Assessment of parasitological findings in heartworm-infected beagles treated with Advantage Multi® for dogs (10% imidacloprid + 2.5% moxidectin) and doxycycline

Abstract

BackgroundAnecdotal reports support the position that the adulticidal heartworm treatment utilizing doxycycline and Advantage Multi®/Advocate® for Dogs (10% imidacloprid + 2.5% moxidectin) has successfully converted antigen-positive dogs to antigen-negative. To date, no controlled experimental studies have demonstrated the adulticidal efficacy of this treatment regimen. The aim of this study was to evaluate the parasitological and clinical efficacy of Advantage Multi® for Dogs (IMD + MOX) and doxycycline in heartworm-infected beagles.MethodsThis study utilized 16 dogs, 8 dogs in each of non-treated control and treated groups. A total of 16 adult Dirofilaria immitis (Missouri strain) were surgically transplanted into the jugular vein of each study dog. The treatment regimen of monthly IMD + MOX topically (per labeled dosage and administration) for 10 months and 10 mg/kg doxycycline BID orally for 30 days was initiated 30 days post-surgical transplant. Echocardiograms, radiographs, complete blood counts, clinical chemistry profiles, heartworm antigenemia and microfilaremia were evaluated every 4 weeks. Serum samples were assayed for heartworm antigen using the DiroCHEK® heartworm antigen test. The DiroCHEK® was performed according to the manufacturer’s recommendations and read using a spectrophotometer at 490 nm.ResultsAll dogs tested positive for the presence of heartworm antigen post-surgical transplant and prior to treatment. Heartworm antigen levels began declining in treated dogs 3 months post-treatment. Non-treated control dogs remained antigen-positive. No microfilariae were detected in treated dogs after 21 days post-treatment. At necropsy, adult heartworms were recovered from all non-treated control dogs with a range of 10–12 adult worms/dog for an average recovery of 10.6 adult heartworms/dog. In the IMD + MOX- and doxycycline-treated dogs, the range of adult heartworms recovered was 0–2 adult worms/dog, with five dogs having no adult heartworms present. The average adult heartworm recovery was 0.6/dog in the treated group. This treatment regimen demonstrated a 95.9% efficacy in eliminating adult heartworms (P < 0.0001).ConclusionsThis study demonstrated that this treatment regimen successfully eliminated D. immitis microfilariae by 21 days post-treatment, reduced heartworm antigen concentration over time, and had a 95.9% efficacy in the elimination of mature adult heartworms. Based on this study, we conclude that this treatment regimen is a relatively quick, reliable and safe option to treat canine heartworm infection as compared to other treatment regimens involving macrocyclic lactones, when the approved drug melarsomine dihydrochloride is unavailable, contraindicated or declined by an owner unable to afford the more costly treatment or concerned about the potential side effects.

Evaluation of heat-treating heartworm-positive canine serum samples during treatment with Advantage Multi® for Dogs and doxycycline

“…Optical density values in the serum samples collected from the IMD + MOX and doxycycline treated group generally began to decline after study day 86, 3 months post-treatment, both pre- and post-heat-treatment (Fig. 3 ) [ 9 ]. Non-treated control dogs remained positive for the presence of heartworm antigen throughout the study, while 5 of the 8 IMD + MOX and doxycycline treated group dogs tested negative for the presence of heartworm antigen and confirmed at necropsy at the termination of the study on Study Days 279–282 (10 months post-treatment).…”

“…Comparing necropsy adult heartworm recovery to end-of-study heartworm antigen results, all heartworm antigen test results correlated with the necropsy adult heartworm recovery for each study dog (Additional file 1 : Figures S1-S4). All 5 IMD + MOX and doxycycline-treated dogs testing negative for the presence of adult heartworms did not have any adults recovered at necropsy, while the remaining 3 IMD + MOX and doxycycline treated dogs that remained positive for the presence of heartworm antigen had 1–2 adult heartworms recovered at necropsy [ 9 ] (Table 1 , Fig. 4 ).…”

“…The experimental groups consisted of non-treated controls and dogs treated with doxycycline and Advantage Multi® for Dogs (10% imidacloprid + 2.5% moxidectin) with 8 dogs in each group. Each study dog had a total of 16 adult heartworms surgically transplanted into the jugular vein, consisting of 11 females and 5 males [ 9 , 10 ]. The treated dogs received 30 days of 10 mg/kg doxycycline BID and 10 monthly topical administrations of imidacloprid + moxidectin (IMD + MOX) every 4 weeks [ 9 ].…”

“…Recently, the efficacy of Advantage Multi® for Dogs (10% Imidacloprid + 2.5% Moxidectin) in combination with doxycycline has been evaluated using the aforementioned study animals [ 9 ]. The use of monthly topical administration of Advantage Multi® for Dogs for ten months along with 30 days of 10 mg/kg doxycycline BID was utilized in experimentally infected dogs.…”

Severe heartworm disease in two dogs cured by an alternative therapy

“…A different doxycycline-ivermectin protocol has shown an effectiveness of 72.7% after 300 days (Grandi et al, 2010). Doxycycline used in combination with imidacloprid and moxidectin has shown 95.9% efficacy in eliminating adult heartworm in experimentally infected dogs (Savadelis et al, 2017). However, there are no studies that compare different alternative protocols in either naturally or experimentally infected dogs.…”