Trinity School of Medicine researchers investigate drug-resistant mould which poses a risk to human health
Aspergillosis is an infection caused by a type of mould (fungus). It is caused by initially breathing in tiny parts of the mould called spores. Aspergillus fumigatus is the most common cause of aspergillosis. While aspergillosis cannot be caught from other people or from animals, the mould is found in many places in the environment, including soil, plants, compost heaps, dust and damp buildings. Although most people who breathe in this mould do not get sick, some will develop aspergillosis, which primarily affects the lungs and causes breathing difficulties. There is a chronic form that may afflict people with underlying lung conditions like cystic fibrosis or chronic obstructive pulmonary disease, known as COPD. An acute form, known as invasive aspergillosis, occurs in patients who have a weakened immune system due to organ transplantation or chemotherapy, or those requiring critical care for severe ‘flu or COVID-19. Aspergillosis affects an estimated 3 million people globally each year. We don’t know the numbers in Ireland as it is not a notifiable disease.
Professor Tom Rogers is a Clinical Microbiologist and Adjunct Professor in Clinical Microbiology in the School of Medicine, Trinity College Dublin (TCD) as well as a visiting professor at Imperial College London. At St James’s Hospital campus, Professor Rogers and his team have investigated invasive fungal infections, including aspergillosis. There is only a limited number of systemically administered antifungal drugs, and the triazole antifungals represent the leading drug class for treating aspergillosis. Resistance to the triazoles in Aspergillus fumigatus therefore represents a potentially serious hazard for patients at risk of aspergillosis. Professor Rogers explains that resistance to antifungal medications is a particular concern for vulnerable patients:
“From studies we have done at St James's Hospital campus, we have found a 10% incidence of invasive aspergillosis in high-risk patients often associated with a fatal outcome in spite of antifungal therapy. There is evidence internationally that invasive aspergillosis caused by a triazole resistant strain of Aspergillus fumigatus significantly increases mortality.”
Professor Rogers and his team published a key paper in the prestigious journal Nature Microbiology this month in collaboration with Professor Matthew Fisher at Imperial College. This publication was a major collaborative effort with colleagues from Irish centres including the Tallaght University Hospital (TUH), Royal College of Surgeons Ireland (RCSI), and Beaumont Hospital, as well as multiple international collaborators from the UK and Singapore. Dr Julie Renwick (Department of Clinical Microbiology, TCD), Professor Philip Murphy (TUH), Professor Noel G Mc Elvaney (RCSI) and Dr Alida Talento, Children’s Health Ireland, were co-authors on the Nature Microbiology publication. The landmark study included a genomic analysis of 218 Aspergillus fumigatus isolates from across the UK and Ireland. This work will help scientists and clinicians understand the environmental drivers and genetic basis of evolving fungal drug resistance – a phenomenon that requires urgent attention given the increasing numbers of patients with severe viral respiratory tract infections who are susceptible to opportunistic fungal superinfections.
There is a growing concern that the widespread use of azole fungicides in agriculture is coupled to the increasing isolation of azole-resistant Aspergillus fumigatus from environmental sources. In fact, previous work from Professor Rogers’s group showed that drug-resistant Aspergillus fumigatus was being imported into Ireland on plant bulbs coming from Europe, showing how this pathogen can be spread between countries, and potentially even between continents. Professor Rogers explains the next steps in managing this disease:
“We need more comprehensive screening of the environment to better determine the prevalence of drug-resistant Aspergillus fumigatus. In addition, prospective clinical studies are required to determine the impact of drug-resistance on patient outcomes from aspergillosis infection”
The Nature Microbiology study full-text can be accessed here: https://www.nature.com/articles/s41564-022-01091-2