Invasive aspergillosis: burden of disease, management and surveillance: assessing clinical management challenges and exploring Aspergillus disease surveillance

Abstract

Invasive aspergillosis (IA) is a global health threat with a rising number of at-risk patients. It is classically seen in immunocompromised patients, such as those with a haematological malignancy, or severe and prolonged neutropenia. However, recently IA has also been observed in patients without classical risk factors: patients treated with new therapies that affect the immune system, critically ill patients, and patients with a viral respiratory infection (influenza and more recently COVID-19). Diagnosis and treatment of IA is challenging. Current diagnostic tools have their limitations: a positive culture from a bronchoalveolar lavage (BAL) does not necessarily reflect disease; yet in patients with IA, BAL cultures are often negative and diagnosis depends on detection of fungal biomarkers. Furthermore, antifungal treatment options are limited, and these choices are further reduced by the global spread of environmentally acquired triazole resistance. Disease surveillance is essential for reliable estimates of burden, to improve our understanding of the epidemiology of IA and antifungal resistance, and ultimately improve diagnostic and therapeutic approaches. This was underscored by the COVID-19 pandemic in which secondary infections with IA were observed. In this thesis the burden and management of IA were investigated, and the possibilities for national Aspergillus disease surveillance were explored.