Gabriele Petry

Evaluation of the Efficacy of Imidacloprid 10 % / Moxidectin 2.5 % (Advocate®, Advantage® Multi, Bayer) for the Prevention of Dirofilaria repens Infection in Dogs

The efficacy of imidacloprid 10 %/moxidectin 2.5 % (Advocate®, Advantage® Multi, Bayer) against experimental Dirofilaria (D.) repens infection in dogs was evaluated in a blinded, negative controlled randomised laboratory efficacy study. On SD (study day) 0, eight dogs received a spot-on treatment at a dose of 10 mg imidacloprid and 2.5 mg moxidectin per kg body weight. Another 8 dogs were left untreated. On SD 28 each dog was infected with approximately 75 infective D. repens larvae. Blood samples were collected every 4 weeks after treatment. A modified Knott test was conducted to detect mf (microfilaria). PCR analysis was performed with mf-positive blood samples. On SDs 245 and 246, all dogs were euthanised for detection of D. repens worms. Blood samples of all treated dogs were negative for mf at all sampling days. Blood samples of control dogs were positive for mf in 5 out of 8 control dogs. Individual mf counts ranged from 7 to 2800 mf/ml. In mf-positive blood samples, only D. repens was identified by PCR analysis. During necropsy D. repens worms could be detected in eight untreated control dogs (range: 3–21 worms per dog), whereas no worm could be detected in any of the treated dogs. These results indicate a 100 % preventive efficiency of a single spot-on treatment of imidacloprid 10 %/moxidectin 2.5 % in dogs against experimental infection with D. repens (L3 larvae). The product was well tolerated in all study animals, no treatment related adverse reactions were observed throughout the study.

Evaluation of the Adulticidal Efficacy of Imidacloprid 10 %/Moxidectin 2.5 % (w/v) Spot-on (Advocate®, Advantage® Multi) against Dirofilaria repens in Experimentally Infected Dogs

This study aimed to evaluate the efficacy of imidacloprid 10 %/moxidectin 2.5 % (w/v) spot-on (Advocate®/Advantage® Multi, Bayer) against adult Dirofilaria repens in a blinded, placebocontrolled randomised laboratory study. Twentyfour Beagle dogs were experimentally infected with approximately 75 infective D. repens larvae each on study day (SD) 0. Treatment was initiated on SD 228 after patency had been confirmed in 21 dogs, using a modified Knott Test. Eleven dogs received monthly treatments with imidacloprid/moxidectin at the minimum therapeutic dose (10 mg/kg imidacloprid and 2.5 mg/kg moxidectin) for six consecutive months and 12 control dogs were treated with a placebo formulation. Approximately one month after the last treatment, all dogs were euthanised and necropsied for the detection of D. repens worms. Eleven control dogs harboured live adult D. repens (range 2–11, geometric mean 5.44). Eight of 11 imidacloprid/moxidectin-treated dogs were free of live worms. The live worm count was reduced by 96.2 % (range 0–1, geometric mean 0.21). The majority of dead worms were encapsulated and degenerated. After the first treatment, Knott Tests were negative in all imidacloprid/moxidectin-treated dogs and this status was maintained in 10 dogs until study end. One dog showed a low microfilariae count (1 and 4/mL) on four occasions but was also negative before necropsy. The treatment was well tolerated by all study animals. It is concluded that six consecutive monthly treatments with imidacloprid/moxidectin spot-on are effective and safe against adult D. repens and provide an option for preventing the further spread of this zoonotic parasite.

Efficacy of moxidectin 2.5% and imidacloprid 10% in the treatment of ocular thelaziosis by Thelazia callipaeda in naturally infected dogs

Thelazia callipaeda (Spirurida, Thelaziidae) has been documented as agent of ocular infection in domestic animals (dogs and cats), wildlife (e.g., foxes, hares, rabbits), and humans. In the last two decades, this parasitosis has been increasingly reported in several European countries. Both adult and larval stages of the eyeworm are responsible for symptoms ranging from mild (e.g., lacrimation, ocular discharge, epiphora) to severe (e.g., conjunctivitis, keratitis, and corneal opacity or ulcers). The present study evaluated the clinical efficacy and safety of imidacloprid 10% and moxidectin 2.5% spot on (Advocate(®), Bayer Animal Health) in comparison to milbemycin oxime/praziquantel tablets (Milbemax(®), Novartis-Animal Health), as positive control, in the treatment of canine thelaziosis in naturally infected dogs and, a third group was used as an untreated control. Forty-seven dogs (27 females and 20 males) harbouring at least one live adult worm of T. callipaeda in one eye were enrolled from an endemic area of southern Italy. Each dog was then weighed and assigned in accordance with a random treatment allocation plan to one of the treatment groups (G1: imidacloprid 10% and moxidectin 2.5% spot on, G2: Untreated control and G3: milbemycin oxime/praziquantel tablets). On Day (D) 7, 14, 28 and 35 dogs were physically examined and the infection level was assessed by examination of both eyes, including conjunctival pouch and third eyelid for live adult T. callipaeda count and clinical scores. Dogs in G1 were treated on D0 and D28, whereas those in G3 on D0 and D7. Efficacy in G1 was 100% at each day post treatment (p<0.01). For the G3 group efficacy was 57.39% on D7 (p<0.05), 92.79% on D14 and 100% on D28 and D35 (p<0.01). The application of the spot on formulation moxidectin 2.5% and imidacloprid 10% was highly effective in the treatment of canine thelaziosis caused by T. callipaeda. Advocate(®) spot on can be recommended for the control of T. callipaeda infection, considering that this formulation is currently licensed in Europe for the treatment of a wide range of parasites affecting dogs.

Treatment of Naturally Notoedres cati-infested Cats with a Combination of Imidacloprid 10 % / Moxidectin 1 % Spot-on (Advocate® / Advantage® Multi, Bayer)

Notoedric mange (feline scabies) is a rare, but highly contagious disease of cats and kittens caused by Notoedres cati (N. cati), which can infest other animals and also humans. The study objective was to determine the efficacy and safety of 10 % imidacloprid/ 1 % moxidectin (Advocate®/Advantage® Multi spot-on for cats) against natural N. cati infestation in cats. Sixteen cats were randomly assigned to treatment group or negative control using pre-treatment mite counts. The treatment group received a single spot on treatment of the investigational veterinary product (IVP) according to label instructions. The control group stayed untreated. Five cats from the negative control were treated with the IVP at the end of the study and observed for 28 days to increase the treatment group. Skin scrapings and mite counts were performed 28 days post treatment (p.t.). Notoedric skin lesion assessments with clinical scoring were performed regularly. Five animals had to be removed prematurely from the study population due to different reasons. The number of viable N. cati mites in all treated animals 28 days p.t. was zero compared with 2.8 ± 3.0 in the negative control, being significantly lower for treated cats (p = 0.0019, Wilcoxon test). The resulting efficacy was 100 %. Clinical cure based on skin lesion assessment was achieved 28 days p.t. in 100 % of all treated animals completing 28 study days. The IVP was well tolerated and applied at the minimal therapeutic dose (10 mg imidacloprid/1 mg moxidectin/kg body weight) a high therapeutic efficacy in curing N. cati infestations and feline scabies clinical symptoms was recorded.

Prevention of Lactogenic Toxocara cati Infections in Kittens by Application of an Emodepside/Praziquantel Spot-on (Profender®) to the Pregnant Queen

This study aimed to evaluate the efficacy of an emodepside 2.1 % (w/v)/praziquantel 8.6 % (w/v) topical solution (ProfenderR spot-on for cats) in the prevention of lactogenic Toxocara cati infections. A controlled test was performed with two groups of 8 cats with confirmed pregnancy. All cats were infected with daily doses of 2000 T. cati eggs for 10 consecutive days starting 50 days post conception to produce an acute infection. Treatment was performed 60 days post conception. Queens in the treatment group received the emodepside/praziquantel solution at the minimum therapeutic dose (3 mg/kg emodepside and 12 mg/kg praziquantel), while the control group was treated with a placebo spot-on. Efficacy was evaluated 56 days post partum by necropsy of one randomly selected kitten of each litter and comparison of the worm burdens between the study groups. Additionally the necropsy results were supported by quantification of worms expelled with the faeces after deworming of the remaining kittens and all queens. The treatment in late pregnancy resulted in an efficacy of 98.7 % (p < 0.0001). All necropsied control kittens were infected (geometric mean 30.6). Seven of 8 kittens from treated mothers were free of T. cati (geometric mean 0.4). Worm counts after deworming reflected the results obtained at necropsy. No side effects of the treatment were observed. It is concluded that treatment with an emodepside/praziquantel spot-on solution during late pregnancy effectively prevents lactogenic transmission of T. cati to the offspring. The study design facilitated the generation of reliable data, while at the same time a minimum number of animals was sacrificed.

Evaluation of the Clinical Efficacy and Safety of a Spot-on Combination of Imidacloprid 10 % / Moxidectin 2.5 % (Advocate®, Advantage® Multi) in Comparison to an Untreated Control Group in the Treatment of Capillaria boehmi in Naturally Infected Dogs

Capillaria boehmi affects the upper respiratory tract of domestic and wild canids. The aim of the present study was to investigate the efficacy of imidacloprid 10 % / moxidectin 2.5 % spot-on (Advocate®, Advantage® Multi, Bayer) in dogs naturally infected by C. boehmi. Twenty dogs infected with C. boehmi were randomly allocated to two groups: T1 (10 dogs) received a single treatment of Advocate® using the recommended dose on day 0 and T2 (10 dogs) served as an untreated control group. The reduction of the faecal egg counts (EPG) from baseline (days -6 ± 2 and -2 ± 2) to study completion was set as the primary efficacy criterion; clinical assessments of the upper respiratory tract and a rhinoscopy to visualize the parasites were used as secondary efficacy criteria. Eight dogs in T1 were not shedding eggs on days 28 ± 2 (reduction of EPG 99.66 %). A second treatment was administered to two dogs still positive on days 30 ± 3. A second efficacy evaluation was performed on days 42 ± 2 (study completion), when the two dogs tested negative. The mean number of EPG at study completion was 0 in T1 and 368.49 in T2. The difference between the groups was statistically significant (P < 0.01). Treatment efficacy at study completion was 100 %. None of the T1 dogs showing clinical signs on day 0 were symptomatic on days 28 ± 2. No adverse events occurred. The results show that Advocate® is safe and effective in the treatment of canine nasal capillariosis. Original Article WAAVP_2017.indb 65 29.06.17 15:33 S66 EndoparasitEs EndoparasitEs

Efficacy of Emodepside plus Toltrazuril Oral Suspension for Dogs (Procox ® , Bayer) against Trichuris vulpis in Naturally Infected Dogs

The efficacy of emodepside plus toltrazuril oral suspension for dogs (Procox®, Bayer) against Trichuris vulpis was evaluated in a controlled, blinded and randomised laboratory study. Twenty naturally infected dogs were included. Dogs in the treatment group received the minimum therapeutic dose of 0.45 mg emodepside and 9 mg toltrazuril per kg body weight, while dogs in the control group were left untreated. Efficacy was calculated based on worm counts after necropsy on Day 7 post treatment. Additionally, all faeces were collected and examined for expelled worms. The treatment was 100 % effective. A total of 233 adult worms (geometric mean 17.0) and 3 immature adult worms were found in the control group at necropsy. Adequacy of infection was demonstrated. The treated group excreted a total of 186 adult worms within 2 days after treatment. Additionally, all dogs were co-infected with Uncinaria stenocephala. Efficacy against this parasite was 99.8 %. No side effects of the treatment were observed. This study demonstrates that in addition to the formerly proven efficacy against Toxocara canis, Ancylostoma caninum and Uncinaria stenocephala, emodepside plus toltrazuril suspension is also effective against T. vulpis and thus represents a convenient treatment option for dogs co-infected with whipworms and coccidia.