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Despite many successes in the control of human infectious diseases they continue to pose a considerable risk to human health. The global distributions of pathogens are driven by ecological factors and the magnitude and extent of transmission are influenced by the dynamics of human behaviour. Viruses such as chikungnunya virus, Zika virus, dengue virus, and Ebola virus have recently expanded geographically. However, prior to their expansion there was little quantitative evidence available to identify locations that may be susceptible to transmission and to evaluate the likelihood of virus introduction to such locations. In this thesis statistical modelling techniques were applied with the aim of understanding infectious disease ecology, determining the main drivers of disease occurrence, and predicting the magnitude and regional spread of an outbreak in real-time. My results provide estimates of the populations now living in areas with possible transmission of chikungunya virus, show that the seasonal dynamics of Zika infection coupled with data on international travel, can better predict the arrival of the virus into new locations. Analyses of regional outbreaks of viruses including Ebola virus in West Africa and Yellow fever virus in Angola and the Democratic Republic Congo, show that patterns of human mobility strongly predict the real-time spread of disease. Further, I demonstrate that the impact of human movement varies considerably depending on the time of the outbreak (expanding versus declining phase) and the country of interest. The results and conclusions of these studies are discussed in the context of improving our understanding of infectious disease dynamics and of informing public health policies, interventions, and control efforts.

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Currently, we are experiencing a global epidemic of obesity and its associated comorbidities, such as hypertension, diabetes and certain types of cancer, which in turn create a great burden on healthcare resources. Obesity is the result of an imbalance between energy intake and energy expenditure, therefore understanding mechanisms which regulate energy balance and body mass are crucial in order to prevent and treat obesity. To better understand the regulation of body mass and energy intake, two dietary intervention regimes were investigated: an acute starvation experiment and long term caloric restriction. Daily fluctuations in energy intake and energy expenditure and their impact on weight changes are not closely linked over the short term in un-manipulated circumstances; therefore this suggests that the simple set point model of body mass regulation is not accurate. The dual intervention point model provides a useful alternative to the set-point idea, and provides a conceptual basis for understanding why such parameters would not be associated in day to day measurements of un-manipulated animals. As predicted from this model more extreme manipulations - specifically 24h starvation and 29 days of restricted energy intake by 30% - caused animals to enable a series of compensatory responses that were similar but not identical. In particular these included elevation of daytime activity, and a strong hyperphagia following restoration of food supply that lasted up to 4 days but was restricted to the night time. It was found that NPY changes probably did not underpin the post restriction hyperphagia but that changes in AgRP and POMC were probably more 8 significant. Peripheral signals including leptin, insulin and TNFα are also important in relaying the peripheral status to the brain. Data suggested that TNFαR1 is critical to mediating the physical activity changes in both 24h and prolonged CR and the level of hyperphagia. In summary, this work has generated novel information on physiological, behavioural and molecular cues of body mass regulation, which contributes to a better understanding and provides useful insights for the prevention and treatment of obesity.

The maintenance of human sleeping sickness and nagana across sub-Saharan Africa depends on cyclical transmission of trypanosomes through tsetse flies. Previous work showed that the symbiotic bacterium <i>Sodalis glossinidius</i> was involved in susceptibility to trypanosome infection. Streptozotocin (a toxic analogue of the bacterium’s main food source) has been recently shown to decrease trypanosome infection rates in the offspring of treated tsetse. In the present work streptozotocin did remove <i>S. glossinidius</i> from the offspring of treated flies but it was not possible to generate a line of tsetse free from <i>S. glossinidius</i> infection. Other potential factors involved in acquisition of trypanosome infection were then examined. A range of antioxidants or cyclic GMP were shown to prevent trypanosomes death in the tsetse midgut. The process was shown to be independent of protein synthesis as D-cysteine (an unphysiological isomer of L-cysteine) also enhanced midgut infection rates. Further experiments showed that cGMP could significantly inhibit trypanosome death when fed up to 96 h post-infection, whereas antioxidants only functioned for 48 h post-infection. Moreover it was found that maturation of established midgut infections could be regulated by environmental stimuli as well as by antioxidants. Cold shock of infected flies as well as addition of L-cysteine but not D-cysteine to the bloodmeal resulted in significant increases in maturation rates, while nitric oxide synthase inhibitors reduced maturation rates. It is concluded that reactive oxygen species play a major role in killing trypanosomes entering the tsetse midgut and that cysteine containing proteins and/or nitric oxide are essential for differentiation of established midgut infections into mammalian infective salivary gland infections.