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.

Here, we propose the establishment of a large European and global collaboration to include national surveillance units from both within and outside the European Union. This collaboration will facilitate cooperation between neurologists, epidemiologists and neuropathologists 1) to harmonize the protocols involved in patient documentation, biomaterial sampling/ storage, biomarker testing/assay analysis and data sharing; and 2) to standardise a more precise diagnosis in patients with RPD by analysis of the biochemical markers in the cerebrospinal fluid and blood. We will work on standardisation of tests that are currently available and harmonise their use between centers worldwide. We will define standards for biochemically based diagnosis in most relevant rapid progressive dementia such as CJD and rpAD. As an add-on value, we will define criteria for early differential diagnosis between rapid progressive neurodegenerative or potentially reversible dementia.