Efficacy of oral moxidectin against susceptible and resistant isolates of Dirofilaria immitis in dogs. 2017

Tom L McTier, and Robert H Six, and Aleah Pullins, and Sara Chapin, and John W McCall, and Douglas Rugg, and Steven J Maeder, and Debra J Woods
Zoetis, Veterinary Medicine Research and Development, Kalamazoo, MI, USA. tom.mctier@zoetis.com.

BACKGROUND Monthly topical and sustained-release injectable formulations of moxidectin are currently marketed; however, an oral formulation, while approved at a dose of 3 μg/kg, is not currently marketed in the United States. Although resistance of heartworms to all macrocyclic lactone (ML) heartworm preventives (ivermectin, milbemycin, selamectin and moxidectin) has been demonstrated, to date no data have been reported on the effectiveness of oral moxidectin against recent isolates of Dirofilaria immitis. METHODS A total of nine studies were conducted to determine the efficacy of moxidectin against a range of older and recently sourced heartworm isolates. Dogs (groups of three to eight) were inoculated with 50 D. immitis infective larvae (L3) from nine different isolates (MP3, Michigan, JYD-34, ZoeMO-2012, ZoeKy-2013, ZoeLA-2013, GCFL-2014, AMAL-2014 and ZoeAL-2015) and treated 28-30 days later with single oral doses of 3 μg/kg of moxidectin. Additionally, one group of dogs that was inoculated with JYD-34 was treated monthly for 3 consecutive months beginning 30 days post inoculation. Dogs were held for approximately 4 months after the initial (or only) treatment and then necropsied for recovery of adult heartworms. RESULTS A single dose of 3 μg/kg of moxidectin was 100% effective in preventing the development of five of nine heartworm isolates (MP3, Michigan, ZoeKy, GCFL and ZoeAL isolates), confirming their susceptibility to oral moxidectin at this dose. MP3 and Michigan are isolates sourced from the field more than 9 years ago, while ZoeKy, ZoeAL and GCFL were isolated from the field within the past 2 to 3 years. Against JYD-34, ZoeMO, ZoeLA and AMAL isolates, a single dose of 3 μg/kg of moxidectin was not completely effective, with efficacies of 19%, 82%, 54% and 62%, respectively, demonstrating resistance of these heartworm isolates to oral moxidectin at this dosage. Three consecutive monthly doses of 3 μg/kg of moxidectin were also incompletely effective against the JYD-34 isolate, with an efficacy of 44%. JYD-34 was originally isolated in 2010, while ZoeMO, ZoeLA and AMAL were isolated within the past 2 to 3 years. CONCLUSIONS A single oral dose (3 μg/mg) of moxidectin was 100% effective in preventing the development of ML-susceptible heartworm isolates while being incompletely effective against ML-resistant isolates.

UI MeSH Term Description Entries
D004183 Dirofilaria immitis A filarial parasite primarily of dogs but occurring also in foxes, wolves, and humans. The parasite is transmitted by mosquitoes. Dog Heartworm,Dirofilaria immitides,Dog Heartworms,Heartworm, Dog,Heartworms, Dog,immitis, Dirofilaria
D004184 Dirofilariasis Infection with nematodes of the genus DIROFILARIA, usually in animals, especially dogs, but occasionally in man. Heartworm Disease,Dirofilariases,Disease, Heartworm
D004283 Dog Diseases Diseases of the domestic dog (Canis familiaris). This term does not include diseases of wild dogs, WOLVES; FOXES; and other Canidae for which the heading CARNIVORA is used. Canine Diseases,Canine Disease,Disease, Canine,Disease, Dog,Diseases, Canine,Diseases, Dog,Dog Disease
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004341 Drug Evaluation Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals. Evaluation Studies, Drug,Drug Evaluation Studies,Drug Evaluation Study,Drug Evaluations,Evaluation Study, Drug,Evaluation, Drug,Evaluations, Drug,Studies, Drug Evaluation,Study, Drug Evaluation
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D005369 Filaricides Pharmacological agents destructive to nematodes in the superfamily Filarioidea.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D018942 Macrolides A group of often glycosylated macrocyclic compounds formed by chain extension of multiple PROPIONATES cyclized into a large (typically 12, 14, or 16)-membered lactone. Macrolides belong to the POLYKETIDES class of natural products, and many members exhibit ANTIBIOTIC properties. Macrolide

Related Publications

Tom L McTier, and Robert H Six, and Aleah Pullins, and Sara Chapin, and John W McCall, and Douglas Rugg, and Steven J Maeder, and Debra J Woods
November 2017, Parasites & vectors,
Tom L McTier, and Robert H Six, and Aleah Pullins, and Sara Chapin, and John W McCall, and Douglas Rugg, and Steven J Maeder, and Debra J Woods
December 1978, Journal of helminthology,
Tom L McTier, and Robert H Six, and Aleah Pullins, and Sara Chapin, and John W McCall, and Douglas Rugg, and Steven J Maeder, and Debra J Woods
June 1977, Modern veterinary practice,
Tom L McTier, and Robert H Six, and Aleah Pullins, and Sara Chapin, and John W McCall, and Douglas Rugg, and Steven J Maeder, and Debra J Woods
September 2001, Parassitologia,
Tom L McTier, and Robert H Six, and Aleah Pullins, and Sara Chapin, and John W McCall, and Douglas Rugg, and Steven J Maeder, and Debra J Woods
April 2024, Parasites & vectors,
Tom L McTier, and Robert H Six, and Aleah Pullins, and Sara Chapin, and John W McCall, and Douglas Rugg, and Steven J Maeder, and Debra J Woods
February 2023, Parasites & vectors,
Tom L McTier, and Robert H Six, and Aleah Pullins, and Sara Chapin, and John W McCall, and Douglas Rugg, and Steven J Maeder, and Debra J Woods
January 1995, The Veterinary record,
Tom L McTier, and Robert H Six, and Aleah Pullins, and Sara Chapin, and John W McCall, and Douglas Rugg, and Steven J Maeder, and Debra J Woods
May 1984, American journal of veterinary research,
Tom L McTier, and Robert H Six, and Aleah Pullins, and Sara Chapin, and John W McCall, and Douglas Rugg, and Steven J Maeder, and Debra J Woods
October 1985, Nihon juigaku zasshi. The Japanese journal of veterinary science,
Tom L McTier, and Robert H Six, and Aleah Pullins, and Sara Chapin, and John W McCall, and Douglas Rugg, and Steven J Maeder, and Debra J Woods
October 2020, Parasites & vectors,
Copied contents to your clipboard!