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THE UNIVERSITY OF TENNESSEE COLLEGE OF VETERINARY MEDICINEDEPARTMENT OF <<INSERT DEPARTMENT NAME HERE ON MASTER SLIDE>>

Fungi of Ophthalmic Importance

Diane Hendrix, DVM, DACVOProfessor of Ophthalmology

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Mycology

• Fungi are eukaryotic organisms

Yeasts

• Unicellular

• Elliptical to spherical

• Generally 3-5 µm in diameter

• Reproduce by budding

Molds

• Multi-cellular

• Branching tubular hyphae

• 2-10 µm in diameter

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Dimorphic

• Fungi that can grow as either yeasts or molds

Polymorphic

• Fungi that exhibit multiple forms simultaneously

• Environmental temperature, nutrient factors and kinetic factors determine the type of growth observed.

Mycology

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Reproductive Cycle of Fungi

• Sexual, asexual or both

• Simple mitosis of somatic nuclei and budding

• Apical extension of the cell wall

Mycology

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• Septa

• Fungal cell walls contain ergosterol

Mycology

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Fungi and the eye• Not permanent floral residents

• Transient colonizers of the external eye• Predominant fungal isolates

from normal equine eyes

• Aspergillus

• Alternaria

• Penicillium

• Fusarium

• Cladosporium

• Absidia

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Ocular defenses

• An intact corneal epithelium provides resistance to fungal penetration and infection.

• Unfavorable environment for the growth of any opportunistic fungi due to:

– Normal ocular surface flora

– Normal lacrimal flow

– Mechanical movements of eyelids and nictitans

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• Normal body temperature prevents many fungi from becoming pathogenic.

• The lower temperature of the cornea may partially explain the predilection for keratomycosis.

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• Adherence via adhesins– The outer fibrillar layer of yeast and

filamentous fungal cell wall is composed of mannan or mannoprotein

• Fungal invasiveness – is directly related to the fungal load and

inversely proportional to the intensity of inflammatory response.

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• Phenotypic switching or morphogenesis – Method of adaptation used by some microbes in

different microenvironments to survive inside infected hosts.

– This permits fungi to survive in the presence of anti-fungal drugs and resist anti-microbial therapy.

– Intrahyphal hyphae or hypha-in-hypha and thickened fungal cell walls

• Mycotoxins• Proteases

– Matrix metalloproteinases

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Immunity

• Primarily cell mediated

• Local immunosuppression by corticosteroids may predispose an animal to a fungal infection

• Systemic or topical antibacterial agents

– alter normal flora

– decrease natural microbial barriers

– encourage colonization and growth of fungi

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Vascularization

• Certain fungal isolates produce metabolites that inhibit vascular tubule formation in vitro, thus altering the host vascular response to the fungi.

Welch PM, .In vitro analysis of antiangiogenic activity of fungi isolated from clinical cases of equine keratomycosis. Vet Ophthalmol. 2000;3(2-3):145-151.

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Keratomycosis

• Most commonly diagnosed in the horse but has been reported in dogs, cats and birds.

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Equine Keratomycosis

Common environmental

fungi

– Aspergillus

– Penicillium

– Fusarium

• Other organisms

• Candida infections

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• Cytology

• Culture

• Histopathology

Diagnosis of fungal disease

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Confocal microscopy

VO 2011 Jan;14(1):1-9

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Treatment

• Sensitivities to standard drugs vary by region.

• Voriconazole - broad spectum of activity and penetrates into the AC.

• Natamycin

• Silver sulfadiazine can be applied every 4 to 5 hours.

• No fungi were routinely sensitive to fluconazole.

Keratomycosis

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Canine fungal keratitis

• Predisposing factors

• Use cytology with culture

• Many types of fungal organisms have been isolated.

Vet Ophthalmol. 2015 Sep 24. doi: 10.1111/vop.12313.

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SYSTEMIC MYCOSES

Blastomyces

Cryptococcus

Coccidioides

Histoplasma

Aspergillus

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• Most of these fungi are dimorphic.

• All cause uveitis, chorioretinitis, endophthalmitis and optic neuritis.

• The host inflammatory response is generally suppurative acutely and pyogranulomatouschronically.

• Host tissues can be damaged directly by inflammatory processes or by degradativeenzymes produced by the fungi.

Systemic Mycoses

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Pathogenesis

• Dimorphic switching

• Residing in phagocytes

• Remodeling cell walls

• Adherence

Systemic Mycosis

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Dimorphic fungi adaptations• All primary fungal

pathogens.

• All have features that facilitate growth in tissue

• Phase transition or dimorphic switching is essential for the pathogenesis for all thermally dimorphic fungi.

FEMS Microbiol Rev. 2015 Nov;39(6):797-811. doi: 10.1093/femsre/fuv035.

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Signalling pathways for dimorphic switch• These signalling pathways also co-regulate

processes important for adaptation to this environment, such as adaptation to oxidative stress.

• Phase specific genes have been identified, but little is known about controlling expression.

• The predominant stimulus for switch is temperature.

• Conversion to yeast is accelerated following phagocytosis of B.dermatitidis spores by alveolar macrophages.

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• Some fungi reside within phagocytic cells of the host as this shields organisms from the rest of the immune system.

• Other dimorphic fungi use the yeast cell form to avoid phagocytosis and the cytotoxic environment of the phagolysosomal system; instead, they are adapted to tolerating the adaptive immune responses.

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Surviving within the macrophage phagolysosome

• Iron– Host cells restrict iron through sequestration by high-affinity

iron-binding proteins.– Host T-cells produce(IFNγ) which down regulates surface

transferrin receptors and NO production– Fungi utilize high-affinity iron uptake systems such as reductive

iron assimilation and non-reductive, siderophore-based iron assimilation.

• Calcium plays an important role in H. capsulatum infection.– Large amounts of calcium are essential for H. capsulatum

hyphal growth but not yeast suggesting that yeast cells are adapted to surviving in low calcium environments such as the macrophage phagolysosome.

– Bad1 is a yeast-specific calcium-binding protein which is essential for pathogenicity in B. dermatiditis.

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Other survival strategies• Rapid remodeling of the cell wall to prevent

recognition by phagocytic cell PRRs. • Proteins required for oxidative stress

resistance are components of the extracellular proteome of H. capsulatumyeast cells.

• Heat shock proteins have developed to allow for a response to changes in environmental temperature.

• BAD-1 protein allows binding to host lung tissue, the extracellular matrix, and cellular receptors via glycosaminoglycans.

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Blastomycosis

• Blastomyces dermatitidis

• Dimorphic fungus

• Occurs primarily in dogs and humans

• Primarily in North America, also occurs in India and Africa

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• Tolerance for ammonia

• Cases in close proximity to water

Blastomycosis

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Trends

• Increase in prevalence over 2 decades

• Increasing trend in diagnoses from February to November

• No correlation between temperatures and rainfall

Blastomycosis

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Human cases in endemic states

• Increased percentage of population over age 65

• Decreased maximum temperature

• Increased mercury and decreased copper soil content.

Blastomycosis

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Transmission• Inhalation

• Nares

• Infection establishes in the lungs initially.

• Then hematogenous or lymphatic spread.

Blastomycosis

J Immunol, 2015,194: 1796–1805

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Morphology

• 5 to 20 µm in diameter

• a thick, refractile, double-contoured cell wall

• broad-based budding

• PMNs and granulomas

Blastomycosis

botit.botany.wisc.edu/.../images/blasto.jpg

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Pathogenesis• Generally considered an extracellular pathogen

• Nearly 80% of spores were inside cells at 24 h postinfection

• Most spores were located inside of alveolar macrophages

• Real-time imaging showed rapid uptake of spores, conversion to yeast, and intracellular multiplication during in vitro coculture.

• Depletion of alveolar macrophages actually curtailed infection.

Blastomycosis

J Immunol, 2015,194: 1796–1805

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Blastomycosis in Dogs

• Young large breed dogs

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Blastomycosis• Ocular disease occurs in 30% to 43% of

dogs.

• Conjunctival nodules

• Anterior uveitis

• Chorioretinitis

• Retinal detachment

• Panophthalmitis

• Secondary glaucoma

• Optic neuritis

• Orbital cellulitis

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Blastomycosis

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VO 14:2 pp 137‐141, 2011

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In Cats• Less common than in

dogs

• Common clinical signs– respiratory

– CNS

– lymph nodes

– skin

– GI tract

– urinary systems

• Ocular signs• anterior uveitis

• rubeosis iridis

• keratic precipitates

• retinal detachment

• chorioretinitis with granulomas

Blastomycosis

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Blastomycosis in Other Species

• a dolphin, bats, horses, a polar bear, black bear, rat, non-domestic felides, lemur, alpaca and kinkajou.

• Ocular lesions have not been reported.

• Transmission to humans from bites, scratches, necropsies

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• Aspirates • draining tracts

• enlarged lymph nodes

• vitreous

• MVista™ Blastomyces antigen EIA (urine)

• Easily cultured

DiagnosisBlastomycosis

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Histopathology

• Most commonly: choroiditis and retinal detachment

• Pyogranulomatous inflammation

• Lens rupture is seen in 50% of enucleated eyes.

• Choroidal inflammation is more severe in the nontapetal choroid

• Organisms are observed primarily in the choroid

Blastomycosis

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Treatment

• Itraconazole • Commercial vs generic vs compounded

• Fluconazole

• Amphotericin B

• +/- Prednisone

Blastomycosis

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Prognosis• Varies by location and extent of

inflammation within the eye and response to therapy.

Blastomycosis

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Cryptococcosis

• C neoformans andgattii

• A saprophytic, round, yeast-like fungus, 3.5-7 µm in diameter

• Forms a 1-30 µm thick heteropolysaccharide capsule

• Always produces a capsule in tissues

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• Form 1 or 2 buds, blastoconidia, that are connected to the parent cell by a narrow isthmus

• Buds may break off when small

• Unlike other dimorphic fungi, the yeast form is always found under normal laboratory conditions and in infected tissues.

Cryptococcosis

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C neoformans

• Worldwide distribution esp temperate regions

• Infects a variety of domestic and wild animals and humans.

• Many serotypes

• Usually compromised immune systems

Cryptococcosis

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C gattii

• Isolated from the bark and leaf litter of eucalyptus trees and trees in Pacific Northwest.

• Incidence is increasing in Pacific Northwest and California

• Usually non–immunocompromised people

• Incubation has been > 8 years

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Pathogenesis• The prevalence in cats is ≥ that of dogs • Inhalation of airborne organisms• Unencapsulated in the environment • Arrival in upper respiratory tract causes

nasal granulomas. • 7-14% of animals have asymptomatic

colonization of the nasal passages. • Production of a thick capsule and

abundant release of glycoprotein into the circulation are hallmarks of virulence.

Cryptococcosis

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Cryptococcosis

• Capsule interferes with– antigen presentation

– subsequent immune response

– elimination of the organisms

• Hematogenousdissemination

• Vertical transmission

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Cryptococcosis neoformans• Establishment and spread of infection in the

host are highly dependent on immunity.

• Incidence in HIV/AIDS patients is decreasing dramatically.

• Immunosuppression does not appear to play a role in veterinary patients.

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Immune response• The complement system and phagocytic

effector cells are the major players in the non-specific host immune response.

• Phagocytosis is triggered by direct recognition of the yeast or by receptor-mediated recognition via complement or antibodies.

• Macrophages’ importance is becoming obvious.

• Melanin-like production

Cryptococcosis

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Current Biology 16, 2161–2165, November 7, 2006

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Disease in Dogs

• Young, adult dogs

• CNS signs are typically multifocal

• Cutaneous disease

• 25% have fever

Cryptococcosis

Rev. Soc. Bras. Med. Trop. vol.46 no.5 Uberaba Sept./Oct. 2013

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Disease in DogsOcular abnormalities

– Granulomatous chorioretinitis

– Retinal hemorrhage

– Papilledema

– Retinal detachment

– Optic neuritis

– Anterior uveitis

– Retrobulbar abscess with lysis

Cryptococcosis

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Disease in Cats

• Upper respiratory signs

• Hard subcutaneous nodules over the bridge of the nose

• Lymphadenomegaly

• Ulcerative or proliferative lesions in the oral cavity

• Papules or nodules

• Neurologic signs depend on location

Cryptococcosis

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Ocular Abnormalities• exudative retinal

detachment

• granulomatous chorioretinitis

• panophthalmitis

• anterior uveitis

• optic neuritis

• adnexal disease

Cryptococcosis

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Disease in Other Species

– Mallocan Cockatoo

• bilateral retinal detachments

• exophthalmia secondary to disease in the sinuses

– Ferret

• chorioretinitis

• carriers

Cryptococcosis

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Diagnosis

• Clinical signs

• Identification or culture

• Serology

– The latex cryptococcal agglutination test for antigen

– CSF serology may be more sensitive for CNS cryptococcosis

Cryptococcosis

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Histopathology• Gelatinous mass with

little inflammation• Severe granulomatous

reaction • Ocular lesions predominantly in the optic nerve,

retina and choroid

• Dissemination found more often in dogs than cats

• In cats, granulomas typically found in affected tissues

Cryptococcosis

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Histopathology• poorly stained

pleomorphic yeasts

• wide capsular halo

• “soap bubble” appearance on H&E

Cryptococcosis

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Treatment• Azole antifungals

• Amphotericin B

• Strain resistance

• Judicious use of steroids

Cryptococcosis

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Coccidioidomycosis

• Coccidioides immitis and Coccidioides posadasii

• Only found in the mycelial phase in specific locals

• Lower Sonoran Life Zone

– sandy, alkaline soil, high environmental temperatures, low annual rain fall, and low elevation

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Pathogenesis• Inhalation

• Incubation period is 1-3 weeks

• Dissemination involves a reproductive cycle of spherules to endospores to new spherules.

• Disseminated disease affects bones, eyes, heart, pericardium, testicles, brain, spinal cord and visceral organs

• Cell mediated immune response

Coccidioidomycosis

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Disease in Dogs

Systemic signs

– cough

– fever

– weight loss

– bone involvement 65%

Coccidioidomycosis

• localized peripheral lymphadenomegaly

• draining skin lesions

• CNS involvement

• cardiac

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Ocular signs • Conjunctivitis

• Keratitis

• Glaucoma /Iris bombé

• Uveitis

• Hyphema

• Cataracts

• Retinal detachment

• Granulomatous panuveitis

• Chorioretinitis

• Orbital cellulitis

• Most cases are unilateral

Coccidioidomycosis

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Disease in dogs

• Young, adult, large breed

• Outdoors

• Roaming

• Desert access

Coccidioidomycosis

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Disease in Cats

Systemic signs– fever

– inappetance

– bone lesions

– respiratory disease

– weight loss

Ocular signs– conjunctival masses

– fluid filled periorbital swellings

– anterior uveitis

– chorioretinitis

– retinal detachment

Skin lesions are most common

Coccidioidomycosis

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Coccidioidomycosis

Caroline Betbeze, DVM, MS, DACVO, Veterinary Specialty Center of Tucson

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Disease in Other SpeciesRing tailed lemur

Llama

Rhinoceros

Chimpanzee

Koala

Coccidioidomycosis

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Diagnosis

Clinicopathologically

– Hyperglobulinemia

– Hypoalbuminemia

Radiography

– Osteomyelitis

– Diffuse interstitial pattern in the lungs

Coccidioidomycosis

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DiagnosisCytologically

– unstained preparations show 10-80 µm round, double-walled structures with endospores.

Coccidioidomycosis

• IgM both appears and disappears early

• IgG persists longer.

• The CF titer is indicative of severity.

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Histopathology• More suppurative,

destructive, and more prone to progress to panophthalmitis than other mycoses

• Anterior uveal involvement may be more common with C. immitis.

Coccidioidomycosis

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Histoplasmosis• Histoplasma capsulatum is widely distributed in soil.• Most of N. and S. America• A mycelial stage is present in the soil.• Fungi convert to a budding yeast phase in lungs.

• The organisms in the yeast phase are 2-4 µm.

Am J Trop Med Hyg 20:288, 1971.

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Pathogenesis

• Grow as mold preferably on bird and bat guano at ambient temps

• Probably acquired by inhalation of microconidia

• Incubation ~ 12-16 days

• Reproduce by budding

Histoplasmosis

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Pathogenesis• Organisms are phagocytized by

mononuclear cells and undergo intracellular replication.

• Lymphatic and hematogenousdissemination then occur.

Histoplasmosis

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Disease in Dogs

• GI tract or liver.

• Pyrexia, malaise and coughing occur

Histoplasmosis

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Ocular signs in dogs• Relatively rare• Blepharitis • Conjunctivitis• Pyogranulomatous chorioretinitis• Anterior uveitis• Optic neuritis• Experimentally, ocular lesions are seen in

66% of cases.

Histoplasmosis

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Disease in Cats• Similarly susceptible hosts as dogs

• Young cats (<4 years of age)

• Most cats have disseminated disease

Histoplasmosis

• Bone lesions

• Skin lesions

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Ocular signs• conjunctivitis

• granulomatous blepharitis

• granulomatous chorioretinitis

• retinal detachment

• optic neuritis

Histoplasmosis

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13 year old FS DSH

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Treatment and diagnosis• Itraconazole

– Median duration of 5 months – Overall survival at time of discharge for cats

was 55%.

• Fluconazole has similar mortality and recrudescence rates.

• Antigenuria was detected in 17/18 cats with a histopathologic or cytopathologic diagnosis

Histoplasmosis

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Disease in other species• H. farciminosum in horses

• Snow leopards in Mexico

• Wild European hedgehog in Germany

• Bengal tiger Wisconsin

• Eclectus parrot

• Rabbit

Histoplasmosis

Brandao JVDI 2014

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Histoplasmosis

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Diagnosis• Histology (using GMS)

• Culture

• Urine antigen

• Splenic changes in cats

Histoplasmosis

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Histopathology

• varies from other mycoses

Histoplasmosis

• diffuse granulomatous and lymphocytic choroiditis with little suppuration and destruction

• usually numerous organisms

• visible as small spherical bodies within the cytoplasm of macrophages

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Aspergillus spp.

• Ubiquitous in the environment

• A. fumigatus– 3-5 µm in diameter– Repeated dichotomous branching– Uniform directional orientation– Hyphae branch at approximately a 45° angle from

the main hyphae– Septae

• Has been reported in many species. • In most species, except for the dog, is usually

confined to the pulmonary system.

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Transmission• Inhalation of microconidia• Nasal cavity is the most

frequently reported area of infection in the dog

• German Shepherds• Most human ophthalmic

infections are related to immunosuppression and spread from adjacent sinus infections.

Aspergillus spp.

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Disease in dogs• Paraparesis, paraplegia, limb

weakness

• Pyrexia

• Diskospondylitis

• Watery diarrhea

• Discharging sinus tracts

Aspergillus spp.

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Ocular signs

• Swollen irides

• Vitreal cells

• Chorioretinitis

• Retinal detachments

• Orbital aspergillosis 2° to invasion from the sinus

• Ocular signs often occur several mos before generalized illness

Aspergillus spp.

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Vet Ophthalmol. 2018 Mar;21(2):182-187

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Disease in cats• A. fumigatus, Neosartorya spp., A. udagawae

and A. viridinutans• Sino-orbital aspergillosus

– history of sneezing and nasal discharge – exophthalmia or presence of a mass or ulcer in the

pterygopalatine fossa. • Lesions are characterized by necrosis, well-

vascularized granulomatous inflammation and PAS + fungal hyphae.

• Variable resistance to antifungals• Very poor prognosis even with medical and

surgical therapy.

Aspergillus spp.

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V.R. Barrs et al. / The Veterinary Journal 191 (2012) 58–64

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Vet Clin North Am Small Anim Pract. 2014 Jan;44(1):51-73. doi: 10.1016/j.cvsm.2013.08.001. Epub 2013 Sep 17.

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Disease in other species• Alpaca

– Blind, retinal detachments and hemorrhages

– Optic neuritis

– Necropsy revealed pulmonary and renal lesions

• Birds

o Air sac disease

o One week after an acute episode in a turkey flock, cloudiness of the eye with severe conjunctivitis was associated with paralysis in broiler breeders.

o Blepharitis, keratitis and keratoconjunctivitis (turbid discharge, cloudy cornea, and cheesy yellow exudates within the conjunctival sac) in numerous species.

Aspergillus spp.

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Pathology

Gross findings on necropsy– white nodular lesions in the

myocardium, skeletal muscles, diaphragm, kidneys, liver, and spleen

Aspergillus spp.

• Ocular findings may include foci of lymphocytes, macrophages, fibrin and aggregates of septate hyphae adjacent to the lens capsule. In addition, the hyphae may penetrate the lens capsule.

• Pyogranulomatous

• Organisms can be seen in the vitreous, retina and choroid.

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PathologyAspergillus spp.

• The organisms are PAS positive, linear with 5-15 segments, occasional focal bulges, club formation and branching.

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Diagnosis• +/- humoral antibodies

• associated with debilitation or immunologic suppression

• identification and culture

• vitreocentesis

• galactomannan

Aspergillus spp.

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Candida albicans

• Dimorphic fungus

• May cause either localized or generalized disease

Candida spp.

• Local proliferation in wounds or mucosal surfaces is the first step of infection

• Usually in immunosuppressed or debilitated animals

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Protothecosis

• Achlorophyllous algae

• P. zopfii and P. wickerhamii are pathogenic

• P. zopfii is most commonly isolated from dogs

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• Cells are spherical to oval• Range from 1-13 µm in

diameter• Hyaline cell wall is ~ 0.5

µm thick• The cytoplasm is granular

and basophilic• The nucleus is small and

centrally located

Protothecosis

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• Reproduction: endosporulation with cleavage of the parent cell resulting in the release of 2-20 or more endospores

• Empty hyaline shells may be visible among intact cells within lesions.

Protothecosis

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Protothecosis

• environmental contaminant

• minimally pathogenic

• does not spread between hosts

• Europe, Asia, Oceania, and N. America

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Pathogenesis

• Immunosuppression, especially if cell-mediated immunity, favors establishment of infection.

• Another mechanism is the inablility of the host’s PMNs to specifically destroy Protothecaafter phagocytosis.

• Biofilms may assist in pathogenesis

• In humans, infection is usually cutaneous, subcutaneous, or bursal.

• The colon is the probable site of primary infection and entry for disseminated disease in dogs.

Protothecosis

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Fluorescent microscopy image of P. wickerhamii(“biofilm-negative”) on the bottom of the well after 3-day culture (scale bar = 50 µm).

Three-dimensional reconstructed images of biofilms obtained with confocal laser scanning microscope (b) fluorescent microscopy images of biofilm at various magnifications (scale bar = 50 μm); Lett Appl Microbiol. 2015 Dec;61(6):511-7. doi:

10.1111/lam.12497. Epub 2015 Nov 2.

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Disease in Dogs

• hemorrhagic diarrhea or colitis is primary sign

• blindness may be initial complaint

• predisposition for the Collie breed and females

• lymphatic, nervous, renal and pulmonary systems are commonly involved

• very poor prognosis

Protothecosis

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Clinical signs

• Weight loss• Debility• Renal failure• Intermittent bloody diarrhea• Chronic ulcerative skin lesions• CNS

– severe depression– deafness– ataxia– circling– paresis

www.vet.uga.edu/vpp/clerk/hall/fig1.jpg

Protothecosis

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Clinical signs

• anterior uveitis

• retinal detachment

• chorioretinitis

• blindness

• 2º glaucoma

Protothecosis

210137

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Diagnosis• Wright’s stain can be done

on specimens obtained by vitreocentesis, CSF tap, or colonic scrapings.

• GMS or PAS

• extracellular, round to oval

• thin, unstained walls

• may contain endospores

• readily grown in culture

Protothecosis

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Histopathology

• spherical to oval from 2-20 µm

• a refractile cell wall that stains with PAS or GMS

• multiple daughter cells form enclosed within a single cell wall

Protothecosis

• lesions identical to those of blastomycosis

• the algae are free or within macrophages

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• 18 month old domestic short hair cat

• Completely indoors

• History of trauma

• RDVM saw hyphema.

• Was treated for anterior uveitis, responded and then returned 4 days later.

Esmeralda

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• Complete blood count - WNL

• Chemistry panel - WNL

• FIV, FELV, toxoplasmosis - Negative

RDVM

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• Physical exam – WNL

• Minimal hyphema

• Continued topical therapy but discontinued oral prednisolone

Two weeks after reported trauma

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• Physical exam – WNL

One week after initial visit to UT

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• Aqueocentesis

• Thoracic radiographs

• Crypto antigen, blasto & histo AGID

• FIP

One week after initial visit to UT

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• Aqueocentesis– Suppurative inflammation

– Non degenerative

– Not indicative of sepsis

– No organisms seen

– Culture

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• Thick walled cavitary lung mass 1.5 cm

• Mild diffuse interstitial pattern

• Differentials: granuloma, abscess, parasite

• Fecal exam– Negative for paragomimus

Thoracic radiographs

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2 weeks later…

http://thunderhouse4-yuri.blogspot.com/2012/12/blastomyces-dermatitidis.html

http://www.pf.chiba-u.ac.jp/gallery/fungi/b/Blastomyces_dermatitidis_colony.htm

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• Itraconazole

• Blasto titer positive at 6 weeks

• Lungs normal on radiographs at 6 weeks

Treatment

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• 10-year-old female spayed Rottweiler

• Three week history of intermittent hyphema and ocular swelling

• Treated with topical prednisone, oral prednisone, amoxicillin, and doxycycline

Shadow

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• Physical exam: WNL

• Ocular exam findings– OD normal

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• Chemistries– Hypercalcemia

– Hyperphosphatemia

– Elevated ALP, AST, ALT

Blood work

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• WBC 3.4 L xl0E3/uL

• REC 6.11 xl0E3/uL

• TPP 7.4 g/dL

• ABS 1.9 x10E3/uL

• ABS BAN .6 xl0E3/uL

• ABS LYM .047 x10E3/uL

• ABS MON .204 xl0E3/uL

• ABS EOS .034 x10E3/uL

• 5.1-14

• 5.6-8.7

• 5.7-7.9

• 2.65-9.8

• 0-.3

• 1.1-4.6

• .165-.85

• 0-.85

CBC

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• Physical exam on WNL

• Ophthalmic findings: no change

• Creatinine kinase: 286 (40 –I59)

• Euthanasia

One week later

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• Gross abnormalities– Buphthalmia

– White to tan streaking on myocardium

– Enlarged sternal lymph nodes

Necropsy

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• Coalescing clusters of algal organisms in myocardium

• Basophilic capsules up to 50 µm in length

• Up to 4 endospores

• Many lymphocytes and plasma cells

• Same organisms in the eye and sternal lymph nodes

Microscopic findings

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• 13 year old FS DSH

• Ocular and PE findings WNL OU except for:

Hot Shot

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• Fine needle aspirates of the skin lesions, conjunctival biopsies, and bloodwork.

• CBC and chemistry panel were considered within normal limits.

http://www.eclinpath.com/atlas/cytology-2/infectious-agents-cytology/

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• Thoracic radiographs showed a mild bronchiolar pattern more consistent with an asthma-type pattern than a fungal disease.

• Urinalysis was WNL.• FeLV/FIV status was negative.• Cryptococcal antigen enzyme immunoassay

was positive. • Hot Shot was started on Itraconazole (30 mg

PO BID) and topical Miconazole cream OS QID.

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• Itraconazole and topical miconazoletreatment resulted a decrease in the cryptococcal antigen titers, but they did not return to zero, and the adnexal lesions never fully resolved.

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• The patient was switched from oral itraconazole to oral Terbinafine, and at the next recheck exam the lesions had worsened.

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• HISTOPATHOLOGICAL DESCRIPTION:• Slide 1: Eyelid (OS): The dermis is expanded and replaced by infiltrates of

numerous macrophages, lesser neutrophils, plasma cells, and lymphocytes that surround numerous clusters or sheets of yeast organisms.

• Yeasts have a round, lightly basophilic nucleus (6-8um) surrounded by a thick clear capsule (5-10um).

• There is mild focal ulceration of the epithelium.• Slide 2: Nictitans (OS): The submucosa is expanded and replaced by

infiltrates of numerous macrophages, lesser• neutrophils, plasma cells, and lymphocytes that surround sheets of myriad

yeast organisms. Yeasts have a round, lightly basophilic nucleus (6-Sum) surrounded by a thick clear capsule (5-10um). There is multifocal attenuation of the conjunctival epithelium.

• MORPHOLOGIC DIAGNOSIS:• Slide 1: Eyelid (OS): Severe diffuse pyogranulomatous blepharitis with

intralesional yeast organisms (Cryptococcus)• Slide 2: Nictitans (OS): Severe diffuse pyogranulomatous conjunctivitis with

intralesional yeast organisms (Cryptococcus)

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• Culture

• Suseptible: Amphotericin B, Fluconazole, Itraconazole, Natamycin, Miconazole, Terbinafine, Clotrimazole

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• The patient was switched to oral fluconazole

• Last recheck exam the cat was in remission

• Cryptococcus antigen titers were negative.

• Recommended that the owner finish current prescription of Fluconazole (30 more days).

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