Now showing 1 - 10 of 118
  • Publication
    Journal Article
    Comprehensive observational study evaluating the enduring effectiveness of 4CMenB, the meningococcal B vaccine against gonococcal infections in the Northern Territory and South Australia, Australia: study protocol.
    (2024-05-08)
    Marshall, Helen
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    Ward, James
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    Wang, Bing
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    Andraweera, Prabha
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    McMillan, Mark
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    Flood, Louise
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    Bell, Charlotte
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    Sisnowski, Jana
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    ; ; ; ; ;
    Leong, Lex
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    Lawrence, Andrew
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    Whiley, David M
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    Karnon, Jonathan
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    van Hal, Sebastian
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    Lahra, Monica M
    The effectiveness of antibiotics for treating gonococcal infections is compromised due to escalating antibiotic resistance; and the development of an effective gonococcal vaccine has been challenging. Emerging evidence suggests that the licensed meningococcal B (MenB) vaccine, 4CMenB is effective against gonococcal infections due to cross-reacting antibodies and 95% genetic homology between the two bacteria, and that cause the diseases. This project aims to undertake epidemiological and genomic surveillance to evaluate the long-term protection of the 4CMenB vaccine against gonococcal infections in the Northern Territory (NT) and South Australia (SA), and to determine the potential benefit of a booster vaccine doses to provide longer-term protection against gonococcal infections.This observational study will provide long-term evaluation results of the effectiveness of the 4CMenB vaccine against gonococcal infections at 4-7 years post 4CMenB programme implementation. Routine notifiable disease notifications will be the basis for assessing the impact of the vaccine on gonococcal infections. Pathology laboratories will provide data on the number and percentage of positive tests relative to all tests administered and will coordinate molecular sequencing for isolates. Genome sequencing results will be provided by SA Pathology and Territory Pathology/New South Wales Health Pathology, and linked with notification data by SA Health and NT Health. There are limitations in observational studies including the potential for confounding. Confounders will be analysed separately for each outcome/comparison.The protocol and all study documents have been reviewed and approved by the SA Department for Health and Well-being Human Research Ethics Committee (HREC/2022/HRE00308), and the evaluation will commence in the NT on receipt of approval from the NT Health and Menzies School of Health Research Human Research Ethics Committee. Results will be published in peer-reviewed journals and presented at scientific meetings and public forums.
  • Publication
    Journal Article
    Genomic Surveillance of Invasive Meningococcal Disease During a National MenW Outbreak in Australia, 2017-2018.
    (2024-05-02)
    Sotheran, Emily
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    Lane, Courtney R
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    Horan, Kristy
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    Stevens, Kerrie
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    Guglielmino, Christine
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    Bradbury, Susan
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    Kennedy, Karina
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    Cooley, Louise
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    McEwan, Belinda
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    Kahler, Charlene M
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    Mowlaboccus, Shakeel
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    Speers, David J
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    ; ;
    Leong, Lex
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    Warner, Morgyn
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    Williamson, Deborah A
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    McVernon, Jodie
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    Lahra, Monica
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    Jennison, Amy V
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    Howden, Benjamin P
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    Andersson, Patiyan
    In Australia, invasive meningococcal disease (IMD) incidence rapidly increased between 2014 and 2017 due to rising serogroup W (MenW) and MenY infections. We aimed to better understand the genetic diversity of IMD during 2017 and 2018 using whole genome sequencing data.Whole genome sequencing data from 440 Australian IMD isolates collected during 2017 and 2018 and 1737 international MenW:CC11 isolates collected in Europe, Africa, Asia, North America, and South America between 1974 and 2020 were used in phylogenetic analyses; genetic relatedness was determined from single-nucleotide polymorphisms.Australian isolates were as follows: 181 MenW (41%), 144 MenB (33%), 88 MenY (20%), 16 MenC (4%), 1 MenW/Y (0.2%), and 10 nongenogroupable (2%). Eighteen clonal complexes (CCs) were identified, and 3 (CC11, CC23, CC41/44) accounted for 78% of isolates (343/440). These CCs were associated with specific serogroups: CC11 (n = 199) predominated among MenW (n = 181) and MenC (n = 15), CC23 (n = 80) among MenY (n = 78), and CC41/44 (n = 64) among MenB (n = 64). MenB isolates were highly diverse, MenY were intermediately diverse, and MenW and MenC isolates demonstrated the least genetic diversity. Thirty serogroup and CC-specific genomic clusters were identified. International CC11 comparison revealed diversification of MenW in Australia.Whole genome sequencing comprehensively characterized Australian IMD isolates, indexed their genetic variability, provided increased within-CC resolution, and elucidated the evolution of CC11 in Australia.
  • Publication
    Journal Article
    Comparison of Melioidosis Indirect Hemagglutination Assay between Three Testing Laboratories in Australia.
    (2023-03-27)
    Armstrong M
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    Morgan J
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    Kazey O
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    ;
    Norton R
    Melioidosis caused by Burkholderia pseudomallei causes significant morbidity and mortality in Southeast Asia and northern Australia. Clinical manifestations remain diverse, including localized skin infection, pneumonia, and chronic abscess formation. Culture remains the gold standard of diagnosis, with serology and antigen detection tests playing a role if culture is unfeasible. Serologic diagnosis remains challenging, with limited standardization across different assays. In areas of endemicity, high rates of seropositivity have been documented. The indirect hemagglutination assay (IHA) is one of the more widely used serologic tests in these areas. In Australia, only three centers perform the test. Annually, laboratory A, laboratory B, and laboratory C perform approximately 1,000, 4,500, and 500 tests, respectively. A comparison of a total of 132 sera was analyzed from the routine quality exchange program between these centers from 2010 until 2019. Overall, 18.9% of sera tested had an interpretative discrepancy between laboratories. IMPORTANCE This study found significant discrepant results between three Australian centers offering the melioidosis indirect hemagglutination assay (IHA), despite testing the same samples. We have highlighted that the IHA is a nonstandardized test, which had different source antigens at each of the different laboratories. Melioidosis is a global disease, is associated with significant mortality, and is perhaps under recognized. It is likely to have increasing impact with changing weather patterns. The IHA has been used frequently as an adjunct to the diagnosis of clinical disease and is the mainstay of determining seroprevalence within populations. Despite its relative ease of use, especially in low resource settings, our study highlights the significant limitations of the melioidosis IHA. It has wide ranging implications, serving as an impetus for developing better diagnostic tests. This study is of interest to practitioners and researchers working in the various geographic regions affected by melioidosis.
      3422
  • Publication
    Journal Article
    Using Genomics to Understand the Epidemiology of Infectious Diseases in the Northern Territory of Australia.
    The Northern Territory (NT) is a geographically remote region of northern and central Australia. Approximately a third of the population are First Nations Australians, many of whom live in remote regions. Due to the physical environment and climate, and scale of social inequity, the rates of many infectious diseases are the highest nationally. Molecular typing and genomic sequencing in research and public health have provided considerable new knowledge on the epidemiology of infectious diseases in the NT. We review the applications of genomic sequencing technology for molecular typing, identification of transmission clusters, phylogenomics, antimicrobial resistance prediction, and pathogen detection. We provide examples where these methodologies have been applied to infectious diseases in the NT and discuss the next steps in public health implementation of this technology.
      4824
  • Publication
    Journal Article
    Clinical Manifestations Associated with Bartonella henselae Infection in a Tropical Region.
    (2020-10-05)
    Tay SY
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    ;
    Bartonella henselae is a zoonotic Gram-negative Bacillus associated with self-limited regional lymphadenopathy. In recent decades, an expanding spectrum of clinical manifestations has been described, in part, due to improved diagnostics. However, updated epidemiological data are sparse. We retrospectively reviewed the clinical features of 31 patients with B. henselae infection older than 15 years from 2005 to 2019, in the tropical Top End of Australia. Our annual disease incidence of 1.3 cases per 100,000 population is lower than that in the national database surveillances in the United States, but the hospitalization incidence of 0.9 per 100,000 population in our region is higher than those reported in the literature, with an average length of stay of 9 days. Patients were more commonly male, aboriginal, and aged less than 14 years (median age: 7 years), living in a rural setting with presentation during our monsoon season. The disease spectrum included lymph node disease (74%), organ peliosis, endocarditis, cutaneous lesions, parapharyngeal abscess, parotitis, and neurologic and ocular syndromes. Lymph node disease was far commoner in children than the more serious systemic B. henselae infections associated with adults (P = 0.074). Although no deaths were reported, significant morbidities were observed. Two endocarditis cases presented with glomerulonephritis, and hematological and neurological features mimicking vasculitis, and consequently received immunosuppressants. One case was only diagnosed after representation with serial embolic strokes. Given the heterogeneity of disease manifestations with nonspecific symptoms and significant consequences, a timely and accurate diagnosis is needed to avoid unnecessary treatments or interventions.
      968
  • Publication
    Journal Article
    Current antimicrobial susceptibility of first-episode melioidosis Burkholderia pseudomallei isolates from the Northern Territory, Australia.
    (2014-08)
    Crowe A
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    McMahon N
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    ;
    Burkholderia pseudomallei is a saprophytic Gram-negative bacterium responsible for the tropical infectious disease melioidosis. Melioidosis is endemic to northern Australia and Southeast Asia. In this study, 234 isolates of B. pseudomallei obtained from the first positive clinical specimen from 234 consecutive patients diagnosed with melioidosis between October 2009 and September 2012 were reviewed. All isolates were susceptible to meropenem and ceftazidime. In total, 226 isolates (96.6%) were susceptible to doxycycline and 232 (99.1%) were susceptible to trimethoprim/sulfamethoxazole (TMP/SMX; co-trimoxazole). Primary resistance of B. pseudomallei to ceftazidime and/or meropenem is exceedingly rare and clinicians can be confident in the current treatment guidelines for melioidosis. Whether the very low rates of TMP/SMX resistance seen in Australia reflect the global situation requires further studies using Etest, especially to clarify the rate of resistance in Thailand.
      1102
  • Publication
    Journal Article
    The new screening program to prevent cervical cancer using HPV DNA: getting the balance right in maintaining quality.
    (2018-07-30)
    Garland SM
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    Dimech W
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    Collignon P
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    Cooley L
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    Nimmo GR
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    Smith DW
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    Rawlinson W
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    Costa A-M
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    Higgins G
    Along with the reduction in human papillomavirus (HPV) infection and cervical abnormalities as a result of the successful HPV vaccination program, Australia is adopting a new screening strategy. This involves a new paradigm moving from cervical cytological screening to molecular nucleic acid technology (NAT), using HPV DNA assays as primary screening for cervical cancer prevention. These assays must strike a balance between sufficient clinical sensitivity to detect or predict high-grade cervical lesions, the precursor to cervical cancer, without being too sensitive and detecting transient infection not destined for disease. Ensuring the highest quality HPV NAT is thus a priority in order to reduce the possibility of falsely negative screens and manage the risk associated with false positive HPV NAT results. How to do this needs informed discussion and ongoing refinement of the screening algorithm. This is of relevance as more countries move to more sensitive HPV NAT tests for secondary prevention of cervical cancer and as more HPV assays become available. This article is protected by copyright. All rights reserved.
      1256
  • Publication
    Journal Article
    The spectrum of presentations of unintentional carbon monoxide poisoning.
    (2023-12-21)
    Stephenson, Lilli
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    Van Den Heuvel, Corinna
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    Byard, Roger W
    Carbon monoxide (CO) is an odourless and tasteless gas which can be produced by the incomplete combustion of carbon-containing fuels. Compared to vehicular CO suicides, unintentional cases (excluding those related to fires) are much less common. Increased education surrounding the risks associated with the accumulation of CO in enclosed spaces has contributed to a reduced incidence of unintentional CO poisonings. However, such cases may remain undetected, particularly in domestic and recreational settings where scene findings are often non-specific. The current study of unintentional CO poisonings in South Australia and the Northern Territory, each with a unique climate (Mediterranean and tropical respectively), demonstrated differences in the circumstances of death. Several cases where individuals used carbon-producing fuel sources for heat, both in domestic and vehicular settings and without adequate ventilation, resulted in fatal outcomes. Less common scenarios involved faults in equipment (e.g. a hot water heater), vehicle faults resulting in the accumulation of fatal levels of CO in enclosed spaces, and inadvertent introduction of CO into a diving oxygen supply in a recreational aquatic setting. In ascertaining the cause of death, other considerations include the potential role of underlying chronic cardiovascular and respiratory disease and age which may increase an individual's susceptibility to CO toxicity. Understanding the wide variety of presentations and contributing factors in cases of fatal CO poisoning including consideration of climate-specific differences in domestic and extra-domestic settings may enable improved detection at autopsy.
      354
  • Publication
    Journal Article
    Combination of Vancomycin and β-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial.
    (2016-01-15)
    Davis JS
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    Sud A
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    O'Sullivan MVN
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    Robinson JO
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    Ferguson PE
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    Foo H
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    van Hal SJ
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    Howden BP
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    Binks PM
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    Kirby A
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    Tong SYC
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    Majumdar S
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    Gordon C
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    Jeremiah C
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    Leung G
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    Brischetto A
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    Crowe A
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    Dakh F
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    Whykes K
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    Kirkwood M
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    Menon M
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    Somerville L
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    Subedi S
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    Owen S
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    Liu E
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    Zhou F
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    Robinson O
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    Coombs G
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    Pollet S
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    Davis R
    In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and antistaphylococcal β-lactams for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Prospective clinical data are lacking. In this open-label, multicenter, clinical trial, adults with MRSA bacteremia received vancomycin 1.5 g intravenously twice daily and were randomly assigned (1:1) to receive intravenous flucloxacillin 2 g every 6 hours for 7 days (combination group) or no additional therapy (standard therapy group). Participants were stratified by hospital and randomized in permuted blocks of variable size. Randomization codes were kept in sealed, sequentially numbered, opaque envelopes. The primary outcome was the duration of MRSA bacteremia in days. We randomly assigned 60 patients to receive vancomycin (n = 29), or vancomycin plus flucloxacillin (n = 31). The mean duration of bacteremia was 3.00 days in the standard therapy group and 1.94 days in the combination group. According to a negative binomial model, the mean time to resolution of bacteremia in the combination group was 65% (95% confidence interval, 41%-102%; P = .06) that in the standard therapy group. There was no difference in the secondary end points of 28- and 90-day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity. Combining an antistaphylococcal β-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant end points are warranted. Australian New Zealand Clinical Trials Registry: ACTRN12610000940077 (www.anzctr.org.au).
      1546
  • Publication
    Case Reports
      518