The effectiveness of maternal pertussis vaccination for protecting Aboriginal and Torres Strait Islander infants against infection, 2012-2017: a retrospective cohort study.

OBJECTIVES: To evaluate the effectiveness of maternal pertussis vaccination for preventing pertussis infections in Aboriginal and Torres Strait Islander infants under seven months of age. STUDY DESIGN: Retrospective cohort study; analysis of linked administrative health data. SETTING, PARTICIPANTS: Mother-infant cohort (Links2HealthierBubs) including all pregnant women who gave birth to live infants (gestational age ≥ 20 weeks, birthweight ≥ 400 g) in the Northern Territory, Queensland, and Western Australia during 1 January 2012 - 31 December 2017. MAIN OUTCOME MEASURES: Proportions of women vaccinated against pertussis during pregnancy, rates of pertussis infections among infants under seven months of age, and estimated effectiveness of maternal vaccination for protecting infants against pertussis infection, each by Indigenous status. RESULTS: Of the 19 892 Aboriginal and Torres Strait Islander women who gave birth to live infants during 2012-2017, 7398 (37.2%) received pertussis vaccine doses during their pregnancy, as had 137 034 of 259 526 non-Indigenous women (52.8%; Indigenous v non-Indigenous: adjusted odds ratio, 0.66; 95% confidence interval [CI], 0.62-0.70). The annual incidence of notified pertussis infections in non-Indigenous infants declined from 16.8 (95% CI, 9.9-29) in 2012 to 1.4 (95% CI, 0.3-8.0) cases per 10 000 births in 2017; among Aboriginal and Torres Strait Islander infants, it declined from 47.6 (95% CI, 16.2-139) to 38.6 (95% CI, 10.6-140) cases per 10 000 births. The effectiveness of maternal vaccination for protecting non-Indigenous infants under seven months of age against pertussis infection during 2014-17 was 68.2% (95% CI, 51.8-79.0%); protection of Aboriginal and Torres Strait Islander infants was not statistically significant (36.1%; 95% CI, -41.3% to 71.1%). CONCLUSIONS: During 2015-17, maternal pertussis vaccination did not protect Aboriginal and Torres Strait Islander infants in the NT, Queensland, and WA against infection. Increasing the pertussis vaccination rate among pregnant Aboriginal and Torres Strait Islander women requires culturally appropriate, innovative strategies co-designed in partnership with Indigenous organisations and communities.

Genome-Wide Analysis of Genetic Risk Factors for Rheumatic Heart Disease in Aboriginal Australians Provides Support for Pathogenic Molecular Mimicry.

Background: Rheumatic heart disease (RHD) after group A streptococcus (GAS) infections is heritable and prevalent in Indigenous populations. Molecular mimicry between human and GAS proteins triggers proinflammatory cardiac valve-reactive T cells. Methods: Genome-wide genetic analysis was undertaken in 1263 Aboriginal Australians (398 RHD cases; 865 controls). Single-nucleotide polymorphisms were genotyped using Illumina HumanCoreExome BeadChips. Direct typing and imputation was used to fine-map the human leukocyte antigen (HLA) region. Epitope binding affinities were mapped for human cross-reactive GAS proteins, including M5 and M6. Results: The strongest genetic association was intronic to HLA-DQA1 (rs9272622; P = 1.86 × 10-7). Conditional analyses showed rs9272622 and/or DQA1*AA16 account for the HLA signal. HLA-DQA1*0101_DQB1*0503 (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.09-1.90; P = 9.56 × 10-3) and HLA-DQA1*0103_DQB1*0601 (OR, 1.27; 95% CI, 1.07-1.52; P = 7.15 × 10-3) were risk haplotypes; HLA_DQA1*0301-DQB1*0402 (OR 0.30, 95%CI 0.14-0.65, P = 2.36 × 10-3) was protective. Human myosin cross-reactive N-terminal and B repeat epitopes of GAS M5/M6 bind with higher affinity to DQA1/DQB1 alpha/beta dimers for the 2-risk haplotypes than the protective haplotype. Conclusions: Variation at HLA_DQA1-DQB1 is the major genetic risk factor for RHD in Aboriginal Australians studied here. Cross-reactive epitopes bind with higher affinity to alpha/beta dimers formed by risk haplotypes, supporting molecular mimicry as the key mechanism of RHD pathogenesis.

Mobile phones support adherence and retention of indigenous participants in a randomised controlled trial: strategies and lessons learnt.

BACKGROUND: Ensuring adherence to treatment and retention is important in clinical trials, particularly in remote areas and minority groups. We describe a novel approach to improve adherence, retention and clinical review rates of Indigenous children. METHODS: This descriptive study was nested within a placebo-controlled, randomised trial (RCT) on weekly azithromycin (or placebo) for 3-weeks. Indigenous children aged ≤24-months hospitalised with acute bronchiolitis were recruited from two tertiary hospitals in northern Australia (Darwin and Townsville). Using mobile phones embedded within a culturally-sensitive approach and framework, we report our strategies used and results obtained. Our main outcome measure was rates of adherence to medications, retention in the RCT and self-presentation (with child) to clinic for a clinical review on day-21. RESULTS: Of 301 eligible children, 76 (21%) families declined participation and 39 (13%) did not have access to a mobile phone. 186 Indigenous children were randomised and received dose one under supervision in hospital. Subsequently, 182 (99%) children received dose two (day-7), 169 (93%) dose three (day-14) and 180 (97%) attended their clinical review (day-21). A median of 2 calls (IQR 1-3) were needed to verify adherence. Importantly, over 97% of children remained in the RCT until their clinical endpoint at day-21. CONCLUSIONS: In our setting, the use of mobile phones within an Indigenous-appropriate framework has been an effective strategy to support a clinical trial involving Australian Indigenous children in urban and remote Australia. Further research is required to explore other applications of this approach, including the impact on clinical outcomes. TRIAL REGISTRATION: ACTRN12608000150347 (RCT component).

Health professionals' perceptions about the adoption of existing guidelines for the diagnosis of fetal alcohol spectrum disorders in Australia.

BACKGROUND: Despite the availability of five guidelines for the diagnosis of fetal alcohol spectrum disorders (FASD), there is no national endorsement for their use in diagnosis in Australia. In this study we aimed to describe health professionals' perceptions about the adoption of existing guidelines for the diagnosis of FASD in Australia and identify implications for the development of national guidelines. METHODS: We surveyed 130 Australian and 9 international health professionals with expertise or involvement in the screening or diagnosis of FASD. An online questionnaire was used to evaluate participants' familiarity with and use of five existing diagnostic guidelines for FASD, and to assess their perceptions about the adoption of these guidelines in Australia. RESULTS: Of the 139 participants surveyed, 84 Australian and 8 international health professionals (66.2%) responded to the questions on existing diagnostic guidelines. Participants most frequently reported using the University of Washington 4-Digit Diagnostic Code (27.2%) and the Canadian guidelines (18.5%) for diagnosis. These two guidelines were also most frequently recommended for adoption in Australia: 32.5% of the 40 participants who were familiar with the University of Washington 4-Digit Diagnostic Code recommended adoption of this guideline in Australia, and 30.8% of the 26 participants who were familiar with the Canadian guidelines recommended adoption of this guideline in Australia. However, for the majority of guidelines examined, most participants were unsure whether they should be adopted in Australia. The adoption of existing guidelines in Australia was perceived to be limited by: their lack of evidence base, including the appropriateness of established reference standards for the Australian population; their complexity; the need for training and support to use the guidelines; and the lack of an interdisciplinary and interagency model to support service delivery in Australia. CONCLUSIONS: Participants indicated some support for the adoption of the University of Washington or Canadian guidelines for FASD diagnosis; however, concerns were raised about the adoption of these diagnostic guidelines in their current form. Australian diagnostic guidelines will require evaluation to establish their validity in the Australian context, and a comprehensive implementation model is needed to facilitate improved diagnostic capacity in Australia.

Researchers' experience with project management in health and medical research: results from a post-project review.

BACKGROUND: Project management is widely used to deliver projects on time, within budget and of defined quality. However, there is little published information describing its use in managing health and medical research projects. We used project management in the Alcohol and Pregnancy Project (2006-2008) http://www.ichr.uwa.edu.au/alcoholandpregnancy and in this paper report researchers' opinions on project management and whether it made a difference to the project. METHODS: A national interdisciplinary group of 20 researchers, one of whom was the project manager, formed the Steering Committee for the project. We used project management to ensure project outputs and outcomes were achieved and all aspects of the project were planned, implemented, monitored and controlled. Sixteen of the researchers were asked to complete a self administered questionnaire for a post-project review. RESULTS: The project was delivered according to the project protocol within the allocated budget and time frame. Fifteen researchers (93.8%) completed a questionnaire. They reported that project management increased the effectiveness of the project, communication, teamwork, and application of the interdisciplinary group of researchers' expertise. They would recommend this type of project management for future projects. CONCLUSIONS: Our post-project review showed that researchers comprehensively endorsed project management in the Alcohol and Pregnancy Project and agreed that project management had contributed substantially to the research. In future, we will project manage new projects and conduct post-project reviews. The results will be used to encourage continuous learning and continuous improvement of project management, and provide greater transparency and accountability of health and medical research. The use of project management can benefit both management and scientific outcomes of health and medical research projects.

Paediatricians' knowledge, attitudes and practice following provision of educational resources about prevention of prenatal alcohol exposure and Fetal Alcohol Spectrum Disorder.

AIM: The study aims to provide paediatricians in Western Australia (WA) with educational resources (http://www.ichr.uwa.edu.au/alcoholandpregnancy) about the prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder, and assess changes in their knowledge, attitudes and practice about fetal alcohol syndrome (FAS) and alcohol consumption in pregnancy. METHODS: Following our 2004 survey of paediatricians, we developed and distributed educational resources to 159 paediatricians in WA in 2007. Six months later, we surveyed these paediatricians and compared their responses with results from 2004 using prevalence rate ratios (PRRs) and 95% confidence intervals (CIs). RESULTS: Of 133 eligible paediatricians, 82 (61.7%) responded: 65.9% had seen the resources, of these 66.7% had used them and 29.6% said the resources had helped them change, or influenced their intent to change, their practice. There was no change in the proportion that knew all the essential features of FAS (18.3% in 2007; 20.0% in 2004) or had diagnosed FAS (58.5% in 2007; 58.9% in 2004). An increased proportion (75.6% in 2007; 48.9% in 2004) agreed that pregnant women should completely abstain from consuming alcohol (PRR 1.55, 95% CI 1.21-1.97). Only 21.7% (no increase from 2004) routinely asked about alcohol use when taking a pregnancy history. CONCLUSIONS: We recommend that asking about alcohol use during pregnancy should be emphasised in paediatric training. Unless paediatricians' capacity to ask about alcohol consumption when taking a pregnancy history and to diagnose FAS is increased, FAS will remain under-diagnosed in Australia and opportunities for management, early intervention and prevention will be overlooked.

Collaborating with consumer and community representatives in health and medical research in Australia: results from an evaluation.

OBJECTIVE: To collaborate with consumer and community representatives in the Alcohol and Pregnancy Project from 2006-2008 http://www.ichr.uwa.edu.au/alcoholandpregnancy and evaluate researchers' and consumer and community representatives' perceptions of the process, context and impact of consumer and community participation in the project. METHODS: We formed two reference groups and sought consumer and community representatives' perspectives on all aspects of the project over a three year period. We developed an evaluation framework and asked consumer and community representatives and researchers to complete a self-administered questionnaire at the end of the project. RESULTS: Fifteen researchers (93.8%) and seven (53.8%) consumer and community representatives completed a questionnaire. Most consumer and community representatives agreed that the process and context measures of their participation had been achieved. Both researchers and consumer and community representatives identified areas for improvement and offered suggestions how these could be improved for future research. Researchers thought consumer and community participation contributed to project outputs and outcomes by enhancing scientific and ethical standards, providing legitimacy and authority, and increasing the project's credibility and participation. They saw it was fundamental to the research process and acknowledged consumer and community representatives for their excellent contribution. Consumer and community representatives were able to directly influence decisions about the research. They thought that consumer and community participation had significant influence on the success of project outputs and outcomes. CONCLUSIONS: Consumer and community participation is an essential component of good research practice and contributed to the Alcohol and Pregnancy Project by enhancing research processes, outputs and outcomes, and this participation was valued by community and consumer representatives and researchers. The National Health and Medical Research Council in Australia expects researchers to work in partnership and involve consumer and community representatives in health and medical research, and to evaluate community and consumer participation. It is important to demonstrate whether consumer and community participation makes a difference to health and medical research.

Reference exome data for Australian Aboriginal populations to support health-based research.

Whole exome sequencing (WES) is a popular and successful technology which is widely used in both research and clinical settings. However, there is a paucity of reference data for Aboriginal Australians to underpin the translation of health-based genomic research. Here we provide a catalogue of variants called after sequencing the exomes of 50 Aboriginal individuals from the Northern Territory (NT) of Australia and compare these to 72 previously published exomes from a Western Australian (WA) population of Martu origin. Sequence data for both NT and WA samples were processed using an 'intersect-then-combine' (ITC) approach, using GATK and SAMtools to call variants. A total of 289,829 variants were identified in at least one individual in the NT cohort and 248,374 variants in at least one individual in the WA cohort. Of these, 166,719 variants were present in both cohorts, whilst 123,110 variants were private to the NT cohort and 81,655 were private to the WA cohort. Our data set provides a useful reference point for genomic studies on Aboriginal Australians.

'Links2HealthierBubs' cohort study: protocol for a record linkage study on the safety, uptake and effectiveness of influenza and pertussis vaccines among pregnant Australian women.

INTRODUCTION: Pregnant women and infants are at risk of severe influenza and pertussis infection. Inactivated influenza vaccine (IIV) and diphtheria-tetanus-acellular pertussis vaccine (dTpa) are recommended during pregnancy to protect both mothers and infants. In Australia, uptake is not routinely monitored but coverage appears sub-optimal. Evidence on the safety of combined antenatal IIV and dTpa is fragmented or deficient, and there remain knowledge gaps of population-level vaccine effectiveness. We aim to establish a large, population-based, multi-jurisdictional cohort of mother-infant pairs to measure the uptake, safety and effectiveness of antenatal IIV and dTpa vaccines in three Australian jurisdictions. This is a first step toward assessing the impact of antenatal vaccination programmes in Australia, which can then inform government policy with respect to future strategies in national vaccination programmes. METHODS AND ANALYSIS: 'Links2HealthierBubs' is an observational, population-based, retrospective cohort study established through probabilistic record linkage of administrative health data. The cohort includes births between 2012 and 2017 (~607 605 mother-infant pairs) in jurisdictions with population-level antenatal vaccination and health outcome data (Western Australia, Queensland and the Northern Territory). Perinatal data will be the reference frame to identify the cohort. Jurisdictional vaccination registers will identify antenatal vaccination status and the gestational timing of vaccination. Information on maternal, fetal and child health outcomes will be obtained from hospitalisation and emergency department records, notifiable diseases databases, developmental anomalies databases, birth and mortality registers. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Western Australian Department of Health, Curtin University, the Menzies School of Health Research, the Royal Brisbane and Women's Hospital, and the West Australian Aboriginal Health Ethics Committees. Research findings will be disseminated in peer-reviewed journals, at scientific meetings, and may be incorporated into communication materials for public health agencies and the public.

Research protocol for the Picture Talk Project: a qualitative study on research and consent with remote Australian Aboriginal communities.

INTRODUCTION: Research with Indigenous populations is not always designed with cultural sensitivity. Few publications evaluate or describe in detail seeking consent for research with Indigenous participants. When potential participants are not engaged in a culturally respectful manner, participation rates and research quality can be adversely affected. It is unethical to proceed with research without truly informed consent. METHODS AND ANALYSIS: We describe a culturally appropriate research protocol that is invited by Aboriginal communities of the Fitzroy Valley in Western Australia. The Picture Talk Project is a research partnership with local Aboriginal leaders who are also chief investigators. We will interview Aboriginal leaders about research, community engagement and the consent process and hold focus groups with Aboriginal community members about individual consent. Cultural protocols will be applied to recruit and conduct research with participants. Transcripts will be analysed using NVivo10 qualitative software and themes synthesised to highlight the key issues raised by the community about the research process. This protocol will guide future research with the Aboriginal communities of the Fitzroy Valley and may inform the approach to research with other Indigenous communities of Australia or the world. It must be noted that no community is the same and all research requires local consultation and input. To conduct culturally sensitive research, respected local people from the community who have knowledge of cultural protocol and language are engaged to guide each step of the research process from the project design to the delivery of results. ETHICS AND DISSEMINATION: Ethics approval was granted by the University of Sydney Human Research Ethics Committee (No. 2012/348, reference:14760), the Western Australia Country Health Service Ethics Committee (No. 2012:15), the Western Australian Aboriginal Health Ethics Committee and reviewed by the Kimberley Aboriginal Health Planning Forum Research Sub-Committee (No. 2012-008). Results will be disseminated through peer review articles, a local Fitzroy Valley report and conference presentations.

Consensus diagnostic criteria for fetal alcohol spectrum disorders in Australia: a modified Delphi study.

OBJECTIVE: To evaluate health professionals' agreement with components of published diagnostic criteria for fetal alcohol spectrum disorders (FASD) in order to guide the development of standard diagnostic guidelines for Australia. DESIGN: A modified Delphi process was used to assess agreement among health professionals with expertise or experience in FASD screening or diagnosis. An online survey, which included 36 Likert statements on diagnostic methods, was administered over two survey rounds. For fetal alcohol syndrome (FAS), health professionals were presented with concepts from the Institute of Medicine (IOM), University of Washington (UW), Centers for Disease Control (CDC), revised IOM and Canadian diagnostic criteria. For partial FAS (PFAS), alcohol-related neurodevelopmental disorder (ARND), and alcohol-related birth defects (ARBD), concepts based on the IOM and the Canadian diagnostic criteria were compared. SETTING/PARTICIPANTS: 130 Australian and 9 international health professionals. RESULTS: Of 139 health professionals invited to complete the survey, 103 (74.1%) responded, and 74 (53.2%) completed one or more questions on diagnostic criteria. We found consensus agreement among participants on the diagnostic criteria for FAS, with the UW criteria most commonly endorsed when compared with all other published criteria for FAS. When health professionals were presented with concepts based on the Canadian and IOM diagnostic criteria, we found consensus agreement but no clear preference for either the Canadian or IOM criteria for the diagnosis of PFAS, and no consensus agreement on diagnostic criteria for ARND. We also found no consensus on the IOM diagnostic criteria for ARBD. CONCLUSIONS: Participants indicated clear support for use of the UW diagnostic criteria for FAS in Australia. These findings should be used to develop guidelines to facilitate improved awareness of, and address identified gaps in the infrastructure for, FASD diagnosis in Australia.

RE-AIM evaluation of the Alcohol and Pregnancy Project: educational resources to inform health professionals about prenatal alcohol exposure and fetal alcohol spectrum disorder.

The objective was to evaluate the Alcohol and Pregnancy Project that provided health professionals in Western Australia (WA) with educational resources to inform them about prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder (FASD). The authors developed, produced, and distributed educational resources to 3,348 health professionals in WA. Six months later, they surveyed 1,483 of these health professionals. The authors used the RE-AIM framework (reach, effectiveness, adoption, implementation, and maintenance) to evaluate the project. The educational resources were effective in producing a 31% increase in the proportion of health professionals who routinely provided pregnant women with information about the consequences of drinking alcohol during pregnancy. One hundred percent of the settings adopted the project, it reached 96.3% of the target population, it was implemented as intended, and the resources were maintained (http://www.ichr.uwa.edu.au/alcoholandpregnancy). The educational resources for health professionals have potential to contribute to reducing prenatal alcohol exposure and FASD.

"Mutual" obligation in Indigenous health: can shared responsibility agreements be truly mutual?

Shared responsibility agreements between the Australian Government and Indigenous communities are based on a concept of mutual obligation but have overtones of paternalism and imposition. The nature and extent of choice in any such agreements need to be established.