The Univeristy of Melbourne The Royal Melbourne Hopspital

A joint venture between The University of Melbourne and The Royal Melbourne Hospital

Dr Alex Stewart

Meet our graduate researchers - Dr Alex Stewart

Research title: The role of cytochrome polymorphisms in primaquine metabolism and effects on its activity in radical cure of Plasmodium vivax infection.

McCarthy Group 

Started PhD studies in 2022 

Tell us about your PhD research

My PhD project will investigate the role of genetic polymorphisms in the metabolism of primaquine, an anti-malarial medication. Primaquine is the only anti-malarial approved by the World Health Organization that targets the liver stage of Plasmodium vivax malaria. Without radical cure (treatment of both the blood and liver stages of P. vivax) individuals are at risk of recurrent episodes of malaria, which can result in significant morbidity. Primaquine has been available for decades, however, its use has been limited by the risk of life-threatening haemolytic anaemia in glucose-6-dehydrogenase (G6PD) deficient individuals. More recently, issues with efficacy have been have been identified, with relapses of P. vivax occurring despite treatment with primaquine. These relapses have been associated with cytochrome P450 2D6 (CYP2D6) polymorphisms that confer reduced metabolism of primaquine. My PhD project will investigate this relationship through a multi-stage study in Madagascar. First, community surveys will be carried out to identify individuals with CYP2D6 polymorphisms of interest (those predicted to have reduced primaquine metabolism). This will be followed by primaquine metabolism studies in uninfected individuals with CYP2D6 polymorphisms of interest identified from the first stage. This will enable the correlation of primaquine metabolism with CYP2D6 polymorphisms. Finally, we will further assess this relationship through longitudinal follow-up of infected individuals treated with primaquine for radical cure. Madagascar is an ideal place to carry out this research due to the population admixture and hence, the variation of genetic polymorphisms.


What and where did you study/work/undertake placement/training before your PhD?

I completed my medical school at Imperial College London and then moved to Australia after internship. As I was interested in infectious diseases I undertook an Resident Medical Officer (RMO) position at Royal Darwin Hospital, which was a great introduction into infectious diseases in Australia. I subsequently completed basic physician training in Brisbane. I then took time out of training and completed the Diploma of Tropical Medicine and Hygiene at the London School of Hygiene and Tropical Medicine. I was able to put these skills into practice through working for Medecins Sans Frontieres for 18 months in Myanmar, South Sudan and Ethiopia. My time in Ethiopia included involvement in field research and allowed me to develop an understanding of the challenges and rewards of combining research, program management and clinical work in a remote location. After returning to Australia, I completed my infectious diseases advanced training in Brisbane, Cairns and Melbourne and commenced working as an infectious diseases physician in 2020, at the start of the COVID-19 pandemic. Unfortunately, this delayed my PhD plans due to the border closures and inability to travel to planned field sites in Madagascar, so I deferred commencement of my PhD for two years. 


What made you decide to first undertake a PhD and choose the Doherty Institute?  

During my advanced training in infectious diseases I was exposed to a variety of research and clinician-scientists in the Australian setting. The variety and combination of clinical work and research, particularly the translation of research to the bedside, made me consider undertaking a PhD. I also had a strong interest in global health and was keen to explore how I could combine global health with research and clinical work in Australia. During my advanced training I was fortunate to work with Professor James McCarthy and through discussions with him I identified a PhD project that suited my interests and research goals. Additionally, the Doherty Institute and the University of Melbourne were further drawcards, due to the resources and expertise available, particularly the exposure to different researchers and groups and the opportunities to collaborate. 


How do you combine your PhD research with your role as an infectious diseases physician?

I am undertaking my PhD on a part-time basis, which allows me to continue my clinical work as an infectious diseases physician. As my research is field-based, a large part of my PhD work is grouped together during research trips to Madagascar. This then allows sufficient time for clinical work in between. Combining clinical work and research, particularly the overseas components, does require coordination and the balancing of responsibilities, which can be challenging at times. However, I am very fortunate to have a supportive clinical department and PhD supervisors, which allows me to combine these two roles.


When do you hope to complete and what are your plans post-PhD?

Following completion of my PhD I hope to continue the combination of research, global health and clinical work, as a clinician-scientist. While my current research is based overseas, I believe that there are far reaching implications and broad applicability to the Australian setting. I hope that I can combine research in Australia and overseas, particularly as my research interests develop and overlap with clinical issues in Australia, such as the increasing role of pharmacogenomics in clinical practice.


What advice do you have for an infectious diseases physician who is considering a PhD?

The combination of clinical work and a PhD allows for variation in work every day. I really enjoy the change in focus after a few hard weeks of clinical work or vice versa. The most important aspect for me has been having a supportive supervisor and clinical unit, as I have found that this really makes a huge difference. So, in addition to ensuring that your PhD topic captures your interests, make sure that the institution, supervisors and colleagues are the right fit.