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

Parasit Vectors. 2017 May 19;10(1):245. doi: 10.1186/s13071-017-2190-9.


Background: Anecdotal 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.

Methods: This 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.

Results: All 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).

Conclusions: This 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.

Keywords: Advantage Multi®; Advocate®; Canine heartworm disease; Dirofilaria immitis; Doxycycline; Heartworm treatment; Macrocyclic lactone treatment; Moxidectin.

MeSH terms

  • Administration, Topical
  • Animals
  • Antigens, Helminth / blood
  • Dirofilaria immitis / drug effects*
  • Dirofilaria immitis / isolation & purification
  • Dirofilariasis / drug therapy*
  • Dirofilariasis / parasitology
  • Dog Diseases / drug therapy*
  • Dog Diseases / parasitology
  • Dogs
  • Doxycycline / administration & dosage
  • Doxycycline / therapeutic use*
  • Drug Therapy, Combination
  • Filaricides / administration & dosage
  • Filaricides / therapeutic use*
  • Macrolides / administration & dosage
  • Macrolides / therapeutic use*
  • Microfilariae / drug effects
  • Microfilariae / isolation & purification
  • Neonicotinoids / administration & dosage
  • Neonicotinoids / therapeutic use*
  • Nitro Compounds / administration & dosage
  • Nitro Compounds / therapeutic use*
  • Treatment Outcome


  • Antigens, Helminth
  • Filaricides
  • Macrolides
  • Neonicotinoids
  • Nitro Compounds
  • imidacloprid
  • Doxycycline
  • moxidectin