Infections in patients receiving chemotherapy or cancer immunotherapy, biologics for inflammatory diseases (e.g. rheumatoid arthritis, Crohn’s disease) and transplant recipients are a significant cause of morbidity and mortality. Infections account for 73% of the non-relapse-related mortality in bone marrow transplant recipients.

Infections in these groups (i.e. collectively known as the immunocompromised host) are normally caused by organisms that those with a normal immune system can usually overcome (e.g. Nocardia, cytomegalovirus [CMV], Pneumocystis jirovecii, Aspergillus, Strongyloides). Death due to infections with these organisms is associated with high mortality rates (up to 89%) in the immunocompromised host.  

These infections (known as opportunistic infections [OI]) are also very costly. Research performed in conjunction with Mr. Jake Valentine (B. Biomed Hons student) and Dr. Ananda-Rajah (Department of Infectious Diseases) demonstrated that the direct additional median costs of invasive aspergillosis are AUD$55,642/case. Infections in the immunocompromised host (ICH) also can have indirect effects. They can delay the administration of subsequent courses of chemotherapy; which consequently, reduces cancer cure rates. They also can trigger or exacerbate graft-versus-host-disease (GVHD) in bone marrow transplant recipients and allograft rejection in solid organ transplant (SOT) recipients, respectively; further driving the high morbidity and mortality rates.     

These infections can be difficult to diagnose so clinicians rely on antimicrobial prophylaxis and empiric therapy to reduce the incidence of and mortality rates from OI. However, antimicrobial prophylaxis and empiric therapy are not without their limitations including drug-drug interactions, drug-related toxicity, cost and the emergence of antimicrobial resistance. Thus, there is a need to improve current strategies and develop new strategies for the improved management of these complex and critically ill patient groups.     

As a result, our research concentrates on: 1) improving the prevention, early diagnosis and treatment of infection in the ICH; 2) epidemiological studies to determine risk for and outcomes of opportunistic infections; 3) host immune responses; 4) virulence mechanisms; 5) host-pathogen interactions and 6) resistance mechanisms.

One of the exciting projects being performed by Prof. Orla Morrissey’s group includes the UPPRITE Study, a world-first randomised controlled trial comparing universal antifungal prophylaxis to pre-emptive antifungal therapy to determine the optimal strategy for fungal infection management post-lung transplantation. It has a number of sub-studies including a cost analysis, the determination of airway cytokine profiles in those with Aspergillus infection vs. those without and a pharmacokinetic analysis of posaconazole levels in the airways.  The results generated from this trial and the related sub-studies will translate into significant changes in clinical practice, globally.

Another research project currently being undertaken by Prof. Morrissey and her group includes the determination of immune recovery post-bone marrow transplantation.  This work is aimed at individualising antimicrobial prophylaxis and vaccination rather than using the current “one-size fits all” approach. This individualised approach will allow us to more precisely to start or cease antimicrobial prophylaxis or vaccinate to, in turn, reduce the incidence of break-through OI or vaccine-preventable infections, unnecessary drug toxicity, ineffective vaccination, and resistance. Our preliminary data have been published in Clinical Translational Immunology and further data are likely to significantly contribute to a global change in practice in the near future.

Prof. Morrissey’s group also uses cutting-edge genomics to identify virulence and novel resistance mechanisms in a large collection of Aspergillus isolates.  

Projects available for honours, Masters and PhD students. Postdoctoral fellows should contact Prof Morrissey directly to discuss opportunities.

Professor Orla Morrissey is an Infectious Diseases Physician at Alfred Health, Melbourne and Senior Lecturer in the Department of Infectious Diseases at Monash University, Melbourne. Dr. Morrissey is a lead clinician within the Immunocompromised Host Consult Service at Alfred Health.

Professor Morrissey is active in the research sphere: determining the epidemiology of a variety of opportunistic infections; determining Aspergillus virulence factors and examining inflammatory responses to Aspergillus. 

She is co-chair of the Australia and New Zealand Mycoses Interest Group and has been instrumental in the development of national and international guidelines for the management of infections in immunocompromised hosts.

Dr. Morrissey has co-authored over 70 publications. She is a principal investigator on a number of government and philanthropic funded projects including a randomised controlled trial examining the efficacy and safety of two different strategies for the management of fungal infections in lung transplant recipients.