Doherty Institute - Research Publications

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    Multiparameter immunohistochemistry analysis of HIV DNA, RNA and immune checkpoints in lymph node tissue
    Richardson, ZA ; Deleage, C ; Tutuka, CSA ; Walkiewicz, M ; Del Rio-Estrada, PM ; Pascoe, RD ; Evans, VA ; Reyesteran, G ; Gonzales, M ; Roberts-Thomson, S ; Gonzalez-Navarro, M ; Torres-Ruiz, F ; Estes, JD ; Lewin, SR ; Cameron, PU (ELSEVIER, 2022-02-01)
    The main barrier to a cure for HIV is the persistence of long-lived and proliferating latently infected CD4+ T-cells despite antiretroviral therapy (ART). Latency is well characterized in multiple CD4+ T-cell subsets, however, the contribution of regulatory T-cells (Tregs) expressing FoxP3 as well as immune checkpoints (ICs) PD-1 and CTLA-4 as targets for productive and latent HIV infection in people living with HIV on suppressive ART is less well defined. We used multiplex detection of HIV DNA and RNA with immunohistochemistry (mIHC) on formalin-fixed paraffin embedded (FFPE) cells to simultaneously detect HIV RNA and DNA and cellular markers. HIV DNA and RNA were detected by in situ hybridization (ISH) (RNA/DNAscope) and IHC was used to detect cellular markers (CD4, PD-1, FoxP3, and CTLA-4) by incorporating the tyramide system amplification (TSA) system. We evaluated latently infected cell lines, a primary cell model of HIV latency and excisional lymph node (LN) biopsies collected from people living with HIV (PLWH) on and off ART. We clearly detected infected cells that coexpressed HIV RNA and DNA (active replication) and DNA only (latently infected cells) in combination with IHC markers in the in vitro infection model as well as LN tissue from PLWH both on and off ART. Combining ISH targeting HIV RNA and DNA with IHC provides a platform to detect and quantify HIV persistence within cells identified by multiple markers in tissue samples from PLWH on ART or to study HIV latency.
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    Bats and Coronaviruses in the Context of COVID-19.
    Wang, L ; Ahn, M ; Anderson, DE (Chinese Center for Disease Control and Prevention, 2021-02-12)
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    Exploring a proposed WHO method to determine thresholds for seasonal influenza surveillance.
    Tay, EL ; Grant, K ; Kirk, M ; Mounts, A ; Kelly, H ; Cook, AR (Public Library of Science (PLoS), 2013)
    INTRODUCTION: Health authorities find thresholds useful to gauge the start and severity of influenza seasons. We explored a method for deriving thresholds proposed in an influenza surveillance manual published by the World Health Organization (WHO). METHODS: For 2002-2011, we analysed two routine influenza-like-illness (ILI) datasets, general practice sentinel surveillance and a locum medical service sentinel surveillance, plus laboratory data and hospital admissions for influenza. For each sentinel dataset, we created two composite variables from the product of weekly ILI data and the relevant laboratory data, indicating the proportion of tested specimens that were positive. For all datasets, including the composite datasets, we aligned data on the median week of peak influenza or ILI activity and assigned three threshold levels: seasonal threshold, determined by inspection; and two intensity thresholds termed average and alert thresholds, determined by calculations of means, medians, confidence intervals (CI) and percentiles. From the thresholds, we compared the seasonal onset, end and intensity across all datasets from 2002-2011. Correlation between datasets was assessed using the mean correlation coefficient. RESULTS: The median week of peak activity was week 34 for all datasets, except hospital data (week 35). Means and medians were comparable and the 90% upper CIs were similar to the 95(th) percentiles. Comparison of thresholds revealed variations in defining the start of a season but good agreement in describing the end and intensity of influenza seasons, except in hospital admissions data after the pandemic year of 2009. The composite variables improved the agreements between the ILI and other datasets. Datasets were well correlated, with mean correlation coefficients of >0.75 for a range of combinations. CONCLUSIONS: Thresholds for influenza surveillance are easily derived from historical surveillance and laboratory data using the approach proposed by WHO. Use of composite variables is helpful for describing influenza season characteristics.
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    Delays in Patient Presentation and Diagnosis for Buruli Ulcer (Mycobacterium ulcerans Infection) in Victoria, Australia, 2011-2017.
    Coutts, SP ; Lau, CL ; Field, EJ ; Loftus, MJ ; Tay, EL (MDPI AG, 2019-07-04)
    Uncertainty regarding transmission pathways and control measures makes prompt presentation and diagnosis for Buruli ulcer critical. To examine presentation and diagnosis delays in Victoria, Australia, we conducted a retrospective study of 703 cases notified between 2011 and 2017, classified as residing in an endemic (Mornington Peninsula; Bellarine Peninsula; South-east Bayside and Frankston) or non-endemic area. Overall median presentation delay was 30 days (IQR 14-60 days), with no significant change over the study period (p = 0.11). There were significant differences in median presentation delay between areas of residence (p = 0.02), but no significant change over the study period within any area. Overall median diagnosis delay was 10 days (IQR 0-40 days), with no significant change over the study period (p = 0.13). There were significant differences in median diagnosis delay between areas (p < 0.001), but a significant decrease over time only on the Mornington Peninsula (p < 0.001). On multivariable analysis, being aged <15 or >65 years; having non-ulcerative disease; and residing in the Bellarine Peninsula or South-East Bayside (compared to non-endemic areas) were significantly associated with shorter presentation delay. Residing in the Bellarine or Mornington Peninsula and being notified later in the study period were significantly associated with shorter diagnosis delay. To reduce presentation and diagnosis delays, awareness of Buruli ulcer must be raised with the public and medical professionals, particularly those based outside established endemic areas.
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    Potential for the Australian and New Zealand paediatric intensive care registry to enhance acute flaccid paralysis surveillance in Australia: a data-linkage study
    Hobday, LK ; Thorley, BR ; Alexander, J ; Aitken, T ; Massey, PD ; Cretikos, M ; Slater, A ; Durrheim, DN (BMC, 2013-08-21)
    BACKGROUND: Australia uses acute flaccid paralysis (AFP) surveillance to monitor its polio-free status. The World Health Organization criterion for a sensitive AFP surveillance system is the annual detection of at least one non-polio AFP case per 100,000 children aged less than 15 years, a target Australia has not consistently achieved. Children exhibiting AFP are likely to be hospitalised and may be admitted to an intensive care unit. This provides a potential opportunity for active AFP surveillance. METHODS: A data-linkage study for the period from 1 January 2005 to 31 December 2008 compared 165 non-polio AFP cases classified by the Polio Expert Panel with 880 acute neurological presentations potentially compatible with AFP documented in the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry. RESULTS: Forty-two (25%) AFP cases classified by the Polio Expert Panel were matched to case records in the ANZPIC Registry. Of these, nineteen (45%) cases were classified as Guillain-Barré syndrome on both registries. Ten additional Guillain-Barré syndrome cases recorded in the ANZPIC Registry were not notified to the national AFP surveillance system. CONCLUSIONS: The identification of a further ten AFP cases supports inclusion of intensive care units in national AFP surveillance, particularly specialist paediatric intensive care units, to identify AFP cases that may not otherwise be reported to the national surveillance system.
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    Circulating Vaccine-Derived Poliovirus Type 1 and Outbreak Response - Papua New Guinea, 2018
    Bauri, M ; Wilkinson, AL ; Ropa, B ; Feldon, K ; Snider, CJ ; Anand, A ; Tallis, G ; Boualam, L ; Grabovac, V ; Avagyan, T ; Reza, MS ; Mekonnen, D ; Zhang, Z ; Thorley, BR ; Shimizu, H ; Apostol, LNG ; Takashima, Y (CENTERS DISEASE CONTROL, 2019-02-08)
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    The emergence and spread of one Coxsackievirus A16 Genogroup D novel recombinant strain that caused a clustering HFMD outbreak in Shanghai, China, 2016
    Wang, J ; Teng, Z ; Chu, W ; Fang, F ; Cui, X ; Guo, X ; Zhang, X ; Thorley, BR ; Zhu, Y (NATURE PUBLISHING GROUP, 2018-07-18)
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    Determinants and Gaps in Preventive Care Delivery for Indigenous Australians: A Cross-Sectional Analysis
    Bailie, C ; Matthews, V ; Bailie, J ; Burgess, P ; Copley, K ; Kennedy, C ; Moore, L ; Larkins, S ; Thompson, S ; Bailie, RS (FRONTIERS MEDIA SA, 2016-03-10)
    BACKGROUND: Potentially preventable chronic diseases are the greatest contributor to the health gap between Aboriginal and Torres Strait Islander peoples and non--Indigenous Australians. Preventive care is important for earlier detection and control of chronic disease, and a number of recent policy initiatives have aimed to enhance delivery of preventive care. We examined documented delivery of recommended preventive services for Indigenous peoples across Australia and investigated the influence of health center and client level factors on adherence to best practice guidelines. METHODS: Clinical audit data from 2012 to 2014 for 3,623 well adult clients (aged 15-54) of 101 health centers from four Australian states and territories were analyzed to determine adherence to delivery of 26 recommended preventive services classified into five different modes of care on the basis of the way in which they are delivered (e.g., basic measurement; laboratory tests and imaging; assessment and brief interventions, eye, ear, and oral checks; follow-up of abnormal findings). Summary statistics were used to describe the delivery of each service item across jurisdictions. Multilevel regression models were used to quantify the variation in service delivery attributable to health center and client level factors and to identify factors associated with higher quality care. RESULTS: Delivery of recommended preventive care varied widely between service items, with good delivery of most basic measurements but poor follow-up of abnormal findings. Health center characteristics were associated with most variation. Higher quality care was associated with Northern Territory location, urban services, and smaller service population size. Client factors associated with higher quality care included age between 25 and 34 years, female sex, and more regular attendance. CONCLUSION: Wide variation in documented preventive care delivery, poor follow-up of abnormal findings, and system factors that influence quality of care should be addressed through continuous quality improvement approaches that engage stakeholders at multiple levels (including, for example, access to care in the community, appropriate decision support for practitioners, and financial incentives and context appropriate guidelines).
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    Hospitalisation, morbidity and outcomes associated with respiratory syncytial virus compared with influenza in adults of all ages
    Leaver, B ; Smith, B ; Irving, L ; Johnson, D ; Tong, S (WILEY, 2021-12-01)
    BACKGROUND: Respiratory syncytial virus (RSV) is understood to be a cause of significant disease in older adults and children. Further analysis of RSV in younger adults may reveal further insight into its role as an important pathogen in all age groups. METHODS: We identified, through laboratory data, adults who tested positive for either influenza or RSV between January 2017 and June 2019 at a single Australian hospital. We compared baseline demographics, testing patterns, hospitalisations and outcomes between these groups. RESULTS: Of 1128 influenza and 193 RSV patients, the RSV cohort was older (mean age 54.7 vs. 64.9, p < 0.001) and was more comorbid as determined by the Charlson Comorbidity Index (2.4 vs. 3.2, p < 0.001). For influenza hospitalisations, the majority admitted were aged under 65 which was not the case for RSV (61.8% vs. 45.6%, p < 0.001). Testing occurred later in RSV hospitalisations as measured by the proportion tested in the emergency department (ED) (80.3% vs. 69.2%, p < 0.001), and this was strongly associated with differences in presenting phenotype (the presence of fever). RSV was the biggest predictor of 6-month representation, with age and comorbidities predicting this less strongly. CONCLUSION: RSV is a significant contributor to morbidity and hospitalisation, sometimes outweighing that of influenza, and is not limited to elderly cohorts. Understanding key differences in the clinical syndrome and consequent testing paradigms may allow better detection and potentially treatment of RSV to reduce individual morbidity and health system burden. This growing area of research helps quantify the need for directed therapies for RSV.
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    Public Health Response to Imported Case of Poliomyelitis, Australia, 2007
    Carnie, JA ; Lester, R ; Moran, R ; Brown, L ; Meagher, J ; Roberts, JA ; Thorley, BR (CENTERS DISEASE CONTROL, 2009-11-01)
    Australia, along with 36 other countries in the Western Pacific Region, was declared free of poliomyelitis by the World Health Organization in October 2000. Yet, the persistence of wild poliovirus in the 4 remaining polio-endemic countries-Afghanistan, India, Nigeria, and Pakistan-poses a risk for its importation into all countries declared polio free. We describe the public health response and outcomes resulting from the importation of a wild poliovirus infection in Melbourne, Australia, in July 2007. This response, based on an assessment of the risk for transmission, included offering vaccination with inactivated polio vaccine to the contacts and placing the index patient in isolation and the household contacts in quarantine until consecutive fecal specimens were negative for poliovirus by culture. The experience gained from the polio importation event in Australia may assist other polio-free countries to prepare for, and respond to, a similar event. No secondary clinical cases resulted from this importation.