Invasive Aspergillosis by Aspergillus flavus: Epidemiology, Diagnosis, Antifungal Resistance, and Management

Abstract

Aspergillus flavus is the second most common etiological agent of invasive aspergillosis (IA) after A. fumigatus. However, most literature describes IA in relation to A. fumigatus or together with other Aspergillus species. Certain differences exist in IA caused by A. flavus and A. fumigatus and studies on A. flavus infections are increasing. Hence, we performed a comprehensive updated review on IA due to A. flavus. A. flavus is the cause of a broad spectrum of human diseases predominantly in Asia, the Middle East, and Africa possibly due to its ability to survive better in hot and arid climatic conditions compared to other Aspergillus spp. Worldwide, ~10% of cases of bronchopulmonary aspergillosis are caused by A. flavus. Outbreaks have usually been associated with construction activities as invasive pulmonary aspergillosis in immunocompromised patients and cutaneous, subcutaneous, and mucosal forms in immunocompetent individuals. Multilocus microsatellite typing is well standardized to differentiate A. flavus isolates into different clades. A. flavus is intrinsically resistant to polyenes. In contrast to A. fumigatus, triazole resistance infrequently occurs in A. flavus and is associated with mutations in the cyp51C gene. Overexpression of efflux pumps in non-wildtype strains lacking mutations in the cyp51 gene can also lead to high voriconazole minimum inhibitory concentrations. Voriconazole remains the drug of choice for treatment, and amphotericin B should be avoided. Primary therapy with echinocandins is not the first choice but the combination with voriconazole or as monotherapy may be used when the azoles and amphotericin B are contraindicated.

Discrimination of Aspergillus flavus from Aspergillus oryzae by matrix‐assisted laser desorption/ionisation time‐of‐flight (MALDI‐TOF) mass spectrometry

“…Analysis of macroscopic and microscopic characteristics is the most commonly used approach to diagnose for the aetiological agents of invasive and non‐invasive aspergillosis . Accurate species‐level identification of the pathogen responsible for invasive aspergillosis has become a major challenge in the management of the disease because very closely related species in the Aspergillus genus, including A flavus show different patterns of susceptibility to the main antifungal agents . Huang et al reported a poor accuracy rate of a culture‐based method for the species‐level discrimination among Aspergillus isolates, especially those belonging to cryptic and novel species.…”

SUMOylation in Human Pathogenic Fungi: Role in Physiology and Virulence

“…Furthermore, invasive aspergillosis involving severe infections of the lungs are primarily caused by A. fumigatus and associated with a mortality rate of < 90% in undiagnosed or late-diagnosed cases [47,61,62]. A. flavus, besides being the second most prevalent causative agent of invasive aspergillosis after A. fumigatus, also infects several crops and contributes substantially to aflatoxin-related deaths [63]. Other medically important fungi, causing deep-seated infections of visceral organs, such as the lungs, include Blastomyces dermatitidis, Paracoccidioides brasiliensis, Histoplasma capsulatum [64,65].…”

Invasive Aspergillosis in Transplant Recipients

“…The most common etiological agent of invasive aspergillosis with a high morality is A. fumigatus, responsible for the majority (up to 90%) of cases in humans [1,12,[15][16][17][18][19]. It is followed by A. flavus, which causes up to 10% of cases of…”