Clinicopathological and diagnostic imaging findings in a dog with neurocandidiasis.

Neurocandidiasis is systemic candidiasis with central nervous system involvement. This case report describes the clinical presentation, diagnostic test results, and histopathology of a dog with neurocandidiasis. A 3-year-old German shepherd dog was presented for a 3-day history of abnormal mentation, neck pain, and ataxia. Magnetic resonance imaging (MRI) scan of the brain revealed multifocal, small, round, intra-axial lesions within the forebrain. Examination of the cerebrospinal fluid revealed severe neutrophilic inflammation. Extensive testing for infectious diseases was negative. The dog was administered immunosuppressive doses of corticosteroids. The dog's clinical signs improved transiently but got worse 12 days after starting the treatment. Repeat MRI scan revealed multiple, intra-axial, target-like nodular lesions scattered throughout the brain parenchyma. In the temporal muscles, nodules were seen. Cytology of the fine needle aspirates of the nodules in the temporal muscles revealed a neutrophilic inflammation with hyalohyphomycosis. Postmortem examination was compatible with a severe systemic fungal infection. Candida albicans was isolated from the brain, kidney, and heart.

Fatal Pulmonary and Cerebellar Zygomycosis due to Rhizomucor pusillus in a Ringed Seal (Pusa hispida).

A 4-year-old captive ringed seal (Pusa hispida) was treated with subcutaneous antibacterial injections for pus exuding wounds in the skin and associated blubber following a bite attack. Three months after the incident, the animal presented nystagmus and died the following day. At necropsy, there was a 25 × 18 × 25 mm well-delineated, opaque nodular mass in the lung, besides the skin ulcers and localized areas of discoloration in the blubber correlating with the bite wound and injection sites. Histopathology of the pulmonary mass demonstrated severe eosinophilic inflammatory infiltration among numerous intralesional fungal hyphae. The hyphae were irregularly branched, broad and aseptate, consistent of zygomycosis. Magnetic resonance imaging was conducted on the head, which was initially frozen intact, revealing diffuse areas of hyperintensity in the cerebellum. Restricted histopathologic examination of the cerebellum showed severe granulomatous inflammation well spread within the neuroparenchyma, associated with abundant intralesional fungal hyphae similar to those appreciated in the pulmonary mass. Molecular analyses of the fungi in the pulmonary and cerebellar tissue identified the etiologic agent in both sites as Rhizomucor pusillus. The likely route of infection is through inhalation of R. pusillus spores or fragmented hyphae from the environment that developed into an initial pulmonary infection, becoming the source of hematogenous dissemination to the cerebellum. The skin and blubber lesions likely contributed to immunosuppression. Zygomycosis is uncommon in pinnipeds, and the present report emphasizes the importance of considering zygomycete dissemination even when the primary focus is highly confined.

Characterization and phylogenetic analysis of a Cunninghamella bertholletiae isolate from a bottlenose dolphin (Tursiops truncatus).

BACKGROUND: Cunninghamella is a genus of the order Mucorales which includes saprophytic species, rarely causing mycoses. The most frequently reported in human mycoses is the thermophilic species Cunninghamella bertholletiae. However, this species does not appear to cause mucormycosis in animals, so there is scarce information about C. bertholletiae isolates from animals. AIMS: In this paper we describe the phenotypic and genotypic characterization, and the phylogenetic analysis, of an isolate of C. bertholletiae involved in a central nervous system mucormycosis in a dolphin. METHODS: The isolate studied in this publication was characterized using the current morphological and physiological identification system for Cunninghamella species. DNA sequencing and analysis of the D1/D2 regions of the 26S rRNA gene and the ITS-5.8S rRNA gene sequences were also performed. RESULTS: Colonies were fast-growing, white at first, although they became tannish-gray, covering the whole plate after 7 days of incubation at 30 and 40°C. Limited growth was observed after 7 days at 45°C. The micromorphology showed characteristic erect sporangiophores. The identification of the isolate was confirmed by DNA sequencing of the D1/D2 regions of the 26S and the ITS-5.8S (ITS) rRNA gene sequencing. CONCLUSIONS: In the phylogenetic study, the isolate clustered in the same clade as C. bertholletiae neotype strain although some differences were observed in the ITS sequences. In the cetacean cases, the possible sources of infection are unclear. The reasons why this pathogen has been found only in cetaceans and not in other domestic or wild animals are at the moment unknown and need further study.

Clinical Features and Magnetic Resonance Imaging Findings in 7 Dogs with Central Nervous System Aspergillosis.

BACKGROUND: Systemic aspergillosis is a manifestation of Aspergillus sp. infection that can result in central nervous system (CNS) involvement with marked alterations in CNS function. Information regarding the clinical presentation and magnetic resonance imaging (MRI) findings in cases of aspergillosis with CNS involvement is lacking, resulting in a need for better understanding of this disease. HYPOTHESIS/OBJECTIVES: The primary objectives were to describe the clinical features and MRI findings in dogs with CNS aspergillosis. The secondary objectives were to describe clinicopathologic findings and case outcome. ANIMALS: Seven dogs with CNS aspergillosis. METHODS: Archived records from 6 institutions were reviewed to identify cases with MRI of CNS aspergillosis confirmed with serum galactomannan enzyme immunoassay (EIA) testing, culture, or supported by histopathology. Signalment, clinical, MRI, clinicopathologic, histopathologic, and microbiologic findings were recorded and evaluated. RESULTS: Aspergillosis of the CNS was identified in 7 dogs from 3 institutions. The median age was 3 years and six were German Shepherd dogs. Five dogs had signs of vestibular dysfunction as a component of multifocal neurological abnormalities. The MRI findings ranged from normal to abnormal, including hemorrhagic infarction and mass lesions. CONCLUSIONS AND CLINICAL IMPORTANCE: Until now, all reported MRI findings in dogs with CNS aspergillosis have been abnormal. We document that CNS aspergillosis in dogs, particularly German Shepherd dogs, can be suspected based on neurologic signs, whether MRI findings are normal or abnormal. Confirmatory testing with galactomannan EIA, urine, cerebrospinal fluid (CSF) or tissue culture should be performed in cases where aspergillosis is a differential diagnosis.

Clinical and imaging findings in five dogs with intracranial blastomycosis (Blastomyces dermatiditis).

Fungal infections affecting the central nervous system are rare. The purpose of this study was to describe clinical and imaging findings in dogs with intracranial blastomycosis (Blastomyces dermatiditis). The radiology database was searched retrospectively for patients with a diagnosis of intracranial blastomycosis which had computed tomography performed as part of their diagnostic work-up. Medical records and imaging studies were reviewed. Five dogs met the inclusion criteria. Major presenting complaints were stertor/nasal discharge (n=2), exophthalmos (n=1), and seizures (n=2). Clinical and laboratory findings were variable. Computed tomographic examination revealed a single contrast-enhancing intra-axial mass (n=1), a nasal mass disrupting the cribriform plate (n=3), and an intracranial mass extending into the orbit and nasal cavity (n=1). Findings in intracranial blastomycosis in dogs are variable, and the disease may mimic other inflammatory disorders or neoplasia.

Spraguea (Microsporida: Spraguidae) infections in the nervous system of the Japanese anglerfish, Lophius litulon (Jordan), with comments on transmission routes and host pathology.

Anglerfish from the genus Lophius are a globally important commercial fishery. The microsporidian Spraguea infects the nervous system of these fish resulting in the formation of large, visible parasitic xenomas. Lophius litulon from Japan were investigated to evaluate the intensity and distribution of Spraguea xenomas throughout the nervous system and to assess pathogenicity to the host and possible transmission routes of the parasite. Spraguea infections in L. litulon had a high prevalence; all fish over 403 mm in standard length being infected, with larger fish usually more heavily infected than smaller fish. Seventy percent of all fish examined had some gross visible sign of infection. The initial site of development is the supramedullary cells on the dorsal surface of the medulla oblongata, where all infected fish have parasitic xenomas. As the disease progresses, a number of secondary sites typically become infected such as the spinal, trigeminal and vagus nerves. Fish with infection in the vagus nerve bundles often have simultaneous sites of infection, in particular the spinal nerves and along the ventral nerve towards the urinary bladder. Advanced vagus nerve infections sometimes form xenomas adjacent to kidney tissue. Spraguea DNA was amplified from the contents of the urinary bladders of two fish, suggesting that microsporidian spores may be excreted in the urine. We conclude that supramedullary cells on the hindbrain are the primary site of infection, which is probably initiated at the cutaneous mucous glands where supramedullary cells are known to extend their peripheral axons. The prevalence of Spraguea infections in L. litulon was very high, and infections often extremely heavy; however, no associated pathogenicity was observed, and heavily infected fish were otherwise normal.

Cerebral phaeohyphomycosis in a green iguana (Iguana iguana).

Cerebral phaeohyphomycosis was diagnosed in a 4-year-old green iguana (Iguana iguana) with paroxysmal spastic paralysis of all limbs and circling motion. Formalin-fixed tissues were collected at necropsy examination and submitted for evaluation. The left cerebrum and the left ventricle were replaced by a solid brown coloured mass. Microscopical examination revealed the presence of necrotizing and granulomatous encephalitis affecting the cerebrum, cerebellum and brainstem, with severe vasculitis and intralesional dematiaceous fungal hyphae. No other lesions or fungi were found in other organs. Fungi were identified as Oidiodendron spp. by sequence analysis of the internal transcribed spacer (ITS) region 1 extracted from formalin-fixed and paraffin wax-embedded brain tissue. This case represents the first report of phaeohyphomycosis with tropism for the central nervous system in a reptile. In the absence of fresh tissue, the diagnosis in such cases may be assisted by molecular analysis of fixed tissue specimens.

Central nervous system blastomycosis in a dog.

An adult golden retriever was presented for progressive neurologic dysfunction. Clinical examination suggested brainstem disease. Blastomycosis was diagnosed based on fine-needle aspiration cytology of a normal sized lymph node and a positive blastomycosis urine antigen test. Systemic blastomycosis with neurologic involvement was confirmed at necropsy.

Mycotic encephalitis and nephritis in a dog due to infection with Cladosporium cladosporioides.

The dematiaceous fungus Cladosporium cladosporioides is a widely distributed saprophyte that is reported to occasionally infect the lung, skin, eye and brain of humans. This report describes a German shepherd dog with granulomatous encephalitis and nephritis due to C. cladosporioides infection. Although the fungal organisms appeared non-pigmented in haematoxylin and eosin stained sections, they were readily identified with histochemical stains. Semi-nested polymerase chain reaction using universal fungal primers amplified fungal DNA from fixed tissue that had identity to that of C. cladosporioides on sequencing.

Phaeohyphomycosis in a snow leopard (Uncia uncia) due to Cladophialophora bantiana.

Phaeohyphomycosis caused by Cladophialophora bantiana was diagnosed in a 5-month-old snow leopard with spastic paralysis of the hind legs and inability to defaecate or urinate. At post-mortem examination, a greenish soft mass resembling an abscess was found on one side of the epidural space at the fourth lumbar vertebral body. Histological examination revealed a purulent meningitis with myelomalacia. Dematiaceous fungal hyphae, present within the inflammatory infiltrate, were identified as C. bantiana by culture and sequence analysis of the 18S ribosomal RNA gene. This neurotropic fungus rarely affects organs other than the brain in human beings and cats, and has been reported only occasionally in Europe. The case described suggests that phaeohyphomycosis due to C. bantiana infection may be recognized more frequently in the future and the possible involvement of organs other than the brain should be borne in mind.

Fungal infections of the central nervous system in the dog and cat.

Fungal infections of the central nervous system (CNS) in dogs and cats are uncommon. The purpose of this paper is to review the clinical signs, diagnostic tests, and therapeutic options of fungal infections of the CNS in the dog and cat. Clinical signs are dependent on lesion location and are often multifocal. Extraneural involvement is common. Antemortem diagnosis can be difficult and is definitively made via cytology, biopsy, or culture of an affected organ or cerebrospinal fluid (CSF). Magnetic resonance imaging can support a diagnosis and may assist in therapeutic decisions. Fungal serology can support a diagnosis when direct visualization of the organism is not possible. Long-term azole maintenance therapy is suggested to enhance survival and prevent relapse. Serial cerebrospinal fluid evaluation and magnetic resonance imaging may identify early relapse.

Posaconazole therapy for systemic coccidioidomycosis in a chimpanzee (Pan troglodytes): a case report.

Systemic coccidioidomycosis was diagnosed in a 4-year-old male chimpanzee (Pan troglodytes) with ascites and failure to thrive. Physical examination, laboratory and radiological studies, and exploratory laparotomy showed signs of systemic fungal infection that included penetration into the central nervous system (CNS). Serum and cerebrospinal fluid (CSF) titres, along with ascites cytology findings, confirmed the presence of Coccidioides immitis. However, the organism could not be cultured from the CSF. Treatment with fluconazole 10 mg kg(-1) daily for 6 months was not associated with clinical improvement. Subsequent treatment with posaconazole 50 mg kg(-1) daily for approximately 24 months resulted in negative serum titres and improved clinical status. Illness not directly related to the C. immitis infection caused the chimpanzee's deterioration and eventual killing. Histological examination performed during necropsy provided no evidence of coccidioidomycosis; however, a positive C. immitis serum antibody titre was noted. The successful suppression of coccidioidomycosis observed in this chimpanzee suggests that posaconazole may have a role in the treatment of CNS infections caused by susceptible fungi.

Cryptococcus neoformans var. gattii in the koala (Phascolarctos cinereus): a review of 43 cases of cryptococcosis.

Details of 11 previously reported cases and 32 new cases of cryptococcosis in captive and wild koalas were analysed. Cryptococcus neoformans var. gattii accounted for all 29 cases in which varietal status was determined. No age or sex predisposition was observed. The respiratory tract was the primary focus of disease in 77% of cases. Although the lower respiratory tract was affected most commonly (60% of cases), 30% of cases had upper respiratory tract lesions and 14% had both. Dissemination was common, especially to the central nervous system (37% cases). Local extension to surrounding tissues was a feature of upper respiratory tract disease. Other tissues showing cryptococcal invasion included lymph nodes (19%), gastrointestinal tract (12%), kidneys (12%), spleen (9%) and skin (7%). Only three cases (7%) had no respiratory tract or central nervous system involvement, two cases of primary skin inoculation and one case of primary lymphadenopathy. Late presentation was a likely factor in the high proportion of cases with disseminated disease (40%). The proportion of koala cases with involvement of the central nervous system, lower respiratory tract and skin, parallels what has been reported for immunocompetent people. Cryptococcosis in the koala appears to be an excellent naturally occurring model for examination of the cryptococcal host-parasite relationship in all species.

Cryptococcosis of the central nervous system in a dog.

A 3-year-old female German Shepherd Dog was evaluated for progressive mental obtundation and vestibular signs. Central nervous system cryptococcosis was diagnosed on the basis of growth of Cryptococcus neoformans in fungal culture of CSF, as well as detection of the organism in CSF via microscopy. Cryptococcal capsular latex antigen agglutination titer was 1:262,144 in CSF and 1:1,048,576 in serum samples. Imaging with magnetic resonance augmented diagnosis. The dog improved after long-term treatment with fluconazole. Fluconazole is useful in the treatment of CNS cryptococcosis, because it attains high concentration in the CNS. Long-term therapy is often required for resolution of clinical signs, and affected animals may require long-term follow-up with periodic evaluation of CSF via fungal culture and latex agglutination tests. Monitoring serum latex agglutination test results may provide a safe, less invasive means of monitoring response to treatment.

Fatal systemic phaeohyphomycosis in a cat due to Cladophialophora bantiana.

We report a case of fatal systemic mycosis in a 9-year-old cat. Diagnosis of phaeohyphomycosis was made by histology. Morphological and molecular identification of the fungus isolated from the lesions yielded the species Cladophialophora bantiana. This species is well known to be a neurotropic fungus causing cerebral pyogranulomatous lesions in humans. In this case, the lesions were widespread, distributed without the involvement of central nervous system. The origin of systemic manifestation is still unknown and no evidence of immunosuppression was found. It is the first feline case of C. bantiana infection reported in Europe.

Cryptococcal pyelonephritis in a dog.

A 5-year-old castrated male Golden Retriever was evaluated for polyuria, polydipsia, and progressive regurgitation thought to be a result of bacterial pyelonephritis and megaesophagus. Bacteriologic culture of urine failed to yield clinically relevant growth, and results of a urine sediment examination were normal. With time, intention tremors and progressive neurologic dysfunction were also observed. At necropsy, a diagnosis of cryptococcal disease was confirmed histologically and immunohistochemically. Findings in the dog of this report were indicative of nephrogenic diabetes insipidus with polyuria and polydipsia caused by cryptococcal pyelonephritis. Neurologic manifestations of systemic cryptococcus infection included megaesophagus, esophageal hypomotility, and regurgitation attributed to localization of cryptococcal organisms in the brain stem in the region of the dorsal motor nucleus of the vagus nerve. To the authors' knowledge, this is the first report of polyuria secondary to cryptococcal pyelonephritis.

Cerebral phaeohyphomycosis caused by Cladosporium spp. in two domestic shorthair cats.

Two domestic shorthair cats presented for clinical signs related to multifocal central nervous system dysfunction. Both cats had signs of vestibular system involvement and anisocoria, and one had generalized seizure activity. Cerebrospinal fluid analysis revealed a neutrophilic pleocytosis with protein elevation in one cat and pyogranulomatous inflammation in the second. Electroencephalography and brain-stem auditory-evoked potentials in the first cat confirmed cerebral cortical and brain-stem involvement. Euthanasia was performed in both cats, and postmortem diagnoses of phaeohyphomycosis secondary to Cladosporium spp. were made based on histopathology and fungal culture in both cats.

Pyogranulomatous meningoencephalitis associated with dematiaceous fungal (Cladophialophora bantiana) infection in a domestic cat.

A 6-month-old, castrated male domestic cat with progressive neurological signs of 2-3 weeks duration was necropsied. Macroscopic findings were restricted to the brain and included irregularly shaped, well-delineated but unencapsulated areas of intense black pigmentation involving the rostral portion of both cerebral hemispheres. Microscopically, numerous brown, oblong, segmented branching hyphae and conidial-like structures and extensive pyogranulomatous inflammation were identified throughout the cerebral lesion and in adjacent blood vessels. Hyphae and oval conidia were best demonstrated with either Gomori methenamine silver or periodic acid-Schiff stain. Fungal infection in the brain of this cat was unrelated to any concurrent immunodeficiency syndrome or immunosuppressive treatment. This report deals with a case of cerebral phaeohyphomycosis from which a different species of dematiaceous fungus, Cladophialophora bantiana, was isolated and identified.