Evaluation of the therapeutic and preventive efficacy of 2.5 % moxidectin / 10 % imidacloprid (Advocate(®), Bayer animal health) in dogs naturally infected or at risk of natural infection by Dirofilaria repens.

The objective of this GCP-compliant clinical field study was to evaluate the efficacy of the combination of moxidectin (minimum dose of 2.5 mg/kg body weight) and imidacloprid (minimum dose of 10.0 mg/kg body weight) spot-on (Advocate(®)) as a preventive and therapeutic treatment of natural infection by Dirofilaria repens in dogs in the Czech Republic.There were two arms of the study, both negatively controlled. 34 animals were randomly allocated to two groups of the treatment arm; 90 negative animals were randomly allocated to the prevention arm groups. All enrolled dogs were observed physically and blood was sampled monthly for Dirofilaria repens microfilaria counts for 18 months by modified Knott test and PCR. 34 dogs were positive for microfilaria and enrolled in the treatment arm of this study (treated: 18, untreated: 16). The reduction of the log-transformed microfilaria counts was significantly higher in the treatment group on day 28 (p = 0.007), 56, 84 and 112 (p < 0.001). All animals treated were negative after a single treatment. In the untreated control group 93.75 % remained positive (p < 0.001). 87 dogs were negative for microfilaria prior to allocation to the "preventive" arm (treated: 49; untreated: 38; 3 excluded). One dog in the untreated control group became positive for Dirofliaria repens microfilaria, while none of the treated dogs became positive. Advocate(®) was effective in the treatment of dogs infected with microfilaria of Dirofilaria repens. Due to the low rate of natural infections the preventive efficacy could not be proven, but no dog treated became positive.

New insights into morphological and biological features of Capillaria aerophila (Trichocephalida, Trichuridae).

Capillaria aerophila is a trichuroid nematode affecting the respiratory system of dogs, cats, wild carnivores and, occasionally, humans. Animals become infected by ingesting larvated eggs or earthworms, which act as facultative intermediate hosts. The aim of this work is to present new insights into morphological and biological features of this neglected lungworm. Typical features of C. aerophila eggs, differentiating them from those of most known trichuroid whipworms (i.e. size, asymmetry of bipolar plugs and a wall with a network of anastomosing ridges), were detected upon light and scanning electron microscopy. Eggs of C. aerophila were used for in vitro development. Light microscopy showed typical features of C. aerophila eggs: size, asymmetry of bipolar plugs and a wall with a network of anastomosing ridges. All these features were confirmed upon SEM, in that C. aerophila eggs showed an outer densely striated and net-like shell. Eggs of T. vulpis, used for a comparative analysis, were bigger than those of C. aerophila and showed a thick and smooth wall at both light and scanning electron microscopy. Eggs started to develop after 35 days from shedding and mobile larvae were observed in the eggs after two months. The results of this study provide key information on the biological cycle of C. aerophila and present key morphological characters for the identification of eggs in faeces.

Efficacy of a single topical application of Advantage Multi (= Advocate) Topical Solution (10% imidocloprid + 2.5% moxidectin) in the treatment of dogs experimentally infected with Crenosoma vulpis.

Crenosoma vulpis is a metastrongylid lungworm of canids causing chronic respiratory disease in dogs in parts of North America and Europe. The objective of this study was to determine the efficacy of imidacloprid 10% + moxidectin 2.5% (Advantage Multi/Advocate Topical Solution) against C. vulpis infection in experimentally infected dogs. Eighteen beagles (9 M, 9 F) were each given 100 infective third-stage larvae of C. vulpis. The 16 dogs (8 M, 8 F) with the highest faecal larval counts were stratified by gender and larval counts and randomly assigned to a treatment group. Group 1 received placebo only; group 2 was given a single topical treatment of Advantage Multi/Advocate (10 mg/kg imidacloprid/2.5 mg/kg moxidectin) at 4 weeks PI. Dogs were euthanised at 8 weeks PI and the lungs were removed and examined for the presence of adult worms by lung flush. The mean (geometric) number for adult C. vulpis recovered in untreated dogs was 70.0 (range 58 to 87) compared with 0.0 in animals treated with Advantage Multi/Advocate. The resulting efficacy against C. vulpis was 100%. The number of C. vulpis was significantly lower for treated dogs than the burden shown in the untreated group (p = 0.003).

Efficacy and safety of imidacloprid 10%/moxidectin 1% spot-on formulation in the treatment of feline aelurostrongylosis.

The objective of the present study was to evaluate the efficacy and safety of the antiparasitic spot-on formulation containing imidacloprid 10%/moxidectin 1% (Advocate, Bayer) in the treatment of natural feline infection with the lungworm Aelurostrongylus abstrusus (Nematoda, Strongylida). The efficacy of Advocate administered once was tested in comparison to a control oral formulation containing fenbendazole 18.75% (Panacur Intervet) administered over three consecutive days based on larvae per gramme of faeces (LPG), measured on days 28 +/- 2 following treatment and compared to counts on days -6 to -2. In total 24 cats treated either with Advocate (n = 12) or with Panacur (n = 12) were included. Mean LPG postbaseline (days 28 +/- 2) were low in both treatment groups, i.e., 0 LPG for Advocate and 1.3 LPG for Panacur. Reduction of post-baseline larval counts showed Advocate (100% reduction) to be superior in efficacy compared to the control product (99.29% reduction). No treated animals showed adverse events. This trial demonstrated that both Advocate spot-on formulation and Panacur oral paste are safe and effective in the treatment of aelurostrongylosis in cats. Future practical perspectives in feline medicine and the major advantages of the spot-on product compared to the oral paste are discussed.

Efficacy and safety of emodepside 2.1%/praziquantel 8.6% spot-on formulation in the treatment of feline aelurostrongylosis.

The objective of the present study was to evaluate the efficacy and safety of the antiparasitic spot-on formulation containing emodepside 2.1%/praziquantel 8.6% (Profender, Bayer) in the treatment of natural feline infection with the lungworm Aelurostrongylus abstrusus (Nematoda, Strongylida). Efficacy of Profender given once at the licensed dose was tested in comparison to a control oral formulation containing fenbendazole 18.75% (Panacur, Intervet) given over three consecutive days at the licensed dose. Efficacy assessment was based on larvae per gramme of faeces (LPG) counts, measured on days 28 +/- 2 following treatment and compared to counts on days -6 to -2. In total 24 cats treated either with Profender (n = 12) or with Panacur (n = 12) were included in the assessment of efficacy and safety. Mean LPG post-baseline counts (days 28 +/- 2) were 1.3 LPG for both Profender and Panacur, demonstrating similar efficacy of 99.38% for Profender and 99.29% for the control product. No treated animals showed adverse events. This trial demonstrated that both Profender spot-on formulation and oral paste Panacur are safe and effective in the treatment of aelurotrongylosis in cats. Future practical perspectives in feline medicine and the major advantages of the spot-on product compared to the oral paste are discussed.

Comparative efficacy and safety of two treatment regimens with a topically applied combination of imidacloprid and moxidectin (Advocate) against generalised demodicosis in dogs.

This laboratory study compared the efficacy of two treatment regimens using an imidacloprid (10%)/moxidectin (2.5%) topical formulation (Advocate, Bayer) on dogs with generalised demodicosis. Sixteen dogs were randomly allocated to two equal groups. One group was treated at 28-day intervals for 12 weeks and the second group at weekly intervals for 15 weeks. Mite numbers were estimated and demodectic lesions were evaluated on each dog before treatment and at approximately 28-day intervals thereafter. Consistently greater reduction in mite numbers was recorded for the weekly treatment regimen. Dogs treated at weekly intervals exhibited markedly fewer clinical signs and greater hair regrowth and weight gain than those treated at 28-day intervals. To assess the safety of a weekly treatment interval in dogs, a study was done in which the investigational compound was administered at weekly intervals at five times the recommended dose for a period of 16 consecutive weeks. Apart from transient erythema at the site of administration in one dog and scaliness of the skin in another, no clinical signs of toxicity could be observed. Assessment of 27 blood parameters indicated that only basophils were outside the reference values on days +13 and +69, during the safety trial period.

Treatment of naturally occurring, asymptomatic Giardia sp. in dogs with Drontal Plus flavour tablets.

The administration of three consecutive daily doses of the recommended 1x dose of Drontal Plus flavour tablets (Bayer) was examined for its effect on Giardia sp. cyst-shedding in 7 treated and 7 untreated random-source dogs. Dogs were treated on study days 0, 1 and 2. Cysts were quantified using direct immunofluorescent labelling on days -7, -5, -3 and -2, and daily from day 1 through 11. Three treated dogs never shed cysts again during the study, one shed again only on day 4, and the remaining three dogs started to shed again on days 8, 9 and 11. The mean numbers of cysts per gramme in the faeces of the treated dogs were significantly reduced (t-tests using log(10)(counts)) on days 1 and 2 (geometric means: controls = 447,000; treated = 1,050; p = 0.004) and days 3 to 8 (geometric means: controls = 23,400; treated 5.0; p < 0.001). Four controls that had been consistently positive, changed to negative status on day 11, and thus, on the final day of the trial, there were only three positive control and three positive treated dogs. Three consecutive days of treatment with Drontal Plus flavour tablets halted Giardia sp. cyst shedding by dogs. But starting six days post third treatment, some of the dogs started shedding cysts again. Since the prepatent period of Giardia sp. can be as short as 4 days, shedding of Giardia sp. cysts 6 days after treatment could be caused by a reinfection.

Synergistic effect of febantel and pyrantel embonate in elimination of Giardia in a gerbil model.

The objectives of the study were to determine the optimal dose of febantel, pyrantel embonate and a combination of febantel/pyrantel embonate required to effectively treat Giardia in a gerbil model and to determine if there is a synergistic effect with the two drugs. SPF gerbils were infected by oral inoculation with 105 Giardia duodenalis trophozoites (day 0). On days 5 to 7, animals (n = 6) were treated once daily via oral gavage with febantel, pyrantel embonate, febantel and pyrantel embonate, metronidazole or placebo. Gerbils were euthanised 24 hours after last treatment and duodenal trophozoites were enumerated on a haemocytometer to obtain a concentration of trophozoites/ cm of gut. Febantel alone, effectively eliminated Giardia trophozoites at 160 and 80 mg/kg. Pyrantel embonate did not eliminate Giardia from the animals but significantly reduced parasite counts at all dosages. Febantel combined with pyrantel embonate effectively eliminated Giardia trophozoites at 160, 80 and 40 mg/kg. Metronidazole did not eliminate Giardia trophozoites from the gut. All placebo-treated animals were heavily infected with Giardia trophozoites. It can be concluded that febantel is more effective in elimination of Giardia infections when combined with pyrantel embonate compared to the agents used alone.

Efficacy of imidacloprid 10%/moxidectin 1% (Advocate/Advantage Multi) against fleas (Ctenocephalides felis felis) on ferrets (Mustela putorius furo).

Ferrets (Mustela putorius furo) are becoming increasingly popular as pets and are kept in households with other pet animals such as dogs and cats, from which they may catch flea infestations with the predominant flea species Ctenocephalides felis. In this study, the efficacy of imidacloprid/moxidectin spot-on (Advocate/Advantage Multi) was investigated in the therapy and prevention of flea infestation in ferrets. Sixteen adult ferrets of varying weights and ages and of both sexes were included. Ferrets were infested with 50 fleas each on days -7, -1, 7, 14, 21, and 28. On study day -6, the animals were randomized into two groups based on body weight and flea count. Each ferret allocated to group 1 was treated with 0.4 ml of imidacloprid 10%/moxidectin 1% (Advocate/Advantage Multi). The ferrets in group 2 remained untreated. Flea counts were performed by combing 24 to 48 h after infestation. The primary efficacy criterion was the reduction in the number of fleas at each time point post treatment compared to the ferrets in the untreated control group. On day 1, the therapeutic efficacy was 100%. The preventative efficacy was 100% at 1 and 2 weeks post treatment, and it was >97% and >90% at 3 and 4 weeks post treatment. No local or systemic side effects were observed in any of the ferrets treated.

Field efficacy of phoxim 50% (ByeMite) against the poultry red mite Dermanyssus gallinae in battery cages stocked with laying hens.

Infestations with the poultry red mite Dermanyssus gallinae represent a major ectoparasite problem in poultry and can affect egg layers worldwide. There is presently a lack of an ectoparasiticide in Europe for poultry which can assure a 0-day withholding period for eggs. In this study, ByeMite (phoxim 50%, Bayer HealthCare, Animal Health Division) was administered to treat a D. gallinae infestation in a poultry house stocked with egg-laying hens kept in a cage system. A layer house was sprayed twice within a 7-day interval using a solution containing 2000 ppm phoxim and a similar layer house was used as an untreated control unit. Specially developed D. gallinae traps made of cardboard were used to assess the mite density in both layer houses during a 49-day period after the treatment. In order to collect mites, the traps were placed on days--1, 2, 6, 9, 13, 20, 34 and 48 and always removed after 24 h. The collected mites were counted and differentiated according to their developmental stage (mite eggs, larvae, nymphs, adults). Three days after the first spray treatment, the efficacy against all mite stages (larvae, nymphs, adults) was 96.1%, and from day 7 post-treatment until the end of the trial (day 49) the efficacy exceeded 99%. In contrast, in the untreated layer house (negative control group) the mite population showed a 400% increase. No treatment-related side effects in chickens were detectable. It is concluded that two administrations of ByeMite within a 7-day interval are highly effective against D. gallinae infestations in a stocked poultry house.

Clinical trials of efficacy of praziquantel horse paste 9% against tapeworms and its safety in horses.

The aim of this study with horses and a few ponies naturally infected with tapeworms was to confirm in clinical trials the efficacy and safety of a praziquantel horse paste 9%. The field trials were conducted in 1997 and 1998 in Canada, France, Germany and New Zealand. A secondary aim of the study in Canada was to determine if a 24h post-treatment fecal sample provides the best estimate of the prevalence of tapeworms in horses when using a fecal examination technique. Fecal samples were taken from each of 1062 animals at least three times pre-treatment (PRT). In Canada, fecal samples were examined using the Cornell-Wisconsin centrifugal flotation technique, and in France, Germany and New Zealand using a centrifugation/flotation technique. In each trial, the animals were randomized into two treatment groups: praziquantel horse paste 9% at 1mg/kg body weight (BW) and untreated. Fecal samples were taken from each animal nine times post-treatment and over a period of 5 weeks. In Canada, a fecal sample was taken also at 24h after treatment. Personnel examining the samples were "blinded" to treatment groups. On the day of treatment, each treated animal was examined for adverse reactions to the paste 10min after treatment and then hourly for 4h. Thereafter, each animal was examined once daily for 5 weeks. In Canada, Germany and New Zealand, the only tapeworm egg found was Anoplocephala perfoliata. In France, A. perfoliata was the most common species and a few animals had A. magna and Paranoplocephala mamillana. The prevalence of A. perfoliata among animals sampled in Canada, France, Germany and New Zealand was 51.8, 34.4, 13.1 and 26.2%, respectively. A total of 248 animals were treated with the praziquantel paste and all except one accepted it readily. There were 292 animals completing the study, 219 treated and 73 untreated. In Canada, Germany and New Zealand, the efficacy of the praziquantel horse paste 9% against A. perfoliata was 100%. In France, the efficacy against A. perfoliata, A. magna and P. mamillana was 90.9, 100 and 100%, respectively. The best estimate of prevalence for A. perfoliata in a herd was derived from fecal samples taken 24h after treatment. At 24h, 22 of 23 treated horses were positive, whereas on any day pre-treatment fewer horses were positive. Adverse reactions observed were mild to moderate colic and in only two treated horses.