Infectious Diseases - Research Publications

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    Treatment access is only the first step to hepatitis C elimination: experience of universal anti-viral treatment access in Australia
    Doyle, JS ; Scott, N ; Sacks-Davis, R ; Pedrana, AE ; Thompson, AJ ; Hellard, ME ; Dietze, P ; McBryde, E ; Sievert, W ; Stoove, M ; Higgs, P ; Petrie, D ; Vickerman, P (WILEY, 2019-05)
    BACKGROUND: Global targets to eliminate hepatitis C (HCV) might be met by sustained treatment uptake. AIM: To describe factors facilitating HCV treatment uptake and potential challenges to sustaining treatment levels after universal access to direct-acting anti-virals (DAA) across Australia. METHODS: We analysed national Pharmaceutical Benefits Scheme data to determine the number of DAA prescriptions commenced before and after universal access from March 2016 to June 2017. We inferred facilitators and barriers to treatment uptake, and challenges that will prevent local and global jurisdictions reaching elimination targets. RESULTS: In 2016, 32 877 individuals (14% of people living with HCV in Australia) commenced HCV DAA treatment, and 34 952 (15%) individuals commenced treatment in the first year of universal access. Treatment uptake peaked at 13 109 DAA commencements per quarter immediately after universal access, but more than halved (to 5320 in 2017 Q2) within 12 months. General practitioners have written 24% of all prescriptions but with a significantly increased proportion over time (9% in 2016 Q1 to 37% in 2017 Q2). In contrast, hepatology or infectious diseases specialists have written a declining share from 74% to 38% during the same period. General practitioners provided a greater proportion (47%) of care in regional/remote areas than major cities. CONCLUSIONS: Broad treatment access led to rapid initial increases in treatment uptake, but this uptake has not been sustained. Our results suggest achieving global elimination targets requires more than treatment availability: people with HCV need easy access to testing and linkage to care in community settings employing a diverse prescriber base.
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    Intrahousehold Transmission of Pandemic (H1N1) 2009 Virus, Victoria, Australia
    van Gemert, C ; Hellard, M ; McBryde, ES ; Fielding, J ; Spelman, T ; Higgins, N ; Lester, R ; Vally, H ; Bergeri, I (CENTERS DISEASE CONTROL & PREVENTION, 2011-09)
    To examine intrahousehold secondary transmission of pandemic (H1N1) 2009 virus in households in Victoria, Australia, we conducted a retrospective cross-sectional study in late 2009. We randomly selected case-patients reported during May-June 2009 and their household contacts. Information collected included household characteristics, use of prevention and control measures, and signs and symptoms. Secondary cases were defined as influenza-like illness in household contacts within the specified period. Secondary transmission was identified for 18 of 122 susceptible household contacts. To identify independent predictors of secondary transmission, we developed a model. Risk factors were concurrent quarantine with the household index case-patient, and a protective factor was antiviral prophylaxis. These findings show that timely provision of antiviral prophylaxis to household contacts, particularly when household members are concurrently quarantined during implementation of pandemic management strategies, delays or contains community transmission of pandemic (H1N1) 2009 virus.
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    Hepatitis C Transmission and Treatment in Contact Networks of People Who Inject Drugs
    Rolls, DA ; Sacks-Davis, R ; Jenkinson, R ; McBryde, E ; Pattison, P ; Robins, G ; Hellard, M ; Noymer, A (PUBLIC LIBRARY SCIENCE, 2013-11-01)
    Hepatitis C virus (HCV) chronically infects over 180 million people worldwide, with over 350,000 estimated deaths attributed yearly to HCV-related liver diseases. It disproportionally affects people who inject drugs (PWID). Currently there is no preventative vaccine and interventions feature long treatment durations with severe side-effects. Upcoming treatments will improve this situation, making possible large-scale treatment interventions. How these strategies should target HCV-infected PWID remains an important unanswered question. Previous models of HCV have lacked empirically grounded contact models of PWID. Here we report results on HCV transmission and treatment using simulated contact networks generated from an empirically grounded network model using recently developed statistical approaches in social network analysis. Our HCV transmission model is a detailed, stochastic, individual-based model including spontaneously clearing nodes. On transmission we investigate the role of number of contacts and injecting frequency on time to primary infection and the role of spontaneously clearing nodes on incidence rates. On treatment we investigate the effect of nine network-based treatment strategies on chronic prevalence and incidence rates of primary infection and re-infection. Both numbers of contacts and injecting frequency play key roles in reducing time to primary infection. The change from "less-" to "more-frequent" injector is roughly similar to having one additional network contact. Nodes that spontaneously clear their HCV infection have a local effect on infection risk and the total number of such nodes (but not their locations) has a network wide effect on the incidence of both primary and re-infection with HCV. Re-infection plays a large role in the effectiveness of treatment interventions. Strategies that choose PWID and treat all their contacts (analogous to ring vaccination) are most effective in reducing the incidence rates of re-infection and combined infection. A strategy targeting infected PWID with the most contacts (analogous to targeted vaccination) is the least effective.
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    The Spread of Influenza A(H1N1) pdm09 in Victorian School Children in 2009: Implications for Revised Pandemic Planning
    Fielding, JE ; Bergeri, I ; Higgins, N ; Kelly, HA ; Meagher, J ; McBryde, ES ; Moran, R ; Hellard, ME ; Lester, RA ; Nishiura, H (PUBLIC LIBRARY SCIENCE, 2013-02-26)
    BACKGROUND: Victoria was the first state in Australia to experience community transmission of influenza A(H1N1)pdm09. We undertook a descriptive epidemiological analysis of the first 1,000 notified cases to describe the epidemic associated with school children and explore implications for school closure and antiviral distribution policy in revised pandemic plans. METHODS: Records of the first 1,000 laboratory-confirmed cases of influenza A(H1N1)pdm09 notified to the Victorian Government Department of Health between 20 May and 5 June 2009 were extracted from the state's notifiable infectious diseases database. Descriptive analyses were conducted on case demographics, symptoms, case treatment, prophylaxis of contacts and distribution of cases in schools. RESULTS: Two-thirds of the first 1,000 cases were school-aged (5-17 years) with cases in 203 schools, particularly along the north and western peripheries of the metropolitan area. Cases in one school accounted for nearly 8% of all cases but the school was not closed until nine days after symptom onset of the first identified case. Amongst all cases, cough (85%) was the most commonly reported symptom followed by fever (68%) although this was significantly higher in primary school children (76%). The risk of hospitalisation was 2%. The median time between illness onset and notification of laboratory confirmation was four days, with only 10% of cases notified within two days of onset and thus eligible for oseltamivir treatment. Nearly 6,000 contacts were followed up for prophylaxis. CONCLUSIONS: With a generally mild clinical course and widespread transmission before its detection, limited and short-term school closures appeared to have minimal impact on influenza A(H1N1)pdm09 transmission. Antiviral treatment could rarely be delivered to cases within 48 hours of symptom onset. These scenarios and lessons learned from them need to be incorporated into revisions of pandemic plans.
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    Eradication of Hepatitis C Infection: The Importance of Targeting People Who Inject Drugs
    Hellard, M ; Doyle, JS ; Sacks-Davis, R ; Thompson, AJ ; McBryde, E (WILEY, 2014-02)
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    The role of a hepatitis C virus vaccine: modelling the benefits alongside direct-acting antiviral treatments
    Scott, N ; McBryde, E ; Vickerman, P ; Martin, NK ; Stone, J ; Drummer, H ; Hellard, M (BMC, 2015-08-20)
    BACKGROUND: Hepatitis C virus (HCV) elimination is being seriously considered globally. Current elimination models require a combination of highly effective HCV treatment and harm reduction, but high treatment costs make such strategies prohibitively expensive. Vaccines should play a key role in elimination but their best use alongside treatments is unclear. For three vaccines with different efficacies we used a mathematical model to estimate the additional reduction in HCV prevalence when vaccinating after treatment; and to identify in which settings vaccines could most effectively reduce the number of treatments required to achieve fixed reductions in HCV prevalence among people who inject drugs (PWID). METHODS: A deterministic model of HCV transmission among PWID was calibrated for settings with 25, 50 and 75% chronic HCV prevalence among PWID, stratified by high-risk or low-risk PWID. For vaccines with 30, 60 or 90% efficacies, different rates of treatment and vaccination were introduced. We compared prevalence reductions achieved by vaccinating after treatment to prevent reinfection and vaccinating independently of treatment history in the community; and by allocating treatments and vaccinations to specific risk groups and proportionally across risk groups. RESULTS: Vaccinating after treatment was minimally different to vaccinating independently of treatment history, and allocating treatments and vaccinations to specific risk groups was minimally different to allocating them proportionally across risk groups. Vaccines with 30 or 60% efficacy provided greater additional prevalence reduction per vaccination in a setting with 75% chronic HCV prevalence among PWID than a 90% efficacious vaccine in settings with 25 or 50% chronic HCV prevalence among PWID. CONCLUSIONS: Vaccinating after treatment is an effective and practical method of administration. In settings with high chronic HCV prevalence among PWID, even modest coverage with a low-efficacy vaccine could provide significant additional prevalence reduction beyond treatment alone, and would likely reduce the cost of achieving prevalence reduction targets.
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    Description of social contacts among student cases of pandemic influenza during the containment phase, Melbourne, Australia, 2009
    van Gemert, C ; McBryde, ES ; Bergeri, I ; Sacks-Davis, R ; Vally, H ; Spelman, T ; Sutton, B ; Hellard, M (WORLD HEALTH ORGANIZATION, REGIONAL OFFICE WESTERN PACIFIC, 2018)
    INTRODUCTION: Students comprised the majority of early cases of influenza A(H1N1)pdm09 in Melbourne, Australia. Students and school settings were targeted for public health interventions following the emergence of pH1N1. This study was conducted to describe changes in social contacts among the earliest confirmed student cases of pH1N1 in Melbourne, Australia, to inform future pandemic control policy and explore transmission model assumptions. METHODS: A retrospective cross-sectional behavioural study of student cases with laboratory-confirmed pH1N1 between 28 April and 3 June 2009 was conducted in 2009. Demographics, symptom onset dates and detailed information on regular and additional extracurricular activities were collected. Summary measures for activities were calculated, including median group size and median number of close contacts and attendance during the students' exposure and infectious periods or during school closures. A multivariable model was used to assess associations between rates of participation in extracurricular activities and both school closures and students' infectious periods. RESULTS: Among 162 eligible cases, 99 students participated. Students reported social contact in both curricular and extra-curricular activities. Group size and total number of close contacts varied. While participation in activities decreased during the students' infectious periods and during school closures, social contact was common during periods when isolation was advised and during school closures. DISCUSSION: This study demonstrates the potential central role of young people in pandemic disease transmission given the level of non-adherence to prevention and control measures. These finding have public health implications for both informing modelling estimates of future pandemics and targeting prevention and control strategies to young people.