Aspergillus-Human Interactions: From the Environment to Clinical Significance

Abstract

Aspergillus species are ubiquitous fungi found in the environment worldwide. The most common Aspergillus species causing diseases in humans are A. fumigatus, A. flavus, A. niger, and A. terreus. However, species causing human infections are also depending on human immune status. Host immune status and previous underlying diseases are important factors leading to different clinical manifestations and different disease spectra of Aspergillus infections. The most severe form of Aspergillus infections is invasive aspergillosis in human tissue, especially invasive pulmonary aspergillosis (IPA), which has high morbidity and mortality in immunocompromised patients. ICU patients with influenza infections and COVID-19 infections are recently risk factors of invasive pulmonary aspergillosis. New diagnostic criteria include galactomannan antigen assays, nucleic acid amplification assays, and lateral flow assays for early and accurate diagnosis. Voriconazole and the newest azole, isavuconazole, are antifungals of choice in IPA. Nevertheless, azole-resistant Aspergillus strains are increasing throughout the world. The etiology and spreading of azole-resistant Aspergillus strains may originate from the widespread use of fungicides in agriculture, leading to the selective pressure of azole-resistant strains. Therefore, there is a necessity to screen Aspergillus antifungal susceptibility patterns for choosing an appropriate antifungal agent to treat these invasive infections. In addition, mutations in an ergosterol-producing enzyme, i.e., lanosterol 14-α demethylase, could lead to azole-resistant strains. As a result, the detection of these mutations would predict the resistance to azole agents. Although many novel azole agents have been developed for invasive Aspergillus infections, the rate of novel antifungal discovery is still limited. Therefore, better diagnostic criteria and extensive antifungal resistant Aspergillus screening would guide us to better manage invasive Aspergillus infections with our existing limited resources.