International health: Overview
Cryptococcal Meningitis and Cryptococcosis-associated Immune Reconstitution Inflammatory Syndrome (C-IRIS)
Project leader: Dr Christina Chang
Cryptococcal meningitis is a serious fungal brain infection with a predilection for persons with weakened immune systems. Driven by the HIV epidemic, cryptococcal meningitis is the most common cause of adult meningitis (brain lining infection); untreated all die within 6 months. Even with adequate antifungal therapy and anti-HIV-medications, patients often represent with yet another episode of neurological deterioration mimicking their previously treated brain infection – many of these episodes are caused by a phenomenon called cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS). A high fungal load and a dysregulated immune system are likely to be the main drivers. Understanding why, when and whom are likely to experience C-IRIS is critical for risk-stratification and treatment strategies.
In collaboration with Professor Martyn French (University of Western Australia) and collaborators from University of KwaZulu-Natal (UKZN), South Africa, we conducted a 130-person, prospective, longitudinal, cohort study based in Durban, South Africa from September 2009 till September 2011. We designed and built-in a number of basic science studies including blood and cerebrospinal fluid immunology assays, mycology work and virology studies to explore the determinants of C-IRIS – this formed the basis for a Monash University PhD study and a Masters of Medicine at UKZN.
Stored specimens from this well-characterised study is being further utilised to support the immunological exploration of C-IRIS and the characteristics of HIV virus in the central nervous system compared to blood – work undertaken by two South African PhD students at UKZN, supervised by Professor Thumbi Ndung’u, director of HIV Pathogenesis programme. Other sub-studies include surgical shunting of cerebrospinal fluid, natural killer cell immunology assays and molecular typing of cryptoccal isolates. New collaborators and novel project ideas are welcome.
Information for Students: Research Opportunities
Please see below for project and contact details, or download the Department of Infectious Diseases Research Project Handout.
Projects and opportunities:
a) Host genetics
b) Fungal virulence
c) Proteomics and metabolomics
Contact person: Dr Christina Chang
All other student inquiries:
Please contact Jasminka Sterjovski (Research Manager and Student Co-ordinator)
|Dr Christina Chang|
Professor Martyn French (University of Western Australia)
Professor Thumbi Ndung’u (University of KwaZulu-Natal)
Chang CC, Dorasamy AA, Gosnell BI, Elliott JH, Spelman T, Omarjee S, Naranbhai V, Coovadia Y, Ndung’u T, Moosa M-YS, Lewin SR, French MA. Clinical and mycological predictors of Cryptococcosis-associated Immune reconstitution inflammatory syndrome (C-IRIS). AIDS 2013;27:2089-2099
Chang CC, Lim A, Omarjee S, Levitz SM, Gosnell BI, Spelman T, Elliott JH, Carr WH, Moosa M-YS, Ndung’u T, Lewin SR, French MA. Cryptococcosis-IRIS is associated with lower Cryptococcus-specific IFN-gamma responses before antiretroviral therapy but not higher T-cell responses during therapy. Journal of Infectious Diseases 2013 (e-published ahead of print)
Chang CC, Omarjee S, Lim A, Spelman T, Gosnell BI, Carr WH, Elliott JH, Moosa M-YS, Ndung’u T, French MA, Lewin SR. Chemokine receptor expression in cerebrospinal fluid of HIV-infected patients with cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS). Journal of Infectious Diseases 2013 (e-published ahead of print)
Chang CC, Crane M, Zhou J, Mina M, Post JJ, Cameron BA, Lloyd AR, Jaworowski A, French MA, Lewin SR. HIV and co-infections. Immunological Reviews 2013;254:114-42. doi: 10.1111/imr.12063.