ABSTRACT OF THE WEEK

Veterinary parasitology
Volume 176 | Issue 2-3 (March 2011)

Comparative efficacy of four commercially available heartworm preventive products against the MP3 laboratory strain of Dirofilaria immitis.

Vet Parasitol. March 2011;176(2-3):189-94.

B L Blagburn¹, A R Dillon, R G Arther, J M Butler, J C Newton

¹ Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA. blagbbl@vetmed.auburn.edu

Abstract

A controlled laboratory study was conducted to evaluate the efficacy of four commercial products administered as a single treatment for the prevention of heartworm disease caused by Dirofilaria immitis in dogs. Forty-four commercially sourced Beagle dogs, 6-7 months of age, were received at the test site (Auburn University, Department of Pathobiology) on Study Day (SD) -72 to begin acclimation. On SD -30, each dog was inoculated subcutaneously with 100 infective, third-stage D. immitis larvae (MP3 strain, TRS Laboratories, Inc., Athens, GA). On SD -1, 40 dogs weighing 18.2-25.3 lbs were ranked by decreasing body weight and randomized to five groups of eight dogs each. On SD 0, the dogs assigned to Group 1 were treated orally with ivermectin/pyrantel pamoate chewable tablets, Group 2 dogs were treated orally with milbemycin oxime flavored tablets, Group 3 dogs were treated with selamectin topical solution, and Group 4 dogs were treated with imidacloprid/moxidectin topical solution. Group 5 dogs remained nontreated. Dosages for dogs in Groups 1-4 were based on the individual body weight of each dog and current labeled dose banding for each commercial product. All dogs were fasted overnight prior to treatment. Food was returned four hours after treatment. Animals were observed for abnormal clinical signs involving eyes, feces, respiration, behavioral attitude, locomotion/musculature, or skin conditions at prescribed intervals immediately after treatment and at twice daily intervals thereafter. On SD 90, whole blood was collected and tested for adult heartworm antigen. On SDs 119/120, the dogs were euthanized and subjected to necropsy examination for recovery of adult D. immitis and/or worm fragments. At necropsy, all 8 dogs in the nontreated group were infected with adult D. immitis (34-70 worms/dog, geometric mean (GM)=51.6 worms/dog). One or more adult D. immitis and/or worm fragments were recovered from 7 of 8 of the dogs each in Groups 1-3 (87.5% were heartworm positive). The respective GM worm burdens/dog for Groups 1-3 was 2.3, 2.4, and 2.3 which resulted in 95.6, 95.4 and 95.5% efficacy, respectively. No worms were recovered from any of the 8 dogs in Group 4 resulting in 100% efficacy.

Companion Notes

Controlled, laboratory study comparing the efficacy of 4 heartworm preventives against the MP3 laboratory strain of Dirofilaria immitis

- supported by Bayer HealthCare, Animal Health (1 author is an employee)

Study design

- introduction on the treatment of canine heartworm disease (CHD)

- currently available preventives include macrocyclic lactone (ML) preventives

- ivermectin

- milbemycin oxime

- moxidectin

- selamectin

- reports from Center for Veterinary Medicine - Food and Drug Administration

- reports increasing numbers of lack of efficacy claims

- increase is particularly high where challenge rates are high

- one strain of D immitis recently used to evaluate a potential new anthelmintic

(MP3 laboratory strain; TRS Laboratories Inc., Athens, GA)

- this strain found less susceptible to a traditionally effective preventive

(ivermectin-based preventative (Bayer HealthCare, Animal Health))

- “in a limited number of dogs”

- Bayer HealthCare Animal Health markets a topical for heartworm prevention

(Advantage Multi® [imidacloprid + moxidectin] Topical Solution)

- also used for broad spectrum internal/external parasite control in dogs

- in laboratory studies on one topical treatment at lowest label dose

- 100% efficacy vs D immitis when given 30-45 days post-infection

- moxidectin is highly lipophilic and achieves high plasma levels

- study population: 40 commercial-source beagles from 6-7 months of age

- procedure:

- day -30: each dog inoculated sc with 100 infective, 3^rd-stage D immitis larvae

(MP3 strain, TRS Laboratories, Inc., Athens, GA)

- day -1: 40 dogs from 18.2-25.3 lbs ranked by decreasing body weight

- then randomized into 5 groups of 8 dogs each

- day 0: (dosages based on labeled dose of each commercial product)

- dogs fasted overnight before treatment

- food returned 4 hours after treatment

- group 1: ivermectin/pyrantel pamoate chewable tablets PO

(Heartgard® Plus Chewables for Dogs, Merial Ltd., Duluth, GA)

- group 2: milbemycin oxime flavored tablets PO

(Interceptor® Flavor Tabs, Novartis Animal Health, Greensboro, NC)

- group 3: selamectin topical solution

(Revolution®, Pfizer Animal Health, Exton, PA)

- group 4: imidacloprid/moxidectin topical solution

(Advantage Multi® for Dogs, Bayer HealthCare, Animal Health, KS)

- group 5: nontreated

- assessment methods

- animals observed for adverse events at prescribed intervals

- immediately after treatment

- then at twice daily intervals

- whole blood collected on day 90 to test for adult heartworm antigen

(Dirochek® Canine Heartworm Antigen Test Kit, Symbiotics Corp)

- day 119/120: necropsy to collect adult D immitis and worm fragments

- worm motility assessed by placing worm in saline at 37° C

- if fragment(s) detected, 1 additional worm added to total count

Results

- worms numbers at necropsy by group

- group 1: ivermectin/pyrantel pamoate chewable tablets PO

- 7 of the 8 dogs had 1 or more adult D immitis and/or worm fragments

- ≥ 6 worms recovered from 1 dog in the group

- 1 dog had 3 sex:F worms, 3 sex:M worms and 2 fragments

- total count: 7

- 87.5% were heartworm positive

- geometric mean (GM): 2.3; 95.6% efficacy

- group 2: milbemycin oxime flavored tablets PO

- 7 of the 8 dogs had 1 or more adult D immitis and/or worm fragments

- ≥ 6 worms recovered from 1 dog in the group

- 1 dog had 4 sex:F worms, 1 sex:M worm and 2 fragments

- total count: 6

- 87.5% were heartworm positive

- geometric mean (GM): 2.4; 95.4% efficacy

- group 3: selamectin topical solution

- 7 of the 8 dogs had 1 or more adult D immitis and/or worm fragments

- ≥ 6 worms recovered from 1 dog in the group

- 1 dog had 4 sex:F worms and 5 sex:M worms

- total count: 9

- 87.5% were heartworm positive

- geometric mean (GM): 2.3; 95.5% efficacy

- group 4: imidacloprid/moxidectin topical solution

- no worms detected in any of the 8 dogs; 100% efficacy

- group 5: all 8 dogs infected with adult D immitis worms

- 34-70 worms/dog; GM: 51.6 worms/dog

- 4-6 dogs in groups 1-3 harbored at least 1 sex:F worm

- day 90 adult heartworm antigen was negative in all dogs

- supporting fact that dogs were heartworm negative before entry to study

- adverse events: none thought related to any of the 4 preventives

“Results of this study indicate that a single topical dose of imidacloprid/moxidectin topical solution is 100% effective against the MP3 strain of D. immitis under the conditions of this study, while only 12.5% of the dogs in the ivermectin/pyrantel, milbemycin oxime and selamectin treatment groups remained heartworm free.”

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