Fungal diseases Flashcards
What dog breed has a higher frequency of Malassezia pachydermatis in the nose, mouth, vulva and axilla compared to other species?
Basset hounds
What type of immunity is required to clear Coccidioides infection?
cell-mediated immunity (T-lymphocytes)
What is the most common dermatophyte pathogen in people? Clinical presentation?
Trichophyton rubrum; onchomycoses (toe nail fungus)
What are the types of Lagenidiosis and associated clinical signs?
cutaneous - ulcerative, nodular, mass-like cutaneous lesions with draining tracts; pelvic limb edema; local, thoracic, or abdominal lymphadenopathy; rupture of infected great vessels in the abdomen may result in hemoabdomen
What is the mechanism of action of terbinafine?
inhibits fungal sterol biosynthesis - reversibly inhibits the membrane-bound enzyme squalene epoxidase in a concentration-dependent manner –> prevents conversion of lanosterol to cholesterol and/or ergosterol
Mode of transmission of Cryptococcus?
inhalation of basidiospores from environment
T/F: Oomycosis is considered zoonotic.
False - infective stage is the zoospore – Does not form in tissue, only standing water
T/F: It is difficult to culture organsisms that cause Hyalohyphomycosis.
False - readily isolated on routine culture; further identification based on colony and conidial morphology and PCR and sequencing of ribosomal RNA genes
Major clinical signs of histoplasmosis
cough, tachypnea, organomegaly, gastrointestinal signs, pallor
Mechanism of action of lufenuron?
benzoylphenylurea drug that disrupts chitin synthesis – chitin is a critical component of the exoskeleton of arthropods (& outer cell wall of fungi)
T/F: histoplasma capsulatum can be seen on cytology from affected tissues.
True - usually intracellular within mononuclear phagocytes
What is the optimal therapy for cats with cryptococcosis with CNS involvement?
amphotericin B and 5-flucytosine
Characteristics of yeast form of Sporothrix spp.
cell wall contains glucans and galactose-containing polysaccharides and melanin
What the two types of Pythiosis and associated clinical signs?
cutaneous - ulcerative, nodular, mass-like cutaneous lesions with draining tracts; gastrointestinal form - weight loss, anorexia, vomiting, diarrhea, hematochezia
What is a unique finding on dermoscopy in cats with dermatophytosis?
opaque, slightly curved or broken hairs with a homogenous thickness (“comma hairs”)
Malassezia overgrowth is favored by skin diseases with altered stratum corneum barrier function through aberrant cornification. What diseases are implicated in this category?
zinc-responsive dermatosis, hepatocutaneous syndrome, endocrinopathies (hypothyroidism and hyperadrenocorticism), atopic dermatitis, congenital ichthyosis, thymoma-associated dermatosis, paraneoplastic alopecia, feline facial acne
What is the best diagnostic test for Coccidioidomycosis?
serum antibody
How do keratinocytes recognize Malassezia antigens?
through Toll-like receptors
What is the most common systemic mycosis of cats?
Cryptococcosis
Most commonly isolated species of Candida to cause disease in dogs and cats
Candida albicans
Subcutaneous dermatophytic infections have been most commonly reported in what breed(s)?
Persian cats and Yorkshire terriers
Geographic distribution of Candida spp.
worldwide – normal inhabitants of the gastrointestinal, urogenital and cutaneous flora; can slo be isolated from soil, inanimate objects, and hospital environments
What does the Blastomyces antigen test detect?
cell wall galactomannan antigen
T/F: A positive fungal culture with Candida is diagnostic as the cause of disease.
False - commensals of mucosa, so positive cultures should be interpreted in light of clinical signs
Environmental conditions that favor Sporothrix species
humid condition (92-100% humidity), temperatures between 25-30 degrees C, prefer moist soil that is rich in decaying vegetation
T/F: Cats may still have hairs that glow with a Wood’s lamp after clinical cure of dermatophytosis
True - the pteridine pigment remains detectable on the tips of the hairs as they grow out, even though the infection may be eliminated (will remain after hairs are culture negative)
Histopathologic features of Coccidioidomycosis
neutrophils, macrophages, fibrosis, with occasional endosporulating or non-endosporulating spherules; multinucleated giant cells can contain spherules; often no spherules are found**
There is moderate evidence for treatment of Malassezia dermatitis in dogs for what treatment(s)?
3% chlorhexidine shampoo, ketoconazole 5-10 mg/kg SID-BID, itraconazole 5 mg/kg SID or 2 consecutive days/week
How does Coccidioides grow in the environment? In tissue?
exist in the environment as mycelium – haploid, multinucleated, barrel-shaped arthroconidia (arthrospores) that alternate with smaller, thin-walled, nonviable cells; in tissue - exist as spherules
What is seen on histopathology with a fungal kerion?
granuloma or pyogranuloma formation, often with fragments of hair shafts containing fungal spores
What is the preferred medium for the isolation and quantification of Malassezia pachydermatis?
Modified Dixon’s agar
Cytological characteristics of Coccidioides
granulomatous to pyogranulomatous inflammation with spherules – round, deeply basophilic, double-walled, slightly crinkled structures; spherules are generally low in numbers; endospores may be identified where spherules have ruptured and can be found within phagocytes - endospores are 2-5 um in diameter, surrounded by a thin, nonstaining halo
Opportunistic fungal infection caused by pigmented hyphal or yeast forms
phaeohyphomycosis
T/F: Animals affected with Pythiosis are usually immunocompromised.
False - usually immunocompetent
Eumycotic mycetoma histopathological characteristics
nodular masses of granulomatous inflammation with fibrosis and exudate containing embedded granules of masses of septate, branching fungal hyphae (0.2-6um in diameter), bordered by hyaline eosinophilic Splendore-Hoeppli material arranged radially or smoothly contoured
T/F: The Aspergillus glactomannan antigen ELISA assay is positive in some animals with hyalohyphomycosis.
True - with paecilomycosis (Paecilomyces) – due to antigen cross-reactivity
T/F: Blastomyces can be seen on cytologic specimens from affected tissues.
True (usually) - Blastomyces dermatitidis yeasts
Clinical signs of iodine toxicity
ocular and nasal discharge, dry scaly coat, vomiting, depression and collapse
T/F: Lime sulfur is sporicidal against dermatophyte spores
TRUE
Under what conditions does Histoplasma capsulatum grow in the environment?
moist, humid, nitrogen-rich soil
What is the most common lipid-dependent Malassezia organism isolated from the ear canals of cats?
Malassezia nana
T/F: Cryptococcus is zoonotic.
False - pets may act as a sentinel species for humans
What are possible reasons for a false positive Dermatophyte PCR test?
fomite carriage or nonviable fungal organisms from a successfully treated infection
Size of pythium insidiosum on histopathology
wide (2-7 um, 4 um mean), have nonparallel walls, are infrequently septate and occasionally branch at right angles
What breed of dog may be predisposed to phaeohyphomycosis and hyalohyphomycosis?
german shepherd dogs
T/F: Malassezia yeasts are the most abundant fungal organisms on healthy canine skin.
False - filamentous contaminants from the environment (Alternaria, Cladosporium, Epicoccum) were predominant
Describe the pathogenesis of histoplasmosis
microconidia are inhaled from environment –> microconidia transition to unicellular yeast, which replicates by budding –> fungus binds to CD11-CD18 integrins on alveolar macrophages and is phagocytized –> replicates within macrophages –> destroys them and recruits more inflammatory cells
Mechanism of action of griseofulvin?
inhibits nucleic acid synthesis and cell mitosis by arresting division in metaphase; interferes with function of spindle microtubules; causes morphological changes in fungal cells and may antagonize chitin synthesis in fungal cell wall
Most common serum biochemical abnormality with histoplasmosis
mild to severe hypoalbuminemia
In which species is disseminated cryptococcosis more common: dogs or cats?
dogs
Mechanism of action of ketoconazole?
similar to itraconazole - inhibits lanosterol 14-alpha demethylase –> leads to ergosterol depletion and accumulation of aberrant and toxic sterols in the cell membrane
What stain highlights melanin in the cell wall of organisms implicated in phaeohyphomycosis?
Fontana-Masson stain
Cytological characteristics of histoplasma capsulatum
yeasts are 2-4 um in diameter, oval, have a basophilic center and are surrounded by a clear halo (similar in size to Sporothrix spp but different in shampe)
Which fungal disease can manifest as cutaneous lesions, lymphocutaneous lesions, or multifocal lesions?
Sporotrichosis
Appearance of Blastomyces dermatitidis on cytology
yeasts that are 8-15 um in diameter, have a thick, refractile cell wall, and exhibit broad based budding (daughter cells are nearly as large as the parent cell when they detach)
What species of fungi implicated in hyalohyphomycosis is resistant to Amphotericin B?
Paecilomyces spp. - are susceptible to azoles
What is the immunologically active portion of the cell wall of dermatophytes?
glycopeptide
T/F: Dermatophytes can be part of the normal skin microbiome of dogs or cats.
FALSE
What type of immunity is required to clear blastomyces infection?
natural immunity - neutrophils and alveolar macrophages can clear conidia; once in yeast form - control of infection also depends on T lymphocytes -> stimulate macrophages to kill the yeasts (cell-mediated immunity); humoral immunity is not essential for resolution of infection
T/F: Dermatophytosis acquired from environment alone is rare.
TRUE
Opportunistic fungal infection caused by non-pigmented hyphal forms
hyalohyphomycosis
Which antifungal drug has the poorest antifungal activity against dermatophytes: fluconazole, griseofulvin, itraconazole, ketoconazole, or terbinafine?
fluconazole
Which antifungal drug has the lowest MIC for dermatophytes: fluconazole, griseofulvin, itraconazole, ketoconazole, or terbinafine?
terbinafine
T/F: Pythium insidiosum hyphae are visible on routine H&E sections.
False - are identified as clear spaces surrounded by a narrow band of eosinophilic material; Need GMS stain to visualize
T/F: Serology alone should not be used as a basis for diagnosis of lagenidiosis.
True - serologic testing can cross-react with pythium and other fungal or nonfungal infections
Opportunistic fungal infection characterized by fibrosing granuloma with black or white tissue grains (pigmented or nonpigmented fungi)
eumycotic mycetoma
Cytological characteristics of Phaeohyphomycosis
Dark-walled, irregularly septate hyphae or yeast-like cells, solitary or in small groups or chains; pyogranulomatous inflammation
Cytological characteristics of Rhinosporidiosis
pyogranulomatous to suppurative inflammation, numerous immature to mature R. seeberi endospores; endospores are round to oval (10-15 um) and have a thick cell wall
What treatment has shown promise in the prevention of Malassezia otitis externa associated with allergic skin disease?
twice weekly topical hydrocortisone aceponate application
What genera of fungi have been associated with phaeohyphomycosis?
Alternaria, Bipolaris, Cladophialophora, Curvularia, Exophiala, Fonsecaea, Moniliella, Phialophora, Ramichloridium, Ulocladium, Scolecobasidium
What is the possible mechanism of Malassezia’s resistance to azoles?
reduced affinity due to alterations in drug target enzyme by increased expression of the target gene (ERG11) encoding this enzyme or by increased efflux by overexpression of genes encoding membrane transport proteins of the ABC transporter (CDR1/CDR2) or the major facilitator (MDR1) superfamilies
How long after exposure to dermatophytes do clinical lesions appear?
1-3 weeks
Zoophilic dermatophytes that affect the pig?
Microsporum nanum
T/F: Organisms are usually scarce with aspergillosis.
False - plentiful and characterized by broad (3-6 um) septate, dischotomously branched hyphae
What testing for Lagenidiosis provides a defnitive diagnosis and allows differentiation beetween the two pathogenic species?
culture followed by PCR and rRNA gene sequencing
Aspergillus spp. are intrinsically resistant to what antifungal drug?
fluconazole
T/F: Absorption of fluconazole is enhanced by giving it with food.
False - it is water soluble
What is the primary reservoir of histoplasma capsulatum?
intestinal tracts and guano of bats; can also be found in high concentrations in decaying avian guano
Microscopic appearance of macroconidia of Microsporum canis
Spindle or canoe-shaped, >= 6 cells with thick walls with outer spines on surface and terminal knob; Young colonies may have <6 cells
T/F: Both immediate and delayed-type hypersensitivities have been documented against Malassezia antigens.
True - delayed reactions reported in Basset hounds
T/F: Cats are more susceptible to Sporotrichosis than dogs.
TRUE
Major clinical signs of Sporotrichosis
cutaneous nodules or draining skin lesions, lymphadenopathy
What species of dermatophyte causes prominent scaling but minimal alopecia because it infects surface keratin but does not invade hair?
Microsporum persicolor
Adverse effects documented with lime sulfur treatment?
drying of the footpads, loss of hair on the ears, drying of the hair coat, yellow discoloration of white cats
Phaeohyphomycosis histopathological characteristics
foci of granulomatous, pyogranulomatous or lymphocyte-rich granulomatous dermatitis and panniculitis containing pigmented fungal organsism in small aggregates throughout the lesion. Hyphae are septate, 2-6um wide, and branched or unbranched. Fungal elements are usually intracellular within epithelioid macrophaes and multinucleated giant cells
T/F: Malassezia has a high risk of zoonosis.
False - overall quite low unless severely immunocompromised
____ are cylindrical, thread-like strctures of fungi that grow at the tips and can either branch or fork.
Hyphae
What is the treatment of choice for eumycotic mycetoma?
aggressive surgical excision of infected tissue; adjunctve medical therapy following surgery with itraconazole, voriconazole, posaconazole
Microscopic appearance of macroconidia of Microsporum gypseum
rowboat shaped, each containing <6 cell with thin walls
T/F: Cats without a breed predilection for Malassezia overgrowth or an underlying hypersensitivity disorder most often have visceral neoplasia or other serious internal disease.
TRUE
What similarities are possible on histopathology between pemphigus and dermatophytosis?
acantholytic intraepidermal pustules and interface dermatitis
What causes the color change in Dermatophyte Test Medium when dermatophytes are present?
(yellow to red) - result of pH change triggered by fungal growth
Treatment of choice for feline cryptococcosis
fluconazole - good penetration to brain, eye, and urinary tract; other treatment options include itraconazole, ketoconazole, amphotericin B
Best treatment for blastomycosis in dogs
itraconazole, also amphotericin B is effective
What is the infective form of dermatophytes?
arthrospore - formed by fragmentation of fungal hyphae into very small infective spores
______ are responsible for asexual reproduction of fungi and are nonmotile spores generated by mitosis and can come in many shapes and sizes.
Conidia
Black-grain eumycotic mycetomas are most often caused by what fungi?
Curvularia spp
T/F: Antibiotic use is an independent risk factor for development of Malassezia dermatitis.
False - never been reported in any published studies
T/F: Coccidioides is zoonotic.
False - pets may act as a sentinel species for humans
T/F: Gentamicin has antifungal activity against Malassezia pachydermatis.
True - so does netilmicin, tobramycin, and framycetin (in vitro susceptibility)
What is the infective form of Rhinosporidium seeberi?
small round spore (7-15 um) that develops in tissues into large (100-450 um) spherical bodies known as sporangia
T/F: Serology alone is diagnostic for pythiosis.
True - highly sensitive and specific ELISA for anti-Pythium insidiosum antibodies
What is the purpose of topical therapy in treatment of dermatophytosis?
to decrease the infectious, contagious and zoonotic risks by disinfecting the hair coat and minimizing contamination of the environment
For what fungal disease has localized hyperthermia been used with some success? Why?
Sporotrichosis - Sporothrix spp. are temperature sensitive
What do dermatophytes produce that digest keratin into usable peptides and amino acids?
endoproteases (subtilisins and fungalysins) and exoproteases
What fungal organisms multiply by broad-based budding?
Malassezia, Blastomyces
What is the clinical presentation of a fungal kerion?
single or multiple erythematous, alopecic, dome-shaped, exudative nodules
Clinical signs of phaeohyphomycosis
cutaneous nodules, nasal mass - may appear grossly pigmented (often confused with melanomas)
Histopathologic features of Candidiasis
spongiotic neutrophilic pustular inflammation, parakeratosis, ulceration with exudation - Candida present in superficial exudates; Yeasts, pseudohyphae, and hyphae are best visualized with PAS or GMS stains: yeasts are more numerous on the surface of the lesions, whereas hyphae and pseudohyphae extend into the epidermis
Most common species of Cryptococcus to infect dogs?
Cryptococcus neoformans
T/F: When a hair enters telogen, fungal growth of dermatophytes stops.
True - infection continues with keratin production, when a hair enters telogen, keratin production stops and fungal growth ceases
What cytokine is important in clinical cure of dermatophytosis and protection against re-infection?
interferon-gamma
Species of aspergillus associated with sinonasal aspergillosis
Aspergillus fumigatus
Most common geophilic dermatophyte to infect animals and humans after contact with contaminated soil?
Microsporum gypseum complex
Characteristics of Candida spp. organisms
reproduce by budding; yeasts are small (3-6 um) and ovoid (blastospores) –> budding results in formation of new yeast cells, pseudohyphae (chains of elongated yeast cells), and true septate hyphae
Does serology for Pythium insidiosum detect antigen or antibody?
Antibody
Describe the pathogenesis of Sporotrichosis
cutaneous inoculation –> converts to yeast form
White-grain eumycotic mycetomas are most often caused by what fungi?
Pseudallescheria boydii or Acremonium spp
Which is more sensitive and specific for diagnosis of Histoplasmosis: Antibody or Antigen ELISA?
Antigen; false positives can occur with the antibody test in endemic areas (result of exposure or previous recovery)
Which is more sensitive and specific for diagnosis of Aspergillosis: Antibody or Antigen ELISA?
Antibody - negative result does not rule out disease, but a positive result is strongly supportive (for Sinonasal aspergillosis); For disseminated aspergillosis - an Aspergillus galactomannan antigen ELISA assay has high sensitivity
What body sites are most commonly colonized by Malassezia pachydermatis in dogs?
perioral/lip region (81% of dogs), interdigital skin (60-70%), perianal skin/anal mucosa (55%)
What organisms associated with Zygomycosis cause cutaneous lesions similar to Pythiosis and Lagenidiosis?
Basidiobolus and Conidiobolus spp.
T/F: Animals with Lagenidiosis often have nonresectable disease.
True - located in thorax, abdomen, or regional lymph nodes
Histopathologic features of Lagenidiosis
pyogranulomatous and eosinophilic inflammation associated with broad, irregularly branching, infrequently spetate hyphae with nonparallel walls; right-angle branching is occasionally observed, scant to thin eosinophilic sleeve may be noted around the hyphae
Zoophilic dermatophytes that affect voles? Rodents/Rabbits/Hedgehogs?
Voles: Microsporum persicolor; Rodents/rabbits/hedgehogs: Trichophyton mentagrophytes complex
What antifungal drug is contraindicated to use in cats that are FIV positive?
griseofulvin - can cause bone marrow suppression
T/F: Cats with FeLV or FIV have decreased fungal diveristy on their skin.
False - have INCREASED fungal diversity
What is the clinical presentation of a pseudomycetoma or mycetoma?
nodules that fistulate, ulcerate, and drain serous to puruluent debris with tissue grains
What species of Cryptococcus cause the majority of disease in dogs, cats, and humans?
Cryptococcus neoformans and Cryptococcus gatii
Describe the environmental conditions that favor development of coccidioidomycosis
in endemic areas, often follows a cycle of moist conditions (required for growth of the organism in the soil), a dry period, then soil disruption by heavy rainfall, earthquakes, dust storms, prolonged droughts, or construction
What causes hairs to have the characteristic green fluorescence with a Wood’s lamp when infected with M. canis?
water-soluble chemical metabolite (pteridine) located within the cortex or medulla of the hair
T/F: Fungal culture is the gold standard for diagnosis of dermatophytosis.
False - no one test was identified as a gold standard - diagnosed by complementary diagnostic tests, including Wood’s lamp and trichogram, dermatophyte culture, biopsy with fungal stains for atypica infections/nodular infections
What is the mode of action of nystatin?
altered cell membrane permeability mediated by preferential binding to ergosterol
What is a zoophilic dermatophyte species?
adapted to living on animal hosts
Histopathlogic features of Pythiosis
eosinophilic pyogranulomatous inflammation with multiple foci of necrosis, surrounded by neutrophils, eosinophils, and macrophages – organisms are typically found within areas of necrosis at the center of granulomas - on H&E are identified as clear spaces surrounded by a narrow band of eosinophilic material
How does Sporothrix grow in the environment? In tissue?
hyphae in environmetal tissues; grow as yeast in tissue
Strong evidence for treatment of Malassezia dermatitis in dogs exist for only what treatment?
2% miconazole/2% chlorhexidine shampoo twice weekly
What is the primary site of infection with cryptococcosis in dogs and cats?
nasal cavity (pulmonary parenchymal involvement is rare)
Mechanism of action of itraconazole
inhibits fungal cytochrome p450 enzyme 14-alpha demethhylase to prevent conversion of lanosterol to ergosterol (ergosterol maintains cell wall integrity and activity)
Mode of transmission of Histoplasma
inhalation of microconidia from environment
How does Blastomyces grow in environment? In tissue?
Environment: mycelial form - hyphae in the soil produce conidia; tissue: thick-walled budding yeast
T/F: Malassezia pachydermatis is more susceptible to nystatin than ketoconazole.
False - inferior to ketoconazole and terbinafine
What is the treatment of choice for pythiosis?
aggressive surgical resection of all infected tissues with wide margins followed by treatment with itraconazole and terbinafine
Major differences between feline and canine sporotrichosis?
feline - usually MANY organisms present; canine - FEW organisms present; therefore FELINE SPOROTRICHOSIS is more of a zoonotic concern
What systemic treatment options are available for dermatophytosis? Which are the most effective?
Itraconazole, terbinafine > Griseofulvin > Ketoconazole or Fluconazole
What are the two polyene cyclic macrolides used in clinical practice?
amphotericin B and nystatin
T/F: Most dogs and cats with cryptococcosis have underlying immunosuppressive illness.
FALSE
Clinical signs of hyalohyphomycosis
cutaneous lesions, nasal mucosal involvement, keratitis, osteomyelitis, pneumonia, disseminated disease with involvement of lymph nodes, kidneys, liver, spleen, bone, intervertebral discs, and/or CNS
Causative organism of Rhinosporidiosis
Rhindosporidium seeberi; aquatic protistan parasite - impossible to culture
What is the treatment of choice for phaeohyphomycosis?
aggressive surgical resection followed by medical therapy with itraconazole or posaconazole for 3-6 months
Describe the pathogenesis of coccidioidomycosis
arthroconidia are inhaled & phagocytosed by alveolar macrophages –> enlarge into a spherule (8-100 um in diameter) –> endospores develop within the spherule –> released when the spherule ruptures –> attracts neutrophils
Histopathologic features of Zygomycosis
Histologic hallmark is the presence of a wide (2.5 to 25 um) eosinophilic sleeve that surrounds the hyphae**; hyphae are broad, thin-walled and occasionally septate; hyphal diameter is larger for Basidiobolus spp. and Conidiobolus spp. than for Pythium insidiosum
T/F: Tissue specimens should be ground or macerated prior to culture when Zygomycosis is suspected.
False - this may destroy the organism
What antifungal drugs are recommended to treat histoplasmosis?
ketoconazole, itraconazole, fluconazole, amphotericin B
What has been reported to account for poor bioavailability of compounded itraconazole?
absence of cyclodextrin - carrier compound shown to improve gastrointestinal absorption
What species of Zygomycosis typically infects mucocutaneous sites and causes sinusitis?
Conidiobolus
What immune response is important for clearance of cryptococcosis?
cell-mediated immunity: production of Th1 type cytokines such as IL-2, TNF-alpha, IFN-gamma and a granulomatous inflammatory response
Major clinical signs of Blastomycosis
fever, anorexia, cough, tachypnea, nodular or ulcerative cutaneous lesions, ocular lesions (uveitis, chorioretinitis, panophthalmitis), lameness, neurological signs
What Malassezia species have been isolated from cats?
Malassezia pachydermatis, Malassezia sympodialis, Malassezia globosa, Malassezia furfur, Malassezia nana, and Malassezia slooffiae
Why is it not recommended to treat dogs with 5-flucytosine?
dogs can develop toxic epidermal necrolysis within 10-14 days of initiating therapy
Cytological characteristics of Hyalohyphomycosis
Fungi are nonpigmented, frequently septate, branching hyphae that are often pleomorphic with pyogranluomatous inflammation; Phialosimplex may cause yeast-like forms in tissue
Zoophilic dermatophytes that affect the horse?
Microsporum equinum, Trichophyton equinum
What species of systemic fungal diseases can be cultured in routine laboratory settings without risk to the laboratory staff? Why?
Cryptococcus - grows as a yeast on routine fungal media
T/F: Cryptococcus organisms can survive and replicate within phagocytic cells
TRUE
T/F: Candidiasis is most common in immunocompromised hosts.
True - diabetes mellitus, immunosuppressive drugs, prolonged borad-spectrum antibacterial drugs have been associated
What is the active ingredient/compound in Lime Sulfur that is fungicidal?
hydrogen sulphide
Which is more sensitive and specific for diagnosis of Coccidioidomycosis: Antibody or Antigen ELISA?
Antibodies (IgM or IgG)
T/F: Sporotrichosis is zoonotic.
True - direct transmission can follow contact between infected cats and humans (esp cat bites or scratches)
What antifungal drugs are recommended to treat Coccidioidomycosis?
fluconazole, itraconazole, ketoconazole, amphotericin B
What is resposible for the pigment in the fungal cell wall present in phaeohyphomycosis?
melanin
T/F: You cannot distinguish between pythiosis, lagenidiosis, or zygomycosis based on cytology alone.
True - all have a similar appearance: pyogranulomatous and eosinophilic inflammation with hyphae - broad, rarely septate with tapered, rounded ends
Microscopic appearance of macroconidia of Trichophyton spp.
cigar shaped and rare; Microconidia are common and often spinal hyphae
Diagnostics available for Pythium
Antibody serology, cytology, culture, histopathology, PCR assays
Which hyphae are larger: Pythium insidiosum or Lagenidium spp.?
Lagenidium spp.
Mode of transmission of Aspergillosis
inhalation of conidia from environment
What are the two species of Coccidioides that cause disease?
Coccidioides immitis and Coccidioides posadasii
T/F: Lagenidium spp. hyphae are visible on routine H&E sections.
TRUE
T/F: Itraconazole concentrations are higher in tissue than plasma.
True - especially in adipose tissue and sebaceous glands (it is highly lipophilic!)
What are the unique components of Dermatophyte Test Medium?
has antibiotics to suppress bacterial and contaminant fungal overgrowth and has a color indicator to aid in recognition of dermatophyte species
Major clinical signs of Rhinosporidiosis
pedunculated or sessile masses within the nasal cavity (usually in the rostral third), sneezing, epistaxis
Virulence factors of Cryptococcus
polysaccharide capsule; laccase (makes melanin), enzymes such as phospholipase, urease, and superoxide dismutase
What species of Malassezia is primarily associated with the feline claw fold?
Malassezia slooffiae
What treatment monitoring is recommended for daily oral terbinafine in dogs?
hepatic enzymes - due to reports of reversible, mild-moderate elevations of ALT and ALP
What type of immunity is required to clear sporotrichosis?
cell-mediated immunity (T-lymphocytes)
Adverse events reported with itraconazole?
anorexia; elevations in liver enzymes; cutaneous vasculitis (doses greater than 10 mg/kg) - dogs only
Cytological characteristics of Cryptococcus
pyogranulomatous to granulomatous inflammation with numerous pleomorphic (round to elliptical, 2-20 um in diameter) yeast-like organisms; narrow-based budding, surrounded by a mucinous capsule of variable thickenss, which forms a clear or refractile halo
T/F: Lagenidiosis has only been reported in dogs.
True - Pythiosis has been reported in horses, cattle, dogs and cats
Histopathologic features of Cryptococcosis
can appear as cystic degenration or vauolation of the dermis/subcutis (soap bubbles); nodular to diffuse pyogranulomatous to granulomatous dermatitis and panniculitis containing numerous organisms
What fungus grows on fungal isolation media as a white mold with production of pigmented conidia?
Sporothrix spp.
Mode of transmission of Blastomyces
inhalation of conidia from envrionment; cutaneous inoculation
Mode of transmission of Sporotrichosis
cutaneous inoculation or inhalation of conidia (minor)
What organisms are associated with Zygomycosis?
Basidiobolus and Conidiobolus spp., Rhizopus, Absidia, Mucor spp.
Opportunistic fungal infection caused by wide, infrequently septate, nonpigmented hyphae associated with pyogranulomatous and eosinophilic inflammation
zygomycosis
Describe the pathogenesis of cryptococcosis
Inhalation of basidiospores –> in tissue the basidiospores convert to the yeast form –> replicates by forming one or two daughter cells (buds) that are connected to the parent cell by a narrow base
Treatment of choice for sporotrichosis
itraconazole > fluconazole, ketoconazole; refractory disease can be treated with supersaturated potassium or sodium iodide, terbinafine, or amphotericin B
Mode of transmission of Candidiasis
usually an invasion of commensal yeasts secondary to immune suppression (normal inhabitant of mucocutaneous skin and GI tract, genital tract)
Is itraconazole fungistatic or fungicidal?
BOTH - at low doses it is fungistatic and at high doses it is fungicidal
T/F: Terbinafine inhibits cytochrome p450.
FALSE
Skin lesions associated with candidiasis
exudative and pustular to ulcerative inflammation of the lips, oral mucosa, and external ear canal; sharply delineated ulcers with erythematous borders and a malodorous surface with moist gray-white exudate; chronic lesions are thickened, alopecic, and hyperkeratotic
Which is more sensitive and specific for diagnosis of Sporotrichosis: Antibody or Antigen ELISA?
Antibody - detects antibody to Sporothrix cell wall antigens; no antigen tests are currently available
Which is more sensitive and specific for diagnosis of Blastomycosis: Antibody or Antigen ELISA?
Antigen; false positives can occur with the antibody test in endemic areas (result of exposure or previous recovery)
Ketoconazole can lead to increased plasma concentrations of what drugs?
ivermectin, midazolam, cyclosporine (among others)
Zoophilic dermatophytes that affect cattle?
Trichophyton verrucosum
Why is phaeohyphomycosis poorly responsive to medical therapy?
pigmented fungi are poorly responsive to medical therapy in part because melanin is a virulence factor
T/F: Chlorhexidine as a monotherapy for dermatophytosis is poorly effective and is not recommended.
True - must be combined with miconazole
Within tissues, what cells are most important in the defense against Candida spp.?
neutrophils – candida blastospores are phagocytized and destroyed by neutrophils
DDx for Sporothrix on cytology
Histoplasma capsulatum, Cryptococcus spp., Candida spp., Leishmania infantum (less likely Toxoplasma gondii and Neospora caninum)
T/F: Cytologic examination of affected tissues with coccidioidomycosis has high sensitivity.
False - organisms may be difficult to accurately identify
T/F: Devon rex and Cornish rex cats are prone to high carriage rates of Malassezia yeasts.
False - only devon rex and sphynx cats, NOT Cornish rex
Histopathologic findings with Histoplasmosis
pyogranulomatous or granulomatous inflammation with intralesional yeasts; lymphocytes and plasma cells may also be present; with chronicity, may see fibrosis or mineralization (dogs)
What is the geographic distribution of Coccidioides?
Southwestern US, Mexico, parts of Central and South America (NE Brazil, Argentina, Paraguay, and Bolivia)
Which is more sensitive and specific for diagnosis of Cryptococcosis: Antibody or Antigen ELISA?
Antigen – detects the cryptococcal polysaccharide capsular antigen
What is the environmental niche for Cryptococcus neoformans?
weathered bird (especially pigeon) guano, can also be found in decaying plant matter
How do Candida yeast adhere to and colonize mucosa?
ligand-receptor and/or hydrophobic interactions; ligands = afflutinin-like family and hyphal wall protein family, receptors on the mucosal epithelial cells = E-cadherin, fibrinogen, fibronectin, thrombin, collagen, laminin, and vitronectin-binding proteins
Zoophilic dermatophytes that affect the cat and dog?
Microsporum canis
What stain helps to highlight the capsule of Cryptococcus on biopsy?
Mayer mucicarmine – stains organism’s capsule RED
Why is it not recommended to culture Blastomyces dermatitidis?
it grows as a mycelium in the laboratory and poses a risk to lab workers
What is the only species of Malassezia that can utilize lipid fractions from Sabouraud’s dextrose agar for growth?
Malassezia pachydermatis
Under what circumstances has candiadiasis been reported?
compromised host resistance (diabetes mellitus, HAC, neoplasia, viral infections, cytotoxic chemo, prolonged glucocorticoid tx), factors that alter superficial keratin barrier (maceration, chronic trauma, or burns), upset normal flora (prolonged broad spectrum antibiotic therapy)
What type of immunity is required to clear dermatophytosis?
cell-mediated – also involved in developing resistance to reinfection
T/F: Cats who are seropositive for FIV and/or FeLV are at increased risk for dermatophytosis.
False - seropositive status alone does not increase the risk
Does hyalohyphomycosis occur more commonly in dogs or cats?
dogs
Why are Malassezia lipid dependent?
lack fatty acid synthase gene - cannot synthesize long-chained (C14 or C16) fatty acids de novo
Cytological characteristics of Candidiasis
Candida blastospores, pseudohyphae and true hyphae can be seen in specimens from ears, skin, urine, or other bodily fluids; small yeasts (3-6 um) and ovoid (blastospheres)
T/F: It is not recommended to culture Sprothrix spp. due to human health risks.
False - culture is required for definitive diagnosis
T/F: It is difficult to culture organsisms that cause Phaeohyphomycosis.
False - readily isolated on routine culture; further identification based on colony and conidial morphology and PCR and sequencing of ribosomal RNA genes
Histopathologic findings with Blastomycosis
granulomatous or pyogranulomatous inflammation with intra-lesional budding yeasts; may also have multinucleated giant cells, fibroblasts, and large number of lymphocytes
Treatment of choice for Zygomycosis
aggressive surgical resection followed by medical therapy with itraconazole for 2-3 months
T/F: Candida will grow on blood agar.
True - grows on blood agar and Sabouraud’s dextrose agar
What genera of fungi have been associated with hyalohyphomycosis?
Acremonium, Fusarium, Geotrichum, Paecilomyces, Pseudallescheria, Sagenomella, Scedosporium
What type of immunity is required to clear histoplasma capsulatum infection?
Th1 immune response – production of IFN-gamma activates macrophages to destroy the fungus
Is itraconazole better absorbed in a basic or acidic environment?
acidic (it is highly lipophilic and a weak base compound)
Why is it not recommended to culture Histoplasma capsulatum?
it grows as a mycelium in the laboratory and poses a risk to lab workers
What is a geophilic dermatophyte?
associated primarily with the decomposition of keratin of hair, feathers, and horn present in soil after the keratinized products have been shed from the host
What stain helps to highlight the capsule of Cryptococcus on cytology?
India ink
Why does Pythium insidiosum stain poorly with periodic acid Schiff stain?
lack of chitin in cell wall
Major clinical signs of Coccidioidomycosis
cough, fever, inappetance, weight loss, tachypnea, lameness, subcutaneous masses or draining skin lesions, lymphadenopathy, neurologic signs, ocular lesions (uveitis, chorioretinitis, endophthalmitis), pericarditis
What is the major defense mechanism against Candida spp.?
neutrophils and T-cell mediated immunity
Histopathologic features of Malassezia dermatitis
hyperkeratosis, multifocal parakeratotic hyperkeratosis; characteristic budding, bottle-shaped yeasts and often cocci over an irregular spongiotic epidermal hyperplasia – extends to follicular infundibula (best place to find the yeast organisms)
What is the difference between septate or coenocytic micelium?
septate micelium - divided into compartments separated by cross walls formed at right angles, each septa has pores and compartment has a single nucleus; Coenocytic mycelium are not compartmentalized
Treatment of choice for Lagenidiosis
aggressive surgical resection of all infected tissues with wide margins followed by treatment with itraconazole and terbinafine
How can different species of Malassezia be identified?
DNA sequencing (or mass spectrometry)
Most common species of Cryptococcus to infect cats?
Cryptococcus gatii
Where are the fungi located in a typical ringworm lesion?
central portion contains dead fungi, viable fungi at the periphery causes a red ring
Treatment of choice for Candidiasis
correct underlying disease, keep dry and clean; topical antifungals (nystatin, azoles, amphotericin B, terbinafine) +/- oral antifungals (fluconazole - urine; ketoconazole or itraconazole)
T/F: Histoplasmosis is rare in cats.
False - cats are as susceptible to histoplasmosis as dogs (second most common systemic fungal infection in cats)
What breed(s) of cat(s) are prone to high carriage rates of Malassezia yeasts
Devon rex and sphynx cats
Why is it not recommended to culture Coccidioides?
culture is a health hazard to lab employees
Why are there no susceptibility tests currently available for Malassezia?
Malassezia pachydermatis does not exhibit sufficient growth in the standard defined (and lipid-free) RPMI 1640 medium to permit the reference method use for susceptibility
Why is medical therapy for pythiosis typically unrewarding?
ergosterol is generally lacking in the oomycete cell membrane (and ergosterol is the target for most antifungal drugs)
What breeds are at increased risk of Malassezia dermatitis?
West Highland white terriers, English setters, shih tzus, basset hounds, American cocker spaniels, boxers, dachshunds, poodles, and Australian silky terriers
Mode of transmission of Coccidioides?
inhalation of arthroconidia from the environment; rarely cutaneous inoculation
Causative organism of Sporotrichosis
Sporothrix schenckii complex - Sporothrix globosa, S. brasiliensis, S. schenckii, S. albicans, S. luriei
Cytological characteristics of Sporotrichosis
pyogranulomatous inflammation; cats: large #s of round to cigar-shaped yeasts intracellularly within neutrophils or macrophages and extracellularly; 4-6 um in diameter and can exhibit single bud with a narrow base
What stain highlights the hyphae of pythiosis?
Gomori’s methenamine silver (GMS) – do NOT stain well with periodic acid Schiff stain
DDX for Rhinosporidiosis
Nasal neoplasia, cryptococcosis, sinonasal aspergillosis, nasal mites (Pneumonyssoides caninum), foreign bodies
T/F: Dogs are at greater risk of blastomycosis compared to humans
True - 10X higher risk for dogs
Treatment of choice for hyalohyphomycosis
Discontinuation of immunosuppressive therapy, systemic antifungals - itraconazole, amphotericin B, voricoanzole, posaconazole
T/F: Cats infected with cryptococcus are systemically unwell.
False - cryptococcosis is usually a chronic infection in cats and animals are usually otherwise well but may have mild lethargy and inappetance
T/F: Absorption of both ketoconazole and itraconazole is enhanced by giving with food.
True
What are the different types of mycetomas?
Actinomycotic mycetomas (Actinomyces spp or Nocardia spp), Dermatophytic mycetomas, Eumycotic mycetomas (non-dermatophyte fungi)
What is the first line treatment of Malassezia dermatitis in cats?
itraconazole
_____ are an interconnected network of hyphae that develops as hyphae grow.
Micelium
Adverse events reported with griseofulvin?
teratogenic, bone marrow suppression (cats)
What are the virulence factors of Blastomyces?
cell surface glycoprotein = BAD-1 (adhesin that binds to host cell receptors on macrophages); other cell wall compoments such as alpha-1,3-glucan
What are the stages of dermatophyte infection?
1) Adherence of arthroconidia to corneocytes (2-6 hours afer exposure); 2) Fungal conidial germination and penetration into stratum corneum (4-6, maybe 24 hours); 3) Dermatophyte invasion of keratinized structures (7 days)
What is the preferred specimen for culture of Pythium insidiosum?
small pieces of fresh, nonmacerated tissue –> cultured on vegetable extract agar supplemented with streptomycin and ampicillin –> mycelial growth observed within 12-24 hours
Does phaeohyphomycosis occur more commonly in dogs or cats?
cats
The blastomyces cell wall antigen test cross reacts with what other organism?
histoplasma (false positives may occur when an animal has histoplasmosis)
Yeasts with narrow-based budding
Sporothrix, Cryptococcus, Candida
What are the important traits that distinguish oomycetes from fungi?
production of motile, flagellate zoospores that act as infective elements in wet environments; oomycete cell membrane generally lacks ergosterol or chitin - have cellulose and beta-glucan
What creates the color change with dermatophytes in DTM?
dermatophytes preferentially use the protein in the medium as they begin to grow –> produce alkaline metabolites that cause the medium to turn red
When does the color change in a DTM plate occur with saprophytic fungi?
Long after appearance of the colonies; saprophytic fungi metabolize the carbohydrates first –> produce acidic metabolites that do not change the color of the medium
After the CHO source has been depleted, saprophytes use the proteins and produce a red color change
What is the only saprophytic fungi that produces a red color change in DTM at the same time the colonies appear?
Scopulariopsis brevicaulis – tan to light brown, smooth or mealy colony
What 4 species of dermatophytes have some strains that fluoresce with the Wood’s lamp?
“Distorted CATS” -
- Microsporum distortum
- Microsporum canis
- Microsporum audouinii
- Trichophyton schoenleini
Gross appearance of Microsporum canis on Sabouraud’s dextrose agar
- Flat
- Spreading
- White to cream colored surface
- Cottony with radial grooves
- Reverse pigment is golden yellow to brownish yellow
Microscopic appearance of Microsporum canis from a fungal culture
Macroconidia are spindle-shaped
>6 cells
Thick-walled
Terminal knob
Gross appearance of Microsporum gypseum on Sabouraud’s dextrose agar
- Flat
- Spreading
- Suede-like to granular
- Deep cream to twany-buff to pale cinnamon colored red surface
- Reverse pigment is yellow-brown often with a central darker brown spot
Microscopic appearance of Microsporum gypseum from a fungal culture
Ellipsoidal, thin-walled
4-6 celled macroconidia
What are the most common causes of dermatophytosis in the horse?
Trichophyton equinum #1
T. mentagrophytes
T. verrucosum
M. equinum
M. gypseum
What are the growth requirements for the most common species of dermatophytes in the horse?
Trichophyton equinum - needs niacin added to Sabouraud’s dextrose agar
What are the components of Dermatophyte Test Medium
- Sabouraud’s dextrose agar
- Cycloheximide
- Gentamicin
- Chlortetracycline
- Phenol red
What are the components of Enhanced sporulation agar/rapid sporulating media
- Dextrose agar
- Petones
- Chloramphenicol
- Gentamicin
- Cycloheximide
- Bromothymol
What are the growth requirements for the most common species of dermatophytes in cattle?
Trichophyton verrucosum – needs thiamine +/- inositol added to Sabouraud’s dextrose agar
What is in PMS Fungal/TZANCK Stain
Toluidine blue and basic fuschin in 30% ethyl alcohol
Are fungi gram positive or gram negative?
gram positive
What species of dermatophyte is thought to be the most common in pigs?
Nannizzia nana – zoophilic and geophilic
Appearance of Nannizzia nana on fungal culture on Sabouraud’s dextrose agar
- flat
- white to cream colored
- suede-like to powdery surface
- brownish-orange reverse pigment
Appearance of Nannizzia nana on cytology from fungal cultures
Macroconidia are ovoid to pyriform with 1-3 cells
Appearance of Trichophyton equinum on fungal culture on Sabouraud’s dextrose agar
- Flat
- white to cream colored
- suede to powdery
- brownish-orange reverse pigment
Appearance of Trichophyton equinum on cytology from fungal cultures
Abundant microconidia
Rare clavate, smooth, thin-walled macroconidia
Appearance of Trichophyton mentagrophytes on fungal culture on Sabouraud’s dextrose agar
- flat
- white to cream colored
- powdery to granular surface
- red-brown submerged peripheral fringe and reverse pigment
Appearance of Trichophyton mentagrophytes on cytology from fungal culture
- numerous single-celled microconidia –> often in dense clusters
- microconidia are hyaline, smooth-walled and are predominantly spherical to subspherical
- spherical chlamydoconidia
- spiral hyphae
- smooth, thin-walled, clavate shaped, muticelled macroconidia
Appearance of Trichophyton verrucosum on fungal culture on Sabouraud’s dextrose agar
- glabrous, heaped, folded white colony
- no reverse color
Appearance of Trichophyton verrucosum on cytology from fungal culture
- clavate to pyriform microconidia
- macroconidia are rare, “rat-tail” or “string-bean” shaped
How are dermatophytosis and trichomycosis nodularis different?
dermatophytosis - fungal infection of hair shaft (intrafollicular) and stratum corneum
trichomycosis nodularis - fungal infection of hair shaft (extra-follicular)
Microsporum canis
Microsporum canis
Microsporum gypseum
Microsporum gypseum
Trichophyton mentagrophytes
Trichophyton mentagrophytes
