School of Mathematics and Statistics - Research Publications

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    Diagnosis and Antiviral Intervention Strategies for Mitigating an Influenza Epidemic
    Moss, R ; McCaw, JM ; McVernon, J ; Davis, CT (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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    Likely effectiveness of pharmaceutical and non-pharmaceutical interventions for mitigating influenza virus transmission in Mongolia
    Bolton, KJ ; McCaw, JM ; Moss, R ; Morris, RS ; Wang, S ; Burma, A ; Darma, B ; Narangerel, D ; Nymadawa, P ; McVernon, J (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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    Drivers and consequences of influenza antiviral resistant-strain emergence in a capacity-constrained pandemic response
    Dafilis, MP ; Moss, R ; McVernon, J ; McCaw, J (ELSEVIER SCIENCE BV, 2012-12)
    Antiviral agents remain a key component of most pandemic influenza preparedness plans, but there is considerable uncertainty regarding their optimal use. In particular, concerns exist regarding the likelihood of wide-scale distribution to select for drug-resistant variants. We used a model that considers the influence of logistical constraints on diagnosis and drug delivery to consider achievable 'reach' of alternative antiviral intervention strategies targeted at cases of varying severity, with or without pre-exposure prophylaxis of contacts. To identify key drivers of epidemic mitigation and resistance emergence, we used Latin hypercube sampling to explore plausible ranges of parameters describing characteristics of wild type and resistant viruses, along with intervention efficacy, target coverage and distribution capacity. Within our model framework, 'real world' constraints substantially reduced achievable drug coverage below stated targets as the epidemic progressed. In consequence, predictions of both intervention impact and selection for resistance were more modest than earlier work that did not consider such limitations. Definitive containment of transmission was unlikely but, where observed, achieved through early liberal post-exposure prophylaxis of known contacts of treated cases. Predictors of resistant strain dominance were high intrinsic fitness relative to the wild type virus, and early emergence in the course of the epidemic into a largely susceptible population, even when drug use was restricted to severe case treatment. Our work demonstrates the importance of consideration of 'real world' constraints in scenario analysis modeling, and highlights the utility of models to guide surveillance activities in preparedness and response.