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Aspergillosis

By Joseph Taboada, DVM, DACVIM, Professor and Associate Dean, Office of Student and Academic Affairs, School of Veterinary Medicine, Louisiana State University

Aspergillosis is caused by several Aspergillus spp, especially A fumigatus and A terreus. A niger, A nidulans, A viridinutans, A flavus, and A felis are being recognized more commonly with increasing use of molecular techniques for identification. Aspergillus infection is found worldwide and in almost all domestic animals and birds as well as in many wild species. It is primarily a respiratory infection that may become generalized; however, tissue predilection varies among species. The most common forms are pulmonary infections in poultry and other birds; mycotic abortion in cattle; guttural pouch mycosis in horses; infections of the nasal and paranasal tissues, intervertebral sites, and kidneys of dogs; and sinonasal, sino-orbital, and pulmonary infection in domestic cats.

Clinical Findings and Lesions:

In birds, aspergillosis (see Aspergillosis) is primarily bronchopulmonary, with dyspnea, gasping, and polypnea accompanied by somnolence, anorexia, and emaciation. Mycotic tracheitis has also been described. Torticollis and disturbances of equilibrium are seen when infection disseminates to the brain. Yellow nodules of varying size and consistency or plaque lesions are found in the respiratory passages, lungs, air sacs, or membranes of body cavities. Fur-like growth of fungus may be found on the thickened walls of air sacs. Other species with bronchopulmonary aspergillosis may have nodular lesions in the lungs or an acute pneumonia accompanied by serosanguineous fluid in the pleural cavity and a fibrinous pleuritis.

In ruminants, aspergillosis may be asymptomatic, appear in a bronchopulmonary form, cause mastitis, or cause placentitis and abortion. Mycotic pneumonia may be rapidly fatal. Signs include pyrexia; rapid, shallow, stertorous respiration; nasal discharge; and a moist cough. The lungs are firm, heavy, and mottled and do not collapse. In subacute to chronic mycotic pneumonia, the lungs contain multiple discrete granulomas, and the disease grossly resembles tuberculosis (see Tuberculosis and other Mycobacterial Infections).

In the absence of pneumonia, infected cows generally have no signs except for abortion; a dead fetus is aborted at 6–9 mo gestation, and the fetal membranes are retained. Lesions are found in the uterus, fetal membranes, and often the fetal skin. In the uterus, the intercaruncular areas are grossly thickened, leathery, dark red to tan, and contain elevated or eroded foci covered by a yellow-gray adherent pseudomembrane. Maternal caruncles are dark red to brown, and the adherent fetal cotyledons are markedly thickened. Cutaneous lesions in aborted fetuses consist of soft, red to gray, elevated, discrete foci that resemble ringworm.

In horses, epistaxis and dysphagia are common complications of gutturomycosis (see Guttural Pouch Mycosis). The infected guttural pouch is characterized by a necrotizing inflammation and is thickened, hemorrhagic, and covered by a friable pseudomembrane. Mycotic rhinitis characterized by dyspnea and nasal discharge has also been described. Aspergillosis can be a rapidly fatal disease associated with diffuse pulmonary invasion. In these cases, acute enteritis is often a predisposing factor. The colitis is thought to result in a profound neutropenia that decreases the immunocompetence of the host, followed by the invasion of Aspergillus from disrupted intestinal mucosa. Locomotor and visual disturbances, including blindness, may occur when the infection spreads to the brain and optic nerve.

In dogs, aspergillosis is typically localized to the nasal cavity or paranasal sinuses and is usually caused by infection with A fumigatus. Nasal aspergillosis is seen mainly in dolichocephalic breeds; it begins in the posterior region of the ventral maxilloturbinate with signs of lethargy, nasal pain, ulceration of the nares, sneezing, unilateral or bilateral sanguinopurulent nasal discharge, frontal sinus osteomyelitis, and epistaxis. Gross lesions vary considerably with site of infection, but the mucosa of the nasal and paranasal sinuses may be covered by a layer of necrotic material and white to gray-white fungal growth. The mucosa and the underlying bone may be necrotic with loss of bone definition on radiographs or CT.

Disseminated disease in dogs is seen most often in middle-age, female German Shepherds and usually involves A terreus, A deflectus, and A niger. The clinical signs of disseminated aspergillosis may include lethargy, lameness, anorexia, weight loss, muscle wasting, pyrexia, hematuria, urinary incontinence, generalized lymphadenopathy, and neurologic deficits. Lesions are frequently found in the abdominal and thoracic lymph nodes, kidneys, spleen, and vertebrae. Discospondylitis is common.

In cats, sinonasal and sino-orbital disease is seen most often. Aspergillosis is rare in cats compared with dogs. Sinonasal disease can present similarly to the disease in dogs, but sino-orbital disease can be very aggressive, often causing severe facial swelling. In some cases, a mass in the pterygopalatine fossa or ulceration of the hard palate may be seen. The CNS may be invaded, causing neurologic signs.

Diagnosis:

Radiographs in dogs with nasal aspergillosis may show generalized radiolucence of the nasal cavity secondary to turbinate tissue destruction. Frontal sinus osteomyelitis is seen in as many as 80% of dogs. Cross-sectional imaging via CT is more sensitive than plain radiographs in demonstrating consistent changes. Visualization of fungal plaques by rhinoscopy together with serologic and either mycologic or radiographic evidence of disease is often how a diagnosis is made. A diagnosis based on culture results alone is not appropriate, because aspergilli are ubiquitous and can be isolated from the nasal cavities of healthy dogs. Positive culture results should be supported by demonstration of narrow, hyaline, septate, branching hyphae within lesions or by serologic tests. The agar-gel double-diffusion test for serum antibody is generally considered unreliable. Dogs with systemic disease usually have neutrophilia, often with a left shift, and a nonregenerative anemia. Azotemia, hyperglobulinemia, hypoalbuminemia, and hypercalcemia are common. Ultrasound usually reveals abdominal lymphadenopathy and renal lesions. Systemic disease is usually diagnosed by culture of the organism, often from urine. A blood and urine galactomannan antigen assay for diagnosis of systemic aspergillosis in dogs has been described to have moderate sensitivity and specificity.

Treatment:

In dogs, topical treatment is considered the treatment of choice for nasal and paranasal aspergillosis. Several surgical techniques and drug regimens have been used with varying success. Clotrimazole formulated in a polyethylene glycol base is generally considered the first-line treatment. It can be administered through indwelling tubes trephined into the frontal sinuses or via the nares as a single infusion. If infusion is via the nares, Foley catheters are used to instill 0.5 g in each side of the nasal cavity. The infused solution is left in place for 1 hr, during which the dog’s position is changed periodically to maximize penetration. There is an ~80% success rate using local infusions in this manner. Enilconazole, 10 mg/kg, instilled bid for 7–14 days, via tubes implanted surgically into the frontal sinuses, has also been used with a similar success rate. Drugs given systemically have included ketoconazole, itraconazole, fluconazole, voriconazole, and posaconazole. Fluconazole (2.5–10 mg/kg, divided bid) and itraconazole (5–10 mg/kg/day) are cost-effective options. Ketoconazole (5–10 mg/kg, bid for 6–8 wk), although cost-effective, is not as effective clinically. Voriconazole (3–6 mg/kg/day) is probably the most effective of the azole antifungals for treating aspergillosis, but the cost is much higher than that of the other choices.

In horses, surgical exposure and curettage have been used to treat gutturomycosis. Topical natamycin and oral potassium iodide have been reported effective in cases of Aspergillus infection. Itraconazole (3 mg/kg, bid for 84–120 days) has been reported effective in Aspergillus rhinitis in horses.

Bovine mastitis has been treated successfully with combined intra-arterial and intramammary injection with miconazole.

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