Now showing 1 - 10 of 37
  • Publication
    Journal Article
    Hepatitis C Virus Antiviral Drug Resistance and Salvage Therapy Outcomes Across Australia.
    (2024-03-31)
    Wang, Dao Sen
    ;
    Phu, Amy
    ;
    McKee, Kristen
    ;
    Strasser, Simone I
    ;
    Sheils, Sinead
    ;
    Weltman, Martin
    ;
    Sellar, Sue
    ;
    Davis, Joshua S
    ;
    Young, Mel
    ;
    Braund, Alicia
    ;
    Farrell, Geoffrey C
    ;
    Blunn, Anne
    ;
    Harding, Damian
    ;
    Ralton, Lucy
    ;
    Muller, Kate
    ;
    Davison, Scott A
    ;
    Shaw, David
    ;
    Wood, Marnie
    ;
    Hajkowicz, Krispin
    ;
    Skolen, Richard
    ;
    ; ;
    Doyle, Adam
    ;
    Tuma, Rhoda
    ;
    Hazeldine, Simon
    ;
    Lam, Wendy
    ;
    Edmiston, Natalie
    ;
    Zohrab, Krista
    ;
    Pratt, William
    ;
    Watson, Belinda
    ;
    Zekry, Amany
    ;
    Stephens, Carlie
    ;
    Clark, Paul J
    ;
    Day, Melany
    ;
    Park, Gordon
    ;
    Kim, Hami
    ;
    Wilson, Mark
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    McGarity, Bruce
    ;
    Menzies, Natalie
    ;
    Russell, Darren
    ;
    Lam, Thao
    ;
    Boyd, Peter
    ;
    Kok, Jen
    ;
    George, Jacob
    ;
    Douglas, Mark W
    Hepatitis C virus (HCV) infection can now be cured with well-tolerated direct-acting antiviral (DAA) therapy. However, a potential barrier to HCV elimination is the emergence of resistance-associated substitutions (RASs) that reduce the efficacy of antiviral drugs, but real-world studies assessing the clinical impact of RASs are limited. Here, an analysis of the impact of RASs on retreatment outcomes for different salvage regimens in patients nationally who failed first-line DAA therapy is reported.We collected data from 363 Australian patients who failed first-line DAA therapy, including: age, sex, fibrosis stage, HCV genotype, NS3/NS5A/NS5B RASs, details of failed first-line regimen, subsequent salvage regimens, and treatment outcome.Of 240 patients who were initially retreated as per protocol, 210 (87.5%) achieved sustained virologic response (SVR) and 30 (12.5%) relapsed or did not respond. The SVR rate for salvage regimens that included sofosbuvir/velpatasvir/voxilaprevir was 94.3% (n = 140), sofosbuvir/velpatasvir 75.0% (n = 52), elbasvir/grazoprevir 81.6% (n = 38), and glecaprevir/pibrentasvir 84.6% (n = 13). NS5A RASs were present in 71.0% (n = 210) of patients who achieved SVR and in 66.7% (n = 30) of patients who subsequently relapsed. NS3 RASs were detected in 20 patients (20%) in the SVR group and 1 patient in the relapse group. NS5B RASs were observed in only 3 patients. Cirrhosis was a predictor of relapse after retreatment, as was previous treatment with sofosbuvir/velpatasvir.In our cohort, the SVR rate for sofosbuvir/velpatasvir/voxilaprevir was higher than with other salvage regimens. The presence of NS5A, NS5B, or NS3 RASs did not appear to negatively influence retreatment outcomes.
  • 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
    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
    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
    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
    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
    Molecular epidemiology of hepatitis B in the Indigenous people of northern Australia.
    (2013-07-01) ;
    Littlejohn, Margaret
    ;
    Locarnini, Stephen A
    ;
    Whiting, Sarah
    ;
    Hajkowicz, Krispin
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    Cowie, Benjamin C
    ;
    Bowden, David S
    ;
    Tong, Steven Y C
    ;
    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
    Viral hepatitis in correctional facilities in the Northern Territory of Australia 2003-2017.
    (2021-06-16)
    Sullivan, Richard P
    ;
    ; ;
    Heggie, Hugh
    ;
    Davis, Joshua S
    ;
    ;
    BACKGROUND: The demographic of Northern Territory prison population differs than elsewhere in Australia and the prevalence of hepatitis B and hepatitis C may therefore be somewhat different from other jurisdictions. There has been no study which has specifically described the serological results of a large proportion of prisoners in Northern Territory correctional facilities over an extended period of time. METHODS: This retrospective longitudinal study reviewed serological results and testing rates for hepatitis B, and hepatitis C performed in correctional facilities in the Northern Territory of Australia between July 1st, 2003 and June 30th, 2017. RESULTS: The proportion of positive records over 14 years for hepatitis B surface antigen (HBsAg) was 641/12,066 (5.3, 95% CI 4.9-5.7), for hepatitis B core antibody (anti-HBc) 4937/12,138 (40.1, 95%CI 39.8-41.6), for hepatitis B surface antibody (anti-HBs) 6966/13,303 (52.4, 95% CI 51.5-53.2), and for hepatitis C antibody 569/12,153 (4.7, 95% CI 4.3-5.1). The proportion of prisoners tested for hepatitis B and hepatitis C has decreased since 2015, while a high proportion of prisoners remain non-immune to hepatitis B. CONCLUSION: There is a relatively high proportion of positive serological markers of hepatitis B, and a lower proportion of positive hepatitis C serology in the Northern Territory's correctional facilities compared to overall Australian rates. As the proportion of prisoners tested for hepatitis B and C has decreased recently, and a high proportion of prisoners remain non-immune to hepatitis B, there are opportunities to increase testing and vaccination rates in this population.
      1317
  • Publication
    Journal Article
    Robust and prototypical immune responses toward influenza vaccines in the high-risk group of Indigenous Australians.
    (2021-10-12)
    Hensen L
    ;
    Nguyen THO
    ;
    Rowntree LC
    ;
    Damelang T
    ;
    Koutsakos M
    ;
    Aban M
    ;
    Hurt A
    ;
    Harland KL
    ;
    Auladell M
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    van de Sandt CE
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    Blacker C
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    Oyong DA
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    Loughland, JR
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    Webb JR
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    Wines BD
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    Hogarth PM
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    Flanagan KL
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    Plebanski M
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    Wheatley A
    ;
    Chung AW
    ;
    Kent SJ
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    Miller A
    ;
    Clemens EB
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    Doherty PC
    ;
    Nelson J
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    Tong SYC
    ;
    Kedzierska K
    Morbidity and mortality rates from seasonal and pandemic influenza occur disproportionately in high-risk groups, including Indigenous people globally. Although vaccination against influenza is recommended for those most at risk, studies on immune responses elicited by seasonal vaccines in Indigenous populations are largely missing, with no data available for Indigenous Australians and only one report published on antibody responses in Indigenous Canadians. We recruited 78 Indigenous and 84 non-Indigenous Australians vaccinated with the quadrivalent influenza vaccine into the Looking into InFluenza T cell immunity - Vaccination cohort study and collected blood to define baseline, early (day 7), and memory (day 28) immune responses. We performed in-depth analyses of T and B cell activation, formation of memory B cells, and antibody profiles and investigated host factors that could contribute to vaccine responses. We found activation profiles of circulating T follicular helper type-1 cells at the early stage correlated strongly with the total change in antibody titers induced by vaccination. Formation of influenza-specific hemagglutinin-binding memory B cells was significantly higher in seroconverters compared with nonseroconverters. In-depth antibody characterization revealed a reduction in immunoglobulin G3 before and after vaccination in the Indigenous Australian population, potentially linked to the increased frequency of the G3m21* allotype. Overall, our data provide evidence that Indigenous populations elicit robust, broad, and prototypical immune responses following immunization with seasonal inactivated influenza vaccines. Our work strongly supports the recommendation of influenza vaccination to protect Indigenous populations from severe seasonal influenza virus infections and their subsequent complications.
      2510
  • Publication
    Journal Article
    Blood-borne viruses in the haemodialysis-dependent population attending Top End Northern Territory facilities 2000-2009.
    (2012-07) ;
    Jabbar Z
    ;
    Gagan F
    ;
      To describe the incidence and prevalence of blood-borne viruses (BBV) including: hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and human T-cell leukaemia virus type-1 (HTLV) in the haemodialysis-dependent population of the Top End of the Northern Territory (TENT).   We retrospectively reviewed the serology of BBV in a longitudinal fashion in the haemodialysis-dependent population treated in the TENT of Australia from 2000 to 2009 inclusive. HBV, HCV, HIV and HTLV serology on commencement of dialysis and at exit or January 2010, whichever was earlier, as well as demographic details were collected. Patients with a change in serological status had all serology reviewed.   Four-hundred and forty patients were included in the analysis. Of these, 84.3% were Indigenous and 55.4% female, with a median age of 50 (IQR 43-59) years at the commencement of haemodialysis. Evidence of past HBV infection was documented in 42.7% and 8.9% were hepatitis B surface antigen-positive. Positive serology for HTLV was documented in 2.2%, 1.6% were hepatitis C antibody-positive and no individual was HIV-positive. Three patients had a definite change in their HBV serology over time; this equates to an absolute seroconversion risk of 0.1 per 100 person years or 0.0006 per dialysis episode.   In this cohort, there was a high rate of past and current hepatitis B infection but low rates of seroconversion while on haemodialysis.
      1211