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

Abstract

Background Administration of four to six consecutive monthly doses of 24 µg/kg moxidectin alone shows high effectiveness in preventing the maturation of macrocyclic lactone (ML)-resistant heartworm strains, Dirofilaria immitis JYD-34 and ZoeLA. This laboratory study evaluated the efficacy of six consecutive monthly oral doses of Simparica Trio® (moxidectin/sarolaner/pyrantel) compared to six monthly doses of either Heartgard® Plus (ivermectin/pyrantel) or Interceptor® Plus (milbemycin oxime/praziquantel) against ML-resistant D. immitis ZoeLA strain. Methods Beagle dogs were inoculated with 50 third-stage (L3) D. immitis larvae (ZoeLA) 30 days prior to the first treatment. Dogs were randomized to treatment (six animals in each group) with six monthly oral doses of placebo, Simparica Trio, Heartgard Plus, or Interceptor Plus at their respective label doses. Microfilaria (MF) and antigen tests were conducted periodically, and efficacy was evaluated by necropsy for adult heartworms approximately 9 months after L3 inoculation. Results Adult heartworms were recovered from all six placebo dogs, with a geometric mean of 35.5 worms (range, 23–48). Five of the six dogs treated with Simparica Trio were infected with a geometric mean of 1.0 worms (range, 0–3), and all remained MF-negative. All Heartgard Plus-treated dogs (six) were infected with a geometric mean of 32.5 worms (range, 22–38); five of these dogs were MF-positive at day 236. All Interceptor Plus-treated dogs (six) were infected with a geometric mean of 22.8 worms (range, 10–34); five of these dogs were MF-positive at day 236. The efficacy of six consecutive doses with Simparica Trio, Heartgard Plus, and Interceptor Plus against ZoeLA was 97.2, 8.5, and 35.9%, respectively. Adult worm counts for the Simparica Trio-treated group were significantly lower (P < 0.0001) than placebo control, Heartgard Plus, and Interceptor Plus-treated groups. Adult worm counts for Heartgard Plus and Interceptor Plus were not significantly different from placebo (P > 0.05). Conclusions Simparica Trio prevented microfilaremia in all dogs and was highly effective (97.2%) and significantly better than either Heartgard Plus (8.5%) or Interceptor Plus (35.9%) in preventing the development of the ZoeLA ML-resistant heartworm strain when administered for six consecutive months in this comparative laboratory efficacy study. Graphical Abstract

A review of moxidectin vs. other macrocyclic lactones for prevention of heartworm disease in dogs with an appraisal of two commercial formulations

“…Over all studies, preventive efficacy of moxidectin against resistant strains was between 95.9 and 99.3%, while the efficacy of ivermectin and milbemycin was between 8.5 and 63.9%. Dogs receiving oral moxidectin had significantly lower geometric mean worm counts than dogs receiving Heartgard ® Plus, Interceptor ® Plus or no heartworm prevention (80,81). It should be noted that the oral moxidectin dose in all studies was ≥24 μg/kg, which was considered the optimal dose in a dose-finding study on resistant D. immitis strains (82).…”

“…Five of the seven studies also reported the number of dogs testing positive for heartworm antigen and microfilariae at different time points (79)(80)(81). At the final evaluation time point, one dog receiving the extended-release moxidectin injectable PH12 tested positive for heartworm antigen in one of two studies, whereas all (6 of 6) or most (5 of 6) dogs receiving ivermectin, milbemycin oxime, or no heartworm preventive tested positive for heartworm antigen and microfilariae at the final evaluation time points in the two studies.…”

“…In most studies, Heartgard® Plus (ivermectin/pyrantel) and Interceptor® Plus (milbemycin oxime/praziquantel) served as positive controls. These were compared with either the extended-release moxidectin injectable PH12 ( 79 ), the oral moxidectin combination product Simparica Trio® (moxidectin, sarolaner, and pyrantel) ( 80 ), or moxidectin dosed at 24 μg/kg (the minimum dose in Simparica Trio®) ( 81 ). Two studies specifically investigated the efficacy of Advantage® Multi (topical moxidectin) compared to ivermectin, milbemycin oxime, and selamectin in various combination formulations ( 63 , 64 ).…”

Moxidectin: heartworm disease prevention in dogs in the face of emerging macrocyclic lactone resistance

“…In a recent laboratory study, Simparica Trio, containing 24 µg/kg moxidectin, 1.2 mg/kg sarolaner and 5 mg/ kg pyrantel, and Heartgard Plus and Interceptor Plus (n = 6) were administered in six consecutive monthly oral doses at the labeled dose rates after receiving an inoculation of 50 ZoeLA strain D. immitis L3 on day −30 [50]. Dogs were necropsied approximately 9 months post-inoculation and evaluated for the presence of circulating MF and heartworm antigen on days 180, 210, and 236.…”

“…No dogs treated with Simparica Trio tested positive for the presence of circulating MF at any time during this study, with only two of the six dogs testing positive for heartworm antigen. All six dogs treated with Heartgard Plus and Interceptor Plus had adult worms present at necropsy, with a geometric mean of 32.5 and 22.8 adults recovered, and preventive efficacy of 8.5% and 35.9%, respectively (Table 3) [50]. On day 236, all Heartgard Plus-and Interceptor Plustreated dogs were positive for the presence of heartworm antigen, and five of the total six dogs for each group were positive for circulating MF, indicating the possibility of infected dogs being able to transmit ML-resistant heartworm strains despite proper use of these preventive products.…”