Comparative preventive efficacy of ProHeart® 12, Heartgard® Plus and Interceptor® Plus against a macrocyclic lactone-resistant strain (JYD-34) of heartworm (Dirofilaria immitis) in dogs

Abstract

Background The current studies compared ProHeart® 12, Heartgard® Plus and Interceptor® Plus for preventive efficacy against JYD-34, a macrocyclic lactone (ML)-resistant strain of Dirofilaria immitis in dogs. Methods In two studies, each using 24 adult beagles, dogs were allocated to four treatment groups (n = 6): placebo-treated control; ProHeart 12 as per label (0.5 mg/kg moxidectin); Heartgard Plus (HGP) as per label (minimum 6 µg/kg ivermectin); and Interceptor Plus (INP) as per label (minimum 0.5 mg/kg milbemycin oxime). In both studies, ProHeart 12 was administered as a single subcutaneous dose on day 0, and HGP and INP were administered orally on days 0, 30, 60, 90, 120 and 150. In Studies 1 and 2, dogs were inoculated with 50 third-stage heartworm larvae (JYD-34 strain) on days −30 and 165, respectively. In Study 2, treatment for both HGP and INP was continued on days 180, 210, 240, 270, 300 and 330. Adult heartworm recoveries were performed on day 185 in Study 1 and on day 360 in Study 2. Results In Studies 1 and 2, all placebo-treated dogs developed adult heartworm infections (geometric mean, 29.9 and 34.9 worms/dog, respectively). A single dose of ProHeart 12 was 100% effective in preventing the development of adult JYD-34 heartworms when treatment was initiated 30 days after heartworm inoculation, while six consecutive monthly doses of HGP and INP were only 10.5% and 14.6% effective, respectively. The mean worm count for the ProHeart 12-treated group was significantly lower (P < 0.0001) than that for the placebo control, HGP- and INP-treated groups. In Study 2, the dogs treated with ProHeart 12 had an efficacy of 98.3%. All dogs treated with HGP and INP for 12 consecutive months had adult heartworms with efficacies of 37.7% and 34.9%, respectively. The mean worm count for the ProHeart 12-treated dogs was significantly lower (P < 0.0001) than those for the control group, HGP- and INP-treated groups. Conclusions A single administration of ProHeart 12 was 98–100% effective in preventing the development of the ML-resistant JYD-34 heartworm strain and was significantly better than multiple consecutive monthly doses of either Heartgard Plus or Interceptor Plus in both studies. Graphic Abstract

Preventive efficacy of six monthly oral doses of Simparica Trio®, Heartgard® Plus, and Interceptor® Plus against a macrocyclic lactone-resistant strain (ZoeLA) of heartworm (Dirofilaria immitis) in dogs

“…The preventive efficacies provided by Simparica Trio against the ML-resistant D. immitis strain evaluated in the present study support the outcomes from previous studies [ 4 , 10 ]. Comparisons of data from the present and previous studies are presented in Table 4 .…”

“… a Moxidectin administered at exact 24 µg/kg dosage. Simparica Trio (24 µg/kg moxidectin + 1.2 mg/kg sarolaner + 5 mg/kg pyrantel), Heartgard Plus (6 µg/kg ivermectin + 5 mg/kg pyrantel), and Interceptor Plus (500 µg/kg milbemycin oxime + 5 mg/kg praziquantel) administered according to commercial label directions, which resulted in administration of 24 to 48 µg/kg moxidectin, 6.2–15.5 µg/kg of ivermectin and 0.5 to 1.2 mg/kg milbemycin oxime b Treatment administration days: one monthly treatment: day 0 [ 4 ]; three monthly treatments: days 0, 28, and 56 [ 4 ]; four monthly treatments: days 0, 30, and 60 [ 9 ], six monthly treatments: days 0, 30, 60, 90, 120, and 150 [ 9 , 10 , studies from this paper], and for one study, six monthly treatments were provided prior to and after inoculation on day 165 (treatments on days 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330) [ 10 ] c Each dog inoculated with 50 D. immitis L3 on day -30, with adult heartworm recovery at necropsy 133–273 days after inoculation d Data reference: McTier et al [ 4 ] e Data reference: Kryda et al [ 9 ] f Data reference: McTier et al [ 10 ] g Data reference: this paper …”

“…The isolate was validated as an infective strain through positive heartworm antigen test results, the diagnosis of circulating MF, and adult worm recovery in recipient animals following inoculation of L3 that were derived directly from MF obtained from the original field case. This D. immitis strain has been demonstrated to be resistant to MLs [ 4 , 8 , 10 ].…”

“…The pharmacokinetic properties of moxidectin along with its high degree of lipophilicity, which results in superior bioavailability, make it an attractive compound, either as a stand-alone or in a combination endectocide, for use as a heartworm preventive in the face of emerging resistance [ 11 ]. Against ML-resistant D. immitis , increasing the oral monthly moxidectin dosage from 3 µg/kg (the original approved oral dose for heartworm prevention) to 24 µg/kg of moxidectin and increasing the consecutive number of monthly administered doses has been shown to improve its efficacy [ 4 , 10 ]. Moxidectin at 0.5 mg/kg is also effective in an extended-release injectable form against ML-resistant strains [ 10 ].…”

“…Against ML-resistant D. immitis , increasing the oral monthly moxidectin dosage from 3 µg/kg (the original approved oral dose for heartworm prevention) to 24 µg/kg of moxidectin and increasing the consecutive number of monthly administered doses has been shown to improve its efficacy [ 4 , 10 ]. Moxidectin at 0.5 mg/kg is also effective in an extended-release injectable form against ML-resistant strains [ 10 ]. A new oral chewable tablet Simparica Trio ® utilizes this increased moxidectin dosage (ranging from 24 to 48 µg/kg) in combination with the ectoparasiticide sarolaner and the nematodicide pyrantel.…”