Fungal Skin Diseases Flashcards
1
Q
A fungus in the sexual state is termed a ____ and in the asexual state is termed an _____.
A
teleomorph
anamorph
2
Q
Define hyphae
A
Hyphae are cylindrical, thread-like structures that grow at the tips and can either branch or
fork. They can also fuse, which is referred to as hyphal fusion or anastomosis.
3
Q
Define mycelium
A
Micelium are an interconnected network of hyphae that develops as hyphae grow. They can be septate or coenocytic
4
Q
Define conidida
A
Conidia are responsible for asexual reproduction and are nonmotile spores generated by mitosis and can come in many shapes and sizes
5
Q
What are two major physiological barriers to fungal growth?
A
Temperature
- The optimal growth range for fungi is considerably lower than body temp.
• Oxidation-reduction potential
6
Q
What are the different species classifications of dermatophytes?
A
• Zoophilic dermatophytes
- Microsporum canis, M. equinum, and T. equinum are adapted to living on animals, rarely found in the soil, and will occasionally infect humans.
- Sylvatic dermatophytes
• T. mentagrophytes, M. persicolor are zoophilic dermatophytes adapted to living on rodents or hedgehogs.
• Anthropophilic dermatophyte
- Epidermophyton, T. tonsurans, T. rubrum - adapted to humans, rarely infects animals as a reverse zoonosis.
• Geophilic dermatophyte
- Microsporum gypseum occurs in the soil as saprophytes, but under favorable conditions, can infect humans and animals if skin or immune system is compromised.
7
Q
Define arthrospores
A
- typical infective portion. Form by segmentation and fragmentation of fungal hyphae.
8
Q
Fungal Proteolytic Acantholytic Dermatoses
A
Pathogenic dermatophytes secrete numerous endo- and exoproteases that belong to several families such as subtilisins, fungalysin metalloproteases, dipeptylpeptidases and amino or carboxypeptidases. Trichophyton enzymes have been shown to induce acantholysis when added in vitro to human skin explants. Superficial acantholytic pustular Trichophyton dermatophytosis has been reported in two horses and four dogs.
9
Q
Superficial Pustular Dermatophytosis in Dogs and Horses
A
- Trichophyton spp. invade primarily the stratum corneum of the epidermis and/or follicular infundibula, and they can recruit neutrophils that will later accumulate in a subcorneal location.
- The histopathological findings of this fungal dermatosis also resemble those of PF with subcorneal pustular neutrophil-predominant pustules containing acantholytic keratinocytes.
- Lymphocyte-rich interface dermatitis may be seen also in dogs with this disease
- dermatophytes might not be detected with conventional hematoxylin-eosin - special stains (e.g. periodic acid Schiff [PAS] or Gomori’s methenamine silver [GMS]) and serial sections of the sample are needed to visualize the organisms in the stratum corneum.
- Hair invasion by dermatophytes, if present, is minimal.
10
Q
What do the walls of fungi consist of?
A
chitin, chitosan, glucan, mannan.
11
Q
What is a single vegetative filament of fungus?
A
hypha or hyphae (numerous)
12
Q
Hyphae are septate if they have visions between cells, or sparsely seepage is they have many nuclei in the cell. The latter is known as what?
A
Coenocytic
13
Q
What is the term should ben used only for an asexual propagule or unit that give rise to genetically identical organisms.
A
conidium
a conidiophore is a simple or branched mycelium bearing conidia or conidiogenous cells.
14
Q
What is a fungal cell that fives rise to conidium?
A
Conidiogenous cell
15
Q
The asexual state of fungal is called the ____ and the sexual state is known that the ___ state.
A
anamorph
telomorph
Dermatophytes are primary found in the anamorphic states.
16
Q
What are the features that distinguish oomycetes from fungi?
A
- Their cell wall are composed primarily from B 1,3 - glucan polymers and cellulose with very little chitin ( in contrast for fungal cell walls which contain large amount of chitin and ergosterol)
- Utilization of mycolaminarin (a b - 1,3-glucan) for energy storage
- Diploidy at the vegetative state
- Complex life cycle involving sexual and asexual reproduction
- Asexual reproduction involve formation of sporangium that produces motile zoospores bearing two flagella. zoospores adhere to the surface of plants or animals, germinate, and then penetrate into tissues of the host.
17
Q
What are the most common species of saprophytic molds found on dogs?
A
Alternaria, Aspergillus, Auerobasidium, Chrysosporium, Cladosporium, Mucor, Penicillium and Rhizopus.
18
Q
What are the most common species of saprophytic molds found on cats?
A
Alternaria, Aspergillus, Chrysosporium, Cladosporium, Mucor, Penicullium, Rhodotorula and Scopulariopsis,
19
Q
Cats infected with what disease(s) ahem a greater diversity of guns isolated from their skin and mucosal surfaces?
A
FeLV/and/or FIV
20
Q
What two anti fungal treatments are polyene antifungals that bind with ergosterol in fungal cell membranes, resulting in altered cell permeability and death. It is NOT effective against dermatophytes.
A
Nystatin and amphotericin B 3%
21
Q
What class of antifungals inhibits synthesis of ergosterol, triglycerides, phospholipid, chitin and oxidative and peroxidative enzymes.
A
Azoles
22
Q
What two anti-fungal treatments are considered allyamines that bind to stratum corneum and penetrate the hair follicles. They inhibit ergosterol biosynthesis and squalene epoxidase for treatment of Candida and Dermatophytes.
A
Naftine Cream and terbinafine
**Naftin cream has some antiinflammatory effects
23
Q
What is the MOA of Griseofulvin?
A
Fungistatic, binds to keratin and inhibits cell wall synthesis, nucleic acid synthesis and cell mitosis by arresting division at metaphase, interfering with the function of spindle microtubules, morphogenic changes in fungal cells and possible antagonizing chitin synthesis in the fungafcell wall. This agent is primarily active against growing cells, although dormant cells may be inhibited from reproducing.
- *Fermentation product of Penicillium
- Can not use in cats with FIV/FeLV
24
Q
What are the two forms of Griseofulvin and which is 2-4 times more bioavailable?
A
Micronized crystal is 2-4 times more bioavailable than the ultramicrobized Gris-PEG.
**Effective ONLY against dermatophytes and is teratogenic
25
After oral administration, Griseofulvin may be detected in the stratum corneum within 8 hour to 3 days. The high-test concentrations are attains in the ____ and lowest in the ____ layers.
Highest in the SC and lowest in the SB
The drug is carried to the stratum corneum by diffusion, sweating and TEWL and is deposited in keratin precursors cells and remains bound during the differentiation process.
26
What are the anti-inflammatory effects of Griseofulvin?
Supresses delayed-type hypersensitivity reactions and irritant reactions in the skin.
27
Systemically administered azaleas include imidazole and triazoles. They inhibit the cytochrome P450 enzyme ______, thereby inhibiting conversion of ____ to _____ and causing accumulation of C14 methylated steroids.
Lanosterol 14-Demethylase
Lanosterol to ergosterol sterol (found in cell membranes of fungi)
Other actions include an inhibition of intracellular triglyceride and phospholipid biosynthesis, inhibition of cell wall chitin synthesis and inhibition of oxidative and peroxidative enzymes.
28
The potency of each azole is related to its affinity for binding to the _______ moiety.
cytochrome P450
29
What are the common drug interactions of the azoles?
Interactions with azoles are well recognized - antihistamines (terfenadine, asstemizole), GI motility agents (cisapride), benzdiazapines, calcium channel blockers, anticonvulsants, antimycobacterial agents and CSA.
30
Ketoconazole inhibits ____ thereby blocking conversion of deoxycorticosterone to corticosterone.
11-hydroxylase
It also interacts with membrane phospholipids and inhibits yeast transformation to mycelial forms. Additional antifungal actions involve inhibition of purine uptake and impairment of triglyceride and/or phospholipid biosynthesis.
At higher concentrations, it may have a direct physiochemical effect on the fungal cell membrane = fungicidal action.
31
What are some of the contraindications for using ketoconazole?
Not as effective for aspergillosis and sporotrichosis
Avoid use with mitotane, rifampin, and theophylline.
Alters metabolism of diphenylhydantoin, rifampin, barbiturates and CSA.
Absorption is decreased if given with H2 blockers, antacids or PPI.
32
What effect can ketoconazole have on coat?
reversible lightening of coat
33
What are the anti-inflammatory effects of ketoconazole?
Supression of neutrophil chemotaxis and lymphocyte blastogenic response, inhibition of 5-lipooxygenase activity and inhibition of leukotriene production.
34
What is the MOA of itraconazole?
Inhibits cytochrome P450 14a demethylase, preventing ergosterol synthesis in fungal cell membranes; binds wearing to mammalian P450.
~ Bioavailability is only 40% with fasting; increases when give with food. Oral suspension is 70%.
Highly protein bound and concentrates in the lipophilic tissues of keratin.
Secrete in sebum
Increased potency, wider range of action and decreased toxicity compared to ketoconazole.
35
What are the contraindication of itraconazole?
Do not administer concurrently with cisapride, terfenadine = fatal cardiac arrhythmia. It can lead to vasculitis at higher doses.
Prolong effects and increased toxicity of midazolam, CSA, GC, AH, quinidine, dioxin, vincristine, warfarin, sulfonyureas,. Concurrent antacids, H2 blockers and anticholinergics are contraindicated.
36
Because itraconazole is more specific for fungal than mammalian cytochrome P450 enzymes - it does not interfere with ______ synthesis.
sterol
37
What drug is considered a bis-triazole?
Fluconazole
Inhibits sterol and CP450 synthesis. It has a higher affinity fo fungal enzyme than KCZ or ITZ.
GI absorption is not affected by food or gastric pH.
Penetrates well into CNS and ocular tissue.
38
What are the contraindication with FCZ?
Reduce dose in renal insufficiency; avoid use in pregnant animals.
Cimetidine may interfere with absorption.
FCS potentiates activity of anticoagulants, thiazide diuretics, rifampin, CSA, glipizide, antihistamines, diphenyldantoin and theophylline.
39
Terbinafine inhibits ergosterol biosynthesis and squalene epoxidase, resulting in fungal cell wall ergosterol deficiency and intracellular accusation of what?
Squalene
40
What is Terbinafine MOA?
It is fungicidal (most dermatophytes, Asper and Sporothrix) and fungistatic - less effective against yeast.
Because it is generally not inhibitory to CP450 systems, it is more selective than azoles.
41
Drug delivery of Terbinafine is primarily via _____
Sebum
42
What are the contraindications for terbinafine?
Reduce dosage with renal and/or hepatic insufficiency. May be used in pregnancy. Few drug interactions (cimetidine increased blood contractions where as rifampin decreases it).
43
For terbinafine, what drug increases blood concentrations and which drug decreases blood concentrations?
Cimetidine increases blood concentrations.
| Rifampin decreases blood concentration.
44
What anti-fungal is classified as a fluorinated pyrimidine?
Flucytosine
45
Fungal cell walls are susceptible to Flucyosine if they contain what enzyme? This enables 5-fluorocytosine to be taken into the fungal cell, where it is deaminated by cytosine deaminase to 5-fluoro-21-deoxyuridylic acid.
Cytosine permease
46
What are the indications for using flucytosine?
Used in combination with amphotericin B for Candida, Cryptococcus, Aspergillus and phaeohypomecosis. Not effective against dermatophytes.
47
What drug is a polyene anti fungal and originally isolate from a soil sample containing Streptomycin nodosus?
Amphotericin B
It is a fungistatic polyene antibiotic that disrupts fungal and bacterial cell membranes by irreversible binding with ergosterol. This results in altered cell permeability, leakage of intracellular constiuetnts and cell death.
It also binds to cholesterol in mammalian cell membranes and is relatively toxic.
It is administered IV and completed with lipids. It is taken up by macrophages that carry the drug to sites of fungal-induced inflammation.
Not effective against Dermatophytes
Do not use in renal or hepatic failure.
48
Amphotericin B stimulates lymphocytes, macrophage and neutrophil function and induces production of what inflammatory mediator?
TNFa
49
Which form of amphotericin b is used in dogs for systemic mycosis and leishmaniasis?
L-AMB and ABD (can use in cats too)
50
Amphotericin B is nephrotoxic due to what mechanism?
Amb increases intracellular Ca in vascular smooth muscle cells and stimulates eicosanoid synthesis, resulting in reduced renal blood flow. May also cause hypokalemia, weight loss and nonregenerative anemia.
51
What inorganic halogen is highly effective in the treatment of cutaneous sporotrichosis?
Iodides
52
What drug is a Benzoylphenyl urea, an insect growth regulatory that acts by inhibiting chitin synthesis, polymerization and depostion?
Lufenuron - inhibitor of chitin synthesis and cell wall synthesis
53
What is a cyclic hexapeptide that inhibits 1,3 - B-D-glycansynthase, thereby blocking cell wall synthesis in fungi.
Caspofungin - Echinocandin Class
54
What inflammatory mediatory has been shown to enhance activity of phagocytes abasing fungi, both in vitro and in rats?
IFN-y
55
Which species of microsporum is a natural resident and occasional pathogen of mice and voles?
Microsporum persicolor
56
Hair shafts containing infectious M. canis arthrospores can remain infectious int he environment for up to how many months?
18 months
57
When an animal is exposed to a dermatophyte, an infection may be established. The typical infective portion of the organisms is the ______.
Arthrospore
Arthrospores are formed by segmentation and fragmentation of fungal hyphae and may be carries by dust particles, air currents, fomites and ectoparasites include fleas.
Arhtrospores adhere strongly to keratin and can germinate within 6 hours after contact with the skin.
58
What is the difference between endothix and ectotrix?
Hair is invaded in both ectothrix and endothrix infections. Ectothrix fungi produce masses of arthrospores on the surface of hair shafts, whereas endothrixs do not.
59
Hyphae penetrate the hair cuticle and growth within the hair shaft until what keratogenous zone is reached?
Adamson fringe
60
How does spontaneous resolution of dermatophytosis occur?
Spontaneous resolution occurs when infected hairs enter the telogen phase or if an inflammatory reaction is incited. when hair enters telogen, keratin production slows and stops; because the dermatophyte required actively growing hairs for survival, fungal froth also slow and stops. Infectious arthrospores may remain on the hair shaft, but reinfection off that particular hair follicle doe snot occur until it reenters anagen.
61
What two species of dermatophytes produce tannins that diminish cell mediated immune response and indirectly inhibit stratum corneum turnover?
T. rubrum and T. metagrophytes
62
M. canis has been shown to possess multiple enzymatic properties, which can vary according to the strain of fungus. What is the keratinase produced by M. canis leading to more inflammation and pruritus?
u-chymotrypsin-type serine proteinase
63
What breeds may have a genetic breed predisposition to developing dermatophytosis?
Persians
Yorkie and Manchester terries have a predisposition to devilment of T. Mentagrophytes
64
Severe dermatophytosis and dermatophytic pseudomycetoma with marked lymph node involvement have been reported in Yorkies in association with what two species of dermatophytes?
M. canis
| T. Metagrophytes
65
What two species of dermatophytes do not invade hairs and are visualized in scales?
M. persicolor and Epidermophyton floccosum
66
Using PCR, detection of what gene appears to be rapid and specific for dermatophytes?
chitin synthase 1 gene
67
It is recommended that therapy be continued until ____ successive fungal cultures performed at weekly intervals by brush technique are negative.
three
68
According to the text book, there ar show many lipid-dependent species of Malassezia
Textbook - six lipid dependent.
***Currently, the genus Malassezia includes 16 species, of which 15 are lipid-dependent and are most frequently recovered from humans, ruminants and horses (Malassezia furfur, M. globosa, M. obtusa, M. restricta, M.slooffiae, M. sympodialis, M. dermatis, M. nana, M. japonica,M. yamatoensis, M. equina, M. caprae and M.cuniculi, M. brasiliensis, M. psittaci).
The only non-lipid-dependent species, M.pachydermatis is commonly recovered from cats and dogs.
69
Malassezia belong to the ______ yeasts. They are characterized by a multilayered cell wall and reproduce by _______ budding
basidiomycetous
| unilateral
70
In general what is important for adherence of M. Pachydermatis to corneocytes? What is the ligand on canine corneoctytes?
Trypsin sensitive proteins and glycoproteins on yeast cell walls
mannosyl-bearing carbohydrate residues on canine coenocytes serve as ligands for adhesions.
71
How many different Malassezia protein antigens have been identified by Western blotting?
14
72
Dogs with Malassezia have elevated serum concentrations of _________; compared to healthy dogs; however, these do not appear to be protective against infection.
immunoglobulin A and G
73
Basset hounds have an increased or decreased lymphocyte response to Malassezia compared to healthy dogs?
decreased
**Suggesting cell-mediated immunity may be more important that humoral responses in protecting from disease.
In this study, healthy basset hounds experiences significantly greater in vitro lymphocyte blastogenic response to M pachermatis antigen than basset hour with Malassezia dermatitis.
74
Histologically, how is Malassezia dermatitis characterized?
Characterized by prominent exocytosis of lymphocytes (CD-3 positive) and a sub-epithelial accumulation of mast cells, which suggest a hypersensitivity reaction.
75
Widespread Malassezia dermatitis in cats has been associated with which concurrent diseases?
FIV infections, thymoma, and pancreatic adenocarcinoma.
76
Genetic predisposition would appear to be important in which breeds?
WHWT, basset hound, Cocker spaniel, Shih Tzu, English setter, poodles, boxer, CKCS, Australian and silky terriers, GSD, and dachshund.
77
Over what percentage of dogs have concurrent dermatoses, especially allergies, keratinization defects, endocrinopathies and bacterial pyodermas?
70%
40% have concurrent staph pyoderma (of the 70%)
78
What breed of cat may be predisposed to paronychia associated with M. pachydermatis?
Devon rex
This breed has also been reported to develop greasy seborrheic dermatitis and otitis (M. sympodialis)
79
M. pachydermatis is unique in that it grows well in _____ without lipid supplementation, however lipid dependent Malassezia species will not grow on this agar. Due to the presence of lipid-dependent yeasts on the skin of cats, the use of lipid-supplemented media, especially the modified Dixon’s medium or Leeming medium, is required.
Sabouraud dextrose
80
What two growth media support to growth of all species of Malassezia on cats?
Modified Dixon Agar
| Leeming medium support growth of all Malassezia species.
81
In subcutaneous mycoses, what is the term that has been used for subcutaneous and systemic disease causeed by fungi that develop in the host tissue int he form of dark-walled (pigmented, dematiaceous) fungal elements?
Chromomycosis
82
Chromomycosis can be separated into what two forms?
Phaehyphomycosis - the organism appears as septate hyper and yeast-like cells.
Chromoblastomycosis - the fungus is present as large rounded, dark walled cells (sclerotic bodies, chromo bodies, Medlar bodies)
83
What term has been proposed to encompass all opportunistic infections caused by nondematiaceous fungi, the basic tissue forms of these being hyaline hyphae elements that are septate, branched or unclenches and non pigmented in tissues?
Hyalohyphomycosis
Examples of these are Fusarium, Penicillium, Scedosporium, Geotrichum, and Paecilomycyes.
84
What does the term phycomycosis mean?
this term is used to describe organisms appearing in tissues as broad, sparsely septate hyphae surrounded by pyodranulomatous and eosinophilic inflammation.
Organisms that cause this type of reaction are the oomycetes and zygomycosis.
85
Describe Zygomycotic Organisms
These organisms are angiotropic, their invasion of blood vessels results in embolization and necrosis of the surrounding tissue.
Mucomycosis and entomophthoromycosis.
86
What is the name of a unique infection wherein the organisms is present in tissues within granules or grains associated with tumefaction and draining sinus?
Mycetoma - they can be eumycotic or actinomycetes.
Eumycotic - fungi
Acinomycotic - Actinomyces and Nocardia
87
Sporotrichosis is caused by what ubiquitous dimorphic fungus which exists as a saprophyte in the soil and organic debris?
Sporothrix schenckii
Lives as mycelial form in decaying material (rose bushes, moldy hay, straw)
Puncture wounds in dogs (hunting) and fights in cats; humans get it from cats and ants.
After inoculation, it converts into yeast form.
88
Describe Sporotrichosis in dogs
Usually occurs in hunting dogs and presents as multiple firm nodules, ulcerating plaques on head, pinnae and trunk.
Lesions are not painful; secondary nodules form along lymphatic vessels called 'cording'.
Treatment with supersaturated solution of potassium iodide.
For disseminated disease, treat with Amphotericin B and itraconazole.
89
Describe Sporotrichosis in Cats
Male intact cats
Lesions re common on the head, distal labs and tail base regions.
Affected areas ulcerate, drain a purulent exudate.
Most have necropsy evidence of LN involvement.
Treatment of choice is itraconazole
Guarded prognosis
90
How do you diagnose Sporotrichosis?
Pleomorphic yeast that is round, oval or cigar shaped, 5-9um long
Retractile cell wall - making it look like the organism has a capsule and gets confused with Cryptococcus neoformans.
Stain with PAS or GMS
Fluorescent AB test in dogs will help if culture is negative
PCR assays have been used to detect the chitin synthase 1 gene in DNA extracted from cats.
91
What are pyogranulomatous nodules that contain tissue grains or granules composed of dense colonies of organisms and necrotic debris?
Mycetoma
Surgical excision is treatment of choice
Most grow on Sabourad Agar
92
What organisms cause 'black grain' mycetomas?
Cladophialophora, Curvularia, Exophiala, Leptosphaeria, Madurella, Pyrenochaeta, Staphylotrichum, Torula.
***Curvularia geniculta is the common dark grain eumycotic mycetoma
93
What organisms cause 'white - unpigmented' mycetomas?
Acremonium and Pseudallescheria
94
What is the most commonly reported fungus causing eumycotic mycetoma in the US?
Pseudallescheria boydii - the asexual form is Scedosporium apiospermum.
**Most common unpigmented eumycotic mycetoma
95
What are the common characteristics of Chromomycosis?
Caused by saprophytic fungi found in carious soils and organic materials.
Infection occurs via wound contamination - especially splinters and bites.
Form pigmented hyphae elements (NOT grains) and stains with Masson Fontana.
Scedosporium prolificans is the most common cause of disseminated phaeohyphomycosis in humans.
96
Phaehyphomycosis (Chromomycosis) in dogs and cats - characteristic features
Rare in dogs - GSD are predisposed to infection.
| Rare in cats - The lesions may be blue-gray perhaps owing to the pigmented nature of the fungi.
97
Describe the diagnosis and treatment of Phaehyphomycosis (Chromomycosis)
Pigmented fungal hyphae may be visible on cytology
Numerous fungal elements are present as broad, irregular pigmented septate braches or unbranch with occasional chlamydoconidia and numerous oval pigmented yeast forms called medlar bodies 'copper pennies'.
Stain with Masson Fontana
Surgical excision followed by chemotherapy (preferred tx)
Terbinifine is effective in some human cases
98
Hyalohyphomycosis (adiaspiromycosis) are opportunist infection by ______ fungi that form hyphae elements in tissues.
non pigmented
Aspergillosis is not included in this classification
Most common organisms are acremonium (cephalosporin), Fusarium, Geotrichum, Paecilomyces, Penicillium and Pseudollscheria.
GSD are predisposed to these infections
99
Which hyalohyphomycosis (adiaspiromycosis) organism is a ubiquitous soil saprophyte and a minor component of the normal flora or the oral cavity, GI tract and skin?
Geotrichum candidum
100
Which hyalohyphomycosis (adiaspiromycosis) organism is a saprophytic yeast-like fungus that exists in nature and decaying material?
Paecilmyces spp.
101
What are the clinical features of hyalohyphomycosis (adiaspiromycosis)?
Common sites are the claw beds, skin, eyes and joints.
| Acremomium and Pseudoallescheria may also produce mycetoma (nodules that contain tissue grains)
102
What is the diagnosis and treatment of hyalohyphomycosis (adiaspiromycosis)?
Non-pigmented yeastlike cells ad septate hyphae may be found on cytology
Grow on Sabouraud dextrose agar
Biopsies will demonstrate the presence of non pigmented hyphae in the tissues
Few dogs survive - if localized then surgical excision.
103
What class of fungi is known component of normal skin and haricot flow. These organisms have been isolated from insects AND The feces of amphibians and reptiles.
Zygomycosis
The three orders are Mucorales, Mortierelles and Entomophthorales.
104
The are the clinical features of zygomycosis?
Rare in dogs and cats
Most common sign is fatal GI disease
Conidiobolus typically infects mucocutaneous sites and causes sinusitis.
Basidiobolus is usually found in the SQ on the trunk and rare invades blood vessels of disseminates.
Vascular invasion and hematagemous spread is more common in mucomycosis then in entomophthoromycosis.
105
What is diagnosis and treatment of Zygomycosis?
Cytology reveled numerous eosinophils surrounding poorly stained hyphae
GMS the hyphae appear broad, thin-walled and occasionally septate.
Fungal elements are usually at the center of necrosis
Stain well with GMS and variably with PAS
Potato flake agar containing ampicillin and streptomycin is an excellent culture media for this species
106
Potato flake agar containing ampicillin and streptomycin is an excellent culture media for what species?
Zygomycosis
107
What is an aquatic organisms that rely on aquatic plants and other organisms substances for their normal life cycle.
Pythiosis
They differ from fungi in producing motile flagellate zoospores and having cell walls that contain cellulose and B-glucan with NO chitin and a bit of ergosterol.
108
How do oomyctes differ from fungi?
They differ from fungi in producing motile flagellate zoospores and having cell walls that contain cellulose and B-glucan with NO chitin and a bit of ergosterol.
These motile zoospores show chemotaxis toward damaged plant or animal tissues and hairs. once close to heir host, the zoospores become sluggish, loose their flagella and become encysted on the tissue. The organisms then develop germ tubes in the direction of the affected tissue which facilitate hyphae penetration.
109
What is the species of Phythium isolated from dogs, cats and horses?
Pythium insiosum
110
What are the clinical features of Phythium in dogs and cats?
Dogs can be affected with either cutaneous or GI phthisis
Large-breed, male, young - GSD and Labs
Usually on leg, face or tailhead and are pruritic
Lesions may contain "knicker" which are yellowish gritty coral-like bodies = Pythium hyphae
Rare in cats
111
What are the diagnosis and treatment of Phythium in dogs and cats?
Cytology shows numerous eosinophils and few fungal elements
Stain great with GMS
Hyphae occasionally invade blood vessels (especially arteries)
Pythium antigen evident with indirect immunoperoxidase technique.
Blood agar or Sabourad Dextrose agar
Surgical excision + Itraconazole and Terbinfine post-op
ELISA serology should be performed every 2-3 months and before surgery
112
What is the clinical signs, diagnosis and treatment of Lagenidiosis?
The hyphae are larger than those of Pythium.
Young dogs in the Southeast are most commonly affected
GMS stain works great
The preferred medium for culture is peptone-yeast-glucse again containing ampicillin and streptomycin.
System disease is commonly present so imaging of chest and abdomen before surgery is required.
Follow surgery with itraconazole and terbinafine.
113
What is the preferred media for growing Lagenidiosis?
The preferred medium for culture is peptone-yeast-glucose agar containing ampicillin and streptomycin.
114
What is a dimorphic saprophytic fungus that is also known as Chicago disease?
Blastomyces dermatidis
Growth of the organisms in the environment requires moist, acidic soil rich in organic material.
Decaying wood and waste substrates (Beaver Dams) and heavy rain will release the infectious spores.
Infection is acquired by inhalation of spores from he mycelial growth in the environment and turn into yeast once established.
115
What gene controls the change of fungus from the mycelial form to the yeast form?
bys-1
116
What are the two antigens that are important virulence factors that function in adherence of the yeast to host cells and also act as immune modulators to suppress inflammatory responses?
BAD1 and WI-1
117
Blastomycosis in dogs and cats
Dogs have a 10 times increased risk of infection compared to humans.
Young intact male dogs of large and sporting breeds (especially Doberman Punchers, Labs, Coonhouns, pointers and Weimeraners are at an creased risk
Occurs commonly in the Fall
Dogs living within 400m of water have a 10x increased risk
A majority of dogs with Blasto have lung lesions (85%) and Skin lesions (20-50%)
Nasal planum and claw beds are preferred sites
Siamese cats are predisposed to Blastomycosis - rare otherwise
118
How do you diagnose Blastomycosis?
Cytology reveals round to oral yeastlike fungi (8-15 uM) with broad-based budding and have athick retractile double contoured cell wall.
Stai with PAS, GMS or Gridley fungal stain.
Not safe to culture
Urine Blastmyces Test (MiraVista) - most sensitive with disseminated disease (cross reaction with Histo, Crypto and Asper)
119
How do you treat Blastomycosis?
Itraconazole is drug of choice in dogs (or Fluconazole)
120
What is the cause and pathogenesis of Cocciomycosis?
Dimorphic saprophyhtic soil fungus
Sandy alkaline soils, high temps, dry and low elevation.
Southwestern US
Rainfall disrupts the soil and release arthroconidia - dispersed by wind.
Inhalation is route of infection
Arthroconidia enter bronchioles and alveoli - extend to peribronchiolar tissue. In the lungs, arthroconidia transition into giant spherules filled with endospores then spread hematogenously.
121
What are the two species of Cocciomycosis?
Coccidiodes immitis - San Joaquin Valley of California
Coccidiodes posadasii - is found in other areas including Arizona, Texas, New Mexico, Nevada, Utah and Canada.
122
Which two breeds are predisposed to developing disseminated infections?
Doberman Pinchers and Boxers
123
What are the clinical signs of Coccidiomycosis?
Young male dogs
Coughing, dyspnea, fever, skin lesions, ocular lesions
Skin lesions almost ALWAYS occur over bone (especially the distal aspects of long bones)
Rare in cats
124
How do you diagnose coccidiomycosis?
Fungal elements on cytology will be in the form of spherules or endospores; but may be difficult to find.
Don't culture it!
Immunodiffusion and ELISA can be helpful in monitoring response to treatment
You can treat with ketoconazole, fluconazole or itraconazole with good prognosis if there is no bone involvement.
125
What is the most common systemic mycosis in cats?
Cryptococcis
The most common causing disease is C. Neoformans and C gattii (Eucalyptus).
Yeastlike fungus that is associated with droppings, dilth and debris of pigeon roots and found worldwide. The nitrogen rich alkaline environment promotes growth of organisms.
They can survive up to 2 years!
126
How many types of servers for crytococcus are recognized and how are they differentiated?
Molecular studies have have redefined the variants into three subtypes: C. neoformans var grubii (A), C. neoformans var gatti (B and C), neoformans var neoformans (D)
*Difference in capsular polysaccharides.
127
What are the known virulence factors for cryptococcus?
polysaccharide capsule, melanin, mannitol, lactase, phenol oxidase and other enzymes.
Melanin protects the fungal cells from toxic hydroxyradials and oxudative stress.
The capsule is composed of glucuronoxylomannan; two capsular genes CAP59 and CAP64
128
What is the cryptococcus capsule composed of and what are the two genes identified?
The capsule is composed of glucuronoxylomannan; two capsular genes CAP59 and CAP64.
The capsule thickens following invasion of host.
129
What is the primary route of infection for crytococcus?
The primary route of infection is through to be via inhalation with an occasional cat developing localized lesions associated with a penetrating wound.
Most cases in dogs and cats begin with colonization of the nasal mucosa with later hematagenous spread to lymph nodes, skin and bones.
Meningitis is most common in humans.
130
What are the clinical signs and diagnosis of Crytococcus?
Young, large breed (GSD, Dobermann, Great Danes, Cockers)
Young adult cats (Siamese)
Clinical signs include rhino sinusitis, CNA and eyes; skin lesions are present in 20-40% of cases in dogs and cats = marker of generalized disease.
Yeastlike organisms with NARROW based budding, mutinous capsule with clear or refactile halo.
Biopsy shows a "soap bubble" appears due to vacuolation of dermis.
131
What stain is recommended for identifying cryptococcus organisms?
India ink stain has been recommended because the organisms do not take up stain and appear as silhouettes against a black background.
132
On biopsy of cryptococcus, what stain is used to effectively visualize the capsule?
Mayer mucicarmine is a useful special stain because it stains the organisms capsule red.
GMS, AS and Fontana will also work.
133
What test is used to identify Cryptococcal capsule antigens?
They can be detected in serum using a latex agglutination test.
This is highly sensitive and specific. Negative results can be seen with only cutaneous lesions in cats.
False positives can occur with cross-reaction to disinfectants and soap.
Titers can persist for yeast after diagnosis without clinical signs.
134
What media is recommended for culture Cryptococcus (especially in a nasal cavity due to secondary bacterial contamination)?
Birdseed agar containing antibiotics is recommended for sue when culturing site, such as the nasal cavity, where they may be heavy bacterial contamination.
It grows well o Sabouraud dextrose agar - growth is inhibited by cycloheximide.
135
What is the recommended treatment for Cryptococcus?
Amphotericin B is the most effective anti-cryptooccal agent and is it recommended to use in combination with flucytosine for cats with CNS disease.
The azoles are recommended for less severely affected cases.
Therapy should be continued until the antigen titer is 0; then recheck every 6 months for recurrence.
136
What is a dimorphic saprophytic soil fungus that prefers areas with warm, moist, humid conditions and soil containing nitrogen-rich organic matter (bird and bad excrement)?
Histoplasmosis
The two varieties are histoplasmosis capsulatum var. capsulatum and histoplasmosis capsulatum var. duboisii.
The telemoprh is Ajellomyces capsulatum
137
What is the pathogenesis of histoplasmosis?
The usual route of exposure is inhalation of infective microconidia. Once in the lungs, the microconidia convert to the yeast phase. Yeast are engulfed by phagolysosomes within macrophages and disseminated via lymphatic and blood vessels to organs that are rich in mononuclear phagocytes.
The occurrence of FI histoplasmosis without respiratory tract involvement suggests that ingestion may be another route of infections, but experimental studies using oral administration of spore have railed to price GI disease.
138
What are the common clinical signs in cats and dogs with histoplasmosis?
Young dogs - Weimeraners, Brittany Spaniels, pointers with large bowel diarrhea.
Young female cats - lesions are anywhere on body and characterized by papule, ulcers, draining tracts.
139
How do you diagnose histoplasmosis?
Cytology revealed very small (2-4um) round yeast with basophilic center and lighter halo caused y shrinkage of the yeast cell during staining.
Thoracic radiographs of dogs and cat with histoplasmosis show diffuse interstitial pattern.
Antigen detection assay that identified a polysaccharide antigen of H. capsulatum is a sensitive test for the diagnosis of acute pulmonary of disseminated histoplasmosis.
Ab detection 2-6 weeks after after infection can be helpful.
140
How do you treat histoplasmosis?
Drug of choice is itraconazole; combine with Amphotericin B for severe disseminating infections.
Fluconazole is not recommended because it is not effective as itraconaozle.
Monitor treatment for up to 2 years with antigen levels in urine and serum.
141
What pathogen is from the family of Cryptococcacae. The yeast phase is normal inhabitants of the alimentary, upper respiratory and genital mucosa of mammals. It can cause opportunistic infections of skin, mucosa , external ear and claws.
Candida spp.
Once in the body, Luther spread of infection correlates with cell mediated immunocompetence and neutrophil function.
Candida produced acid proteinases and keratinases and phopholipases to facilitate entry into tissue.
142
What are the clinical signs of Candida?
Candida has a predilection for mucous membranes, mucocutaneous junctions or areas in which moisture may persist and macerate the skin, such as the external ear canal and intertriginous regions.
Pruritus may be intense.
143
What is the cytological difference between Candida and Malassezia?
Candida show narrow based and multilateral budding.
Grows on Sabourad agar.
PCR, ELISA and latex agglutination tests are also available to detect in blood and urine.
144
How do you treat Candidia?
Excessive moisture must be avoided. For local lesions, clipping, drying and topical antigun agent are usually effective.
Ketoconazole or itraconazole are the drug of choice.
145
What disease is an asymptomatic fungal infection of the extrafollicular portion of the hair shaft?
Piedra
It is caused by Piedraia Horta (Black Piedra) and Trichosporon beigelii (white Piedra).
146
How is Piedra diagnosed and what is the treatment of choice?
Microscopic examination of affected hairs shows nodules on and encircling the hair shafts. These nodules may result in breaking the hair shaft.
Examination also revealed extrapilar and intrapilar hyphae arranged perpendicularly to the hair shaft.
Shave hairs off and/or treat with terbinafine.
147
What is the most common agent involved in Aspergillus infections?
Aspergillus fumigatus
Only been reported in dogs - common in GSD
Treatment with Amphotericin B and itraconazole are recommended.
For Nasal Aspergillosis, the most successful therapeutic regiment is enilconazole administered topically through tubes implanted in the nasal chamber.
148
What is a saprophytic chlorophyllous algae that is found in soil, raw and treated sewage, the slime flux of trees, swimming pools and stagnant water?
Protothecosis
The portal of entry appears to be the colon in disseminated infections and wound contamination in cutaneous lesions.
149
What is the Prototheca organism culture from cutaneous lesions vs. disseminated disease?
Prototheca Wickerhamii is isolated from cutaneous infections
| Prototheca zopfii is alway isolated from disseminated infections in dogs.
150
What breed of dog is predisposed to developing Prototheca?
Collies appear to be predisposed and the majority of infections have occurred in females.
In systemic involvement, about 67% have ocular involvement = leukocoria. Disemminated disease frequently have colitis plus ocular/CNS involvement; no skin lesions. Organisms in urine sediment is an indication of dissemination.
Usually no systemic signs with cutaneous involvement.
151
What is the diagnosis and treatment of Prototheca?
The characteristic morphologic form of Prototheca is a morula, wherein internal separation of spherules into multiple endospores results in a wheel-like or daisy-like appearance.
Amphotericin B and Tetracycline work synergistically to inhibit growth in vitro = successful in humans (cutaneous)
Amphotericin B and itraconazole is recommended for disseminated disease.
152
Conidia are responsible for ______ reproduction and are nonmotile spores generated by mitosis and can come in many shapes and sizes.
asexual
*Dermatophytes are isolated as asexual fungal organisms (anamorphs).
153
Clinically healthy cats and dogs can carry which six species of fungi?
Alternaria, Aspergillus, Cladosporium, Penicillium, Rhizopus, and Trichoderma.
Represent repeated transient contamination by airborne fungi or soil fungi.
Cats with FIV or FeLV have a greater fungal diversity on their skin.
154
What are the two major physiological barriers to fungal growth?
Temperature
- The optimal growth range for fungi is considerably lower than body temp.
• Oxidation-reduction potential
155
List examples of zoophilic dermatophytes
Microsporum canis, M. equinum, and T. equinum are adapted to living on animals, rarely
found in the soil, and will occasionally infect humans
156
List examples of sylvatic dermatophytes
T. mentagrophytes, M. persicolor are zoophilic dermatophytes adapted to living on rodents or hedgehogs.
157
List examples of anthropophilic dermatophyte
Epidermophyton, T. tonsurans, T. rubrum - adapted to humans, rarely infects animals as a
reverse zoonosis
158
List examples of geophilic dermatophytes
Microsporum gypseum occurs in the soil as saprophytes, but under favorable conditions, can infect humans and animals if skin or immune system is compromised
159
What is the typical infective portion of dermatophytes?
Arthrospores - typical infective portion. Form by segmentation and fragmentation of fungal hyphae
160
What are the breed predisposition for developing dermatophytosis in cats and dogs?
Yorkshire terriers, Pekingese/Persian and Himalayans to M. Canis.
Parson Russell Terrier to T. mentagrophytes
161
Hair fragments containing infectious arthrospores can remain infectious for more than __ months if protected from UV light
18
162
Describe the 4 stages of dermatophyte infections
- Arthrospores adhere strongly to keratin.
- Conidial germination within 6 hours of contact.
- Invasion of cornified tissues (stratum corneum, hair shafts, claws) by producing proteolytic enzymes (e.g. keratinase, elastase, and collagenase)
- Mechanical injury and increased humidity facilitate penetration
163
Infection of the hair shaft does not progress below zone where cornification occurs - what is that area called?
Keratogenous zone, Adamson’s fringe
164
What immune response is the principal means of resolving dermatophytosis and developing resistance to reinfection?
Cell-mediated immune response
165
Regarding dermatophyte antigens, what is the immunologically active portion of the cell wall? The carbohydrate portion is involved in immediate-type hypersensitivity and the peptide portion is involved in delayed-type hypersensitivity.
Glycopeptide
166
What is the difference between a fungal kerion and pseudomycetoma?
Kerion - eruptive nodular mass that may ulcerate and develop draining tracts. These are usually solitary nodules on the face and forelimbs of dirty digging dogs.
Pseudomycetoma - deep granulomatous nodular dermal and subcutaneous mass containing distorted fungal hyphae seen almost exclusively in Persian cats, may have tissue grains.
167
What species of microsporum causes causes prominent scaling but minimal alopecia because it infects surface keratin but does not invade hair?
M. persicolor
168
When using the Woods lamp, what wave length is needed for determining the presence of M. canis? What produces the fluorescence?
320-400nm
The fluorescence is the result of a water soluble chemical metabolite, pteridine, produced by actively growing fungi within the cortex or medulla of hair, and not on scale or claw material.
169
DTM contains what compounds and what is used as a pH indicator?
Dermatophyte test medium (DTM) contains nutrient medium, bacterial and saprophytic fungal growth inhibitors (gentamicin, tetracycline, and cycloheximide), and phenol red as a pH indicator
170
Describe the phenotypic differences of M. canis, M. gypseum and Trichophytan on DTM
M. canis colonies have a white top surface, yellow-orange reverse pigment underside, are flat with a depressed center, and have a cotton or wool consistency.
M. gypseum colonies have a cinnamon brown top surface, yellow to tan underside, are flat, and have a face powder consistency.
Trichophyton spp. colonies have white to cream top surface and tan to brown to red underside
171
Keratinocytes recognize Malassezia antigens via Toll-like receptors, which leads to up regulation of ___ and ___ and down regulation of IL-1⍺
IL-10 and TGF-β
172
Why can Malassezia (which is technically 'lipid dependent') grow on Sabouraud Agar?
They utilize lipid fractions within the peptone component of Sabouraud’s dextrose agar
173
What are the PAMPs associated with Malassezia? PRRS?
PAMPS - mannan, zymosan
PRRs - Langerin, a C-type lectin (protein that binds carbohydrates in a calcium -dependent manner), is expressed by Langerhans cells and recognizes mannose and beta-glucans.
174
Missense mutation in what gene that encodes lanosterol 14-alpha-demethylase, a target side for azoles has been identified?
ERG11
175
Curvularia geniculata, Madurella, Acremonium, and Pseudallescheria are associated what what class of fungi?
Eumycotic mycetoma
176
What class of fungi are caused by species of pigmented fungi (dematiaceous) with dark-walled, septate hyphae, including Alternaria, Drechslera, Exophiala, Phialophora, Bipolaris spp., Cladosporium spp., Curvularia spp., and Wangiella spp.
Phaeohyphomycosis (chromomycosis)
177
What group of fungi are similar to phaeohyphomycosis, except fungal hyphae are non pigmented (nondematiaceous), including Pseudallescheria sp., Acremonium sp., Fusarium sp., Paecilomyces sp., and Geotrichum sp. Organisms have septet branching or non-branching hyphal (mycelial) tissue morphology?
Hyalohyphomycosis (paecilomycosis, adiaspiromycosis)
178
What is a saprophytic dimorphic fungus found in moist organic debris that grows as hyphae at environmental temperatures and yeast form in tissue?
S. schenckii
179
What is P. insidiosum is not a true fungus?
Its cell walls do not contain chitin and instead have cellulose and β- glucan. The cytoplasmic membrane lacks ergosterol, the sexual process is oogamy, and the organism develops biflagellate zoospores (infective stage) in wet environments
180
Basidiobolus sp. and Conidiobolus sp are classified into what group of fungi?
Entomophthoromycosis which is considered a Zygomycosis (the other being mucormycosis)
Basidiobolus has only been reported in the horse.
Conidiobolus has been reported in horses, llamas, sheep, and dogs
181
Curvularia spp. and Madurella spp. are associated with ____ mycetomas and Scedosporium/Pseudallescheria complex is usually associated with ____.
black-grained
| white grains.
182
Definitive identification of organism in eumycotic mycetoma and phaeohyphomycosis requires which diagnostic technique?
culture
183
To diagnose Lagenidiosis, it must be cultured from fresh tissue followed by what diagnostic technique?
ribosomal RNA gene sequencing
184
Zygomycosis requires culture to differentiate between _____, because zygomycosis CAN respond to anti fungal treatment.
Oomycetes
185
Pythium stains poorly with which stain because of the lack of chitin? Which may be needed to see thick-walled, sparsely septate hyphae, 2-7 μm in diameter, with occasional branching?
PAS
| Gomori’s methenamine silver
186
What may act as a virulence factor in the development of phaeohyphomycosis.
Melanin
187
BAD1 mediates adherence to ____ and ___ on cell membranes. BAD1 also depresses the production of tumor necrosis factor-alpha, which is important for phagocyte killing of fungal organisms and recovery from disease.
CR3 and CD14
188
In Cryptococcus, inhalation of blastoconidia, basidiospores, or poorly encapsulated yeast cells quickly germinate to yeast in mucosae or within phagosomes to avoid being killed by neutrophils and macrophages. Yeast-derived enzyme is essential for survival of Cryptococcus yeast in mucosae?
glucosylceramide synthase
189
What type of media will differentiate C. neoformans from C. gatti?
Canavanine-glycine-bromothymol blue agar (CGB) differentiates C. gatti from C. neoformans, as C. gatti grows and turns agar blue!
190
What are the dermatophyte species affecting large animals?
Trichophyton verrucosum is most common in cattle, sheep, goats, camelids. T. nanum (N. nanum) in swine, less commonly M. canis, M. gypseum (N. gypseum), M. persicolor (N. persicolor), T. mentagrophytes, T. verrucosum, T. tonsurans.
191
T. verrucosum requires what B vitamin and some strains require inositol for growth?
Thiamine (B1)
192
Compare and contrast the cell walls of True Fungi vs. Oomycetes
Oomycetes contain b-glucan and cellulose in cell walls with minimal ergosterol and no chitin.
193
Compare and contrast the microscopic findings for the following organisms (size, shape, where found if applicable)
- Blastomyces dermatitidis
- Histoplasma capsulatum
- Cryptococcus neoformans
- Coccidioides immitis
- Sporothrix schenckii
Blastomycoses: 8-15uM, broad-based budding, double contoured cell wall, found in moist acidic environment (mid-atlantic)
Histoplasmosis: 2-4uM round organisms, narrow-based budding, found in macrophages (yeast form), Ohio/Mississippi river valleys
Cryptococcidiosis: 2-20uM round to elliptical organisms, narrow-based budding, pigeon dropping, pacific northwest
Coccidioidomycosis: 20-200uM spherules or 2-5uM endospores, southwest, dry/alkaline soil
Sporotrichosis: 3-5uM, round, oval or cigar-shaped, decaying debris (rose bushes?)
