Chapter 110 Fungal Infections Marie E. Kerl, DVM, DACVIM, DACVECC KEY POINTS • Fungal infections typically are slowly progressive diseases; however, respiratory, ocular, and gastrointestinal involvement can cause an emergency situation. • Diagnosis is made most commonly with direct visualization of fungal organisms. • Treatment includes antifungal drug therapy and supportive measures for specific organ involvement. INTRODUCTION Systemic fungal infections cause significant morbidity and mortality in dogs and cats in most regions of the United States. These pathogens gain entry through a single portal and disseminate to affect multiple body systems. Although affected individuals frequently present with chronic illness, fungal infections can precipitate emergency presentations for acute respiratory distress, severe gastrointestinal (GI) disease, central nervous system (CNS) disease, or acute blindness. This chapter focuses on clinical signs, diagnosis, and prognosis of the most common systemic mycoses of dogs and cats including blastomycosis, histoplasmosis, coccidiomycosis, and cryptococcosis, and will address treatment of fungal infections in general. BLASTOMYCOSIS Blastomycosis is caused by infection with fungal spores of Blastomyces dermatitidis, most commonly via inhalation and respiratory colonization. Environmental conditions favoring fungal growth include moist, acidic soil with decaying vegetation or animal feces. Geographic regions with the greatest prevalence of blastomycosis include the Mississippi, Missouri, and Ohio River valleys and the Great Lakes areas of the United States and Canada.1 Infection typically occurs when an animal inhales conidiophores from the environment, but inoculation by penetration can cause localized disease. Dogs are affected more commonly than cats.1,2 Following inhalation, infective conidia are phagocytized by macrophages and transformed to the thick-walled yeast phase (8 to 12 μm) that bud to form daughter cells with broad-based attachments (Color Plate 110-1, A). Yeast may produce a localized infection or may disseminate to distant sites.3 Clinical Signs Affected dogs are typically young adult, large breed, and of either gender.4 Clinical signs develop weeks to months after exposure to the organism and include anorexia, depression, lethargy, weight loss, cachexia, and fever. Physical examination findings include respiratory signs (tachypnea, dyspnea, cyanosis, respiratory distress, pulmonary thromboembolism), lymphadenopathy, ocular changes (uveitis, retinal detachment, secondary glaucoma), dermal nodules, bone lesions, and CNS abnormalities.1,3-5 Pyogranulomatous inflammation occurs as a result of stimulation of cell-mediated immunity.3 Blastomycosis is an uncommon fungal disease in cats.2 Clinical signs are similar to those in dogs, except cats more commonly exhibit CNS disease and develop large dermal abscesses.2,3 Diagnosis Complete blood count (CBC) may reveal mild nonregenerative anemia, mature neutrophilia, or neutrophilia with left shift. Possible abnormalities on serum biochemical profile include hypoalbuminemia, hyperglobulinemia, and hypercalcemia.1,4 Thoracic radiographs reveal a diffuse or nodular interstitial pattern, alveolar infiltrates, hilar lymphadenopathy, or a combination of these in 70% of cases. Bone involvement most commonly affects the appendicular skeleton. Radiographic lesions (osteolysis with periosteal proliferation and soft tissue swelling) are similar to those seen in primary osteosarcoma.1,3,4 Definitive diagnosis relies on identifying organisms retrieved from affected sites. The site of involvement dictates the method of sampling. Aspirating affected lymph nodes, dermal lesions, or eyes (vitreous) yields organisms reliably. Lung aspirate, tracheal wash, and bronchoalveolar lavage (BAL) are frequently nondiagnostic because of the interstitial location of the organisms.4 Culture is unnecessary if cytologic or histopathologic examination demonstrates characteristic organisms. Caution should be exercised when handling infected tissues because the yeast form is infective to humans.1 Serologic testing should be considered when multiple attempts to identify the organism have failed. Agar gel immunodiffusion (AGID) is the serologic test most commonly used to identify antibodies to Blastomyces organisms, with sensitivity reported to be 41% to 90%, and specificity of 90% to 100%.6,7 AGID is often negative early in the course of disease and may remain positive even with clinical resolution of disease. AGID in cats is unrewarding.2 Antigen testing for Blastomyces dermatitidis has become available (MiraVista Diagnostics, Indianapolis, IN).8 This test in an enzyme immunoassay that can be performed on serum or urine from affected dogs, has greater sensitivity (serum sensitivity 87%, urine sensitivity 93%) than antibody testing, and appears to have a low rate of false-positive results in uninfected dogs.8 Prognosis The prognosis of a patient with blastomycosis is generally good unless there is CNS or severe pulmonary involvement.1 Approximately 70% to 75% of dogs receiving antifungal therapy survive. Dogs with severe respiratory infections or multiple body system involvement are more likely to die within the first week of therapy. Brain involvement is associated significantly with treatment failure. Most animals that die during or soon after treatment do so because of the subsequent inflammatory response associated with sudden death of many fungal organisms. HISTOPLASMOSIS Histoplasmosis is caused by infection with the soil-borne, dimorphic fungus Histoplasma capsulatum. This organism survives wide temperature variations. Moist soil containing bird or bat waste favors growth. Regions of the United States with greatest prevalence are the Ohio, Missouri, and Mississippi river valleys.9-11 Soil contaminated with Histoplasma capsulatum contains free-living microconidia (2 to 5 μm) or macroconidia (5 to 18 μm) that cause mammalian infection. Route of entry is typically respiratory; however, oral exposure may occur because some animals have only GI signs.10 Dissemination occurs to any organ. Lungs, GI tract, lymph nodes, spleen, liver, bone marrow, eyes, and adrenal glands are most commonly affected. The incubation period is 12 to 16 days in dogs, but clinical signs may be absent or insidious.3 Exposure to highly contaminated environments may cause point-source outbreaks in dogs and humans. Cats and dogs are equally likely to develop histoplasmosis.11 Clinical Signs Most affected dogs are large breed, young adults. Males are slightly predisposed, and hunting breeds are overrepresented.3,10 Disseminated histoplasmosis with GI involvement accounts for most clinical presentations.11 GI signs include both small and large intestinal diarrhea, weight loss, hypoalbuminemia, intestinal bleeding (melena or hematochezia), and tenesmus. Hepatosplenomegaly occurs in up to 50% of dogs. Coughing, tachypnea, dyspnea, or pleural effusion occurs with pulmonary involvement. Less specific findings include fever, anorexia, and depression. In contrast to blastomycosis, histoplasmosis is less frequently associated with bone, ocular, or dermal lesions.11 Cats with histoplasmosis have slightly different clinical signs than dogs. Cats younger than 4 years are affected most commonly, with no breed or gender predilection.9,11 Clinical signs include weight loss, depression, fever, anorexia, and anemia. Specific GI signs are identified less commonly. Pulmonary involvement results in dyspnea, tachypnea, and abnormal lung sounds. Lymphadenopathy and hepatosplenomegaly occur with dissemination. Bone marrow involvement can cause various blood cell deficiencies. Dermal, ocular, and oral lesions occur uncommonly. Only gold members can continue reading. 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Chapter 110 Fungal Infections Marie E. Kerl, DVM, DACVIM, DACVECC KEY POINTS • Fungal infections typically are slowly progressive diseases; however, respiratory, ocular, and gastrointestinal involvement can cause an emergency situation. • Diagnosis is made most commonly with direct visualization of fungal organisms. • Treatment includes antifungal drug therapy and supportive measures for specific organ involvement. INTRODUCTION Systemic fungal infections cause significant morbidity and mortality in dogs and cats in most regions of the United States. These pathogens gain entry through a single portal and disseminate to affect multiple body systems. Although affected individuals frequently present with chronic illness, fungal infections can precipitate emergency presentations for acute respiratory distress, severe gastrointestinal (GI) disease, central nervous system (CNS) disease, or acute blindness. This chapter focuses on clinical signs, diagnosis, and prognosis of the most common systemic mycoses of dogs and cats including blastomycosis, histoplasmosis, coccidiomycosis, and cryptococcosis, and will address treatment of fungal infections in general. BLASTOMYCOSIS Blastomycosis is caused by infection with fungal spores of Blastomyces dermatitidis, most commonly via inhalation and respiratory colonization. Environmental conditions favoring fungal growth include moist, acidic soil with decaying vegetation or animal feces. Geographic regions with the greatest prevalence of blastomycosis include the Mississippi, Missouri, and Ohio River valleys and the Great Lakes areas of the United States and Canada.1 Infection typically occurs when an animal inhales conidiophores from the environment, but inoculation by penetration can cause localized disease. Dogs are affected more commonly than cats.1,2 Following inhalation, infective conidia are phagocytized by macrophages and transformed to the thick-walled yeast phase (8 to 12 μm) that bud to form daughter cells with broad-based attachments (Color Plate 110-1, A). Yeast may produce a localized infection or may disseminate to distant sites.3 Clinical Signs Affected dogs are typically young adult, large breed, and of either gender.4 Clinical signs develop weeks to months after exposure to the organism and include anorexia, depression, lethargy, weight loss, cachexia, and fever. Physical examination findings include respiratory signs (tachypnea, dyspnea, cyanosis, respiratory distress, pulmonary thromboembolism), lymphadenopathy, ocular changes (uveitis, retinal detachment, secondary glaucoma), dermal nodules, bone lesions, and CNS abnormalities.1,3-5 Pyogranulomatous inflammation occurs as a result of stimulation of cell-mediated immunity.3 Blastomycosis is an uncommon fungal disease in cats.2 Clinical signs are similar to those in dogs, except cats more commonly exhibit CNS disease and develop large dermal abscesses.2,3 Diagnosis Complete blood count (CBC) may reveal mild nonregenerative anemia, mature neutrophilia, or neutrophilia with left shift. Possible abnormalities on serum biochemical profile include hypoalbuminemia, hyperglobulinemia, and hypercalcemia.1,4 Thoracic radiographs reveal a diffuse or nodular interstitial pattern, alveolar infiltrates, hilar lymphadenopathy, or a combination of these in 70% of cases. Bone involvement most commonly affects the appendicular skeleton. Radiographic lesions (osteolysis with periosteal proliferation and soft tissue swelling) are similar to those seen in primary osteosarcoma.1,3,4 Definitive diagnosis relies on identifying organisms retrieved from affected sites. The site of involvement dictates the method of sampling. Aspirating affected lymph nodes, dermal lesions, or eyes (vitreous) yields organisms reliably. Lung aspirate, tracheal wash, and bronchoalveolar lavage (BAL) are frequently nondiagnostic because of the interstitial location of the organisms.4 Culture is unnecessary if cytologic or histopathologic examination demonstrates characteristic organisms. Caution should be exercised when handling infected tissues because the yeast form is infective to humans.1 Serologic testing should be considered when multiple attempts to identify the organism have failed. Agar gel immunodiffusion (AGID) is the serologic test most commonly used to identify antibodies to Blastomyces organisms, with sensitivity reported to be 41% to 90%, and specificity of 90% to 100%.6,7 AGID is often negative early in the course of disease and may remain positive even with clinical resolution of disease. AGID in cats is unrewarding.2 Antigen testing for Blastomyces dermatitidis has become available (MiraVista Diagnostics, Indianapolis, IN).8 This test in an enzyme immunoassay that can be performed on serum or urine from affected dogs, has greater sensitivity (serum sensitivity 87%, urine sensitivity 93%) than antibody testing, and appears to have a low rate of false-positive results in uninfected dogs.8 Prognosis The prognosis of a patient with blastomycosis is generally good unless there is CNS or severe pulmonary involvement.1 Approximately 70% to 75% of dogs receiving antifungal therapy survive. Dogs with severe respiratory infections or multiple body system involvement are more likely to die within the first week of therapy. Brain involvement is associated significantly with treatment failure. Most animals that die during or soon after treatment do so because of the subsequent inflammatory response associated with sudden death of many fungal organisms. HISTOPLASMOSIS Histoplasmosis is caused by infection with the soil-borne, dimorphic fungus Histoplasma capsulatum. This organism survives wide temperature variations. Moist soil containing bird or bat waste favors growth. Regions of the United States with greatest prevalence are the Ohio, Missouri, and Mississippi river valleys.9-11 Soil contaminated with Histoplasma capsulatum contains free-living microconidia (2 to 5 μm) or macroconidia (5 to 18 μm) that cause mammalian infection. Route of entry is typically respiratory; however, oral exposure may occur because some animals have only GI signs.10 Dissemination occurs to any organ. Lungs, GI tract, lymph nodes, spleen, liver, bone marrow, eyes, and adrenal glands are most commonly affected. The incubation period is 12 to 16 days in dogs, but clinical signs may be absent or insidious.3 Exposure to highly contaminated environments may cause point-source outbreaks in dogs and humans. Cats and dogs are equally likely to develop histoplasmosis.11 Clinical Signs Most affected dogs are large breed, young adults. Males are slightly predisposed, and hunting breeds are overrepresented.3,10 Disseminated histoplasmosis with GI involvement accounts for most clinical presentations.11 GI signs include both small and large intestinal diarrhea, weight loss, hypoalbuminemia, intestinal bleeding (melena or hematochezia), and tenesmus. Hepatosplenomegaly occurs in up to 50% of dogs. Coughing, tachypnea, dyspnea, or pleural effusion occurs with pulmonary involvement. Less specific findings include fever, anorexia, and depression. In contrast to blastomycosis, histoplasmosis is less frequently associated with bone, ocular, or dermal lesions.11 Cats with histoplasmosis have slightly different clinical signs than dogs. Cats younger than 4 years are affected most commonly, with no breed or gender predilection.9,11 Clinical signs include weight loss, depression, fever, anorexia, and anemia. Specific GI signs are identified less commonly. Pulmonary involvement results in dyspnea, tachypnea, and abnormal lung sounds. Lymphadenopathy and hepatosplenomegaly occur with dissemination. Bone marrow involvement can cause various blood cell deficiencies. Dermal, ocular, and oral lesions occur uncommonly. Only gold members can continue reading. Log In or Register to continue Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window) Related Related posts: Deteriorating Mental Status Hyperthermia and Fever Ventilator-Associated Lung Injury Allergic Airway Disease in Dogs and Cats and Feline Bronchopulmonary Disease Stay updated, free articles. Join our Telegram channel Join Tags: Small Animal Critical Care Medicine Sep 10, 2016 | Posted by admin in SMALL ANIMAL | Comments Off on Fungal Infections Full access? Get Clinical Tree