School of Mathematics and Statistics - Research Publications
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ItemAnatomy of a seasonal influenza epidemic forecast(Department of Health, Australian Government, 2019-03-15)Bayesian methods have been used to predict the timing of infectious disease epidemics in various settings and for many infectious diseases, including seasonal influenza. But integrating these techniques into public health practice remains an ongoing challenge, and requires close collaboration between modellers, epidemiologists, and public health staff. During the 2016 and 2017 Australian influenza seasons, weekly seasonal influenza forecasts were produced for cities in the three states with the largest populations: Victoria, New South Wales and Queensland. Forecast results were presented to Health Department disease surveillance units in these jurisdictions, who provided feedback about the plausibility and public health utility of these predictions. In earlier studies we found that delays in reporting and processing of surveillance data substantially limited forecast performance, and that incorporating climatic effects on transmission improved forecast performance. In this study of the 2016 and 2017 seasons, we sought to refine the forecasting method to account for delays in receiving the data, and used meteorological data from past years to modulate the force of infection. We demonstrate how these refinements improved the forecast’s predictive capacity, and use the 2017 influenza season to highlight challenges in accounting for population and clinician behaviour changes in response to a severe season.
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ItemAccounting for Healthcare-Seeking Behaviours and Testing Practices in Real-Time Influenza Forecasts(MDPI, 2019-01-11)For diseases such as influenza, where the majority of infected persons experience mild (if any) symptoms, surveillance systems are sensitive to changes in healthcare-seeking and clinical decision-making behaviours. This presents a challenge when trying to interpret surveillance data in near-real-time (e.g., to provide public health decision-support). Australia experienced a particularly large and severe influenza season in 2017, perhaps in part due to: (a) mild cases being more likely to seek healthcare; and (b) clinicians being more likely to collect specimens for reverse transcription polymerase chain reaction (RT-PCR) influenza tests. In this study, we used weekly Flutracking surveillance data to estimate the probability that a person with influenza-like illness (ILI) would seek healthcare and have a specimen collected. We then used this estimated probability to calibrate near-real-time seasonal influenza forecasts at each week of the 2017 season, to see whether predictive skill could be improved. While the number of self-reported influenza tests in the weekly surveys are typically very low, we were able to detect a substantial change in healthcare seeking behaviour and clinician testing behaviour prior to the high epidemic peak. Adjusting for these changes in behaviour in the forecasting framework improved predictive skill. Our analysis demonstrates a unique value of community-level surveillance systems, such as Flutracking, when interpreting traditional surveillance data. These methods are also applicable beyond the Australian context, as similar community-level surveillance systems operate in other countries.
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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.
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ItemNo Preview AvailableRetrospective forecasting of the 2010-2014 Melbourne influenza seasons using multiple surveillance systems(CAMBRIDGE UNIV PRESS, 2017-01)Accurate forecasting of seasonal influenza epidemics is of great concern to healthcare providers in temperate climates, since these epidemics vary substantially in their size, timing and duration from year to year, making it a challenge to deliver timely and proportionate responses. Previous studies have shown that Bayesian estimation techniques can accurately predict when an influenza epidemic will peak many weeks in advance, and we have previously tailored these methods for metropolitan Melbourne (Australia) and Google Flu Trends data. Here we extend these methods to clinical observation and laboratory-confirmation data for Melbourne, on the grounds that these data sources provide more accurate characterizations of influenza activity. We show that from each of these data sources we can accurately predict the timing of the epidemic peak 4-6 weeks in advance. We also show that making simultaneous use of multiple surveillance systems to improve forecast skill remains a fundamental challenge. Disparate systems provide complementary characterizations of disease activity, which may or may not be comparable, and it is unclear how a 'ground truth' for evaluating forecasts against these multiple characterizations might be defined. These findings are a significant step towards making optimal use of routine surveillance data for outbreak forecasting.
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ItemNo Preview AvailableEpidemic forecasts as a tool for public health: interpretation and (re)calibration(WILEY, 2018-02)OBJECTIVE: Recent studies have used Bayesian methods to predict timing of influenza epidemics many weeks in advance, but there is no documented evaluation of how such forecasts might support the day-to-day operations of public health staff. METHODS: During the 2015 influenza season in Melbourne, Australia, weekly forecasts were presented at Health Department surveillance unit meetings, where they were evaluated and updated in light of expert opinion to improve their accuracy and usefulness. RESULTS: Predictive capacity of the model was substantially limited by delays in reporting and processing arising from an unprecedented number of notifications, disproportionate to seasonal intensity. Adjustment of the predictive algorithm to account for these delays and increased reporting propensity improved both current situational awareness and forecasting accuracy. CONCLUSIONS: Collaborative engagement with public health practitioners in model development improved understanding of the context and limitations of emerging surveillance data. Incorporation of these insights in a quantitative model resulted in more robust estimates of disease activity for public health use. Implications for public health: In addition to predicting future disease trends, forecasting methods can quantify the impact of delays in data availability and variable reporting practice on the accuracy of current epidemic assessment. Such evidence supports investment in systems capacity.
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ItemModel selection for seasonal influenza forecasting.(Elsevier BV, 2017-02)Epidemics of seasonal influenza inflict a huge burden in temperate climes such as Melbourne (Australia) where there is also significant variability in their timing and magnitude. Particle filters combined with mechanistic transmission models for the spread of influenza have emerged as a popular method for forecasting the progression of these epidemics. Despite extensive research it is still unclear what the optimal models are for forecasting influenza, and how one even measures forecast performance. In this paper, we present a likelihood-based method, akin to Bayes factors, for model selection when the aim is to select for predictive skill. Here, "predictive skill" is measured by the probability of the data after the forecasting date, conditional on the data from before the forecasting date. Using this method we choose an optimal model of influenza transmission to forecast the number of laboratory-confirmed cases of influenza in Melbourne in each of the 2010-15 epidemics. The basic transmission model considered has the susceptible-exposed-infectious-recovered structure with extensions allowing for the effects of absolute humidity and inhomogeneous mixing in the population. While neither of the extensions provides a significant improvement in fit to the data they do differ in terms of their predictive skill. Both measurements of absolute humidity and a sinusoidal approximation of those measurements are observed to increase the predictive skill of the forecasts, while allowing for inhomogeneous mixing reduces the skill. We discuss how our work could be integrated into a forecasting system and how the model selection method could be used to evaluate forecasts when comparing to multiple surveillance systems providing disparate views of influenza activity.
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ItemForecasting influenza outbreak dynamics in Melbourne from Internet search query surveillance data(WILEY, 2016-07)BACKGROUND: Accurate forecasting of seasonal influenza epidemics is of great concern to healthcare providers in temperate climates, as these epidemics vary substantially in their size, timing and duration from year to year, making it a challenge to deliver timely and proportionate responses. Previous studies have shown that Bayesian estimation techniques can accurately predict when an influenza epidemic will peak many weeks in advance, using existing surveillance data, but these methods must be tailored both to the target population and to the surveillance system. OBJECTIVES: Our aim was to evaluate whether forecasts of similar accuracy could be obtained for metropolitan Melbourne (Australia). METHODS: We used the bootstrap particle filter and a mechanistic infection model to generate epidemic forecasts for metropolitan Melbourne (Australia) from weekly Internet search query surveillance data reported by Google Flu Trends for 2006-14. RESULTS AND CONCLUSIONS: Optimal observation models were selected from hundreds of candidates using a novel approach that treats forecasts akin to receiver operating characteristic (ROC) curves. We show that the timing of the epidemic peak can be accurately predicted 4-6 weeks in advance, but that the magnitude of the epidemic peak and the overall burden are much harder to predict. We then discuss how the infection and observation models and the filtering process may be refined to improve forecast robustness, thereby improving the utility of these methods for healthcare decision support.
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ItemModel-Informed Risk Assessment and Decision Making for an Emerging Infectious Disease in the Asia-Pacific Region(PUBLIC LIBRARY SCIENCE, 2016-09)BACKGROUND: Effective response to emerging infectious disease (EID) threats relies on health care systems that can detect and contain localised outbreaks before they reach a national or international scale. The Asia-Pacific region contains low and middle income countries in which the risk of EID outbreaks is elevated and whose health care systems may require international support to effectively detect and respond to such events. The absence of comprehensive data on populations, health care systems and disease characteristics in this region makes risk assessment and decisions about the provision of such support challenging. METHODOLOGY/PRINCIPAL FINDINGS: We describe a mathematical modelling framework that can inform this process by integrating available data sources, systematically explore the effects of uncertainty, and provide estimates of outbreak risk under a range of intervention scenarios. We illustrate the use of this framework in the context of a potential importation of Ebola Virus Disease into the Asia-Pacific region. Results suggest that, across a wide range of plausible scenarios, preemptive interventions supporting the timely detection of early cases provide substantially greater reductions in the probability of large outbreaks than interventions that support health care system capacity after an outbreak has commenced. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates how, in the presence of substantial uncertainty about health care system infrastructure and other relevant aspects of disease control, mathematical models can be used to assess the constraints that limited resources place upon the ability of local health care systems to detect and respond to EID outbreaks in a timely and effective fashion. Our framework can help evaluate the relative impact of these constraints to identify resourcing priorities for health care system support, in order to inform principled and quantifiable decision making.