Dr Tihana Bicanic and colleagues have identified key pathogen and host factors affecting the outcome of cryptococcal fungal infections.
Cryptococcus is an important opportunistic infection in people living with HIV, responsible for more than 100,000 deaths a year from cryptococcal meningitis. Using samples collected during clinical trials in Africa, Dr Bicanic has identified a range of factors associated with poor outcomes. Two projects funded by a Wellcome Trust Strategic Award in medical mycology and fungal immunology have enabled her team to gain additional insights into Cryptococcus and host responses.
Working in Tanzania, Dr Neil Stone analysed Cryptococcus isolated directly from spinal fluid samples to confirm that a mechanism of drug resistance identified in experimental animal models – transient chromosomal duplication – also occurs in human infection. Resistance to fluconazole, the drug typically used to treat Cryptococcus in Africa, was associated with duplication of the chromosome on which the gene encoding the target of fluconazole is located. The se of combination therapy with flucytosine prevented resistance from emerging.
Dr Bicanic and Dr Shichina Kannambath undertook the first ever genome wide association study of susceptibility to cryptococcal meningitis. The study, which compared patients with HIV and low CD4 counts with or without disseminated cryptococcal infection, identified several susceptibility loci relevant to phagocytosis and macrophage activation.
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