Controlled Clinical Trial Using Terbinafine Nebulization to Treat Wild Lake Erie Watersnakes (Nerodia sipedon insularum) with Natural Ophidiomycosis
Ophidiomycosis (snake fungal disease) is an emerging disease caused by the fungus Ophidiomyces ophiodiicola.1 To mitigate the disease’s impact on individual snakes, a controlled clinical trial was conducted using terbinafine nebulization3 to treat snakes with ophidiomycosis. Twenty-five wild-caught Lake Erie watersnakes (Nerodia sipedon insularum) with apparent ophidiomycosis (skin lesions present, qPCR2 positive for O. ophiodiicola) were divided into control and treatment groups using matched pairs. Treatment snakes were nebulized with a terbinafine solution (Terbinafine hydrochloride USP 2 mg/ml solution made from grinding up 250 mg tablets, Sigma-Aldrich, St. Louis, MO, and dissolving in 0.9% saline) for 30 min daily for 30 days; control snakes received 0.9% saline. Lesions were tracked weekly and qPCR was repeated after 30 days of treatment. Persistently qPCR-positive snakes received multiple nebulization courses. Terbinafine nebulization reduced fungal quantity by 90.2%, 90.3%, and 98.5% after two, three, and four courses, while fungal quantities in saline-treated snakes were 31.4, 14.7, 8.1, and 10.2 times higher after one, two, three, and four courses. One treatment snake was qPCR negative after two courses, then recrudesced; two others were qPCR negative after three and four courses, without recrudescence. The mortality rates were 75% and 69.2% in the control and treatment groups, respectively. Of the three control and four treatment snakes alive after the fourth course, two showed complete resolution of disease (15.4% of treatment snakes, 0% of control snakes), and five showed persistent disease (15.4% of treatment snakes, 25% of control snakes). These results indicate that, while terbinafine nebulization is a promising treatment for ophidiomycosis, snakes may require multiple nebulization courses and disease may not always resolve completely despite treatment.
The authors thank the staff at the Stone Lab for their assistance capturing snakes in the field and the students in the Wildlife Epidemiology Lab at the University of Illinois, College of Veterinary Medicine for their help caring for snakes during the trial.
1. Allender MC, Baker SJ, Wylie D, Loper D, Dreslik MJ, Phillips CA, Maddox C, Driskell EA. Development of snake fungal disease after experimental challenge with Ophidiomyces ophiodiicola in cottonmouths (Agkistrodon piscivorous). PLoS One. 2015;10(10):e0140193.
2. Allender MC, Bunick D, Dzhaman E, Burrus L, Maddox C. Development and use of a real-time polymerase chain reaction assay for the detection of Ophidiomyces ophiodiicola in snakes. J Vet Diagn Invest. 2015;27(2):217–220.
3. Kane LP, Allender MC, Archer G, Leister K, Rzadkowska M, Boers K, Souza M, Cox S. Pharmacokinetics of nebulized and subcutaneously implanted terbinafine in cottonmouths (Agkistrodon piscivorus). J Vet Pharmacol Ther. 2017;40:575-579.