A novel combination of fipronil and permethrin (Frontline Tri-Act®/Frontect®) reduces risk of transmission of Babesia canis by Dermacentor reticulatus and of Ehrlichia canis by Rhipicephalus sanguineus ticks to dogs

BACKGROUND : The ability of Frontline Tri-Act®/Frontect®, a topical ectoparasiticide containing fipronil and permethrin for dogs, to prevent the transmission of Babesia canis as well as Ehrlichia canis was evaluated by infesting dogs with infected vector ticks. METHODS : For the Babesia canis study, 16 dogs were randomly allocated to two groups. Eight dogs were treated on day 0 with a topical spot-on formulation containing 6.76 % w/v fipronil plus 50.48 % w/v permethrin and eight dogs served as the untreated control group. Dermacentor reticulatus ticks, with a B. canis infection rate ranging between 2 and 10 %, were placed onto dogs on days 7, 14, 21 and 28. In situ tick counts were performed on Days 9, 16 and 23. Ticks were counted and removed on Day 30. Infection of the dogs with B. canis was monitored by rectal temperature readings, clinical examinations and blood smears as well as PCR and IFA (indirect fluorescent antibody assay). For the Ehrlichia canis study, another 16 dogs were allocated to two groups. Eight dogs were treated with the fipronil and permethrin combination on days 0 and 28 and eight dogs served as untreated controls. Rhipicephalus sanguineus ticks, carrying an infection rate of 13 % for E. canis, were released in the sleeping kennels of the dogs on days 7, 14, 21, 28, 35, 42, 49 and 56. Ticks were counted in situ on the dogs on a weekly basis. All ticks were removed and counted on the final assessment day 58. Infection of the dogs with E. canis was monitored by rectal temperature, clinical examinations, and testing of blood samples by PCR, IFA and platelet counts. RESULTS : B. canis was transmitted by D. reticulatus ticks to all eight untreated control dogs and to one treated dog, which was confirmed by blood smears, PCR and IFA. E.canis was transmitted by R. sanguineus ticks to all eight untreated control dogs. Two of the dogs in the treated group were found positive based on PCR and/or IFA. CONCLUSIONS : Frontline Tri-Act®/Frontect® significantly lowered the risk for dogs to acquire a B. canis infection by 87.5 % over a challenge period of 28 days. The risk for dogs to acquire E. canis was reduced by 75 % over a period of 56 days.Merial S.A.S., a Sanofi company, France.http://www.parasitesandvectors.comam201

Efficacy and speed of kill of a topically applied formulation of dinotefuran-permethrin-pyriproxyfen against weekly tick infestations with Rhipicephalus sanguineus (sensu lato) on dogs

BACKGROUND : Rhipicephalus sanguineus (sensu lato) is a vector of canine babesiosis, anaplasmosis and ehrlichiosis. In order to reduce the chance of transmission of these diseases, an ectoparasiticide should rapidly repel or kill new infestations with this tick. The primary objective of the present study was to evaluate the treatment and preventive acaricidal efficacy of Vectra® 3D (54.45 mg/ml of dinotefuran, 396.88 mg/ml of permethrin and 4.84 mg/ml of pyriproxyfen) against R. sanguineus (s.l.) measured at 2, 8, and 48 h after treatment and weekly re-infestation. METHODS : Twenty-four dogs were each infested with 50 adult R. sanguineus (s.l.) on Day -7 and allocated to three groups (n = 8) based on tick counts: an untreated control group (Group 1), and two groups (Groups 2 and 3) treated with Vectra®3D. The dogs in each group were infested with 50 ticks on Day -2. Vectra®3D was administered topically to the dogs on Day 0. Ticks were counted, in situ at 2 and 8 h after treatment on dogs in Groups 1 and 3. Group 3 was then withdrawn from the study and ticks were counted and removed from the dogs in Groups 1 and 2, 48 h after treatment. On Days 7, 14, 21, 28, 35 and 42, the dogs in Groups 1 and 2 were re-infested with 50 ticks, which were then counted in situ at 2 and 8 h, and counted and removed at 48 h after re-infestation. RESULTS : Ticks from the initial infestation were visually unaffected by 2 and 8 h after treatment. However, by 2 h after weekly re-infestation the arithmetic mean (AM) efficacy of Vectra® 3D from Days 7 through 28 ranged from 61.1 to 78.8 %, falling to 60.1 and 47.4 % on Days 35 and 42 respectively. By 8 h after weekly re-infestation, the AM efficacy ranged from 89.1 to 97.4 % falling to 81.4 and 69.8 % on Days 35 and 42 respectively. The AM efficacy 48 h after treatment after the initial infestation was 22.9 % but after weekly re-infestation the efficacy at 48 h ranged from89.1 to 100.0 %, falling to 86.0 and 81.1 % on Days 35 and 42 respectively. CONCLUSION : Vectra® 3D demonstrated significant efficacy against new infestations of adult R. sanguineus (s.l.) ticks within 2 h of infestation as compared to the untreated control group and achieved over 89.1 % efficacy within 8 h of infestation for up to 4 weeks after administration. These results indicate that Vectra® 3D has a rapid and significant efficacy against new infestations of adult R. sanguineus (s.l.) ticks and should therefore be considered as part of a strategy against important vector-borne diseases in dogs.Ceva Santé Animalehttp://www.parasitesandvectors.comam2016Veterinary Tropical Disease

Comparative efficacy of oral administrated afoxolaner (NexGard™) and fluralaner (Bravecto™) with topically applied permethrin/imidacloprid (Advantix®) against transmission of Ehrlichia canis by infected Rhipicephalus sanguineus ticks to dogs

BACKGROUND : The ability of the topical spot-on Advantix® (50 % permethrin/10 % imidacloprid) to prevent transmission of Ehrlichia canis by infected Rhipicephalus sanguineus ticks to dogs has previously been reported. The recent market introduction of chewable tablets containing the novel compounds, afoxolaner (NexGard™) and fluralaner (Bravecto™) enabled us to conduct a comparative efficacy study with respect to the ability of these three products to block transmission of E. canis by ticks to dogs. The speed of kill, immediate drop-off rate and anti-attachment efficacy of the respective products were also studied. METHODS : The study was a blinded parallel group design, wherein 32 dogs were randomised into four different groups of eight dogs. Group 1 served as negative placebo control, group 2 and 3 were treated on Days 0, 28 and 56 with NexGard™ and Advantix®, respectively. Group 4 was dosed once on Day 0 with Bravecto™. For tick efficacy assessments 50 non-infected ticks were placed onto the dogs on Days 30, 35, 42, 49, 56, 63, 70, 77 and 84 and on animal tick counts were performed at 3 h, 6 h and 12 h after infestation. To evaluate the ability to block transmission of E. canis, each dog was challenged by releasing 80 adult E. canis-infected R. sanguineus ticks into their sleeping kennels on Days 31, 38, 45 and 52. The animals were monitored for clinical signs of monocytic ehrlichiosis (pyrexia and thrombocytopenia) and were tested for E. canis DNA by PCR and for specific antibodies using IFA. A dog was considered infected with E. canis if both PCR and IFA yielded positive test results up to Day 84. RESULTS : Mean arithmetic tick counts on dogs treated with the Advantix® spot-on were significantly (P < 0.0005) lower throughout the study as compared with the negative controls and was, with respect to the speed of kill and resulting onset of acaricidal efficacy, superior over NexGard™ and Bravecto™ at all time points in the 12 h period observed (3 h, 6 h and 12 h). None of the dogs treated with the Advantix® spot-on became infected with E. canis, whereas six out of eight untreated control dogs acquired the infection. Furthermore, E. canis infection was diagnosed in four out of eight dogs treated with NexGard™ and in two out of eight dogs treated with Bravecto™. CONCLUSIONS : The speed of kill of the two recently registered systemic compounds against R. sanguineus was not sufficiently fast to prevent transmission of E. canis and resulted in only low partial blocking and protection capacity while Advantix® effectively blocked transmission of E. canis to dogs in the challenge period and thus provided adequate protection for dogs against monocytic ehrlichiosis.Bayer Animal Health GmbH, Monheim, Germanyhttp://www.parasitesandvectors.comam2016Veterinary Tropical Disease

Determination of the effective dose of a novel oral formulation of sarolaner (Simparica™) for the treatment and month-long control of fleas and ticks on dogs

AbstractThree laboratory studies were conducted to determine the appropriate dose of sarolaner, a novel isoxazoline, for the treatment and month-long control of infestations of fleas and ticks on dogs. In the first study, dogs were treated orally with sarolaner suspension formulations at 1.25, 2.5 or 5.0mg/kg, and infested with Dermacentor reticulatus, Rhipicephalus sanguineus ticks and with Ctenocephalides felis felis (cat flea) prior to treatment and then weekly for up to 8 weeks. Fleas and ticks were counted 48h after treatment and after each subsequent infestation at 24h for fleas and 48h for ticks. The lowest dose of sarolaner (1.25mg/kg) provided 100% efficacy against fleas from treatment through Day 35 and 98.4% at Day 56. This dose of sarolaner resulted in 99.7–100% control of both species of ticks through Day 28. In Study 2, dogs were dosed orally with placebo or sarolaner suspension formulations at 0.625, 1.25 or 2.5mg/kg and infested with Ixodes scapularis prior to treatment and weekly for 6 weeks, Amblyomma americanum (pretreatment and Day 26), Dermacentor variabilis (Day 33) and A. maculatum (Day 41). Ixodes scapularis was the most susceptible; the lowest dose (0.625mg/kg) providing>95% efficacy through Day 43. Efficacy against D. variabilis on Day 35 was>95% at 1.25 and 2.5mg/kg, whereas the 0.625mg/kg dose gave only 61.4% efficacy. Amblyomma spp. were the least susceptible ticks; efficacy of the 1.25mg/kg dose at Day 28 for A. americanum was markedly lower (88.5%) than achieved for D. reticulatus (100%) at Day 28 and also lower than for D. variabilis at Day 35 (96.2%). In Study 3, dogs were dosed orally with placebo or sarolaner in the proposed commercial tablet (Simparica™) at 1.0, 2.0 or 4.0mg/kg, and infested with A. maculatum, one of the ticks determined to be dose limiting, prior to treatment and then weekly for 5 weeks. All doses gave 100% control of the existing infestation. The two highest dosages resulted in >93% control of subsequent challenges for 5 weeks. There was no significant improvement in efficacy provided by the 4.0 mg/kg dose over the 2.0mg/kg dose (P>0.05) at any time point. The 2.0mg/kg dose was superior to the 1.0mg/kg on Day 14 (P=0.0086) and as efficacy for 1.0mg/kg declined below 90% at Day 28, a single 1mg/kg dose would not provide a full month of tick control. Thus, 2.0mg/kg was selected as the sarolaner dose rate to provide flea and tick control for at least one month following a single oral treatment

The efficacy of a generic doxycycline tablet in the treatment of canine monocytic ehrlichiosis

The objective of the present study was to evaluate the therapeutic efficacy of a generic doxycycline tablet (DoxyVet®) against Ehrlichia canis infection in dogs. Canine monocytic ehrlichiosis is caused by the bacterium E. canis and transmitted by the brown kennel tick (Rhipicephalus sanguineus). Six disease-free and tick-free dogs were infested with E. canisinfected ticks. Once diagnosed (with polymerase chain reaction [PCR] analysis and platelet counts) as positive for infection, doxycycline tablets were administered orally once a day for 20 consecutive days, at a target dose level of 10 mg/kg. The actual dose administered was calculated as ranging between 10 mg/kg and 11.7 mg/kg. The PCR analysis, 28 days after the first administration of the tablets, failed to detect E. canis in any of the dogs. On Day 56 of the study, four of the dogs were diagnosed with E. canis for the second time and a fifth dog was diagnosed on Day 70. The platelet counts of the sixth dog remained within normal levels and it was discharged from the study on Day 84. Doxycycline tablets were then administered to the remaining five infected dogs for 28 consecutive days. Four of these dogs had no positive PCR results during the following 3 months. The fifth dog was diagnosed with E. canis for the third time 58 days after the last tablets of the second treatment had been administered, after which it was rescue treated (doxycycline for a further 28 days). The results indicate that doxycycline administered in tablet form (DoxyVet®) at 10 mg/kg – 11.7 mg/kg body mass once daily for 28 consecutive days clears most dogs of infection. The importance of a concomitant tick-control programme is therefore stressed.http://www.jsava.co.zaam201

Comparative speed of kill, repellent (anti-feeding) and acaricidal efficacy of an Imidacloprid/flumethrin collar (Seresto®) and a fipronil/(S)-methoprene/eprinomectin/praziquantel spot-on (Broadline®) against Ixodes ricinus (Linné, 1758) on cats

Speed of kill, repellent (anti-feeding) and acaricidal efficacy of an imidacloprid 10% (w/w) /flumethrin 4.5% (w/w) collar (Seresto®, Bayer) and a spot-on formulation of fipronil 8.3% (w/v) /(S)-methoprene 10% (w/v) /eprinomectin 0.4% (w/v) /praziquantel 8.3% (w/v) (Broadline®, Merial) against artificially-induced infestations with Ixodes ricinus on cats, were assessed in a parallel group design, randomized, controlled study. Twenty-four cats were included and randomly allocated to treatment groups or non-treated controls. Starting on Day (D) 7 after treatment until D28, cats were each infested with 50 I. ricinus at weekly intervals. Ticks were counted in situ on the cats at 6, 12 and 24 h and upon removal 48 h after each infestation. Based on arithmetic means, Seresto® proved to be 100% effective against adult I. ricinus at all assessment times (6, 12, 24 and 48 h after infestation) throughout the month-long study. Broadline® was 0% to 16.7% effective at 6 h, 26.8% to 50.0% effective at 12 h, while at 24 h after infestation efficacy peaked at 81.5% on D15 declining to 31.5% on D29. Based on the 48 h tick counts, the efficacy of Broadline® peaked at 100% on D16 after treatment and decreased to 83.2% by D30. The Seresto® collar provided significantly faster speed of kill and better persistent acaricidal effectiveness against Ixodes ricinus on cats compared to Broadline® spot-on. The additional repellent (antifeeding) effect of Seresto® prevents parasites from taking a blood meal and thereby reduces the risk of vectorborne disease pathogen transmission.Bayer Animal Healthhttp://link.springer.com/journal/4362016-08-31hb2015ab201

Efficacy and safety of a novel oral isoxazoline, sarolaner (Simparica™), for the treatment of sarcoptic mange in dogs

AbstractThe efficacy of the novel isoxazoline, sarolaner (Simparica™) was investigated in dogs with clinical signs consistent with sarcoptic mange and harbouring natural infestations of Sarcoptes scabiei. One placebo-controlled laboratory study and one multi-centred field study with a commercial comparator containing imidacloprid/moxidectin (Advocate® spot-on) were conducted. Oral or topical treatments were administered on Days 0 and 30. Up to 10 skin scrapings were taken for the assessment of S. scabiei infestations from each dog before treatment and on Days 14, 30, 44 and 60 in the laboratory study, and on Days 30 and 60 in the field study. In the laboratory study, efficacy was calculated based on the percent reduction of mean live mite counts compared to the placebo group. In the field study parasitological cure rate (% dogs free of mites) was determined and non-inferiority of sarolaner to the control product was assessed.In the laboratory study 44 mixed breed dogs were enrolled in four batches. Due to decreasing mite counts in the placebo treated dogs, immunosuppression with dexamethasone (0.4mg/kg three times per week for two weeks) was initiated in all dogs on study at that time (n=6) and those subsequently enrolled (n=14). In the field study, dogs were enrolled in a 2:1 ratio (sarolaner:comparator); 79 dogs were assessed for efficacy and safety, and an additional 45 dogs were assessed for safety only. There were no treatment related adverse events in either study.In the laboratory study, no mites were found on any sarolaner-treated dogs 14 days after the first treatment except for one dog that had a single mite on Day 44. In the field study, the parasitological cure rate was 88.7% and 100% in the sarolaner group and 84.6% and 96.0% in the imidacloprid/moxidectin group, on Days 30 and 60, respectively. Statistical analysis showed that sarolaner was non-inferior to imidacloprid/moxidectin at both time points. The clinical signs of sarcoptic mange, including hair loss, papules, pruritus, erythema, and scaling/crusting improved throughout the study.Sarolaner was safe, achieved 100% reduction in the numbers of S. scabiei detected and resulted in marked improvement of the clinical signs of sarcoptic mange in dogs following two monthly oral administrations

Efficacy of an imidacloprid/flumethrin collar against fleas, ticks, mites and lice on dogs

BACKGROUND: The studies reported here were conducted to ascertain the efficacy of imidacloprid/flumethrin incorporated in a slow-release matrix collar, against infestations of dogs by fleas, ticks, mites and lice. Efficacy was evaluated against the flea Ctenocephalides felis felis, the ticks Rhipicephalus sanguineus, Ixodes ricinus, Ixodes scapularis, Dermacentor reticulatus and Dermacentor variabilis, the mite Sarcoptes scabiei and the biting louse Trichodectes canis. METHODS: Groups of collar-treated dogs (n = 7–10) were infested with fleas and/or ticks at monthly intervals at least, over a period of up to 8 months. Efficacy against fleas was evaluated 24 to 48 h after treatment and 24 h after each re-infestation. Efficacy against ticks was evaluated at 48 h (acaricidal), 6 h (repellent) and 48 h (sustained) after infestation. The effect of regular shampooing or immersion in water on the efficacy of the collars was also tested. Efficacy against flea larvae was assessed by incubating blanket samples after dog contact with viable flea eggs. Effectiveness against lice and mites was evaluated after treatment of naturally infested animals. With the exception of the mites, efficacy was calculated by comparison with untreated negative control groups. RESULTS: Efficacy against fleas (24 h) generally exceeded 95%, and against flea larvae it exceeded 99% for 8 months. Sustained acaricidal (48 h) efficacy, covering a period of 8 months was 100% against I. ricinus, starting 2 days after treatment (in vivo), and 100% against I. scapularis (in vitro), above 97% against R. sanguineus, generally above 97% against D. reticulatus and above 90% for D. variabilis. Repellent (6 h) efficacy 2 days after treatment and continuing for 8 months was consistently 100% against I. ricinus, and above 90% against R. sanguineus. Regular shampooing affected efficacy against fleas and ticks to a lesser extent than regular immersion in water. The collars eliminated Trichodectes canis within 2 days and Sarcoptes scabiei within 3 months. CONCLUSION: The rapid insecticidal and acaricidal properties of the medicated collars against newly-acquired infestations of fleas and ticks and their sustained high levels of preventive efficacy have been clearly shown. Consequently they have the potential to prevent the transmission of vector-borne diseases and other conditions directly associated with infestation throughout an entire season of parasite abundance.DS, EMK, JJF and WD designed the study design and protocols and JJF and EMK carried out the studies. DS, JJF, EMK and WD and IGH compiled and analysed the data. IGH was responsible for the first draft of the manuscript, which was then substantially revised by all authors. All authors read and approved the final manuscript.These clinical studies were completely funded by Bayer Animal Health GmbH, Monheim, Germany, of which D. Stanneck (Germany) and K. Krieger are employees, and by Bayer HealthCare LLC, Animal Health (USA). ClinVet is an independent Contract Development Organisation, which was contracted to manage the conduct of a part of these studies. I.G. Horak is a long-term, contract employee of Clinvet and an Honorary Professor at the Universities of the Free State and Pretoria. The authors are sincerely grateful to all monitors, investigators and the staff of the study locations either linked to the authors or serving as independent CROs who took part in the numerous studies and ensured that the high GCP and GLP standards were adhered to.http://www.parasitesandvectors.com/content/5/1/102am2013ab201

Efficacy of orally administered fluralaner (BravectoTM) or topically applied imidacloprid/moxidectin (Advocate®) against generalized demodicosis in dogs

BACKGROUND : This laboratory study compared the efficacy of Bravecto™ (fluralaner), formulated as a chewable tablet, with the efficacy of Advocate® (imidacloprid/moxidectin), formulated for topical administration, against naturally acquired generalized demodicosis in dogs. METHODS : Sixteen dogs, all diagnosed with generalized demodectic mange, were randomly allocated to two equal groups. Bravecto™ chewable tablets were administered once orally at a minimum dose of 25 mg fluralaner/kg body weight to one group of dogs, while the second group was treated topically on three occasions at 28-day intervals with Advocate® at a minimum dose of 10 mg imidacloprid/kg body weight and 2.5 mg moxidectin/kg body weight. Mites were counted in skin scrapings and demodectic lesions were evaluated on each dog before treatment and at 28-day intervals thereafter over a 12 week study period. Deep skin scrapings (~4 cm2) were made from the same five sites on each dog at each subsequent examination. RESULTS : After single oral administration of Bravecto™ chewable tablets, mite numbers in skin scrapings were reduced by 99.8% on Day 28 and by 100% on Days 56 and 84. Mite numbers in the dogs treated topically on three occasions at 28-day intervals with Advocate® were reduced by 98.0% on Day 28, by 96.5% on Day 56 and by 94.7% on Day 84. Statistically significantly (P ≤ 0.05) fewer mites were found on Days 56 and 84 on the Bravecto™ treated dogs compared to Advocate® treated dogs. A marked decrease was observed in the occurrence of erythematous patches, crusts, casts and scales in the dogs treated with Bravecto™ and in the occurrence of erythematous patches in the dogs treated with Advocate®. With the exception of one dog in each treated group, all dogs exhibited hair regrowth ≥ 90% at the end of the study in comparison with their hair-coat at study start. CONCLUSIONS : Single oral administration of Bravecto™ chewable tablets is highly effective against generalized demodicosis, with no mites detectable at 56 and 84 days following treatment. In comparison, Advocate®, administered three times at 28-day intervals, is also highly effective against generalized demodicosis, but most dogs still harboured mites at all assessment time points. Both treatments resulted in a marked reduction of skin lesions and increase of hair re-growth 12 weeks after the initial treatment.http://www.parasitesandvectors.comam201