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

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.

Macrocyclic lactone anthelmintic-induced leukocyte binding to Dirofilaria immitis microfilariae: Influence of the drug resistance status of the parasite

“…This in turn will be influenced by the route of administration; different preparations, one topical, the other a long-lasting injectable were used by Blagburn et al (2016) and Bourguinat et al (2015) respectively. McTier et al (2017) reported that JYD-34 was resistant to oral administration of moxidectin. In small ruminants the use of moxidectin to control ivermectin-resistant nematodes resulted in the rapid development of moxidectin resistance (Kaplan et al, 2007) which suggests that the use of moxidectin-based preventatives will provide only a short-term solution, if any.…”

“…There are conflicting accounts of the efficacy of moxidectin as a preventative against these resistant worms, which may reflect the dose of drug the parasite is exposed to following different routes of administration. One resistant isolate, JYD-34, was reported to remain susceptible to topically applied moxidectin (Blagburn et al, 2016), in that no adult worms were present at necropsy following experimental infection with infective L3 larvae and treatment, but to be resistant to either one or three oral doses (3 μg/kg) of the drug (McTier et al, 2017). Another isolate, Jd2009-2, was fully resistant to a long-acting injectable formulation of the drug given 6 months after infection (Bourguinat et al, 2015).…”

Preventive efficacy of four or six monthly oral doses of 24 µg/kg moxidectin compared to six monthly doses of Heartgard® Plus or Interceptor® Plus against macrocyclic lactone-resistant heartworm (Dirofilaria immitis) strains in dogs

“…Both isolates were validated as infective strains through the diagnosis of circulating microfilariae, positive heartworm antigen test results, and adult worm recovery in recipient animals following inoculation of L 3 that had been derived directly from microfilariae obtained from the original field cases. Both ZoeLA and JYD-34 D. immitis strains have been demonstrated to be resistant to MLs [4,10].…”

Efficacy of a new oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced ascarid infections in dogs

“…To provide reliable efficacy against this stage, pyrantel is needed in the combination. Moxidectin at a single oral dose of 3 µg/kg was shown to be effective against susceptible Dirofilaria immitis isolates [29], and more recent studies have confirmed its efficacy in the prevention of canine heartworm (L 4 stages) and lungworm (L 5 stage) disease at 24 µg/ kg in combination with pyrantel and sarolaner [30,31]. The dosage of moxidectin in Simparica Trio ™ has been selected in dose titration studies against these vascular nematodes [31,32].…”