African trypanosomiasis is a protozoan infection affecting tens of thousands of people and millions of livestock animals across sub-Saharan Africa. In humans the disease is fatal without chemotherapeutic intervention and in animals it causes a severe anaemia that greatly impairs productivity. Available drug compounds are difficult to administer and unacceptably toxic. A natural product, ascofuranone, inhibits a key trypanosome specific respiratory enzyme, trypanosome alternative oxidase, and was shown over a decade ago to be trypanocidal using both in vitro and in vivo experiments. The compound suffers from rapid metabolism and contains several functionalities undesirable in a drug compound. Despite the promising activity the lack of applicable synthetic methods available hampered the development of chemotherapeutics from ascofuranone. In this work, novel synthetic routes were completed to explore the lead compound. New synthetic methods were successfully developed using palladium catalysed Suzuki couplings and Lewis acid catalysed rearrangements. Ortho-lithiation approaches also afforded potent novel inhibitors. Of particular note is a benzisoxazole, which is expected to alleviate many of the metabolic issues associated with ascofuranone. Alternate heterocycle analogues were explored and an interesting indazole analogue obtained. Finally, chemical methods were developed towards the benzisoxazole and indazole motifs with carboxylic acids, amenable to diversification by amide coupling. A preliminary range of novel amide containing 5, 6-heterocycles were synthesized to begin SAR exploration of these structures.

This thesis examines the Influenza A/H5N1 virus in action through an ethnographic study focused on the entwined concepts of risk and modernity. The objective is to explain why the response to the virus has been challenged in Indonesia. Concerned with policy formulation, and everyday practice, the thesis argues that assemblages of historical, political, institutional and knowledge‐power processes create multiple hybrid constructions of risk and modernity, which challenge technical responses based on epistemological positions and institutional arrangements that do not allow for such hybridity. The thesis is organised into four sections. The first section (chapters 1 – 3) introduces the virus and its terrain, outlines a constructivist position, and argues that conceptually risk and modernity have multiple, dynamic, power‐laden forms. The second section (chapters 4 – 6) contrasts constructions of risk and modernity among the actors and networks responding to the emergence, spread and persistence of the H5N1 virus, with the constructions of affected people in Indonesia. The third section (chapters 7 – 9) investigates the multi‐directional processes that occur when ‘global' policies and practices encounter ‘local' social and political settings, and vice versa, through three empirical case studies of the response to H5N1 in Indonesia between 2005 and 2010. The final section (chapter 10) provides a set of reflections and conclusions. Given the conceptual plurality of risk and modernity, and the multiple overlapping interacting hybrid constructions that have been empirically demonstrated in the case of H5N1, it is concluded that reductive, science‐based, governmentally‐orientated responses which treat nature as a matter of separate, fixed identity do not allow for such hybridity. The virus in action in Indonesia shows that any divide between nature and society is artificial and deceiving. Technical disease control responses need to incorporate understandings which accept the dynamics of culture, politics, and power.

This research work is on time-delayed models of infectious diseases dynamics. The dynamics of infectious diseases are studied in the presence of time delays representing temporary immunity or latency. We have designed and analysed time-delayed models with various parameters to simulate disease dynamics, in a view to gaining insight into the behaviour of a population in the presence of infectious diseases, and the reaction of the population to changes in the management procedure of such infections.