Abstract
Cryptic species in Aspergillus section Fumigati are increasingly recognised as pathogens in humans and animals. The A. viridinutans complex (AVC) has recently expanded to comprise 10 ...species, of which six are known to be pathogenic, including A. udagawae, A. felis, A. pseudofelis, A. parafelis, A. pseudoviridinutans, and A. wyomingensis. They cause locally invasive and disseminated invasive disease syndromes, including chronic pulmonary aspergillosis and invasive aspergillosis in humans, invasive fungal rhinosinusitis in cats, and disseminated invasive aspergillosis in dogs. In contrast to A. fumigatus, AVC species are characterized by higher minimum inhibitory concentrations (MICs) of antifungal drugs and the infections they cause are typically more chronic and more refractory to therapy. This review, of relevance for one-health practitioners, explores the history of the AVC as well as current phylogenetic relationships, secondary metabolite production, environmental distribution, clinical syndromes, and antifungal susceptibility patterns.
Aspergillosis is a major cause of severe respiratory disease in birds. The prevalence of cryptic section Fumigati and other non-Aspergillus fumigatus species as causative agents is unknown. Species ...identity was determined in 30 isolates from affected birds from zoos, pet birds and poultry by PCR of the ITS1-5.8S-ITS2 and partial β-tubulin genes. The most prevalent isolate was A. fumigatus sens. str. in 87% (26) cases. Other Aspergillus species were identified in 13% (4) cases, including A. restrictus (1), A. flavus sens. str. (2), and A. nidulans-clade (1). This is the first report of A. restrictus causing avian disease.
Invasive fungal infections (IFI) due to species in Aspergillus section Fumigati (ASF), including the Aspergillus viridinutans species complex (AVSC), are increasingly reported in humans and cats. The ...risk of exposure to these medically important fungi in Australia is unknown. Air and soil was sampled from the domiciles of pet cats diagnosed with these IFI and from a nature reserve in Frankston, Victoria, where Aspergillus viridinutans sensu stricto was discovered in 1954. Of 104 ASF species isolated, 61% were A. fumigatus sensu stricto, 9% were AVSC (A. felis-clade and A. frankstonensis sp. nov.) and 30% were other species (30%). Seven pathogenic ASF species known to cause disease in humans and animals (A. felis-clade, A. fischeri, A. thermomutatus, A. lentulus, A. laciniosus A. fumisynnematus, A. hiratsukae) comprised 25% of isolates overall. AVSC species were only isolated from Frankston soil where they were abundant, suggesting a particular ecological niche. Phylogenetic, morphological and metabolomic analyses of these isolates identified a new species, A. frankstonensis that is phylogenetically distinct from other AVSC species, heterothallic and produces a unique array of extrolites, including the UV spectrum characterized compounds DOLD, RAIMO and CALBO. Shared morphological and physiological characteristics with other AVSC species include slow sporulation, optimal growth at 37°C, no growth at 50°C, and viriditoxin production. Overall, the risk of environmental exposure to pathogenic species in ASF in Australia appears to be high, but there was no evidence of direct environmental exposure to AVSC species in areas where humans and cats cohabitate.
Fungal rhinosinusitis, including sinonasal aspergillosis (SNA) and sino-orbital aspergillosis (SOA), is the most common type of aspergillosis encountered in cats. Other focal forms of aspergillosis ...including disseminated invasive aspergillosis occur less frequently. SOA is an invasive mycosis that is increasingly recognized and is most commonly caused by Aspergillus felis, a close relative of Aspergillus fumigatus. SNA can be invasive or noninvasive and is most commonly caused by A fumigatus and Aspergillus niger. Molecular methods are required to correctly identify the fungi that cause SNA and SOA. SNA has a favorable prognosis with treatment, whereas the prognosis for SOA remains poor.
A 2‐year‐old male desexed Ragdoll cat with a 1‐year history of sneezing and nasal discharge presented with a large subcutaneous cervical mass, identified as the right medial retropharyngeal lymph ...node on computed tomography (CT). A right orbital mass, destructive sino‐nasal cavity disease and multiple pulmonary nodules were also identified. Aspergillus felis was cultured from the lymph node. After treatment with posaconazole and liposomal amphotericin B the lymph node enlargement and orbital mass resolved but left frontal sinus involvement and pulmonary lesions persisted despite additional caspofungin therapy. The cat was euthanized 14 months after diagnosis with dysphagia and chronic progressive exophthalmos. A meningeal granuloma with intravascular fungal hyphae was identified at post‐mortem and A felis was cultured from the left frontal sinus and a right retrobulbar fungal granuloma. This case demonstrates that disseminated disease is a possible sequel to invasive fungal rhinosinusitis caused by A felis in cats.
The past decade has seen an increase in aspergillosis in humans and animals due to
species complex members. Azole resistance is common to these infections, carrying a poor prognosis.
gene mutations ...are the main cause of acquired azole resistance in
This study aimed to determine if the azole-resistant phenotype in
complex members is associated with
mutations or extrolite profiles. The
gene of clinical and environmental isolates was amplified using novel primers, antifungal susceptibility was tested using the Clinical and Laboratory Standards Institute methodology, and extrolite profiling was performed using agar plug extraction. Very high azole MICs were detected in 84% of the isolates (31/37). The MICs of the newer antifungals luliconazole and olorofim (F901318) were low for all isolates.
sequences revealed 113 nonsynonymous mutations compared to the sequence of wild-type
M172A/V and D255G, previously associated with
azole resistance, were common among all isolates but were not correlated with azole MICs. Two environmental isolates with nonsusceptibility to itraconazole and high MICs of voriconazole and isavuconazole harbored G138C, previously associated with azole-resistant
Some novel mutations were identified only among isolates with high azole MICs. However,
homology modeling did not cause a significant protein structure change for these mutations. There was no correlation between extrolite patterns and susceptibility. For
complex isolates,
mutations and the extrolites that they produced were not major causes of antifungal resistance. Luliconazole and olorofim show promise for treating azole-resistant infections caused by these cryptic species.
The prevalence of azole resistance in Aspergillus fumigatus is uncertain in Australia. Azole exposure may select for resistance. We investigated the frequency of azole resistance in a large number of ...clinical and environmental isolates.
A. fumigatus isolates 148 human, 21 animal and 185 environmental strains from air (n = 6) and azole-exposed (n = 64) or azole-naive (n = 115) environments were screened for azole resistance using the VIPcheck™ system. MICs were determined using the Sensititre™ YeastOne YO10 assay. Sequencing of the Aspergillus cyp51A gene and promoter region was performed for azole-resistant isolates, and cyp51A homology protein modelling undertaken.
Non-WT MICs/MICs at the epidemiological cut-off value of one or more azoles were observed for 3/148 (2%) human isolates but not amongst animal, or environmental, isolates. All three isolates grew on at least one azole-supplemented well based on VIPcheck™ screening. For isolates 9 and 32, the itraconazole and posaconazole MICs were 1 mg/L (voriconazole MICs 0.12 mg/L); isolate 129 had itraconazole, posaconazole and voriconazole MICs of >16, 1 and 8 mg/L, respectively. Soil isolates from azole-exposed and azole-naive environments had similar geometric mean MICs of itraconazole, posaconazole and voriconazole (P > 0.05). A G54R mutation was identified in the isolates exhibiting itraconazole and posaconazole resistance, and the TR34/L98H mutation in the pan-azole-resistant isolate. cyp51A modelling predicted that the G54R mutation would prevent binding of itraconazole and posaconazole to the haem complex.
Azole resistance is uncommon in Australian clinical and environmental A. fumigatus isolates; further surveillance is indicated.
Clinical relevance:
In contrast to superficial fungal infections, such as dermatophytosis, invasive fungal infections (IFIs) are characterised by penetration of tissues by fungal elements. Disease ...can spread locally within a region or can disseminate haematogenously or via the lymphatics. The environment is the most common reservoir of infection. Since fungal spores are airborne, indoor cats are also susceptible to IFIs. Some environmental fungi are ubiquitous and present globally, while others are endemic or hyperendemic within specific geographic regions. Zoonotic pathogens include Microsporum canis, Sporothrix schenckii and Sporothrix brasiliensis.
Aim:
In the first of a two-part article series, the approach to the investigation of feline IFIs and oomycoses is reviewed. As well as tips for diagnosis, and information on the ecological niche and distribution of fungal pathogens, the review covers clinical presentation of the most common IFIs, including cryptococcosis, histoplasmosis, blastomycosis, coccidioidomycosis, sporotrichosis, phaeohyphomycosis, aspergillosis and dermatophytic pseudomycetoma, as well as the oomycoses pythiosis, lagenidiosis and paralagenidiosis. In Part 2, the spectrum of activity, mechanisms of action, pharmacokinetic and pharmacodynamic properties and adverse effects of antifungal drugs are reviewed, and the treatment and prognosis for specific IFIs and oomycoses are discussed.
Evidence base:
The review draws on published evidence and the authors' combined expertise in feline medicine, mycology, dermatology, clinical pathology and anatomical pathology.
Feline aspergillosis Barrs, Vanessa R; Talbot, Jessica J
The Veterinary clinics of North America. Small animal practice
44, Številka:
1
Journal Article
Recenzirano
Feline aspergillosis includes sinonasal aspergillosis (SNA), sino-orbital aspergillosis (SOA), other focal invasive forms, and disseminated disease. SOA is an invasive mycosis that is being ...increasingly recognized, and is most commonly caused by a recently discovered pathogen Aspergillus felis. SNA can be invasive or noninvasive and is most commonly caused by Aspergillus fumigatus and Aspergillus niger. Molecular methods are required to correctly identify the fungi that cause SNA and SOA. SNA has a favorable prognosis with treatment, whereas the prognosis for SOA remains poor.
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