Doherty Institute - Research Publications
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ItemInhibition of Influenza A Virus by Human Infant Saliva(MDPI, 2019-08)Innate antiviral factors in saliva play a role in protection against respiratory infections. We tested the anti-influenza virus activities of saliva samples taken from human infants, 1-12 months old, with no history of prior exposure to influenza. In contrast to the inhibitory activity we observed in mouse and ferret saliva, the activity of human infant saliva was complex, with both sialic acid-dependent and independent components, the proportion of which differed between individuals. Taken as a whole, we showed that the major anti-influenza activity of infant saliva is acquired over the first year of life and is associated with sialic acid-containing molecules. The activity of sialic acid-independent inhibitors was lower overall, more variable between individuals, and less dependent on age. The results show that the saliva of very young infants can provide a degree of protection against influenza, which may be critical in the absence of adaptive immunity.
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ItemPrior exposure to immunogenic peptides found in human influenza A viruses may influence the age distribution of cases with avian influenza H5N1 and H7N9 virus infections(CAMBRIDGE UNIV PRESS, 2019)The epidemiology of H5N1 and H7N9 avian viruses of humans infected in China differs despite both viruses being avian reassortants that have inherited six internal genes from a common ancestor, H9N2. The median age of infected populations is substantially younger for H5N1 virus (26 years) compared with H7N9 virus (63 years). Population susceptibility to infection with seasonal influenza is understood to be influenced by cross-reactive CD8+ T cells directed towards immunogenic peptides derived from internal viral proteins which may provide some level of protection against further influenza infection. Prior exposure to seasonal influenza peptides may influence the age-related infection patterns observed for H5N1 and H7N9 viruses. A comparison of relatedness of immunogenic peptides between historical human strains and the two avian emerged viruses was undertaken for a possible explanation in the differences in age incidence observed. There appeared to be some relationship between past exposure to related peptides and the lower number of H5N1 virus cases in older populations, however the relationship between prior exposure and older populations among H7N9 virus patients was less clear.
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ItemInsights from mathematical modelling on the proposed WHO 2030 goals for scabies.(F1000 Research Ltd, 2019)Scabies was adopted by the World Health Organization (WHO) as a Neglected Tropical Disease in 2017. There is currently no formal global scabies control programmes or existing WHO guidelines on scabies control although at least two countries, Fiji and Ethiopia, have adopted national approaches to scabies control. In February 2019 WHO held a first Informal Consultation on a Framework for Scabies Control, in part as a response to multiple national requests for guidance on public health management in high disease burden areas. Below we outline control strategies proposed at this meeting and summarise the role that modelling can play in supporting the development of evidence to translate these proposals into formal WHO recommendations and national and global control programmes. Provisional proposals discussed at the WHO Informal Consultation for a scabies control programme include the use of mass drug administration when the community prevalence of scabies is ≥ 10% (generally considered to reflect a childhood prevalence of at least 20%) and the use of intensified case management when the prevalence is below 10%.
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ItemSources, perceived usefulness and understanding of information disseminated to families who entered home quarantine during the H1N1 pandemic in Victoria, Australia: a cross-sectional study(BMC, 2011-01-04)BACKGROUND: Voluntary home quarantine of cases and close contacts was the main non-pharmaceutical intervention used to limit transmission of pandemic (H1N1) 2009 influenza (pH1N1) in the initial response to the outbreak of the disease in Australia. The effectiveness of voluntary quarantine logically depends on affected families having a clear understanding of what they are being asked to do. Information may come from many sources, including the media, health officials, family and friends, schools, and health professionals. We report the extent to which families who entered home quarantine received and used information on what they were supposed to do. Specifically, we outline their sources of information; the perceived usefulness of each source; and associations between understanding of recommendations and compliance. METHODS: Cross-sectional survey administered via the internet and computer assisted telephone interview to families whose school children were recommended to go into home quarantine because they were diagnosed with H1N1 or were a close contact of a case. The sample included 314 of 1157 potentially eligible households (27% response rate) from 33 schools in metropolitan Melbourne. Adjusting for clustering within schools, we describe self-reported 'understanding of what they were meant to do during the quarantine period'; source of information (e.g. health department) and usefulness of information. Using logistic regression we examine whether compliance with quarantine recommendations was associated with understanding and the type of information source used. RESULTS: Ninety per cent understood what they were meant to do during the quarantine period with levels of understanding higher in households with cases (98%, 95% CI 93%-99% vs 88%, 95% CI 84%-91%, P = 0.006). Over 87% of parents received information about quarantine from the school, 63% from the health department and 44% from the media. 53% of households were fully compliant and there was increased compliance in households that reported that they understood what they were meant to do (Odds Ratio 2.27, 95% CI 1.35-3.80). CONCLUSIONS: It is critical that public health officials work closely with other government departments and media to provide clear, consistent and simple information about what to do during quarantine as high levels of understanding will maximise compliance in the quarantined population.
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ItemOptimal timing of influenza vaccine during pregnancy: A systematic review and meta-analysis(WILEY, 2019-09)BACKGROUND: Pregnant women have an elevated risk of illness and hospitalisation from influenza. Pregnant women are recommended to be prioritised for influenza vaccination during any stage of pregnancy. The risk of seasonal influenza varies substantially throughout the year in temperate climates; however, there is limited knowledge of how vaccination timing during pregnancy impacts the benefits received by the mother and foetus. OBJECTIVES: To compare antenatal vaccination timing with regard to influenza vaccine immunogenicity during pregnancy and transplacental transfer to their newborns. METHODS: Studies were eligible for inclusion if immunogenicity to influenza vaccine was evaluated in women stratified by trimester of pregnancy. Haemagglutination inhibition (HI) titres, stratified by trimester of vaccination, had to be measured at either pre-vaccination and within one month post-vaccination, post-vaccination and at delivery in the mother, or in cord/newborn blood. Authors searched PubMed, Scopus, Web of Science and EMBASE databases from inception until June 2016 and authors of identified studies were contacted for additional data. Extracted data were tabulated and summarised via random-effect meta-analyses and qualitative methods. RESULTS: Sixteen studies met the inclusion criteria. Meta-analyses found that compared with women vaccinated in an earlier trimester, those vaccinated in a later trimester had a greater fold increase in HI titres (1.33- to 1.96-fold) and higher HI titres in cord/newborn blood (1.21- to 1.64-fold). CONCLUSIONS: This review provides comparative analysis of the effect of vaccination timing on maternal immunogenicity and protection of the infant that is informative and relevant to current vaccine scheduling for pregnant women.
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ItemNo Preview AvailableSteps to solving the infant biometric problem with ridge-based biometrics(INST ENGINEERING TECHNOLOGY-IET, 2018-11)
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ItemQuantity or quality? Assessing relationships between perceived social connectedness and recorded encounters(PUBLIC LIBRARY SCIENCE, 2018-11-29)INTRODUCTION: Higher levels of social connectedness are associated with better physical and mental health outcomes, but measures of connectedness are often study specific. Prior research has distinguished between perceived and received (quantifiable) measures of social connectedness, with differing impacts on health, sometimes mediated by place of residence. This analysis investigated the relationship between perceptions of social support/connection and quantifiable measures of social encounters, by neighbourhood, to inform understanding of place-based differences in connectedness and health outcomes. METHODS: Negative binomial regression models were used to determine associations between perceptions of social connectedness (perceived community connections and social involvement) and the number of recorded daily social encounters as a proxy for received support/connectedness. Analyses were undertaken across two Local Government Areas (LGAs) in Melbourne with disparate socio-economic profiles to examine potential modification of social connectedness measures by neighbourhood of residence. RESULTS: Two measures of perceived connectedness had a clear relationship with recorded daily social encounters-feeling a sense of community belonging (RR 1.20 (1.04, 1.37), p = 0.010) and having family or friends close by (RR 1.30 (1.10,1.54), p = 0.002 "neither" compared to "disagree", (RR 1.15 (1.04, 1.26), p = 0.006 "agree" compared to "disagree"). Involvement in a local church, sporting or social club was associated with a greater number of daily social encounters for respondents who participated a few times a year (RR 1.17 (1.05,1.32), p = 0.006) or often (RR 1.23 (1.12,1.36), p<0.001) compared to never. In the less affluent LGA, active contributions to neighbours and community through assistance and volunteering were a frequent driver of social connection. Differences in patterns between the two areas were found with some measures of perception showing stronger relationships with recorded daily encounters in one area but not the other. CONCLUSIONS: These results indicate substantial complexity in the relationship between perceptions of social connectedness and recorded daily social encounters/received connectedness, meaning that one cannot be reliably extrapolated from the other. Drivers of individuals' social connections also varied by area of residence. These findings offer new insights into potential mediators of the association between connectedness and wellbeing.
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ItemDiagnosis and Antiviral Intervention Strategies for Mitigating an Influenza Epidemic(PUBLIC LIBRARY SCIENCE, 2011-02-04)BACKGROUND: Many countries have amassed antiviral stockpiles for pandemic preparedness. Despite extensive trial data and modelling studies, it remains unclear how to make optimal use of antiviral stockpiles within the constraints of healthcare infrastructure. Modelling studies informed recommendations for liberal antiviral distribution in the pandemic phase, primarily to prevent infection, but failed to account for logistical constraints clearly evident during the 2009 H1N1 outbreaks. Here we identify optimal delivery strategies for antiviral interventions accounting for logistical constraints, and so determine how to improve a strategy's impact. METHODS AND FINDINGS: We extend an existing SEIR model to incorporate finite diagnostic and antiviral distribution capacities. We evaluate the impact of using different diagnostic strategies to decide to whom antivirals are delivered. We then determine what additional capacity is required to achieve optimal impact. We identify the importance of sensitive and specific case ascertainment in the early phase of a pandemic response, when the proportion of false-positive presentations may be high. Once a substantial percentage of ILI presentations are caused by the pandemic strain, identification of cases for treatment on syndromic grounds alone results in a greater potential impact than a laboratory-dependent strategy. Our findings reinforce the need for a decentralised system capable of providing timely prophylaxis. CONCLUSIONS: We address specific real-world issues that must be considered in order to improve pandemic preparedness policy in a practical and methodologically sound way. Provision of antivirals on the scale proposed for an effective response is infeasible using traditional public health outbreak management and contact tracing approaches. The results indicate to change the transmission dynamics of an influenza epidemic with an antiviral intervention, a decentralised system is required for contact identification and prophylaxis delivery, utilising a range of existing services and infrastructure in a "whole of society" response.
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ItemLikely effectiveness of pharmaceutical and non-pharmaceutical interventions for mitigating influenza virus transmission in Mongolia(WORLD HEALTH ORGANIZATION, 2012-04)OBJECTIVE: To assess the likely benefit of the interventions under consideration for use in Mongolia during future influenza pandemics. METHODS: A stochastic, compartmental patch model of susceptibility, exposure, infection and recovery was constructed to capture the key effects of several interventions--travel restrictions, school closure, generalized social distancing, quarantining of close contacts, treatment of cases with antivirals and prophylaxis of contacts--on the dynamics of influenza epidemics. The likely benefit and optimal timing and duration of each of these interventions were assessed using Latin-hypercube sampling techniques, averaging across many possible transmission and social mixing parameters. FINDINGS: Timely interventions could substantially alter the time-course and reduce the severity of pandemic influenza in Mongolia. In a moderate pandemic scenario, early social distancing measures decreased the mean attack rate from around 10% to 7-8%. Similarly, in a severe pandemic scenario such measures cut the mean attack rate from approximately 23% to 21%. In both moderate and severe pandemic scenarios, a suite of non-pharmaceutical interventions proved as effective as the targeted use of antivirals. Targeted antiviral campaigns generally appeared more effective in severe pandemic scenarios than in moderate pandemic scenarios. CONCLUSION: A mathematical model of pandemic influenza transmission in Mongolia indicated that, to be successful, interventions to prevent transmission must be triggered when the first cases are detected in border regions. If social distancing measures are introduced at this stage and implemented over several weeks, they may have a notable mitigating impact. In low-income regions such as Mongolia, social distancing may be more effective than the large-scale use of antivirals.
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ItemReducing disease burden in an influenza pandemic by targeted delivery of neuraminidase inhibitors: mathematical models in the Australian context(BMC, 2016-10-10)BACKGROUND: Many nations maintain stockpiles of neuraminidase inhibitor (NAI) antiviral agents for use in influenza pandemics to reduce transmission and mitigate the course of clinical infection. Pandemic preparedness plans include the use of these stockpiles to deliver proportionate responses, informed by emerging evidence of clinical impact. Recent uncertainty about the effectiveness of NAIs has prompted these nations to reconsider the role of NAIs in pandemic response, with implications for pandemic planning and for NAI stockpile size. METHODS: We combined a dynamic model of influenza epidemiology with a model of the clinical care pathways in the Australian health care system to identify effective NAI strategies for reducing morbidity and mortality in pandemic events, and the stockpile requirements for these strategies. The models were informed by a 2015 assessment of NAI effectiveness against susceptibility, pathogenicity, and transmission of influenza. RESULTS: Liberal distribution of NAIs for early treatment in outpatient settings yielded the greatest benefits in all of the considered scenarios. Restriction of community-based treatment to risk groups was effective in those groups, but failed to prevent the large proportion of cases arising from lower risk individuals who comprise the majority of the population. CONCLUSIONS: These targeted strategies are only effective if they can be deployed within the constraints of existing health care infrastructure. This finding highlights the critical importance of identifying optimal models of care delivery for effective emergency health care response.