Infections in Immunocompromised Hosts
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 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.
Our research focuses 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 infection;
3) host immune responses
4) virulence mechanisms
5) host-pathogen interactions
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 cost analysis, the determination of airway cytokine profiles in those with Aspergillus infection vs. those without 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 start or cease antimicrobial prophylaxis or vaccination 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.
Student Research Opportunities
Opportunities exist within our group to pursue BMedSc, Honours and PhD projects.
Please contact Prof Morrissey directly if you would like to pursue research in her group.
Selected recent publications
Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.
Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, Clancy CJ, Wingard JR, Lockhart SR, Groll AH, Sorrell TC, Bassetti M, Akan H, Alexander BD, Andes D, Azoulay E, Bialek R, Bradsher RW, Bretagne S, Calandra T, Caliendo AM, Castagnola E, Cruciani M, Cuenca-Estrella M, Decker CF, Desai SR, Fisher B, Harrison T, Heussel CP, Jensen HE, Kibbler CC, Kontoyiannis DP, Kullberg BJ, Lagrou K, Lamoth F, Lehrnbecher T, Loeffler J, Lortholary O, Maertens J, Marchetti O, Marr KA, Masur H, Meis JF, Morrisey CO, Nucci M, Ostrosky-Zeichner L, Pagano L, Patterson TF, Perfect JR, Racil Z, Roilides E, Ruhnke M, Prokop CS, Shoham S, Slavin MA, Stevens DA, Thompson GR, Vazquez JA, Viscoli C, Walsh TJ, Warris A, Wheat LJ, White PL, Zaoutis TE, Pappas PG. Clin Infect Dis. 2019 Dec 5. pii: ciz1008. doi: 10.1093/cid/ciz1008. [Epub ahead of print]
"Definitions of invasive fungal disease are critical for early diagnosis to guide early treatment and consequently improve survival rates. These definitions are also critical for unbiased clinical trials research and for epidemiological surveillance studies. Sixty-five global experts, including Prof. Orla Morrissey (Department of Infectious Diseases), have recently updated the definitions for invasive fungal disease which now become the new reference standard for clinical, epidemiological and diagnostic research."