Invasive fungal infections and oomycoses in cats 2. Antifungal therapy.

CLINICAL RELEVANCE: Invasive fungal infections (IFIs) and oomycoses (hereafter termed invasive fungal-like infections [IFLIs]) are characterised by penetration of tissues by fungal elements. The environment is the most common reservoir of infection. IFIs and IFLIs can be frustrating to treat because long treatment times are usually required and, even after attaining clinical cure, there may be a risk of relapse. Owner compliance with medication administration and recheck examinations can also decline over time. In addition, some antifungal drugs are expensive, have variable interpatient pharmacokinetic properties, can only be administered parenterally and/or have common adverse effects (AEs). Despite these limitations, treatment can be very rewarding, especially when an otherwise progressive and fatal disease is cured. AIM: In the second of a two-part article series, the spectrum of activity, mechanisms of action, pharmacokinetic and pharmacodynamic properties, and AEs of antifungal drugs are reviewed, and the treatment and prognosis of specific IFIs/IFLIs - dermatophytic pseudomycetoma, cryptococcosis, sino-orbital aspergillosis, coccidioidomycosis, histoplasmosis, sporotrichosis, phaeohyphomycosis, mucormycosis and oomycosis - are discussed. Part 1 reviewed the diagnostic approach to IFIs and IFLIs. EVIDENCE BASE: Information on antifungal drugs is drawn from pharmacokinetic studies in cats. Where such studies have not been performed, data from 'preclinical' animals (non-human studies) and human studies are reviewed. The review also draws on the wider published evidence and the authors' combined expertise in feline medicine, mycology, dermatology, clinical pathology and anatomical pathology. ABBREVIATIONS FOR ANTIFUNGAL DRUGS: AMB (amphotericin B); FC (flucytosine); FCZ (fluconazole); ISA (isavuconazole); ITZ (itraconazole); KCZ (ketoconazole); PCZ (posaconazole); TRB (terbinafine); VCZ (voriconazole).

Invasive Fungal Infections and Oomycoses in Cats: 1. Diagnostic approach.

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.

Histopathological Grading, Clinical Staging and CD 31 Expression of Canine Splenic Hemangiosarcoma.

Canine hemangiosarcoma is a common, highly fatal tumor of older dogs, and predictors of survivability may provide clinically useful information. The objectives of this case series were to determine if a previously published tumor histological grading scheme, the level of tumor cellular atypia, clinical staging, or the level of CD 31 expression were useful for predicting the survival time in dogs with splenic hemangiosarcoma. Canine splenic hemangiosarcomas from 16 dogs were histologically graded, clinically staged, and assessed for CD 31 expression. Medical records were reviewed, the date of death was obtained, and survival data were analyzed statistically. Histopathological grading and clinical staging of canine splenic hemangiosarcomas, and the expression of CD 31 by the tumor cells were not significantly associated with the median survival time of the dogs in this study. However, strong expression of CD 31 by canine splenic hemangiosarcoma tumor cells was observed in dogs with short survival times, which warrants further studies to evaluate the potential prognostic value of CD 31 expression for the survival of dogs with splenic hemangiosarcoma.

First Report of Autochthonous Canine Leishmaniasis in Hong Kong.

Canine leishmaniasis is a zoonotic disease caused by Leishmania infantum; transmitted by the bite of phlebotomine sand flies. Leishmania infantum amastigotes were identified by cytology from a locally born Hong Kong dog exhibiting nasal, cutaneous, and systemic disease who was part of a kennel of eight dogs. All eight kennel dogs were subsequently tested serologically by enzyme-linked immunosorbent assay (ELISA) and by polymerase chain reaction (PCR) followed by DNA sequencing for L. infantum infection. The local dog was seropositive and blood and splenic tissue were PCR positive for L. infantum whilst the other kennel dogs were negative on serology and PCR. Autochthonous transmission was suspected for the local dog as Hong Kong lacks known vectors of L. infantum. Either vertical transmission from the deceased dam who had previously died with disease suspicious for leishmaniasis or horizontal transmission from a second non-locally born kennel dog who had been diagnosed previously with leishmaniasis was possible. This is the first recorded autochthonous case of canine leishmaniasis in Hong Kong. Leishmaniasis should be considered as a differential for cutaneous or systemic illness in local untraveled dogs in Hong Kong. In addition, as dogs serve as L. infantum reservoirs for human infection attention should be paid to the possibility of leishmaniasis emerging in Hong Kong.

Successful management of feline pemphigus foliaceus with pentoxifylline and topical hydrocortisone aceponate.

The treatment regimen for feline pemphigus foliaceus (PF), an autoimmune disease caused by auto-antibodies against proteins of the desmosome junction, usually includes high doses of oral or parenteral immunosuppressive drugs, typically glucocorticoids. This case adds to a growing body of evidence that topical hydrocortisone aceponate is effective for the treatment of feline PF, and demonstrates the practical use of a non-invasive diagnostic method for histopathology when owners refuse a biopsy to support a clinical diagnosis of PF. Finally, this case highlights an international trend of owner-initiated treatment of feline infectious peritonitis (FIP) using unlicensed, unregistered drugs.

Multifocal giant apocrine cystadenomas in a miniature poodle.

Apocrine cystadenomas have rarely been reported in dogs. Herein, a dog with multiple, large (1.0-7.0 cm) fluctuant and cystic skin masses on the right pelvic limb and chest is described. Histopathological evaluation revealed cystic cavities lined by single to multiple layers of apocrine epithelium with papillary projections, consistent with apocrine cystadenoma.

Les cystadénomes apocrines ont rarement été décrits chez le chien. Ici, un chien avec de multiples masses cutanées larges (1.0-7.0 cm), kystiques et fluctuantes sur le membre pelvien et le thorax, est décrit. L'évaluation histopathologique a montré des cavités kystiques entourées de couches simples à multiples d'épithélium apocrine avec projections papillaires, compatible avec un cystadénome apocrine.

Raramente se describen cistoadenomas apocrinos en perros. En este artículo se describe el caso de un perro con masas cutáneas múltiples, grandes (1,0 a 7,0 cm) fluctuantes y quísticas en la extremidad pélvica derecha y el pecho. La evaluación histopatológica reveló cavidades quísticas revestidas por capas individuales o múltiples de epitelio apocrino con proyecciones papilares, compatibles con cistoadenoma apocrino.

Os cistadenomas apócrinos já foram raramente descritos em cães. Descreve-se aqui o caso de um cão com múltiplas massas cutâneas grandes (1,0-7,0 cm), flutuantes e císticas no membro pélvico direito e no tórax. A avaliação histopatológica revelou cavidades císticas revestidas por uma a várias camadas de epitélio apócrino com projeções papilares, consistentes com cistadenoma apócrino.

Rare Generalized Form of Fungal Dermatitis in a Horse: Case Report.

A rare case of Geotrichum spp. dermatitis in a horse is presented. After unrelated, previous surgery and antibiotic treatment, a saddle horse showed well-circumscribed areas of non-pruritic alopecia. Suspecting allergic skin disease, the horse was treated with corticosteroids. The skin lesion spread, and a second veterinarian was consulted. At clinical examination, the horse was lethargic, pyretic and hair was shedding/easily epilated over the head, neck, shoulders, and legs and the hind legs were swollen. Blood analysis revealed mild leucocytosis and hyperglobulinemia. Hair, skin scraping, and skin biopsy ruled out parasites and bacteria; cytology identified yeast-like structures with hyphae or pseudohyphae. Geotrichum candidum was isolated on culture. Treatment consisted of stable disinfection, topical application of an antifungal solution, vitamins C and E supplementation and allowing the horse to graze in sunlight for at least 6 h/day. At 3-weeks follow-up, the horse had gained weight, alopecia was decreased, and all other clinical parameters were normal. Antifungal treatment was continued twice a week for three months. This study suggests Geotrichum candidum may cause skin lesions in horses after long-term use of corticosteroids or antibiotics. To avoid unnecessary and prolonged suffering in cases of dermatitis, veterinarians should be promptly consulted, appropriate diagnostic procedures conducted, so that a definitive diagnosis can be reached, and an appropriate treatment regimen implemented.

MYCOTIC DERMATITIS IN JUVENILE FRESHWATER CROCODILES (CROCODYLUS JOHNSTONI) CAUSED BY NANNIZZIOPSIS CROCODILI.

Nannizziopsis crocodili, a contagious, keratinophilic fungus, was identified from biopsied tissue in a captive juvenile freshwater crocodile during an outbreak of severe multifocal dermatitis affecting four of five crocodiles. Lesions progressed from superficial, well-demarcated ulceration of scales, to black pigmentation, localized edema, erythema, and flattening of the scales. Treatment with topical enilconazole provided clinical improvement in three of four crocodiles but all developed terminal gout. One crocodile did not develop clinical disease despite long-term exposure. This is the first report of N. crocodili in freshwater crocodiles and in a location remote to the index Australian case.

Vaccination with FAdV-8a induces protection against inclusion body hepatitis caused by homologous and heterologous strains.

Fowl aviadenoviruses (FAdV) are important avian pathogens, responsible for several poultry diseases prevalent worldwide, including inclusion body hepatitis (IBH). FAdV intraspecies cross-protection has been clearly demonstrated, but there is little evidence that any interspecies cross-protection exists. The present study aimed to assess the inter- and intraspecies protection between three FAdV field isolates (FAdV-8a, FAdV-8b, FAdV-11) identified in association with severe IBH outbreaks. Inocula prepared using inactivated plaque-purified virus with adjuvant Montanide™ ISA 71VG, were injected intramuscularly into 3-week-old SPF chickens. At 6-weeks of age, the birds were challenged with 106 TCID50 of homologous or heterologous virus intraperitoneally, and full post mortem examination performed at 4 days post-challenge. Various tissues were examined for gross and histological lesions and assessed for the presence of virus by PCR-HRM. All homologous-type vaccine/challenge groups exhibited protection against IBH lesions with no virus detected in the tissues. Unvaccinated groups challenged with virus showed evidence of FAdV-induced lesions; however, FAdV-8a demonstrated lower pathogenicity compared with FAdV-8b and FAdV-11. In the heterologous-type vaccine/challenge groups, FAdV-8a vaccine was shown to protect against challenge with both FAdV-8b and FAdV-11. FAdV-8a and 8b belong to species E and were therefore anticipated to cross-protect. However, FAdV-11 belongs to species D and therefore cross-protection by FAdV-8a was an uncharacteristic and unique finding of this study. Further research is required to disseminate the molecular basis for the interspecies cross-protection between FAdV-8a and FAdV-11. Nonetheless, the FAdV-8a isolate was shown to have substantial potential as a vaccine candidate in countries where FAdV-8a, 8b or 11 are prevalent.

Primary Hepatic Neuroendocrine Carcinoma Treated with Doxorubicin and Cyclophosphamide in a Dog.

A 7 yr, 6 mo old male neutered Australian cattle dog cross presented to a referral hospital with a large abdominal mass. An abdominal ultrasound revealed multifocal lesions throughout the liver, which were suspicious for intrahepatic metastasis, with no evidence of extrahepatic metastatic disease. Cytology indicated neoplasia of epithelial origin, with neuroendocrine neoplasia the primary suspicion. The patient was started on a maximally tolerated chemotherapy protocol of doxorubicin and metronomic cyclophosphamide. Stable disease was found on repeat abdominal ultrasounds, and the patient tolerated the protocol well. On completion of five doxorubicin doses, the dog was continued on metronomic cyclophosphamide and meloxicam. Progressive hepatic disease was found at 10 mo. The patient was euthanized 15.5 mo (465 days) after commencing treatment. Histopathology and immunohistochemistry (synaptophysin) performed on liver collected postmortem indicated (primary) hepatic neuroendocrine carcinoma. Primary hepatic neuroendocrine carcinomas are rare in dogs, and there is no standard of care for treatment. To the authors' knowledge, this is the first report of a primary hepatic neuroendocrine carcinoma treated with high-dose doxorubicin and metronomic cyclophosphamide.

Chronologic Analysis of Gross and Histologic Lesions Induced by Field Strains of FAdV-1, FAdV-8b, and FAdV-11 in Six-Week-Old Chickens.

Inclusion body hepatitis (IBH) is a disease affecting broiler chicken flocks worldwide. Several serotypes of fowl adenovirus (FAdV) have been implicated in disease outbreaks, with and without immunosuppression as a predisposing factor. IBH usually occurs in flocks up to 30 days of age; it is seldom seen in older birds. The objective of this study was to determine whether the pathogenicity for older birds of three FAdV field strains, belonging to serotypes 1, 8b, and 11, in the absence of immunosuppressive factors, was akin to that for younger birds, and to establish an effective and economical disease model for assessing cross-protection between serotypes. To achieve this objective, the gross pathology, histopathology, and dissemination of virus were examined at multiple time points after inoculation of 6-wk-old, specific-pathogen-free chickens via intraperitoneal injection. Both FAdV-8b and FAdV-11 generated lesions typical of those associated with outbreaks of IBH, and they were shown to be primary pathogens. The presence and severity of hepatic lesions were used to define two disease stages: degeneration (1-5 days postinoculation) and convalescence (6-14 days postinoculation). During the degenerative stage, FAdV-8b was detected in the liver, kidney, and gizzard of most birds, whereas FAdV-11 was predominantly detected in the liver, and both viruses persisted in the gizzard into convalescence. The pathogenesis of two IBH-associated FAdV strains in 6-wk-old chickens confirms their high level of virulence and also provides an effective experimental model for investigation of cross-protection between FAdVs. It also demonstrates persistence of the virus in the gizzard long after infection, supporting the notion that it is a site of viral shedding.

Chronological analysis of gross and histological lesions induced by field strains of fowl adenovirus serotypes 1, 8b and 11 in one-day-old chickens.

Fowl adenoviruses (FAdVs) cause diseases in domestic chickens, including inclusion body hepatitis (IBH), with immunosuppression believed to play a role in their pathogenesis. To gain a better understanding of the pathogenesis and chronology of disease caused by FAdVs, the gross pathology, histopathology and dissemination of virus were examined at several different time points, after inoculation of one-day-old specific pathogen-free chickens with FAdV-1, FAdV-8b or FAdV-11 via the ocular route. FAdV-8b had a slightly greater virulence than FAdV-11, but both were primary pathogens. The presence and severity of hepatic lesions were used to define the three stages of the disease: incubation (1-3 days post-inoculation, PI), degeneration (4-7 days PI) and convalescence (14 days PI). Both viruses were detected in the liver, kidney, bursa, thymus and gizzard of most birds during the degenerative stage, and persisted in the gizzard into convalescence. The FAdV-1 isolate was found to be apathogenic, but virus was detected in the bursa and/or gizzard of several birds between 2 and 7 days PI. This is the first study examining the chronology of gross and microscopic lesions of pathogenic and apathogenic FAdVs in association with viral presence in multiple tissues. It was concluded that both FAdV-8b and FAdV-11 are primary pathogens, and that these strains may play a role in immunosuppression.

Squamous cell carcinoma with vascular invasion in a diamondback rattlesnake (Crotalus adamanteus).

Squamous cell carcinoma (SCC) is a common neoplasm diagnosed in domestic and wild animals, including several species of reptiles. However, reports of SCC invading vasculature or metastasizing in snakes are lacking. This report documents a case of SCC in an adult male eastern diamondback rattlesnake (Crotalus adamanteus) with a unique presentation and invasion into several small- to medium-sized vessels, suggestive of a metastatic process. What was initially suspected to be an abscessed tail was ultimately determined to be SCC originating at the base of the rattle.