Ivermectin and milbemycin oxime in experimental adult heartworm (Dirofilaria immitis) infection of dogs.

BACKGROUND: The US Food and Drug Administration reports an increase in the frequency of reports of lack of effectiveness claims for heartworm (HW) prevention products. HYPOTHESIS: At their labeled doses, single doses of commercially available HW prevention products are not completely effective against all field isolates of HW. ANIMALS: Forty-two HW-free dogs experimentally inoculated with a recent HW field isolate. METHODS: Placebo-controlled, blinded laboratory clinical trial. Dogs randomly allocated to 1 of 3 treatment groups with 14 dogs per group. Groups were untreated control or p.o. dosed with milbemycin oxime (MBO) or ivermectin (IVM). Dogs were inoculated with 50 HW third stage larvae 30 days before dosing and necropsy was performed on Day 123 after treatment to enumerate adult HW. RESULTS: Thirteen of 14 control dogs had adult HW detected at necropsy with a geometric mean worm count of 22.3. One HW was found in 1 dog in each of the MBO and IVM treatment groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Two currently approved macrocyclic lactone HW preventives used at their labeled dose rates were <100% effective against a recent HW field isolate, supporting the hypothesis that the effectiveness of a single dose of these preventives can vary. This is important in guiding clients on expectations of product effectiveness.

Imidacloprid plus moxidectin topical solution for the prevention of heartworm disease (Dirofiloria immitis) in dogs.

A topically applied formulation containing 10% imidacloprid+2.5% moxidectin (Advocate/Advantage multi) has been developed for monthly application to dogs for the prevention of canine heartworm (HW) disease caused by Dirofilaria immitis; and for the treatment and control of flea infestations, mite infestations, and intestinal nematode infections. The efficacy of this formulation to prevent canine HW disease was confirmed at three study locations which included the use of 88 purpose-bred beagles 6-8 months of age. Two of these studies also evaluated the effects of post-treatment water exposure or shampooing on product performance. Each dog was infected with 50 third-stage D. immitis larvae on test days -30 to -45. Dogs were blocked according to gender and body weight on test day -1. Topically applied test articles were administered once on test day 0 as follows: 10% imidacloprid+2.5% moxidectin (52 dogs); 2.5% moxidectin mono solution (eight dogs); 10% imidacloprid mono solution (16 dogs); and placebo solution (12 dogs). Treatment dosages were applied to provide a minimum of 10 mg/kg imidacloprid and/or 2.5 mg/kg moxidectin. Subgroups of dogs were exposed to water to simulate swimming/rain exposure at designated post-treatment intervals. Additional dogs were shampooed at 90 min, 4 h, or 24 h post-treatment. All dogs were necropsied 110-119 days post-treatment for recovery of adult D. immitis. No adult D. immitis were recovered at necropsy from any of the dogs receiving 10% imidacloprid+2.5% moxidectin or 2.5% moxidectin mono solution, demonstrating 100% efficacy for prevention of D. immitis infection. A total of 701 adult D. immitis were recovered at necropsy from dogs receiving 10% imidacloprid mono solution or placebo (range of 11-40 D. immitis/dog). The efficacy of 10% imidacloprid+2.5% moxidectin treatment for the prevention of HW disease was not decreased when dogs were shampooed as early as 90 min post-treatment, or when dogs immersed in water 5 times post-treatment at weekly intervals.

Evaluation of the speed of kill of fleas and ticks with Frontline Top Spot in dogs.

The speed of kill of a spot-on formulation of fipronil (Frontline Top Spot, Merial Limited, Duluth, GA) against adult cat fleas (Ctenocephalides felis) and brown dog ticks (Rhipicephalus sanguineus) was evaluated in dogs in a commercial laboratory setting. Forty dogs were allocated to 20 replicates of two based on sex and pretreatment flea counts. Within each replicate, dogs were randomly allocated to an untreated control group or to treatment with fipronil, administered topically as a spot-on per label instructions. The technical staff performing the flea and tick counts were unaware of treatment group assignments. Each dog was infested with approximately 100 unfed adult fleas on Day -8 or -6 and on Day -1. Each dog also was infested with approximately 50 unfed adult ticks on Day -1. Treatments were administered on Day 0 according to body weight. Flea and tick counts were performed on four randomly selected dogs from each treatment group at approximately 6, 12, 18, 24, and 48 hours after treatment. Flea and tick count reductions for dogs treated with fipronil were significant (P < .05), as compared with untreated controls, at 18, 24, and 48 hours after treatment. Controlled efficacy of fipronil against C. felis and R. sanguineus ranged from 94% to 100% at these evaluation times. This study demonstrated that the speed of kill of fipronil, applied topically as a spot-on, was 100% against C. felis fleas on dogs within 12 to 18 hours after treatment and 100% against R. sanguineus ticks between 24 and 48 hours after treatment.

Persistent efficacy of doramectin against experimental challenge with Ostertagia ostertagi in cattle.

Two studies were conducted in North America to evaluate the persistent efficacy of doramectin injectable solution against experimental challenge with infective larvae of Ostertagia ostertagi. In both studies, four groups of 10 randomly-assigned calves, negative for trichostrongyle-type eggs on fecal examination, were treated subcutaneously in the midline of the neck with saline (1 ml 50 kg-1) on Day 0 or doramectin (200 micrograms kg-1 = 1 ml 50 kg-1) on Day 0, 7, or 14. Two additional calves from the same pool of animals were randomly assigned as larval-viability monitors and received no treatment. Beginning on Day 14 and continuing through Day 28, the 40 treated calves each were given approximately 1000 infective larvae of O. ostertagi by gavage daily; the two larval-viability monitors were inoculated in a similar manner with approximately 30,000 larvae as a single dose on Day 28. Animals were slaughtered on Day 42 in one study and on Days 42, 43, or 46 in the second. The abomasum from each calf was harvested and processed for worm recovery. A 2% aliquot of abomasal contents plus wash was examined for worm quantification and identification. Geometric mean O. ostertagi burdens were calculated from the log (O. ostertagi count + 1) and were used to estimate percentage reduction. In both studies, doramectin injectable solution was > or = 99.6% efficacious in reducing infection resulting from challenge with infective larvae of O. ostertagi for at least 21 days posttreatment; by 28 days posttreatment, efficacy was 87.3% in one study and 99.7% in the other.