International health: Overview

Cryptococcal Meningitis and Cryptococcosis-associated Immune Reconstitution Inflammatory Syndrome (C-IRIS)

Project leader: Dr Christina Chang

Email: christina.chang@burnet.edu

Overview

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
d) Pharmacokinetics/pharmacodynamics

Contact person: Dr Christina Chang

Email: christina.chang@burnet.edu

All other student inquiries:

Please contact Jasminka Sterjovski (Research Manager and Student Co-ordinator)

Email: jasminka.sterjovski@monash.edu

Staff Members:

Collaborators:

Professor Martyn French (University of Western Australia)

Professor Thumbi Ndung’u (University of KwaZulu-Natal)

Key Publications:

• 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.