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Title: Novel strategies for treatment and prevention of HIV-associated cryptococcal meningitis
Author: Jarvis, Joseph Nicholas
ISNI:       0000 0004 2730 0230
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2011
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Cryptococcal meningitis (CM) is a leading cause of death in HIV -infected patients in Africa. The thesis examines novel strategies for treatment and prevention of HIV - associated CM, and reports: i) A literature review of HIV -associated CM. ii) The results of a large combined cohort analysis identifying high baseline fungal burden and abnormal mental status as key determinants of mortality in patients with CM. iii) A description of the epidemiology, clinical features and outcomes of CM in Cape Town, based on a series of observational cohort studies, showing that CM is the commonest cause of adult meningitis in Cape Town, with an in- hospital mortality of ~30%, and that ART roll-out has yet to substantially reduce the number of cases or impact on in-hospital mortality. iv) A report of a randomized controlled trial demonstrating that the novel immunotherapeutic strategy of short course adjunctive IFN-y increases the rate of clearance of cryptococcal infection in HIV -associated CM. v) Results from flow cytometry and luminex analysis examining immune responses to cryptococcal infection in late stage HIV -infection, and assessing the effect of adjunctive IFN-y on the host immune response. vi) The results of a large trial demonstrating that screening for cryptococcal antigenaemia on entry into ART programmes allows the identification of patients at risk of developing CM, potentially enabling their prevention. The thesis is based on fieldwork carried out over a three-year period in Cape Town, South Africa, followed by additional laboratory work at the National Institutes of Health, Bethesda, USA and St. George's University of London.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available