Systemic Fungal Systemic Fungal Infections in Small Infections in Small AnimalsAnimals

Colleen HockColleen Hock

May 12, 2010May 12, 2010

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The Mycotic AgentsThe Mycotic Agents

Blastomyces dermatitidisBlastomyces dermatitidis Histoplasma capsulatumHistoplasma capsulatum Coccidioides immitisCoccidioides immitis

– All are dimorphic (mold and yeast All are dimorphic (mold and yeast forms)forms)

– Cause primarily respiratory disease Cause primarily respiratory disease by evasion of the host immune by evasion of the host immune responseresponse

BlastomycosisBlastomycosis

Blastomyces dermatitidisBlastomyces dermatitidis South east, south central, and South east, south central, and

upper midwest near river valleys upper midwest near river valleys and lakesand lakes

Moist and shaded areas with Moist and shaded areas with increased organic matter (soil and increased organic matter (soil and wood)wood)

http://www.familyvet.com/Dogs/Fungi.html

Blastomycosis: Clinical Blastomycosis: Clinical SignsSigns Dogs: DyspneaDogs: Dyspnea

Anorexia Anorexia

DepressionDepression Lameness Lameness

LymphadenopathyLymphadenopathy Skin Lesions Skin Lesions +/- occular +/- occular

manifestations manifestations +/- Orchitis +/- Orchitis

Cats: DyspneaCats: Dyspnea Nasal Nasal dischargedischarge

Cough Cough Lethargy Lethargy Weight loss Weight loss

**Pneumonia and weight loss are **Pneumonia and weight loss are the the most common presentations** most common presentations**

BlastomycosisBlastomycosis

Occular blastomycosis: Panophthalmitis

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http://www.njmoldinspection.com/vetmycology/vetblastomycosis.html

Cutaneous blastomycosis:Dermatitis

Blastomycosis: Blastomycosis: PathogenesisPathogenesis

Inhale sporesInhale spores

Deposit in the alveoliDeposit in the alveoli

Acute Pulmonary PhaseAcute Pulmonary Phase

Self-limiting control Self-limiting control

of asexual reproductionof asexual reproductionAsexual 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: Blastomycosis: DiagnosisDiagnosis History, Clinical signs, and Diagnostic History, Clinical signs, and Diagnostic

findingsfindings Definitive diagnosis must show the Definitive diagnosis must show the

organismorganism

Cytology: TTW, BAL, LN aspirates, fluid Cytology: TTW, BAL, LN aspirates, fluid from the anterior chamber of the from the anterior chamber of the eye, draining tracts, prostatic eye, draining tracts, prostatic fluid, and CSF fluid, and CSF

Never Culture Blastomyces because of Never Culture Blastomyces because of danger to personneldanger to personnel

http://www.pharmacy-and-drugs.com/illnessessimages/blastomycosis2.jpg

Blastomycosis: Blastomycosis: DiagnosisDiagnosis Serology (AGID) is helpful if the organism Serology (AGID) is helpful if the organism

cannot be definitively diagnosed.cannot be definitively diagnosed.- Sensitivity and Specificity > 90% - Sensitivity and Specificity > 90%

Thoracic Radiographs indicated when Thoracic Radiographs indicated when respiratory signs present:respiratory signs present:- interstitial pattern- interstitial pattern- nodular interstitial pattern/diffuse miliary- nodular interstitial pattern/diffuse miliary

- tracheobronchial lymphadenopathy- tracheobronchial lymphadenopathy

http://www.vet.uga.edu/vpp/clerk/mordecai/index.php

Blastomycosis: Blastomycosis: Pyogranulomatous Pyogranulomatous Inflammation Inflammation

Nodular Interstitial Nodular Interstitial Pattern/Diffuse Milliary Pattern/Diffuse Milliary PatternPattern

www.vet.uga.edu/vpp/clerk/mordecai/figure1.jpg

Differentials-Lymphoma-Fungal pneumonia-Pneumoconiosis-Hematogenous bacterial pneumonia-Metastases from thyroid or mammary carcinoma

Blastomycosis: Fungal Blastomycosis: Fungal GranulomaGranuloma

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

Fungal Osteomyelitis: Fungal Osteomyelitis: Blastomyces Blastomyces dermatitidisdermatitidis

http://cal.vet.upenn.edu/projects/saortho/chapter_37/37mast.htm

Fungal Osteomyelitis vs. Bone Fungal Osteomyelitis vs. Bone TumorsTumors

http://www.acvs.org/AnimalOwners/HealthConditions/SmallAnimalTopics/BoneTumorsinCatsandDogs/

http://people.upei.ca/lpack/vetrad/VCA%20341/VCA%20341%20Lecture%207%20Musculoskeletal%20Part%201.ppt#362,49,Fungal Osteomyelitis

Blastomycosis: Blastomycosis: TreatmentTreatment Amphotercin BAmphotercin B

- IV, nephrotoxic- IV, nephrotoxic- Lipid soluble form that is less - Lipid soluble form that is less toxictoxic

IatroconazoleIatroconazole- less toxic- less toxic- oral administration- oral administration- more expensive- more expensive

http://www.cvs.com/CVSApp/images/health/A1055050.JPG

HistoplasmosisHistoplasmosis

Histoplasma capsulatumHistoplasma capsulatum Found in soil near avian species Found in soil near avian species

(especially starlings) and bats(especially starlings) and bats 3 forms in dogs: pulmonary, 3 forms in dogs: pulmonary,

disseminated, and subclinicaldisseminated, and subclinical Rare and progressive in catsRare and progressive in cats

http://www.familyvet.com/Dogs/Fungi.htmlhttp://www.familyvet.com/Dogs/Fungi.html

Histoplasmosis: Histoplasmosis: Clinical SignsClinical Signs DogsDogs

- coughing- coughing- dyspnea- dyspnea- anorexia- anorexia- weight loss- weight loss- depression- depression- ascites- ascites- ulcerated oral and/or - ulcerated oral and/or nasal mucosa nasal mucosa- anemia- anemia- lymphadenopathy- lymphadenopathy- thrombocytopenia- thrombocytopenia- fever- fever- diarrhea- diarrhea

CatsCats- weight loss- weight loss- lethargy- lethargy- fever (fluctuant)- fever (fluctuant)

http://cat.uab.cat/Publications/2005/SEP05/starlings.jpg

http://www.fs.fed.us/r8/caribbean/wildlife-facts/2007/wildlife-facts_images_2007/2-brazilian_free-tailed_bat.jpg

Histoplasmosis: Histoplasmosis: PathogenesisPathogenesis

Inhale or ingest microconidia or hyhae

Conversion to yeast within the host

Yeasts engulfed by macrophages and they replicate intracellularly

Immune system isoverwhelmed

Hematogenous and Lymphatic spread

Clear infection

Histoplasmosis: Histoplasmosis: DiagnosisDiagnosis

Cytology: exudates, TTW, FNA Cytology: exudates, TTW, FNA (LN’s), and Bone Marrow(LN’s), and Bone Marrow

HistopathologyHistopathology SerologySerology Blood smearBlood smear

http://www.google.ca/imgres?imgurl=http://www.vet.uga.edu/vpp/clerk/edison/Fig4ADJ

Histoplasmosis: Histoplasmosis: DiagnosisDiagnosis Radiographs:Radiographs:

- pulmonary interstitial pattern with - pulmonary interstitial pattern with miliary or nodular infiltrates miliary or nodular infiltrates- Abdomen: hepatomegaly, splenomegaly, and - Abdomen: hepatomegaly, splenomegaly, and ascites ascites- Gastogram: Barium highlights thickening of - Gastogram: Barium highlights thickening of the the intestinal wall and mucosa intestinal wall and mucosa- Abdominal Ultrasound for gi thickening- Abdominal Ultrasound for gi thickening- Bone: osteolysis with periosteal proliferation- Bone: osteolysis with periosteal proliferation

Endemic areas: may see patients with Endemic areas: may see patients with calcification in the thorax or abdomen calcification in the thorax or abdomen secondary to persistence of the organismsecondary to persistence of the organism

HistoplasmosisHistoplasmosis

http://www.vet.uga.edu/vpp/clerk/edison/Fig4ADJ.jpg

HistoplasmosisHistoplasmosis

http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/51108.htm

HistoplasmosisHistoplasmosis

http://www.vet.uga.edu/vpp/clerk/edison/index.php

Histoplasmosis: Histoplasmosis: Fungal osteomyelitisFungal osteomyelitis

http://cal.vet.upenn.edu/projects/saortho/chapter_37/37F8.jpg

Histoplasmosis: Histoplasmosis: TreatmentTreatment Iatroconazole: lower toxicityIatroconazole: lower toxicity

http://www.my-online-pharmacy.net/i/products/sporanox.jpg

CoccidiomycosisCoccidiomycosis

Coccidioides immitisCoccidioides immitis Soil in arid or semi-arid regions Soil in arid or semi-arid regions Virulent reputationVirulent reputation Epidemics after rainy season followed Epidemics after rainy season followed

by a droughtby a drought

http://www.familyvet.com/Dogs/Fungi.htmlhttp://www.familyvet.com/Dogs/Fungi.html

Coccidiomycosis: Clinical Coccidiomycosis: Clinical SignsSigns

DogsDogs- dyspnea- dyspnea- anorexia- anorexia- cough- cough- weight loss- weight loss- lameness- lameness- draining tracts- draining tracts- abscesses- abscesses- lymphadenopathy- lymphadenopathy- meningitis- meningitis

Signs can range Signs can range from flu-like from flu-like symptoms to severe symptoms to severe pneumonia when pneumonia when pulmonary tissue pulmonary tissue involvedinvolved

Can see extensive Can see extensive damage to bones, damage to bones, joints, skin, and CNS joints, skin, and CNS when dissemination when dissemination occursoccurs

Fatal when Fatal when immunocompromiseimmunocompromisedd

Coccidiomycosis: Coccidiomycosis: PathogenesisPathogenesis

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 lungdamage

Dissemination

Coccidiomycosis: Coccidiomycosis: DiagnosisDiagnosis Cytology: exudate, TTW, LN or Cytology: exudate, TTW, LN or

bone biopsybone biopsy Wet mount with 10% KOHWet mount with 10% KOH

- endospores 2-5 um- endospores 2-5 um- spherules 10-100 um- spherules 10-100 um- mycelial form= dangerous- mycelial form= dangerous

SerologySerology Radiographs: Thorax and bones Radiographs: Thorax and bones

Coccidiomycosis: wet Coccidiomycosis: wet mountmount

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CoccidiomycosisCoccidiomycosis

http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/51104.htm

Coccidiomycosis: Coccidiomycosis: Fungal osteomyelitisFungal osteomyelitis

http://www.familyvet.com/Dogs/Fungi.htmlhttp://www.familyvet.com/Dogs/Fungi.html

Coccidiomycosis: fungal Coccidiomycosis: fungal osteomyelitisosteomyelitis

http://cal.vet.upenn.edu/projects/saortho/chapter_37/37mast.htmhttp://cal.vet.upenn.edu/projects/saortho/chapter_37/37mast.htm

Coccidiomycosis: Coccidiomycosis: TreatmentTreatment

Ketoconazole: helps to prevent Ketoconazole: helps to prevent disseminationdissemination

IatroconazoleIatroconazole

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ReferencesReferences http://www.vet.uga.edu/vpp/clerk/mordecai/index.phphttp://www.vet.uga.edu/vpp/clerk/mordecai/index.php http://www.familyvet.com/Dogs/Fungi.htmlhttp://www.familyvet.com/Dogs/Fungi.html http://cal.vet.upenn.edu/projects/saortho/chapter_37/37mast.htmhttp://cal.vet.upenn.edu/projects/saortho/chapter_37/37mast.htm http://www.acvs.org/AnimalOwners/HealthConditions/SmallAnimalTopics/BoneTumorsihttp://www.acvs.org/AnimalOwners/HealthConditions/SmallAnimalTopics/BoneTumorsi

nCatsandDogs/nCatsandDogs/ http://www.pharmacy-and-drugs.com/illnessessimages/blastomycosis2.jpghttp://www.pharmacy-and-drugs.com/illnessessimages/blastomycosis2.jpg http://veterinarymedicine.dvm360.com/vetmed/ArticleStandard/Article/detail/596603http://veterinarymedicine.dvm360.com/vetmed/ArticleStandard/Article/detail/596603 http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/51108.htmhttp://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/51108.htm http://www.vet.uga.edu/vpp/clerk/edison/Fig4ADJ.jpghttp://www.vet.uga.edu/vpp/clerk/edison/Fig4ADJ.jpg http://www.vet.uga.edu/vpp/clerk/edison/index.phphttp://www.vet.uga.edu/vpp/clerk/edison/index.php http://cal.vet.upenn.edu/projects/saortho/chapter_37/37F8.jpghttp://cal.vet.upenn.edu/projects/saortho/chapter_37/37F8.jpg http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/51104.htmhttp://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/51104.htm http://www.vet.uga.edu/vpp/clerk/edison/indexhttp://www.vet.uga.edu/vpp/clerk/edison/index Songer, J.G., & Post, K.W. (2003). Veterinary Microbiology. St Louis: Elsevier.Songer, J.G., & Post, K.W. (2003). Veterinary Microbiology. St Louis: Elsevier. http://www.acvs.org/AnimalOwners/HealthConditions/SmallAnimalTopics/http://www.acvs.org/AnimalOwners/HealthConditions/SmallAnimalTopics/

BoneTumorsinCatsandDogs/BoneTumorsinCatsandDogs/ http://people.upei.ca/lpack/vetrad/VCA%20341/VCA%20341%20Lecturehttp://people.upei.ca/lpack/vetrad/VCA%20341/VCA%20341%20Lecture

%207%20Musculoskeletal%20Part%201.ppt#362,49,Fungal Osteomyelitis%207%20Musculoskeletal%20Part%201.ppt#362,49,Fungal Osteomyelitis