The Open UniversitySkip to content

Cryptococcal Meningitis in The Tropics: Defining the Problem and Refining the Management

Beardsley, Justin (2018). Cryptococcal Meningitis in The Tropics: Defining the Problem and Refining the Management. PhD thesis. The Open University.

Full text available as:
PDF (Version of Record) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (4MB) | Preview
Google Scholar: Look up in Google Scholar


The basis of my thesis is the CryptoDex trial, a randomized controlled trial of adjunctive dexamethasone in HIV-associated cryptococcal meningitis, in 6 countries in Southeast Asia and Africa. This trial, which demonstrated harm from dexamethasone, is presented in detail in Chapter 6. To contextualize the trial, and to get a better sense of the burden of cryptococcal meningitis in Vietnam, I estimated the burden of all the major invasive fungal infections in Vietnam. An actuarial approach to making these estimates was used, and showed that the leading fungal pathogen is likely to be Aspergillus. The CryptoDex trial was stopped early on the basis of an excess of adverse events in the intervention arm. Therefore, in chapter 7, I investigate the ethical, statistical, and logistical issues around stopping clinical trials early, and provide a detailed case study of our experience with early termination. Finally, to better understand how the harmful effects of dexamethasone were mediated, I characterized markers of immune response in the cerebrospinal fluid of the study patients and described their relationship with clinical and microbiological outcomes. Here I found that dexamethasone shifted CSF cytokine concentrations from a Th1 to a Th2 profile, and that this was associated with poorer clearance of fungi.

Item Type: Thesis (PhD)
Copyright Holders: 2017 The Author
Keywords: meningitis; glucocorticoids; steroids; clinical ethics; research ethics; clinical trials
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM)
Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Associated Research Centre: Oxford University Clinical Research Unit Vietnam
Item ID: 53423
Depositing User: Justin Beardsley
Date Deposited: 27 Mar 2018 12:35
Last Modified: 23 Jan 2020 19:03
Share this page:

Download history for this item

These details should be considered as only a guide to the number of downloads performed manually. Algorithmic methods have been applied in an attempt to remove automated downloads from the displayed statistics but no guarantee can be made as to the accuracy of the figures.

Actions (login may be required)

Policies | Disclaimer

© The Open University   contact the OU