Emerging Aspergillus Species Almost Exclusively Associated With Primary Immunodeficiencies

Abstract

Invasive aspergillosis (IA) is the most serious mold infection encountered in patients with iatrogenic immunosuppression. IA is also a major cause of mortality and morbidity in individuals with primary immunodeficiency (PID). Although Aspergillus fumigatus is the most common etiologic agent of IA reported in PID patients, followed by A. nidulans, multiple poorly recognized Aspergillus species such as A. udagawae, A. quadrilineatus, A. pseudoviridinutans, A. tanneri, A. subramanianii, and A. fumisynnematus have been reported almost exclusively from patients with inborn defects in host antifungal defense pathways. Infection in PID patients exhibits patterns of disease progression distinct from those in iatrogenic immunosuppression. Specifically, the disease can be extrapulmonary and chronic with a tendency to disseminate in a contiguous manner across anatomical planes. It is also more refractory to standard antifungal therapy. This synopsis summarizes our understanding of emerging rare Aspergillus species that primarily affect patients with PIDs but not those with acquired immunodeficiencies.

Efficacy of Olorofim (F901318) against Aspergillus fumigatus , A. nidulans , and A. tanneri in Murine Models of Profound Neutropenia and Chronic Granulomatous Disease

“…Table 1 shows the antifungal susceptibility profiles of seven Aspergillus spp. that have been documented from CGD patients with cases of IA (16). Olorofim showed potent and consistent in vitro activity against all seven Aspergillus spp.…”

“…Although VRC is currently the recommended first-choice treatment for IA (10), the drug showed no therapeutic efficacy against infections caused by some of these emerging Aspergillus spp. (16). Since olorofim demonstrated potent in vivo efficacy against A. tanneri, we predict that olorofim will be effective in treating IA caused by other Aspergillus spp.…”

“…This is of significant importance, since the prevalence of azole-resistant A. fumigatus is increasing (27), and the emergence of drug-resistant non-fumigatus Aspergillus spp. as a cause of IA in CGD patients is a growing concern (16).…”

“…The potent activity of olorofim has also been demonstrated in experimental animal models of disseminated infections caused by A. fumigatus (20) and A. flavus (21). In the present study, we aimed to assess the in vivo efficacy of olorofim against A. fumigatus and two other Aspergillus spp., A. nidulans and A. tanneri, which are either more refractory to or nonresponsive to currently available antifungal treatment (16).…”

Diagnostic biomarkers for invasive aspergillosis utilizing weighted gene co-expression network analysis

“…Aspergillus species appear widely in our environment, most ubiquitously in soil, water and decaying plant matter [26]. There are more than 250 species, which were identi ed as the Aspergillus species, and infections caused by Aspergillus species are the primary cause of fatality in patients with chronic granulomatous disease [27,28]. Moreover, there is the most dread of mortality (about 85%-100%) in compromised patients with central nervous system aspergillosis [29].…”