Lesson 48 - Systemic Fungal Infections in Small Animals

What makes animals more susceptible to systemic mycoses?

1. Immune mediated Disease

2. Immunosuppressive therapy

3. Splenectomy

What are the portals of entry for fungal diseases?

1. respiratory tract

2. GI tract

3. skin

What is the primary portal of entry for fungal diseases?

respiratory tract

What do the clinical signs of fungal disease depend on?

what system is affected

What are the clinical signs of a systemic fungal disease?

1. weight loss

2. lymphadenopathy

3. pyrexia

What are the clinical signs of a respiratory fungal disease?

1. cough

2. dyspnea

3. exercise intolerance

What other systems can have clinical signs from fungal infections?

1. Skin

2. Ophthalmologic

3. Nasal

4. Gastrointestinal

5. Lymph nodes

6. Vascular

How can fungal diseases be diagnosed?

1. cytology (fluids, scrapes)

2. histopathology of masses

3. culture

4. molecular techniques

5. antigen specific tests

6. serology

What is important about using histopathology for diagnosing fungal diseases?

might need special stains, so let the lab know you are suspecting a fungal disease

What is important to know about using culture to diagnose fungal diseases?

takes a long time and could be zoonotic and put staff at risk

What is important to know about using serology to diagnose fungal diseases?

1. Often not diagnostic

2. Antigen vs. Antibodies

3. Paired samples

What is important about treatment of fungal diseases?

1. difficult

2. expensive

3. long treatment courses

4. dependent on pharmacologics of antifungals

What are the different drug targets for antifungals?

1. membrane function

2. cell wall synthesis

3. nucleic acid synthesis

4. ergosterol synthesis

What are the different categories of antifungals?

1. Azole derivatives

2. Microorganism produced antibiotics

3. Chitin synthesis inhibitors

4. Allylamine derivatives

5. Potassium iodide

6. Flucytosine

What are the azole derivitives?

1. imidazoles

2. triazoles

What is an imidazole drug?

ketoconazole/nizoral

How can ketoconazole/nizoral be used?

with Amphotericin B

What are the triazoles?

1. fliconazole/diflucan

2. itraconozole/sporanox

3. clotrimazole/lotrimin

4. enilconazole

5. posiconazole

6. voriconazole/vfend

What is important to know about fluconazole/diflucan?

1. Good for CNS, urine, ocular

2. Can cause PU/PD

What is important to know about itraconozole/sporanox?

1. Good for skin

2. Must be given with food

What is clotrimazole/lotrimin good for treating?

nasal aspergillosis

What is important to know about posiconazole?

need therapeutic drug monitoring

What is important to know about voriconazole/vfend?

1. crosses BBB

2. do not use in cats

3. expensive

How do azole derivatives work?

1. inhibit ergosterol synthesis via cytochrome P-450

2. loading dose (14 days to steady state)

3. can use in conjunction with a low amphotericin B dose

What antifungals are used for almost all systemic mycoses?

azole derivatives

What are the side effects of azoles?

1. Dose related

2. Ketoconazole often affects the liver and adrenals

3. Cytochrome P450 drug interactions

4. Skin

5. GI in cats

What kind of antifungal is amphotericin B?

macrolide antibiotic

How does amphotericin B work?>

binds to sterols in fungal cell membranes

What are the downsides of using amphotericin B?

1. significant hepatic and renal toxicity

2. needs monitoring

3. poor bioavailability

What is the safest amphotericin B form?

abelcet lipid based (expensive)

How does flucytosine work?

inhibits protein synthesis via DNA and RNA inhibition

When would you use flucytosine with amphotericin B?

cats with cryptococcosis

What are the pharmacokinetics of flucytozine?

1. wide tissue distribution

2. penetrates BBB

What are the side effects of flucytosine?

1. Diarrhea

2. Anorexia

3. Vomiting

4. Dose dependent bone marrow suppression

What is terbinifine useful for?

add on for many fungal diseases

How does allylamine work?

inhibits ergosterol biosynthesis

What are the pharmacokinetics of terbinifine?

1. Well distributed in the skin

2. May have use systemically in conjunction with itraconazole for pythiosis

What are the side effects of terbinifine?

1. GI

2. Hepatic

3. Cutaneous reactions

What causes blastomycoses?

Blastomyces dermatitidis

What kind of fungus is blastomycosis?

1. dimorphic

2. soil disruption

Where does blastomycosis like to disseminate to?

1. bones

2. eyes

3. lungs

4. lymph nodes

5. skin

6. prostate

How is blastomycosis differentiated from yeast?

broad based budding

What animals are prone to blastomycosis infection?

1. young, male, large breed dogs

2. sporting/hunting breeds

3. dogs that go in water

What is the incubation period for blastomycosis?

5-12 weeks

How do inhaled conidiophores (blastomycosis) cause disease?

1. disseminates to lungs, LN, eyes, skin, bones, prostate

2. Mø activation

3. +/- Hyper Ca++

4. cell mediated immune response

5. pyogranulomatous inflammation

Why can blastomycosis cause hypercalcemia?

pyogranulomatous inflammation and macrophage activation

What are the clinical signs of blastomycosis?

1. depends on system affected

2. 65-85% pulmonary signs (dry cough)

3. lymphadenopathy

4. cutaneous signs (especially cats)

5. opthalmologic signs

6. lameness

7. neurological signs (mostly in cats)

How is blastomycosis diagnosed?

1. PE

2. fundic examination

3. CBC and Chem

4. cytology/histopathology

5. serology

What are the definitive diagnostic methods for blastomycoses?

1. organism identification on cytology, histopathology, or culture

2. antigen testing

How can blastomycosis infections manifest in the eyes?

1. Anterior uveitis

2. Panophthalmitis

3. Chorioretinitis

4. Retinal detachment

5. Optic neuritis

What treatment options should you consider for recurring ophthalmic blastomycoses infections?

enucleation

How are blastomycoses infections treated?

1. itraconozole with food

2. treat for at lease 3-6 months until no clinical signs

3. loading dose for first 3-5 days

4. supportive care

What percent of patients respond to blastomycoses treatment?

70%

When is prognosis for blastomycoses infection poorer?

hypoxic with more than 3 systems affected

What should you do when treating a patient with severe hypoxemia from a blastomycoses infection?

combination therapy with amphotericin B lipid complexed

What causes histoplasmosis?

Histoplasma capsulatum

What are the characteristics of histoplasmosis?

1. Dimorphic

2. Soil saprophyte

3. Outbreaks associated with chicken coops, bird roosts, and bat habitats

4. 12-16 day incubation

5. usually infects younger animals

What are the characteristics of a histoplasmosis infection that spreads to the lungs or GI?

1. Disseminates to lymph nodes, liver, spleen, BM, eyes

2. Granulomatous inflammation

What are the clinical signs of a histoplasmosis infection in cats?

1. Insidious and non-specific

2. Depression, fever, weight loss, pale mm

3. Hepatomegaly

4. Splenomegaly

5. Retinal pigment proliferation or edema

6. Chorioretinitis, anterior uveitis, Panophthalmitis

What dog breeds are overrepresented when it comes to histoplasmosis infections?

male pointers, weimaraners, and brittneys

What are the GI clinical signs of histoplasmosis infections in dogs?

1. Often large intestinal diarrhea early on

2. Small intestinal signs as disease progresses

3. Fever, anorexia, depression, severe weight loss

How is histoplasmosis diagnosed?

1. CBC

2. blood smear

3. chemistry

4. serology

5. imaging

What would you see on a blood chemistry with a histoplasmosis infection?

hypoalbuminemia and hypercalcemia

What are the methods of definitively diagnosing a histoplasmosis infection?

1. organism identification using cytology, histology, or culture

2. antigen testing

How is histoplasmosis treated?

1. itraconozol for 4-6 months until clinical signs resolve

2. supportive care

What are some examples of GI supportive care for a histoplasmosis infection?

1. Proper nutrition

2. Highly digestible diet

3. Pre and pro-biotics

4. +/- fiber

5. +/- anti-diarrheal

What are some examples of respiratory supportive care for a histoplasmosis infection?

1. oxygen

2. bronchodilators

What causes coccidiomycosis?

Coccidioides immitis or posadasii

What causes valley fever/rheumatism in humans (reportable)?

coccidiomycosis

What is the primary route of coccidiomycosis infection?

respiratory

What are the life cycles of coccidiomycosis?

parasitic and saphrophytic

What is on all rule out lists in CA and AZ?

coccidiomycosis

What dogs are prone to coccidiomycosis infections?

young, male intact, medium to large outdoor large breed dogs

What is the disease progression of coccidiomycosis?

1. Host immunocompetence

2. Mild clinically silent pulmonary disease

3. Fatal multisystem dissemination

4. Depends on areas of dissemination

5. Hilar lymphadenopathy, coughing, difficulty swallowing

6. Host controls disease or dies

What are the clinical signs of coccidiomycosis?

1. Depends on areas of dissemination

2. Hilar lymphadenopathy

3. Coughing

4. Difficulty swallowing

5. Lethargy

6. Anorexia

7. Fever

8. Chronic lameness

9. Cervical or head pain

10. Weight loss

How is coccidiomycosis often diagnosed in endemic areas?

clinical signs and lymphadenopathy

How is coccidiomycosis diagnosed?

1. Thoracic radiographs for perihilar lymphadenopathy

2. IMMY antibody test

3. Precipitin test early in disease to detect IgM antibodies

4. Complement fixation of IgG antibodies

5. Culture is dangerous

How does the IMMY coccidiomycosis antibody test work?

1. 30 minutes

2. Might help antimicrobial stewardship

3. Choose antifungal before an antimicrobial

What can persistence of a precipitin test indicate about a coccidiomycosis infection?

dissemination

How is coccidiomycosis treated?

1. Azoles if outpatient (Itra/fluconazole)

2. Amphotericin B lipid complex if life threatening

3. Antifungal Combinations

4. Allylamine add on

Why should all dogs with suspected coccidiomycosis infections be treated?

1. historically high mortality

2. if they get sick 25% will disseminate and die

3. Minimum of 4-6 months beyond clinical cure

4. Relapse common

What causes cryptococcosis?

1. Cryptococcus neoformans

2. C. gattii

What are the characteristics of cryptococcosis?

1. Saphrophytic yeast

2. World wide

3. Avian habitats from pigeon droppings

4. Nasal cavity, skin, sinuses, paranasal tissues, and lungs

5. Local Invasion of skin, eyes, CNS

6. Systemic dissemination via lungs

What is the more virulent and CNS invasive cryptococcosis species?

c. gattii

What is the most common fungal infection of cats?

cryptococcus

What are the clinical signs of cryptococcosis?

1. Upper Respiratory/Nasopharyngeal

2. Respiratory discharge, proliferative masses

3. Snoring, stertor, dyspnea

4. CNS, ocular

5. Depression and anorexia

6. Additional signs associated with systemic dissemination

How is cryptococcosis diagnosed?

1. CBC/Chem

2. Imaging (CT)

3. +/- CSF tap

4. Serology not really useful

5. Organism identification using cytology, histopathology, or culture

6. antigen testing

7. molecular typing

8. anti-fungal susceptibility

How is cryptococcosis treated?

1. fluconozole if CNS symptoms present

2. itraconazole

3. combination treatment using an azole, amphotericin B and flucytosine if infection is systemic

4. treat for 2 months after clinical signs resolve

5. monitor serum antigen test for a 2-4 fold decrease per month of treatment

6. recheck chem monthly

7. should consider surgical debridement for fungal plaques

What causes aspergillosis?

Aspergillus fumigatus

What are the characteristics of aspergillosis?

1. Ubiquitous filamentous fungi

2. Local or disseminated infection

3. Nasal passages and frontal sinuses

4. Progressive and invasive

What dogs are prone to aspergillosis infections?

young to middle aged mesaticephalic and dolichocephalic breeds

What are the clinical signs of aspergillosis?

1. Facial pain

2. Mucoid to hemorrhagic and crusting nasal discharge

3. Nasal depigmentation

4. Anorexia

5. Sneezing

6. Neurologic or ocular

7. Masticatory muscle atrophy

How is aspergillosis diagnosed?

1. Imaging (skull rads, skull CT, endoscopy)

2. Cytology/histopathology/fungal culture

3. Nasal biopsies

How is aspergillosis treated?

1. Topical clotrimazole (1% )/enilconazole

2. 85% will be cured after 1 treatment

3. +/- oral Itraconazole or fluconazole + terbinafine

4. Combination therapy in cats

5. Disseminated

How is aspergillosis treated in immunocompromised patients?

1. GS IgA

2. Azoles, +/- Amph B lipid complex, surgical removal of granulomas

3. Poor prognosis

What causes sporothrix?

Sporothrix schenckii

What are the characteristics of sporothrix?

1. Dimorphic

2. Saprophytic

3. Chronic granulomatous disease

4. Cutaneous, lymphocutaneous, disseminated

What is the usual entry point of sporothrix?

skin post trauma

How is sporothrix diagnosed?

1. cytology

2. histopathology

3. culture (be careful)

What species is harder to treat for sporothrix infections?

cats much harder to treat than dogs