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Background: Rhipicephalus sanguineus sensu lato (s.l.) and Ctenocephalides felis are among the most important year-round ectoparasites of dogs. The persistent efficacy of one treatment with fluralaner injectable suspension (Bravecto ® 150 mg/ml powder and solvent for suspension for dogs, referred to as Bravecto ® injectable) was investigated in a negative-controlled, randomised, partially blinded 12-month laboratory study., Methods: A total of 20 dogs were randomly allocated to two equal groups (treatment and control). Treatment-group dogs were injected subcutaneously on study day 0 with the investigational veterinary product at the recommended dose of 15 mg fluralaner/kg body weight (0.1 mL/kg), whereas the control group dogs received saline solution (0.1 mL/kg). Each dog was infested with 50 (25 female, 25 male) adult R. sanguineus s.l. and 100 adult C. felis 2 days before treatment, 5 and 28 days after treatment, and then once monthly for a 12-month period. Live tick and flea counts were performed 48 h after treatment or subsequent infestation, respectively. Efficacy was determined by comparing arithmetic means of the treatment group tick and flea counts with those of the control group. Infestation was considered adequate if at least 25.0% of ticks and 40.0% of fleas were recovered from at least six dogs in the control group at the respective assessment times., Results: Adequate R. sanguineus s.l. and C. felis infestations of control group dogs were observed at each time point. Arithmetic mean treatment group values were significantly lower than those of the control group at all time points. The immediate efficacy when treating existing infestations of R. sanguineus s.l. and C. felis (infestation 2 days before treatment), was 49.7% and 89.7%, respectively. The persistent efficacy against post-treatment re-infestations was 94.4-100% against R. sanguineus s.l. and 92.2-100% against C. felis. Seven dogs in the control group developed flea allergy dermatitis due to the repeated re-infestations over the study period, whereas no dogs in the treatment group were affected. No clinically relevant side effects were observed over the entire study period., Conclusions: The fluralaner injectable suspension (Bravecto ® injectable) provides 1 year of efficacy against R. sanguineus s.l. and C. felis infestations in dogs following a single treatment, allowing once-yearly treatment, which can significantly improve owner compliance with year-round protection of dogs., (© 2024. The Author(s).)

Background: Canine acaricides with rapid onset and sustained activity can reduce pathogen transmission risk and enhance pet owner experience. This randomized, complete block design, investigator-masked study compared the speed of kill of Amblyomma americanum provided by three monthly-use isoxazoline-containing products., Methods: Eight randomized beagles per group were treated (day 0), per label, with sarolaner (combined with moxidectin and pyrantel, Simparica Trio™), afoxolaner (NexGard™), or lotilaner (Credelio™), or remained untreated. Infestations with 50 adult A. americanum were conducted on days - 7, - 2, 21, and 28, and tick counts were performed on day - 5 (for blocking), and at 4, 8, 12, 24, 48, and 72 h following treatment and subsequent infestations. Efficacy calculations were based on geometric mean live tick counts. A linear mixed model was used for between-group comparisons., Results: On day 0, only lotilaner significantly reduced an A. americanum infestation by 12 h (43.3%; P = 0.002). Efficacy of lotilaner and afoxolaner at 24 h post-treatment was 95.3% and 97.6%, respectively, both significantly different from sarolaner (74%) (P = 0.002, P < 0.001, respectively). On day 21, at 12 h postinfestation, lotilaner efficacy (59.6%) was significantly different from sarolaner (0.0%) (P < 0.001) and afoxolaner (6.3%) (P < 0.001). At 24 h, lotilaner efficacy (97.4%) was significantly different (P < 0.001) from sarolaner and afoxolaner (13.6% and 14.9%, respectively). On day 28, at 12 h postinfestation, lotilaner efficacy (47.8%) was significantly different from sarolaner (17.1%) (P = 0.020) and afoxolaner (9.0%) (P = 0.006). At 24 h, lotilaner efficacy (92.3%) was significantly different from sarolaner 4.9% (P < 0.001) and afoxolaner (0.0%) (P < 0.001). Speed of kill for sarolaner and afoxolaner, but not lotilaner, significantly declined over the study period. Following reinfestation on day 28, neither sarolaner nor afoxolaner reached 90% efficacy by 48 h. By 72 h, sarolaner efficacy was 97.4% and afoxolaner efficacy was 86.3%. Only lotilaner achieved ≥ 90% efficacy by 24 h post-treatment and 24 h postinfestation on days 21 and 28. Time to ≥ 90% efficacy following new infestations consistently occurred 24-48 h earlier for lotilaner compared with sarolaner or afoxolaner., Conclusions: Credelio (lotilaner) has a more rapid onset of acaricidal activity against A. americanum than Simparica Trio (sarolaner-moxidectin-pyrantel) and NexGard (afoxolaner). Only lotilaner's speed of tick kill is sustained throughout the dosing period., (© 2024. The Author(s).)

Background: Triatoma infestans, Triatoma brasiliensis, Triatoma pseudomaculata and Rhodnius prolixus are vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. Chickens serve as an important blood food source for triatomines. This study aimed to assess the insecticidal activity of fluralaner (Exzolt ® ) administered to chickens against triatomines (R. prolixus, T. infestans, T. brasiliensis and T. pseudomaculata)., Methods: Twelve non-breed chickens (Gallus gallus domesticus) were randomized based on weight into three groups: negative control (n = 4); a single dose of 0.5 mg/kg fluralaner (Exzolt ® ) (n = 4); two doses of 0.5 mg/kg fluralaner (Exzolt ® ) (n = 4). Nymphs of 3rd, 4th and 5th instars of R. prolixus, T. infestans, T. brasiliensis and T. pseudomaculata (all n = 10) were allowed to feed on chickens before treatment, and at intervals of 1, 7, 14, 21, 28, 35 and 56 days after treatment, with insect mortality determined., Results: Treatment with two doses of fluralaner showed higher insecticidal efficacy against R. prolixus, T. infestans and T. brasiliensis compared to the single-dose treatment. Similar insecticidal efficacy was observed for T. pseudomaculata for one and two doses of fluralaner. Insecticidal activity of fluralaner (Exzolt ® ) against triatomine bugs was noted up to 21 and 28 days after treatment with one and two doses of fluralaner, respectively., Conclusions: The results demonstrate that treatment of chickens with fluralaner (Exzolt ® ) induces insecticidal activity against triatomines for up to 28 days post-treatment, suggesting its potential use as a control strategy for Chagas disease in endemic areas., (© 2024. The Author(s).)

Background: Tungiasis is a neglected tropical disease caused by the adult female sand flea (Tunga penetrans). Dogs are considered important reservoirs of T. penetrans in Brazil. The aim of this study was to determine the monthly insecticidal efficacy of a single oral administration of fluralaner at a dose of 10-18 mg/kg (Bravecto ® 1-Month, also registered as Defenza ® in some countries; MSD Animal Health) in dogs naturally infested with T. penetrans., Methods: This clinical trial was conducted in a rural community located in Ilhéus, Bahia, Brazil. A total of 64 dogs were selected and distributed in a completely randomized design between a treated group (TG) that received one single dose of Bravecto ® 1-Month (Defenza ® ) and a negative control group (CG) that received no treatment. Each group was composed of 32 dogs. The evaluations took place on days 0, 7 ± 2, 14 ± 2, 21 ± 2, 28 ± 2, 35 ± 2, and 42 ± 2 post treatment, in which the dogs were inspected to evaluate the infestation stage and classify lesions associated with tungiasis. The primary efficacy was determined from the percentage of treated dogs free of fleas (stage II and III lesions) after administration of the formulation at each evaluation time. Secondary efficacy was based on the number of active lesions (stages II and III) in each group at each evaluation time. The clinical condition of the animals was defined based on the Severity Score for Acute Dog Tungiasis (SCADT), which is related to the number and severity of lesions., Results: The primary efficacy of the product was greater than 95.0% from days 7 to 21 and reached 100.0% between days 28 and 42, with a significant association between treatment and infestation decline (P < 0.025) between days 7 and 42. Secondary drug efficacy was greater than 99.9% from days 7 to 21, reaching 100.0% between days 28 and 42 (P < 0.05). The treated dogs also scored lower on the SCADT than the control animals did during the entire clinical evaluation period (P < 0.05)., Conclusions: A single administration of Bravecto ® 1-Month (Defenza ® ) was effective in eliminating Tunga penetrans infestations, as well as in preventing parasitism for at least 42 days after treatment., (© 2024. The Author(s).)

Background: Aelurostrongylus abstrusus is one of the most important respiratory nematodes of felines. Infections may lead to respiratory clinical signs with varying severity or even death, emphasizing the need for preventive treatment of cats with outdoor access to circumvent patent infections., Methods: Therefore, the preventive efficacy of a spot-on formulation of 280 mg/ml fluralaner and 14 mg/ml moxidectin (Bravecto ® Plus spot-on solution for cats, MSD) against A. abstrusus was evaluated in a negative controlled, randomized and partially blinded efficacy study with 28 purpose-bred cats in a non-terminal design. In three different treatment regimes, the minimum recommended dose of 40 mg fluralaner and 2.0 mg moxidectin/kg bodyweight (BW) was administered once at 12, 8 or 4 weeks (study group G1, G2 and G3, respectively) prior to experimental infection with 300 third-stage A. abstrusus larvae, while G4 served as placebo-treated control., Results: From 30 to 46 days post infection (dpi; SD 114 to 130), faeces were sampled to monitor first-stage larvae (L1) excretion for efficacy determination. Secondary efficacy criteria, including respiratory parameters, serological antibody levels and computed tomography (CT) findings, were assessed once before enrolment (SD -7 to -1) and before infection (SD 75 to 83). After infection, CT evaluation was performed once at 47-50 dpi (SD 131 to 134), and respiratory parameters and antibody levels were regularly assessed twice or once a week, respectively (1 up to 78 dpi, SD 85 up to 162). All animals in the control group excreted L1 by 33-37 dpi and remained positive throughout the study period from 41 to 46 dpi (SD 125 to 130). In the treatment groups, only one animal each of G1 and G2 excreted L1 at two consecutive days, and four cats of G1, two of G2 and three of G3 were positive on single occasions. While the geometric mean (GM) of the maximum number of excreted L1 per 5 g of faeces was 7380.89 in the control group (G4), GMs were significantly lower in the treatment groups with 1.63 in G1, 1.37 in G2 and 0.79 in G3. Thus, based on GMs, the reduction in excreted L1 exceeded 99.9% in all three treatment groups. Based on CT severity scores, all lungs of the animals of the control group showed severe pulmonary changes post infection, whereas lungs of the cats of the treatment groups were either unaltered (4 animals), mildly (11 animals), or moderately altered (5 animals). Moreover, seroconversion was observed in all cats of the control group, but not in those of the treatment groups., Conclusions: The combination of diagnostic methods used in this non-terminal study yielded coherent and reliable results. A single administration of Bravecto ® Plus spot-on solution for cats was well tolerated and effective in the prevention of aelurostrongylosis for at least 12 weeks., (© 2024. The Author(s).)

Background: Orally administered fluralaner (13.64% w/w) is effective for treating canine generalized demodicosis. A study was initiated to assess the efficacy of a novel 5.46% w/w fluralaner chewable tablet formulation for monthly administration in the treatment of this disease., Methods: Client-owned dogs diagnosed with generalized demodicosis were acclimatized to laboratory conditions and randomized to receive either orally administered fluralaner (Bravecto ® 1-Month) (10.0 to 14.4 mg/kg body weight) (n = 8) or topical imidacloprid-moxidectin (Advocate ® for dogs, Elanco) applied per label on days 0, 28, and 56 (n = 8), or more frequently for ongoing severe demodicosis. On days -2, 28, 56, and 84, deep skin scrapings were taken from five sites on each dog for mite identification and counting, and semiquantitative clinical assessments of generalized demodicosis were recorded. Primary efficacy was based upon arithmetic mean mite count reductions relative to pre-treatment., Results: By day 28, mean pre-treatment mite counts, > 600 in both groups, were significantly reduced by 99.7% and 89.5% (both P < 0.001) in the fluralaner and imidacloprid-moxidectin groups, respectively. Parasitological cure (100% reduction in mite counts on days 56 and 84) was achieved in all fluralaner-treated dogs (100%) and in two imidacloprid-moxidectin-treated dogs (25%). In the imidacloprid-moxidectin group, the reduction in mean mite counts was 89.5% (day 28), 94.4% (day 56), and 97.5% (day 84). All study dogs were free of crusts on days 56 and 84. Scales resolved by day 84 in all fluralaner-treated dogs and in three imidacloprid-moxidectin-treated dogs. All fluralaner-treated dogs and five imidacloprid-moxidectin-treated dogs had > 90% hair regrowth on day 84., Conclusion: Three consecutive monthly orally administered treatments with fluralaner (5.46% w/w) flavored chewable tablets (minimum dose rate 10 mg/kg body weight) eliminated Demodex canis mites from dogs diagnosed with generalized demodicosis., (© 2022. The Author(s).)

Background: Dogs are the reservoir host of Leishmania infantum, the agent of zoonotic visceral leishmaniasis (VL), which is transmitted by the bite of phlebotomine sand flies. The sand fly Phlebotomus perniciosus is the main vector of zoonotic VL in the western Mediterranean region. Fluralaner has been shown to effectively kill this vector. The aim of this study was to evaluate the insecticidal efficacy of oral fluralaner in dogs bitten by P. perniciosus., Methods: Two parallel-group, negative-controlled, randomized, masked laboratory trials with equivalent designs were performed in two different locations using two different pathogen-free laboratory-bred P. perniciosus strains for the challenge. In each trial, 12 purpose-bred beagles, initially ranked on natural attractiveness to sand flies, were randomly allocated to two groups (6 animals/group). Dogs in one group received fluralaner orally at the approved dose on day 0, and dogs in the control group were not treated. Each dog was subsequently exposed to an average of 70 unfed live sand fly females on days 1, 28, 56 and 84. Viability of blood-fed females was then evaluated for up to 96 h after exposure, and insecticidal efficacy was measured as the survival rate of flies fed on the fluralaner-treated dogs versus that of dogs in the control group. Significance was calculated for the proportion of live fed sand fly counts from treated versus control group dogs., Results: Comparison of the survival proportions between treated and control groups showed that fluralaner insecticidal efficacy was highly significant in both trials (P < 0.001 or P < 0.01 in different assessments) through to day 56. In the first trial, efficacy reached 100% on days 1 and 28, and 99.1% on day 56; in the second trial, the insecticidal efficacy was 98.5, 100 and 85.9%, respectively on the same days. On day 84, efficacy was in the range of 53-57% (P < 0.05) in the first trial and 0% in the second trial., Conclusion: A single oral fluralaner administration to dogs under laboratory conditions results in strong and reproducible insecticidal efficacy against P. perniciosus for at least 8 weeks., (© 2021. The Author(s).)

Background: Triatomines are responsible for the vector transmission of the protozoan parasite Trypanosoma cruzi, which causes Chagas disease. Triatoma brasiliensis is the main vector of the parasite in Brazil, and dogs are an important reservoir of the parasite. The aim of this study was to evaluate the insecticidal effect of fluralaner (Bravecto ® ) on T. brasiliensis after a blood meal in treated dogs., Methods: Healthy mongrel dogs (n = 8) were recruited from the Zoonoses Control Center (ZCC) in the city of Natal, Rio Grande do Norte, Brazil, and randomized into two groups, a fluralaner (Bravecto ® )-treated group (n = 4) and a control group (n = 4). Colony-reared third-, fourth- and fifth-instar nymphs of T. brasiliensis nymphs (n = 10) were allowed to feed on dogs from both groups for 30-40 min, once monthly, for up to 12 months. Bug mortality was observed up to 5 days after each blood meal., Results: Mortality in triatomines which had a blood meal on fluralaner (Bravecto ® )-treated dogs was 100% for up to 7 months after treatment, with mortality decreasing to 66.4% after 8 months, 57% after 9 months, 35% after 10 months, 10% after 11 months and 0% after 12 months. The mortality of triatomines that fed on non-treated control dogs was always ≤ 2.5%., Conclusions: Our results suggest that fluralaner (Bravecto ® ) treatment of dogs induces long-term mortality of T. brasiliensis after the blood meal. This is a potential approach to be used to control vector transmission of T. cruzi, the etiological agent of Chagas disease, especially in endemic areas., (© 2021. The Author(s).)

Background: The study objective was to examine cat owner ectoparasiticide purchases in the United States and estimate the impact of purchase gaps on timely ectoparasite protection administration. These purchase gaps lead to periods of time when cats are unprotected from ectoparasites., Methods: Ectoparasiticide purchase transactions for individual cats from 671 U.S. veterinary clinics from January 1, 2017 through June 30, 2019 were evaluated to determine time "gaps" between doses of ectoparasiticides purchased in a defined 12-month period. Ectoparasiticides examined were topically applied products that contained fluralaner, fipronil/(S)-methoprene/pyriproxyfen, imidacloprid/pyriproxyfen or selamectin as active ingredients. The duration of protection following administration of one dose was 8-12 weeks for the fluralaner-containing product and one month for the other products., Results: Ectoparasiticide purchase records were obtained from 114,853 cat owners and analysis found that most owners bought ≤ 6 months of protection during the year, with 61-75% (depending on the product) purchasing just 1-3 months of protection. The size of the average purchase gap was determined for all dose combinations out to 12 months of protection (5-7 doses for fluralaner and 12 doses for the other three products dosed monthly. The largest gaps occurred between the first and second doses and the second and third doses. Average purchase gaps for the four different products between doses 1 and 2 ranged from 11.2 to 13.9 weeks and between doses 2 and 3 ranged from 7.7 to 12.2 weeks. The fraction of purchases separated by gaps and the average length of the gap tended to decrease with increasing number of doses purchased. Owners purchasing the 8 to 12-week duration product containing fluralaner provided ectoparasite protection ("doses plus gap period") for a larger proportion of each 2-dose period compared with owners purchasing products administered monthly., Conclusions: When cat owners purchase flea and tick medication, gaps between subsequent purchases reduces the proportion of time ectoparasite protection can be provided. The duration of the gap between doses has an impact on the effectiveness of flea/tick medication because it inserts a period without flea and tick protection between doses of flea and tick medication. The gaps between purchases were shorter and the period of ectoparasite protection was larger for owners purchasing a 12-week product than for owners purchasing a monthly product.

Background: Capillaria aerophila and Capillaria boehmi parasitize the respiratory system of wild and domestic carnivores. Capillaria aerophila inhabits the trachea and bronchi of dogs and cats, while C. boehmi affects the nasal cavities and sinuses of dogs. In dogs the infection may be subclinical or characterized by varying respiratory distress., Methods: The present study evaluated the efficacy of an oral formulation containing milbemycin oxime and afoxolaner (NEXGARD SPECTRA ® ) in dogs naturally infected with C. aerophila and/or C. boehmi from three enzootic areas of Italy. Dogs were enrolled pending fecal examination and molecular confirmation of respiratory capillarioses. Dogs were allocated in two groups: Group 1 (G1, 25 dogs), treated with a negative control product with no anthelmintic activity (afoxolaner, NEXGARD ® ), and Group 2 (G2, 26 dogs), treated with NEXGARD SPECTRA ® . At the day of treatment administration (Day 0), all dogs were clinically examined. Dogs were again subjected to clinical and fecal examinations at Days 28 (± 4) and 56 (± 2). The primary criterion for treatment efficacy was the reduction of fecal Capillaria egg counts in G2 compared with G1. The regression of/recovery from baseline clinical signs was considered as a further efficacy criterion., Results: Percentage reduction of fecal Capillaria egg counts in the NEXGARD SPECTRA ® group compared to the control group was > 97% on Day 28 and 100% on Day 56, respectively (p < 0.05 for both time points). Twelve of the 13 dogs in the NEXGARD SPECTRA ® group with respiratory signs prior to treatment were free of clinical signs at the end of the study. Conversely, the six control group dogs with respiratory signs prior to treatment remained symptomatic., Conclusions: Results of the present study showed that NEXGARD SPECTRA® was safe and highly efficacious in the reduction of C. aerophila and C. boehmi eggs after one treatment with a complete reduction of the egg output after the second administration associated with a recovery from respiratory signs.

Background: The feline lungworm Aelurostrongylus abstrusus affects the lower respiratory tract in cats worldwide. As infections may lead to chronic respiratory changes or even death, preventive treatment in cats with outdoor access is warranted., Methods: The preventive efficacy of a spot-on solution (Bravecto® Plus spot-on solution for cats, MSD) against cat aelurostrongylosis was evaluated using three different preventive treatment regimes in a negative controlled, randomized and partially blinded laboratory efficacy study with 31 purposed-bred cats. The minimum recommended dose of 2.0 mg moxidectin + 40 mg fluralaner/kg bodyweight was applied once 12 (Group [G]1), 8 (G2) or 4 (G3) weeks before experimental infection with 300 third-stage larvae (L3) of A. abstrusus. Another group served as untreated control (G4). Individual faecal samples were analysed as of day 30 post infection (pi) to monitor larvae excretion. Necropsy was performed at days 47-50 pi. The lungs were examined macroscopically for pathological findings and (pre-)adult worms were counted to assess preventive efficacy., Results: Beginning at day 32-40 pi, all cats of the control group were constantly shedding larvae of A. abstrusus, whereas only one animal of G1 excreted larvae at several consecutive days. In addition, two cats of G1 and G3 and three of G2 were positive on a single occasion. The geometric mean (GM) of the maximum number of excreted larvae was 7574.29 in the control group compared to 1.10 (G1), 1.19 (G2) and 0.53 (G3), resulting in a GM reduction of > 99.9% in all treatment groups. All lungs of the control animals showed severe or very severe alterations at necropsy, while in 94.44% of the treated cats lung pathology was rated as absent or mild. The GM number of (pre-)adult A. abstrusus retrieved from the lungs was 26.57 in the control group, 0.09 in G1 and 0.00 in G2 and G3. Thus, GM worm count reduction was 99.66% in G1 and 100% in G2 and G3., Conclusions: A single application of Bravecto® Plus spot-on solution at a dose of 2.0 mg moxidectin + 40 mg fluralaner/kg bodyweight reliably prevents cat aelurostrongylosis for at least 12 weeks.

Background: Sarcoptic mange causes significant animal welfare and occasional conservation concerns for bare-nosed wombats (Vombatus ursinus) throughout their range. To date, in situ chemotherapeutic interventions have involved macrocytic lactones, but their short duration of action and need for frequent re-administration has limited treatment success. Fluralaner (Bravecto®; MSD Animal Health), a novel isoxazoline class ectoparasiticide, has several advantageous properties that may overcome such limitations., Methods: Fluralaner was administered topically at 25 mg/kg (n = 5) and 85 mg/kg (n = 2) to healthy captive bare-nosed wombats. Safety was assessed over 12 weeks by clinical observation and monitoring of haematological and biochemical parameters. Fluralaner plasma pharmacokinetics were quantified using ultra-performance liquid chromatography and tandem mass spectrometry. Efficacy was evaluated through clinical assessment of response to treatment, including mange and body condition scoring, for 15 weeks after topical administration of 25 mg/kg fluralaner to sarcoptic mange-affected wild bare-nosed wombats (n = 3). Duration of action was determined through analysis of pharmacokinetic parameters and visual inspection of study subjects for ticks during the monitoring period. Methods for diluting fluralaner to enable 'pour-on' application were compared, and an economic and treatment effort analysis of fluralaner relative to moxidectin was undertaken., Results: No deleterious health impacts were detected following fluralaner administration. Fluralaner was absorbed and remained quantifiable in plasma throughout the monitoring period. For the 25 mg/kg and 85 mg/kg treatment groups, the respective means for maximum recorded plasma concentrations (C max ) were 6.2 and 16.4 ng/ml; for maximum recorded times to C max , 3.0 and 37.5 days; and for plasma elimination half-lives, 40.1 and 166.5 days. Clinical resolution of sarcoptic mange was observed in all study animals within 3-4 weeks of treatment, and all wombats remained tick-free for 15 weeks. A suitable product for diluting fluralaner into a 'pour-on' was found. Treatment costs were competitive, and predicted treatment effort was substantially lower relative to moxidectin., Conclusions: Fluralaner appears to be a safe and efficacious treatment for sarcoptic mange in the bare-nosed wombat, with a single dose lasting over 1-3 months. It has economic and treatment-effort-related advantages over moxidectin, the most commonly used alternative. We recommend a dose of 25 mg/kg fluralaner and, based on the conservative assumption that at least 50% of a dose makes dermal contact, Bravecto Spot-On for Large Dogs as the most appropriate formulation for adult bare-nosed wombats.

Background: Successful canine sarcoptic mange treatment requires immediate efficacy to eliminate active mites, and sustained activity to prevent re-infestation from in-contact animals and fomites. With extended acaricidal activity, fluralaner has been shown to be effective for treating this disease. To confirm this potential under field conditions, two fluralaner formulations were administered to mite-infested, client-owned dogs., Methods: Households qualified for inclusion if they had at least one dog positive for Sarcoptes scabiei mites, confirmed by skin scraping, and at least one dog with clinical signs evocative of sarcoptic mange. Households were allocated to groups of dogs to receive a single treatment with either oral (Bravecto ® chewable tablets, MSD Animal Health) or topical (Bravecto ® Spot-on, MSD Animal Health), fluralaner at a dose of ≥ 25 mg/kg (range 25-56 mg/kg) on Day 0, or two treatments with oral sarolaner (Simparica ® tablets, Zoetis) (Days 0 and 28) at ≥ 2 mg/kg (2-4 mg/kg). All dogs in each household were treated with the same product. On the enrolment day and subsequently on Days 28, 56 and 84, deep skin scrapings were taken from at least five different body areas judged to be most likely to have active mite infestation. At each visit, the dog's mange-associated skin lesions were recorded, and pruritus level was assessed., Results: There were 98 participating households and 135 dogs enrolled across Albania, France, Italy and Portugal. On Day 28, more than 90% of dogs in each group were negative for mites. On Days 56 and 84, all study dogs were free of mites and most dermatological signs of sarcoptic mange had resolved. There were no treatment-related adverse events in any group., Conclusions: A single treatment of client-owned, sarcoptic mange-affected dogs with either fluralaner chewable tablets or fluralaner spot-on formulation proved a safe and effective treatment of infestations with S. scabiei var. canis, maintained through 84 days (12 weeks) after treatment.

Background: The Australian paralysis tick, Ixodes holocyclus, causes tick paralysis in dogs and cats in the eastern coastal regions of Australia. Prevention is the best option to protect dogs against this potentially fatal disease and sarolaner provides rapid and sustained efficacy against I. holocyclus. In this laboratory study, the efficacy of two combination endectocides containing sarolaner + moxidectin + pyrantel (Simparica Trio™) and afoxolaner + milbemycin (NexGard Spectra ® ) was evaluated against an artificial infestation of I. holocyclus., Methods: Twenty-four (n =24) foxhounds were randomly allocated to three treatment groups and artificially infested with 30 adult female viable ticks on Days - 1, 7, 14, 21, 28 and 35. On Day 0, dogs in each treatment group were treated with either Drontal ® (control group), Simparica Trio™ at the label dose to provide minimum doses of sarolaner (1.2 mg/kg), moxidectin (24 µg/kg) and pyrantel (5 mg/kg) or NexGard Spectra ® to provide minimum doses of afoxolaner (2.5 mg/kg) and milbemycin (0.5 mg/kg). Live tick counts were performed at 48 and 72 hours after treatment and after each re-infestation on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for control dogs based on geometric means., Results: Against an existing infestation, efficacy of both Simparica Trio™ and NexGard Spectra ® was 99.6% and 100% at 48 and 72 h time points, respectively (P = 1.000). Against subsequent weekly infestations, treatment with Simparica Trio™ and NexGard Spectra ® resulted in efficacy of ≥ 97.7% and ≥ 95.5% (P ≥ 0.0911), respectively at the 48 h time point and at the 72 h time point, Simparica Trio™ and NexGard Spectra ® resulted in efficacy of ≥ 99.0% and ≥ 98.4% (P ≥ 0.0511), respectively. There were no treatment-related adverse events in the study., Conclusions: Single doses of Simparica Trio™ and NexGard Spectra ® were highly efficacious and provided comparable efficacy against the Australian paralysis tick, I. holocyclus for up to 35 days.

Background: Amblyomma americanum and Rhipicephalus sanguineus (sensu lato) nymphs commonly feed on and transmit pathogens to dogs (Canis familiaris). Control of immature and adult tick life stages is necessary to fully protect animals. We evaluated efficacy of oral fluralaner (Bravecto ® ) against induced infestations with A. americanum and R. sanguineus (s.l.) nymphs on dogs in two experiments., Methods: In each experiment, 10 dogs were administered oral fluralaner chewable tablets one time on Day 0 at a targeted minimum dose of 25 mg/kg body weight and 10 dogs remained non-treated controls. Dogs were infested with two groups of 50 A. americanum nymphs and two groups of 50 R. sanguineus (s.l.) nymphs on Days -1, 6, 28, 56 and 84. At 48 h and 72 h post-infestation, nymphs were collected from dogs, assessed as live or dead, and enumerated into categories defining attachment and engorgement status. Fluralaner efficacy was determined in separate analyses against all live nymphs and against live-fed nymphs, i.e. live nymphs that were attached to dogs at the time of collection and/or were engorged. Fluralaner was considered effective when mean numbers of live ticks were reduced in fluralaner-treated dogs by ≥ 90%., Results: Fluralaner efficacy against all live and live-fed A. americanum nymphs in the first experiment was > 94% on all collection days. Efficacy against all live R. sanguineus (s.l.) nymphs in the first experiment was  > 96% on all collection days  excluding the 48 h counts for infestations on Days 28 (83.7%), 56 (82.9%) and 84 (86.7%); efficacy against live-fed R. sanguineus (s.l.) nymphs was > 95% on all 48 h/72 h count days. Fluralaner efficacy against all live A. americanum nymphs in the second experiment was > 93% on all collection days for 8 weeks excluding the 48 h count for infestation on Day 56 (87.8%); efficacy against live-fed A. americanum nymphs was > 91% on all count days for 8 weeks. Efficacy against all live R. sanguineus (s.l.) nymphs in the  second experiment was > 91% on all 72 h collection days  except for infestations on Days 28 (76.8%) and 56 (86.3%); efficacy against live-fed R. sanguineus (s.l.) nymphs was 100% on all 72 h count days., Conclusions: A single administration of oral fluralaner to dogs is effective against A. americanum and R. sanguineus (s.l.) nymphs for up to 12 weeks.

Background: Recent reports indicate that the isoxazoline compounds have the potential to provide safe and effective treatment of canine generalized demodicosis, a condition that has been traditionally difficult to cure. Controlled field studies are needed to confirm this potential. A study was therefore initiated to investigate the efficacy of a single oral or spot-on treatment with fluralaner, an isoxazoline, compared with multiple topical treatments with imidacloprid-moxidectin, in dogs naturally affected by generalized demodicosis., Methods: Veterinary clinics in 5 European countries enrolled 134 dogs diagnosed with generalized demodicosis. Dogs were randomized to treatment with either fluralaner chewables, fluralaner spot-on, or topical imidacloprid-moxidectin in a 2:2:1 ratio. Both fluralaner formulations were administered once, at the approved dose rate, on Day 0. Imidacloprid-moxidectin was administered per label on Day 0, and every 4 weeks, more frequently if necessary. At each visit (Days 0, 28, 56, 84), dogs were monitored for demodectic mites using deep skin scrapings and observed for health and for severity of skin lesions. Treatment was considered efficacious if more than 90% of the dogs were free of live mites at both Days 56 and 84., Results: Of 124 dogs completing the study, 57 were diagnosed with juvenile-onset demodicosis and 67 with the adult-onset form. A single treatment with oral or spot-on fluralaner was efficacious, each eliminating mites from at least 98.0% of treated dogs on Days 56 and 84. Against juvenile-onset demodicosis, efficacy of the oral and spot-on formulations was 96.0% and 100%, respectively, and against adult-onset demodicosis 100% and 96.7%. Multiple administrations of imidacloprid-moxidectin were not efficacious, eliminating mites from 87.5% of dogs (92.0% with juvenile-onset demodicosis cured; 81.8% with adult-onset demodicosis). All groups showed a marked reduction in skin lesions by Day 28, with continuing clinical improvement at each subsequent visit through Day 84. There were no treatment-related adverse events., Conclusions: A single administration of fluralaner chewables or fluralaner spot-on is highly effective against with juvenile-onset and adult-onset forms of generalized canine demodicosis. Topically applied imidacloprid-moxidectin at weekly to monthly intervals over the 84-day study did not achieve the proportion of mite-free dogs required to demonstrate efficacy.

Background: One randomized, controlled clinical field study was conducted in 18 general veterinary practices throughout the USA to evaluate the safety and efficacy of a novel oral chewable combination tablet, Simparica Trio™, containing sarolaner, moxidectin and pyrantel for the treatment and prevention of fleas on dogs., Methods: Client-owned dogs, from households of three or fewer dogs were eligible for enrollment. Four hundred and twenty-two dogs from 251 households were enrolled. Households were randomly assigned in a 2:1 ratio to treatment with either Simparica Trio™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) or afoxolaner (NexGard ® , Boehringer-Ingelheim) at the label dose. One dog per household was selected as the primary dog for efficacy evaluations. Treatments were dispensed and dogs were dosed in their home environment on Day 0 and on approximately Day 30. Flea counts and examination for clinical signs of flea allergy dermatitis (FAD) were performed at the initial visit the day before or on Day 0 prior to treatment and on Days 30 and 60. Additionally, all dogs were examined for general health at each visit and blood and urine were collected for clinical pathology at screening and Day 60., Results: Simparica Trio™ reduced geometric mean live flea counts by 99.0% by Day 30 and by 99.7% by Day 60. As a result of the rapid reduction in flea infestations, clinical signs associated with FAD substantially improved following treatment. Simparica Trio™ was well-tolerated and a diverse range of concomitant medications were administered to dogs during the course of the study. Simparica Trio™ chewable tablets were well-accepted by dogs, with the majority of flavored chewable tablets (91.9%) voluntarily consumed by free choice without, or when offered in food., Conclusions: Simparica Trio™ administered orally once monthly for two consecutive treatments was safe and effective against natural flea infestations and substantially improved clinical signs associated with FAD in client-owned dogs in a field study conducted in the USA.

Background: Lyme disease (LD) is an increasing public health threat in temperate zones of the northern hemisphere, yet relatively few methods exist for reducing LD risk in endemic areas. Disrupting the LD transmission cycle in nature is a promising avenue for risk reduction. This experimental study evaluated the efficacy of fluralaner, a recent oral acaricide with a long duration of effect in dogs, for killing Ixodes scapularis ticks in Peromyscus maniculatus mice, a known wildlife reservoir for Borrelia burgdorferi in nature., Methods: We assigned 87 mice to 3 fluralaner treatment groups (50 mg/kg, 12.5 mg/kg and untreated control) administered as a single oral treatment. Mice were then infested with 20 Ixodes scapularis larvae at 2, 28 and 45 days post-treatment and we measured efficacy as the proportion of infesting larvae that died within 48 h. At each infestation, blood from 3 mice in each treatment group was tested to obtain fluralaner plasma concentrations (C p )., Results: Treatment with 50 mg/kg and 12.5 mg/kg fluralaner killed 97% and 94% of infesting larvae 2 days post-treatment, but no significant effect of treatment on feeding larvae was observed 28 and 45 days post-treatment. Mouse C p did not differ significantly between the two tested doses. Mean C p decreased from 13,000 ng/ml in the 50 mg/kg group and 4000 ng/ml in the 12.5 mg/kg group at Day 2 to < 100 ng/ml in both groups at Day 45., Conclusions: We provide the first evidence that fluralaner is effective for killing immature ticks in Peromyscus mice, a first step in evaluating its potential for treating wild rodents as a public health intervention to reduce LD risk in endemic areas.

Background: Canine demodicosis is classified as localised or generalised according to the extent of the disease. Chronic generalised demodicosis is a difficult skin disease to treat and unlikely to resolve without therapy. This laboratory study compared the efficacy of two topical spot-on medications, fluralaner or a combination of imidacloprid and moxidectin, against naturally acquired generalised demodicosis in dogs., Methods: Sixteen client-owned dogs with naturally acquired generalised demodicosis were randomly allocated to 1 of 2 study groups consisting of 8 dogs each. On Day 0, dogs in 1 group were treated once with fluralaner spot-on solution. Dogs in the other group were treated with the imidacloprid/moxidectin spot-on solution on 3 occasions (Days 0, 28 and 56) or weekly in severe cases. Mites were counted in skin scrapings and demodectic lesions were evaluated on each dog before treatment, and at 28-day intervals over the 12-week period. Deep skin scrapings were made from the same 5 sites on each dog at each examination., Results: After administration of fluralaner, miticidal efficacy was 99.7% at Day 28, > 99.9% at Day 56 and 100% at Day 84. Efficacy in dogs treated topically with the imidacloprid and moxidectin combination, was 9.8% at Day 28, 45.4% at Day 56 and 0% at Day 84, and was significantly (P < 0.01) lower than the fluralaner treated group at each post-treatment time point., Conclusions: A single topical administration of fluralaner eliminated Demodex sp. mites on dogs with generalised demodicosis. Topical imidacloprid/moxidectin combination treatment administered 3 times at 28-day intervals, or more frequently, did not eliminate mites from most treated dogs.

Background: Leishmania infantum is the parasite responsible for the disease in humans known as zoonotic visceral leishmaniasis (ZVL). Dogs are considered the main domestic reservoir of ZVL and sand flies are the proven vectors. The use of systemic insecticides in dogs has been studied as an alternative strategy to control ZVL in endemic areas. One systemic insecticide in dogs, fluralaner, has a proven anti-sand fly effect in membrane-fed studies. However, the efficacy and duration on sand flies directly feeding from dogs treated with fluralaner remains unknown., Methods: Direct feeding bioassays were performed on 10 beagle dogs that had been randomly assigned to two groups: one with five dogs orally treated with Bravecto® (fluralaner) and other five as a control. About 30 females of Phlebotomus papatasi were allowed to directly feed from dogs at seven days before the administration of the treatment and Days 3, 17, 31, 45 and 73 post-treatment. Sand fly mortality after feeding was observed every 24 h for 5 days. The Kaplan-Meyer method, Henderson-Tilton formula and a negative binomial mixed model were used to respectively calculate: (i) mortality and its 95% confidence interval (CI); (ii) efficacy of the insecticide at killing sand flies in 24 h; and (iii) differences in the risk of sand fly death at 24 h after feeding., Results: Control sand fly mortality 24 h after feeding was always ≤ 20% and mortality in the fluralaner group ranged from 2% (95% CI: 0-4%) 7 days before treatment to 100% at 3 days post-treatment. Fluralaner efficacy was 100, 93, 94 and 75% at Days 3, 17, 31 and 45, respectively (P < 0.0001). The increase in the risk of sand fly death was 32.9 (95% CI: 4-263), 76 (95% CI: 8-705), 95.8 (95% CI: 9-1029) and 10.6 times (95% CI: 1.43-79) on Days 3, 17, 31 and 45, respectively CONCLUSIONS: The efficacy of fluralaner, orally administered to dogs, against sand-flies was above 90% for 31 days. Fluralaner administered to dogs should be further evaluated as a control strategy in ZVL endemic areas.

Background: The efficacy of the fixed combination of fluralaner plus moxidectin for the treatment of Otodectes cynotis infestations was evaluated in cats after topical application., Methods: Sixteen cats experimentally infested with O. cynotis were allocated randomly to two groups of 8 cats each. One group was treated topically with the fixed combination of fluralaner plus moxidectin at the minimum dose rate of 40 mg fluralaner and 2 mg moxidectin/kg body weight. The other group was treated with physiological saline solution. Before and 14 and 28 days after treatment the ears of all cats were examined otoscopically for live mites and for the amount of debris and cerumen. Twenty-eight days after treatment, the cats were sedated and had both ears flushed to obtain the total number of live mites per animal. Efficacy was calculated, based on the results of the ear flushing, by comparing mean live mite counts in the fluralaner plus moxidectin treated group versus the saline group., Results: A single topical application of the fixed combination of fluralaner plus moxidectin to cats reduced the mean mite counts by 100% (P < 0.001) by 28 days after treatment. No mites were visible during otoscopic examination at either 14 or 28 days after treatment. All fluralaner plus moxidectin treated cats had less ceruminous exudate 28 days after treatment compared to pre-treatment and 14 days after treatment. No treatment related adverse events were observed in any cats enrolled in the study., Conclusions: Single topical application of the fixed combination of fluralaner plus moxidectin was highly effective against O. cynotis infestations in cats.

Background: Fluralaner provides efficacy against feline ectoparasites following topical administration. Moxidectin is routinely used to treat gastrointestinal nematode infections and prevent heartworm disease caused by Dirofilaria immitis. Praziquantel is routinely used to treat feline tapeworm infections. The safety of a fluralaner plus moxidectin combination topical solution (Bravecto™ Plus, MSD Animal Health) was assessed when administered concurrently with a commercially available praziquantel topical solution (Droncit™ Spot-on, Bayer Animal Health GmbH). The highest dose rates in clinical use were tested., Results: Concurrent topical administration of a fluralaner plus moxidectin and a praziquantel product did not result in adverse findings. One out of ten cats receiving praziquantel only (control group), and two out of ten cats receiving fluralaner plus moxidectin and praziquantel (treatment group) had dandruff-like flakes in their coat at the application site. Two out of the ten control cats and three cats out of the ten treatment group cats had very small amounts of unidentified material (minute crusts or crumbs) at the application site which was only visible during close inspection., Conclusions: The concurrent treatment of cats with fluralaner plus moxidectin and praziquantel at the maximum dose in clinical use was well tolerated.

Background: A spot-on formulation containing fluralaner (280 mg/ml) plus moxidectin (14 mg/ml) (Bravecto® Plus) was developed for the treatment of nematode infections as well as providing 12 weeks of protection against insect and acarine parasites in cats. The effectiveness and safety of this product against feline gastrointestinal nematodes was assessed in naturally-infested, client-owned cats under field conditions in Albania, Bulgaria, Germany and Hungary., Methods: To be eligible for enrollment in this investigator-blinded study cats had to be at least 10 weeks-old, weigh at least 1.2 kg, be clinically healthy, and have a faecal sample testing positive for nematodes no more than eight days prior to treatment. Cats were stratified into blocks of three in order of presentation at each center and randomly allocated in a 2:1 ratio to be treated topically on Day 0 with fluralaner plus moxidectin (minimum dose rates 40 mg/kg and 2 mg/kg, respectively) or emodepside plus praziquantel (minimum dose rates 3 mg/kg and 12 mg/kg, respectively) (Profender®). Faecal samples were collected from cats prior to treatment and 14 ± 4 days later., Results: There were 182 cats randomized to the fluralaner plus moxidectin group, and 91 to the emodepside plus praziquantel group. Prior to treatment the most commonly identified nematode egg was Toxocara cati, found in 79.1 and 82.4% of cats in the fluralaner plus moxidectin and emodepside plus praziquantel groups, respectively. Eggs of Toxascaris leonina were found in 8.2 and 6.6% of cats; of hookworms in 30.8 and 24.2%; and of Capillaria spp. in 7.1 and 4.3%, respectively. After treatment, faecal samples from 98.3% of fluralaner plus moxidectin treated and 96.6% of emodepside plus praziquantel-treated cats were free of nematode ova. Geometric mean faecal egg count reductions for T. cati, the only eggs found in post-treatment faecal samples, were 99.97% and 99.93%, respectively. Treatment with fluralaner plus moxidectin was non-inferior to emodepside plus praziquantel. Both products were safe and well tolerated by cats treated under field conditions., Conclusions: This field study confirms that, in addition to 12-week extended duration flea and tick control, fluralaner plus moxidectin provides broad spectrum treatment of nematodes in cats.

Background: A spot-on formulation containing fluralaner (280 mg/ml) plus moxidectin (14 mg/ml) (Bravecto® Plus) has been developed to provide broad spectrum parasite protection for cats. The effectiveness and safety of this product against ticks and fleas was assessed in a randomized, controlled, 12-week study in client-owned cats in Germany and Spain., Methods: Eligible households containing at least one cat with at least two fleas and/or two ticks were allocated randomly in a 2:1 ratio to a single treatment with fluralaner plus moxidectin on Day 0, or three 4-weekly treatments with fipronil (Frontline®). Veterinary staff, masked to treatment, completed tick and flea counts on each cat at 14 ± 2 (2 weeks), 28 ± 2 (4 weeks), 56 ± 2 (8 weeks) and 84 ± 2 days (12 weeks) after the initial treatment., Results: In total, 707 cats (257 with ticks) from 332 households (236 with fleas) were included. Ixodes ricinus (78%) and Rhipicephalus sanguineus complex (18%) ticks were the most commonly identified. Tick and flea counts were lower in the fluralaner plus moxidectin group than in the fipronil group throughout the study and the efficacy of fluralaner plus moxidectin exceeded 97 and 98%, respectively. At 12 weeks, 94.1 and 93.3% of cats from the fluralaner plus moxidectin and 92.2 and 60.3% of cats from the fipronil group were free of ticks and fleas, respectively. Fluralaner plus moxidectin was non-inferior to fipronil (P < 0.0001) at all assessments and superior to fipronil at 2 and 8 weeks for the proportion of cats free of ticks (P < 0.0001). Fluralaner plus moxidectin was superior to fipronil for the proportion of both households and cats free of fleas (P < 0.0001). Both products were safe and well tolerated., Conclusions: A single application of fluralaner plus moxidectin spot-on was well tolerated by cats and highly effective for 12 weeks against ticks and fleas. Fluralaner plus moxidectin was non-inferior to fipronil for the proportion of ectoparasite-free and consistently superior to fipronil in controlling fleas.

Background: Veterinary clinic transaction records from the USA were examined to determine dog owner purchase patterns for three prescription ectoparasiticides. In-clinic purchases of formulations of fluralaner (with 12-week duration per dose) were compared with dog owner purchases of afoxolaner and spinosad (both with 4 week duration per dose) in a population of 231,565 dogs over a 12 month period. Prior studies in human and animal medicine have suggested that patients more closely adhere to prescriber dosing recommendations when they receive a longer-duration medication., Results: Veterinary clinic transaction records were examined for the period June 2014 through March 2017 using records from approximately 650 veterinary clinics. Ectoparasiticide purchase patterns were compared for two products (afoxalaner and spinosad) with monthly dosing and one product (fluralaner) with an extended (12 week) dosing interval. The average dog owner who obtained fluralaner purchased significantly more months of flea/tick protection (5.7 months) over the 12-month study period than the average dog owner that selected either afoxolaner (4.6 months) or spinosad (3.3 months). The proportion of dog owners who obtained only one dose of ectoparasiticide per 12-month period was 42% for fluralaner, 30% for afoxolaner and 37% for spinosad. The proportion of dog owners who obtained 2 doses or less per 12-month period was 67% for fluralaner, 52% for afoxoalaner and 67% for spinosad. Owners that obtained fluralaner were significantly more likely to obtain 7.0-12.0 months of flea and tick protection and significantly less likely to purchase 1.0-6.9 months compared with dog owners who purchased afoxolaner or spinosad., Conclusions: Dog owners who obtained a flea and tick medication with a longer duration of action acquired significantly more months of protection in a year than dog owners who obtained shorter duration (1 month) products. Dog owners were better able to adhere to veterinary recommendations on ectoparasites control with a longer-acting flea/tick medication.

Background: Dipylidium caninum is a common tapeworm of dogs contracted from ingestion of fleas containing the infective cysticercoid stage. Fluralaner is a systemically distributed isoxazoline class insecticide that delivers highly effective activity against fleas and ticks for up to 12 weeks after a single oral or topical treatment. This study evaluated the impact of this flea insecticidal efficacy on the transmission of D. caninum to dogs., Methods: Dogs were weighed and treated with a cestocide and then randomly assigned to 3 groups of 8. Fluralaner was administered topically (at the commercial dose) to one group and orally to another group while the third received topically administered sterile water. All dogs were subsequently infested with about 100 D. caninum infected Ctenocephalides felis at 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77 and 83 days after treatment. Visual proglottid inspections and counts were conducted daily from 35 to 113 days post-treatment. Post-treatment D. caninum incidence was calculated for each group and compared between treated and untreated groups., Results: All 8 dogs in the placebo-treated group became infected with D. caninum while no shed proglottids were observed at any point during the post-treatment period from any dog in either fluralaner treated group., Conclusions: The insecticidal efficacy of a single treatment of either orally or topically administered fluralaner prevented D. caninum transmission from infected fleas to susceptible dogs for up to 12 weeks following administration.

Background: A multi-centre field trial was conducted to evaluate the efficacy of afoxolaner based chewables (NexGard® or NexGard Spectra®) for the treatment of generalised demodicosis caused by Demodex canis in dogs under field conditions in France, Italy and Poland., Methods: Client-owned dogs, diagnosed positive for Demodex mites by pre-treatment skin scrapings and presenting clinical signs of generalised demodicosis were included. Dogs were orally treated with afoxolaner three times at monthly intervals. Of the 50 dogs enrolled, 48 completed the whole study. Efficacy of the treatments was assessed monthly by Demodex mite counts and physical examination with special regard to the severity and extension of skin lesions., Results: Treatments were well tolerated in all dogs and resulted in a rapid reduction of mites, with all post-treatment mite counts significantly lower than baseline. The number of mites was reduced by 87.6%, 96.5% and 98.1% on Days 28, 56 and 84, respectively. In addition, the skin lesion severity and extent scores as well as the pruritus were all significantly lower at all post-treatment visits compared to the pre-treatment assessment., Conclusions: This clinical field study demonstrated that monthly administrations of afoxolaner in NexGard® or NexGard Spectra®, offered a convenient and reliable solution for the treatment of canine generalised demodicosis.

Background: Heartworm medications and many oral or topical flea and tick products are provided as monthly doses while a newer oral flea/tick product, fluralaner (BRAVECTO® Chew), is re-dosed at a 12-week interval. This study focused on whether there was a difference in the number of heartworm medication doses that were purchased in the 12-months follow-up period for dogs that receive either fluralaner or other flea/tick medications that are dosed monthly., Methods: Clinic transaction records of heartworm medication purchases for over 200,000 dogs were examined to compare the purchase of heartworm preventative protection by dog owners that also receive flea and tick medications of differing efficacy durations., Results: Annual purchases of heartworm medication for dogs by owners that receive a flea and tick medication dosed at 12-week intervals was incrementally higher than the number of doses purchased for dogs receiving monthly flea and tick medications. The average number of monthly doses per year was slightly over 7 months for both categories of product. The distribution of purchases of monthly doses was also similar between groups., Conclusions: Dog owners who purchase a longer-acting flea and tick medication purchase as much heartworm medication annually for their dogs as dog owners who purchase monthly flea and tick medication. On average, dog owners who gave their dog fluralaner obtained significantly more months of heartworm preventative protection compared with dog owners who gave their dog a monthly flea and tick medication, although the biological significance of this increase in doses is very small.

Background: From three days following host attachment, the Australian paralysis tick, Ixodes holocyclus, secretes a neurotoxin that annually causes paralysis in approximately 10,000 domestic pets. Lotilaner, a novel isoxazoline formulated in a chewable flavoured tablet (Credelio TM ), produces rapid onset of acaricidal activity in dogs, with an efficacy duration of at least one month. Two studies were performed to determine the efficacy of lotilaner against I. holocyclus infestations over 3 months., Methods: Both studies included 16 dogs, ranked according to I. holocyclus counts on Day -5 (from infestations on Day -8) and blocked into pairs. One dog in each pair was randomized to be a sham-treated control, the other to receive lotilaner at a minimum dose rate of 20 mg/kg on Day 0. Dogs were dosed in a fed state. Infestations were performed in both studies on Days -8 (to determine the tick carrying capacity of each dog) -1, 28, 56, 70, 77 and 84, and additionally in Study 1 on Day 91, in Study 2 on Days 14 and 42. In Study 1, ticks were counted and assessed as alive or dead at 24, 48 and 72 h post-initial infestation and post-subsequent re-infestations. In study 2, ticks were counted at 24, 48 and 72 h post-dosing or post-re-infestation. Efficacy was determined by the percent reduction in live attached tick counts in the lotilaner group compared to control., Results: Within 48 h post-treatment in Study 1 and within 72 h post-treatment in Study 2 all lotilaner-group dogs were free of live ticks. By 72 h post-infestation, efficacy in Study 1 remained at 100% through Day 87, except on Day 31 when a single tick was found on one dog, and through Day 59 in Study 2. Efficacy exceeded 95% through the final assessment in each study (Days 94 and 87 in Studies 1 and 2, respectively)., Conclusion: These results demonstrate that lotilaner quickly kills existing I. holocyclus infestations. By providing 95.3-100.0% protection through at least 87 days post-treatment, lotilaner can be a valuable tool in reducing the risk of tick paralysis in dogs.

Background: Doses of flea and tick medication acquired by dog owners over a 12 month period were determined from veterinary hospital transaction records in Spain. The number of months of flea and tick protection potentially obtained by dog owners prescribed fluralaner, a flea and tick medication with a 12 week re-dosing interval, was compared with months of flea and tick protection obtained by dog owners prescribed monthly oral or spot-on products. Prior studies in human and veterinary medicine have suggested that longer-acting medications benefit patients by providing improved adherence to provider recommendations., Results: Dog owners took home, on average, significantly more months of protection when they obtained the 12 week duration product fluralaner (4.3 months) than they did when they obtained other flea and tick products providing 1 month of protection [3.24 months (oral), 2.9 months (spot-on)]. Many dog owners (46-64%) obtained only one dose of flea and tick product each year, regardless of the duration of protection offered by the product. Significantly more dog owners obtained 7-12 months of protection when they were prescribed fluralaner (15.7%) by their veterinarians compared with dog owners prescribed monthly flea and tick products [6.8% (oral), 8.3% (spot-on)]., Conclusion: Veterinary prescription of fluralaner delivers more months of potential flea and tick protection as shown by dog owner acquisition of flea and tick medication. The use of a longer-acting medication requires the administration of fewer doses and may translate into better adherence to veterinary ectoparasite control recommendations.

Background: An investigation was conducted in West Central Florida, USA to evaluate the efficacy of either topically applied fluralaner or topically applied selamectin to control flea infestations, minimize dermatologic lesions and reduce pruritus in naturally flea infested cats over a 12-week period. When dogs were present in the households, they were treated with either oral fluralaner (if household cats were treated with topical fluralaner) or oral sarolaner (if household cats were treated with topical selamectin)., Methods: Thirty-one cats in 20 homes were treated once with fluralaner topical solution on day 0 and 18 dogs in these homes were administered a single fluralaner chewable. Twenty-nine cats in 18 homes were treated once monthly with a selamectin topical solution for 3 treatments and 13 dogs in these same homes were treated once monthly for 3 treatments with a sarolaner chewable. Fleas on cats were counted by flea combing, fleas on dogs were estimated using visual area counts and fleas in the indoor premises were assessed using intermittent-light flea traps. Blinded-assessments of feline dermatologic lesions were conducted monthly and pruritus severity was evaluated by pet owners., Results: A single topical application of fluralaner reduced flea populations on cats by 96.6% within 7 days and by 100% at 12 weeks post-treatment. This efficacy was significantly greater than selamectin treatment where single topical application reduced flea populations on cats by 79.4% within 7 days of initial treatment and 3 consecutive monthly treatments reduced flea populations by 91.3% at the end of 12 weeks. At the end of the 12-week study, all fluralaner-treated cats were flea-free and this was significantly greater than the 38.5% of selamectin treated cats that were flea-free. At the end of the study, fleas were completely eradicated (from cats, dogs and homes) in 95.0% of fluralaner treatment group homes, significantly greater than the 31.3% of selamectin/sarolaner treatment group homes with complete flea eradication. Owner reported cat pruritus was reduced similarly in both treatment groups. Significant improvements in dermatologic lesion scores were achieved by day 30 in fluralaner treated cats and by day 60 in selamectin treated cats., Conclusions: An in-home investigation in subtropical Florida found that 1 application of topical fluralaner eliminated flea infestations on cats and in homes significantly more effectively than 3 consecutive monthly doses of selamectin.

Background: Safety and efficacy of the combined monthly use of spot-on fipronil 6.76% w/v / permethrin 50.48% w/v (Frontline Tri-Act®) and chewable tablets of afoxolaner 1.9% w/w / milbemycin oxime 0.4% w/w (NexGard Spectra®) in dogs was evaluated in a field study over a period of 6 months., Methods: Forty-one healthy dogs living in highly endemic area for canine leishmaniosis and other canine vector borne diseases (VBD) were included in the study at the beginning of the Leishmania transmission season. Sixteen dogs were pet dogs living each in a single household; twenty-five dogs were hunting dogs living in three kennels. At inclusion, the dogs were ELISA (rapid test) negative for antibodies to Anaplasma, Borrelia, Ehrlichia, and for antigens of Dirofilaria. The dogs were also negative for blood microfilariae at the Knott's test, and no clinical or haematological abnormalities were observed. Of the included dogs, six hunting, apparently healthy, dogs were ELISA (rapid test) positive to Leishmania, and some were naturally infected by gastrointestinal nematodes (58.5%) and/or infested by fleas (58.5%) and ticks (9.8%). All the included dogs were treated at Days 0, 28, 56, 84, 112 and 140, and followed-up for efficacy until the study end (Day 168)., Results: No adverse events related to the two products, nor skin reactions, general signs, or changes in the haematological profile, were observed during the study. At Day 14, anthelminthic efficacy was 100% for Toxocara canis, Toxascaris leonina and Capillaria aerophila, while few hunting dogs were still shedding eggs of Trichuris vulpis (1/25 hunting dog) and Ancylostomatidae (9/25 hunting dogs). All pet dogs were nematode free at the end of the study. Hunting dogs were free of roundworms and whipworms. Twenty-four hours after the first treatment, 95.8% of the ectoparasite infested dogs were free from fleas and ticks. Ectoparasites were significantly controlled during the 6-month study period, with 100% efficacy on both fleas and ticks from Day 56 to Day 168. Blood and serum samples collected on Day 168 were tested for vector-borne pathogens using same methods of the inclusion and no new seroconversions or circulating blood microfilariae were observed., Conclusions: Concomitant use of Frontline Tri-Act® and NexGard Spectra® in dogs for six months was well tolerated. The combination was effective in controlling fleas, ticks, gastro-intestinal nematodes, and neither new seroconversion to the tested vector-borne pathogens nor blood microfilariae were detected in treated dogs at the end of the study.

Background: Lotilaner is a new member of the isoxazoline class for treatment of flea and tick infestations in cats. This laboratory study with lotilaner vanilla-yeast flavoured chewable tablets (Credelio TM , Elanco) investigated the safety in healthy kittens starting at 8 weeks of age in a randomized, blinded, parallel-group design. Lotilaner tablets were given orally once a month over eight months at one, three and five times the upper level of the maximum recommended dose range (26 mg/kg)., Methods: The safety of lotilaner flavoured chewable tablets was assessed in healthy kittens when administered orally every 4 weeks for 8 months at the highest recommended dose rates, i.e. 1× (26 mg/kg) and at elevated dose rates, i.e. 3× (78 mg/kg) and 5× (130 mg/kg). Sixteen male and 16 female healthy 8-week-old kittens, with a mean body weight of 0.79 kg and 0.75 kg, respectively, were randomized to an untreated control group or lotilaner groups at dose rates of 26 mg/kg (1×), 78 mg/kg (3×), or 130 mg/kg (5×) every four weeks over eight months. The control group was sham-dosed. All animals were fed within 30 minutes prior to treatment. Safety assessment included general health observations, detailed clinical observations, complete physical/neurological examinations, including ophthalmological examinations, electrocardiographic (ECG) and clinical pathology evaluations (haematology, clinical chemistry and urinalysis), food and water consumption, body weight, pharmacokinetic blood collections, organ macroscopic and microscopic examinations., Results: Systemic exposure to lotilaner was confirmed during the course of the study in all treated animals with the exception of the control group. No treatment-related effects were seen on daily clinical observations, food consumption (wet), ophthalmoscopic, physical/neurological and microscopic examinations. Statistically significant differences were recorded in some of the clinical pathology parameters, body weights, food consumption (dry), electrocardiograms, and organ weights, but none of the recorded observations was considered to be of clinical relevance., Conclusions: Lotilaner, when administered once monthly over eight months at the highest recommended dose and overdoses of three- and five-fold, to 8-week-old healthy kittens, is well tolerated.

Background: Credelio TM (lotilaner) is an oral ectoparasiticide from the isoxazoline class developed for the treatment of flea and tick infestations in cats. It is formulated as a pure S-enantiomer in flavoured chewable tablets. The pharmacokinetics of lotilaner were investigated after intravenous or oral administration and under fed or fasted conditions in cats. Twenty-six adult cats were enrolled in a pharmacokinetic study evaluating either intravenous or oral administration of lotilaner. Following the oral administration at a dosage of 6 mg/kg, under fed or fasted conditions, or intravenous administration of 3 mg/kg, blood samples were collected up to 35 days after treatment. Lotilaner blood concentrations were measured using a validated liquid chromatography/tandem mass spectrometry method. Pharmacokinetic parameters were calculated by non-compartmental analysis. In addition, in vivo enantiomer stability of lotilaner was evaluated in a separate bioanalytical study., Results: Following oral administration in fed cats, lotilaner was readily absorbed and peak blood concentrations reached within four hours. The terminal half-life was 33.6 days. Food enhanced the absorption, providing close to 100% oral bioavailability and reduced the inter-individual variability. Following intravenous administration, lotilaner had a low clearance of 0.13 l/kg/day, large volumes of distribution V z and V ss of 5.34 and 5.37 l/kg, respectively and a terminal half-life of 28.7 days. In addition, there was no in vivo racemization of lotilaner., Conclusions: The pharmacokinetic properties of lotilaner administered orally as a flavoured chewable tablet (Credelio TM ) were studied in detail. With a T max of 4 h and a terminal half-life of 33.6 days under fed conditions, lotilaner provides a rapid onset of flea and tick killing activity with consistent and sustained efficacy for at least one month in cats.

Background: Lotilaner, approved for dogs as a chewable tablet formulation, has separately been developed for oral use in cats (Credelio TM chewable tablets for cats), to meet the need for an easy to use, safe and rapidly effective parasiticide. It is a valid cat- and owner-friendly alternative to topical products. This manuscript describes three pivotal laboratory studies assessing the efficacy and speed of kill of lotilaner in cats against Ixodes ricinus ticks following a single oral administration, at a dose rate close to 6 mg/kg., Methods: In Studies 1 and 2, efficacy and safety were evaluated 48 h after treatment and post-treatment weekly infestations in 16 cats, against untreated controls, for 35 days. In Study 3, efficacy and safety were assessed in 8 lotilaner-treated cats until Day 35, before and after 24 h incubation of the female live ticks removed from the animals 12, 18 and 24 h after dosing and subsequent weekly infestations., Results: Efficacy was > 99% on days 23 and 37, and 100% on all other timepoints in Study 1. In Study 2 it was > 98% on Days 9 and 37, and 100% on all other days. In Study 3, on Day 0, lotilaner was > 90% efficacious, pre- and post-incubation at all time-points. On Day 7, at 12 hours after infestation, efficacy was 100%, pre- and post-incubation. On Day 14, there was a 66.5% reduction in geometric mean live tick counts in treated cats compared to controls, increasing, after incubation, to 94.4%. Afterwards, efficacy decreased below 90% while tick counts in the treated groups remained significantly lower compared to controls. At 18 hours, lotilaner was ≥ 90% efficacious through Day 37, increasing to 100% at 24 hours, on all study days, with the exception of Day 28 (98.9 and 99.1% pre- and post-incubation, respectively). There were no treatment-related adverse events., Conclusions: At the minimum dose rate of 6 mg/kg, lotilaner was efficacious against I. ricinus ticks. In addition, lotilaner was effective against this tick within 12 hours of treatment, reaching 100% efficacy within 24 hours. Lotilaner sustained a rapid kill of newly infesting I. ricinus through 35 days. By quickly killing ticks that infest cats, lotilaner has the potential to contribute to the reduction of tick-borne pathogens transmission.

Background: Fluralaner (Bravecto®, Merck Animal Health, Madison, NJ, USA) is a novel isoxazoline that provides up to 12 weeks flea and tick control when administered orally to dogs. Two assessor-blinded studies, one in dogs, the other in cats evaluated the sustained efficacy of a topical fluralaner formulation against fleas in a simulated home environment (SHE)., Methods: Animals were ranked and blocked into groups of two using flea counts completed 24 hours following Ctenocephalides felis infestations placed on dogs on Day -64, and on cats on Day -36. Within blocks animals were randomized to a treatment group, 10 animals per group, one group to receive fluralaner spot-on (minimum dose rate for dogs, 25 mg/kg; for cats, 40 mg/kg), the other to be a sham-treated control. Animals were then placed into their SHE, one animal per pen or cage and then infested with 100 C. felis at weekly intervals. Dogs were infested from Day -56 through -21 and cats on Days -28 and -21. Fleas were counted and removed from each dog and cat on Day -1. Study animals were then held in clean pens/cages until treatment on Day 0. One day later, after treatment, all animals were returned to their home environment (SHE). Additional 50-flea challenges were placed on each animal on Days 22, 50 and 78. Fleas were counted and replaced on all animals on Day 1 and weekly thereafter for 12 weeks., Results: Arithmetic mean counts in control-group animals exceeded 10 fleas at all post-treatment assessments except on Days 1, 7 and 14. All control-group animals remained infested at each assessment from Day or 28 through Day 84, thereby validating the challenge methodology. Fluralaner efficacy was 100% on all occasions except for 2 fleas found on 1 dog on Day 1, and 3 fleas on 1 dog on Day 14. One flea was recovered from 1 fluralaner treated cat on Day 1. There were no treatment-related adverse events., Conclusion: A single application of a topical formulation of fluralaner is well tolerated and highly effective in the prevention of flea infestations of dogs and cats throughout the 12 weeks following treatment.

Background: Infestation of cats with the Australian paralysis tick, Ixodes holocyclus continues to be a threat because of the paralysis that can result from attachment of just a single tick. The outcome can be fatal, particularly if tick removal and treatment is not initiated soon after the onset of paralysis. However, there are no published studies to guide veterinarians and owners on preventive measures. A study was therefore initiated to determine the efficacy of a systemically-acting, spot-on formulation of fluralaner (Bravecto ® ) for cats against existing I. holocyclus infestations, and to investigate the duration of protection following a single administration., Methods: Healthy domestic cats, short or long-hair, immunized against holocyclotoxin, were randomly allocated to two groups of 10 cats per group, to receive either a single topically applied fluralaner treatment or no treatment. Fluralaner treatments were administered on Day 0 at a dose rate of 40 mg/kg. All cats were infested with 10 adult unfed female I. holocyclus on Day -1 and on Days 14, 28, 42, 56, 70 and 84. Ticks were assessed at 24 and 48 h after fluralaner treatment and 24, 48 and 72 hours after each subsequent re-infestation. Ticks were counted but not removed at the 24- and 48-h post-challenge assessments and were removed following the 72-h counts., Results: The efficacy of fluralaner spot-on against an existing I. holocyclus infestation was 100% at 48 h post treatment. Following re-infestations, efficacy remained at 100% at the 72-h assessments for all challenges from Day 14 to Day 84. Differences between mean live tick counts on treated versus control cats were significant at all time points from the first post-treatment assessment (t-test: t (18) = 23.162; P < 0.0001) through the final challenge on Day 84 (t-test: t (18) = 21.153; P < 0.0001). No treatment-related adverse events were observed and there were no abnormal observations at the product application sites., Conclusions: A single treatment of fluralaner spot-on was well tolerated and provided 100% efficacy against I. holocyclus ticks for at least 84 days. Fluralaner spot-on can be a valuable tool to prevent tick infestation in cats, and to control the risk of I. holocyclus-induced paralysis.

Background: Zoonotic visceral leishmaniasis (ZVL) caused by Leishmania (Leishmania) infantum is an important disease in humans and dogs. Different mammal species are reservoirs but dogs are considered to be the main one. Phlebotomine sand flies are the proven vector. Four systemic insecticides approved for their use in dogs were previously selected based on their potential to be used in endemic countries as part of the control programs of ZVL. These insecticides are proved to be safe and effective against the on-label insects and parasites, but there is no information about their activity against phlebotomine sand flies., Methods: The phlebotomine mortality of four systemic insecticides in dogs was evaluated using two randomized clinical trials. For the first trial, thirty dogs were randomly allocated into five groups: four treatments and one control, of equal size. The treatments evaluated were: Guardian®SR, Elanco (moxidectin); Comfortis®, Elanco (spinosad); Bravecto®, Merck Animal Health (fluralaner); and NexGard®, Merial (afoxolaner). Blood from dogs was taken at days 2, 4, 21 and 31 post-treatment (trial 1). The compound that showed the highest efficacy was selected for a second trial (trial 2) with 20 dogs sampled at days 0, 2, 4, 7, 14, 18, 32, 39, 51 and 84 post-treatment. Membrane feeding bioassays with Phlebotomus papatasi were used to evaluate the phlebotomine mortality efficacy of the different treatments. Phlebotomine mortality was observed every 24 h following the membrane feeding during 5 days. A mixed model for a negative binomial logistic regression, and a Cox proportional hazard mixed model were used to estimate phlebotomine mortality due to different treatments., Results: Fluralaner was the only compound that showed significant phlebotomine mortality. Fluralaner maintained the phlebotomine mortality between 60-80% for 30 days after treatment. In trial 1 we found that fluralaner increased the risk of death by 1.9 times (95% CI: 1.02-3.6) and 1.7 times (95% CI: 1.09-2.6) at days 2 and 4 after treatment. The Cox model resulted in an increase of 1.47 (95% CI: 1.1-1.96) times in hazard risk at day 2 and 1.89 (95% CI: 1.35-2.45) at day 4 after treatment. In trial 2 we found that fluralaner increased the risk of death by 1.64 times (95% CI: 1.16-2.54) and 1.97 times (95% CI: 1.23-3.17) at days 14 and 32. The hazard risk was also increased by 1.92 (95% CI: 1.4-2.64) times at day 14 after treatment. Phlebotomine survival including all experimental days was significantly lower in the fluralaner group in both trials., Conclusions: A single oral treatment of fluralaner in dogs induces phlebotomine mortality. Systemic insecticides in dogs should be considered as a potential preventive measure of ZVL.

Background: Preclinical studies have shown that the novel isoxazoline, lotilaner (Credelio™, Elanco) administered orally to dogs, produces rapid flea and tick knockdown and sustained speed of kill for at least a month post-treatment with a wide safety margin. A field study was undertaken to validate pre-clinical results., Methods: Dogs were enrolled at 10 veterinary clinics across the United States. Qualifying households containing up to three dogs and one primary dog with at least 10 fleas were randomized 2:1 to receive lotilaner (Credelio™, Elanco) at the recommended minimum dose of 20 mg/kg, or afoxolaner (Nexgard®, Merial), administered per label, to give a minimum dose of 2.5 mg/kg. Treatments were dispensed on Days 0, 30 and 60 for administration by owners; all household dogs received the same treatment as the primary dog. Post-enrollment flea and tick counts were made on primary dogs on Days 30, 60 and 90, and all dogs were assessed for tablet palatability and safety., Results: For efficacy assessments, data were used from 111 lotilaner-treated dogs and 50 afoxolaner-treated dogs; for safety, 197 and 86 dogs, respectively. Percent reductions from baseline in geometric mean flea counts for the lotilaner group were 99.3, 99.9 and 100% on Days 30, 60 and 90, respectively, and for afoxolaner 98.3, 99.8 and 99.8% (P < 0.001, both groups, all days). On Day 90, 100% of lotilaner-treated dogs and 93% of afoxolaner-treated dogs were flea-free. Too few ticks were present to allow assessment. There were no differences in palatability between products (P = 0.2132), with, respectively, 94% and 96% of lotilaner and afoxolaner treatments accepted when offered by hand, in an empty food bowl or with food. Both treatments were well tolerated, alleviating clinical signs of flea allergy dermatitis (FAD) in dogs affected at enrollment., Conclusion: A single owner-administered lotilaner treatment was greater than 99% effective in reducing mean flea counts within 30 days. Three consecutive monthly lotilaner treatments resulted in a 100% reduction in flea infestations, and a substantial reduction in signs of FAD. Lotilaner flavored tablets were readily accepted under field conditions. The absence of treatment-related adverse events confirms the safety of lotilaner in dogs.

Background: Poultry mites are the most significant pest affecting production systems in the chicken egg-laying industry, altering the health condition of the birds, and causing stress, mortality and decline of egg quality impacting economic performance. Fluralaner is a novel systemic parasiticide that is effective against poultry mites (Dermanyssus gallinae, Ornithonyssus sylviarum) in chickens after oral administration. The evaluation of the safety of this new product in breeder chickens is particularly relevant because poultry mite infestation affects long cycle production systems, such as layers and breeders farms, for which the productivity heavily depends on the health of the reproductive function. This study was designed to investigate the safety for reproductive performances of fluralaner in male and female chickens at 3 times the recommended dose (1.5 instead of 0.5 mg/kg body weight) and 2 times the recommended duration (4 administrations instead of 2 administrations, with a 7 day interval between administrations)., Methods: This randomized, parallel-group, blinded study included 432 Bovans brown parent stock chickens (48 males and 384 females, 17-week old). Birds were randomly assigned to 16 pens (three males and 24 females per pen), and then each pen assigned to one of the two treatment groups (8 pens, i.e. 216 birds per group). Fluralaner was administered via drinking water on a total of four occasions 7 days apart, at daily doses of 1.5 mg fluralaner/kg body weight, equivalent to 3 times the recommended dose of fluralaner per administration and 2 times the recommended number of administrations. Birds supplied with non-medicated drinking water served as controls. The treatments were given at time of peak egg production in the bird's life: i.e. at 30 to 34 week of age. During that period, all adult chickens were clinically observed. The reproductive performances were carefully monitored including the number of eggs laid, egg weight, fertility and hatchability. Furthermore, the health and viability (up to 14 days of life) of randomly selected chicks was also monitored., Results: There were no clinical findings related to fluralaner treatment. There were no statistically significant differences between the reproductive performances of treated and control groups, nor in their progeny chickens viability., Conclusions: Oral administration of fluralaner was well tolerated by breeder chickens with a safety margin of approximately 3-fold obtained. Fluralaner had no effect on the egg number, weight and fertility, and no effect on egg hatchability or chick viability. Based on these results, a safe use of the new mite treatment proposed with fluralaner administered via drinking water is expected in layer and breeder field industrial conditions.

Background: Fluralaner is a novel systemic ectoparasiticide for dogs and cats providing immediate and persistent flea- and tick-control after a single topical dose. Prescribing directions recommend waiting 72 h following topical administration before immersing dogs in water. The objective of this study was to determine whether water immersion immediately prior to treatment or earlier than 72 h post-treatment reduced subsequent treatment efficacy., Methods: Forty (n = 40) dogs were blocked on tick carrying capacity into 5 experimental groups and all but one of the groups (untreated control) were treated topically with fluralaner (Bravecto® Spot-On Solution, Merck Animal Health, Madison, NJ, USA) at the commercial dose. Three of the four remaining groups were immersed in 38-40 °C water for a 5 min bath - either 1 h before treatment; 12 h after treatment; or 24 h after treatment. Seven days after treatment all dogs were challenged with 50 Rhipicephalus sanguineus (sensu lato) ticks and after 24 h attached ticks were counted and removed., Results: Efficacies (compared to the untreated control group) were: 99.3% for no water immersion; 99.6% for immersion 1 h before treatment; 99.3% for immersion 12 h after treatment; and, 100% for immersion 24 h after treatment., Conclusions: Water immersion of dogs around the time of topical fluralaner administration did not reduce subsequent systemic acaricidal efficacy.

Background: The clinical efficacy of fluralaner chewable tablets (Bravecto™, MSD Animal Health) against naturally acquired Linognathus setosus infestations on dogs was evaluated compared with permethrin (Exspot®, MSD Animal Health) treatment., Methods: Privately-owned dogs naturally infested with L. setosus from 21 different households were randomly allocated to two treatment groups. Fourteen dogs were treated once orally with fluralaner and ten dogs were treated once topically with permethrin, at the recommended label dose. Live L. setosus on all dogs were counted before treatment and 1, 7, 28 (both groups) and 84 (fluralaner group) days post-treatment according to a coat parting technique at pre-specified locations and lice species were confirmed microscopically. At the same time points, a veterinary dermatology severity score and an owner's perceived pruritus score were recorded., Results: Percentage reduction in geometric mean L. setosus counts, comparing post- with pre-treatment counts within each group, were 85.7% (day 1), 96.8% (day 7) and 100% (days 28 and 84) for the fluralaner (two-sided two-sample t-test, P ≤ 0.0088 for days 1-84) and 67.5% (day 1), 90.3% (day 7) 99.1% (day 28) for the permethrin group (two-sided two-sample t-test, P ≤ 0.0014 for days 7-28). No lice were seen on fluralaner-treated dogs 28 and 84 days post-treatment. In contrast, two permethrin-treated dogs were re-treated at 7 and 28 days after initial treatment because of observed lice. Owner's perceived pruritus scores were reduced compared to pre-treatment levels by 23.8% (day 1), 31.1% (day 7), 70.4% (day 28) and 99.5% (day 84) after fluralaner treatment and 21.3% (day 1), 45.8% (day 7), and 78.1% (day 28) after permethrin treatment. Dermatological signs were improved compared to pre-treatment levels in both treatment groups., Conclusions: Single oral fluralaner treatment eliminated natural L. setosus infestation on dogs within 28 days and led to complete dermatological recovery that was maintained until the study end on day 84. Single topical permethrin treatment reduced the number of L. setosus by 99.1% at day 28 although two animals required unscheduled re-treatment.

Background: Poultry mites are the most significant pest affecting production systems in the egg-laying industry. Fluralaner is a novel systemic insecticide and acaricide that is effective against poultry mites (Dermanyssus gallinae, Ornithonyssus sylviarum) in chickens after oral administration. This study investigated the safety of oral administration of a 1% solution of fluralaner in drinking water to laying hens at the recommended treatment dose and at multiples of this dose., Methods: One hundred-twenty healthy 28-week-old laying hens, weighing 1.4-2.1 kg at first administration, were included in the study, and allocated to 4 treatment groups of 30 hens each receiving daily doses of 0, 0.5, 1.5 and 2.5 mg fluralaner/kg body weight, equivalent to 0, 1, 3, and 5 times the recommended dose of fluralaner. The product was administered via drinking water on a total of six occasions, as 3-day treatment periods twice with an interval of 4 days with no treatment (treatment on days 1, 2, 3 and 8, 9, 10), representing 3 times the recommended number of administrations. Hens supplied with non-medicated drinking water served as controls. During the study, all hens were clinically observed, and their health was carefully monitored including body weight, food and water consumption, hematology, clinical chemistry, and withdrawal reflex test. Eggs laid over the study were evaluated for main characteristics (e.g. weight, shape, strength, shell thickness and soundness, albumen height, yolk color, Haugh unit and presence of blood and/or meat spots). Following euthanasia of the hens at the end of the second treatment period (day 11) or 18 days later (day 29), complete gross post-mortem examination, including organ weight determination, and histopathological examination of multiple tissues were conducted., Results: There were no clinical findings related to fluralaner treatment. Statistically significant differences between the treated groups and the control group were observed for some clinical pathology parameters; none of these findings were considered to be of clinical nor zootechnical relevance. Organ weights, gross post mortem and histopathological examinations did not reveal any finding associated with treatment with fluralaner., Conclusions: Oral administration of fluralaner via drinking water at the recommended treatment dose (0.5 mg/kg body weight twice at 1-week interval), is well tolerated and has a high safety margin up to an overall dose of 15 times the recommended one (5 times the daily dose given 3 times the number of days) in healthy adult laying hens. Based on the present results, the use of the new mite treatment based on fluralaner administered via drinking water is expected to be safe for laying hens under industrial conditions, and to have no negative impact on their egg quality and production.

Background: The Australian paralysis tick, Ixodes holocyclus, causes paralysis predominantly in dogs and cats in the Eastern coastal regions of Australia. Rapid onset of effect of a parasiticide is critical to minimize the deleterious effects of these tick infestations, especially tick paralysis caused by the salivary neurotoxin. The speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner chewable tablets (Simparica ® ), against I. holocyclus on dogs was evaluated and compared with afoxolaner (NexGard ® ) for 5 weeks after a single oral dose., Methods: Twenty-four (24) dogs were randomly allocated to treatment with either placebo, sarolaner (label dose of 2 to 4 mg/kg as per dosing table), or afoxolaner (label dose of 2.7 to 6.9 mg/kg) based on pre-treatment body weights. Following artificial infestation on Day -1, dogs were examined and live ticks counted at 8, 12, 24 and 48 h after treatment on Day 0, and at 12, 24 and 48 h after subsequent re-infestations on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for placebo dogs based on geometric means., Results: At 8 and 12 h time points on Day 0, sarolaner-treated dogs had significantly lower geometric mean tick counts compared to the dogs treated with afoxolaner (P ≤ 0.0303). Efficacy of sarolaner against an existing infestation was 86.2 and 96.9% compared with that of afoxolaner which had efficacy of 21.3 and 85.0% at 8 and 12 h time points, respectively. Against subsequent weekly re-infestations at 12 h time points, treatment with sarolaner resulted in significantly lower geometric mean tick counts than afoxolaner-treated dogs on all days (P ≤ 0.0077) with the efficacy ranging from 60.2 to 92.2%, compared to 5.8 to 61.0% in the afoxolaner-treated dogs. Against subsequent weekly re-infestations at the 24 h time points on Days 22 and 36, efficacy of sarolaner was significantly higher at 99.2 and 97.9%, respectively, compared with afoxolaner which had efficacy of 92.4 and 91.9% (P ≤ 0.0356). At the 48 h time points following each of the five weekly re-infestations, the mean efficacy results of sarolaner and afoxolaner treated dogs were similar on most occasions. There were no adverse reactions to treatments., Conclusions: In this controlled laboratory evaluation, a single dose of sarolaner had a significantly faster speed of kill against an existing infestation of I. holocyclus, than afoxolaner at 8 and 12 h post-treatment. The rapid and consistent kill of ticks provided by sarolaner within 24 h after a single oral dose and following weekly re-infestations over 35 days suggests this treatment will provide highly effective, rapid and reliable control of ticks over the entire treatment interval, thereby minimizing the risk of tick paralysis in dogs.

Background: Orally administered fluralaner effectively controls fleas and ticks on dogs for 12 weeks. This study evaluates the flea control efficacy achieved with topically applied fluralaner in dogs., Methods: This investigator-blinded, multi-center randomized, positive controlled study evaluated flea control efficacy in dogs following a single owner-applied treatment of topical fluralaner. A positive control group received three treatments, at 4-week intervals, of a commercial formulation of fipronil/(S)-methoprene. All dogs in households randomized to the fluralaner group were dispensed an initial treatment at enrollment and a second treatment at week 12 for an additional 3-week observation of treatment safety. Households with up to five healthy dogs, all at least 12 weeks of age and weighing at least 2 kg (4.4 lb), were randomized in a ratio of 3:1 of fluralaner to positive control. Within households, one primary dog with at least 10 live fleas at enrollment was randomly selected. Flea counts were performed on all primary dogs every 4 weeks through week 12. Efficacy measurement was based on reduction from baseline flea counts. Treatment was considered effective if geometric mean live flea count reductions at weeks 4, 8, and 12 were 90% or greater and significantly different from counts at enrollment. In addition, for each time point the arithmetic mean live flea counts, the efficacy based on arithmetic means, the number and percentage of dogs with at least a 90% reduction in flea count, and the number and percentage of flea free dogs were calculated. Statistical comparisons were also made between treatment groups., Results: At 12 sites, across 10 states, 121 households (221 dogs) were randomized to receive fluralaner and 44 households (100 dogs) were randomized to receive the positive control. Fluralaner was demonstrated to be significantly effective (all P ≤ 0.0001) at 4 weeks (99.8% reduction), 8 weeks (99.9%), and 12 weeks (99.9%). The positive control was significantly different from baseline (all P ≤ 0.0001) and showed a reduction of 81.2% at 4 weeks and was effective at 8 weeks (90.3%) and 12 weeks (93.0%). Arithmetic mean flea count reductions for the fluralaner group at 4, 8, and 12 weeks were 99.8, 99.9, and 99.9%, respectively. For the positive control, arithmetic mean flea count reductions were 58.8, 75.3, and 80.8% at 4, 8, and 12 weeks, respectively. No treatment-related serious adverse events were reported in either group., Conclusions: Owner-applied topical fluralaner treatment was safe in dogs and provided ≥ 99.8% flea control efficacy for 12 weeks.

Background: Fleas are a common ectoparasite of domestic cats and there is a need for novel treatments that improve feline flea control., Methods: This investigator-blinded, multi-center randomized, positive-controlled study evaluated the flea control in cats provided by a single owner-applied treatment with a fluralaner topical formulation compared with a positive control. Households with up to five healthy cats, all at least 12 weeks of age and weighing at least 1.2 kg (2.6 lb), were randomized in an approximate 3:1 ratio of fluralaner to positive control. All cats in households randomized to the positive control group were dispensed three treatments, at 4-week intervals, of a commercial formulation of fipronil/(S)-methoprene. All cats in households randomized to the fluralaner group were dispensed an initial treatment at enrollment and a second treatment at week 12 for an additional 3-week observation of treatment safety. One primary cat with at least five live fleas at enrollment was randomly selected within each household. Flea counts were performed on all primary cats at 4-week intervals through week 12. Efficacy measurement was based on reduction in flea counts from baseline. Treatment was considered effective at weeks 4, 8 and 12 if mean live flea count reductions were 90% or greater and statistically significantly different (P ≤ 0.05) from counts at enrollment., Results: In 18 investigational veterinary clinics across 11 USA states, 116 households (224 cats) were randomized to receive topical fluralaner and 45 households (87 cats) were randomized to the fipronil-methoprene combination. Fluralaner was demonstrated to be effective at 4 weeks (99.1% flea count reduction), 8 weeks (99.5%), and 12 weeks (99.0%), and all reductions were significantly different from the enrollment count (all P < 0.0001). The fipronil-methoprene combination was < 90% effective at each post-treatment assessment, with peak efficacy of 75.4% at 12 weeks (all P < 0.0001). No treatment-related serious adverse events were reported in either group., Conclusions: Owner-applied fluralaner topical treatment was safe in cats and was highly effective in killing fleas over the subsequent 12 weeks.

Background: The efficacy of fluralaner for the treatment of Otodectes cynotis infestations in dogs and cats was evaluated after oral (dogs) or topical administration (dogs and cats). Twenty-four dogs and sixteen cats were experimentally infested with O. cynotis and randomly allocated to equal sized groups (n = 8/group). Dog groups were treated once, either orally with fluralaner at a minimum dose of 25 mg/kg body weight, topically with fluralaner at a dose of 25 mg/kg body weight or topically with saline solution (control). Cat groups were treated once, either topically with fluralaner at a dose of 40 mg/kg body weight or topically with saline solution. Ears of all animals were examined otoscopically for live visible mites and the amount of debris and cerumen before, and 14 and 28 days after treatment. Twenty-eight days after treatment, animals were sedated and both ears were flushed to obtain the total number of live mites per animal. The efficacy was calculated, based on the results of the ear flushing, by comparing mean live mite counts in the fluralaner treated groups versus the saline solution treated group., Results: A single topical treatment of cats with fluralaner reduced the mean mite counts by 100% (P < 0.001) at 28 days after treatment. Similarly, a single oral or topical treatment of dogs with fluralaner reduced the mean mite counts by 99.8% (P < 0.001) at 28 days after treatment. Cats treated topically with fluralaner had no mites visible during otoscopic examination at either 14 or 28 days after treatment. All dogs treated orally or topically with fluralaner had no mites visible during otoscopic examination at 28 days after treatment. At 14 days after treatment, only 1-2 mites were visible in three dogs (oral treatment: 2 dogs, topical treatment: 1 dog). All fluralaner-treated animals showed improvement in the amount of cerumen exudation compared with observations performed before treatment. No treatment related adverse events were observed in any dogs or cats enrolled in these studies., Conclusions: In this study, fluralaner administered topically to cats and orally or topically to dogs was highly effective against Otodectes cynotis mite infestations.