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
d) Pharmacokinetics/pharmacodynamics

Contact person: Dr Christina Chang


All other student inquiries:

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


Staff Members:

Dr Christina Chang
Project leader

Prof Sharon Lewin
Supervisor, Member of executive committee

Dr Julian Elliott
Member of protocol steering committee



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.