Cryptococcal Meningitis in Viet Nam

Day, Jeremy Noel (2010). Cryptococcal Meningitis in Viet Nam. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000f1f2

Abstract

Cryptococcal neoformans is the commonest cause of invasive fungal disease in the world, causing up to 1.5 million cases of meningitis each year, and 1 million deaths. The aims of this thesis were to understand the differences in cryptococcal meningitis in Viet Nam in relation to the HIV infection status of the host, focussing on disease clinical phenotype, prognostic factors and the molecular epidemiology of the infecting isolates. In addition, the thesis examines the antifungal susceptibilities of Vietnamese Cryptococcus spp, how these vary by species and time, and the clinical utility of their measurement.

Patients drawn from two prospective cohorts (HIV infected and HIV uninfected) form the basis of the thesis. The HIV uninfected patients are predominantly immunocompetent. Clinical and investigational findings are compared in relation to the literature. HIV patients had shorter durations of history and more frequent headache, but there were few differences in clinical presentation. Previously published prognostic factors were reassessed; only 3 of 40 (altered consciousness, cerebrospinal fluid (CSF) white cell count, and CSF cryptococcal antigen titre) were independently associated with outcome.

Mortality was significantly higher in HIV infected patients, but the shapes of the survival curves were similar for both groups, most deaths occurring in the first 4 weeks of treatment.

Amplified Fragment Length Polymorphism analysis was used to define the relationships between HIV positive and negative strains - a clade of C. neoformans var grubii with increased propensity to cause disease in immunocompetent patients was identified. The Sensititre® YeastOne® system was used to determine MICs of 7 antifungal drugs. The susceptibility of C. neoformans has decreased significantly over a 13 year period. No relationship with the rate of clearance of yeast from CSF and antifungal MIC was found, but raised amphotericin B MIC after 48 hours incubation may be associated with early death and warrants further investigation.