Bridging the gap between environment and patient; investigating the risk and transmission of antifungal resistance in Aspergillus fumigatus

Aspergillosis is an infectious disease caused by a fungus, which kills around one million people each year. Fungal spores are found ubiquitous in the air and in plant waste material, flower beds and garden soil. People with poorly functioning immune systems are particularly at risk of infection. The azole-class of antifungals are frontline medicines for treatment of aspergillosis and at the same time simultaneously playing an essential role in agriculture and horticulture to protect crops. Inevitably, this dual-use of azoles in agricultural and clinical settings has resulted in resistance spreading from the field to vulnerable patients. Some treatment centres are now finding more than 20% of aspergillosis patients infected with a drug resistant strain of the fungus. There are few alternative treatments and those that do exist are far less effective and less well tolerated by patients. The absence of environmental surveillance to monitor emerging antifungal resistance has hindered the development of strategies to mitigate resistance and alert healthcare sectors about potential problems. To address this problem, we need to develop methods to monitor the emergence of environmental azole resistance and resistance to upcoming dual-use antifungals in this important pathogen. Ultimately this study will provide a foundation to support the development of approaches that disconnects antifungal use in the clinic from its use in agriculture. Within the One-health framework, our knowledge is therefore also relevant for the development of responsible and sustainable crop protection.

Antimicrobial resistance is a global problem, and the rapid emergence of drug resistance of human fungal infections is of high concern. Unfortunately, insufficient research efforts and opportunities in the past have resulted in a lack of surveillance systems to track antifungal resistant Aspergillus fumigatus, as well as an incomplete understanding of how antifungal resistance evolves or can be managed. A. fumigatus is a common, ubiquitous saprophytic fungus that can cause fatal invasive infections in immune-compromised patients. Antifungal azole compounds have been effective in treating Aspergillus diseases in humans and animals but are also used for crop protection against plant pathogenic fungi. Exposure to azole fungicides in the environment is a major driving force for resistance selection and multi-azole resistant A. fumigatus genotypes are globally detected in clinical isolates. This severely threatens human fungal disease management yet appropriate risk assessments for dual-use antifungal compounds are surprisingly lacking. To address this need we will develop tools to detect the emergence of dual-use antifungal resistance and provide appropriate risk assessments strategies. In addition, we aim to bridge the gap between environment and patient by using air sampling surveillance to investigate the exposure risk of antifungal resistant A. fumigatus in a wide range of geographical areas (including EU and Africa). Analysing antifungal resistance patterns will strengthen future surveillance methods and investigations by advancing comprehension of transmission routes.