Systemic Fungal Infections in Small Animals Colleen Hock May 12,

The Mycotic Agents Blastomyces dermatitidis Blastomyces dermatitidis Histoplasma capsulatum Histoplasma capsulatum Coccidioides immitis Coccidioides immitis –All are dimorphic (mold and yeast forms) –Cause primarily respiratory disease by evasion of the host immune response

Blastomycosis Blastomyces dermatitidis Blastomyces dermatitidis South east, south central, and upper midwest near river valleys and lakes South east, south central, and upper midwest near river valleys and lakes Moist and shaded areas with increased organic matter (soil and wood) Moist and shaded areas with increased organic matter (soil and wood)

Blastomycosis: Clinical Signs Dogs: Dyspnea Anorexia Dogs: Dyspnea Anorexia Depression Lameness Lymphadenopathy Skin Lesions +/- occular manifestations +/- Orchitis Depression Lameness Lymphadenopathy Skin Lesions +/- occular manifestations +/- Orchitis Cats: Dyspnea Nasal discharge Cough Lethargy Weight loss Cats: Dyspnea Nasal discharge Cough Lethargy Weight loss **Pneumonia and weight loss are the most common presentations**

Blastomycosis Occular blastomycosis: Panophthalmitis e/detail/ Cutaneous blastomycosis: Dermatitis

Blastomycosis: Pathogenesis Inhale spores  Deposit in the alveoli  Acute Pulmonary Phase   Self-limiting control of asexual reproduction Asexual budding, not eliminated by the immune system OR the patient is immunocompromised  Pyogranulomatous Inflammation within the lungs Lymphatic and Hematogenous Spread of spores  Inflammation in skin, bones, LN’s, eyes, CNS, and/or reproductive tract

Blastomycosis: Diagnosis History, Clinical signs, and Diagnostic findings History, Clinical signs, and Diagnostic findings Definitive diagnosis must show the organism Cytology: TTW, BAL, LN aspirates, fluid from the anterior chamber of the eye, draining tracts, prostatic fluid, and CSF Definitive diagnosis must show the organism Cytology: TTW, BAL, LN aspirates, fluid from the anterior chamber of the eye, draining tracts, prostatic fluid, and CSF Never Culture Blastomyces because of danger to personnel Never Culture Blastomyces because of danger to personnel

Blastomycosis: Diagnosis Serology (AGID) is helpful if the organism cannot be definitively diagnosed. - Sensitivity and Specificity > 90% Serology (AGID) is helpful if the organism cannot be definitively diagnosed. - Sensitivity and Specificity > 90% Thoracic Radiographs indicated when respiratory signs present: - interstitial pattern - nodular interstitial pattern/diffuse miliary Thoracic Radiographs indicated when respiratory signs present: - interstitial pattern - nodular interstitial pattern/diffuse miliary - tracheobronchial lymphadenopathy

Blastomycosis: Pyogranulomatous Inflammation

Nodular Interstitial Pattern/Diffuse Milliary Pattern Differentials -Lymphoma -Fungal pneumonia -Pneumoconiosis -Hematogenous bacterial pneumonia -Metastases from thyroid or mammary carcinoma

Blastomycosis: Fungal Granuloma Differentials -Tumor metastases -Fungal granuloma -Parasitic granuloma -Abscesses -Lymphoma -Malignant histiocytosis -Lymphoid granulomatosis -Cysts/Fluid filled bullae

Fungal Osteomyelitis: Blastomyces dermatitidis rojects/saortho/chapter_3 7/37mast.htm

Fungal Osteomyelitis vs. Bone Tumors nimalTopics/BoneTumorsinCatsandDogs/ 341%20Lecture%207%20Musculoskeletal%20Part%201. ppt#362,49,Fungal Osteomyelitis  

Blastomycosis: Treatment Amphotercin B - IV, nephrotoxic - Lipid soluble form that is less toxic Amphotercin B - IV, nephrotoxic - Lipid soluble form that is less toxic Iatroconazole - less toxic - oral administration - more expensive Iatroconazole - less toxic - oral administration - more expensive

Histoplasmosis Histoplasma capsulatum Histoplasma capsulatum Found in soil near avian species (especially starlings) and bats Found in soil near avian species (especially starlings) and bats 3 forms in dogs: pulmonary, disseminated, and subclinical 3 forms in dogs: pulmonary, disseminated, and subclinical Rare and progressive in cats Rare and progressive in cats

Histoplasmosis: Clinical Signs Dogs - coughing - dyspnea - anorexia - weight loss - depression - ascites - ulcerated oral and/or nasal mucosa - anemia - lymphadenopathy - thrombocytopenia - fever - diarrhea Dogs - coughing - dyspnea - anorexia - weight loss - depression - ascites - ulcerated oral and/or nasal mucosa - anemia - lymphadenopathy - thrombocytopenia - fever - diarrhea Cats - weight loss - lethargy - fever (fluctuant) Cats - weight loss - lethargy - fever (fluctuant) dlife-facts/2007/wildlife- facts_images_2007/2-brazilian_free- tailed_bat.jpg

Histoplasmosis: Pathogenesis Inhale or ingest microconidia or hyhae  Conversion to yeast within the host  Yeasts engulfed by macrophages and they replicate intracellularly   Immune system is overwhelmed  Hematogenous and Lymphatic spread Clear infection

Histoplasmosis: Diagnosis Cytology: exudates, TTW, FNA (LN’s), and Bone Marrow Cytology: exudates, TTW, FNA (LN’s), and Bone Marrow Histopathology Histopathology Serology Serology Blood smear Blood smear k/edison/Fig4ADJ

Histoplasmosis: Diagnosis Radiographs: - pulmonary interstitial pattern with miliary or nodular infiltrates - Abdomen: hepatomegaly, splenomegaly, and ascites - Gastogram: Barium highlights thickening of the intestinal wall and mucosa - Abdominal Ultrasound for gi thickening - Bone: osteolysis with periosteal proliferation Radiographs: - pulmonary interstitial pattern with miliary or nodular infiltrates - Abdomen: hepatomegaly, splenomegaly, and ascites - Gastogram: Barium highlights thickening of the intestinal wall and mucosa - Abdominal Ultrasound for gi thickening - Bone: osteolysis with periosteal proliferation Endemic areas: may see patients with calcification in the thorax or abdomen secondary to persistence of the organism Endemic areas: may see patients with calcification in the thorax or abdomen secondary to persistence of the organism

Histoplasmosis

Histoplasmosis

Histoplasmosis

Histoplasmosis: Fungal osteomyelitis hapter_37/37F8.jpg

Histoplasmosis: Treatment Iatroconazole: lower toxicity Iatroconazole: lower toxicity

Coccidiomycosis Coccidioides immitis Coccidioides immitis Soil in arid or semi-arid regions Soil in arid or semi-arid regions Virulent reputation Virulent reputation Epidemics after rainy season followed by a drought Epidemics after rainy season followed by a drought

Coccidiomycosis: Clinical Signs Dogs - dyspnea - anorexia - cough - weight loss - lameness - draining tracts - abscesses - lymphadenopathy - meningitis Dogs - dyspnea - anorexia - cough - weight loss - lameness - draining tracts - abscesses - lymphadenopathy - meningitis Signs can range from flu-like symptoms to severe pneumonia when pulmonary tissue involved Signs can range from flu-like symptoms to severe pneumonia when pulmonary tissue involved Can see extensive damage to bones, joints, skin, and CNS when dissemination occurs Can see extensive damage to bones, joints, skin, and CNS when dissemination occurs Fatal when immunocompromised Fatal when immunocompromised

Coccidiomycosis: Pathogenesis Inhalation of infective arthroconidia  Deposition in the lung  Microenvironment induces endosporulation  Endospores released  Removed by mononuclear cells  Subclinical or clearance of organisms Immunocompromised patients Extensive lung damage Dissemination 

Coccidiomycosis: Diagnosis Cytology: exudate, TTW, LN or bone biopsy Cytology: exudate, TTW, LN or bone biopsy Wet mount with 10% KOH - endospores 2-5 um - spherules um - mycelial form= dangerous Wet mount with 10% KOH - endospores 2-5 um - spherules um - mycelial form= dangerous Serology Serology Radiographs: Thorax and bones Radiographs: Thorax and bones

Coccidiomycosis: wet mount

Coccidiomycosis

Coccidiomycosis: Fungal osteomyelitis

Coccidiomycosis: fungal osteomyelitis

Coccidiomycosis: Treatment Ketoconazole: helps to prevent dissemination Ketoconazole: helps to prevent dissemination Iatroconazole Iatroconazole

References eTumorsinCatsandDogs/ eTumorsinCatsandDogs/ eTumorsinCatsandDogs/ eTumorsinCatsandDogs/ Songer, J.G., & Post, K.W. (2003). Veterinary Microbiology. St Louis: Elsevier. Songer, J.G., & Post, K.W. (2003). Veterinary Microbiology. St Louis: Elsevier. eTumorsinCatsandDogs/ eTumorsinCatsandDogs/ eTumorsinCatsandDogs/ eTumorsinCatsandDogs/ 7%20Musculoskeletal%20Part%201.ppt#362,49,Fungal Osteomyelitis 7%20Musculoskeletal%20Part%201.ppt#362,49,Fungal Osteomyelitis