SQ and Systemic Mycoses Flashcards
Which type of fungi (generally) are involved in eumycotic mycetomas, pheohyphomycosis, SQ hyalohyphomycosis, zygomycosis?
Saprophytic fungi
-SQ
-Traumatic implantation
-Localized
-Slow spread
Geography of Eumycotic mycetomas
Worldwide. Most frequent near Tropic of Cancer
Geography of phaeohyphomycosis
Worldwide
Where are Pheohyphomycosis organisms located (zoophilic, anthrophilic, etc)
Soil, wood, vegetation
OCCASIONALLY can be found on skin of healthy people and animals
Geography of Sporothrix schenckii
Tropical, subtropical, temperate zones
Central, South America
Africa
Esp Brazil
Geography of Oomycosis in the USA
Gulf coast of US
Otherwise, tropical/subtropical
Season of oomycosis
Late summer, fall
Climate of Zygomycosis
Tropical/subtropical
Most common organisms causing a eumycotic mycetoma
Saprophytes
BLACK GRAIN
*Curvularia geniculata
*Madurella
WHITE GRAIN
*Acremonium
*Pseudallescheria
Black grain mycetomas organisms
*Curvularia geniculata
*Madurella
White grain mycetomas organisms
*Acremonium
*Pseudallescheria
Phaeohyphomycosis’ other name
Chromomycosis
From PIGMENTED fungi
White animals develop phaeohyphomycosis
Cows, horses, cats
RARE in dogs
Phaeohyphomycosis organisms
Pigmented soil saprophytes. Can be normal animal flora. Dark walled, septate hyphae
*Alternaria
*Drechslera
*Exophiala
*Phialophora
*Bipolaris
(Cladosporium
*Curvularia
*Wangiella
Hyalohyphomycosis’ other names
Paecilomycosis
Adiaspiromycosis
NONPIGMENTED fungi
Hyalohyphomycosis Organisms
Nonpigmented fungi w/ septate hyphae
*Pseudallscheria
*Acremonium
*Fusarium
*Paecilomyces
*Geotrichum
*Aspergillus
Sporotrix species within Sporothrix schenckii complex
*Sporothrix brasiliensis
*Sporothrix schenckii
*Sporothrix globosa
*Sporothrix luriei
At what temperature is Sporothrix a yeast? At what temperature is Sporothrix a hyphae
(Dimorphic)
Yeast in TISSUE
Hyphae at ENVIRONMENTAL temperatures
Name 2 dimorphic water molds
*Pythium insidiosum
*Lagenidium
Oomycosis
What is “leeches” “bunkers” “Swamp cancer” “bursattee”
Pythium insidiosum
Why is Pythium not a true fungus
1) NO CHITIN in cell walls
-Instead: cellulose, B-glucan
2) NO ERGOSTEROL in cell membrane
3) Sexual process = oogamy
4) Infective biflagellate zoopspores in wet environments
2 infections classified as Zygomycosis
Entomophthoromycosis
Mucormycosis
Entomophthoromycosis (Zoopagomycota) organisms
Basidiobolus
Conidiobolus
Mucormycosis organisms
Order Mucorales
Rhizopus
Mucor
Lichthimia
Sakenaea
VERY uncommon in small animals
Species (and 1 breed) most likely to develop pheohyphomycosis
Cats»_space;»
GSD dogs are predisposed
Which fungus can be spread via inhalation or trauma
Zygomycosis (Entomophthoromycosis, Mucormycosis)
Which fungus can be spread by free-standing water exposure or minor skin wounds
Oomycosis
How do oomycoses encyst in the skin
Zoospores contact skin, mucosa and encyst via a sticky glycoprotein (adhesion)
Germ tube (hypha) development is stimulated by host body temperature
Invade blood vessels
Proteases weaken host tissue
Characteristics of mycetomas (3)
1) Tumefaction (swelling)
2) Draining tracts
3) Grains (aggregates of fungi)
Clinical lesion of pheohyphomycosis
Pigmented nodule on face (nose, pinnae) and paws of cats
Can be mistaken for melanoma
Clinical lesions of hyalohyphomycosis
Well circumscribed ulcers or nodular masses
-Claws
-Head
-Eyes
-Joints
Sporotrichosis: 3 clinical forms
1) Primary cutaneous form (nodules or plaques at point of entry)
2) Cutaneous- lymphatic form (thick, corded)
3) Disseminated form
Which clinical form of Sporotrichosis is most common in humans and horses
Cutaneous-lymphatic form
Which species develop pythiosis
Horses, Cattle, Dogs, Cats
Which species develop lagenidiosis
Dogs
Species that develops Basidiobolus
Horse
Species that develops Conidobolus
Horses, llamas, sheep, dogs
If a cat has Sporotrichosis that spread to its joints (w/fever, anorexia), is the cat immunosuppressed?
Not necessarily! Disseminated Sporotrix does not require immunosuppression
Signalment for Pythiosis
Young, large breed dogs
Labwork finding common in pythiosis
Eosinophilia
Who is this
Sporothrix schenckii
Ovoid to cigar-shaped
Diagnosis of eumycotic mycetoma or pheohyphomycosis
Culture
Diagnosis of Sporotrichosis
1) Tissue culture (Sabouraud’s agar: white mold that turns brown as pigmented conidia grow.)
2) IHC
3) Antibody immunofluorescense
Diagnosis of pythiosis
1) ELISA (monitor response to treatment. Decreased Ab in 2-3 months after treatment)
2) Culture (careful!)
3) PCR
Diagnosis Lagenidiosis
1) Culture from fresh tissue
2) RNA gene sequencing
Why are dimorphic fungi dangerous to culture?
Mycelial phase is infective to humans
T or F: Splendore Hoeppli will be seen on Sporotrix histopath
True
Which species will have MORE Sporotrix organisms visible on histopath? Which typically has FEW organisms visible?
MORE: Cats
LESS: Dogs, hrses
T or F: Pythium can be visualized on histopath with PAS
FALSE. Cell walls lack chitin
Best stain to visualize Pythium
GMS
(thin splendore hoeppli)
Best stain to visualize Zygomycosis
GMS
Stain poorly with PAS
Similar to oomycosis, but CAN be treated with antifungals.
(thick splendore hoeppli)
T or F: cutaneous eumycotic mycetoma may be fatal
False. Not life-threatening
T or F: Surgical excision of phaeohyphomycosis is usually curative
False. Recurrence is common
Make sure you d/c immunosuppressive meds!
T or F: Hyalohyphomycosis is typically fatal if generalized
True. Disseminated + CNS signs are grave.
Systemic antfungals only help short turn.
Localized lesions only? Tx with surgery
Treatment of Sporotrichosis in cats
Itrafungol >2 months. But difficult
Treatment of Sporotrichosis in dogs, horses
Potassium iodide
*Toxic Iodize AE: oculonasal discharge, vomiting, collapse. D/C KI for 1 week then restart at lower dose
-Ketoconazole, terbinafine, amphotericin B, local hypothermia, surgical resection. Continue 1 mo past clinical cure
Oomycosis prognosis, best treatment option
Prognosis = poor
Tx = wide surgical excision, amputation. AND itraconazole or terbinafine (but no ergosterol, so not great)
Consider Capsofungin (targets beta-glucan in cell wall)
T or F: Sporothrix is zoonotic. Isolate infected cats
TRUE
T or F: Oomycosis is zoonotic
FALSE. Infective zoospores only form in water, not in tissue
T or F: If an animal has cutaneous Histoplasma capsulatum, you should assume they have systemic infection
True.
True for Blasto, Coccidiodes, Crypto, and Histoplasma
Where in the USA is Blastomyces dermatidis most common
*Mississippi, MO, Ohio river valley, mid-Atlantic states, Eastern Canada
*Likes moist soil, like beaver dams. Spread when soil is disrupted
Dogs at higher risk for Blastomycosis
Sporting dogs, hounds
Do not have to be immunocompromised
Mode of transmission of Blastomycosis
1) Inhale conidia –> airway mucosa –> bind alveolar macrophages (adhesins aka BAD1)
2) Spread of conidia via leukocyte trafficking
3) Acute inflammation, tissue damage. Mediated by macrophages
Blastomyces adhesion factor that can cause phagocytosis of conidia
BAD1
Immune response needed to clear Blastomycosis
T-cell mediated
Directed to BAD-1 (adhesin)
Where is Blastomycosis commonly found, other than the skin
Lungs (85%)
Diagnosis of Blastomycosis
Urine ELISA is best!
Serology: 41-90% sensitive, 90-100% specific
Who is this
Blastomyces dermatitidis
Thick walled yeast, broad-based buds
Treatment Blastomyces dermatitidis
Itraconazole is the best
Amphotericin B: nephrotoxic. Can be life saving if needed. Given IV
Fluconazole for urinary tract disease– excreted in urine
Low dose GCs to help with severe lung inflammation
Blastomycosis virulence factors
*BAD1: mediates adherence to CD3, CD14. Decreases TNFa (needed for phagocytosis and disease clearance)
*Cell wall glucans
*Melanin helps resist phagocytosis and killing
*Change polysaccharides on surface to evade immune system; can hide in phagosomes
Coccidiodes immitis, “Valley fever” USA geography
SW US, esp AZ
sporulate after rain –> Arthroconidia are then spread via the wind
Predisposed dogs to Coccidiodes immitis
*Young, male dogs
*Boxers, Dobermans
+/- immunocompromised (more severely affected)
What protects Coccidiodes immitis from phagocytosis
Spherules – too large to be phagocytosed + virulence factors to cause inflammation (mucosal injury and colonization)
Arthroconidia become spherules rapidly upon entering airway
What happens inside Coccidiodes immitis spherules
Endosporulation
When spherules are damaged, endospores are relased and phagocytized by macrophages –> endospores WITHIN macrophages
Most common form of Coccidiodes immitis infection in cats
Skin lesions (nodules w/draining tracts)
Most common form of Coccidiodes immitis infection in dogs
Low grade lower respiratory infection
Who is this
Coccidiodes immitis
Spherules with thick wall +/- endospores
Who is larger: Blastomyces dermatitidis or Coccidiodes immitis
Coccidiodes immitis is MUCH larger.
Coccidiodes also may have endospores; Blasto will not
Best stain to visualize Coccidiodes immitis spherules
Pap stain
(capsular wall = refractile, purple-black. Cytoplasm= yellow. Endospores = red-brown)
Can also use PAS, Wrights stain
T or F: high Coccidiodes immitis IgG titers correlate with more severe disease
False.
There should be IgM within 2-5 weeks; IgG within 8-12 weeks.
Treatment Coccidiodes immitis
Fluconazole for >1 year
(CNS penetration)
Lifelong immunity once animal recovers!
Virulence factors Coccidiodes immitis
*Spherule outer wall glycoprotein: limits cell mediated immunity
*Host tissue arginase I, Coccidiodal urease (tissue damage)
*Laminin and collagen on surface = receptors for fungal ligands; enhances adhesion
Predisposed breeds for Cryptococcus
Dobermans, GSD, Cocker spaniel
Siamese, Abyssinians
More common in immunocompromised, but can happen in healthy animals
2 species of Cryptococcus (1 worldwide and from pigeon poop, 1 tropical and ubiquitous in environment)
Cryptococcus neoformans: worldwide, pigeon poop
Cryptococcus gatti: tropical/subtropical, ubiquitous in environment
What for is the Cryptococcus neoformans in when it is inhaled by the host
Basidiospores or blastoconidia
Germinate into yeast in tissue
What enzyme do Cryptococcus neoformans yeast have to survive in mucosae?
Glucosylceramide synthase
What comprises the Cryptococcus neoformans capsule
1)Glucuronoxylomannan
2) Galactoxylomannan
(polysaccarides)
Where do Cryptococcus neoformans make their capsule
Within phagosomes of macrophages.
Macrophages become distended wit hthe capsule.
Other common clinical signs with Cryptococcus neoformans (other than nodules)
CNS, ocular, osteomyelitis
Most common clinical presentation of Cryptococcus neoformans in cats
Intranasal granulomatous disease (80%)
Who is this
Cryptococcus neoformans
Yeast w/narrow based budding
Mucinotic capsule (refractile halo)
Culture media that can discern Cryptococcus neoformans from Cryptococcus gatti
Canavanine-glycine-bromothymol blue agar (CGB).
C. gatti turns the agar blue
What antigen does the latex agglutination test use for Cryptococcus neoformans
Polysaccharide capsule antigen
(latex particles coated with anticryptococcal ab)
Stain to visualize capsule of Cryptococcus neoformans
Mucicarmine, Alcian blue
(PAS, methenamine silver, Fontana masson will stain organism, but not capsule)
Best treatment for Cryptococcus neoformans
Amphotericin B.
Can work for CNS, despite poor penetration. Stimulates host immunity
BUT Fluconazole is great (CNS and urinary excretion)
Virulence factors for Cryptococcus neoformans
*Phospholipase: injury alveolar type II epithelial cells, limit surfactant production, enhance adhesion, affects phagocytosis
*Polysaccharide capsule: antiphagocytic, immunosuppressive, complement depletion, inhibits leukocyte chemotaxis
*Melanin: yeast survival during CNS infection. Antioxidant.
Histoplasmosis geography
Worldwide. Center of USA
Breeds Histoplasmosis
Pointer, weimeraner, Brittany Spaniel, Working dogs
Mode of transmission Histoplasmosis
Inhalation of microconidia
Histoplasmosis immune response
*Turn from microconidia to yeast in tissue to avoid death by phagocytosis
*Yeast produce proteins to inhibit acidification of Phagolysosomes. Spread via macrophages.
Common signs (other than cutaneous) for Histoplasmosis
GI (large bowel diarrhea)
Who is this
Histoplasma capsulatum
VERY SMALL
Round, basophilic center with a halo (shrinkage from stianing)
Treatment Histoplasmosis
Itraconazole +/- GCs for >4-6 months
Consider Amphotericin B
Voriconazole, Posaconazole
Histoplasmosis virulence factors
*Heat shock proteins 70, 83
*M phase cell cycle enzymes
*Tubular proteins
*Cell wall chitin when in yeast form
*When phagocytosed, yeast RAISE the pH by releasing urease, ammonia, bicarbonate –> Absorb Fe).
*Yeast produce IL-4, interferes with immune resopnse
*Melanin
What stain is this
Gomori’s methenamine silver – GMS (Pythium organisms)
Signalment of cats that are predisposed to Sporothrix
Young adult, male, intact
Outdoor access
Fighting –> affects nose and limbs (also respiratory tract)
Where are nodules from Conidiobolus typically formed on the body
Nares, nasal passages
Horses, dogs»_space;> cats
Ulcerative
How can you differentiate Entomophthoromycosis from oomyctes on histopath
BOTH have eosinophilic sleeve around the organisms
BUT
Basidiobolus/Conidiobolus will stain with PAS (and GMS), and Oomyctes only stain with GMS
Which is more likely to cause pulmonary nodules and vascular invasion: Lagenidium or Pythium
Lagenidium
“Kunkers”
Massive of necrotic debris 2’ Pythium in horses
What has a better prognosis: Lagenidium or Paralagenidium
Paralagenidium. Usually slowly progressive; limited to cutaneous or SQ lesions (not lungs, vessels)
Structures of dimorphic fungi in tissue vs in culture
Tissue: Yeast/spherules
Culture: Hyphae
Name 5 dimorphic fungi important in vet med
1) Blastomycosis
2) Histoplasmosis
3) Coccidiomycosis
4) Sporotrichosis
5) Cryptococcus
Which dimorphic fungus is most commonly associated with puncture or wound contamination, rather than inhalation
Sporothrix
Which cell do most dimorphic fungi live in
Macrophages
Which dimorphic fungus has a tropism for bone, with most cutaneous lesions over a site of osteomyelitis
Coccidiodes
Which histopath stain can stain LIVING fungi ONLY? Which stain can stain BOTH living AND dead fungi
Living only: PAS
Living AND dead: GMS
What characterizes chromoblastomycosis
Sclerotic bodies or Medlar bodies
= large, rounded, thick-walled fungal cells
Pigmented
T or F: the SAME fungal organisms that cause pheohyphomycosis and hyalohyphomycosis can cause eumycotic mycetomas
TRUE
To be a mycetoma, they need to make tissue grains!
