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Title: Cryptococcal meningitis : treatment and prevention
Author: Longley , Nicky
ISNI:       0000 0004 7427 1305
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2018
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Background Cryptococcal meningitis and tuberculosis are the lead causes of mortality in late stage HIV. I examine the treatment and prevention of Cryptococcal disease and early detection of Tuberculosis in Sub- Saharan Africa. Methods I conducted 4 studies: 1. Dose-response effect of high dose fluconazole for HIV-associated Cryptococcal Meningitis. 2. Cryptococcal Antigen Screening in Patients Initiating ART: A Prospective Cohort Study 3. Evaluation of a Public-sector, Provider-initiated Cryptococcal Antigen Screening and Treatment Program. 4. The predictive value of urine lipoarabinomannan lateral-flow assay for incident tuberculosis, hospitalisation and / or death in outpatients during their first year of ART. Results The early fungicidal activity of Fluconazole was significantly greater for 1200mg than it was for 800mg. Incident CM was associated with higher plasma/serum LFA titers. 12-month mortality was 25% in CrAg-positive patients compared with 11.5% in CrAg-negative patients despite pre-emptive fluconazole treatment. 4 out of 10 serum CrAg positive patients agreeing to an LP were found to have evidence of meningeal infection. In the provider initiated CrAg screening program in the public health sector only 26.6% of eligible patients were screened during the first year of the program. Patients testing LAM-positive had a median time to TB treatment of 7 days and were more likely to require hospitalisation and die within the first year of ART. Conclusion Where Amphotericin B is not available or safe to administer, 1200mg of Fluconazole clears infection more rapidly than 800mg. CrAg screening and pre-emptive treatment with fluconazole in patients with late stage HIV reduced the number of cases of CM compared to historic controls. Further studies are needed to refine the treatment of CrAg positive patients. Provider initiated CrAg screening did not achieve optimal levels and may have caused delay in ART initiation. Screening for urinary LAM may reduce the time to TB treatment by 1 week and allow early identification of patients at the highest risk of adverse events in the first year of ART.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available