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