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%)