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A 24-year-old green-winged macaw (Ara chloropterus) was referred to the Louisiana State University Veterinary Teaching Hospital (LSU-VTH) with a severe respiratory condition that was not responding to treatment. The owners noted that the bird had not been vocalizing in a normal manner for approximately 3 weeks before the referral presentation. Initially, the macaw was examined by a local veterinarian who determined that the patient was in poor body condition and had difficulty breathing when excited. Additionally, its uropygial gland appeared enlarged. At that time, the bird was prescribed azithromycin (unknown dose and formulation) and was discharged after the appointment. The macaw showed minimal improvement to treatment and a moist cough with severe dyspnea subsequently developed. The bird presented back to the same referring veterinarian who performed whole-body radiographs revealing multifocal opacities throughout the lung fields and air sacs (Figs 1, 2). At this point, the bird was referred to the LSU-VTH for further diagnostic workup.
Upon presentation to the LSU-VTH, the owners stated that they had owned the macaw since it was a juvenile and it had been purchased from a breeder. The bird was maintained in a 6 X 4 X 4foot wrought iron cage located in the kitchen area of the house. The cage was cleaned on a weekly basis and newspaper was used as the substrate. Located within the cage was a perch, several toys, a swing, and a bowl of water. The bird was handled daily and its diet consisted of a mixture of seed and pellet-based feed (Kaytee Products, Inc., Chilton, WI, USA). Peanuts, fruits (apples, bananas, oranges), and snap beans were provided routinely as well as occasional treats, including sunflower seeds, crackers with peanut butter, animal cookies, cheese puffs, and fruit loops. Other pets within the household included a 20-year-old African grey parrot (Psittacus erithacus) and several dogs. Both birds were maintained in separate enclosures, although their cages were placed next to each other. The owners were unaware of any health issues with the African grey parrot either past or present, but they did state that the macaw was treated for a respiratory condition approximately 8 to 10 years previously.
Upon presentation, the macaw was approximately 5% to 10% dehydrated, paretic, and lethargic. It demonstrated reduced awareness of its surroundings. Its body condition was approximately 1.5 of 5 and it weighed 845 g. The patient displayed an abnormal posture with dropped wings, fluffed feathers, and was breathing heavily with the beak open. Additionally, the physical examination revealed a mildly distended coelomic cavity and an enlarged, fluid-filled uropygial gland.
The bird exhibited decreased ability to move either wings or legs. Cardiopulmonary auscultation did not reveal any significant changes, although turbulent airflow was audible over the dorsal pulmonary fields.
A blood sample was collected from the right jugular vein and was submitted for a complete blood count (CBC) and plasma biochemical analysis. The CBC results revealed a severe leukocytosis (158.9 X [10.sup.3] cells/pL; reference range, 7-22 X [10.sup.3] cells/pL) with marked heterophilia (95%; reference range, 40%-60%), mild anemia (packed cell volume [PCV] 45%; reference range, 47%-55%), and lymphopenia (3%; reference range, 36%-60%). (1) Clumped thrombocytes, few reactive lymphocytes, monocytes, and several toxic heterophils with foamy cytoplasm and toxic granules also were reported on the CBC. Results of the plasma biochemical analysis showed abnormal changes associated with the liver enzymes (aspartate aminotransferase [AST] 1552 U/L; reference range, 90-180 U/L; alkaline phosphatase [ALP] 68 U/L; reference range, 290-750 U/L; gammaglutamyltransferase [GGT] 10 U/L; reference range, 0-4 U/L), a significant increase in creatinine kinase activity (57 279 U/L; reference range, 180-500 U/L), hypoproteinemia (total protein [TP] 2.5 g/dL; reference range, 3.4-4.2 g/dL), hypoalbuminemia (<0.75 g/dL; reference range, 1.3-1.7 g/ dL (7)), hypocalcemia (7.9 mg/dL; reference range, 9.5-10.5 mg/dL), decreased creatinine (<0.2 mg/ dL; reference range, 0.5-0.6 mg/dL), and hyperuricemia (12.3 mg/dL; reference range, 1-6 mg/ dL). (1) The remaining biochemical parameters were within reference intervals. Upon review of the radiographs taken by the referring veterinarian, there was a diffuse and ill-defined increase in opacity present in the lung fields as well as the thoracic and abdominal air sacs. Per owner request, a swab of the conjunctiva, choana, and cloaca, along with whole blood, were submitted to the University of Georgia Infectious Disease Laboratory for chlamydiosis testing via polymerase chain reaction (PCR).
Initial treatment consisted of 100 mL/kg q24h subcutaneous crystalloid fluids along with meloxicam (1 mg/kg IM q24h). The patient was hospitalized in a critical care unit with supplemental oxygen set to achieve an oxygen concentration of 40%.
The next morning, a coelioscopy was performed with a 2.9-mm rigid endoscope to grossly assess the organs and tissues within the coelom. In preparation for the endoscopic procedure, the bird was induced with 5% isoflurane delivered via face mask in a 1.5 L flow of oxygen. Once induced, the patient was intubated with an uncuffed, 4.0-mm endotracheal tube and maintained on 2.0% to 2.5% isoflurane and a 1.5 L flow of oxygen. A 3.0-mm incision was made into the left lateral flank, extending into the coelom. The endoscope was introduced to visualize the viscera and air sacs. The coelom was diffusely occupied by white to semiopaque granulomas that seemed to be coalescing with the air sacs (Figs 3-5). Additionally, airsacculitis was evident due to the thickened appearance of the thoracic air sacs, which appeared white to grey (Fig 4). This abnormal tissue was remarkably vascular, which became even more evident after biopsy (Fig 5). The liver was grossly pale in appearance; however, very little of the coelom could be evaluated because of the size of the masses within the air sacs. Biopsies of the abnormal tissues (air sacs, granulomas, and liver) were harvested and subsequently placed in formalin for histopathologic evaluation. One sample from the liver was saved for cytologic examination. The incision was closed with a single simple interrupted suture (4 polydioxanone; PDS II; Ethicon US, LLC, Somerville, NJ, USA).The patient recovered uneventfully from the procedure. All previous treatments were continued while food and water were provided, since the bird did not present with any sign of inappetence.
Considering the patient's history, presenting clinical signs, and diagnostic test results, potential differential diagnoses included mycobacteriosis, aspergillosis, and neoplastic disease. Mycobacteriosis originally was considered the top differential in this case because of the profound loss of body condition and grossly abnormal coelomic granulomas. In our experience, these granulomas seemed atypical for most aspergillosis cases. Chlamydiosis also was considered because of the profound leukocytosis; however, this was placed very low on the differential list considering endoscopic findings. Based on gross assessment during coelioscopy, the prognosis for the patient was considered grave regardless of disease etiology. Empirical treatment with antifungal drugs was discussed with the owners; however, because of the grave prognosis and financial concerns, the owners were hesitant to make a definitive decision concerning the treatment of the macaw. Unfortunately, the bird was found dead in the incubator the next morning. The owners declined a postmortem examination and chose to take the body home for burial.
The cytology sample from the liver revealed histiocytic inflammation; however, no infectious organisms were observed. The biopsy of the liver showed degeneration of the liver parenchyma with a small infiltration of lymphocytes and granulocytes. The samples collected from the granulomas consisted of a variable amount of connective tissue with locally extensive areas of degenerated leukocytes, primarily heterophils, plasma cells, and histiocytes. Frequently, blood vessel lumina were filled with granulocytes and lined by plump endothelial cells. Small numbers of multinucleated giant cells were noted, along with hyphae that were morphologically consistent with Aspergillus species. Results of avian chlamydiosis testing via PCR were negative.
Aspergillosis is a fungal disease predominantly caused by A fumigatus; however, A niger, A flavus, A nidnlans, and A terreus are believed to be pathogenic as well. Even though aspergillosis per se is not considered a transmissible organism between birds, it is highly infectious for some avian species within a living environment, especially waterfowl (Anseriformes), penguins (Sphenisciformes), turkeys (Meleagris species), birds of paradise (Paradisaeidae), pheasants (Phasianidae), and raptors (gyrfalcons [Falco rusticolus], redtailed hawks [Buteo jamaicensis], goshawks [Accipiter gentilis], golden eagles [Aquila chrysaetos], bald eagles [Haliaeetus leucocephalus], rough-legged hawks [Buteo lagopus], and snowy owls [Bubo scandiacus]). (2-4) Given the specific anatomy of their respiratory system, birds are prone to airborne infections. The primary location of the fungal plaques depends on the course of the infection and can begin in the air sacs, lungs, or upper respiratory tract (eg, nares, choana, larynx, trachea, and syrinx). (2,5,6) In passerine birds, psittacine birds, and waterfowl, aspergillosis can present as a single lesion at the level of the syrinx within the tracheal lumen. These patients typically have a change in the pitch and quality of their vocalizations. Exposure to many Aspergillus species organisms can overwhelm the healthy immune system and may cause development of acute aspergillosis. This acute disease process can have its onset within 3 to 5 days after infection and usually starts with rapid colonization of the lungs. (2) Consequently, birds suffer from increased respiratory effort, lethargy, depression, anorexia, weight loss, emaciation, polydipsia, and polyuria or sudden death. Alternatively, prolonged exposure to a contaminated environment may increase the possibility of chronic aspergillosis development after a prolonged period of subclinical infection. In affected birds with chronic aspergillosis, initial colonization of the fungus can occur in the trachea, syrinx, and primarily the caudal thoracic and abdominal air sacs. Clinical signs associated with Aspergillus species infections may resemble the acute form or show various nonspecific presentations, including change or lack of voice, ataxia, torticollis, seizures, motor deficiency in the rear limbs, oculonasal discharge, conjunctivitis, periorbital swelling, mycotic keratitis, exercise intolerance, and hepatomegaly. (2,3,7) As with gross postmortem observations, generally two forms of tissue reaction are present: granulomatous or infiltrative. The latter form is typical of the serosal membranes and lungs. Regardless of pathophysiology, affected tissues are covered by whitish-grey or greenish caseous structures that may be filamentous in appearance. (5,7)
Diagnosis of aspergillosis is quite challenging and should be based on a comprehensive overview of the history of the patient, clinical signs, and results of physical examination and diagnostic testing, including blood tests and advanced imaging. (2,7) 7A detailed history is a very important step toward diagnosis and should include all husbandry information, including location of the cage, nutrition, daily activities, hygiene practices, and previous medical history. (2) Inappropriate humidity, poor ventilation and sanitation, air contamination, inadequate diet and poor quality of feed may predispose a bird to aspergillosis through inhalation of fungal spores. Patients presented with the history of respiratory distress on physical examination typically demonstrate severe breathing difficulties and audible respiration. Increased expiration effort commonly indicates lower respiratory tract disease, which may suggest the presence of granulomas in the lungs or air sacs. Unfortunately, patients frequently exhibit nonspecific clinical signs on presentation, including anorexia, lethargy, and weight loss. Complete blood count results often are helpful in identifying infectious diseases, such as aspergillosis, as many avian patients commonly suffer a heterophilic leukocytosis of 20 X [10.sup.3] cells/[micro]L or more, lymphopenia, hyperproteinemia, and nonregenerative anemia. By contrast, there may be inconsistencies regarding hematologic reaction to chronic infectious disease processes, and birds diagnosed with aspergillosis can have decreased total protein values and a normal white blood cell count. (2,7) Radiographic images are routinely nondiagnostic as it relates to avian aspergillosis because detailed evaluation of the complex avian respiratory system is limited. Despite the limitations of radiography, survey radiographs still are recommended to gain a general assessment of the patient's respiratory system. Radiographic signs of the disease may include increased soft tissue opacities in the lungs, air sacs, trachea, syrinx, and sinuses as well as asymmetry of the air sacs, with noticeable outlining of the air sac membranes by fluid accumulation or air trapping if airsacculitis is present. (2,3,7) Unfortunately, easy identification of radiographic changes generally gives a poor prognosis. Computed tomography (CT) may provide better visualization of the pathologic findings; however, considering the increased risk of anesthesia in critical patients and inability to obtain a definitive diagnosis, the traditional use of this imaging modality is questionable. (8) Recently an article describing the use of a standing CT evaluation of a bird provides information that allows one to use this imaging modality for critical patients without the risk of general anesthesia. A standing CT image of a bird, without the use of anesthesia, may provide for a more detailed evaluation of a bird's coelomic cavity in severely ill patients. (9) Endoscopy, although considered more invasive, is a better antemortem diagnostic method, in many cases, because it not only allows direct observation of lesions and organs, but it also provides a means to collect biopsy samples from affected tissues for cytologic and histopathologic evaluation. Tracheoscopy and coelioscopy allow one to determine the severity of the disease, help to establish prognosis, determine a treatment plan and monitor treatment response. (2,7) With the increased reliability of diagnostic results with the coelioscopy there also is an elevated risk of the procedure due to the requirement of general anesthesia. With this macaw, the risk of anesthesia was considered worth the result of accurate diagnosis of the disease condition to confirm an appropriate treatment protocol. The patient recovered from the coelioscopy procedure uneventfully and its attitude and condition for the remainder of the day did not deviate from that before the anesthetic event. It does not appear that the coelioscopy procedure contributed to the macaw's death the next day based on the patient's response after recovering from general anesthesia.
Cytologic examination of the samples can be very useful to confirm a diagnosis of aspergillosis, including marked infiltration of granulocytes, macrophages, and giant cells in the presence of fungal elements. Unfortunately, there is no reliable, noninvasive, antemortem diagnostic test that permits definitive diagnosis of an Aspergillus species infection. Microbiologic results obtained from a patient in the absence of lesions or obvious clinical signs are not diagnostic of aspergillosis because the fungus is ubiquitous in the environment. (2) The use of PCR testing, serologic assays (eg, galactomannan assay or enzyme-linked immunosorbent assay [ELISA]) and protein electrophoresis have been described, but at this time no reliable diagnostic tests associated with these methodologies are available for parrot species. (2,7,8) Samples from affected tissues can be cultured; however, fungal growth is slow and inconsistent. Therefore, empirical treatment for fungal disease often is initiated before culture results are obtained.
Treatment of avian aspergillosis in birds usually is protracted but generally provides good clinical results, although complete disease resolution should not be expected. Affected animals typically are treated with oral itraconazole or voriconazole. Additionally, administration of amphotericin B, as a nebulization agent, often is recommended, especially for cases with significant air sac disease. (1,3,4,10) Although the use of terbinafine is widely described in people with Aspergillus species infection, the pharmacologic properties of this substance have not yet been properly described in the therapy of avian aspergillosis." Surgical debridement of the granulomas is not recommended in birds because of the anatomic complexities of the respiratory system, which increases the risk of iatrogenic trauma; however, successful surgical management by endoscopic debridement and laser ablation of granulomas within the lower respiratory tract followed by medical therapy has been reported. (7,12) Research toward development of a vaccination strategy has been done in turkeys, while other reports have cited use of immunostimulants as treatment. (7) Unfortunately, currently no product is available to prevent avian aspergillosis or aid in treatment beyond traditional methods.
This case was submitted by Adrianna Skarbek, DVM, Alyssa M. Scagnelli, DVM, Adrian Whittington, DVM, and Thomas N. Tully Jr, DVM, MS, Dipl ABVP (Avian), Dipl ECZM "(Avian) from the Department of Veterinary Clinical Sciences (Skarbek, Scagnelli, Tully), School of Veterinary Medicine, Louisiana State University, Skip Bertman Drive, Baton Rouge, LA 70803, USA; and North State Animal and Bird Hospital (Whittington), 5208 North State Street, Jackson, MS 39206, USA.
(1.) Carpenter JW, ed. Exotic Animal Formulary, 4th ed. St Louis, MO: Saunders/Elsevier; 2013.
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(3.) Joseph V. Aspergillosis in raptors. Semin Avian Exot Pet. 2000;9(2):66-74.
(4.) DiSomma A, Bailey T, Silvanose C, GarciaMarinez C. The use of voriconazole for the treatment of aspergillosis in falcons (Falco species). J Avian Med Surg. 2007;21(4):307-316.
(5.) Cacciuttolo E, Rossi G, Nardoni S, et al. Anatomopathological aspects of avian aspergillosis. Vet Res Commun. 2009;33(6):521-527.
(6.) Neumann FE. Aspergillosis in domesticated birds. J Comp Pathol 2016; 155(2-3): 102-104.
(7.) Beernaert LA, Pasmans F, Van Waeyenberghe L, et al. Aspergillus infections in birds: a review. Avian Pathol. 2010;39(5):325-331.
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(9.) Marinkovisch M, Quesenberry K, Donovan TA, et al. Use of standing computed tomography for the diagnosis of a primary respiratory adenocarcinoma in a scarlet macaw (Ara macad). J Exot Pet Med. 2017;26(2):101-107.
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(11.) Krautwald-Junghanns ME, Vorbruggen S, Bohme J. Aspergillosis in birds: an overview of treatment options and regimens. J Exot Pet Med. 2015;24(3): 296-307.
(12.) Hernandez-Divers SJ. Endosurgical debridement and diode laser ablation of lung and air sac granulomas in psittaeine birds. J Avian Med Surg. 2002; 16(2): 138-145.
Please evaluate the history and results of physical examination and ancillary diagnostic tests. Formulate a list of differential diagnoses before continuing.
Caption: Figure 1. This ventrodorsal radiographic projection of a green-winged macaw was taken at the referring veterinarian 2 days before presentation to the LSUVTH. The bird presented with severe dyspnea that was not resolving with empirical antimicrobial treatment. Note the diffuse, ill-defined, increase in opacity present within the pulmonary fields, and thoracic and abdominal air sacs (arrows).
Caption: Figure 2. This lateral radiographic projection of the same macaw in Figure 1 was taken at the referring veterinarian 2 days before presentation to the LSU-VTH. Note the severe, diffuse, and ill-defined increase in opacity distributed throughout all air sacs within the coelomic cavity (arrows).
Caption: Figure 3. This image was taken during ceolioscopy of a macaw that presented with severe respiratory dyspnea. Note the white to grey granuloma (arrow) positioned deep to the biopsy forceps. This abnormal tissue was present within the coelom, coalescing with the thoracic air sacs.
Caption: Figure 4. This image was taken immediately before biopsy of the granuloma in Figure 3. Note the gelatinous, white to grey-appearing abnormal tissue (arrows).
Caption: Figure 5. This image was taken immediately after biopsy of the granuloma in Figures 3 and 4. Note that the abnormal tissue is highly vascular with ulcerations noted before and after biopsy (arrows).
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|Publication:||Journal of Avian Medicine and Surgery|
|Article Type:||Case study|
|Date:||Sep 1, 2017|
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