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The parasitic nematode, Teladorsagia (Ostertagia) circumcincta is the primary cause of Parasitic Gastro-Enteritis (PGE) in lambs in Britain. Control of this parasite has largely depended on the use of broad spectrum anthelmintic drugs since their inception three decades ago. Widespread and unconstrained use of anthelmintics has resulted in selection for resistant strains of nematode, particularly within the T. circumcincta species. Control of PGE now involves optimizing parasite control whilst preserving the susceptibility of the parasites to the anti-parasitic drugs. Two aspects of the epidemiology of T. circumcincta are investigated in this thesis. First, the effect of temperature on the development and survival of the free-living stages is investigated. The conventional nematode development models are replaced by more sophisticated and biologically meaningful methods of describing temperature-dependent development rate phenomena in nematodes. The effect of geographical, temporal and developmental variation on the population dynamics of T. circumcincta are explored to determine possible sources of observed variability in infection levels in the field. Next, a suite of models generic to most direct life cycle parasites undergoing intensive drug therapy, is constructed and analysed. Provision is made within these models to explore the impact of important life history events such as refugia and immigration on the evolution of resistance. A novel technique in resistance control involving overwhelming a resistant strain of nematode with a susceptible strain is modelled and suggestions made for the practical implementation of such a method.

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Larval schistosomes infect the human host by penetration of unbroken skin, before gaining access to a blood vessel and beginning their intravascular life. The work in this thesis focuses on the mammalian infection process, as it would be the ideal point to interrupt the life cycle. A whole organism approach was taken, and the life cycle stages before, during and after skin penetration were studied, namely the intra-molluscan germ ball (embryonic cercaria), infective cercaria, and the in vitro cultured day 3 schistosomulum (equivalent to skin stage larva). Confocal microscopy was used for a morphological survey of these life cycle stages, establishing the timeline of cercarial embryogenesis and documenting the impressive changes they undergo. The temporal and spatial gene expression patterns underlying the changes were investigated using the first genome-wide microarray for S. mansoni for transcriptional profiling of the three stages. The known repertoire of molecules likely to be secreted during host entry was greatly expanded, particularly the proteases and venom allergen-like proteins. Genes involved in energy production and conservation were up-regulated in the cercaria, as were several genes encoding proteins deployed immediately on arrival in the skin. Additionally, micro exon genes (MEGs) encoding variant secreted proteins were highly upregulated in the schistosomulum, emphasising their likely role after entry into the mammalian host. The transcription of many tegument and gut-associated genes was also increased in the schistosomulum; cathepsins were particularly notable, even in the cercaria, implying that the larval gut becomes active long before blood feeding begins. The first application of whole mount in situ hybridisation to germ balls confirmed localisation of invadolysin and VAL-10 to the nascent acetabular glands. However, SmKK7 and Sm16 were not expressed in these glands, questioning their putative roles in immunomodulation. Finally, three MEGs were revealed to be expressed in tissues at the host-parasite interface.

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