Clinical evaluation of the safety and efficacy of 10% imidacloprid + 2.5% moxidectin topical solution for the treatment of ear mite (Otodectes cynotis) infestations in dogs.

A clinical field investigation was conducted to evaluate the safety and efficacy of 10% imidacloprid/2.5% moxidectin for the treatment of ear mites (Otodectes cynotis) in dogs. The study was a multi-centered, blinded, positive controlled, randomized clinical trial conducted under field conditions with privately owned pets. A total of 17 veterinary clinics enrolled cases for the study. An otoscopic examination was performed to confirm the presence of O. cynotis residing in the ear of the dog prior to enrollment. A single-dog household was enrolled in the study if the dog had 5 or more ear mites and an acceptable physical examination. A multi-dog household was eligible if at least one dog in the household had 5 or more mites and all dogs in the household had acceptable physical exams and met the inclusion criteria. Qualified households were randomly assigned to treatments to receive either 10% imidacloprid+2.5% moxidectin topical solution or topical selamectin solution (positive control product) according to a pre-designated enrollment ratio of 2:1, respectively. If more than one dog in a multiple dog household had adequate numbers of ear mites, one dog was randomly selected to represent the household for efficacy evaluation prior to treatment. Treatments were administered twice per label and dose banding directions for each product approximately 28 days apart (Days 0 and 28), by the dog's owner at the study site. All dogs in a household were treated on the same day and with the same product. The owners completed a post-treatment observation form one day after each treatment. Post-treatment otoscopic examinations were performed by the investigators or attending veterinarian on Days 28 and 56. Physical examinations were performed on Days 0 and 56. One hundred and four (104) households were evaluated for efficacy on SD 28, and 102 households were evaluated for efficacy on SD 56. The dogs' ages ranged from 2 months to 16 years. A total of 247 dogs were evaluated for safety. Percent efficacy was based on the percentage of dogs cleared of ear mites. Mite clearance on Day 28 was 71% for the imidacloprid+moxidectin group and 69% for the selamectin group. Mite clearance on Day 56 was 82% for the imidacloprid+moxidectin group and 74% for the selamectin group. No serious adverse events associated with either product were observed during the study. The study demonstrated that 10% imidacloprid+2.5% moxidectin applied using two topical treatments, 28 days apart, was safe and achieved similar efficacy against O. cynotis as selamectin treatments applied and evaluated under the same conditions.

Renal effects of Dirofilaria immitis in experimentally and naturally infected cats.

Canine heartworm infection has been associated with glomerular disease and proteinuria. We hypothesized that proteinuria, likely due to glomerular damage, would also be found in cats experimentally and naturally infected with Dirofilaria immitis. Two populations of cats were evaluated, including 80 that were each experimentally infected with 60 infective heartworm larvae as part of a drug safety study, and 31 that were naturally infected with D. immitis. Each had a control population with which to be compared. In the experimentally infected group, we evaluated urine from 64 cats. Ten of these cats were shown to have microalbuminuria 8 months post infection. No cat refractory to infection with larvae and no cats from the control group demonstrated microalbuminuria. All 10 microalbuminuric cats were shown to have significant proteinuria, as measured by the urine protein:creatinine ratio. There was a subtle, but significant, association between worm burden and proteinuria, and although the presence of adult heartworms was required for the development of proteinuria, both microfilaremic and amicrofilaremic cats were affected. Neither the presence of circulating heartworm antibodies and antigen nor the presence of antigenuria predicted the development of proteinuria. Both heavily infected cats (5-25 adult heartworms) and cats with worm burdens compatible with natural infections (1-4 adult heartworms) developed proteinuria, and the relative numbers of cats so affected were similar between heavily and more lightly infected cats. Naturally infected cats, for which only dipstick protein determinations were available, were shown to have a significantly greater incidence of proteinuria (90% vs 35%) than did those in an age- and gender-matched control population. Additionally, the proteinuria in heartworm-infected cats was 3- to 5-fold greater in severity. We conclude that cats infected with mature adult heartworms are at risk for developing proteinuria and that this is recognized relatively soon after infection. While heavier infections may predispose cats to developing proteinuria, this complication is seen in naturally infected cats and experimental cats with worm burdens similar to those seen in natural infections (i.e., "clinically appropriate" worm burdens). The clinical relevance of heartworm-associated proteinuria is yet to be determined.

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

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.

Echocardiographic quantification of Dirofilaria immitis in experimentally infected cats.

The safety of heartworm preventives in heartworm-positive cats has traditionally been evaluated using adult Dirofilaria immitis removed from infected dogs and surgically implanted into the cats. An alternate study model uses infective larvae to establish adult infections in cats. Unfortunately, the number of adult worms resulting from the latter method varies widely from none to more than 30, both unacceptable for studies of natural heartworm infection and for studies evaluating product safety in heartworm-infected cats. We sought to determine infection severity in experimental infections via echocardiography to reduce the chances of enrolling uninfected and heavily infected cats into a study. Eighty adult cats were each inoculated with 60 infective D. immitis larvae and maintained for 8 months to allow for the development of adult worms. Antigen and antibody testing, as well as echocardiographic imaging, were performed to confirm and estimate adult worm burdens. Approximately 8 and 12 months post-infection, echocardiographic examination was performed to confirm and enumerate adult D. immitis populations in the cardiovascular system. Worm burdens were stratified as 0, 1-3, 4-11, and > 11 adults, with 0 being considered uninfected and more than 11 considered too heavily infected to be relevant for anthelmintic studies. Cats with clinically relevant infections (1-10 adults) subsequently received multiple treatments with the investigational drug, and worm burdens were confirmed by necropsy 30 days following the final treatment. Worm burden estimated with echocardiography correlated well, but not precisely, with post-mortem counts (p < 0.001, r2 = 0.67). Echocardiography under-, over-, and exactly estimated heartworm burden 53%, 27%, and 22% of the time, respectively. Although the correct category (0-4) was determined by echocardiography in only 54% of cats, positive cats were distinguished from negative cats 88% of the time and the heaviest infections (> 11) were correctly categorized 95% of the time. Both false negative and false positive results were observed. We conclude that echocardiography is useful for detecting mature experimental heartworm infections, identifying cats that have rejected mature infection, and detecting very heavy heartworm burdens, but it is only moderately accurate in classifying lesser burdens. While echocardiography cannot be relied upon to consistently determine the exact heartworm burden in experimentally infected cats, it is useful in stratifying worm burdens for anthelmintic safety studies.

Imidacloprid/moxidectin topical solution for the prevention of heartworm disease and the treatment and control of flea and intestinal nematodes of cats.

Sixteen controlled laboratory studies, involving 420 kittens and cats, were conducted to evaluate the efficacy and safety of topically applied formulations of imidacloprid and moxidectin for the prevention of feline heartworm disease, treatment of flea infestations and treatment and control of intestinal nematodes. Unit-dose applicators and the dosing schedule used in these studies were designed to provide a minimum of 10mg imidacloprid and 1mg moxidectin/kg. Treatments were applied topically by parting the hair at the base of the skull and applying the solution on the skin. Imidacloprid treatment alone did not display activity against Dirofilaria immitis or intestinal nematodes and moxidectin treatment alone provided little or no activity against adult Ctenocephalides felis infestations. The formulation containing 10% imidacloprid and 1% moxidectin was 100% efficacious against the development of adult D. immitis infections when cats were treated 30 days after inoculation with third-stage larvae. A single treatment with this formulation also provided 88.4-100% control of adult C. felis for 35 days. Imidacloprid/moxidectin was 100% efficacious against adult Toxocara cati and 91.0-98.3% efficacious against immature adults and fourth-stage T. cati larvae. The formulation provided 98.8-100% efficacy against adult Ancylostoma and immature adults and third-stage A. tubaeforme larvae. Monthly topical application with 10% imidacloprid/1% moxidectin is convenient, efficacious and safe for the prevention of feline heartworm disease, treatment of flea infestation and for the treatment and control of intestinal nematode infections of cats.

Safety of imidacloprid plus moxidectin topical solution applied to cats heavily infected with adult heartworms (Dirofilaria immitis).

A topically applied formulation containing 10% imidacloprid+1% moxidectin (Advocate/Advantage multi) has been developed for monthly application to cats for the prevention of feline heartworm (HW) disease caused by Dirofilaria immitis; and for the treatment and control of flea infestations, ear mite infestations, and intestinal nematode infections. A study model was designed to evaluate the safety of this product in cats harboring adult D. immitis infections. Eighty adult cats (40 males/40 females) were each inoculated with 60 third-stage D. immitis larvae on test day (TD) 1. On TD 243-245 echocardiographic imaging was performed on each cat to confirm and estimate the number of adult D. immitis residing in the cardiovascular system. A total of 35 cats were subsequently eligible for safety evaluation based on inclusion criteria. Four treatment groups were established and randomly selected for treatment: imidacloprid+moxidectin solution at the label dose (n=9) (group 1), imidacloprid+moxidectin solution at 5x the Iabel dose (n=9) (group 2), 6% selamectin topical solution (Revolution) at the label dose (positive control, n=8) (group 3), and topical treatment with placebo (negative control, n=9) (group 4). All cats were treated on TD 250. Treatments for groups 1, 3, and 4 were repeated on TDs 278 and 306. Group 2 cats were euthanized and examined for adult D. immitis on TD 288. All other cats were euthanized and examined for adult D. immitis on TD 334. No adverse events attributable to treatment with the test articles were observed during the study. The geometric mean numbers of adult D. immitis recovered at necropsy from treatment groups 1-4 were 2.9, 3.2., 4.0, and 2.7, respectively. There were no statistically significant differences in the comparison of adult D. immitis recovered at necropsy (ANOVA overall group effect P-value of 0.5356). The results of this study demonstrate that imidacloprid+moxidectin topical solution can be used safely in cats heavily infected with adult D. immitis.

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.

Efficacy of imidacloprid for removal and control of fleas (Ctenocephalides felis) on dogs.

OBJECTIVE: To evaluate efficacy of a 9.1% (w/w) imidacloprid solution, applied topically, to remove fleas from dogs and the duration of residual flea control when dogs were exposed to continuing flea infestation. ANIMALS: 32 adult mixed-breed dogs. PROCEDURE: Dogs were allocated to 4 groups of 8 dogs each; dogs of 3 groups received a single dose of imidacloprid, and those of the fourth group received excipient. Each dog was infested with 100 adult fleas on study days -3, -1, 6, 13, 20, 27, and 33. Treatments were applied on day 0. Each dog was examined for live fleas on days -2, 1, 7, 14, 21, 28, and 34. Posttreatment efficacy was determined by comparing the mean number of live fleas remaining on the treated dogs with the mean number of live fleas remaining on the control dogs. RESULTS: All 3 imidacloprid dosages provided flea control > or = 96.9% one day after treatment. Maximal efficacy of all 3 dosages (99.1 to 100%) was observed at 7 days after treatment. Flea control with 3.75 mg of imidacloprid/kg of body weight ranged from 94.4 to 96.9% for days 14 to 28 and decreased to 91.6% by 34 days after treatment. Flea control with 7.5 and 10.0 mg of imidacloprid/kg was 97.8 to 100% through day 28. At day 34, dosages of 7.5 and 10.0 mg of imidacloprid/kg were 97.6 and 96.9% efficacious, respectively. CONCLUSION: 7.5 or 10.0 mg of imidacloprid/kg are equivalent and superior to 3.75 mg/kg for flea control over the course of a 34 day posttreatment period. CLINICAL RELEVANCE: Monthly imidacloprid application of 7.5 to 10 mg/kg will rapidly kill existing and reinfesting flea infestations on dogs and break the flea life cycle by killing adult fleas before egg production begins.

Anthelmintic efficacy of febantel paste in naturally infected calves.

The purpose of the present study was to verify results of the lowest dose (5 mg kg-1) of febantel evaluated in an earlier trial in which there were no differences in efficacies of three dose rates (5, 7.5 and 10 mg kg-1 body weight) against natural gastrointestinal nematode infections of cattle. Fourteen Angus calves (mean weight and age of 155 kg and 525 days, respectively), from the same farm, with relatively heavy (mean of 448 eggs g-1 feces (epg] parasite burdens were selected. After an adjustment period of 8 days in drylot, beginning on 25 July, seven calves were treated with a 45.5% paste formulation of febantel. On Day 7 post-treatment, calves were necropsied for determination of residual worms. Rectal fecal samples were obtained prior to adjustment, at treatment, 5 days post-treatment and at necropsy. On both Day 5 post-treatment and at necropsy a mean of less than 1 epg was recovered from treated calves compared with 765 and 1566 epg, respectively, in control calves. Worms counts at necropsy revealed an efficacy of 98.5% against all adult abomasal worms (Haemonchus placei, 100%, P less than 0.02; Trichostrongylus axei, 99.4%, P less than 0.0001; Ostertagia ostertagi, 90.5%, P less than 0.0002). Treatment was 100% efficacious against adult small and large intestinal worms. However, numbers of Bunostomum phlebotomum, O. radiatum and Trichuris spp. recovered in the control calves were too low to enable a reliable test of drug efficacy. Treatment was not effective against either mucosal or luminal fourth stage larvae of abomasal O. ostertagi.(ABSTRACT TRUNCATED AT 250 WORDS)

Controlled dosage titration of febantel paste in naturally parasitized cattle.

A controlled anthelmintic trial was conducted to determine the efficacy of febantel paste (45.5%) at dosages of 2.5, 5.0, 7.5, and 10.0 mg/kg in calves harboring natural gastrointestinal nematode infections. Dosages of 5.0, 7.5 and 10.0 mg of febantel/kg of body weight were greater than 96% effective in removing adults of Haemonchus contortus, Ostertagia spp, Cooperia spp, and Oesophagostomum radiatum. The 2.5 mg/kg dosage was considered suboptimal because of low efficacy against Ostertagia and Cooperia spp. Efficacies against Trichostronglylus axei, Trichuris spp, Bunostomum phlebotomum, and Stronglyloides papillosus were difficult to determine because fewer numbers of these nematodes were recovered. Efficacies of febantel paste against immature bovine parasites ranged from 83.62% to 97.72%.

Efficacy of febantel paste against naturally acquired gastrointestinal nematodes of cattle.

Twenty calves with naturally acquired gastrointestinal nematode infections were assigned to 10 replicates of 2 calves each and were treated with febantel paste (5 mg/kg of body weight, PO) or an equivalent volume of paste vehicle (control calves). Adverse reactions were not observed after febantel treatment. At necropsy, gastrointestinal nematode counts in febantel-treated calves, compared with control calves, were reduced by over 99% for all major species except Trichuris discolor, counts of which were reduced by only 69%. Counts of gastrointestinal nematode eggs in feces of febantel-treated calves were reduced by 100% after treatment.

Anthelmintic efficacy of febantel combined with praziquantel against Ancylostoma tubaeforme, Toxocara cati, and Taenia taeniaeformis in cats.

Forty cats, each harboring 2 or 3 parasitic infections (Ancylostoma tubaeforme, Toxocara cati, and/or Taenia taeniaeformis), were used to titrate the anthelmintic efficacy of a paste containing 3.4% febantel and 0.34% praziquantel. The cats were allotted into 4 groups (10 cats/group). For 3 consecutive days, the cats were given febantel/praziquantel at 5/0.5 mg/kg/day, 10/1 mg/kg/day, 15/1.5 mg/kg/day, or a blank paste vehicle (control) at 0.29 g/kg of body weight. The recommended dosage of 10 mg of febantel and 1 mg of praziquantel/kg cleared greater than or equal to 98% of the 3 helminth species.

Praziquantel for control of Hymenolepis nana in mice.

Praziquantel was blended into ground mouse feed at 35, 70, and 140 ppm in one replicate and at 140, 210, and 280 ppm in a second replicate. Mice naturally infected with Hymenolepis nana were provided this diet for 7 consecutive days. Reduction of Hymenolepis nana in mice receiving medicated feed when compared to mice receiving nonmedicated feed was 48.9, 73.2, and 87.1%, respectively in replicate 1, and 100% in all three groups in replicate 2. These data suggest that praziquantel blended into the feed at 140 ppm for 7 consecutive days will provide efficacious (87.1-100%) control of Hymenolepis nana in mice. Higher dosages may be necessary for complete elimination of this parasite.

Coccidia of coyotes in eastern Colorado.

Eighty-two coyote fecal samples were collected from eastern Colorado and examined for coccidia. Sporocysts of Sarcocystis were observed in 17 of the samples and oocysts of Isospora ohioensis were observed in two samples. Ten fecal samples contained eimerian coccidia thought to be pseudoparasites of the coyote acquired while ingesting heavily infected rabbits.