Clinical Commentary Conidiobolomycosis JOHN SCHUMACHER* and JIM SCHUMACHER† Department of Clinical Sciences, J

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Clinical Commentary Conidiobolomycosis JOHN SCHUMACHER* AND JIM SCHUMACHER† Department of Clinical Sciences, J. T. Vaughan Teaching Hospital, College of Veterinary Medicine, Auburn University, Alabama 36849-5522; and †Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee 77901-1071, USA.

Conidiobolomycosis is a pyogranulomatous disease of the by pythiosis, lesions caused by C. coronatus do not appear to upper portion of the respiratory tract of horses, man and, be pruritic. These lesions may be similar in appearance to an rarely, other species, caused by infection of the mucosa and ethmoidal haematoma, nasal neoplasia, nasal granulomas submucosa by the fungus, Conidiobolus coronatus. caused by periapical infection of a maxillary premolar, and Conidiobolus was once included in the genus Entomophthora granulomas caused by other fungi that infect the nasal and hence is sometimes referred to as Entomophthora mucosa, such as Rhinosporidium seeberi, Cryptococcus coronatus (Richardson and Shankland 1999). neoforman and Coccidioides immitis. Conidiobolomycosis is part of the disease complex known Nasal or pharyngeal lesions can be biopsied using a mare as equine phycomycosis, which also includes Pythium endometrial biopsy rod guided endoscopically to the lesion. insidiosum (formerly Hyphomyces destruens) and Basidiobolus Granulation tissue, infiltrated by numerous eosinophils, haptosporus (Miller and Campbell 1982, 1984; Miller 1983a). neutrophils, macrophages, plasma cells, lymphocytes, giant Lesions of conidiobolomycosis are found in the upper portion cells and hyphae surrounding necrotic masses, is seen during of the respiratory tract, whereas lesions of pythiosis and histological examination of lesions (French et al. 1985; Zamos basidiobolomycosis are primarily found on the skin and et al. 1996; Steiger and Williams 2000; Taintor et al. 2004). subcutis of the trunk and limbs (Miller 1983b). Special stains, such as Gomori’s silver stain may be required to Infection by Conidiobolus, which is found in the soil and identify hyphae. Diagnosis of conidiobolomycosis is based on decaying organic material (Miller 1983b), can occur while the clinical signs, gross and histological appearance of the lesion, horse is grazing. Because damp and decaying bedding and identification of the causative organism. provides an ideal habitat for the growth of the fungus, Conidiobolomycosis can also be identified from clinical infection may occur when the horse sleeps on decaying tissue samples by PCR (Imhof et al. 2003) or by an damp bedding (Humber et al. 1989). Whether or not the immunodiffusion test, using serum from the affected horse respiratory epithelium must be damaged for entry of the (Kaufman et al. 1990; Steiger and Williams 2000). organism is not known, but bacterial or viral infection of the Treatment of horses affected by conidiobolomycosis respiratory epithelium may perhaps cause mucosal damage includes excision of lesions and parenteral and topical and provide entry for the fungal conidia (Hanselka 1977). administration of antifungal drugs. Excision of nasal and Infection does not seem to be associated with nasopharyngeal lesions of conidiobolomycosis is difficult because lesions at these locations are usually surgically immunodeficiency (Chandler 1997). inaccessible. Although horses with pythiosis have been The most common clinical sign of the disease is a successfully treated with vaccine made from P. insidiosum sanguinolent, mucopurulent nasal discharge (French et al. (Miller 1981; Miller et al. 1983; Mendoza and Newton 2005), 1985; Zamos et al. 1996; Taintor et al. 2004; Robinson et al. immunotherapy for treatment of horses with 2007). One affected horse had a chronic cough caused by conidiobolomycosis does not seem to be effective infection of the proximal half of the trachea (Steiger and (Taintor et al. 2004; R. Glass, L. Mendoza, personal Williams 2000). Granulomas can sometimes be seen at the communications). external nares, but endoscopic examination of the upper Data concerning the in vitro activity of antifungal agents portion of the respiratory tract is usually necessary to observe against Conidiobolus is very limited. Iodides are the most the lesions. C. coronatus causes small growths, 1–3 cm in commonly recommended drugs for treatment of diameter, within the nasal cavity and slightly larger growths, conidiobolomycosis in man (Restrepo 1994) and horses (Scott 1–5 cm diameter, on the external nares. Unlike lesions caused and Miller 2003). Although the most commonly recommended iodide for treatment of horses affected with *Author to whom correspondence should be addressed. conidiobolomycosis is potassium iodide, organic iodide 406 EQUINE VETERINARY EDUCATION / AE / september 2007

(ethylenediamine dihydroiodide, EDDI) may offer advantages Humber, R.A., Brown, C.C. and Kornegay, R.W. (1989) Equine over inorganic iodide (Morris 1983). This iodide is less zygomycosis caused by Conidiobolus lamprauges. J. clin. expensive and maintains high tissue concentrations for a Microbiol. 27, 573-576. longer time than sodium iodide. Many different protocols of Imhof, A., Schaer, C., Schoedon, G., Schaer, D.J., Walter, R.B., administration have been reported (Zamos et al. 1996; Steiger Schaffner, A. and Schneemann, M. (2003) Rapid detection of pathogenic fungi from clinical specimens using LightCycler and Williams 2000; Taintor et al. 2004). EDDI is administered real-time fluorescence PCR. Eur. J. Clin. Microbiol. Infect. Dis. at 20–40 mg/kg bwt, per os, once daily, indefinitely. Sodium 22, 558-560. iodide (67 mg/kg bwt, i.v. once daily) is often administered for Kaufman, L., Mendoza, L. and Standard, P.G. (1990) Immunodiffusion 2–5 days before therapy with orally administered iodide is test for serodiagnosing subcutaneous zygomycosis. J. clin. begun. The mechanism of action of iodide against fungal Microbiol. 28, 1887-1890. organisms is not known. In the authors’ experience, cessation Korenek, N.L., Legendre, A.M. and Andrews, F.M. (1994) Treatment of of therapy with iodides before complete resolution of mycotic rhinitis with itraconazole in three horses. J. vet. Int. Med. conidiobolomycosis seems to cause the disease to be 8, 224-227. refractory to further treatment with iodide. Mendoza, L. and Newton, J.C. (2005) Immunology and Whether or not the fungus has receptors for immunotherapy of the infections caused by Phythium insidiosum. amphotericin B is not known, but several horses have Med. Mycol. 43, 477-486. reportedly responded to intralesional administration of this Miller, R.I. (1981) Treatment of equine phycomycosis by drug (French and Haynes 1985; Zamos et al. 1996). One immunotherapy and surgery. Aust. vet. J. 57, 377-382. horse was also treated with sodium and potassium iodide, Miller, R.I. (1983a) Equine phycomycosis. Comp. cont. Educ. pract. thus obscuring the effect of amphotericin B (Zamos et al. Vet. 5, 472-478. 1996). Literature concerning treatment in man infected with Miller, R.I. (1983b) Nomenclature of fungal diseases, Letter to the Conidiobolus spp. was reviewed, and the outcome of Editor. Vet. Pathol. 20, 251-253. patients treated with amphotericin B was judged to be poor Miller, R.I. and Campbell, R.S. (1982) Clinical observations on equine (Guarro et al. 1999). phycomycosis. Aust. vet. J. 58, 221-226. In an in vitro study, Conidiobolus spp. were resistant to Miller, R.I. and Campbell (1984) The comparative pathology of equine amphotericin B, ketoconazole, miconizole, itraconizole, cutaneous phycomycosis. Vet. Pathol. 21, 325-332. fluconazole, and flucytosine (Guarro et al. 1999). Two Miller, R.I., Wold, D., Lindsay, W.A., Beadle, R.E., McClure, J.J., pregnant mares affected with conidiobolomycosis, however, McClure, J.R. and McCoy, D.J. (1983) Complications associated were treated successfully with orally administered fluconazole with immunotherapy of equine phycomycosis. J. Am. vet. med. (5 mg/kg bwt, q. 12 h, per os, for 6 weeks) (Taintor et al. Ass. 182, 1227-1229. 2004). Although fluconazole is reported to have teratogenic Morris, P. (1983) Sporotrichosis. In: Current Therapy in Equine and embryo toxic effects when used in high doses, foals born Medicine, Ed: N.E. Robinson, W.B. Saunders Co, Philadelphia. to these mares appeared normal. pp 555-556. Treatment of affected horses with the similar antifungal Prades, M., Brown, M.P. and Gronwall, R. (1989) Body fluid and drug, ketaconazole is likely to be unsuccessful, because this endometrial concentrations of ketaconazole in mares after drug is absorbed poorly from the horse’s gastrointestinal tract intravenous injection or repeated lavage. Equine vet. J. 21, 211-214. (Prades et al. 1989). A horse with nasal lesions caused by C. coronatus had no resolution of lesions after 4.5 months of Restrepo, A. (1994) Treatment of tropical mycoses. J. Am. Acad. Dermatol. 31, S91-102. treatment with itraconazole (Korenek et al. 1994). Human patients have been treated for conidiobolomycosis with Richardson, M.D. and Shankland, G.S. (1999) Rhizopus, Rhizomucor, Absidia, and other agents of systemic and subcutaneous trimethoprim-sulphamethoxazole (Restrepo 1994), but we are zygomycoses. In: Manual of Clinical Microbiology, Eds: P.R. unaware of any reports of this drug being used to treat horses Murray, E.J. Baron and M.A. Pfaller, ASM Press, Washington DC. with conidiobolomycosis. pp 1152-1163. Robinson, C.S., Robertson, J.T., Reed, S.M. and Pinchbeck, L.R. (2007) References Treatment of a mare for Conidiobolus coronatus infection. Equine vet. Educ. 19, 396-403. Chandler, F.W. and Watts, J.C. (1997) Zygomycosis. In: Pathology of Scott, D.W. and Miller, W.H. (2003) Equine Dermatology, W.B. Infectious Diseases, Ed: H.D. Connor, Appleton & Lange, Stamford, Saunders, St. Louis. pp 306-313. CT. pp 1113-1119. Steiger, R.R. and Williams, M.A. (2000) Granulomatous tracheitis French, D.D., Haynes, P.F. and Miller, R.I. (1985) Surgical and medical management of rhinophycomycosis (conidiobolomycosis) in a caused by Conidiobolus coronatus in a horse. J. vet. int. Med. horse. J. Am. vet. med. Ass. 186, 1105-1107. 14, 311-314. Guarro, J., Aguilar, C. and Pujol, I. (1999) In vitro antifungal Taintor, J., Crowe, C., Hancock, S., Schumacher, J. and Livesey, L. susceptibilities of Basidiobolus and Conidiobolus spp. strains. (2004) Treatment of conidiobolomycosis with fluconazole in two J. Antimicrob. Chemotherapy 44, 557-560. pregnant mares. J. vet. int. Med. 18, 363-364. Hanselka, D.V. (1977) Equine nasal phycomycosis. Vet. Med. Small Zamos, D.T., Schumacher, J. and Loy, J.K. (1996) Nasopharyngeal Anim. Clin. 72, 251-253. conidiobolomycosis in a horse. J. Am. vet. med. Ass. 208, 100-101.