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.
Highlights
Invasive aspergillosis (IA) is generally encountered in immunocompromised patients with steroid treatment, chemotherapy resulting in severe neutropenia, hematopoietic stem cell, and solid organ transplantation
Experimental in-vivo studies have shown that A. flavus is more virulent than A. fumigatus and other Aspergilli in terms of the time and initial inoculum required in causing mortality in both normal and immunocompromised experimental mice [4]
The spectrum of aspergillosis is broadly classified into four categories: invasive life-threatening infections in immunocompromised persons; sub-acute or chronic infections in patients with structural lung abnormalities or pre-existing pulmonary or sinus disease or some subtle defect in innate immunity; allergic or eosinophilic disease manifested in many forms like allergic bronchopulmonary aspergillosis (ABPA), eosinophilic rhinosinusitis, and extrinsic allergic alveolitis; and locally invasive infections as a result of trauma or surgery such as keratitis or post-operative infections
Summary
Invasive aspergillosis (IA) is generally encountered in immunocompromised patients with steroid treatment, chemotherapy resulting in severe neutropenia, hematopoietic stem cell, and solid organ transplantation. IA has a high mortality rate and Aspergillus fumigatus, A. flavus, A. niger, A. terreus, and A. versicolor are the most common species involved. The genus Aspergillus encompasses more than 250 species and is one of the largest genera of filamentous fungi causing human diseases [1,2]. A. fumigatus is the most common agent of invasive aspergillosis and has been widely studied and reviewed. A. flavus causes clinical syndromes similar to A. fumigatus in humans [3]. Experimental in-vivo studies have shown that A. flavus is more virulent than A. fumigatus and other Aspergilli in terms of the time and initial inoculum required in causing mortality in both normal and immunocompromised experimental mice [4]. A. flavus has been demonstrated to differ from A. fumigatus in terms of geographical distribution, pathogenic potential and antifungal resistance profile [6]. The present review aimed to update the available literature on the epidemiology, antifungal resistance, diagnosis, and management of IA due to A. flavus
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