Detection of the ‘Big Five’ mold killers of humans: Aspergillus, Fusarium, Lomentospora, Scedosporium and Mucormycetes

Abstract

Fungi are an important but frequently overlooked cause of morbidity and mortality in humans. Life-threatening fungal infections mainly occur in immunocompromised patients, and are typically caused by environmental opportunists that take advantage of a weakened immune system. The filamentous fungus Aspergillus fumigatus is the most important and well-documented mould pathogen of humans, causing a number of complex respiratory diseases, including invasive pulmonary aspergillosis, an often fatal disease in patients with acute leukemia or in immunosuppressed bone marrow or solid organ transplant recipients. However, non-Aspergillus moulds are increasingly reported as agents of disseminated diseases, with Fusarium, Scedosporium, Lomentospora and mucormycete species now firmly established as pathogens of immunosuppressed and immunocompetent individuals. Despite well-documented risk factors for invasive fungal diseases, and increased awareness of the risk factors for life-threatening infections, the number of deaths attributable to moulds is likely to be severely underestimated driven, to a large extent, by the lack of readily accessible, cheap, and accurate tests that allow detection and differentiation of infecting species. Early diagnosis is critical to patient survival but, unlike Aspergillus diseases, where a number of CE-marked or FDA-approved biomarker tests are now available for clinical diagnosis, similar tests for fusariosis, scedosporiosis and mucormycosis remain experimental, with detection reliant on insensitive and slow culture of pathogens from invasive bronchoalveolar lavage fluid, tissue biopsy, or from blood. This review examines the ecology, epidemiology, and contemporary methods of detection of these mould pathogens, and the obstacles to diagnostic test development and translation of novel biomarkers to the clinical setting.

Antifungal susceptibilities of opportunistic filamentous fungal pathogens from the Asia and Western Pacific Region: data from the SENTRY Antifungal Surveillance Program (2011–2019)

“…The majority of IMI are a result of the so-called Big Five mold killers of humans [ 3 ]: Aspergillus, Fusarium, Lomentospora, Scedosporium , and the Mucorales. Although the epidemiology of IMI is not well described in the APAC region, surveys indicate a rising incidence of infections due to the Big Five [ 2 , 14 ].…”

“…Invasive mold infections (IMI) threaten to limit the life-saving advances of modern medical technology [ 1 – 3 ]. The genera Aspergillus , Fusarium , Lomentospora , Scedosporium , and molds belonging to the order Mucorales have been termed the “Big Five” mold killers of humans [ 3 ].…”

“…Invasive mold infections (IMI) threaten to limit the life-saving advances of modern medical technology [ 1 – 3 ]. The genera Aspergillus , Fusarium , Lomentospora , Scedosporium , and molds belonging to the order Mucorales have been termed the “Big Five” mold killers of humans [ 3 ]. Whereas much of the literature concerning the species distribution and antifungal resistance profiles of the species causing IMI has focused on isolates from North America and Europe [ 4 – 7 ], the greatest burden of fungal disease in the world resides in the Asia and the Western Pacific (APAC) region [ 2 , 8 ].…”

Aspergillus fumigatus and Its Allergenic Ribotoxin Asp f I: Old Enemies but New Opportunities for Urine-Based Detection of Invasive Pulmonary Aspergillosis Using Lateral-Flow Technology

“…The clinical relevance of this LOD has yet to be determined, but we were nevertheless able to detect the antigen in urine from a patient with acute lymphoid leukaemia diagnosed with probable IPA according to EORTC/MSG criteria. However, further large-scale evaluations of the test need to be performed in order to determine its diagnostic efficacy compared to predicate biomarker tests such as the GM ELISA, and during antifungal treatment which is known to reduce the accuracy of antigen-based tests [2]. A limitation of the test is that it only detects A. fumigatus and other clinically-relevant species in the section Fumigati, but is unable to detect non-fumigatus Aspergillus species (A. flavus, A. nidulans, A. niger, and A. terreus) which also cause IPA in humans.…”

“…Aspergillus fumigatus is the most important opportunistic mould pathogen of humans, causing a number of different respiratory diseases including aspergilloma, allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), and invasive pulmonary aspergillosis (IPA), a lethal lung disease of mainly immunocompromised individuals, especially those with prolonged neutropenia, haematological malignancies, and bone marrow and solid organ transplants [1,2]. Recently, IPA has also been identified as a complication of influenza known as Influenza-Associated Pulmonary Aspergillosis (IAPA), and as a life-threatening co-infection of critically ill COVID-19 ICU patients known as COVID-19-Associated Pulmonary Aspergillosis (CAPA) [3][4][5][6][7].…”