Fungal Disease in Avian Patients

Key Points

  • Aspergillus fumigatus is a ubiquitous organism that grows best in a warm, moist environment.
  • Factors that may promote the growth of Aspergillus spp. include the presence of organic debris like moist bedding, prolonged antibiotic administration, poor sanitation, poor ventilation, and endogenous steroid production secondary to stress or the administration of exogenous steroids.
  • Aspergillosis most frequently causes air sacculitis and pneumonia, but almost any organ system can be affected.
  • Companion bird species most frequently diagnosed with aspergillosis include African Grey, Amazon, and Pionus parrots.
  • The most important fungal disease of juvenile birds is candidiasis. Candida albicans can overgrow in the oropharynx or crop leading to anorexia, oral plaques, ingluvitis, and regurgitation.
  • The presence of avian gastric yeast or Macrorrhabdus ornithogaster may be incidental, or may be associated with depression, weight loss, anorexia, and regurgitation, particularly in small parrots or songbirds.

Introduction

Fungi are among the most common causes of infectious disease in captive birds, and fungal diseases can be challenging to diagnose, as well as treat (Fig 1). Because fungi are typically opportunistic, causing non-contagious disease in susceptible individuals, prevention and treatment require an understanding of etiology as well as predisposing factors.

aspergilloma Divers

Figure 1. Fungal granuloma in the air sacs identified via laparoscopy. Photo credit: Dr. Stephen Divers. Click image to enlarge.

 

Aspergillosis

Etiology

Several species of Aspergillus can cause avian disease. Aspergillus fumigatus is most commonly encountered, followed by A. flavus and A. niger. This opportunistic organism is widely spread in the environment, particularly in warm, humid areas, although dry, dusty conditions are most likely to create the aerosols that lead to infection. Healthy birds can carry spores within their respiratory tract. Disease can occur during times of stress or immunosuppression. Predisposing conditions may include:

  • Malnutrition
  • Corticosteroid use
  • Prolonged antibiotic use
  • Pre-existing disease
  • Poor husbandry (i.e. sanitation, ventilation)
  • Heat (especially in thermo-intolerant species like gyrfalcons [Falco rusticolus])
  • The presence of organic substrate (i.e. moist food, bedding) provides an ideal medium for microbial growth, especially if it subsequently dries out and becomes aerosolized

Aspergillosis should be considered a potential problem in any bird, however species considered more susceptible include:

  • African grey parrots (Psittacus erithacus)
  • Amazon parrot (Amazona spp.)
  • Pionus parrots (Pionus spp.)
  • Gyrfalcons
  • Northern goshawks (Accipiter gentilis)
  • Golden eagles (Aquila chrysaetos)
  • Immature red-tailed hawks (Buteo jamaicensis)
  • Rough-legged hawks (Buteo lagopus)
  • Waterfowl (excluding ducks and geese)
  • Penguins

Clinical picture

Fungal spores enter the body most commonly through inhalation, although localized disease can occur with contact with broken skin or ingestion. Once an infection is established, hematogenous spread can lead to systemic disease. Aspergillosis most commonly involves the caudal air sacs and lungs, although infection can be found almost anywhere in the body including the trachea, sinuses, skin, brain, and eye.

Clinical signs depend on the location and extent of infection, which can present as single granulomas, multiple localized granulomas or plaques, or diffuse, systemic disease. Signs can be subtle and insidious in chronic disease or dramatic with rapid death in acute disease. Birds with lower respiratory tract involvement are typically dyspneic, lethargic, and often anorexic by the time of presentation. Tracheal granulomas often cause an obvious change or loss of voice.

 

Diagnosis

Diagnosis of aspergillosis can be challenging. History and physical examination can provide indications of aspergillosis, and blood work most often reveals toxic heterophilia and hypergammaglobulinemia; occasionally leucopenia can be seen with overwhelming immunosuppression. Space-occupying masses or air sac densities seen on survey radiographs can be another indicator of aspergillosis. Serology is another helpful tool in establishing a diagnosis, but is not reliable as a sole indicator. Definitive diagnosis of aspergillosis is by culture and/or histopathology of infected tissue. Endoscopic examination of air sacs and trachea provides an excellent means for collecting samples while providing an opportunity to directly assess the extent of disease.

 

Therapy

Traditionally, amphotericin B (Fungizone, E.R. Squibb) has been considered the gold standard for antifungal treatment. This fungicidal drug can be used intravenously or topically via nebulization, intratracheal injection, or direct application to air sac lesions. Unlike mammals, renal toxicity does not seem to be a problem in birds given amphotericin B.

Itraconazole (Sporanox, Janssen) is the most commonly used triazole antifungal agent in birds. This fungistatic drug is most effective as a preventative treatment, but when used to treat active disease itraconazole is often paired with nebulized clotrimazole. There have been anecdotal reports of anorexia, depression, and death in African grey parrots given itraconazole at standard drug doses. Other triazoles used include oral ketoconazole, topical enilconazole, and miconazole, although efficacy has not been established for any of these.

More recently, use of oral voriconazole (V Fend, Pfizer) has shown to be an effective treatment in birds with aspergillosis. Pharmacokinetic trials have been reported in chickens, African grey parrots, and Umbrella cockatoos (Cacatua alba). Use caution when determining a voriconazole dose, as the enzymes used to metabolize this broad-spectrum triazole can be saturated at plasma levels and therefore doses should not be extrapolated from one species to another.

Terbinafine (Lamisil, Novartis) has also been described as a treatment for aspergillosis. Terbinafine is generally well tolerated and may be given by mouth or nebulization. Although efficacy has not been established, terbinafine has been used in infections resistant to itraconazole.

 

Candidiasis

Candida albicans is an opportunistic yeast typically found in the upper gastrointestinal tract of birds. While Candida spp. are a normal part of avian gastrointestinal flora, overgrowth occurs when the patient is stressed, immunocompromised, or when normal bacterial flora is suppressed.

Candidiasis is most common in young, growing birds. Clinical signs include anorexia, white oropharyngeal plaques, delayed crop emptying, and regurgitation.

Diagnosis is based on the identification of high numbers of budding yeast on cytology, or much less commonly, by positive culture.

Nystatin is a fungistatic drug used to treat yeast infections. Nystatin is not normally absorbed well, but rather functions as a topical treatment when given by mouth. As it requires contact with yeast to be effective, nystatin must coat the mucous membranes and should not be given with food. Oral fluconazole (Diflucan, Roerig) may be indicated in cases of resistant or severe yeast infection or in cases when ulceration of the crop will allow systemic absorption of nystatin and subsequent nephrotoxicity.

 

Avian gastric yeast

Avian gastric yeast (Macrorrhabdus ornithogaster) is commonly found in budgerigar parakeet or “budgies” (Melopsittacus undulatus), lovebirds, cockatiels (Nymphicus hollandicus), and canaries (Serinus canaria). The pathogenicity of this organism is unknown. Avian gastric yeast can be found in the feces of many apparently healthy birds, but it has also been associated with chronic disease characterized by lethargy, anorexia, weight loss, and regurgitation (Fig 2). Macrorrhabdus has been classically linked with the “going light” syndrome in budgies. Diagnosis is made by finding the organism on a fecal wet-mount in a bird with consistent clinical signs. Amphotericin B may be given orally for avian gastric yeast, and some authors also report success with fluconazole.

Cytologic sample of avian gastric yeast

Figure 2. Cytologic sample of avian gastric yeast (Macrorrhabdus ornithogaster). Image provided by Dr. Gregory Rich. Click image to enlarge.

Cryptococcosis

Cryptococcosis is uncommon in companion birds, but this yeast is commonly found in pigeons. Cryptococcus neoformans may infect the upper respiratory tract leading to rhinitis and sinusitis with periorbital swelling. Infections can disseminate to the brain and/or meninges, as well as the gastrointestinal tract. Diagnosis is often made at necropsy, although the organism can be found on cytology or culture. A zoonotic organism, this yeast can cause meningitis in humans.
 

Summary

For many presenting problems, fungal disease is an important differential diagnosis in the avian patient. Consider aspergillosis as a potential cause of air sacculitis or pneumonia, although virtually any organ system can be affected. Overgrowth of the yeast, Candida albicans can cause stomatitis and ingluvitis, particularly in the juvenile bird or the immunocompromised adult. The avian gastric yeast, Macrorrhabdus ornithogaster, is also an important differential for may be incidental, or may be associated with non-specific signs of illness as well as regurgitation in small psittacine or passerine birds.
 

Table 1. Antifungal agents commonly used in birds

Drug Dose Route Frequency Comments
Amphotericin B 1 mg/kg
1.5 mg/kg
100 mg/kg
IT
IV
PO
q12h
q8-12h
q12h
10-30 days
Clotrimazole 7-10% solution with 5% DMSO in polyethylene glycol Nebulization q12h Have prepared by compounding pharmacy
Fluconazole 5 mg/kg PO q12h
Itraconazole 2.5-5.0 mg/kg
5-10 mg/kg
PO
PO
q24h
q12-24h
African grey parrots
Most spp excluding Grey parrots
7 mg/kg PO q12h for 5 days, then q24h Raptors
Nystatin 300,000 IU/kg PO q12h Requires contact with mucous membranes
Terbinafine 10-15 mg/kg PO q12-24h
Voriconazole 10-12 mg/kg
12-18 mg/kg
PO
PO
q12h
q12h
Raptors
Grey parrots
IT: intratracheal; IV: intravenous; PO: per os; q: every; h: hour; spp: species

References