Introducing Our New Honorary Professor Lewis White8 February 2023
Professor Lewis White recently joined the Centre for Trials Research as an Honorary Professor jointly with the Division of Infection and Immunity at Cardiff University. In the first of two blogs, he discuss his work in fungal infections.
Can you tell us about your background and expertise in the field of fungal infections?
I have worked in the Public Health Wales Mycology Reference laboratory for over 20 years, where I am a consultant clinical scientist and head of the unit. My main focus is advancing the diagnosis of fungal infections through the development of non-culture diagnostics but also looking at host biomarkers (genomics, cytokines/chemokines) that could indicate disease but also risk of developing it, but I am also involved in various clinical trials of novel antifungal therapies. Furthermore, we are trying to improve the surveillance of fungal disease and antifungal resistance. I am fellow of the Royal College of Pathologists and European Confederation of Medical Mycology, I serve on the executive committee of the ESCMID Fungal Infection Study Group and the British Society for Medical Mycology. I am lead of the laboratory working parties of the Fungal PCR Initiative. I have over 130 publications in the field of Medical Mycology, including international guidelines and regularly present at international Mycology and Microbiology/ID conferences.
How will your role as an Honorary Professor in the Division of Infection & Immunity/Centre for Clinical trials contribute to our research on fungal infections?
Cardiff University has a good track record of clinical research on Medical Mycology, which over the years has waned due to retirements and staff relocation. Subsequently, my appointment will re-stimulate this research, granting access to diagnostic and pharmaceutical clinical trials and novel advancements in the surveillance, diagnosis and treatment of fungal infections, all of which are associated with a significant academic output. We also hope to benefit from the skill sets of both units when developing new grant proposals aimed at improving the awareness of fungal disease across Wales but also further afield.
Can you share some details about the specific types of fungal infections you will be focusing on in your research?
The main causes of fungal disease are candidiasis and aspergillosis. Candidiasis, usually becomes invasive post anatomical breakdown or clinical intervention and so is usually encountered in the ICU, neonates, or pts with abdominal issues or with immunosuppression. It is the main cause of invasive fungal disease causing >500,000 cases globally per annum with a mortality rate of 30-40%. Classical diagnosis has a sensitivity of approximately 50%, and we are working on identifying novel strategies to improve this figure.
Aspergillus spores are inhaled daily, usually causing infection with existing respiratory conditions or those with particularly underlying conditions (e.g. AML). There are approximately 300,000 cases globally per annum with a mortality rate of 30-40%, but higher (>70%) when disease is resistant or diagnosis is delayed. We have employed novel diagnostic strategies for invasive aspergillosis in Haematology and ICU patients with existing respiratory viral infections, and are advancing this through the development of host biomarkers.
Pneumocystis pneumonia, is one of the main AIDS defining diseases. However, in the UK it is frequently seen in Haematology and Renal transplant patients. We are working at developing novel strategies to improve the diagnosis of Pneumocystis pneumonia, but more also improve our understanding of new patient cohorts at risk of Pneumocystis pneumonia.
How does your research on fungal infections contribute to the larger field of infectious disease research?
The work we doing utilizes novel technologies, including AI protocols and next generation pipelines with the potential for application to other parts of the ID field. Our work also improves our understanding of how fungal infections can complicate the management of other infectious diseases.
What are some common misconceptions about fungal infections that you hope to address in your next blog?
They are not common or particularly concerning and when they are significant they only occur rarely and in specific patient populations.
How do fungal infections differ from other types of infections and why is it important to study them separately?
The main thing is fungi are eukaryotic pathogens in a eukaryotic host, which complicates treatment but can also complicate diagnosis. Fungi are commensals of the human, but also environmentally ubiquitous so exposure to fungi is inevitable, but most fungi do not require a host to survive. They can cause a wide array of clinical manifestations from sensitization through to disseminated disease. The cause a significant burden of disease that is very much overlooked resulting in significant mortality and morbidity. Diagnosis can be very complicated, as infective burdens can be very low, resulting multifaceted diagnostic strategies. Conversely, given their ubiquitous nature detecting their presence is not always evidence of infection, and so diagnosis can be very complicated.
Can you provide some examples of real-world impact of fungal infections on human health?
The research and stories below give a flavour:
- Mould in the home cause of Toddler’s death (https://www.manchestereveningnews.co.uk/news/greater-manchester-news/mum-tragic-toddler-2-pleaded-25456308)
- Large numbers of fungal meningitis cases caused by tainted steroid injections (https://www.cdc.gov/hai/outbreaks/meningitis.html)
- Fungal Infection post COVID (https://www.cdc.gov/fungal/covid-fungal.html)
- Fungal Infection post Influenza (https://pubmed.ncbi.nlm.nih.gov/30076119/)
- Fungal Infection post tornado (https://www.nejm.org/doi/full/10.1056/NEJMoa1204781)
Huge cost of annual antifungal therapy (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409199/)
How does your research on fungal infections apply to the clinical setting?
Much of what we do improves diagnostic testing or strategies which when implemented into clinical practice can improve patient management by providing an earlier diagnosis but also preventing the use of unnecessary antifungal therapy. For example, in haematology we introduced a biomarker screening strategy for invasive fungal disease which is highly sensitive and when negative can be used to exclude unnecessary empirical antifungal therapy. In doing so we reduced annual antifungal expenditure by approximately £500,000. During the COVID-19 pandemic we incorporated a novel strategy for diagnosing secondary fungal infections in ICU COVID-19 patients where early diagnosis and appropriate antifungal therapy was associated with a significant survival benefit. Being heavily involved in the development of new international guidelines for a range of fungal infections directly impacts patient management on a daily basis. Current research is aimed optimizing surveillance of fungal disease but also antifungal resistance, with an aim of improving our understanding of disease burden but also risk factors associated with disease. Other research is focussed on developing host biomarkers that eventually will be incorporated alongside current fungal diagnostics and utilize AI learning to provide a personalized approach for patients. We also involved in RCTs evaluating novel antifungal drugs that will aid future generations impacted by fungal infection.
What are some of the most promising areas of research in the field of fungal infections currently?
Given the limited number of antifungal drug classes and rising rates of antifungal resistance, the development of novel antifungals is very exciting and critical to the successful management of future cases.The development of host biomarker assays that can help identify individuals at higher risk of infection or even with active infection will move the diagnostic field into the uncharted territory of providing personalized medicine in mycology.
The use of NGS diagnostic strategies has the potential to enhance microbiology services, while WGS will underpin our future understanding of antifungal resistance, fungal epidemiology and evolution, while identifying potential novel antifungal drug targets.
Given the multifaceted approach to diagnosis, we often faced with conflicting evidence, which makes understanding the probability of infection difficult to determine, the use of AI to weigh-up the evidence of infection (both positive and negative) represents a development that significantly improve our day to day management of patients at risk of fungal infection.
How does your research on fungal infections fit into the larger research agenda ?
Historically, the Medical Microbiology section of the Division of Infection & Immunity has had a strong association with mycology, but over time and through retirements this link has been eroded. Consequently, incorporating our research into the division re-establishing these links, with research that truly complements the current research portfolio. (see point 2)
How does your research on fungal infections relate to the research being done in other institutions and organizations around the world?
Given the speciality of medical mycology, much of research is performed in collaboration with other institutions. We have an extensive collaborator network and are recognised globally as centre of excellence for developing, evaluating and incorporating novel diagnostics, in particular Fungal PCR diagnosis, where we are recognised as a global leader in the field. We are also working with international colleagues to improve the surveillance of fungal infections through the development of global networks and also improve the diagnosis and management of fungal disease through the development of international guidelines.
What are some of the future goals and objectives of your research on fungal infections?
Our main goals are to improve the diagnosis and management of fungal disease, which still remains regularly overlooked as a potential clinical complication. Through the development of surveillance for fungal disease we hope to gain a better understanding of disease burden, but also identify a better understanding of the expanding population at risk of fungal infection, in short we hope to improve awareness of fungal infection as a clinical issue.
- Prof. Lewis White
The Centre for Trials Research is a UKCRC-registered clinical trials unit. It is publicly-funded to enable applied research that informs policy in health and social care in Wales and the UK, and is currently running studies across Wales, the UK and internationally. The Centre is funded through Welsh government by Health and Care Research Wales, and Cancer Research UK.