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Title: Chemotherapy of human chronic Schistosomiasis mansoni : the immediate post-treatment immune response and its biological significance
Author: Houghton, Jennifer Brenda
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2010
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available