Avian Aspergillosis: The What, How & When of Infection &

TreatmentSamantha Sander, DVM, Dipl ACZM

University of Illinois College of Veterinary Medicine

What

• Aspergillus fumigatus• A. flavus, A. terreus, A. niger, A.

nidulans, A. viridinutans, A. glaucus, A. clavatus, A. oryzae, A. ustus, A. versicolor

• Infectious, non-contagious fungus

• Common mycotic disease of birds

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Aspergillus fumigatus

• 95% of aspergillosis cases in birds

• Ubiquitous

• Dark blue-green colonies

• Rapidly growing fungus, thermophilic• Growth up to 55oC, survives up to

70oC

• Smaller than most Aspergillus spp.

Current therapy in Avian Medicine & Surgery Speer 2016

Etiology

• Inhalation of spores (conidia)

• Air sacs 1o infection site• Posterior thoracic & abdominal

air sacs• Lung parenchyma of the

parabronchus

• Respiratory infection à green/grey mold growth

• Systemic disease à white/yellow caseous nodules & plaques

• Infection sources• Moldy bedding & feed• High environmental

temperature & humidity

Why birds?

• High average body temperature (38-45oC)

• No epiglottis for particle filtration

• No diaphragm à decreased cough reflex

• Limited ciliated epithelium in respiratory tract

• Greater respiratory surface area

• Thinner air-blood capillary barrier

• Unidirectional air flow in lungs, bidirectional air flow in air sacs à difficult to expel inhaled particles

• Limited free macrophages in respiratory system àdecreased immune presence

Risk Factors

• High antigen exposure• Warm, humid environments, poor ventilation,

poor sanitation• Improperly stored feed

• Mycotoxins also possible

• Immunosuppression• Stress, tetracyclines, vaccination, overcrowding,

migration, wild birds in captivity, traumatic injuries, toxicosis (oil, lead)

• Exposure to aerosolized toxins à mucosal irritation

• Snowy owls, Gyrfalcons, rough-legged hawk, red-tailed hawk, seabirds, waterfowl

Rob Palmer Photography

Clinical Signs

Respiratory• Dyspnea• Tachypnea• Gasping• Open mouth

breathing

Neurologic• Depression• Torticollis

GI• Inappetence• Weight loss• Emaciation

Chronic changes• Debilitation• Voice change• Exercise

intolerance

Pathophysiology

• Chicks• Lungs 1o site of infection (acute dz)

• Adults• Air sacs 1o site of infection (chronic dz)

• White to yellow plaques and nodules (mm-cm)• Lungs, syrinx, air sacs, liver, intestines, brain,

eye, skin

• Hyphae = tissue invasive

• Hematogenous spread possible

• Microscopic lesions: granulomatous inflammation w/ fungal hyphae

Immune Response

• Cellular immunity• Macrophages &

heterophils phagocytize organism

• Hampered by mycotoxins

• Humoral immunity• Antibody reactions for

adaptive immunity• Poorly understood• IgM followed by IgG

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Asper Identification• Colony morphology

• Microscopic characterization of conidia & conidiophores

• PCR• Microsatellite typing

Vet Res Commun (2009) 33:521–527

Diagnosis

• Difficult

• Combination of• History• Clinical presentation• Hematology• Biochemistry• Serologic test• Radiographic changes• Endoscopy• Culture

• Presence of asper without lesions NOT diagnostic

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Clinical Suspicion

• History• Stressful event, underlying

environmental factors, immunosuppression

• Hematology• Elevated WBC (>20-100K

cells/uL)• Heterophilia, left shift• Monocytosis, lymphopenia• Nonregenerative anemia

• Biochemistry• Hyperproteinemia

Asper Panel

• Asper galactomannan (Ag)• Rarely positive in infected falcons• More predictive in turkeys & chickens

• Asper Ab ELISA• Delayed 10-14d• Delayed/absent with immunosuppression• High Ab possible in normal birds• Not sensitive OR specific to infection

• EPH - Improves sensitivity of other tests• ↑ 𝛽 (acute) vs 𝛽 & 𝛾 (chronic) • Low pre-albumin (falcons)• Acute phase response =

• ↑ globulins, 𝛼2, SAA• ↓ Alb

AVIAN DISEASES 49:309–312, 2005

Fancy Blood Tests• Counter-immunoelectrophoresis, agar gel

immunodiffusion• Precipitates antibodies with antigens• Poor sensitivity

• ELISA• Not cross reactive across avian orders• False negatives possible

• Falconiformes 43% marked titers/22% negative

• Owls negative• Penguins 20% negative Origene.com

Seeing Is Believing• Radiographs

• Nodules• Parabronchial pattern, thickening of air

sac walls, reduced coelomic cavity detail, distinct nodular lesions, air sac hyperinflation

• Typically only useful in late state disease

• CT/advanced imaging

• Endoscopy

• Culture not definitive

• Microscopic evaluation of plaques

Current therapy in Avian Medicine & Surgery Speer 2016

Vet Radiol Ultrasound, Vol. 57, No. 1, 2016, pp 16–23.

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Acute Disease

• Rapid onset

• High morbidity/mortality

• Death within 7d

• Dyspnea, anorexia, tail bobbing, open mouth breathing, gasping

• Depression, inappetence, vomiting, crop stasis, ascites, polydipsia, polyuria, cyanosis, neurologic deficits

• White, mucoid exudate, marked congestion in lungs & air sacs

• Multiple pneumonic nodule foci possible• Large granulomas atypical

Vet Res Commun (2009) 33:521–527

Chronic disease• Localized or disseminated disease

• Immune suppression

• Minimal respiratory signs early on

• Decreased appetite, lethargy, weight loss, change/loss of voice, cough, open mouth breathing, cyanosis, polyuria, depression, vomiting

• Air sacculitis, extension into the lungs common

• Milky white tracheal discharge w/ tracheitis

• Granulomas throughout respiratory tract

• More common in adults turkeys, captive raptors, penguins & parrots

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Localized disease

• Upper respiratory tract: chronic rhinitis, sinusitis• +/- malformation of nostrils, beak, cere,

purulent nasal discharge• Wheezing, rhinoliths, oronasal

granulomas

• Mycotic keratitis• Blepharospasm, photophobia, periorbital

swelling, turbid discharge, swollen & adhered eyelids, cloudy cornea, cheesy yellow conjunctival sac exudates

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Disseminated disease

• Encephalitis & meningoencephalitis

• Depression, unilateral wing droop, paralysis, ataxia, weakness, lethargy, unsteady gait, falling onto side or back, torticollis, tremors

Treatment

• Antifungal therapy• 4-6+ mo in some cases

• Oral, IV, TO

• Topical: nebulization, nasal or air sac flushing, endoscopic or surgical irrigation

• No systemic antifungal drugs registered for use in food-producing birds

• Resistance to antifungal drugs reported

• Low safety margin of systemic antifungals

Therapeutics - Azoles

• Inhibit cytochrome P450 dependent demethylase

• Itraconazole & voriconazole most well studied in birds• Itra studies in pigeons, ducks, RTHA• Species specific variability

• Fungistatic, days to reach steady state

• Side effects: anorexia, vomiting, liver toxicity

• Voriconazole = high inter-individual variability• Increased LES in raptors, liver tox in racing pigeons• Poor bioavailability in chickens• Good tissue distribution (respiratory tract, brain)• Nebulizing inj à poor plasma & lung concentrations

(racing pigeons)

Therapeutics –Amphotericin B• Binds cell membrane à cell leakage, death

• Half life much shorter vs. mammals (turkeys, raptors)

• Nephrotoxic in mammals

• Dilute in water (NOT saline) if administered topically

Therapeutics -Terbinafine• Inhibits steroid synthesis

• No therapeutic concentrations in raptors PO

Current therapy in Avian Medicine & Surgery Speer 2016

Prevention

• Minimize risk factors• Adequate ventilation• Cleaning & disinfection

• Prophylactic treatment

• Vaccine studies not promising to date (inconsistent response)