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      Complete clinical response to combined antifungal therapy in two cats with invasive fungal rhinosinusitis caused by cryptic Aspergillus species in section Fumigati

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          Abstract

          Cryptic species in Aspergillus section Fumigati are increasingly reported to cause invasive aspergillosis in humans and animals. These infections are often refractory to treatment because of intrinsic antifungal resistance. We report two cases of invasive fungal rhinosinusitis in domestic cats caused by A. udagawae and A. felis. Clinical signs resolved after combined therapy including posaconazole, caspofungin and terbinafine. Both cases remained asymptomatic more than 2 years from initial presentation.

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          Most cited references18

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          Development and clinical application of a panfungal PCR assay to detect and identify fungal DNA in tissue specimens.

          Given the rise in the incidence of invasive fungal infections (IFIs) and the expanding spectrum of fungal pathogens, early and accurate identification of the causative pathogen is essential. We developed a panfungal PCR assay that targets the internal transcribed spacer 1 (ITS1) region of the ribosomal DNA gene cluster to detect fungal DNA in fresh and formalin-fixed, paraffin-embedded (PE) tissue specimens from patients with culture-proven (n=38) or solely histologically proven (n=24) IFIs. PCR products were sequenced and compared with sequences in the GenBank database to identify the causal pathogen. The molecular identification was correlated with results from histological examination and culture. The assay successfully detected and identified the fungal pathogen in 93.6% and 64.3% of culture-proven and solely histologically proven cases of IFI, respectively. A diverse range of fungal genera were identified, including species of Candida, Cryptococcus, Trichosporon, Aspergillus, Fusarium, Scedosporium, Exophiala, Exserohilum, Apophysomyces, Actinomucor, and Rhizopus. For five specimens, molecular analysis identified a pathogen closely related to that identified by culture. All PCR-negative specimens (n=10) were PE tissues in which fungal hyphae were visualized. The results support the use of the panfungal PCR assay in combination with conventional laboratory tests for accurate identification of fungi in tissue specimens.
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            Aspergillus fumigatus-Related Species in Clinical Practice

            Aspergillus fumigatus is the main etiologic agent of invasive aspergillosis (IA). Other Aspergillus species belonging to the section Fumigati (A. fumigatus complex) may occasionally be the cause of IA. These strains are often misidentified, as they cannot be distinguished from A. fumigatus by conventional morphological analysis and sequencing methods. This lack of recognition may have important consequences as these A. fumigatus-related species often display some level of intrinsic resistance to azoles and other antifungal drugs. A. lentulus, A. udagawae, A. viridinutans, and A. thermomutatus (Neosartorya pseudofischeri) have been associated with refractory cases of IA. Microbiologists should be able to suspect the presence of these cryptic species behind a putative A. fumigatus isolate on the basis of some simple characteristics, such as defect in sporulation and/or unusual antifungal susceptibility profile. However, definitive species identification requires specific sequencing analyses of the beta-tubulin or calmodulin genes, which are not available in most laboratories. Multiplex PCR assays or matrix-assisted laser desorption ionization – time-of-flight mass spectrometry (MALDI-TOF MS) gave promising results for rapid and accurate distinction between A. fumigatus and other Aspergillus spp. of the section Fumigati in clinical practice. Improved diagnostic procedures and antifungal susceptibility testing may be helpful for the early detection and management of these particular IA cases.
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              Sinonasal and sino-orbital aspergillosis in 23 cats: aetiology, clinicopathological features and treatment outcomes.

              Aetiology, clinicopathological findings and treatment outcomes were documented in 23 cats (1.5-13 years of age) with sinonasal (SNA, n=6) or sino-orbital (SOA, n=17) aspergillosis. Cases recruited retrospectively and prospectively were included if fungal hyphae were identified on cytological or histological examination and the fungal pathogen was identified by PCR and DNA sequencing (ITS1 or ITS1-5.8S-ITS2 regions, rDNA gene cluster). Fungal culture was positive in 22/23 cases. In cases of SNA, the fungal pathogen was Aspergillus fumigatus (n=4), Neosartorya fischeri or A. lentulus (n=1) or a non-speciated Neosartorya spp. (n=1). In all cases of SOA (n=17), the fungal pathogen was identified as Neosartorya spp. Nine cats had brachycephalic conformation. Cats with SNA were more likely to be infected with A. fumigatus and had a better prognosis than cats with SOA.
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                Author and article information

                Contributors
                Journal
                Med Mycol Case Rep
                Med Mycol Case Rep
                Medical Mycology Case Reports
                Elsevier
                2211-7539
                02 September 2021
                December 2021
                02 September 2021
                : 34
                : 13-17
                Affiliations
                [a ]Brunswick Central Vet Clinic, 210 Lygon Street, Brunswick East, VIC, 3055, Australia
                [b ]University of Sydney, Faculty of Science, Sydney School of Veterinary Science, Sydney, NSW, 2006, Australia
                [c ]National Mycology Reference Centre, Microbiology & Infectious Diseases, SA Pathology, Frome Rd, Adelaide, South Australia, 5000, Australia
                [d ]Department of Veterinary Clinical Sciences, Jockey Club College of Veterinary Medicine & Life Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong, SAR, China
                Author notes
                []Corresponding author. University of Sydney, Faculty of Science, Sydney School of Veterinary Science, Sydney, NSW, 2006, Australia. vanessa.barrs@ 123456cityu.edu.hk
                [1]

                These authors made equal contributions to the manuscript.

                Article
                S2211-7539(21)00047-6
                10.1016/j.mmcr.2021.08.005
                8437771
                34540573
                bde01a05-bf17-4e23-bf21-75f114e56c71
                © 2021 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 19 July 2021
                : 25 August 2021
                Categories
                Case Report

                sino-orbital,sino-nasal,aspergillosis,cryptic species,caspofungin

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