Dose selection of selamectin for efficacy against adult fleas (Ctenocephalides felis felis) on dogs and cats.

Selamectin, a novel avermectin, was evaluated in two controlled studies (one in Beagles, one in domestic shorthaired cats) to determine an appropriate topical dose for efficacy against adult Ctenocephalides felis felis (C. felis) fleas on dogs and cats for 1 month. For each study, animals were allocated randomly to four treatments. One treatment consisted of the inert formulation ingredients (vehicle) administered as a negative control, and the other three treatments consisted of a single topical dosage of 3, 6, or 9mgkg(-1) of selamectin. In each study, selamectin was administered as a topical dose applied to the skin in a single spot at the base of the neck in front of the scapulae. Dogs and cats were infested with 100 viable unfed C. felis (50 males and 50 females) on days 4, 11, 18, and 27. Seventy-two hours (+/-2h) after each infestation, on days 7, 14, 21, and 30, a comb count to determine the number of viable fleas present on each animal was performed. Efficacy of selamectin on day 30 was used to select an appropriate dose. For dogs and cats, percentage reductions in geometric mean flea comb counts for the three selamectin treatments ranged from 94. 6 to 100% on days 7, 14, and 21, compared with the negative-control treatment. On day 30, reductions in flea comb counts were 81.5, 94.7, and 90.8% for dogs, and 79.8, 98.0, and 96.2% for cats treated with selamectin at 3, 6, or 9mgkg(-1), respectively. For day 30 flea comb counts for dogs and cats, analysis of variance showed that the three selamectin treatments resulted in significantly (P< or =0.05) lower counts than did the negative-control treatment. For dogs and cats, geometric mean flea counts for selamectin administered at a dosage of 3mgkg(-1) were significantly (P< or =0.05) higher than those for the 6 and 9mgkg(-1) treatment dosages combined. There were no significant differences in flea counts between the 6 and 9mgkg(-1) treatments. This analysis was confirmed by linear-plateau modeling. Thus, the optimal dose of selamectin for efficacy against adult fleas for both dogs and cats, as estimated by the turning point (plateau) in the dose response curve, was 6mgkg(-1).

Efficacy and safety of selamectin against fleas and heartworms in dogs and cats presented as veterinary patients in North America.

A series of randomized, controlled, masked field studies was conducted to assess the efficacy and safety of selamectin in the treatment of flea infestations on dogs and cats, and in the prevention of heartworm infection in dogs. In addition, observations were made on the beneficial effect of selamectin treatment on dogs and cats showing signs of flea allergy dermatitis (FAD). In all studies selamectin was applied topically, once per month, in unit doses providing a minimum dosage of 6mgkg(-1). Dogs and cats with naturally occurring flea infestations, some of which also had signs associated with FAD, were assigned randomly to receive three months of topical treatment with selamectin (220 dogs, 189 cats) or a positive-control product (dogs: fenthion, n=81; cats: pyrethrins, n=66). Selamectin was administered on days 0, 30, and 60. Day 0 was defined as the day that the animal first received treatment. Flea burdens were assessed by flea comb counts and clinical evaluations of FAD were performed before treatment, and on days 14, 30, 60, and 90. On days 30, 60, and 90, mean flea counts in selamectin-treated dogs were reduced by 92.1, 99.0, and 99.8%, and mean flea counts in fenthion-treated dogs were reduced by 81.5, 86.8, and 86.1%, respectively, compared with day 0 counts. Also, on days 30, 60, and 90, mean flea counts in selamectin-treated cats were reduced by 92.5, 98.3, and 99.3%, and mean flea counts in pyrethrin-treated cats were reduced by 66.4, 73.9, and 81.3%, respectively, compared with day 0 counts. Selamectin also was beneficial in alleviating signs in dogs and cats diagnosed clinically with FAD. A total of 397 dogs free of adult heartworm infection from four heartworm-endemic areas of the USA were allocated randomly to six months of treatment with selamectin (n=298) or ivermectin (n=99). Selamectin achieved a heartworm prevention rate of 100%, with all dogs testing negative for microfilariae and adult heartworm antigen on days 180 and 300. Selamectin was administered to a total of 673 dogs and 347 cats having an age range of 6 weeks to 19 years (3954 doses). The animals included 19 purebred or crossbred Collies (Bearded, Border, and unspecified). There were no serious adverse events. Results of these studies indicated that selamectin was highly effective in the control of flea infestations in dogs and cats without the need for simultaneous treatment of the environment or of in-contact animals and also was beneficial in alleviating signs associated with FAD. Selamectin also was 100% effective in preventing the development of canine heartworms and was safe for topical use in dogs and cats.

The efficacy of selamectin in the treatment of naturally acquired aural infestations of otodectes cynotis on dogs and cats.

The efficacy of a novel avermectin, selamectin, was evaluated against naturally acquired aural infestations of Otodectes cynotis on dogs and cats. In four controlled and masked studies conducted in the USA and Europe, animals were allocated randomly to treatment with either selamectin at a minimum dosage of 6mgkg(-1) (range, 6-12. 5mgkg(-1)) or the vehicle only from the commercial formulation of selamectin (negative control). Treatments were administered topically in a single spot to the skin of each animal's back at the base of the neck in front of the scapulae. Cats were treated on day 0 only, and dogs were treated either on day 0 only or on days 0 and 30. The ears of dogs were examined otoscopically on day 14 for the presence of viable mites. Mite counts were conducted on day 30 for animals that had received one dose and on day 60 for animals that had received two doses. Percentage reductions in geometric mean mite counts for selamectin treatment compared with the vehicle were 100% for all animals on all count days. Analysis of variance, confirmed by Savage Scores, showed that ln(mite count+1) values were significantly (P< or =0.0015) lower for selamectin than for the vehicle for all animals on all count days. Thus, selamectin administered topically at a minimum dosage of 6mgkg(-1) was safe and 100% effective against naturally acquired aural infestations of O. cynotis in dogs and cats after a single dose or after two doses administered 1 month apart.

Efficacy of selamectin against experimentally induced and naturally acquired infections of Toxocara cati and Ancylostoma tubaeforme in cats.

The efficacy of selamectin against experimentally induced and naturally acquired infections of adult ascarids (Toxocara cati) and adult hookworms (Ancylostoma tubaeforme) was evaluated in five controlled studies in cats. Two studies evaluated the efficacy of selamectin against both ascarid (natural or induced) and hookworm (induced) infections; two studies evaluated the efficacy of selamectin against single natural infections of T. cati or A. tubaeforme; and the fifth study evaluated the efficacy of selamectin against induced infections of A. tubaeforme. Cats received selamectin topically in unit doses designed to deliver a minimum of 6mgkg(-1). Treatments were applied to the skin on each animal's back at the base of the neck in front of the scapulae. For experimentally induced infections, cats were inoculated orally with approximately 500 embryonated eggs of T. cati 56 days prior to treatment and/or approximately 150-250 larvae (L(3)) of A. tubaeforme 30 or 42 days prior to treatment. For both induced and naturally acquired infections, cats were allocated randomly to treatments (6-12 cats per treatment) on the basis of fecal egg counts to receive either selamectin or a vehicle containing the inert formulation ingredients. In all studies, adult worm counts were performed at necropsy 14 days after the last treatment administration. Against T. cati, a single application of selamectin provided a 100% reduction in the geometric mean number of adult worms for both experimentally induced and naturally acquired infections. Against A. tubaeforme, a single administration of selamectin provided a 99.4% reduction in the geometric mean number of adult worms in cats with natural infections, and an 84.7-99.7% reduction in adult worms in cats with induced infections. Two doses of selamectin administered at monthly intervals provided a 91.9% reduction in the geometric mean number of adult A. tubaeforme worms in cats with experimentally induced infections. The geometric mean numbers of adult worms (T. cati and A. tubaeforme) from selamectin-treated cats were significantly (P< or =0.0018) lower than for vehicle-treated cats in all studies. Thus, a single topical unit dosage providing a minimum dosage of 6mgkg(-1) selamectin was highly effective in the treatment of naturally acquired and experimentally induced infections of T. cati and A. tubaeforme in cats.

Comparison of arithmetic and geometric means as measures of a central tendency in cattle nematode populations.

Efficacy calculations in anthelmintic studies require estimates of the central tendency for the nematode populations. Confusion exists among practitioners regarding which measures of central tendency are most appropriate; although the arithmetic mean is frequently used, there are theoretical reasons for preferring the geometric mean. To investigate this controversy, arithmetic and geometric means were compared for their suitability for use in measuring efficacy. Arithmetic and geometric means were compared as measures of central tendency for skewed distributions. The following criteria were developed to facilitate the comparison: (1) probability around the parameter, (2) influence of extreme values, and (3) proximity to the median. Under log-normality, theoretical results demonstrated the superiority of the geometric mean. Modified-bootstrap simulations using empirical data from cattle were used to confirm theoretical expectations. Simulations on log-normal data supported the geometric mean as the better indicator of the central tendency. Additionally, for data not confirmed as log-normal, the superiority of geometric means was demonstrated. In a comparison of precision, it was shown that mean squared error was always smaller for sample geometric means than for arithmetic means when n> or =2. Simulation results added support to that conclusion.

Activity of doramectin against nematode endoparasites of cattle.

A series of 28 controlled anthelmintic studies, involving 634 cattle, was conducted throughout North America and Europe to evaluate the efficacy of doramectin against a broad range of gastrointestinal parasitic nematode species and lungworms in naturally and experimentally infected animals. Within each study, one or two groups were treated with doramectin at 200 micrograms kg-1 and another group received no drug treatment. Worm burdens were estimated by standardised techniques, and efficacy assessed on reduction of worm burdens in doramectin-treated animals. Doramectin was at least 99.6% effective (P < 0.0002) in eliminating the immature and adult stages of the following 14 species of nematodes: Ostertagia ostertagi (including inhibited), Ostertagia lyrata, Haemonchus placei, Trichostrongylus axei, Trichostrongylus colubriformis, Cooperia oncophora (including inhibited), Cooperia pectinata, Cooperia punctata, Cooperia spatulata, Cooperia surnabada, Bunostomum phlebotomum, Strongyloides papillosus, Oesophagostomum radiatum and Dictyocaulus viviparus. Efficacy against adult Trichostrongylus longispicularis, Nematodirus spathiger and Trichuris spp. was 93.1%, 96.5% and 94.6%, respectively. Efficacies against adult and fourth-stage larvae of Nematodirus helvetianus, the dose-limiting species, were 73.3% and 75.5%, respectively.

Efficacy of semduramicin and salinomycin against different stages of Eimeria tenella and E. acervulina in the chicken.

The efficacy of a new ionophore, semduramicin, was compared with salinomycin in a series of in ovo and in vivo trials. Semduramicin was more efficacious than salinomycin against Eimeria tenella sporozoites as judged by oocyst production in embryonated eggs. When the two drugs were given in ovo at 93 h post inoculation (PI), both drugs exerted some effect against late schizogonous stages of E. tenella. In three battery studies, semduramicin (25 ppm) and salinomycin (60 and 66 ppm) were tested against E. tenella and E. acervulina. Medicated feed was withdrawn at 24-h intervals PI to study the stage of action of the anticoccidials. In E. tenella infected chickens, both anticoccidials exerted their maximum effect on weight gain and feed:gain ratio through the first 72 h PI. Semduramicin was more effective than salinomycin in controlling E. tenella lesions and coccidiosis mortality. With E. acervulina, both drugs acted similarly on early life cycle stages and no improvement in performance was recorded when medicated feed was given for longer than 72 h. Semduramicin was more effective than salinomycin in controlling E. acervulina lesions.

Effects of different levels of oocyst inocula of Eimeria acervulina, E. tenella, and E. maxima on plasma constituents, packed cell volume, lesion scores, and performance in chickens.

The effects of different levels of oocyst inocula of Eimeria acervulina, E. tenella, or E. maxima on plasma carotenoids, total plasma lipids, total plasma proteins, packed cell volume (PCV), bird performance, and coccidial lesion scores were determined in male Hubbard chickens. Each test consisted of an uninfected treatment and either four levels (E. tenella and E. maxima) or five levels (E. acervulina) of inocula. Carotenoids and lipids were significantly (P < or = 0.05) depressed by E. acervulina starting at 10(2) oocysts per bird, whereas 10(4) and higher inoculum levels significantly depressed plasma protein. Carotenoids and lipids were significantly depressed by E. tenella beginning at 10(4) oocysts per bird, whereas 10(2) oocysts per bird and greater levels significantly depressed plasma protein. E. maxima significantly depressed carotenoids and lipids beginning at 6.7 x 10(2) oocysts per bird and plasma protein at 6.7 x 10(4) oocysts per bird. PCV was depressed by E. acervulina and E. tenella starting at 10(4) oocysts per bird but was not affected by E. maxima. Weight gain was significantly depressed by E. acervulina beginning at 10(5) oocysts per bird, by E. tenella at 10(4) oocysts per bird, and by E. maxima at 6.7 x 10(4) oocysts per bird. Coefficients of determination (R2) were highest for carotenoids (0.96-0.99), followed by lipids (0.93-0.96), weight gain (0.89-0.91), feed:weight gain ratio (0.89-0.91), and protein and PCV (0.65-0.92). Results demonstrated that plasma carotenoids and lipids were excellent response variables for measuring the effects on broiler chickens of each of the Eimeria spp. tested.

Correlated response in feed efficiency accompanying selection for milk yield in Jerseys.

Gross feed efficiency (milk energy output divided by energy consumed) was measured in 232 Jersey cows resulting from direct selection for milk yield and a control line of 121 daughters of 20 Jersey bulls taken randomly from commercial artificial insemination sampling programs in 1967. Data were collected between 1971 and 1982 from primiparous cows in middle to late lactation in 21 feeding trials of 28 d. Cows were fed hay and silage ad libitum plus grain according to production at the rate of 1 kg grain/3 kg milk. Models for least squares analyses included trial, line, days in milk, and either body weight change (model 1) or energy balance (model 2), estimated as the difference between energy requirements and actual energy intake. Body weight change was an insignificant source of variation, and gross feed efficiency did not differ between genetic lines using model 1. Significant line differences in gross efficiency were obtained after adjusting for energy balance; however, problems of multicollinearity invalidates meaningful inference. Results indicate genetic lines of Jerseys did not differ in gross feed efficiency when fed according to yield and suggest selection has not affected efficiency of direct conversion of nutrients into milk.