School of Mathematics and Statistics - Research Publications

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    Dynamical crises, multistability and the influence of the duration of immunity in a seasonally-forced model of disease transmission
    Dafilis, MP ; Frascoli, F ; McVernon, J ; Heffernan, JM ; McCaw, JM (BMC, 2014-10-04)
    BACKGROUND: Highly successful strategies to make populations more resilient to infectious diseases, such as childhood vaccinations programs, may nonetheless lead to unpredictable outcomes due to the interplay between seasonal variations in transmission and a population's immune status. METHODS: Motivated by the study of diseases such as pertussis we introduce a seasonally-forced susceptible-infectious-recovered model of disease transmission with waning and boosting of immunity. We study the system's dynamical properties using a combination of numerical simulations and bifurcation techniques, paying particular attention to the properties of the initial condition space. RESULTS: We find that highly unpredictable behaviour can be triggered by changes in biologically relevant model parameters such as the duration of immunity. In the particular system we analyse--used in the literature to study pertussis dynamics--we identify the presence of an initial-condition landscape containing three coexisting attractors. The system's response to interventions which perturb population immunity (e.g. vaccination "catch-up" campaigns) is therefore difficult to predict. CONCLUSION: Given the increasing use of models to inform policy decisions regarding vaccine introduction and scheduling and infectious diseases intervention policy more generally, our findings highlight the importance of thoroughly investigating the dynamical properties of those models to identify key areas of uncertainty. Our findings suggest that the often stated tension between capturing biological complexity and utilising mathematically simple models is perhaps more nuanced than generally suggested. Simple dynamical models, particularly those which include forcing terms, can give rise to incredibly complex behaviour.
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    The dynamical consequences of seasonal forcing, immune boosting and demographic change in a model of disease transmission
    Dafilis, MP ; Frascoli, F ; McVernon, J ; Heffernan, JM ; McCaw, JM (ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2014-11-21)
    The impact of seasonal effects on the time course of an infectious disease can be dramatic. Seasonal fluctuations in the transmission rate for an infectious disease are known mathematically to induce cyclical behaviour and drive the onset of multistable and chaotic dynamics. These properties of forced dynamical systems have previously been used to explain observed changes in the period of outbreaks of infections such as measles, varicella (chickenpox), rubella and pertussis (whooping cough). Here, we examine in detail the dynamical properties of a seasonally forced extension of a model of infection previously used to study pertussis. The model is novel in that it includes a non-linear feedback term capturing the interaction between exposure and the duration of protection against re-infection. We show that the presence of limit cycles and multistability in the unforced system give rise to complex and intricate behaviour as seasonal forcing is introduced. Through a mixture of numerical simulation and bifurcation analysis, we identify and explain the origins of chaotic regions of parameter space. Furthermore, we identify regions where saddle node lines and period-doubling cascades of different orbital periods overlap, suggesting that the system is particularly sensitive to small perturbations in its parameters and prone to multistable behaviour. From a public health point of view - framed through the 'demographic transition' whereby a population׳s birth rate drops over time (and life-expectancy commensurately increases) - we argue that even weak levels of seasonal-forcing and immune boosting may contribute to the myriad of complex and unexpected epidemiological behaviours observed for diseases such as pertussis. Our approach helps to contextualise these epidemiological observations and provides guidance on how to consider the potential impact of vaccination programs.
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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.