Fungal Flashcards
MOA Itraconazole
Itraconazole- inhibits lanosterol 14-a-demethylase which interrupts conversion of lanosterol into ergosterol
MOA Terbinafine
Terbinafine- squalene epoxidase inhibitor- allows accumulation of squalene prompting ergosterol depletion
Distribution of Histo
SW
Mode transmission Histoplasmosis
Mode of transmission: inhaled or ingested microconidia by host → replication in ALVEOLAR MACROPHAGES
Dog most common CS Histoplasmosis
GI signs seen in 50-60% of cases - most commonly in small/toy breeds
Respiratory signs seen in 10%
CS cat Histo
Persians overrepresented
Respiratory signs - 40%
Don’t cough when they have respiratory involvement
Ocular manifestations - 25%
Bone involvement - 20%
FeLV co-infection in up to 28% of cases
Bone marrow involvement
Skin involvement
What does Histo bind to on the host
CD11-CD18 integrins on alveolar macrophages → granulomatous inflammatory response in lungs
Common BW changes with Histoplasmosis
CBC: reflects presence of systemic inflammation, non-regenerative anemia common, +/- other cytopenias
>75% hypoalbuminemic (mild to severe)
Cats with liver involvement can have elevated ALT and AST
Most common GI CS in dogs with Histo
Proctitis
How do you dx Histoplasmosis
Organisms occasionally found in blood (20%)
Colonic scrapes can often be diagnostic
Galactomannan test (antigen)
-Similar test to blastomycosis
-*BLASTO AND HISTO CAN CROSS REACT
-Very sensitive (>90%) – urine > serum
Tx of Histo? What if ocular and CNS involvement?
Itraconazole - tx of choice
Fluconazole - Excellent for ocular and CNS penetration
Treat for at LEAST 6 months - decision based on lesion resolution, negative antigen test, clinical signs
Distribution Blastomycosis
Distribution: Midwest to south central
Whos at high risk for Blasto
Young (2-4YO), large breed (>15kg) hunting dogs (Hounds, Labs, Goldens, Pointers), slight male predisposition
Most common CS for blasto
Respiratory signs (common - 85%): tachypnea, harsh lung sounds, cough
Ocular manifestations - anterior uveitis common
Granulomas
Draining tracts
Lameness (osteomyelitis)
Neuro signs (uncommon)
Testicular involvement
What’s the main virulence factor associated with Blasto
BAD-1: cell surface glycoprotein that binds on cell receptor of macrophage
Most sensitive screening test for Blasto
Urine antigen test
Cytology of Blasto
Cytology (FNA, impression smears, lung wash, CSF) - YEAST IN HOST
Broad based budding yeast - thick double refractile wall
Pyogranulomatous inflammation - concurrent presence of neutrophils with activated macrophages, lymphocytes, plasma cells
How to diagnose Blasto
Galactomannan cell wall antigen test
Some cross reactivity with Histoplasma - need cyto to confirm dx
Tracheobronchial enlargement - 25%
Also see with Valley Fever and Histo
Tx Blasto
Itraconazole
Fluconazole and voriconazole - better CNS/ocular than itra
Amphotericin B - warranted if more aggressive/disseminated dz, fail to respond to azoles, do not tolerate azoles
Most common organism for sinonasal Asper? Most common organism for systemic asper?
Sinonasal: Aspergillus fumigatus
Systemic: Aspergillus tereus, deflectus
Most common type of Asper in cats
SINORBITAL
What would you find that is unique to Asper on work-up diagnostics
Renal changes (only fungal disease that goes to kidney)
Findings in radiographs of dogs with Asper
Osteolytic lesions, discospondylitis (20-25% of all cases)
Test of choice for diagnosis of systemic Asper
Aspergillus antigen
Test of choice for diagnosis of sinonasal Asper
Galactomannan urine antigen ELISA - Very good sensitivity for disseminated infx
What can cause a false positive on the Galactomannan urine antigen ELISA?
False positives: other fungal infx, concurrent plasmalyte and vetivex pHlyte (both serum and urine will have false positive - uses fermentation of sorghum by aspergillum)
What antifungal is Asper resistant to
FLUCONAZOLE
2 main species of Cryptococcus in SA
C. neoformans → immunocompromised dogs
C. gattii → immunocompetent animals (mostly cats)
Primary site of infection in dogs and cat with Crypto
: nasal cavity
Most common neuro location for Crypto
forebrain
Nasal aspergillus tx
topical clotrimazole
Most common presentation in dog with Crypto
Neuro signs
Describe the cytology of Crypto
Cytology: thick walled organisms - polysaccharide capsule (dont confuse with fat droplets)
Gold standard for diagnosis of Crypto
Latex agglutination Crypto GMX
No cross reactivity with Histo or Blasto
Serum or CSF
Tx of Crypto
Fluconazole (excellent eye and CNS penetration)
Amphotericin B + 5-flucytosine (most effective but nephrotoxic)
5-flycytosine - contraindicated in dogs
Surgical debridement if large granuloma
Distribution of Coccidiomycosis
Southwest
Clinical signs of Valley Fever
Fever is common (>60%)
Respiratory signs
Coughing - can be secondary to pericardial thickening, pericardial effusion, tracheobronchial lymphadenopathy, pulmonary infiltrates
Testicular abnormalities
CNS signs (>50% seizures)
Non Healing wound (50% of cats)
Hilar lymphadenopathy
Ocular (immune mediated uveitis)
Bone involvement
Almost all infected animals with valley fever have what change on bloodwork
HYPOALBUMINEMIA
uncommonly hypercalcemia
Most sensitive test for Coccidiomycosis
Antibody serology (IgG and IgM)
Most sensitive biomarker (almost 100%)– antibody testing - the one fungal pathogen that this is the choice
Unique adverse effect of itraconazole
Unique adverse effect: vasculitis - skin ulcerations/abscesses
What anti fungal causes neurotoxicity in cats
voriconszole
Medications that affect absorption of azoles (separate them)
PPI, cyclosporine, plavix
Which antigunfal is not a cytochrome p450 substrate
Fluconazole
70% excreted in urine
MOA azoles
MOA: inhibit fungal ergosterol synthesis
Lanosterol 14a-demethylase = cyp450
Drug that interact with azoles
Ivermectin, benzodiazepines, cyclosporine, macrolide abx, corticosteroids, amitriptyline, digoxin
Which fungal diseases use itraconazole as first option
Histo, blasto
What’s the first choice tx for Cryptococcosis and coccidiomycosis
Fluconazole
MOA terbinafine
**Terbinafine - affects ergosterol synthesis - fungal cell membrane = fungus died
- Inhibits squalene epoxide reductase –> builds up in cell
- Well tolerated but GI, hepatotoxicity
Used in combination therapy for pythium
