Condense summary - fungal diseases Flashcards
What is the pathogen which causes histoplasmosis ?
histoplasma capsulatum
what is the pathogenesis of histoplasmosis?
Cx, Dx, Tx
inhaled from the environment and phagocytized by macrophages (attaches to CD11-CD18 integrins). If immunosuppressed does have the ability to cause disseminated disease.
Usually primarily affects cats, dogs can be susceptible to intestinal involvement causing a GI illness characterized by malabsorption
Cx
- Cats: typically, vague and non-specific; 40% of cats will have respiratory involvement
- Dogs: GI involvement is more common (diarrhea, weight loss, fever)
Dx
- CBC: anemia; usually normochromic, normocytic, non-regenerative anemia
- Chemistry: hypoalbuminemia (~ 70-75% of patients)
- Endoscopy in dogs – may present as diffusely thickened gastrointestinal mucosa
- Cytology of affected organs
20% of cats will have fungemia on peripheral blood work
- Most efficient diagnosis: Antigen assay (urine) MIRAVISTA
Tx
- 1st line with an Azole (itroconazole, fluconazole, ketoconazole)
- Rescue treatment with posaconazol
- If severe disseminated disease (lung/neurological involvement), consider amphotericin B
- Supportive care (glucocorticoids, blood transfusion)
How do you diagnose and treat histoplasmosis ?
Dx
- CBC: anemia; usually normochromic, normocytic, non-regenerative anemia
- Chemistry: hypoalbuminemia (~ 70-75% of patients)
- Endoscopy in dogs – may present as diffusely thickened gastrointestinal mucosa
- Cytology of affected organs
20% of cats will have fungemia on peripheral blood work
- Most efficient diagnosis: Antigen assay (urine) MIRAVISTA
Tx
- 1st line with an Azole (itroconazole, fluconazole, ketoconazole)
- Rescue treatment with posaconazol
- If severe disseminated disease (lung/neurological involvement), consider amphotericin B
- Supportive care (glucocorticoids, blood transfusion)
Causative agent and pathogenesis of cryptococcus?
cryptococcus gatti & cryptococcus neoformans
Cryptococcus is acquired from the environment (bird guano) and enters through the nasal cavity. From there the capsule will protect the fungi from phagocytosis and cytotoxic T-cells. Incubation period is usually 2-13 months and from there the fungi can spread either hemategnously or via direct extension (esp. to the meninges)
Common outcome of infection:
- Fungal rhinitis
- Fungal retinitis/chorioretinis
- Fungal meningitis or meningoencephalitis
- Disseminated cryptococcosis
Most common systemic fungal infection of cats (Cats 8 x more likely than dogs)
Cryptococcus Cx, Dx, Tx
Cx
Cats:
- Chronic fungal rhinitis: slow growing ulcerated nasal mass, chronic respiratory signs (sneezing, nasal discharge)
- CNS involvement +/- optic neuritis – obtunded, atypical behavior, ataxia, +/- blindness
Dogs:
-80% fulminant disseminated disease
Dx;
- CBC/Chem: usually non-specific
- CSF analysis: organism commonly seen
- Serological testing – currently gold standard -> Latex Agglutination of cryptococcal polysaccharide antigens (LCAT) – very high sensitivity (> 90%). Can be used to monitor clinical response to treatment. Decreasing titers –> infection clearance. Persistently high titers indicate continued infection
Tx;
- Localized disease – monoazole therapy (e.g., fluconazole) – treatment should be continued until titers become negative (clinician recommend treating 6 months past this or until two negative cryptococcal titers)
- CNS involvement or disseminated disease - amphotericin B + azole therapy
what is the prognosis for cryptococcus?
Prognosis – fair for localized involvement 65-70%
Poor for CNS or disseminated disease
Causative agent of coccidiomyocosis?
Location and species affected?
Coccidioides immitis
This is valley fever
Location: desert area (California, Nevada, New Mexico)
More commonly in dogs
what is the pathogenesis of coccidiodes ?
Inhalation of spore from the environment. These are ingested into macrophages and develop into a spherule containing many different spores, spherule rupture releasing more spore and keeps on avoiding the immune system creating a pyogranulomatous response. Outcome of infection:
- Lung disease (most commonly)
- Disseminated spread if immune response inadequate
aka coccidiomycosis
what is the Cx, Dx, Tx for coccidiomycosis?
Cx
Chronic weight loss, lethargy, low grade fever, signs of respiratory tract involvement (exercise intolerance, harsh cough) – lung involvement –
Disseminated disease (e.g., bone, pericardium, lymph node, skins)
- > 50% if affected cats will present for skin involvement
Dx
- CBC: non-specific, eosinophilia is rare
- Chem: hypoalbuminemia and hyperglobinemia
- X-rays: hilar lymphadenopathy
- Urinalysis – can have significant proteinuria (UP/C ~ 9.5)
- Microbiology testing:
1) Culture – huge Heath-hazard to human
2) Serology testing: antibody assay is favored with sensitivity ~ 100%
IgM detectable in 2-5 weeks, IgG in 6-12 weeks. Low titers 1:2 – 1:16 need to be interpreted in light of clinical signs in endemic areas.
TX (note > 6 months – may be lifelong)
- Respiratory form – recommend monoazole therapy (e.g., fluconazole, itraconazole, Posaconazole)
- Severe disease or severe respiratory signs – consider amphotericin B +/- azole
- Limb amputation, pericardiectomy, enucleation, may have to be considered in severe disseminated disease
what is the prognosis for coccidiomycosis?
Lung involvement alone – good prognosis
CNS involvement – poor
Osteomyelitis – good but will require lifelong treatment
How do azoles work ?
Relevant axoles?
inhibits sterol 14α- demethylase (cytochrome p450) essential for the synthesis of ergosterol a key component of the fungal cell wall (fungistatic). All azoles are teratogenic and should not be given to pregnant animals.
Ketoconazole
- Main indications: Malassezia dermatitis & nasal cryptococcosis
- Penetration: skin, bone, joint, lung (poor BBB penetration)
- Potent inhibitor of mammalian cytochrome p450 and P-glycoprotein
- Can predispose animals to ivermectin toxicity, especially if MDR-1
Itraconazole;
- Main indications: most widely used drug (cryptococcosis, blastomycosis, histoplasmosis, aspergillosis, coccioidomycosis)
- Highly protein bound and agents of choice for fungal osteomyelitis. With inflammation may cross the BBB
- Side effects: GI, Risk of hepatotoxicity
Inhibit cytochrome p450 does not inhibit cortisol production, Ulcerative skin lesion.
Fluconazole
- Main indications: cryptococcus, candida and Malassezia. Aspergillosis species are inherently resistant to fluconazole
- Highly water soluble; can cross the BBB
Amphotericin B
- Mechanism of action: irreversibly bind to ergosterol causing formation of pores which cause leakage of intracellular content (fungistatic but may be fungicidal at high doses)
Indications: systemic disseminated mycosis
- Side effects: Nephrotoxicity (Lipid formulation have decreased nephrotoxicity )
what are drugs that can increase the action of duration of p-glycoprotein and why may these cause adverse side effects with antifungal treatemnts?
increase duration of action of P-glycoprotein drugs (vinca-alkaloids, cyclosporine, digoxin, etc…) May predispose to ivermectin toxicity
Aspergillosis is inherently resistant to which anti-fungal?
fluconazole
what are the main indications for itraconazole ?
cryptococcosis, blastomycosis, histoplasmosis, aspergillosis, coccioidomycosis
What side effects can itraconazole cause?
- GI
- Risk of hepatotoxicity
- Inhibit cytochrome p450 does not inhibit cortisol production
- Ulcerative skin lesion
what is a common target for anti-fungal therapies ?
How is this targeted?
Ergosterole - key component of cell walls
Azoles -> inhibits sterol 14α- demethylase (cytochrome p450) essential for the synthesis of ergosterol (fungistatic)
Amphotericin-B -> irreversibly bind to ergosterol causing formation of pores which cause leakage of intracellular content (fungistatic, maybe fungicidal at high doses)
what is the causative agent of blastomycosis?
Blastomycosis dermatitis
blasto pathogenesis Cx, Dx, Tx
Found next to body of water in the Ohio, Greatlake, and Mississipi valley basin -> suspect to be from decaying plant matter
Believed to be inhaled; however, it can also be inoculated through trauma. A potent virulence factor such as cell surface glycoprotein-1 (BAD-1) which allows blastomycosis to bind to macrophages and modulate the immune response. Outcome of infection include:
- Localized pulmonary disease
- Disseminated disease; it can spread everywhere; however, does have a site of predilection for the skin.
Cx
- Cutaneous lesions – cutaneous mass, ulcer and draining tract
- Lymphadenopathy
- Ocular manifestation
- Respiratory
- Neurological involvement is uncommon in dogs -> Cats more likely to get neurological or intestinal involvement
Dx
- CBC: mild normocytic normochromic anemia
- Chemistry: hyperglobinemia, hypoalbuminemia
- X-rays: varying degree of pulmonary pattern ranging from diffuse to mass-like lesion
- Microbiological testing
- > Cytology of affected organs usually yield good-fair sensitivity (~ 70% from tracheal wash, around 80% for fine needle aspirate)
- > urine to Mira vista (can cross react with histoplasmosis) )Urine sensitivity ~ 94%, Blood sensitivity ~ 87%)
- > Fungal culture poses a high health hazard
- > PCR not validated in vet species
TX
- Monoazole therapy: itraconazole
- Severe disseminated disease, consider amphotericin B
- If severe osteomyelitis or large fungal granuloma present, may need to consider surgical removal of the granuloma
what is the prognosis for blasto?
cure -rate between 50-75%
Poor prognosis if CNS involvement, severe lung disease, or high band count
types of aspergillosis infection ?
pathogenesis ?
Caused by aspergillus spp. which are found ubiquitously in the environment. Depending on the disease can cause a variety of disease presentation
- Sino-nasal aspergillosis (SNA) & Sino-orbital (SOA)
- Bronchopulmonary aspergillosis
- Disseminated aspergillosis
- Keratomycosis
*A. Fumigatus; *
- Breed predisposition: large dolicocephalic breeds (e.g., German Shepherd, Rottweiller, Labrador)
- pathogenesis; fungal spores are deposited in the nasal cavity. Due to a defect of the host local immune response there is colonization and germination the fungal hyphae. These do not invade tissues. The local production of toxins and the host immune response are though to cause the extensive turbinate destruction
A Felis spp novo
- Breed predisposition: brachycephalic cats (Persian and Himalayan)
- Pathogenesis: A. felis spp. novo will invade the submucosa and extend into the orbital bone into the retrobulbar space causing a retrobulbar mass effect.
A terreus, A Deflectus
- disseminated aspergillosis
- Breed predisposition: German Shepherd
- Pathogenesis: Like with sino-nasal aspergillosis there is inhalation of spores which can disseminate to distant organs. This is due to unknown defect in immunity. Anatomical site of predilection include: vertebral end plates (discospondylitis), renal pelvis, spleen and long bones.
what are Cx, Dx and Tx for aspergillosis ?
Cx
Non-specific and depends on location of lesion – more commonly weight loss/lethargy
Dx
- CBC: leukocytosis is present in most dogs
- Chemistry: often hyperglobinemia
- X-rays; Bronchial pattern/pneumonia – >bronchial aspergillosis
- Discospondylitis > 2 sites often present
- Microbiological testing:
- Fungal culture (50% positive urine culture/ 33% blood or CNS culture)
- Serology – Antigen (don’t do antibodies)
Tx
- Systemic antifungal therapy with azole (itraconazole, posiconazole, voriconazole) +/- amphotericin B
- Prognosis guarded – even if enter remission will require lifelong treatment and will relapse
