You see this on cytology. What is it?
Large, rough, thick walled multiseptate macroconidia
What is this?
What is this?
What do you suspect is wrong with this cow?
This cow probably has ringworm. Likely T. verrucosum.
What are you most concerned about for this horse?
Looks like ringworm. Likely T. equinum or M. gypseum.
Multiple dry, scaled, raised lesions
Can be chronic or subclinical.
This is an issue for reptiles and amphibians
What are you concerned about for these patients?
A, Multiple tufted papules and nodules over lateral thorax. These lesions are often confused with urticaria. B, Multiple areas of discrete “nonreactive” alopecia caused by follicular inflammation. C, Widespread alopecia due to coalescence of pustular lesions. Dog had been treated with corticosteroids instead of antibiotics. D, Multiple small crusted follicular papules over tarsal region.
What do you see here?
This hair shaft has been invaded by fungal hyphae and is surrounded by large numbers of ectothrix spores (arrow).
This could be.....
Single circular lesion with alopecia and scaling on rump of dog infected with Trichophyton mentagrophytes.
What are you most concerned about?
Multifocal annular lesions of peripherally expanding alopecia, erythema, and scaling in dog infected with M. canis. Affected area has been shaved to enhance visualization of lesions.
What might this dog have?
Multifocal annular lesions of peripherally expanding alopecia, erythema, and scaling in dog infected with Trichophyton mentagrophytes.
You see all three of these dogs on the same day. Before you grab the wine, what is your leading differential for them?
Symmetrical facial alopecia and hyperpigmentation in dog infected with Trichophyton mentagrophytes. B, Asymmetrical facial alopecia and hyperpigmentation in dog infected with T. mentagrophytes. C, Crusting, alopecia, and hyperpigmentation of nose and ear pinna of dog infected with T. mentagrophytes.
Hmmm.....what test would you order for this little love bug?
This looks like a kerion secondary to M. canis.
Let's order a DTM or dermatophyte PCR
What is a leading differential for this dog?
Parson (Jack) Russell terrier with facial lesions caused by Microsporum persicolor. B, Close-up of facial lesions of Parson (Jack) Russell terrier with M. persicolor.
You're called to an animal shelter to look at these cats. What do you think is happening with them?
A, Scaling and alopecia of ear pinnae in cat infected with Microsporum canis. B, Scaling and alopecia on dorsal neck of cat infected with M. canis.
Hmmm...what is this showing?
Hyphae within and arthrospores surrounding hair infected with Microsporum gypseum.
What do you think is wrong with this claw?
A differential for this cat...
Yikes! What is this?
Numerous yeasts, and cigar bodies (arrow) in a macrophage.
Yucky. What is this?
Mycetoma on foot of dog. B, Mycetoma due to Torula sp. in a cat. Note multiple black tissue trains associated with draining tracts over hip.
What is this?
Mycetoma due to Torula sp. in a cat. Glass slide with plucked hair and crust on right and purulent exudate containing black tissue grains on left.
What is this showing you?
Direct smear from cat with phaeohyphomycosis. Pigmented fungal hyphae within a macrophage.
What's your top differential?
Hemorrhagic bullae and ulcerated nodules caused by Pythium insidiosum on foreleg of German shepherd dog. B, Same dog as in A. Lesions have progressed to form a large ulcerated lesion with invasion of organisms into muscles of foreleg
What's this? What stain?
Numerous hyphae in pyogranulomatous dermatitis
What are you suspecting here?
Large alopecic mass with necrotic foci caused by Pythium insidiosum on back of boxer. B, Surgical débridement of lesion in A shows invasiveness of organisms. C, Closer view of lesion in B showing presence of yellowish “kunkers” (oomycetic hyphae surrounded by necrotic debris and inflammatory cells).
What is this?
Broad-based budding and thick, refractile, double-contoured cell walls are characteristic of Blastomyces dermatitidis organisms (arrows).
Direct smear from dog with coccidiomycosis. Ruptured spherule releasing endospores and surrounded by degenerate neutrophils.
What are you concerned about with this dog?
Canine cryptococcosis. B, Nasal swelling and discharge caused by Cryptococcus neoformans. C, Closer view of nodule on rear leg of dog infected with C. neoformans.
These poor cats. What do you think they have?
A, Nodule involving planum nasale of cat with cryptococcosis. B, Large ulcerative granuloma involving nose of cat with cryptococcosis. C, Swelling with multiple draining tracts over bridge of nose of cat with cryptococcosis.
What the heck?
A, Multiple nodules on face of cat with cryptococcosis. B, Multiple nodules are also present on trunk of cat shown in A. C, Multiple ulcer- ated nodules on head of cat with cryptococcosis. D, Multiple nodules are also present on lips and in oral cavity of cat shown in C
This is a direct smear. What are you concerned for? What stain was used?
Direct smear from cat infected with C. neoformans. India ink staining shows clear halos formed by capsules surrounding organisms.
What is this?
Macrophage containing numerous intracellular yeasts in a direct smear from cat with histoplasmosis.
You saw a wacky looking yeast on this dog? What is your concern?
What did this cat have?
Ulcers over shoulders of cat with candidiasis. B, Closer view of one of ulcers in A. C, Facial lesions of cat with candidiasis. D, Closer view of periocular and perioral lesions of cat in C.
Name that disease...
White piedra (Trichosporon asahii) in a dog. B, Closer view showing white-to-gray concretions encircling hair shafts of dog in A. C, Microscopic examination of hairs from dog in A shows nodules encircling hair shafts.
This is extremely rare. Yeast-like organisms. Name that weird disease.
Rhodotorula dermatitis in cat: alopecia, erythema, and crusting on nose and muzzle. B, Rhodotorula dermatitis in a cat: alopecia and erythema of a lateral digit.
Cutaneous mycoses/dermantophyte/ which microsporum species?
- m. canis
- most common
- Large, rough thick-walled multiseptate macroconidia
Cutaneous mycoses/ dermanophyte/ which microsporum species?
- M. gypseum
- Large, rough thick-walled multiseptate macroconidia
cutaneous mycoses/ dermatophyte/ which microsporum species?
- M. nanum
- Large, rough thick-walled multiseptate macroconidia
cutaneous mycoses/ dermatophyte/ which trichophyton species?
t. mentagrophytes -Differ from Microsporum in their cylindrical, cigar-shaped, thin/thick-walled smooth macroconidia that are produced rarely and in small numbers
cutaneous mycoses/ dermanophyte/ which trichophyton species?
t. verrucosum - Differ from Microsporum in their cylindrical, cigar-shaped, thin/thick-walled smooth macroconidia that are produced rarely and in small numbers
disease? what organisms cause this?
M. canis , M. gypseum , T. erinacei, T. mentagrophytes
Brittle hair, dry and scaly skin, crusts and scabs
T. mentagrophytes cause Kerion (swelling and ulceration)
disease? what organism causes this?
Feline ringworm M. canis
Serve as a primary reservoir - otitis
disease? what organism causes this?
Scaling and alopecia
disease? which organism causes this?
Porcine Ringworm -M. nanum -circular, roughened lesions, usually no hair loss
disease? which organisms cause this?
Equine Ringworm T. equinum and M. gypseum -multiple dry, scaly raised up lesions -chronic and subclinical
ringworm in chickens is due to what organism?
M. gallinae -"favous" or "white comb" -white patches on combs of infected males, may spread to feathers
what organism causes this?
otitis externa Malassezia (shoe-shaped yeasts) -dermatomycoses
cutaneous mycoses/ dermatomycoses/ what organism?
malassezia -lipophilic yeast - footprint shaped -M. pachydermatities causes otits extern and seborrheic dermatitis
seborrheic dermatitis M. pachydermititis= opportunistic pathogen
cutaneous mycoses/ what is this?
Malasezzia shoe-print shaped yeast
dermatomycoses/ cutaneous mycoses/ what is this?
Geotrichum candidum - Hyaline septate hyphae fragment into arthroconidia -soil and decaying matter -amphibians and reptiles
cutaneous mycoses dermatomycoses
SQ mycoses/ what is this?
Sporothrix schenckii -dimorphic, dematiaceous fungus -flouret arrangement dogs, cats horses
direct tissue smear of SQ mycoses
Sporothrix schenckii -cigar shaped yeasts -lymphocutaneous infections= spreads along lymphatics
What's a differential?
sporotrichosis -lesions not painful or pruritic "rose handler's dz" in humans -cats sensitive to iodine so tx with itraconazole
SQ mycoses---> a DZ of Equidae
epizootic lymphangitis -Histoplasma capsulatum var. farciminosum -thermally dimorphic -granulomatous, nodular lesions -pear shaped, double contoured budding yeast
chromoblastomycosis -brown pigmented sclerotic bodies = thick walled muriform cells -firm, ulcerative nodules localized to the feet and legs
Eumycotic mycetoma -rare -fistulous tumor develops foot and/or abdomen
SQ mycoses. causative agent of Bovine Nasal Granuloma
Curvularia -granulomatous swellings in the nasal cavity- white polyps -dematiaceous fungi -contain up to 4 cells and slightly curved
SQ mycoses. also causes bovine nasal granuloma
Bipolaris -macroconidia thick walled, contain 4 or more cells -dematiaceous fungi
systemic mycoses- thermally dimorphic
Blastomycosis -Blastomyces dermatitidis -LUNGS--> skin, eyes, bone -humans, dogs, cats -thick-walled, broad-based budding yeast cells -can be systemic/disseminatioin and cutaneous
systemic mycoses- thermally dimorphic
Blastomycosis -severe biohazard -ohio, missouri, tennessee, mississippi river
systemic mycoses/ thermally dimorphic
Balstomycosis -mold form -hyaline hyphae -spherical conidia that look like a balloon on a short stalk
systemic mycoses/ thermally dimorphic
Coccidiomycosis -Coccidiodes immitis -dogs, horses, llamas -LUNGS----> bone, skin -large spherules with thick walls containing round endospores
systemic mycoses/ thermally dimorphic
Coccidiomycosis -southwestern USA -mycelial form dangerous to handle - mold= alternating barrel-shaped arthroconidia
systemic mycoses/ thermally dimorphic
Histoplasmosis -Histoplasma capsulatum -dogs, cats -pulmonary infections, chronic DZ, GIT in dogs -small yeast cells within M@, round yeast cells with basophilic centers and a clear halo
systemic mycoses/ thermally dimorphic
Histoplasmosis -culture considered biohazard -large, rounded, single celled, tuberculate macroconidia and small microconidia - likes nitrogenous soils -tennessee, mississippi, ohio, missouri
systemic mycoses/ NOT a dimorphic fungi
Cryptococcosis -Cryptococcus neoformans -CAPSULATED YEAST -cats -soil with pigeon excreta
systemic mycoses/ NOT thermally dimorphic
Cryptococcosis -remains in yeast form for both environment and host -unencapsulated in the env. -capsulation of yeast in vivo
opportunistic fungi- DZ in birds
Candidiasis (Thrush, Crop mycosis, Sour crop) -Candida albicans -GIT of birds= crop -white raised pseudomembranes -listlessness and inappetence -tx copper sulfate in water
Candidia albicans -ovoid budding yeast cells with thin walls -pseudohyphae or hyphae may be present -normal inhabitant of nasopharynx, GIT, external genitalia -most frequently infects birds
opportunistic fungi- DZs in other animals besides birds
canidia ablicans -exfoliative dermatitis, otitis externa in dogs -GIT canidiasis in foals and calves -cutaneous and mucocutaneous infections in pigs
Aspergillosis -Aspergillus spp. -respiratory infection -pulmonary infections in birds -mycotic abortion in cattle -guttural pouch mycosis horses -hyaline, septate hyphae that branch dichotomously, -characteristic conidial arrangement
opportunistic fungi DZ in resp tract of birds
Aspergillosis -characteristic white material in abdominal air sacs, lungs or membranes of body cavities
Aspergillosis DZ in ruminants
-mycotic pneumonia- multiple discrete granulomas -bovine mycotic abortion- aborted at 6-9 mos gestation, lesions found in uterus, fetal membranes, fetal skin --- intercaruncular areas thickened, leathery, dark red to tan --- cutaneous lesions on fetus may resemble ringworm
aspergillosis in horses
gutteral pouch mycosis -epistaxis -mycotic plaques=necrotic, inflamed lesions in wall of guttural pouch
pneumocystic pneumonia -most common in horses= cough, exercise intolerance -trophozoites= basophilic, dense, oval with a lobed surface and single nucleus -intracystic bodies= aggregates of oval dense, basophilic structures against a thick, foamy background
pythiosis -Pythium insidiosum=associatedwith water -Equine Pythiosis (Bursatti, Swamp cancer, Leeches) -ulcerative lesions of limbs and ventral abdomen -lesions contain "kunkers" or "leeches"
equine pythiosis -lack chitin and ergosterol -lesions pruritic -tx radical incision the best
canine pythiosis= fungal-like agent
-cutaneous, subcutaneous, GIT infections -poor prognosis -surgical excision best
Bovine protothecal mastitis -achlorophyllic algae, Prototheca zopfii, P. wickerhamii -from dirty env, lack of hygiene -fibrotic hard udder, fall in milk production, clots in milk, increase in somatic cell count -floret-like arrangements
-broad anti fungal activity -bind to sterol components, disrupt cell membrane= internal acidification=halt enzymatic functions -Amphotericin B, Nystatin, Primaricin
-wide spectrum antifunal -block the synthesis of ergosterol=internal cell disruption and cell death -miconazole, ketoconazole, itraconazole, fluconazole
-antifungal -converts to fluorouracil which interferes with RNA and Protein synthesis -used against Cryptococcal meningitis, Candidiasis, Aspergillosis, Chromomycosis, Sporotrichosis
-systemic antifungal (dermatophytes) -fungistatic -disrupts mitotic spindle= production of multinucleate fungal cells
-antifungal -NaI for sporotrichosis (not cats!)
Topical Antifungal Agents
-to control superficial mycotic infections -Amorolfine- interferes with the synthesis of sterols, against dermatophytosis -Terbinafine- decreases synthesis of ergosterol, against dermatophytes, yeast, used in combination with other drugs to enhance efficacy
-low molecular weight microbial metabolites= kill or inhibit growth -Alexander Fleming with Penicillium -use depends on selective toxicity
Inhibition of Cell Wall Synthesis
penicillins (G+), cephalosporins, bacritracin, vancomycin -prevent cross-linking of peptidoglycan chains -interferes with transpeptidation
Injury to Plasma Membrane
Polymyxin B (G-) -bind to membrane phospholipids and resulting in structural disorganization -potentially nephrotoxic and neurotoxic= limited to topical use
Inhibition of Protein Synthesis
-Chloramphenicol-to 50s, inhibits formation of peptide bond -Erythromycin-to 50s, prevents movement of ribosome along mRNA -Tetracyclines- interfere with attachment of tRNA to mRNA-ribosome complex -Streptomycin-change shape of 30s, code on mRNA read incorrectly
Inhibition of NA Replication and Transcription
-Quinolones-block DNA gyrase -Rifampin- blocks DNA-directed RNA polymerase, antimycobacterial activity -Novobiocin-block DNA gyrase
Inhibition of Synthesis of Essential Metabolites
Trimethoprim/ Sulfanilamide-block PABA incorporation into folic acid (required for NA synthesis)
Bacterial mechanisms of antibiotic resistance
-have antibiotic degrading enzyme, antibiotic altering enzyme, antibiotic resistance gene, efflux pump 1. Inherent (natural) resistance 2. Acquired resistance
What is the causative agent of black piedra?
What is the causative agent of white piedra?
Where would you find a lesion from white piedra on a horse?
A grossly visible nodule on the long hairs of the mane, tail and distal limbs
What is the definition of mycetoma?
a unique infection where the organism is present in tissues as granules or grains
Three Cardinal Principles
Leadership, Friendship, Service
What is the definition of 'dematiaceous'?
What is the causative agent of basidiobolomycosis?
Ulcerative granulomatous equine skin disease Basidiobolus ranarum
Zycomycosis - 2 orders: Order Mucorales - 4 genera
Zycomycosis: * Order Mucorales * genera Rhizopus * genera Mucor * genera Absidia * genera Mortierella
Zygomycosis: - 2 Orders - Order Entomophthorales - Two genera
Zygomycosis: * Order Entomophthorales * Genera Conidiobolus * Genera Basidiobolus
What is a characteristic of Conidiobolomycosis coronatus?
* Ulcerative granulomatous equine disease * * Often affects the nostril in horses, leading to mucohemorrhagic nasal discharge and dyspnea due to nasal discharge
What is the causative agent of Mucormycosis in horses?
What is the causative agent of sporotrichosis and what is the usual transmission?
Sporothrix schenkii Wound contamination Steriods/immunosuppressives CI and can cause relapse 4-6 mo after apparent clinical cure
What is the most common form of sporotrichosis in the human?
What is the treatment of choice for sporotrichosis in the horse?
Iodides Treated 30 days past clinical cure
What are the side effects of iodidism (intolerance of iodide meds)?
Variable Scaling/alopecia, depression, anorexia, salivation, nervousness, or CV abnormalities Can also cause abortion in mares
What is the causative agent of Rhinosporidiosis?
Rhinosporidiosis seeberi Affect nostrils, can present as polyps endemic in India and Sri Lanka; only found in the southern US in north america
What is the definition of deep mycosis?
fungal infection of internal organs that may secondarily disseminate by hematogenous spread to the skin Usually from a ubiquitous saprophyte; not contagious
What is the causative agent of Blastomycosis and what are the four elements of the "microfocus model" for geographic distribution?
Blastomyces dermatitidis Four elements: 1. Moisture 2. Soil type (sandy, acid) 3. Presence of wildlife 4. Soil disruption
What are two other colloquial names for Blastomycosis and where is it found?
Gilchrist disease; Chicago disease Mostly in North America -- well defined endemic distribution -- Mississipi, Missouri, New York, Ohio and St. Lawrence River Valleys and mid-Atlantic states
1. Systemic mycoses fungus: Large yeast w/ broad-based buds 2. Endemic: East of Mississippi River 3. Natural habitat: beaver dams, river banks 4. KOH mount- destroys everything except for fungal cell walls (very resilient)
-large spherules with characteristic thick/double wall -endospores similar in size to large yeasts (usually in granulomas)
Caused by Coccidiodes immitis and C. posadasii Dimorphic fungus, mold in soil and spherule in tissue highly contagious arthrospores, inhaled to infect lungs spherules (large) in micro tissue samples Thick doubly refractive wall, filled with endospores erythema nodosum (NE) Amphotericin B or itraconazole
San Joaquin Valley Fever is also known as...?
Coccidiomycosis in horses
* Rare * No age or sex, but Arabians may be more at risk * Dx in late fall and early winter * common present: chronic weight loss, persistent cough, musculoskeletal pain, phasic pyrexia and skin lesions * Cutanous lesions in ~20% and may be the initial clinical sign - -- abscesses ,
Which systemic mycosis is associated with the following things: 1. San Joaquin River Valley 2. Ohio, Mississippi and Missouri river valleys 3. Pigeon droppings.
1. Coccidiomycosis 2. Blastomycosis 3. Cryptococcus
What are the two causative agents of Cryptococcis?
1. Cryptococcus neoformans v. neoformans --- most prevalent in the US and Europe 2. Cryptococcus neoformans v. gatti ---- prevalent in SoCal, Australia, SE Asia, Africa, and S. America ---Can also affect immunocompetent individuals and can be very difficult to treat
What is the typical presentation of Cryptococcosis in the horse?
Rare Rhinitis and/or nasal granulomas, and CNS dz (especially meningitis) Multiple cryptococcal granulomas may occur on the lips
* Meningitis (Most Cs) or Encephalitis in AIDS (opportunistic!) * Pulmonary + Skin Dz * Eti * C.Neoformans Epi * Pigeon droppings Cystic encapsulated yeast masses " Soap Bubbles " due to accumulated cryptococcal capsular polysaccharide Dx * Culture on Sabouraud 's * CSF, sputum, & urine * India ink > CAPSULE NON-dimorphic budding yeasts
What is a special stain to identify Cryptococcus?
Mayer mucicarmine stains the organisms capsule (which is carminophillic) red
Pythium insidosum (oomycete) typically presents with lesions on the _______ of the animal
Ventral aspect. Areas of the body often exposed to water
oomycetes, phyco, swamp cancer, florida horse leeches, seen in gulf coast, habitat is water, moist soil, motile zoospores invade skin, convert to hyphae, granulomatous response, eosinophils are prominent (kunkers/leeches- masses of hyphae, necrotic macrophages, eosinophils), diagnosis- biopsy, histopathology, culture
What is the difference between dermatophytosis vs dermatomycosis?
Dermatophytosis - infection of the keratinized tissues (claw, hair, stratum corneum) caused by a species of Microsporum, Trichophyton, or Epidermophyton Dermatomycosis - caused by non-dermatophyte
What are the 2 genera oomycete most important pathogens of animals?
1. Pythium 2. Lagenidium
The term 'fungus' includes what?
Yeasts (unicellular) and molds (multicellular, filamentous)
What does the cell wall of fungi consists of? (4)
Chitin, chitosan, glucan, mannan
Vegetative filament of a fungus is called?
What is a mass of hyphae known as?
Asexual state of a fungi is called?
Sexual state of a fungi is called?
Dermatophytes are primarily found in what state? (asexual/sexual)
What distinguishes oomycytes from fungi?
Oomycetes cell walls are composed primarily of β-1,3-glucan polymers and cellulose with very little chitin (fungal cell walls are mainly chitin and ergosterol)
What are the major tissue reactions observed with fungal infections?
1. Acute suppurative inflammation and microabscess formation 2. Chronic inflammation - PG 3. Necrosis- fungi invade blood vessels---> infarction-->tissue death
What is the MOA of nystatin and amphotericin B on fungi?
Bind with ergosterol in fungal cell membranes --> altered cell permeability and eventual cell death
Name 6 things azoles inhibit synthesis of?
Ergosterol Triglyceride Phospholipid Chitin Oxidative and perioxidative enzymes
What are naftifine and terbinafine?
MOA of allylamines?
Inhibit ergosterol biosynthesis and squalene epoxidase Bind to stratum corneum and penetrate into hair follicles
MOA of griseofulvin
Binds to keratin and inhibits cell wall synthesis, nucleic acid synthesis, and mitosis Fungistatic
Highest and lowest concentrations of grisofulvin are attained in what locations?
Stratum corneum - highest Basal layers - lowest
MOA of azoles
Inhibit cytochrome P450 enzyme lanosterol 14-demethylase, thus inhibiting conversion of lanosterol --> ergosterol and causing accumulation of C14 methylated sterols
What determines the potency of each azole?
Affinity for binding the cytochrome P450 moiety
What 2 properties allow pulse regime for triazoles and allylamines?
Lipophilic and keratinophilic
Ketoconazole is widely distributed with highest concentrations in what locations? (4)
Liver, kidney, pituitary, adrenals
Where is ketoconazole secreted? (6)
Urine, sweat, sebum, cerumen, saliva, milk
Ketoconazole may require how many days to reach steady state and effective therapeutic concentrations in the skin?
Ketoconazole impairs ergosterol synthesis in fungal cell walls by inhibiting cytochrome P450 enzyme, what other 2 MOAs?
- Interacts with membrane phospholipids - Inhibits yeast transformations to mycelial forms
Contraindications of ketoconazole
Pregnancy or lactation Hepatic dysfunction Thrombocytopenia
Reduced absorption of ketoconazole can be seen with what concurrent meds?
H2 blockers, antacids, proton pump inhibitors
What are the immunomodulatory and antiinflammatory effects of ketoconazole? (4)
- Suppression of neutrophil chemotaxis and lymphocyte blastogenic responses - Inhibition of 5-lipoxygenase activity - Inhibition of leukotriene production
What first choice antifungal should be used for CNS and ocular tissue disease? Keto/itra/fluconazole?
Fluconazole Keto and itra do not penetrate well into CNS or ocular tissues
Oral formulation of itraconazole require how many days to reach steady state?
Where is Itraconazole metabolized and excreted?
Metabolized by liver Excreted in bile and urine
Ketoconazole inhibits 11-hydroxylase. Which means what?
Blocks conversion of deoxycorticosterone to corticosterone ( reduce synthesis of cortisol and testosterone in dogs )
In dogs, what antifungal was reported to cause vasculitis and necroulcerative skin lesions when given at 10mg/kg/day?
Fluconazole is primarily eliminated by what?
Which azole suppresses adrenal/sex hormones?
Which is the most fungal enzyme-specific of the 3 systemic azoles?
Fluconazole Thus side effects are rare
What class of antifungal is terbinafine?
MOA of terbinafine
Inhibits ergoesterol biosynthesis and squalene epoxidase --> fungal cell wall ergosterol deficiency and IC accumulation of squalene
Is terbinafine fungicidal or fungistatic?
How is terbinafine metabolized and excreted?
Does terbinafine generally inhibit cytochrome P450 systems?
No More selective than azoles
What class of antifungal is flucytosine?
What class of drug is amphotericin B?
MOA of amphotericin B
Fungistatic that irreversibly binds to ergosterol
Amphotericin B can enhance cell-mediated immunity by?
Stimulating lymphocyte, macrophage, and neutrophil function and induce production of TNF
Amphotericin B is primarily indicated for treatment of what infections?
Severe systemic mycotic infections
What is a common side effect of Amphotericin B?
How does Amphotericin B cause renal toxicity?
Increases IC Ca in vascular smooth muscle cells and stimulates eicosanoid synthesis, resulting in reduced renal blood flow
MOA of iodides
(exact mechanism uncertain) May facilitate phagocyte killing of fungal cells
Iodides are highly effective in the treatment of what?
Cutaneous and cutaneolymphatic sporotrichosis
MOA of lufenuron
Interfere with formation of fungal cell wall and insect exoskelton (not recc for use as sole agent in fungal infection tx)
MOA of Caspofungin
Cyclic hexapeptide that inhibits 1,3-β-D-glycan synthase (blocking cell wall synthesis in fungi)
What dermatophyte is a natural resident (occ pathogen) of mice and voles?
What dermatophyte is associated with exposure to rodents or their immediate environment?
What dermatophyte is geophilic that inhabits rich soil?
Hair shafts containing infectious M canis arthrospores may remain infectious in the environment for how many months?
Up to 18 months
What is the infective portion of the dermatophyte call?
Arthrospore - formed by segmentation and fragmentation of fungal hyphae
Arthrospore adhere strongly to what in order to germinate?
Do ectothrix of endothrix produce masses of arthrospores on the surface of hair shafts
Dermatophytes produce what 3 keratinolytic enzymes?
- keratinase - elastase - collagenase
Dermatophytes penetrate hair cuticle and grow within the hair shaft until what point?
Keratogenous zone (Adamson fringe)
Dermatophytes require what type of hairs for survival?
Actively growing hairs (anagen)
Which 2 dermatophytes have been shown to produce substances (especially mannans) that diminish cell-mediated immune responses and indirectly inhibit stratum corneum turnover?
Trichophyton rubrum and T mentagrophytes
What is the keratinase from M canis?
μ- chymotrypsin-type serine proteinase
Which dermatophyte can produce proteolytic enzymes that induce keratinocyte acantholysis?
Presence of what ectoparasites can be important in establishment and spread of dermatophytes in cats?
Fleas and Cheyletiella mites
What cat breed has a genetic predisposition to dermatophytes?
What dogs breeds (2) have a genetic predisposition to dermatophytes? And what type?
- Yorkshire and Manchester terriers - Granulomatous dermatophytosis from T mentagrophytes - Yorkies are susceptible to severe forms of dermatophytosis a/c with M canis and T mentagrophytes
What dermatophytes (2) can mimic autoimmune skin disease such as PE or PF (symmetriacl nasal or facial folliculitis and furunculosis)?
T mentagrophytes M persicolar
What is 'sylvatic ringworm'?
Dermatophytosis acquired from wild mammals - more common in adults
What dermatophyte typically produce facial lesions, predominantly scaly or papulopustular and crusty + concurrent depigmentation of the nasal planum and nostrils may occur
Dermatophytic pseudomycetoma has been reported only in what cat breed?
What is a pseudomycetoma?
One or more SC nodules that are often ulcerated and discharging Nodules most commonly over dorsal trunk or tail base
Arthrospores in the environment are infectious for how many months?
Example of reverse zoonosis
Humans transmitting T rubrum (athlete's foot) to cats and dogs
Which dermatophytes (4) have positive a Woods lamp test? (yellow-green color)
M distortum, M canis, M audouinii, , T schoenleinii ("distorted cats")
What % of M canis fluoresce?
Name 2 dermatophytes that do not invade hairs
Epidermophyton floccosum (humans only)
visualized in scales - true epidermophytes
What samples should be taken if M persicolor is suspected?
Surface keratin as fungal hyphae does not invade hairs
What gene is for rapid and specific detection of dermatophytes?
Chitin synthase 1 gene (CHS1)
Dermatophytosis in healthy dogs and shorthaired cats often undergoes spontaneous remission within what time frame?
Which azole is the least effective in the treatment of dermatophytosis in dogs and cats?
Which Malassezia is non lipid dependant? (does not require lipid suppplementation during culture in vitro)
Where is M pachydermatis commonly found on normal cats and dogs?
Skin, ear canals, mucosal surfaces (oral, anal), anal sacs and vagina
List the 6 lipid-dependant species.
Malassezia furfur M globosa M sympodialis M obtusa M restricta M slooffiae
Name the 3 Malassezia spp that has been isolated from healthy cats
Malassezia sympodialis M globosa M furfur
What are the 7 types of strains (sequevars) of M pachydermatis
Ia through Ig
What is the predominant sequevar of M pachydermatis?
Type Ia - ubiquitous
What is the sequevar of M pachydermatis exclusively recovered from dogs?
What proteins on yeast cell walls are important for adherence to canine corneocytes?
Trypsin-sensitive proteins or glycoproteins
What is present on canine corneocytes that serve as ligands for adhesins expressed by M pachydermatis?
Mannosyl-bearing carbohydrate residues
Name the virulence factors expressed by M pachydermatis
Various proteases, lipases, phopholipases, lipoxygenases, phosphatases, glucosidase, galactosidase, leucine arylamidase, urease, zymosan
What processes (5) contribute to the pathogenesis, inflammation and pruritus of Malassezia dermatitis?
Proteolysis, lipolysis, alteration of local pH, eicosanoid release, complement activation
Dogs with Malassezia dermatitis have elevated serum concentrations of what Ig compared to heathy dogs?
IgA and IgG (but they do not appear to be protective against infection)
Histologically, Malassezia dermatitis is often characterized by what?
Prominent exocytosis of lymphocytes (CD3+) Subepithelial accumulation of mast cells (suggest a hypersensitivity reaction)
Malassezia growth is optimal at what pH level?
Widespread Malassezia dermatitis in cats has been associated with what concurrent diseases? (3)
- FIV infection - thymoma - pancreatic adenocarcinoma
What skin disease in Westies is postulated to be a reaction to severe infections with Malassezia?
Numbers of cutaneous M pachydermatis are significantly greater in what body locations of atopic dogs then normal dogs?
Groin, interdigital spaces, ear canals, directly under the tail base
What breed of cat may be predisposed to paronychia associated with M pachydermatis?
Which Malassezia has a more rounded bullous shape and a narrowed-based monopolar budding. And smaller than M pachydermatis?
What is the majority of intraepithelial and dermal lymphocytes in dogs with Malassezia dermatitis?
CD3+ T cells
Will lipid-dependant Malassezia sp grow well on Sabouraud dextrose agar?
What agar/medium are preferred to isolate Malassezia from cats (mainly lipid dependant)?
Modified Dixon agar and Leeming medium
What is chromomycosis?
Subcutaneous and systemic diseases caused by fungi that develop in the host tissue in the form of dark-walled (pigmented, dematiaceous) fungal elements
Chromomycosis can be separate into what 2 forms?
Phaemohyphomycosis and chromoblastomycosis
What is phaemohyphomycosis?
Organism appears as septate hyphae and yeastlike cells
What is chromoblastomycosis?
Fungus present as large rounded, dark-walled cells (sclerotic bodies, chromo bodies, Medlar bodies)
Oomycosis include what spp?
Pythium and Lagenidium
What is mycetoma?
Unique infection Organism is present in tissues within granules or grains associated with tumefaction and draining sinuses
Mycetoma can be eumycotic or actinomycotic. What does that mean?
Actinomycetales order: Actinomyces and Nocardia which are bacteria Eumycotic mycetomas: caused by dematiaceous fungi (black-grained mycetoma) or nonpigmented fungi (white-grained mycetoma)
What is sporotrichosis caused by?
Sporothrix schenckii - a ubiquitous dimorphic fungus, saprophyte in soil
In the environment, Sporothrix exists in what form?
Mycelial form growing on living and decaying plant material
When does Sporothrix convert to its yeast form?
After inoculation into tissues such as puncture wounds by thorns/splinters
What is the characteristic of the cutaneolymphatic form of sporotrichosis?
Nodule on the distal aspect of one limb, with subsequent ascending infection via the lymphatics
How do cats most often acquire sporotrichosis?
Contaminated claws and teeth from another cat (cat fight), especially intact male cats that roam outdoors
What is the most common form of sporotrichosis in humans?
Cutaneolymphatic Most lesions are on extremity or face
Is sporotrichosis zoonotic?
Yes, especially from infected cats
Pleomorphic yeast, round, oval or cigar-shaped
What stains sporothrix?
PAS or Gomori methamine silver (GMS)
True/False. S schenckii grows on Sabouraud dextrose agar at 30 C
What test is useful for diagnosis of sporotrichosis in dogs, especially when cultures are negative
A fluorescent antibody test -Sporothrix antigen-specific direct FA test
PCR testing for sporotrichosis is used to detect what in infected tissues of cats?
Chitin synthase 1 gene in extracted DNA
What treatment is contraindicated in dogs and cats with sporotrichosis?
Glucocorticoids and other immunosuppressive drugs
Local hyperthermia as an adjuvant treatment may be beneficial in what fungal disease?
Sporothrix, because it is temperature sensitive
What is the traditional treatment for sporotrichosis?
Oral administration of a supersaturated solution of potassium iodide
Signs of iodise toxicity?
Ocular and nasal discharge, dry hair coat with excessive scaling, vomiting, depression and collapse. Cats are more sensitive to toxic side effects of iodides
What is the treatment choice of sporotrichosis in cats?
What is the prognosis of cure for sporotrichosis in cats?
What are some unpigmented fungi that cause white-grain mycetomas?
Acremonium and Pseudoallescheria
What is the most commonly reported fungus causing eumycotic mycetoma in the US?
What are the 3 cardinal features of eumycotic mycetoma (maduromycosis)?
- tumefaction - draining tracts - grains (granules) in the discharge
What is the treatment of choice for eumycotic mycetomas?
Surgical excision, as they are often solitary on the limbs of face Medical treatment is often unsuccessful
What are the characteristics of chromomycosis (phaeohyphomycosis and chromoblastomycosis)?
Forming pigmented (diatomaceous) hyphal elements (NOT grains) in tissues, the pigment is MELANIN (virulence factor)
What stains melanin?
What is the most common cause of disseminated pheohyphomycosis in humans?
Clinical features of cutaneous pheohyphomycosis in dogs?
Single or multifocal poorly circumscribed nodules that may ulcerate or develop draining tracts (GSDs may be predisposed)
What are Medlar bodies (“copper pennies”)?
Round to oval pigmented yeast forms in chromomycosis
Hyalohyphomycosis are opportunistic infections by pigmented or non pigmented fungi?
Common sites of inoculation of hylahyphomycosis
Clawbeds, skin, eyes (cornea) and joints
True/False Zygomycetes are a class of fungi that are ubiquitous saprophytes of soil and decaying vegetation and known to be a component of normal skin and haircoat flora
What is this?
Hyphae are often surrounded by eosinophilic "sleeves" (Splendore-Hoeppli phenomenon)
Portal of entry of Zygomycosis may be?
GI, respiratory or cutaneous via wound contamination
Zygomycetes fungal elements stain well with what?
GMS, variably with PAS
Pythium spp rely on what for their normal life cycle?
Aquatic plants and other organic substances
Name differences between fungi and pythiosis (2)
- pythium produce motile flagellate zoospores - cell walls that contains cellulose and β-glucan with no chitin and littler ergoesterol
What fungi can cause skin lesions and fatal GI disease?
Has there been a GI form of pythiosis reported?
Yes, in California
What species of pythiosis is isolated from dogs, cats, humans and horses?
Skin lesions may contain "kunkers". What fungal disease is this?
What are "kunkers"?
Yellowish gritty coral-like bodies composed of Pythium spp hyphae surrounded by necrotic tissue and inflammatory cells
True/False It is common for dogs to have both cutaneous and GI pythiosis
What can you see in gastrointestinal pythiosis?
Weight loss, V/D, haematochezia. Severe segmental transmural thickening of the stomach, small intestines, colon +/- rectum
Where are hyphal elements most common and most numerous?
Within foci of necrosis
What is the treatment of choice for pythiosis?
Wide surgical excision
Which antifungal may be more effective for pythiosis?
Caspofungin - potent inhibitor of β-glucan synthase ( Pythium spp do not share cel wall characteristics with true fungi, thus keto etc is disappointing)
Majority of species in the genus Lagenidium are parasites infection what?
Algae, fungi, shrubcs, nematodes, crustaceans, insect larvae
True/False Systemic disease is commonly present in Lagenidiosis
True PG vasculitis and infection of the great vessels (e.g vena cava), LNs, lung etc
What tests can be used to differentiate between Lagenidium and Pythium?
PCR amplification of DNA from cultures isolates of tissue samples
Blastomycosis is caused by what fungi?
Blastomyces dermatitidis Dimorphic saprophyte fungus
What controls the change of blastomycosis fungus from a mycelial to yeast phase?
The gene bys-1
What is characteristic of Blastomyces dermatitidis organisms?
Broad-based budding and thick, refractile, double-contoured cell walls
Growth of blastomyces require what?
Moist, acidic soil rich in organic material
What is the ideal location for Blastomyces?
What is Gilchrist or Chicago disease?
Blastomycosis - disease of N America
How is blastomycosis usually acquired?
Inhalation of spores from mycelial growth in the environment Spores settle in airways and transform into yeast and primary infection in the lungs
What are the important virulence factors in blastomycosis that function in adherence of the yeast to host cells and suppress inflammatory responses?
BAD1 and WI-1 antigens
Majority (85%) of dogs with blastomycosis have what lesions?
What % of dogs with blastomycosis develop skin lesions?
What are the preferred skin sites in dogs with blastomycosis?
Nasal planum, face, clawbeds
4 lesion locations of blastomycosis in dogs
What cat breed may be predisposed to blastomycosis?
What special stains are used for blastomycosis?
PAS, GMS or Gridley fungal stain
What is most sensitive for dogs with pulmonary blastomycosis?
BALF (bronchioalveolar fluid)
What is the most sensitive for animals with disseminated blastomycosis disease?
Urine (detection of Blastomyces dermatitidis antigens)
What is the drug of choice for blastomycosis in dogs?
Dogs with what fungal disease appear to have a tenfold increased risk compared with humans and can serve as sentinels in humans?
What is Valley Fever/San Joaquin Valley fever?
What is the ecologic niche of coccidiomycosis?
Sandy alkaline soils, high temp, low rainfall, low elevation
What areas has coccidioides been isolated from?
Rodent burrows in desert-like areas
Name the 2 coccidioides
Coccidioides immitis and Coccidioides posadasii
Which coccidioides is found in the San Joaquin Valley of California?
What is the major route of infection of coccidiomycosis?
Inhalation Arthroconidia enter bronchioles and alveoli
What are spherules in coccidiomycosis?
Large, wound, thick-walled spherial cells filled with endospores in the lungs
Other than skin disease, what other clinical signs are usually seen with coccidiomycosis?
Coughing, dyspnea, persistent/fluctuating fever, anorexia, weight loss, lameness, ocular disease
What is the most common systemic mycosis in cats?
Cryptococcosis causes disease in what species?
Cats, people, dogs, ferrets, horses, goats, sheep, cattle, dolphins, birds, koalas and other marsupials
What are the 2 most common Cryptococcus species?
C neoformans and C gattii
Based on molecules studies, what are the 3 subtypes of cryptococcus?
C neoformans var neoformans (serotype D), C neoformans var gattii (serotypes B and C) and C neoformans var grubii (serotype A)
Which cryoptococcus sp infect immunocompetent hosts?
Which cryoptococcus sp infect immunosuppressed hosts?
Where is C neoformans found?
Droppings, filth and debris of pigeon roosts
What promotes the growth of cryptococcal organisms?
Nitrogen-rich alkaline environment (pigeon guano)
What is implicated as the environmental niche for C gattii?
Eucalyptus trees Koala bears may serve as sentinel host
Name some virulence factors of Cryptococcosis
Polysaccharide capsule, melanin, mannitol, lactase, phenol oxidase and other enzymes
How is melanin a virulence factor of cryptococcus?
Melanin protects the fungal cells from toxic hydroxyl radicals and oxidative stress
What makes up the polysaccharide capsule in cryptooccus?And the genes?
Gluconoxylomannan; 2 capsular genes - CAD59 and CAP64
What is the primary route of crypotococcal infection?
Inhalation - occ localized lesions from penetrating wound in cats
What is the most common manifestation of cryptococcosis in people?
True/False Cryptococcal skin lesions are generally a marker of disseminated disease
What stains cryptococcus for cytologic diagnosis?
India ink stain Diff-Quick, Gram stain, new methylene blue
What stains the cryptococcus capsule? And what color?
Mayer mucicarmine stains capsule (carminophilic) red
What is a highly specific and sensitive test for cryptococcosis?
Latex agglutination test detecting crypto capsular antigens in serum or CSF
What is the drug of choice for tx of less severely affected crypto animals?
Azoles - itraconazole
Histoplasma capsulatum prefers what environment/conditions?
Warm, moist, humid conditions, nitrogen-rich organic matter (bird and bat excrement, decaying wood)
What are the 2 varieties of Histoplasmosis?
Histoplasma capsulatum var capsulatum Histoplasma capsulatum var duboisii
What is the route of exposure to Histoplasmosis?
Inhalation of infective microconidia
How is histoplasmosis disseminated?
From the lungs, microconidia convert to yeast phase, which are engulfed by phagolysosomes within macrophages and may be disseminated via lymphatic and blood vessels to organs
What is the most common clinical manifestation of histoplasmosis?
Large-bowel diarrhoea with tenesmus, mucus and hematochezia
Rectal scrapings are a good source of tissue to evaluate for the presence of what organism?
Histoplasma - small round yeast bodies with basophilic center and lighter halo
Name 2 Candida spp that are isolated from ears, nose, oral cavity and anus of normal dogs
Candida albicans and C parapsilosis
What are the virulence factors of Candida?
Acid proteinases and keratinases that degrade stratum corneum and phospholipases that facilitate penetration of tissues
What are the predilection sites for Candidiasis?
Mucous membranes, MCJ, areas of moisture
Candida spp show narrow/broad based and multilateral budding
What is Piedra?
Asymptomatic fungal infection of the extrafollicular portion of the hair shaft caused by Piedraia hortae and Trichosporon beigelii
Match: Black or white piedra Piedraia hortae and Trichosporon beigelii
Piedraia hortae - black Trichosporon beigelii - white
Match: Black/white piedra Temperate climite / tropics
Black piedra - tropics White piedra - temperate climate of S American, Europe, Asia, Japan, SE USA
What is rhinosporidiosis?
Chronic granulomatous disease caused by Rhinosporidium seeberi
What is a sporangia in rhinosporidiosis?
Large spherical bodies that developed in tissues from small round spores
What is the predisposing factor in rhinosporidiosis?
How is rhinosporidiosis infection acquired?
Mucosal contact with stagnant water or dust
What clinical signs are found in dogs with rhinosporidiosis?
Wheezing, sneezing, unilateral seropurulent nasal discharge, epistaxis
What fungi? Single or multiple nasal polyps varying in size, covered with numerous pinpoint white foci
Rhodotorula dermatitis has been reported in what species?
1 cat with FeLV and FIV
What is the most common species encountered in nasal aspergillosis?
What breed is predisposed to disseminated aspergillosis?
Where is Alternaria spp found?
Ubiquitous saprophytic fungi in soil and organic debris. Common flora of canine and feline intergument
True/False Trichosporum spp cause cutaneous disease only
False Cutaneous and systemic disease
Trichosporon beigelii causes what?
White piedra in people, monkeys and horses
How is trichosporonosis diagnosed?
Histopath confirmation of fungal organism in tissue and a host response to the organism
Where is Prototheca spp found?
Soil, raw and treated sewage, swimming pools etc
Where is the portal of entry in disseminated protothecosis?
Match Prototheca wickerhamii Prototheca zopfii Cutaneous and disseminated infection
Prototheca wickerhamii - cutaneous in dogs and cats Prototheca zopfii - disseminated infection in dogs
What is the most common clinical sign of protothecosis?
Bloody diarrhoea, intermittent
Which dog breed appears to be predisposed to protothecosis?
67% of protothecosis have what involvement?
Ocular Leukokoria from vitreous clouding
What is the characteristic morphological form of Prototheca?
Morula - Internal septation of spherules into multiple endospores( wheel-like daisy like appearance)
What skin locations are affected by prototheca?
Pressure points, MCJs (esp nostrils), scrotum and footpads