions, 8,872 (42%) included Concierges providing support around COVID-19 vaccination. Most surveyed residents (191/301, 63%) reported speaking with a Concierge in the previous six months. The self-reported two-dose COVID-19 vaccine uptake was 94% (283/301). Some residents described having meaningful, appreciated conversations with Concierges, and some described superficial interactions. While residents initially welcomed the program, many felt it failed to evolve. Poorly defined management and hiring criteria led to variable program implementation. A need for bicultural workers to continue linking residents with services was discussed. CONCLUSIONS: Concierges' impact on residents may have contributed to high community uptake of COVID-19 testing and vaccination, and had benefits beyond the COVID-19 remit. We recommend the program be revised and continued to inform further preparedness planning and support service access generally. Program models such as this have potential to inform and reassure high-risk communities during a pandemic. In addition, such programs can help overcome vaccine hesitancy and promote protective health behaviours, regardless of whether a pandemic is currently occurring. Ensuring these programs remain responsive to the changing needs of end-users needs over time is imperative.

Mosquitoes provide a transmission route between possums and humans for Buruli ulcer in southeastern Australia.

Buruli ulcer, a chronic subcutaneous infection caused by Mycobacterium ulcerans, is increasing in prevalence in southeastern Australia. Possums are a local wildlife reservoir for M. ulcerans and, although mosquitoes have been implicated in transmission, it remains unclear how humans acquire infection. We conducted extensive field survey analyses of M. ulcerans prevalence among mosquitoes in the Mornington Peninsula region of southeastern Australia. PCR screening of trapped mosquitoes revealed a significant association between M. ulcerans and Aedes notoscriptus. Spatial scanning statistics revealed overlap between clusters of M. ulcerans-positive Ae. notoscriptus, M. ulcerans-positive possum excreta and Buruli ulcer cases, and metabarcoding analyses showed individual mosquitoes had fed on humans and possums. Bacterial genomic analysis confirmed shared single-nucleotide-polymorphism profiles for M. ulcerans detected in mosquitoes, possum excreta and humans. These findings indicate Ae. notoscriptus probably transmit M. ulcerans in southeastern Australia and highlight mosquito control as a Buruli ulcer prevention measure.

Comprehensive Case-Control Study of Protective and Risk Factors for Buruli Ulcer, Southeastern Australia.

To examine protective and risk factors for Buruli ulcer (BU), we conducted a case-control study of 245 adult BU cases and 481 postcode-matched controls across BU-endemic areas of Victoria, Australia. We calculated age- and sex-adjusted odds ratios for socio-environmental, host, and behavioral factors associated with BU by using conditional logistic regression. Odds of BU were >2-fold for persons with diabetes mellitus and persons working outdoors who had soil contact in BU-endemic areas (compared with indoor work) but were lower among persons who had bacillus Calmette-Guérin vaccinations. BU was associated with increasing numbers of possums and with ponds and bore water use at residences. Using insect repellent, covering arms and legs outdoors, and immediately washing wounds were protective; undertaking multiple protective behaviors was associated with the lowest odds of BU. Skin hygiene/protection behaviors and previous bacillus Calmette-Guérin vaccination might provide protection against BU in BU-endemic areas.

I know what you did last summer: a cross-sectional study of personal COVID-19 risk reduction strategies used by Victorian adults, December 2021-January 2022.

OBJECTIVE: We describe COVID-19 risk reduction strategies adopted by Victorian adults during December 2021-January 2022, a period of high COVID-19 infection and limited government mandated public health measures. METHODS: In February 2022, participants of a Victorian-based cohort study (Optimise) completed a cross-sectional survey on risk reduction behaviours during December 2021-January 2022. Regression modelling estimated the association between risk reduction and demographics. RESULTS: A total of 556 participants were included (median age 47 years; 75% women; 82% in metropolitan Melbourne). Two-thirds (61%) adopted at least one risk reduction behaviour, with uptake highest among younger participants (18-34 years; adjusted relative risk (aRR): 1.20, 95% confidence interval [CI]: 1.01, 1.41) and those with a chronic health condition (aRR: 1.17, 95% CI: 1.02, 1.35). CONCLUSIONS: Participants adopted their own COVID-19 risk reduction strategies in a setting of limited government restrictions, with young people more likely to adopt a risk reduction strategy that did not limit social mobility. IMPLICATION FOR PUBLIC HEALTH: A public health response to COVID-19 that focusses on promoting personal risk reduction behaviours, as opposed to mandated restrictions, could be enhanced by disseminating information on and increasing availability of effective risk reduction strategies tailored to segments of the population.

Efficacy of Cognitive-Behavioral Therapy Targeting Severe Fatigue Following Coronavirus Disease 2019: Results of a Randomized Controlled Trial.

BACKGROUND: Severe fatigue following coronavirus disease 2019 (COVID-19) is prevalent and debilitating. This study investigated the efficacy of cognitive-behavioral therapy (CBT) for severe fatigue following COVID-19. METHODS: A multicenter, 2-arm randomized controlled trial was conducted in the Netherlands with patients being severely fatigued 3-12 months following COVID-19. Patients (N = 114) were randomly assigned (1:1) to CBT or care as usual (CAU). CBT, targeting perpetuating factors of fatigue, was provided for 17 weeks. The primary outcome was the overall mean difference between CBT and CAU on the fatigue severity subscale of the Checklist Individual Strength, directly post-CBT or CAU (T1), and after 6 months (T2). Secondary outcomes were differences in proportions of patients meeting criteria for severe and/or chronic fatigue, differences in physical and social functioning, somatic symptoms, and problems concentrating between CBT and CAU. RESULTS: Patients were mainly nonhospitalized and self-referred. Patients who received CBT were significantly less severely fatigued across follow-up assessments than patients receiving CAU (-8.8 [95% confidence interval {CI}, -11.9 to -5.8]); P < .001), representing a medium Cohen's d effect size (0.69). The between-group difference in fatigue severity was present at T1 (-9.3 [95% CI, -13.3 to -5.3]) and T2 (-8.4 [95% CI, -13.1 to -3.7]). All secondary outcomes favored CBT. Eight adverse events were recorded during CBT, and 20 during CAU. No serious adverse events were recorded. CONCLUSIONS: Among patients, who were mainly nonhospitalized and self-referred, CBT was effective in reducing fatigue. The positive effect was sustained at 6-month follow-up. CLINICAL TRIALS REGISTRATION: Netherlands Trial Register NL8947.

ATAGI Targeted Review 2021: the national COVID-19 vaccination program.

Abstract: The overarching goal of the Australian coronavirus disease 2019 (COVID-19) vaccination program has been to protect all people in Australia from the harm caused by the novel coronavirus SARS-CoV-2. This review reflects on the role of the Australian Technical Advisory Group on Immunisation (ATAGI) in the national COVID-19 vaccination program, in terms of the initial programmatic and clinical recommendations in the evolving context of evidence relating to the disease and vaccines, epidemiology, and the program rollout. To fulfil the obligation to provide evidence-based advice to the Minister for Health and Aged Care on the safe, effective and equitable use of COVID-19 vaccines, ATAGI has worked closely with other agencies and committees such as the Therapeutic Goods Administration (TGA) and the Communicable Diseases Network Australia. ATAGI recommendations have sought to optimise the use of the available vaccine doses in achieving the objectives of preventing serious illness and death from COVID-19 while addressing any emerging safety signals following program commencement on 22 February 2021. As of mid-November 2021, the use of COVID-19 vaccines in children aged 5 to 11 years was being considered by the TGA and ATAGI; and emerging evidence, in areas such as use of heterologous vaccine schedules and co-administration with other vaccines, was under review. Despite unprecedented challenges which the delivery of mass COVID-19 vaccination presented to health systems globally, in Australia much was achieved in 2021 with over 90% coverage for primary doses in the vaccine-eligible population. Evaluation, using high quality data and assessment methods, of vaccination program outcomes-such as coverage, vaccine effectiveness and impact-is key to determine whether program objectives have been achieved and where gaps remain. Reflecting on the lessons learned so far would help further improve the national COVID-19 vaccination program and would also benefit programs for other routine vaccines and planning for future pandemics.

Extensive genome analysis identifies novel plasmid families in Clostridium perfringens.

Globally, the anaerobic bacterium Clostridium perfringens causes severe disease in a wide array of hosts; however, C. perfringens strains are also carried asymptomatically. Accessory genes are responsible for much of the observed phenotypic variation and virulence within this species, with toxins frequently encoded on conjugative plasmids and many isolates carrying up to 10 plasmids. Despite this unusual biology, current genomic analyses have largely excluded isolates from healthy hosts or environmental sources. Accessory genomes, including plasmids, also have often been excluded from broader scale phylogenetic investigations. Here we interrogate a comprehensive collection of 464 C. perfringens genomes and identify the first putative non-conjugative enterotoxin (CPE)-encoding plasmids and a putative novel conjugative locus (Bcp) with sequence similarity to a locus reported from Clostridium botulinum. We sequenced and archived 102 new C. perfringens genomes, including those from rarely sequenced toxinotype B, C, D and E isolates. Long-read sequencing of 11 C. perfringens strains representing all toxinotypes (A-G) identified 55 plasmids from nine distinct plasmid groups. Interrogation of the 464 genomes in this collection identified 1045 plasmid-like contigs from the nine plasmid families, with a wide distribution across the C. perfringens isolates. Plasmids and plasmid diversity play an essential role in C. perfringens pathogenicity and broader biology. We have expanded the C. perfringens genome collection to include temporal, spatial and phenotypically diverse isolates including those carried asymptomatically in the gastrointestinal microbiome. This analysis has resulted in the identification of novel C. perfringens plasmids whilst providing a comprehensive understanding of species diversity.

Influenza-associated hospitalisation and mortality rates among global Indigenous populations; a systematic review and meta-analysis.

BACKGROUND: More than 50 million influenza infections and over 100,000 deaths from influenza occur annually. While Indigenous populations experience an inequitable influenza burden, the magnitude of this inequity has not previously been estimated on a global scale. This study compared rates of influenza-associated hospitalisation and mortality between Indigenous and non-Indigenous populations globally. METHODS: A systematic review and meta-analysis was conducted including literature published prior to 13 July 2021. Eligible articles either reported a rate ratio (RR) comparing laboratory-confirmed influenza-associated hospitalisation and/or mortality between an Indigenous population and a corresponding benchmark population, or reported sufficient information for this to be calculated using publicly available data. Findings were reported by country/region and pooled by country and period (pandemic/seasonal) when multiple studies were available using a random-effects model. The I2 statistic assessed variability between studies. RESULTS: Thirty-six studies (moderate/high quality) were included; all from high or high-middle income countries. The pooled influenza-associated hospitalisation RR (HRR) for indigenous compared to benchmark populations was 5·7 (95% CI: 2·7-12·0) for Canada, 5·2 (2.9-9.3) for New Zealand, and 5.2 (4.2-6.4) for Australia. Of the Australian studies, the pooled HRR for seasonal influenza was 3.1 (2·7-3·5) and for pandemic influenza was 6·2 (5·1-7·5). Heterogeneity was slightly higher among studies of pandemic influenza than seasonal influenza. The pooled mortality RR was 4.1 (3·0-5.7) in Australia and 3·3 (2.7-4.1) in the United States. CONCLUSIONS: Ethnic inequities in severe influenza persist and must be addressed by reducing disparities in the underlying determinants of health. Influenza surveillance systems worldwide should include Indigenous status to determine the extent of the disease burden among Indigenous populations. Ethnic inequities in pandemic influenza illustrate the need to prioritise Indigenous populations in pandemic response plans.