Systemic Mycoses Flashcards
What 4 genera typically cause systemic mycoses?
- Coccidioides - inanimate mold, sporangia in tissue
- Histoplasma - inanimate mold, budding yeast in tissue
- Blastomyces - inanimate mold, budding yeast in tissue
- Aspergillus - budding yeast in tissue
How is systemic mycoses transmitted? When is infection primarily seen? Is it contagious?
inhalation
in immunocompromised animals
NO
How do systemic mycoses lesions tend to appear?
granulomatous to pyogranulomatous (lung) with dissemination to bone, skin, CNS, or abdominal visera
What 2 species cause coccidioidomycosis? What are the main hosts and habitat? Site of lesion?
- Coccidioides immitis
- Coccidioides posadasii
dogs, cats, horses, humans
soil of low elevation deserts
primary lesions in lungs with secondary lesions in bones
What are the 6 major virulence factors of Coccidioides?
- adhesins (SOWgp): affinity for extracellular matrix proteins (laminin, fibronectin, collagen)
- β-glucosidase 2: secreted by endospores that play a role in morphology
- chitinase 2 - formation and release of endospored from spherule
- β-1.3-glucanosyltransferase: surface endospore
- serine proteases - stimulation of inflammatory response by digesting elastin, collagen, and Ig
- urease
What parts of Coccidoides have antiibodies made against in early and late infection? What 2 virulence factors elicit Th1 responses?
- EARLY = β-glucosidase (IgM)
- LATE = chitinase 1 (IgG), diagnostically useful and detected by complement fixation
- β-1,3-glucanosyltransferase - results in elevated IFN-γ production and protection against disseminated disease
- urease - protective immunity, activates macrophages
How does Coccidioides grow on media?
SDA or blood - mycelial
- dull colonies gradually develop sparse aerial mycelium
- arthroconidia produced within 5-7 days
What is the pathogenesis of Coccidioides?
- hyphae fragment into arthroconidia, which are inhaled and form spherules in tissues
- spherules rupture and release endospores, which form more spherules
- dissemination from lung to a variety of other tissue is possible, especially CNS, local LN, bone, skin, pericardium, and eyes
Coccidioidomycosis, dog:
Coccidioidomycosis, dissemination:
What are 4 ways that Coccidioidomycosis is diagnosed?
- skin test - coccidioidin
- immunodiffusion - multiple bands = active infection; single band = chronic infection
- complement fixation - Ab titers rise in disseminated disease
- latex agglutination test - IgM in early disease
What are the 4 recommended treatments for Coccidioidomycosis?
- fluconazole*
- ketoconazole*
- itraconazole*
- amphotericin B
What causes Histoplasmosis? What 2 phases does it take? What 3 varieties are there?
Histoplasma capsulatum
- MOLD = 25-30 degrees C, saprophytic
- YEAST = 37 degrees C, parasitic)
vars. capsulatum, duboisii, farciminosum
- histoplasmosis is discussed without regard for varietal distinction
What is the free-living form of Histoplasma capsulatum?
septate hyphae bearing….
- spherical to pyriform microconidia
- tuberculate macroconidia, thick-walled spheroidal cells studded with finger-like projections
What are used for immunodiagnosis of Histoplasmosis?
histoplasmins
What are the 4 major virulence factors of Histoplsma capsulatum?
- adhesins - bind to β-2 integrins on the surface of neutrophils, macrophages, and DC, allowing it to enter without triggering an effective oxidative burst
- calcium-binding protein - chelates available calcium within the phagolysosome, impeding the effectiveness of calcium-requiring lysosomal enzymes
- iron acquisition - removes iron from host iron-binding proteins transferring and lactoferrin
- melanin - reduces the toxicity of hydroxyl radicals, superoxides, and singlet oxygen radicals in the phagolysosome
What are the H and M antigens of Histoplasma capsulatum?
H = β-glucosidase that elicits a cell-mediated immunoresponse to the yeast (parasitic) phase
M = catalase that plays a role in the survival of the yeast phase in the phagolysosome
How does Histoplasma capsulatum survive in the phagolysosome?
it acidifies the environment within the phagolysosome from a pH of <5 to 6-6.5, which reduces the activity of the lysosomal enzymes
What are the 6 classes of Histoplasma capsulatum?
- 1 and 2 = North America
- 3 = Central and South America
- 4 = Florida
- 5 and 6 = human patients with acquires immunodeficiency syndrome from NY and Panama
Where is Histoplasma capsulatum found in the environment? How is it transmitted?
topsoil layers, especially in the presence of bird (starlings, chickens) and bat guano
inhalation of microconida or hyphal fragments
- ingestion, wound infection
Where are the lesion sites of Histoplasmosis?
primarily in lungs with dissemination to intestines and other organs
How does the form of Histoplasmosis compare in the environment and within the host?
ENVIRONMENT = mold with aerial hyphae
HOST = oval, budding yeast that can be phagocytized by immune cells and transported to regional LN and disseminate
Histoplasmosis, cat:
Histoplasmosis, bone dissemination:
- soft tissue swelling
- osteolysis of carpal bones
- collapsed joint spaces
- distal radius has punctate osteolysis
- periosteal reaction in proximal metacarpal
Histoplasmosis:
In what 4 ways is Histoplasmosis diagnosed? What 4 treatments are recommended?
- skin test - Histoplasmin, positive reaction means only exposure
- immunodiffusion
- complement fixation, latex agglutination - humans
- immunofluorescence - yeast cells in exudates and tissue
ketoconazole, itraconazole, fluconazole, amphotericin B
What causes blastomycosis? What 2 forms does it take?
Blastomyces dermatitidis
- MOLD in soil (saprophytic)
- YEAST in tissue (parasitic)
What spores does Blastomyces dermatitidis produce? How does it grow on blood agar?
conidiophores with spherical or oval smooth-walled conidia
at 37 degrees C - thick-walled yeast that reproduces by single buds attached to a broad base
What is the major virulence factor of Blastomyces? What 2 functions does it have?
adhesin (Bad1)
- binds to phagocytic cells resulting in little generation of ROS and nitrogen intermediates
- downregulates the production of proinflammatory cytokines
What are the main hosts of Blastomyces? What is their usual habitat? Where are lesions most common?
dogs, cats, humans
acidic soil rich in organic material
primary lesions in lungs with dissemination to skin and other organs
What are the 6 steps to blastomycosis pathogenesis?
- spore inhalation
- deposit in alveoli
- acute pulomary phase resulting in self-limiting control of asexual reproduction or…..
- asexual budding not eliminated by the immune system (or due to immunocompromisation)
- pyogranulomatous inflammation within the lungs
- lymphatic and hematogenous spread of spores causes inflammation in skin, bones, eyes, CNS, and/or reproductive tract
Blastomycosis:
What is a common presentation when blastomycosis affects the eyes?
subretinal granuloma and serous retinal detachment
- with treatment, retinal detachment should flatten and granuloma should reduce in size
Blastomycosis, cat cutaneous lesions:
In what 4 ways is blastomycosis diagnosed? What is the recommended treatment?
- culture on SDA and direct examination of intracellular yeast
- skin test - lacks sensitivity and specificity
- immunodiffusion, complement fixation, ELISA, counter-immunoelectrophoresis
- immunofluorescence - yeast cells in exudates and tissue
itraconazole**, amphotericin B, ketoconazole
What is the most frequent Aspergillus causing animal and human infection? What kind of fungi are they?
Aspergillus fumigatus
molds consisting of septate hyphae and characteristic asexual fruiting structures borne on conidiophores
What is the characteristic structure found on Aspergillus spp.?
conidiophores - hyphal branches originating by a foot cell in the vegetative mycelium and ending in an expanded vesicle covered by layers of flask-shaped phialides from which chains of pigmented conidia grow
What are the 5 major virulence factors of Aspergillus spp.?
- adhesins - bind to extracellular matrix proteins (collagen, fibronectin, fibrinogen, laminin)
- cell wall - PAMP recognized by Toll-like receptors on the surface of host macrophages, resulting in the secretion of proinflammatory cytokines
- extracellular enzymes - breaks down host tisue, including elastase, protease, phospholipase
- iron acquisition
- melanin pigment - free radical scavenger
Where are Aspergilli found in the environment? How is Aspergillosis acquired?
soil, vegetation, feed, air, water
environmental - inhalation or ingestion
What are the 5 steps to Aspergillosis pathogenesis?
- infection acquired from environmental sources - inhalation/ingestion
- opportunistic pathogen that can impair, overwhelm, or bypass host defense to permit hyphal invasion of tissues
- pulmonary infection with suppurative exudates in the bronchioles
- mycelial growth may extend into blood vessels, leading to vasculitis, thrombus formation, and dissemination
- granulomas can develop in many body organs and are visible as yellowish-grey nodules
What are the most common diseases caused by Aspergillus spp. in cattle, horses, dogs, and birds?
CATTLE: abortion, mastitis, intestinal aspergillosis, pneumonia
HORSES: guttural pouch mycosis*, nasal granuloma, keratomycosis, intestinal aspergillosis
DOGS: nasal aspergillosis, otitis externa, systemic aspergillosis
BIRDS: brooder pneumonia, aspergillosis (pneumonia and air sacculitis)
Aspergillosis, placentitis:
- cattle
- thickened, leathery
- mycotic abortion
Aspergillosis, abortion:
fungal plaques
How are horses most commonly affected with Aspergillosis? How does it commonly present?
guttural pouch mycosis
- nasal discharge, usually unilateral
- swelling of Viborg’s triangle
- cranial nerve and vessel involvement results in epistaxis, unilateral facial paralysis, and dysphagia
What are the 3 major presentations of Aspergillosis in poultry?
- brooder pneumonia - newly hatched chicks inhale aerosols
- pneumonia and air sacculitis - sporadic in young birds
- generalized aspergillosis - stress in captive birds
What is the mos common presentation of Aspergillosis in dogs? How does it present?
nasal aspergillosis in young urban dogs
- chronic nasal discharge, often unilateral
- sneezing
- epistaxis
- damage to nasal mucosa and turbinates
- otitis externa
Aspergillosis, cat:
What is bovine abortion caused by Aspergillus spp. commonly related to? Aspergillosis in chickens?
moldy fodder, poor weather and housing
heavily contaminated litter, poor husbandry
In which dogs are Aspergillosis most common? What practice makes horses more susceptible to Aspergillus keratomycosis?
young dolichocephalic breeds
frequent use of topical antibacterials and steroids that cause immunosuppression and impaired colonization resistance
What is the major factor that limits Aspergillus dissemination?
cell-mediated immunity
- immunization procedures not available
How is Aspergillosis diagnosed? How is the nasal form in dogs treated? Disseminated form?
- direct examination - hyphae, fruiting heads, conidia
- culture
- immunodiffusion
- ELISA, PCR
topical instillation of clotrimazole or enilconazole into the nasal passage and sinuses (itraconazole can be given orally)
itraconazole
What does Pneumocystis carinii cause?
severe pneumonia in immunocompromised (opportunistic!)
- especially horses and dogs
What are the 4 most common diseases caused by Rhisopus spp., Rhizomucor spp., Absidia spp., Mucor spp., and Mortierella spp.? What animals are most affected?
- mycotic bovine abortion
- GI infection marked ulcerative lesions and mesenteric lymphadenitis
- respiratory infection
- hematogenous infection affecting viscera and CNS
ruminants, swine, dogs
