Abstract
BackgroundMonthly 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.MethodsA 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.ResultsA 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.ConclusionsA 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.
Highlights
Topical and sustained-release injectable formulations of moxidectin are currently marketed; an oral formulation, while approved at a dose of 3 μg/kg, is not currently marketed in the United States
All of the original work with oral moxidectin was conducted with a single heartworm isolate (UGA) that had been maintained under laboratory conditions at TRS Labs (Athens, Georgia, USA) for a number of years prior to use in the moxidectin program (John McCall, personal oral communication, October 2016)
The objective of the current study was to assess the efficacy of 3 μg/kg moxidectin, administered orally, in preventing the development of D. immitis isolates collected from various sources over the previous10 years
Summary
Topical and sustained-release injectable formulations of moxidectin are currently marketed; an oral formulation, while approved at a dose of 3 μg/kg, is not currently marketed in the United States. All of the original work with oral moxidectin was conducted with a single heartworm isolate (UGA) that had been maintained under laboratory conditions at TRS Labs (Athens, Georgia, USA) for a number of years prior to use in the moxidectin program (John McCall, personal oral communication, October 2016). This same isolate had been used previously to assess the efficacy of oral ivermectin for heartworm prevention. The objective of the current study was to assess the efficacy of 3 μg/kg moxidectin, administered orally, in preventing the development of D. immitis isolates collected from various sources over the previous years
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