Doherty Institute - Research Publications

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    As Omicron Takes Hold and Other New Variants Arise, COVID-19 Testing Remains the Universally Agreed Tool to Effect Transition From Pandemic to Endemic State.
    Miller, MB ; Ooi, EE ; Rhoads, DD ; Kulldorff, M ; Anderson, DE ; Lee, H ; Gupta, S ; Mel, K (Frontiers Media SA, 2022)
    The COVID-19 pandemic has caused more than 448 million cases and 6 million deaths worldwide to date. Omicron is now the dominant SARS-CoV-2 variant, making up more than 90% of cases in countries reporting sequencing data. As the pandemic continues into its third year, continued testing is a strategic and necessary tool for transitioning to an endemic state of COVID-19. Here, we address three critical topics pertaining to the transition from pandemic to endemic: defining the endemic state for COVID-19, highlighting the role of SARS-CoV-2 testing as endemicity is approached, and recommending parameters for SARS-CoV-2 testing once endemicity is reached. We argue for an approach that capitalizes on the current public health momentum to increase capacity for PCR-based testing and whole genome sequencing to monitor emerging infectious diseases. Strategic development and utilization of testing, including viral panels in addition to vaccination, can keep SARS-CoV-2 in a manageable endemic state and build a framework of preparedness for the next pandemic.
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    Influenza A(H1N1)pdm09 But Not A(H3N2) Virus Infection Induces Durable Seroprotection: Results From the Ha Nam Cohort( )
    Le, NMH ; Sullivan, SG ; Le, QM ; Khvorov, A ; Hoang, VMP ; Nguyen, LKH ; Pham, QT ; Le, TT ; Carolan, L ; Dang, DA ; Tran, ND ; Bryant, JE ; van Doorn, HR ; Wertheim, HFL ; Horby, P ; Fox, A (OXFORD UNIV PRESS INC, 2022-08-12)
    BACKGROUND: The extent to which influenza recurrence depends upon waning immunity from prior-infection is undefined. We used antibody titres of Ha-Nam cohort participants to estimate protection curves and decay trajectories. METHODS: 270 households participated in influenza-like-illness surveillance and provided blood at intervals spanning RTPCR-confirmed transmission. Sera were tested in haemagglutination inhibition assay. Infection was defined as RTPCR+ influenza-like-illness and/or seroconversion. Median protective titres were estimated using scaled-logistic-regression to model pre-transmission titre against infection status in that season, limiting analysis to households with infection(s). Titres were modelled against month since infection using mixed-effects linear regression to estimate decay and when titres fell below protection-thresholds. RESULTS: 295 and 314 participants were infected with H1N1pdm09-like and A/Perth/16/09-like (H3N2Pe09) viruses, respectively between December 2008-2012. The proportion of householders not-infected (protected) rose more steeply with titre for H1N1pdm09 than for H3N2Pe09, and estimated 50% protection titres were 19.6 and 37.3, respectively. Post-infection titres started higher against H3N2Pe09 but decayed more steeply than against H1N1pdm09. Sero-protection was estimated to be sustained against H1N1pdm09 but to wane by 8-months for H3N2Pe09. CONCLUSIONS: Estimates indicate that infection induces durable sero-protection against H1N1pdm09 but not H3N2Pe09, which could in part account for the younger age of A(H1N1) versus A(H3N2) cases.
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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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    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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    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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    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).