Now showing 1 - 10 of 35
  • Publication
    Published Erratum
    Correction: Preventing early childhood transmission of hepatitis B in remote Aboriginal communities in northern Australia.
    (2023-04-03)
    Sullivan RP
    ;
    ;
    Binks P
    ;
    McKinnon M
    ;
    Dhurrkay RG
    ;
    ;
    Bukulatjpi SM
    ;
    Locarnini S
    ;
    Littlejohn M
    ;
    Jackson K
    ;
    Tong STC
    ;
    Davis JS
      3267
  • Publication
    Journal Article
    Risk Factors for Nephrotoxicity in Methicillin-Resistant Staphylococcus aureus Bacteraemia: A Post Hoc Analysis of the CAMERA2 Trial.
    (2022-10-10)
    Legg A
    ;
    Meagher N
    ;
    Johnson SA
    ;
    Roberts MA
    ;
    Cass A
    ;
    Scheetz MH
    ;
    ;
    Roberts JA
    ;
    Davis JS
    ;
    Tong SYC
    BACKGROUND: Clinical risk factors for nephrotoxicity in Staphylococcus aureus bacteraemia remain largely undetermined, despite its common occurrence and clinical significance. In an international, multicentre, prospective clinical trial (CAMERA2), which compared standard therapy (vancomycin monotherapy) to combination therapy (adding an anti-staphylococcal beta-lactam) for methicillin-resistant S. aureus bacteraemia, significantly more people in the combination therapy arm experienced acute kidney injury compared with those in the monotherapy arm (23% vs 6%). OBJECTIVE: The aim of this post hoc analysis was to explore in greater depth the risk factors for acute kidney injury from the CAMERA2 trial. METHODS: Among participants of the CAMERA2 trial, demographic-related, infection-related and treatment-related risk factors were assessed for their relationship with acute kidney injury by univariable and multivariable logistic regression. Acute kidney injury was defined by a modified-KDIGO (Kidney Disease: Improving Global Outcomes) criteria (not including urinary output). RESULTS: Of the 266 participants included, age (p = 0.04), randomisation to combination therapy (p = 0.002), vancomycin area under the concentration-time curve (p = 0.03) and receipt of (flu)cloxacillin as the companion beta-lactam (p < 0.001) were significantly associated with acute kidney injury. On a multivariable analysis, concurrent use of (flu)cloxacillin increased the risk of acute kidney injury over four times compared with the use of cefazolin or no beta-lactam. The association of vancomycin area under the concentration-time curve with acute kidney injury also persisted in the multivariable model. CONCLUSIONS: For participants receiving vancomycin for S. aureus bacteraemia, use of (flu)cloxacillin and increased vancomycin area under the concentration-time curve were risk factors for acute kidney injury. These represent potentially modifiable risk factors for nephrotoxicity and highlight the importance of avoiding the use of concurrent nephrotoxins.
      4796
  • Publication
    Evaluation Study
    Impact of results of a rapid Staphylococcus aureus diagnostic test on prescribing of antibiotics for patients with clustered gram-positive cocci in blood cultures.
    (2012-06) ;
    Gordon CL
    ;
    Tong SYC
    ;
    ;
    Davis JS
    In tropical northern Australia, approximately 20% of Staphylococcus aureus bacteremia is caused by methicillin-resistant Staphylococcus aureus (MRSA). We prospectively evaluated the impact on clinician antibiotic prescribing of the results obtained from performing the GeneXpert MRSA/SA test on 151 positive blood cultures with clustered gram-positive cocci. The GeneXpert result led to earlier appropriate prescription of vancomycin for 54% of patients with MRSA; 25% of patients avoided vancomycin, and 16% of patients had all antibiotics ceased.
      1358
  • Publication
    Journal Article
    Establishing contemporary trends in hepatitis B sero-epidemiology in an Indigenous population.
    (2017) ; ;
    Tong SYC
    ;
    ;
    Beaman M
    ;
    Higgins G
    ;
    Cowie BC
    ;
    Condon JR
    ;
    Davis JS
    Indigenous populations globally are disproportionately affected by chronic hepatitis B virus (HBV) infection however contemporary sero-prevalence data are often absent. In the Indigenous population of the Northern Territory (NT) of Australia the unique C4 sub-genotype of HBV universally circulates. There are no studies of the sero-prevalence, nor the impact of the vaccination program (which has a serotype mismatch compared to C4), at a population-wide level. We examined all available HBV serology results obtained from the three main laboratories serving NT residents between 1991 and 2011. Data were linked with a NT government database to determine Indigenous status and the most recent test results for each individual were extracted as a cross-sectional database including 88,112 unique individuals. The primary aim was to obtain a contemporary estimate of HBsAg positivity for the NT by Indigenous status. Based on all tests from 2007-2011 (35,633 individuals), hepatitis B surface antigen (HBsAg) positivity was 3·40% (95%CI 3·19-3·61), being higher in Indigenous (6·08%[5·65%-6·53%]) than non-Indigenous (1·56%[1·38%-1·76%]) Australians, p<0·0001. Birth cohort analysis showed HBsAg positivity fell over time for Indigenous people, with this decrease commencing prior to universal infant vaccination (which commenced in 1990), with an ongoing but slower rate of decline since 1990, (0·23% decrease per year versus 0·17%). HBsAg positivity is high in the NT, particularly in the Indigenous population. HBsAg positivity has fallen over time but a substantial part of this decrease is due to factors other than the universal vaccination program.
      1530
  • Publication
    Journal Article
    The Darwin Prospective Melioidosis Study: a 30-year prospective, observational investigation.
    (2021-12) ;
    Mayo M
    ;
    Ward LM
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    Kaestli M
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    Webb JR
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    Woerle C
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    ; ; ; ; ; ;
    Huffam SE
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    Janson S
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    ; ; ;
    BACKGROUND: The global distribution of melioidosis is under considerable scrutiny, with both unmasking of endemic disease in African and Pacific nations and evidence of more recent dispersal in the Americas. Because of the high incidence of disease in tropical northern Australia, The Darwin Prospective Melioidosis Study commenced in October, 1989. We present epidemiology, clinical features, outcomes, and bacterial genomics from this 30-year study, highlighting changes in the past decade. METHODS: The present study was a prospective analysis of epidemiological, clinical, and laboratory data for all culture-confirmed melioidosis cases from the tropical Northern Territory of Australia from Oct 1, 1989, until Sept 30, 2019. Cases were identified on the basis of culture-confirmed melioidosis, a laboratory-notifiable disease in the Northern Territory of Australia. Patients who were culture-positive were included in the study. Multivariable analysis determined predictors of clinical presentations and outcome. Incidence, survival, and cluster analyses were facilitated by population and rainfall data and genotyping of Burkholderia pseudomallei, including multilocus sequence typing and whole-genome sequencing. FINDINGS: There were 1148 individuals with culture-confirmed melioidosis, of whom 133 (12%) died. Median age was 50 years (IQR 38-60), 48 (4%) study participants were children younger than 15 years of age, 721 (63%) were male individuals, and 600 (52%) Indigenous Australians. All but 186 (16%) had clinical risk factors, 513 (45%) had diabetes, and 455 (40%) hazardous alcohol use. Only three (2%) of 133 fatalities had no identified risk. Pneumonia was the most common presentation occurring in 595 (52%) patients. Bacteraemia occurred in 633 (56%) of 1135 patients, septic shock in 240 (21%) patients, and 180 (16%) patients required mechanical ventilation. Cases correlated with rainfall, with 80% of infections occurring during the wet season (November to April). Median annual incidence was 20·5 cases per 100 000 people; the highest annual incidence in Indigenous Australians was 103·6 per 100 000 in 2011-12. Over the 30 years, annual incidences increased, as did the proportion of patients with diabetes, although mortality decreased to 17 (6%) of 278 patients over the past 5 years. Genotyping of B pseudomallei confirmed case clusters linked to environmental sources and defined evolving and new sequence types. INTERPRETATION: Melioidosis is an opportunistic infection with a diverse spectrum of clinical presentations and severity. With early diagnosis, specific antimicrobial therapy, and state-of-the-art intensive care, mortality can be reduced to less than 10%. However, mortality remains much higher in the many endemic regions where health resources remain scarce. Genotyping of B pseudomallei informs evolving local and global epidemiology. FUNDING: The Australian National Health and Medical Research Council.
      2062
  • Publication
    Journal Article
    Molecular epidemiology of hepatitis B in the Indigenous people of northern Australia.
    (2013-07-01) ;
    Littlejohn, Margaret
    ;
    Locarnini, Stephen A
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    Whiting, Sarah
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    Hajkowicz, Krispin
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    Cowie, Benjamin C
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    Bowden, David S
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    Tong, Steven Y C
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    Davis, Joshua S
    BACKGROUND AND AIM: The hepatitis B surface antigen was first described in the blood of an Indigenous Australian man, yet little is known about its molecular epidemiology in this population, in which it is endemic. The study aimed to determine the clinical and molecular epidemiology of hepatitis B virus (HBV) in Indigenous people from northern Australia. METHODS: Following ethics approval and informed consent, blood specimens and clinical details from Indigenous adults known to be infected with HBV and who were born and raised in Indigenous communities in northern Australia were obtained. HBV genotypes were determined in isolates with sufficient HBV DNA by polymerase chain reaction by sequencing of the polymerase/surface gene. RESULTS: Between June 2010 and June 2012, 65 patients were recruited from six different regions of northern Australia. Thirty-two patients (49%) were hepatitis B e-antigen-positive, and 48% were hepatitis B e-antibody-positive. No patients were found to be coinfected with hepatitis C virus or human immunodeficiency virus. Of the 49 samples with sufficient viral load for genotyping, 100% were infected with genotype C4, previously only reported from two Indigenous Australians. All isolates had wild-type polymerase gene sequences despite 14 currently or previously receiving antiviral treatment. The canonical sG145R vaccine-escape variant was detected in the surface antigen of virus from two patients. CONCLUSIONS: The exclusive HBV genotype in this ancient population is genotype C4. Whole genome sequencing and clinical follow-up of this cohort are in progress, with the aim of exploring the clinical significance of these findings.
      328
  • Publication
    Journal Article
    "Putting the power back into community": A mixed methods evaluation of a chronic hepatitis B training course for the Aboriginal health workforce of Australia's Northern Territory.
    (2024-01-24) ; ;
    Vintour-Cesar, Emily
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    Wilson, Phillip Merrdi
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    Bunn, Linda
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    Garambaka Gurruwiwi, George
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    Wurrawilya, Shiraline
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    Bukulatjpi, Sarah Mariyalawuy
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    Nelson, Sandra
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    Ross, Cheryl
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    Stuart-Carter, Kelly-Anne
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    Ngurruwuthun, Terese
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    Dhagapan, Amanda
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    Binks, Paula
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    Sullivan, Richard
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    Ward, Linda
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    Schroder, Phoebe
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    Tate-Baker, Jaclyn
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    Davis, Joshua S
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    BACKGROUND: Chronic hepatitis B (CHB) is endemic in the Aboriginal and Torres Strait Islander population of Australia's Northern Territory. Progression to liver disease can be prevented if holistic care is provided. Low health literacy amongst health professionals is a known barrier to caring for people living with CHB. We co-designed and delivered a culturally safe "Managing hepatitis B" training course for the Aboriginal health workforce. Here, we present an evaluation of the course. OBJECTIVES: 1. To improve course participants CHB-related knowledge, attitudes, and clinical practice. 2. To evaluate the "Managing hepatitis B" training course. 3. To enable participants to have the skills and confidence to be part of the care team. METHODS: We used participatory action research and culturally safe principles. We used purpose-built quantitative and qualitative evaluation tools to evaluate our "Managing hepatitis B" training course. We integrated the two forms of data, deductively analysing codes, grouped into categories, and assessed pedagogical outcomes against Kirkpatrick's training evaluation framework. RESULTS: Eight courses were delivered between 2019 and 2023, with 130 participants from 32 communities. Pre- and post-course questionnaires demonstrated statistically significant improvements in all domains, p<0.001 on 93 matched pairs. Thematic network analysis demonstrated high levels of course acceptability and significant knowledge acquisition. Other themes identified include cultural safety, shame, previous misinformation, and misconceptions about transmission. Observations demonstrate improvements in post-course engagement, a deep understanding of CHB as well as increased participation in clinical care teams. CONCLUSIONS: The "Managing hepatitis B" training course led to a sustained improvement in the knowledge and attitudes of the Aboriginal health workforce, resulting in improved care and treatment uptake for people living with CHB. Important non-clinical outcomes included strengthening teaching and leadership skills, and empowerment.
      1338
  • Publication
    Published Erratum
    Correction to: Risk Factors for Nephrotoxicity in Methicillin-Resistant Staphylococcus aureus Bacteraemia: A Post Hoc Analysis of the CAMERA2 Trial.
    (2022-11-19)
    Legg A
    ;
    Meagher N
    ;
    Johnson SA
    ;
    Roberts MA
    ;
    Cass A
    ;
    Scheetz MH
    ;
    ;
    Roberts JA
    ;
    Davis JS
    ;
    Tong SYC
      1956
  • Publication
    Journal Article
    Robust and prototypical immune responses toward COVID-19 vaccine in First Nations peoples are impacted by comorbidities.
    (2023-06)
    Zhang, W
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    Kedzierski, L
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    Chua, B
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    Mayo, M
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    Lonzi, C
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    Rigas, V
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    McQuilten, H
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    Rowntree, L
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    Allen, L
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    Purcell, R
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    Tan, H
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    Petersen, J
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    Chaurasia, P
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    Mordant, F
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    Pogorelyy, M
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    Minervina, A
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    Crawford, J
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    Perkins, G
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    Zhang, E
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    Gras, S
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    Clemens, E
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    Juno, J
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    Audsley, J
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    Khoury, D
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    Holmes, N
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    Thevarajan, I
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    Subbarao, K
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    Krammer, F
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    Cheng, A
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    Davenport, M
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    Grubor-Bauk, B
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    Coates, P
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    Christensen, B
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    Thomas, P
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    Wheatley, A
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    Kent, S
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    Rossjohn, J
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    Chung, A
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    Boffa, J
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    Miller, A
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    Nelson, J
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    Nguyen, T
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    Kedzierska, K
    High-risk groups, including Indigenous people, are at risk of severe COVID-19. Here we found that Australian First Nations peoples elicit effective immune responses to COVID-19 BNT162b2 vaccination, including neutralizing antibodies, receptor-binding domain (RBD) antibodies, SARS-CoV-2 spike-specific B cells, and CD4(+) and CD8(+) T cells. In First Nations participants, RBD IgG antibody titers were correlated with body mass index and negatively correlated with age. Reduced RBD antibodies, spike-specific B cells and follicular helper T cells were found in vaccinated participants with chronic conditions (diabetes, renal disease) and were strongly associated with altered glycosylation of IgG and increased interleukin-18 levels in the plasma. These immune perturbations were also found in non-Indigenous people with comorbidities, indicating that they were related to comorbidities rather than ethnicity. However, our study is of a great importance to First Nations peoples who have disproportionate rates of chronic comorbidities and provides evidence of robust immune responses after COVID-19 vaccination in Indigenous people.
      5716