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This thesis is the first thorough investigation into the immediate post-PZQ (praziquantel) treatment immune response, its regulation and its importance in the development of immunity to infection. Three Ugandan cohorts have been studied. Combining the statistical analyses of the studies has demonstrated that the immediate post-treatment immune response is IgE-mediated and stimulated by schistosome worm antigen. The response involves a co-ordinated activation of IgE-effector cells and production of Th2 cytokines. Importantly, this Th2 response immediately after treatment appears to be the genesis of the immune response which ultimately result sin later post-treatment markers of immunity. The immediate post-PZQ treatment immune response closely resembles the allergic hypersensitivity response but, unlike allergic responses, does not develop to anaphylaxis. Immunoregulation of the post-treatment response was therefore investigated. In particular, soluble cytokine receptors were measured for the first time in samples from schistosome-infected humans. Side effects were recorded for two of the study cohorts in this thesis and it is shown, for the first time, that some side effects are closely associated with the post-treatment immune response whereas others are more related to the dose of PZQ administered. Finally, structural equation modelling was applied to the data from these studies. The results provide a unique overview of the demographic and immunological variation in these treatment-reinfection studies and reinforce the importance of the immediate post-treatment immune response in the development of immunity to schistosome infection.

This study was conducted among 1170 children aged 6 to 65 months in Faki Hashim and Gezira Slanj villages, Sudan, to determine the impact of malaria and insecticide-impregnated bednets on anthropometry and growth. Impregnated bednets were distributed to 581 of 611 F.Hashim children. From June 1997 through March 1998, children were followed up with quarterly anthropometric and blood film surveys, and fortnightly child health questionnaires. In the first survey at the end of June 1997, mean weight-for-age scores corresponded to 87.8% of the NCHS median for females and 85.7% for males. Weight, height and arm circumference appeared to be largely accounted for by age and sex (up to 73%, 86% and 21% of the variance respectively) and by socio-economic influences (0.4% to 3.5%). In contrast, much of the variation in Z scores could not be explained. Quarterly changes in weight averaged +0.4 to +0.7 kg, while mean height gains were between +1.7 and +2.4 cm in 3 months. During the 9 months follow-up, 55.1% of children in F.Hashim and 32.6% in G.Slanj experienced an episode of malaria. The distribution was seasonal with point prevalences ranging between 5.1% and 12.1% in F.Hashim and 0.8% to 3.8% in G.Slanj. Fevers were associated with smaller changes in weight, weight-for-age and arm circumference in the first interval, but only arm circumference in the second interval. Malaria was associated with smaller changes in weight-for-age in the first and second intervals, and with a higher risk of developing stunting over the 9 months, particularly during the third interval. Because the bednets had been introduced into a community without a tradition of using nets, mothers' compliance with using the impregnated bednets was poor. A comparative stub-study among 148 children not using bednets was conducted in the Atashab sector of F.Hashim from January to March 1998. Despite, some evidence of reduced malaria, the impregnated bednets could not be shown to influence anthropometry or growth in F.Hashim.

The thesis is based on a ten month household-based parallel study of the entomological and parasitological features of infection and transmission of lymphatic filariasis, which I conducted in an endemic village in northern Papua New Guinea. The work focused on assessing the role of vector biting patterns as a contributor to the small-scale differences in infection rates seen at both the household and individual levels. Chapter 1 describe the lifecycle of the parasite - <I>Wuchereria bancroft - </I>and the observed heterogeneities in infection at the micro-epidemiological scale. Chapter 2 describes the measurement and treatment of filariasis infection in the village population. Chapter 3 describes the epidemiology of infection in the human population, highlighting the heterogeneities in prevalence and intensity between households and individuals. The basic ecology of the main anthropophilic mosquito species is outlined in Chapter 4. An examination of the relationship between the spatial distribution of the vectors and certain ecological and domestic correlates identifies risk factors which are associated with higher mosquito densities, and therefore higher vector-man contact rates. This is the most detailed analysis of risk factors associated with exposure to lymphatic filariasis thus far. The two main methods of mosquito collection (resting and biting catches) are compared in Chapter 5, showing that in terms of relative densities, species composition and infection rates they are not entirely interchangeable. Chapter 6 describes the observed vector infection rates and monitors the effect of treatment of the host population. In particular it examines the data for evidence of a possible density-dependent relationship between parasite densities in host and vector. The spatial dynamics of infection are synthesised in Chapter 7. Chapter 8 is a general discussion which concludes with suggestions for future research and outlines implications of these findings for the planning and implementation of filariasis control programmes.

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