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 DOI: 10.1177/1098612X13489223

2013 15: 605Journal of Feline Medicine and SurgeryD Radford, Etienne Thiry, Uwe Truyen and Marian C Horzinek

Herman Egberink, Tadeusz Frymus, Tim Gruffydd-Jones, Margaret J Hosie, Hans Lutz, Fulvio Marsilio, Karin Möstl, Alan Katrin Hartmann, Albert Lloret, Maria Grazia Pennisi, Lluis Ferrer, Diane Addie, Sándor Belák, Corine Boucraut-Baralon,

Aspergillosis in Cats: ABCD guidelines on prevention and management  

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JFMS CLINICAL PRACTICE 605

Journal of Feline Medicine and Surgery (2013) 15, 605–610

European Advisory Board on Cat Diseases

www.abcd-vets.orgCorresponding author: Katrin Hartmann

Email: Hartmann@medizinische-kleintierklinik.de

DOI: 10.1177/1098612X13489223© Published by SAGE on behalf of ISFM and AAFP 2013

C L I N I C A L R E V I E W

ASPERGILLOSIS IN CATSABCD guidelines on prevention and management

Katrin Hartmann, Albert Lloret, Maria Grazia Pennisi, Lluis Ferrer*, Diane Addie, Sándor Belák, Corine Boucraut-Baralon, Herman Egberink,Tadeusz Frymus, Tim Gruffydd-Jones, Margaret J Hosie, Hans Lutz, Fulvio Marsilio, Karin Möstl, Alan D Radford, Etienne Thiry, Uwe Truyen, and Marian C Horzinek

Agent properties

Aspergillosis is caused by fungal organisms of the genus Aspergillus.Aspergillus species are ubiquitous saprophytes. The organism is occa-sionally also isolated from healthy animals. There is some confusion in the nomenclature of these fungi. Species

identification only on the basis of phenotypic features probably leadsto overidentification of Aspergillus fumigatus. Some species initiallyidentified as A fumigatus by conventional methods now have been classified as Neosartorya species, Aspergillus lentulus and Aspergillusudagawae using molecular techniques. Differences in virulence and

invasion abilitybetween speciesexist, and severecases commonlyseem to be associated withNeosartorya speciesinfections.1 Speciesincluded in the A fumigatus complexare responsible for themajority of infectionsin cats, but Aspergillus

flavus, Aspergillus nidulans, Aspergillus niger and Aspergillus terreus havealso been detected. Recently, A udagawae, a rare opportunisticpathogen, was identified in a cat causing fatal orbital aspergillosis.2

Epidemiology

Aspergillus species are found worldwide in soil and decaying vegeta-tion. All mammals, including humans, are susceptible to aspergillosis.Immunosuppressed persons (eg, by human immunodeficiency virusinfection) are particularly prone to acquiring the disease. Cats and otheranimals are infected through contamination of the environment. Directtransmission does not occur – thus, aspergillosis is not a zoonosis.

European Advisory Board on Cat DiseasesThe European Advisory Board on Cat Diseases (ABCD) is a bodyof experts in immunology, vaccinology and clinical feline medicinethat issues guidelines on prevention and management of felineinfectious diseases in Europe, for the benefit of the health andwelfare of cats. The guidelines are based on current scientificknowledge of the diseases and available vaccines concerned.

The latest version of the aspergillosis in cats guidelines is available at www.abcd-vets.org

Overview: Aspergillosis is a sporadic mycosisthat occurs worldwide in mammals and birdsand leads to a usually chronic, and only rarelyacute, disease that mainly affects the nasalcavity and sinuses. Infection: Aspergillus species infections arecommonly associated with predisposing local orsystemic factors. Local disease can spread andinvolve the central nervous system or the lungs.Some Aspergillus species can also disseminate,causing systemic infections. In contrast to dogs,in which (nasal) aspergillosis is relativelycommon, aspergillosis is rare in cats, butconsidered an emerging infection. Clinical signs: There are two clinical forms of aspergillosis in cats, the sinonasal form(characterised by signs of chronic nasalinfection) and the newly emerging, more invasivesino-orbital form (characterised by signs oforbital and surrounding tissue invasion). Sino-orbital involvement has been describednow in approximately half of the reported cases.Disease management: Treatment should consistof local and systemic antifungal therapy.

*The ABCD is grateful to Professor Lluís Ferrer, of the FosterHospital for Small Animals, Cummings School of VeterinaryMedicine, Tufts University, USA, who, though not a memberof the Board, contributed to this article.

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REV IEW / ABCD guidelines on aspergillosis

Aspergillosis occurs worldwide. Most of thecases have been reported from Australia, but feline aspergillosis has been described in North America, the United Kingdom,Switzerland, Germany, Japan and Italy.1,3–5 Noage or sex predisposition has been detected. A predisposition was found in brachycephalicbreeds, especially Persian and Himalayancats.1,3,6,7 Reduced drainage of upper respira-tory secretions has been suggested as a predis-posing factor.8 Additional suggested factorsinclude innate defects of mucosal immunity,previous viral upper respiratory tract infec-tions, and antibiotic treatment.3 A relationshipbetween sino-orbital aspergillosis and lym-phoplasmacytic rhinitis in a cat treated withoral prednisone has been suggested,4 indicat-ing that immunosuppression may play a role.No association between aspergillosis andfeline retrovirus infections has been reported.9

Pathogenesis

Infection usually occurs from Aspergillusspecies accumulated in pet food and litter. Thespores are inhaled and deposited in the sino salcavity, the primary site of infection. The fungusmust adhere to the respiratory epithelium, penetrate it, destroy surrounding cells, andresist phagocytosis. Aspergillus species conidiabind to various cell surface proteins using specific adhesion molecules, such as hydro phobins. A fumigatus also produces animmuno suppressive toxin (gliotoxin) thatinhibits macrophage phagocytosis. Othermetabolites impair mucociliary action and pro-long the organisms’ epithelial resistance, whileenzymes (eg, proteases) help to invade tissues.

Figure 1 Exophthalmos of the left eye in a cat with a leftretrobulbar fungal granuloma (sino-orbital aspergillosis). Thereis prolapse of the third eyelid. A partial lateral tarsorrhaphy wasperformed to prevent exposure keratitis. Courtesy of VanessaBarrs, University Veterinary Teaching Hospital, Sydney, Australia

Figure 2 Rightexophthalmos, third eyelidprolapse and oedema andswelling of the right side ofthe face in a cat with a rightretrobulbar and paranasalfungal granuloma. Courtesyof Vanessa Barrs, UniversityVeterinary Teaching Hospital,Sydney, Australia

Figure 3 Ventral expansion of retrobulbar fungal granulomascausing a mass effect in the pterygopalatine fossa in a catwith a right retrobulbar fungal granuloma (arrow). Courtesy ofVanessa Barrs, University Veterinary Teaching Hospital, Sydney,Australia

Figure 4 Thoracic radiograph (laterolateral view) of a cat with pulmonary aspergillosis,confirmed at necropsy. Courtesy of Katrin Hartmann, Ludwig Maximilians University, Munich,Germany

606 JFMS CLINICAL PRACTICE

There are two clinical forms of aspergillosis in cats,the sinonasal and the newly emerging,

more invasive sino-orbital form.

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REV IEW / ABCD guidelines on aspergillosis

Clinical signs

Aspergillosis occurs in two main forms incats, sinonasal aspergillosis (SNA) and sino-orbital aspergillosis (SOA). SNA is charac-terised by more local signs of chronic nasalinfection, such as sneezing, uni- or bilateralserous to mucopurulent nasal discharge, andsometimes epistaxis. Stertorous breathing,granuloma formation, soft tissue masses pro-truding from the nares, and bone lysis are lessfrequent abnormalities.3,7SOA is the more invasive form. The clinical

manifestation depends on the invading fungalspecies, and SOA probably represents anextension of SNA to orbital and subcutaneoustissues, caused by invasive Aspergillus species,like Neosartorya species. Most cats with SOAindeed have a history of nasal discharge, andnasal lesions have been seen at necropsy inaddition to lysis of the orbital lamina identi-fied using imaging techniques.1,4,6 SOA ischaracterised by signs of orbital and sur-

Figure 6 (a) Growth of A fumigatus on malt extract agar (MEA). Colonies are typically olivegreen and velvety due to rapid sporulation. (b) By contrast some species of Aspergillus in the A fumigatus complex that cause sino-orbital aspergillosis are slow to sporulate and thecolonies appear whitish until sporulation occurs. Courtesy of Vanessa Barrs, University VeterinaryTeaching Hospital, Sydney, Australia

Figure 5 (a) Haematoxylin and eosin stained section of a retrobulbar fungal granuloma consisting of a large central granulomasurrounded by smaller satellite granulomas. Centrally each granuloma contains necrotic cellular debris within which branching,septate fungal hyphae are confined, as seen on the Grocott stained section (b). There are surrounding zones of neutrophils andeosinophils, macrophages, fibroblasts and a peripheral cuff of lymphocytes and plasma cells. Courtesy of Vanessa Barrs, UniversityVeterinary Teaching Hospital, Sydney, Australia

JFMS CLINICAL PRACTICE 607

rounding tissue invasion, including unilateralexophthalmos, third eyelid prolapse (Figure1), conjunctival hyperaemia and keratitis(Figure 2). In some cases, a mass in thepterygo palatine fossa (Figure 3) or an ulcera-tion of the hard palate, or even extension anddestruction of the nasal cavity (sometimeswith swelling and skin ulcers), can be seen.The central nervous system can be involvedleading to neurological signs, peripheralvestibular signs and blindness, and regionallymphadenopathy and fever can occur. Atypical cases of aspergillosis have been

reported, including pneumonia (Figure 4) andpyothorax in a diabetic cat,10 a cat with generalised systemic infection,5 and a cat withulcerative keratitis.11Laboratory abnormalities in cats with

aspergillosis are non-specific and the result ofchronic inflammation. Hyperglobulinaemia isthe most frequently reported abnormali-ty.1,6,12,13

Immunity

Immunity against Aspergillus species infectionis poorly understood. Many cats develop anti-bodies, but some cats produce only low orundetectable antibody levels (mostly in casesof A fumigatus infection).7 Additionally, catscan produce antibodies without clinical dis-ease, which is likely the result of non-invasivemucous membrane colonisation that occurs inmany healthy cats.

Diagnosis

Diagnosis is based on demonstration of fungalhyphae by cytology or histology (Figure 5) anddefinitive confirmation by fungal culture(Figure 6). Advanced imaging techniques(computed tomography [CT] or magnetic reso-

a b

Sino-orbitalinvolvementhas been

described nowin

approximatelyhalf of the

reported cases.

a b

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608 JFMS CLINICAL PRACTICE

nance imaging [MRI]) arehelpful to assess diseaseextension and to find the best location for obtainingdiagnostic samples duringrhinoscopy (Figure 7) [EBMgrade IV].7 CT and MRI arealso important tools to ruleout neoplasia. However, in astudy including 10 cats (fivewith aspergillosis), CT find-ings neither allowed dis crim -ination between differentfungal infections nor distin-quished aspergillosis fromneoplasia [EBM grade III].14

Direct detection of the organismA definitive diagnosis is usually obtained byhistology and detection of the organism inbiopsy specimens obtained by rhinoscopy(Figure 8) or nasal cavity lavage techniques[EBM grade III]. As Aspergillus species can befound on mucosal surfaces of healthy animals,infection can only be diagnosed if samples aretaken from a deep layer of tissue, and it isimportant to take samples directly from affect-ed areas. Within tissues, Aspergillus speciesgrows with branched, septate hyphae (2–5 µmdiameter). Cytology of fine needle aspirates of orbital

or palatine lesions can sometimes demon-strate fungal hyphae, but a negative resultdoes not rule out aspergillosis. If cultured on special growth media (eg,

Sabouraud agar), Aspergillus species formmycelia with clearly visible conidia on conid-iophores within 5–7 days (Figure 9). A singlepositive culture from swabs or secretionswithout histological evidence is not diagnos-tic, as the organism is ubiquitous.

Polymerase chain reaction has recently beenoffered for the detection of Aspergillus species,but its relevance in veterinary medicine is notyet clear.15A new non-invasive test is the measurement

of serum galactomannan, a polysaccharidefungal cell wall component by one-stage,immunoenzymatic sandwich ELISA. Overall,the test is moderately specific, but has a poorsensitivity and, thus, is not very helpful torule out the disease [EBM grade IV].16

Detection of antibodiesAspergillus species antibody testing for cats isavailable on the basis of agar gel immuno -diffusion, latex agglutination, counter-immuno -electrophoresis or ELISA. Due to high numbersof positive results in healthy cats (up to 15%),positive test results should always be evaluatedin combination with clinical signs and histologyresults. Negative results should also be inter-preted with caution, as some individuals onlyproduce low amounts of antibodies (mostlywhen infected with A fumigatus) that might bemissed. Antibody testing was not useful in twoof four cats with fungal rhinitis [EBM gradeIV].7 Nevertheless, antibody measurement cangive useful hints in some potentially affectedcats when interpreted carefully and can be veryhelpful in the decision to perform more inva-sive diagnostics [EBM grade III].1

Treatment

No prospective controlled studies exist on thetreatment of aspergillosis in cats, and theavailable information is based only on retro-spective case reports. In general, response totherapy and prognosis in SNA is good whenintensive and sufficiently long treatment isinstituted. Response to treatment is less suc-cessful in invasive SOA, and the prognosis isworse.8 In systemic aspergillosis, the progno-sis is generally poor. In SNA, the treatment of choice is a

Figure 8 Rhinoscopy being performed in a cat with chronicnasal discharge to obtain samples for histology and culture of Aspergillus species. Courtesy of Bianka Schulz, LudwigMaximilians University, Munich, Germany

Figure 9 A fumigatus conidial heads from a squashpreparation of fungal plaques (inset) in a Scottish shorthaircat with sinonasal aspergillosis. Courtesy of Vanessa Barrs,University Veterinary Teaching Hospital, Sydney, Australia

Figure 7 Rhinoscopicfindings in a cat withsinonasal aspergillosis.Courtesy of Bianka Schulz,Ludwig Maximilians University,Munich, Germany

RE V IEW / ABCD guidelines on aspergillosis

As Aspergillusspecies can be found onmucosal

surfaces ofhealthy animals,infection can

only bediagnosed ifsamples aretaken from adeep layer of

tissue.

EBM gradesThe ranking systemfor grading the levelof evidence ofvarious statementswithin this article isdescribed on page 533 of thisSpecial Issue.

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JFMS CLINICAL PRACTICE 609

Drug Dose Comments

Clotrimazole Single or multiple intranasal local instillation

Itraconazole 5 mg/kg q12h PO Suggested drug of choice after local treatment (should be given for at least 2–3 months or 1 monthbeyond clinical cure)

Fluconazole 1.25–2.5 mg/kg q12h PO Should be considered in cases of CNS infection (should be given for at least 2–3 months or 1 monthbeyond clinical cure)

PO = oral, CNS = central nervous system

Systemic treatment for aspergillosis (most commonly used drugs)Table 1

Figure 10 Local infusion ofclotrimazole under generalanaesthesia in a cat withsinonasal aspergillosis.Courtesy of Bianka Schulz,Ludwig Maximilians University,Munich, Germany

Figure 11 Retrobulbargranuloma after radicalorbital debridement surgery.Courtesy of Vanessa Barrs,University Veterinary TeachingHospital, Sydney, Australia

com bination of systemic antifungal treatment (itraconazole, fluconazole, amphotericin B,posaconazole, voraconazole or terbinafine) incombination with local therapy, using clo -trimazole or enilconazole intranasal infusionsunder general anaesthesia (Table 1) [EBMgrade III]. Systemic antifungal treatmentshould be administered over several months,and owners should be informed early aboutthe long treatment required. Based on caseseries, best choices for systemic treatment areitraconazole (5 mg/kg q12h PO) alone or incombination with amphotericin B, or the newazoles posaconazole (2.5–4.5 mg/kg q12h PO)and voriconazole (5–12 mg/kg q24h PO) [EBMgrade III]. Voriconazole looks like a promisingdrug, but can result in adverse neurologicaleffects, including ataxia, paraplegia and cra-nial nerve deficits.17 Therefore, voriconazoleshould only be used in selected cases untilmore studies on safety in cats have been per-formed. In cases of central nervous systeminvolvement, fluconazole (1.25–2.5 mg/kgq12h PO) is a good option.The local treatment is usually performed with

infusion of clotrimazole (Figure 10). Thisrequires access to affected tissues and is lesseffective when the infection occurs deep in thetissue. Surgical debridement of gross fungallesions (Figure 11) before local treatment is rec-ommended to increase the chance of completeremission [EBM grade III].8,18A single intranasalinfusion of clotrimazole led to long-term resolu-tion of clinical signs in two studies, involvingthree cats3 and two cats [EBM grade IV].19Multiple local treatments probably are better to

reduce relapses. Systemic treatment solelywithout local infusions is not as successful. Fourcats with fungal rhinitis were treated with itra-conazole orally; when therapy was discontin-ued, clinical signs recurred [EBM grade IV].7In SOA, treatment is more difficult. In severe

SOA, surgery is necessary – either lateralorbitotomy or eye enucleation.13 In a series ofthree cases with SOA, two cats were treatedwith voriconazole and surgery with successfulresults [EBM grade IV].13 Other drugs havebeen used in cats with SOA, includingechinocandins in two cats, caspofungin as single treatment with good results in one cat[EBM grade IV],1 and micafungin in one catshowing no success.2 In one case, posacona-zole cured a cat with SOA which had notresponded to itraconazole plus amphotericin B[EBM grade III];12 in another case, long clinicalremission was achieved with posaconazoleafter no improvement with itraconazole plusterbinafine treatment [EBM grade III].18If only the eyes are involved, local treatment

can be successful. An 8-year-old cat that suffered from ulcerative keratitis with stromalloss, stromal infiltrate, corneal oedema, peri limbal vascularisation and miosis wastreated with 1% voriconazole solution, andthe keratomycosis resolved successfully [EBMgrade III].11Although associated with a poor prognosis,

one cat with pulmonary aspergillosis was suc-cessfully managed with a combination of sur-gery (lung lobectomy and chest drainage) andsystemic itraconazole therapy for 1 month[EBM grade IV].10

REV IEW / ABCD guidelines on aspergillosis

When treatedaggressivelyand for longenough, theprognosis forsinonasal

aspergillosis is good; it isguarded insino-orbital, and poor insystemic

aspergillosis.

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610 JFMS CLINICAL PRACTICE

< Aspergillosis is a fungal disease occurring worldwide; it is lesscommon in cats than in dogs.

< Animals are infected through contamination from theenvironment; direct transmission does not occur.

< Aspergillosis is not a zoonosis; humans also acquire theinfection from the environment.

< In cats, aspergillosis occurs in two main forms: the sinonasal,and the more invasive sino-orbital form.

< Diagnosis relies on detection of the organism in affectedtissues, usually by cytology or histology.

< Treatment should consist of local and systemic antifungaltherapy.

< When treated aggressively and for long enough, the prognosisfor sinonasal aspergillosis is good; it is guarded in sino-orbital, and poor in systemic aspergillosis.

KEY POINTS

Available online at jfms.com Reprints and permission: sagepub.co.uk/journalsPermissions.nav

References

1 Barrs VR, Halliday C, Martin P, Wilson B, Krockenberger M,Gunew M, et al. Sinonasal and sino-orbital aspergillosis in23 cats: aetiology, clinicopathological features and treat-ment outcomes. Vet J 2012; 191: 58–64.

2 Kano R, Itamoto K, Okuda M, Inokuma H, Hasegawa A andBalajee SA. Isolation of Aspergillus udagawae from a fatalcase of feline orbital aspergillosis. Mycoses 2008; 51: 360–361.

3 Tomsa K, Glaus TM, Zimmer C and Greene CE. Fungal rhini-tis and sinusitis in three cats. J Am Vet Med Assoc 2003; 222:1380–1384, 1365.

4 Barachetti L, Mortellaro CM, Di Giancamillo M, Giudice C,Martino P, Travetti O, et al. Bilateral orbital and nasalaspergillosis in a cat. Vet Ophthalmol 2009; 12: 176–182.

5 Schulz B, Unterer S, Hartmann A, Werckenthin C,Brühschwein A and Hartmann K. Diagnostik und therapieder nasalen aspergillose bei der katze – fallbeschreibungund literaturübersicht. Tierärztl Prax 2007; 35: 281–286.

6 Hamilton HL, Whitley RD and McLaughlin SA.Exophthalmos secondary to aspergillosis in a cat. J Am AnimHosp Assoc 2000; 36: 343–347.

7 Whitney BL, Broussard J and Stefanacci JD. Four cats withfungal rhinitis. J Feline Med Surg 2005; 7: 53–58.

8 Barrs VR, Beatty JA, Lingard AE, Malik R, Krockenberger MB,Martin P, et al. Feline sino-orbital aspergillosis: an emergingclinical syndrome. Aust Vet J 2007; 85: N23.

9 Goodall SA, Lane JG and Warnock DW. The diagnosis andtreatment of a case of nasal aspergillosis in a cat. J SmallAnim Pract 1984; 25: 627–633.

10 Hazell KL, Swift IM and Sullivan N. Successful treatment ofpulmonary aspergillosis in a cat. Aust Vet J 2011; 89: 101–104.

11 Labelle AL, Hamor RE, Barger AM, Maddox CW and Breaux

CB. Aspergillus flavus keratomycosis in a cat treated withtopical 1% voriconazole solution. Vet Ophthalmol 2009; 12:48–52.

12 McLellan GJ, Aquino SM, Mason DR, Kinyon JM and MyersRK. Use of posaconazole in the management of invasiveorbital aspergillosis in a cat. J Am Anim Hosp Assoc 2006; 42:302–307.

13 Smith LN and Hoffman SB. A case series of unilateral orbitalaspergillosis in three cats and treatment with voriconazole.Vet Ophthalmol 2010; 13: 190–203.

14 Karnik K, Reichle JK, Fischetti AJ and Goggin JM. Computedtomographic findings of fungal rhinitis and sinusitis incats. Vet Radiol Ultrasound 2009; 50: 65–68.

15 Lau A, Chen S, Sorrell T, Carter D, Malik R, Martin P, et al.Development and clinical application of a panfungal PCRassay to detect and identify fungal DNA in tissue speci-mens. J Clin Microbiol 2007; 45: 380–385.

16 Whitney J, Beatty JA, Martin P, Dhand NK, Briscoe K andBarrs VR. Evaluation of serum galactomannan detection fordiagnosis of feline upper respiratory tract aspergillosis.Vet Microbiol 2013; 162: 180–185.

17 Quimby JM, Hoffman SB, Duke J and Lappin MR. Adverseneurologic events associated with voriconazole use in 3 cats.J Vet Intern Med 2010; 24: 647–649.

18 Giordano C, Gianella P, Bo S, Vercelli A, Giudice C, DellaSanta D, et al. Invasive mould infections of the naso-orbitalregion of cats: a case involving Aspergillus fumigatus and anaetiological review. J Feline Med Surg 2010; 12: 714–723.

19 Furrow E and Groman RP. Intranasal infusion of clotrima-zole for the treatment of nasal aspergillosis in two cats. J AmVet Med Assoc 2009; 235: 1188–1193.

Prevention

Due to the ubiquitous occurrence and the highresistance of the pathogen, prophylaxis ishardly possible. Although an association ofaspergillosis with immunosuppression is not clearly established, prophylactic measuresin immunocompromised animals consist ofreducing exposure. Therefore, immunosup-pressed animals should be kept indoors.

Funding

The authors received no specific grant from anyfunding agency in the public, commercial or not-for-profit sectors for the preparation of this article. TheABCD is supported by Merial, but is a scientificallyindependent body.

Conflict of interest

The authors do not have any potential conflicts ofinterest to declare.

REV IEW / ABCD guidelines on aspergillosis

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