Aspergillosis: This fungal disease of the respiratory system is the most commonly occuring disease among wild birds held in captivity and an occasional, but always possible problem in companion birds. Though it may occur in individuals of virtually any species, there are clearly species predilections. Among raptors, goshawks, gyrfalcons, immature red-tailed hawks, golden eagles, and snowy owls seem more likely to have the disease. Among other non-companion bird penguins, flamingoes, ostriches, and arctic waterfowl (eiders) are commonly afflicted by the disease either upon introduction to captivity or sporadically during long-term keeping. Companion birds most often exhibiting the disease are African grey parrots and various Amazon parrots, but any species may be vulnerable under the right circumstances.

Those factors that have been implicated as causal factors in the development of aspergillosis include shipping, overcrowding, malnutrition, poor ventilation, neonates, geriatric, and birds subjected to antibiotics, corticosteroids, or repiratory irritants such as disinfectant fumes, cigarette smoke, or ammonia.

Several forms of the disease are recognized. An acute form occurs when a bird is exposed to a large number of spores from a point source. What develops is hundreds of miliary foci of inflammation mostly in the lung. This form is known as "brooder pneummonia" when it affects neonates and it arises as a result of environmental contamination in the hatcher or brooder and the under developed respiratory defense mechanisms of the neonatal bird. In adult birds, it occurs from exposure to clouds of spores in poorly kept food or bedding. Moldy silage, leaf piles, poorly kept straw or shavings, and eucalyptus bark have been implicated as sources. Other forms are more chronic diseases and include focal lesions in the trachea or the syrinx, lungs, airsacs, pericardium, and occasionally the brain or anterior chamber of the eye. In fact, aspergillosis can occur anywhere there is compromised tissue -- skin lesions have been encountered under wet bandages on occasion. In all of the chronic forms, some degree of host immunosuppression is implicated in the pathogenesis.

The management and diagnosis of aspergillosis has proven difficult due to:

Most expressions of the disease involve the respiratory system, although lesions may occur in immunologically-deficient sites such as the eye and portions of the CNS. However, the early clinical signs of the chronic forms do not necessarily and most often do not result in expression of respiratory signs. Rather the signs are subtle and non-specific, such as:

Diagnosis is established based upon clinical suspicion (signs, species, sex, time of year), antibody detection (ELISA^a), tracheal culture and/or washes, airsac washes, blood work and endoscopy. Radiology is generally of limited value as a diagnostic tool during stages of development where treatment is a reasonable possibility. Clinical suspicion coupled with positive tracheal culture (taken from deep within the trachea with a nasopharyngeal swab^g) and an elevated white cell count (15,000 to 100,000 cc/mm³+) is taken as circumstantial evidence of occurrence and the basis upon which to commence treatment. Endoscopy is invaluable as it allows examination of the trachea and the airsaccs for lesions referable to aspergillosis. Whereas well-developed granulomas or lesions that are sprouting fungal hyphae leave little doubt, in many early cases, one sees hypervascularized airsac only.

The ELISA test measures antibody presence. A positive result indicates either active infection, long-term exposure, or an elevated antibody level resulting from a previous infection. A negative result indicates no antibodies, either as a result of lack of disease or inability to produce them. It is a good screening test, and when used in conjunction with other parameters and it aids the clinician establish a diagnosis. Other useful serological evaluations include protein eletrophoresis as aspergillosis has a fairly distinct eletrophoretic signature, and antigen capture ELISA. The latter detects structural and metabolic components of the organism present in the plasma and theoretically ought to be advantageous since detection does not rely on the host's antibody response. A PCR test has been reported for use in detecting human aspergillosis, but has not yet been applied to birds. All of these latter tests need further evaluation against known cases of aspergillosis to determine their clinical utility.

Treatment options for aspergillosis are limited. Drugs used in treatment of aspergillosis have included 5-fluorocytosine^b(5FC), itraconazole^c, fluconazole^d, clotrimazole^e and amphotericin B^f. Only the latter is fungicidal. Developed in the 1950's, it remains the gold standard against which other antifungal agents are compared. It, along with 5FC, itraconazole, and clotrimazole, and particularly the latter two in combination, have documented efficacy in treating known cases of aspergillosis; fluconazole appears to be ineffective (Orosz et al). Enilconazole and ketoconazole have been used with a modicum of success by individual clinicians also. Of all the azole compounds, itraconazole appears to have the greatest activity against Aspergillus spp. Accordingly, it is the most widely used antifungal agent, presently.

In individuals with elevated ELISA values or vague signs of illness that are attributable to aspergillosis based on clinical suspicion, tracheal culture and elevated white cell count, 5FC (120 mg/kg/day in two or three divided doses) has been effective, apparently, in some cases involving raptors over the last 15 years. Recently, itraconazole (5-10 mg/kg sid or bid), has supplanted 5FC and the other azoles and is regarded as the drug of choice, both for treatment of active cases as well as prophylactic treatment. However, pharmacologic data is lacking for most avian species and there have been no controlled studies comparing its efficacy to that of Amphotericin B. Further, a study by Lumeij et al. in pigeons showed that while a dosing regimen of 10.3 mg/kg q6 hours for 12 doses yielded plasma levels well above the needed minimial inhibitory concentration for Aspergillus spp, very little of the drug was actually found in the lung tissue itself

For more severe cases, the predominant treatment protocols rely on the intravenous administration of Amphotericin B for 3 - 5 days with orally administered itraconazole and nebulized clotrimazole. Amphotericin B should be diluted to a final concentration of 0.1 mg/ml in 5% dextrose or sterile water (not saline) prior to administration. While not uniformly effective, owing to the variability of the presentation of many cases, nonetheless, this combination has been effective in recovering some very severe cases of pulmonary and air sac aspergillosis.

Surgical removal of lesions, especially those in the nasal sinuses, trachea, syrinx, and abdominal airsacs is recommended when feasible, especially for those in the upper respiratory tree. Nasal lesions may be removed by repeated lavage, currettege, or trephination of sinuses. Tracheal and syringeal lesions are removed by tracheostomy or endoscopically-guided resection. Intratracheal treatment with Amphotericin B follows such removal. About 1.0 mg/kg is diluted to a volume of 1 - 2 cc in sterile water (not saline) and injected through the glottis with a curved, ball-tipped feeding needle or a soft red rubber tube. This is repeated twice daily for several days. On occasion, clinicians have installed indwelling cannulas into abdominal airsacs and lavaged them in similar fashion. Enilconazole and amphotericn B gel preparations (e.g. mixed with sterile surgical lubricant) have also been recommended for local installation into airsacs.

A new drug, voriconazole, is currently undergoing trials for treating human aspergillosis. Similar tests are in the planning stages at The Raptor Center at the University of Minnesota in conjunction with Pfizer and University of Minnesota Hospitals. Compared to itraconazole, minimal inhibitory concentrations for Aspergillus spp. were lower and the volume distribution, especially into the CNS, was better for voriconazole. Dosage information is not yet available. Lamisil is another new antifungal drug currently under evaluation.

In conclusion, depending on the site of the lesions and the severity of the disease there are many permutations to treatment. The mainstay at the present time, however, is a 3 - 5 days course of amphotericin B along with oral itraconazole and nebulized clotrimazole for extended periods of time – upwards of three months. Progress is monitored by following serial total white blood cell counts and ELISA values. Treatment is continued for a period of time beyond the return of these parameters to normal or near normal levels.

Clearly aspergillosis is to be prevented or treated while subclinical. Prophylactic treatment with 5FC or itraconazole is recommended for newly captured, newly admitted birds of species that have an established track record of susceptibility. The usual program is to give 5FC at 75 mg/kg bid or itraconazole at 5-10 mg/kg bid for two weeks. The course of treatment may be extended if clinical indications warrant. This approach should also extend to individuals of highly susceptible species that are undergoing change of management e.g. transfer to new owner or new enclosure, regardless of age or other circumstance. Treatment for one week prior to the move and two weeks after is recommended. Among raptors, domestically-reared gyrfalcons and gyr-hybrids, should be provided this prophylactic regimen from a period beginning at 45 days of age through 75-90 days of age. If extreme heat conditions prevail during the months of August and September in any given locale, young gyrfalcons should be provided extended prophylactic treatment during this time.

Vaccination for aspergillosis is clearly needed to replace these extensive prophylactic treatment programs. Presently none is available and current research is not promising. As an alternative, agents that stimulate the immune system may have clinical utility

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