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How often have you asked yourself: "I wonder how many fish are in that lake?" Probably never, but if you ever did, then this is the lecture for you. The solution is easy (Seuss, 1960), but raises the question of how good the answer is. I will answer this by looking at confidence intervals. In the lecture, I will discuss what a confidence interval is and how to calculate it using techniques for calculating probabilities in poker. I will also look at how these ideas have been used in epidemiology, the study of disease, to estimate the number of people with diabetes. [1] Seuss, Dr. (1960). "One Fish Two Fish Red Fish Blue Fish". Random House Books.

Mathematical models are now used routinely to inform national and global policy-makers on issues that threaten human health or which have an adverse impact on the economy. In the first part of this talk I will provide an overview of mathematical epidemiology starting with the classical deterministic model and leading to some of the current challenges. I will then present some of my recently published work which provides computationally-efficient methods for studying a mathematical model incorporating household structure. We will conclude by briefly discussing some "work-in-progess" which utilises these methods to address the issues of inference, and mixing pattern and contact structure, for emerging infections.

Markov population processes are popular models for studying a wide range of phenomena including the spread of disease, the evolution of chemical reactions and the movements of organisms in population networks (metapopulations). Our ability to use these models effectively can be limited by our knowledge about parameters, such as disease transmission and recovery rates in an epidemic. Recently, there has been interest in devising optimal experimental designs for stochastic models, so that practitioners can collect data in a manner that maximises the precision of maximum likelihood estimates of the parameters for these models. I will discuss some recent work on optimal design for a variety of population models, beginning with some simple one-parameter models where the optimal design can be obtained analytically and moving on to more complicated multi-parameter models in epidemiology that involve latent states and non-exponentially distributed infectious periods. For these more complex models, the optimal design must be arrived at using computational methods and we rely on a Gaussian diffusion approximation to obtain analytical expressions for Fisher's information matrix, which is at the heart of most optimality criteria in experimental design. I will outline a simple cross-entropy algorithm that can be used for obtaining optimal designs for these models. We will also explore the improvements in experimental efficiency when using the optimal design over some simpler designs, such as the design where observations are spaced equidistantly in time.

The mathematical study of human-to-human transmissible pathogens has established itself as a complementary methodology to the traditional epidemiological approach. The classic susceptible--infectious--recovered model paradigm has been used to great effect to gain insight into the epidemiology of endemic diseases such as influenza and pertussis, and the emergence of novel pathogens such as SARS and pandemic influenza. The modelling paradigm has also been taken within the host and used to explain the within-host dynamics of viral (or bacterial or parasite) infections, with implications for our understanding of infection, emergence of drug resistance and optimal drug-interventions. In this presentation I will provide an overview of the mathematical paradigm used to investigate both biological and epidemiological infectious diseases systems, drawing on case studies from influenza, malaria and pertussis research. I will conclude with a summary of how infectious diseases modelling has assisted the Australian government in developing its pandemic preparedness and response strategies.

An important component of pathogen evolution at the population level is evolution within hosts, which can alter the composition of genotypes available for transmission as infection progresses. I will present a deterministic multi-scale model, linking the within-host competition dynamics with the transmission dynamics at a population level. I will take HIV as an example of how this framework can help clarify the conflicting evolutionary pressure an infectious disease might be subject to.

Immune system memory, also called immunity, is gained as a result of primary infection or vaccination, and can be boosted after vaccination or secondary infections. Immunity is developed so that the immune system is primed to react and fight a pathogen earlier and more effectively in secondary infections. The effects of memory, however, on pathogen propagation in an individual host (in-host) and a population (epidemiology) are not well understood. Mathematical models of infectious diseases, employing dynamical systems, computer simulation and bifurcation analysis, can provide projections of pathogen propagation, show outcomes of infection and help inform public health interventions. In the Modelling Infection and Immunity (MI^2) lab, we develop and study biologically informed mathematical models of infectious diseases at both levels of infection, and combine these models into comprehensive multi-scale models so that the effects of individual immunity in a population can be determined. In this talk we will discuss some of the interesting mathematical phenomenon that arise in our models, and show how our results are directly applicable to what is known about the persistence of infectious diseases.

Epidemic models have proved useful in a number of applications in epidemiology. In this work, I will present two areas that we have used modelling to make informed decisions. Firstly, we have used an age structured mathematical model to describe the transmission of Respiratory Syncytial Virus in a developed country setting and to explore different vaccination strategies. We found that delayed infant vaccination has significant potential in reducing the number of hospitalisations in the most vulnerable group and that most of the reduction is due to indirect protection. It also suggests that marked public health benefit could be achieved through RSV vaccine delivered to age groups not seen as most at risk of severe disease. The second application is in the optimal design of studies aimed at collection of household-stratified infection data. A design decision involves making a trade-off between the number of households to enrol and the sampling frequency. Two commonly used study designs are considered: cross-sectional and cohort. The search for an optimal design uses Bayesian methods to explore the joint parameter-design space combined with Shannon entropy of the posteriors to estimate the amount of information for each design. We found that for the cross-sectional designs, the amount of information increases with the sampling intensity while the cohort design often exhibits a trade-off between the number of households sampled and the intensity of follow-up. Our results broadly support the choices made in existing data collection studies.

Visceral Leishmaniasis (VL) is targeted for elimination from the Indian Sub-Continent. Progress has been much better in some areas than others. Current control is based on earlier diagnosis and treatment and on insecticide spraying to reduce the density of the vector. There is a surprising dearth of specific information on the epidemiology of VL, which makes modelling more difficult. In this seminar, I describe a simple framework that gives some insight into the transmission dynamics. We conclude that the majority of infection comes from cases prior to diagnosis. If this is the case then, early diagnosis will be advantageous, but will require a test with high specificity. This is a paradox for many clinicians and public health workers, who tend to prioritise high sensitivity.

Medley, G.F., Hollingsworth, T.D., Olliaro, P.L. & Adams, E.R. (2015) Health-seeking, diagnostics and transmission in the control of visceral leishmaniasis. Nature 528, S102-S108 (3 December 2015), DOI: 10.1038/nature16042