Publications by authors named "Julian Liebenberg"

30 Publications

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Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel in cats against Toxocara cati and Dipylidium caninum.

Parasite 2021 2;28:28. Epub 2021 Apr 2.

Boehringer-Ingelheim Animal Health, 3239 Satellite Blvd, Duluth, GA 30096, USA.

NexGard Combo, a novel topical antiparasitic product for cats, combines the insecticide/acaricide esafoxolaner with the nematocide eprinomectin and cestodicide praziquantel. The efficacy of this combination product was evaluated against two common endoparasites of global occurrence in cats, the nematode Toxocara cati and the cestode Dipylidium caninum, in five controlled studies using naturally or experimentally infected cats with parasites of North American, South African or European origin. Cats evaluated in these studies harbored patent infection of the target parasite confirmed through a pre-treatment fecal examination. In each study, cats were allocated randomly to two groups of equal size (8 or 10 cats per group per study), one group treated with a placebo (mineral oil) and the other with NexGard Combo. Both treatments were administered once as a spot-on at 0.12 mL per kg body weight to deliver the minimum label dosage (1.44 mg/kg esafoxolaner, 0.48 mg/kg eprinomectin, and 10.0 mg/kg praziquantel) to the NexGard Combo-treated cats. To determine efficacy, geometric mean parasite counts seven to 12 days after treatment of placebo-treated (control) cats and NexGard Combo-treated cats were compared. The efficacy of NexGard Combo was 98.8% and 100% against adult T. cati in two studies; and 98.0%, 98.3% and 93.2% against D. caninum in three studies. No adverse events related to treatment were observed throughout the studies. These studies demonstrate high efficacy against these major feline endoparasites and excellent acceptability of the novel topical antiparasitic combination of esafoxolaner, eprinomectin and praziquantel.
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http://dx.doi.org/10.1051/parasite/2021024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019557PMC
April 2021

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against ear mite (Otodectes cynotis) infestations in cats.

Parasite 2021 2;28:26. Epub 2021 Apr 2.

Boehringer-Ingelheim Vetmedica GmbH, Kathrinenhof Research Center, Walchenseestr. 8-12, 83101 Rohrdorf, Germany.

Esafoxolaner, a purified enantiomer of afoxolaner with insecticidal and acaricidal properties, is combined with eprinomectin and praziquantel, nematodicidal and cestodicidal compounds, in NexGard Combo, a novel topical endectoparasiticide formulation for cats. The efficacy of this formulation was assessed against Otodectes cynotis in two laboratory studies conducted in South Africa and in the USA with local isolates, and in one field trial conducted in Europe. In each study, cats were randomly allocated to a placebo-treated control group and a novel formulation-treated group. In the laboratory studies, cats were treated at the minimum recommended dose; in the field trial, cats were treated at label dose. All included cats were diagnosed positive for O. cynotis prior to treatment by otoscopy. The main variable of efficacy was a comparison of the number of live O. cynotis collected in both ear canals of all cats in the treated and control groups, one month after treatment. Efficacy of the novel topical formulation exceeded 97% in the three studies. These studies demonstrated the high effectiveness of NexGard Combo in cats for the treatment of O. cynotis infestations. No health abnormalities were attributed to the treatment in any of the studies.
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http://dx.doi.org/10.1051/parasite/2021022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019571PMC
April 2021

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against adult cat flea Ctenocephalides felis and flea egg production in cats.

Parasite 2021 2;28:21. Epub 2021 Apr 2.

Boehringer-Ingelheim Animal Health, Missouri Research Center, 6498 Jade Rd., Fulton, MO 65251, USA.

Esafoxolaner, a purified enantiomer of afoxolaner with insecticidal and acaricidal properties, is combined with eprinomectin and praziquantel in NexGard Combo, a novel topical endectoparasiticide formulation for cats. The efficacy of this novel formulation against adult and immature stages of Ctenocephalides felis fleas was tested in four experimental studies. Two studies were designed to test adulticide efficacy, one to test inhibition of immature stages, and one to test both adulticide efficacy and inhibition of immature stages. In each study, cats were randomly allocated to a placebo control group or to a novel formulation group treated once at the minimum recommended dose. Cats were experimentally infested weekly for one to two months with unfed C. felis originating from North America or Europe. For adulticide efficacy evaluations, live fleas were counted 24 h after treatment and after subsequent weekly infestations. For immature stages, flea eggs were collected and counted weekly for evaluation of egg production inhibition and incubated for larval hatching evaluation. In the three studies testing adult fleas, curative efficacies, 24 h after treatment, were 92.1%, 98.3% and 99.7%; preventive weekly efficacies, 24 h after weekly infestations, remained higher than 95.5% for at least one month. In the two studies testing immature stages, egg production and larval hatching was significantly reduced for at least one month. These studies provide robust evidence of efficacy of the novel formulation against experimental adult flea infestations and for the prevention of environmental contamination by immature flea stages, for at least one month.
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http://dx.doi.org/10.1051/parasite/2021017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019553PMC
April 2021

Insecticidal efficacy of afoxolaner against bedbugs, Cimex lectularius, when administered orally to dogs.

Parasite 2021 2;28. Epub 2021 Feb 2.

ClinVet, PO Box 11186 Universitas, 9321, Bloemfontein, South Africa.

The objective of this experimental study was to assess the insecticidal efficacy of afoxolaner (NexGard) against bedbugs (Cimex lectularius) on dogs. For each challenge, 20 bedbugs were placed in two chambers positioned in contact to the dog's skin for 15 min, after which live fed parasites were counted and incubated for survival evaluations. On Day 0, 7 dogs assigned to the treated group were administered afoxolaner orally at the registered dose. All 14 dogs were challenged on Days 1, 7, 14, 21 and 28, and the collected live fed C. lectularius incubated for 72 h (Day 1), and 72 h and 96 h (Days 7, 14, 21 and 28) for survival evaluation. The percent feeding in the control group ranged from 95% to 98.6% and the percent of live fed bedbugs at 96 h ranged from 99.3% to 100% in the control group, demonstrating the viability of the strain and their capacity to feed on dogs. Significantly fewer live fed bedbugs were counted in the treated group, compared to the control group, at all time-points. The reduction of live fed C. lectularius in the afoxolaner group was 41.4% at 72 h after the Day 1 challenge, and 77.2%, 82.7%, 85.0% and 63.5% at 96 h after the Days 7, 14, 21 and 28 challenges, respectively. It is hypothesized that monthly treatment of dogs with afoxolaner could help in preventing a bed bug population from installing in a household if bedbugs bite dogs in the presence of humans.
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http://dx.doi.org/10.1051/parasite/2021004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852378PMC
February 2021

Efficacy of a novel chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against four common tick species infesting dogs in Europe.

Parasit Vectors 2020 Mar 1;13(1):100. Epub 2020 Mar 1.

Zoetis, Veterinary Medicine Research and Development, 333 Portage St., Kalamazoo, MI, 49007, USA.

Background: Tick infestations can cause direct deleterious effects to dogs as a result of tick blood-feeding, and indirectly ticks can transmit disease agents that can be detrimental to the health of both dogs and humans. Six laboratory studies were conducted to support dosage selection and efficacy confirmation of a novel combination of sarolaner, moxidectin and pyrantel against four tick species that commonly infest dogs in Europe.

Methods: Two studies were conducted against Dermacentor reticulatus (one of which was a dose determination study), two against Ixodes ricinus, and one each against Ixodes hexagonus and Rhipicephalus sanguineus (sensu lato). In each study, eight purpose-bred Beagle or mix-breed dogs were randomly allocated to each treatment group and infested with 50 unfed adult ticks on Days-2, 5, 12, 19, 26 and 33. On Day 0 dogs were treated orally with placebo or the combination product. In the dose determination study, dogs received sarolaner at point dosages of 0.6 mg/kg, 1.2 mg/kg or 2.4 mg/kg in combination with moxidectin and pyrantel, and in all other studies dogs received Simparica Trio™ to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt). Efficacy was assessed based on live tick counts conducted 48 hours after treatment and each weekly infestation.

Results: There were no treatment-related adverse events in any study. In the dose determination study, 1.2 mg/kg sarolaner was the lowest dosage evaluated that provided > 90% efficacy for at least 28 days and therefore was selected as the dosage to provide tick control for at least one month following a single oral treatment. In the dose confirmation studies, a single oral dose of Simparica Trio™ provided ≥ 99.2% efficacy against existing infestations of all tick species, and against re-infestations efficacy was ≥ 97.2% against D. reticulatus for 28 days and against all other species for 35 days.

Conclusions: These studies support the sarolaner dose selected and confirm the efficacy of a single oral dose of Simparica Trio™ against existing infestations and re-infestations of the common tick species infesting dogs in Europe for at least one month.
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http://dx.doi.org/10.1186/s13071-020-3949-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049386PMC
March 2020

Immediate and persistent efficacy of sarolaner (Simparica™) against Haemaphysalis elliptica on dogs.

Parasit Vectors 2019 Sep 5;12(1):431. Epub 2019 Sep 5.

Zoetis Inc., 333 Portage Street, Kalamazoo, Michigan, 49007, USA.

Background: The southern African yellow dog tick, Haemaphysalis elliptica, occurs in eastern and southern Africa and adults infest domestic and wild carnivores. This tick species is also a vector of the highly virulent Babesia rossi pathogen, the causative agent of canine babesiosis in sub-Saharan Africa. Sustained high levels of efficacy of a parasiticide are not only important in protecting dogs against the direct effects of tick infestation, but also in reducing the risk of tick-borne diseases. Sarolaner (Simparica™ chewable tablets) has been reported to be effective against the major tick species infesting dogs in Europe and the USA, including representatives from the genera Amblyomma, Ixodes, Rhipicephalus and Dermacentor. Until now no efficacy evaluations have been reported against species of the genus Haemaphysalis. The objective of the study was to confirm the efficacy of a single 2 mg sarolaner/kg oral dose of Simparica™ against induced infestations with H. (R.) elliptica, an important parasite of dogs in southern Africa.

Methods: This blinded, randomised, single centre, placebo controlled efficacy study followed a parallel group design and was conducted on two groups consisting of eight purpose-bred dogs each. Animals were treated orally, once on Day 0, with either a placebo compound (Group 1) or Simparica™ (Group 2). Simparica™ was administered orally at a dose rate of 2 mg sarolaner/kg body weight. The dogs were infested with ticks on Days - 7, - 2, 5, 12, 19, 26 and 33, with removal counts conducted on Days - 5, 2, 7, 14, 21, 28 and 35.

Results: A single oral administration of Simparica™ (sarolaner) at a minimum dose of 2 mg/kg resulted in a 100% efficacy against existing infestations of H. (R.) elliptica on dogs and a 100% reduction in live ticks following weekly re-infestations for 35 days. Moreover, the immediate and persistent high levels of efficacy observed in this study for 35 days is consistent with those observed in previous studies against ticks in other genera.

Conclusions: The efficacy of sarolaner (Simparica™), administered orally to dogs at the minimum label dose of 2.0 mg/kg, was demonstrated against existing and weekly re-infestations of H. (R.) elliptica for at least 5 weeks. Efficacy of 100% was achieved against existing infestations as well as weekly re-infestations.
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http://dx.doi.org/10.1186/s13071-019-3696-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728933PMC
September 2019

Early Babesia canis transmission in dogs within 24 h and 8 h of infestation with infected pre-activated male Dermacentor reticulatus ticks.

Parasit Vectors 2018 01 17;11(1):41. Epub 2018 Jan 17.

Clinvet International, P.O. Box 11186, Universitas, Bloemfontein, 9321, South Africa.

Background: This study was designed to assess the ability of fed male Dermacentor reticulatus ticks to transmit Babesia canis to dogs after being detached from previous canine or ovine hosts.

Methods: The study was an exploratory, parallel group design conducted in two trials. All the animals were sero-negative for babesiosis prior to enrolment. In a first trial, donor dogs and donor sheep were infested with Babesia canis infected male and uninfected female ticks for 72 h. The ticks were detached and the second group of host dogs were infested for 24 h before tick removal. In a second trial, the experiment was repeated but the donor animals were infested for 88 h and the second group of host dogs were infested for 8 h prior to tick removal. After infestation, the dogs were maintained under clinical surveillance and blood samples were collected for blood smear, IFA and PCR analysis. A dog was considered infected if any of these tests were positive.

Results: All of the dogs (6 out of 6) were infected after being exposed to pre-activated male ticks for 24 h. Half of the dogs were infected after being exposed to pre-activated ticks for 8 h: 1 out of 3 dogs infested with ticks removed from sheep and 2 out of 3 dogs infested with ticks removed from dog. All the infected dogs were positive to blood smear, IFA and PCR. Three of these dogs exhibited elevated body temperature (> 39.4 °C).

Conclusions: This study demonstrates the ability of male D. reticulatus to transmit B. canis to dogs. The study also illustrates for the first time that, regardless of the first host on which ticks may attach and start feeding, Babesia canis can be transmitted to dogs within 8 h of infestation. Since no minimal transmission time can be established for all possible natural situations, a strategy of prevention based on anti-attachment or repellency is recommended.
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http://dx.doi.org/10.1186/s13071-018-2637-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772715PMC
January 2018

Efficacy of lotilaner (Credelio™), a novel oral isoxazoline against naturally occurring mange mite infestations in dogs caused by Demodex spp.

Parasit Vectors 2017 Nov 1;10(1):532. Epub 2017 Nov 1.

ClinVet International (pty) Ltd, Uitsigweg, Bainsvlei, 9338, Bloemfontein, Republic of South Africa.

Background: The oral systemic efficacy of lotilaner (Credelio™, Elanco) was evaluated against Demodex spp. in naturally infested dogs with generalized demodicosis.

Methods: In this study, 10 dogs with clinical signs of generalized demodicosis and positive for Demodex spp. mites based on skin scrapings were assigned to a single group orally treated with lotilaner (minimum dose of 20 mg/kg) on Days 0, 28 and 56.

Results: For lotilaner-treated dogs, pre-treatment mite counts based on skin scrapings performed at five different sites were reduced by > 99.9% (P < 0.0001) up to 56 days after the first and second monthly doses. No live mites were detected after Day 56 out to and including Day 84 post-treatment for 100% efficacy of each dog's Demodex mite infestation. Nine of 10 dogs were 100% mite-free from Day 28 (first evaluation) through Day 84 (end of study) and live mites were only found once on one dog (Day 56) following treatment with lotilaner. All dogs in the lotilaner-treated group showed marked improvement in the clinical signs of demodicosis and there were no drug associated adverse events. A marked improvement in hair re-growth was observed in all the dogs from 6 weeks following initiation of treatment.

Conclusions: In this study lotilaner administered at a minimum oral dose of 20 mg/kg was highly effective in reducing and eliminating live mite counts in dogs with natural infestations of Demodex spp.
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http://dx.doi.org/10.1186/s13071-017-2472-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664441PMC
November 2017

Assessment of the insecticidal activity of afoxolaner against Aedes aegypti in dogs treated with NexGard.

Parasite 2017 23;24:39. Epub 2017 Oct 23.

Boehringer Ingelheim Animal Health, 29 avenue Tony Garnier, 69007 Lyon, France.

Twelve healthy dogs were studied in this parallel group, blinded, randomised, and negative controlled efficacy study. On Day -1, the 12 dogs included were ranked within sex in descending order of individual pre-treatment (Day -5) fed mosquito counts and randomly allocated by blocks of two dogs to the untreated control group or the afoxolaner-treated group. NexGard (Merial, now part of Boehringer Ingelheim Animal Health) was administered orally on Day 0 in accordance with the European label instructions. On Days 1, 7, 14, 21 and 28, all dogs were exposed for a duration of 1 hour to 50 ± 5 unfed Aedes aegypti females. After each exposure, mosquitoes were collected after 1 hour and assessed for viability during collection and at 24 ± 2 hours. The arithmetic (and geometric) mean values of live fed mosquito counts at 24 hours after the exposure periods for the negative control group ranged from 33.7 (32.3) to 49.8 (49.7), indicating that this was a vigorous mosquito strain. There was no significant difference between control and treated groups in the number of live and fed mosquitoes at each 1 hour post-exposure collection time. Based on arithmetic and geometric mean values at 24 hours after each exposure, significantly fewer live fed mosquitoes were recorded in the treated group, compared to the negative control group, throughout the study (p < 0.001). The afoxolaner insecticidal efficacy against A. aegypti varied from 98% (Day 2) to 75.3% (Day 29) based on arithmetic means, and 98.7% (Day 2) to 89.8% (Day 29) based on geometric means.
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http://dx.doi.org/10.1051/parasite/2017042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5654328PMC
July 2018

Evaluation of the efficacy of sarolaner (Simparica®) in the prevention of babesiosis in dogs.

Parasit Vectors 2017 Sep 6;10(1):415. Epub 2017 Sep 6.

Clinvet International, PO Box 11186, 9321, Uitsig Road, Universitas, Bloemfontein, 9338, South Africa.

Background: Canine babesiosis is a clinically significant emerging vector-borne disease caused among others by the protozoan Babesia canis. The efficacy of sarolaner (Simparica®; Zoetis; at the minimum recommended label dose of 2.0 mg per kg bodyweight) in the prevention of babesiosis was evaluated in twenty-four dogs randomly allocated to either a placebo-treated group or one of two sarolaner-treated groups. At 21 or 28 days after treatment administration, dogs were infested with 50 ± 4 Dermacentor reticulatus ticks of which 25% were confirmed to be infected with Babesia canis. Blood samples were collected from each dog prior to tick infestation and weekly thereafter until 49 days after infestation. The blood was assayed for B. canis antibodies using an indirect immunofluorescence test (IFAT) and for B. canis DNA by PCR assay. A dog was a priori defined as B. canis-positive if it tested positive by both IFAT and PCR at any time during the study.

Results: No treatment-related adverse reactions were recorded during the study. All placebo-treated animals displayed clinical signs due to babesiosis and tested positive on both IFAT and PCR. None of the sarolaner-treated animals displayed any clinical symptoms or tested positive on both IFAT and PCR, resulting in a 100% efficacy in the prevention of canine babesiosis (P = 0.0002).

Conclusion: When given 21 or 28 days before tick infestation, a single treatment with sarolaner at the minimum recommended label dose of 2.0 mg per kg body weight prevented the transmission of B. canis by D. reticulatus to dogs.
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http://dx.doi.org/10.1186/s13071-017-2358-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5588728PMC
September 2017

The sustained speed of kill of ticks (Rhipicephalus sanguineus) and fleas (Ctenocephalides felis felis) on dogs by a spot-on combination of fipronil and permethrin (Effitix) compared with oral afoxolaner (NexGard).

Vet Parasitol 2017 Aug 10;243:52-57. Epub 2017 Jun 10.

Virbac SA, BP27, 06511 Carros Cedex, France. Electronic address:

The rapid speed of kill of a spot-on, combination of fipronil-permethrin (Effitix, Virbac) was shown against infestations of Rhipicephalus sanguineus and Ctenocephalides felis on dogs. Efficacy was determined against new infestations at weekly intervals for one month after treatment. Dogs were allocated randomly to either an untreated control or to a single administration, given on Day 0, of either topical fipronil-permethrin (6.7-13.4mg/kg and 60-120mg/kg, respectively) or oral afoxolaner (2.72-6.8mg/kg), based on pre-treatment, host-suitability flea counts. Dogs were infested with 50, unfed, adult R. sanguineus on Days 7, 14, 21 and 28, and with 100C. felis on Days 8, 15, 22 and 29. Tick counts were performed 0.5, 2, 6, 12 and 24h, and flea counts were performed 0.5 and 24h after each infestation. No treatment-related adverse reactions occurred. Dogs in the untreated group maintained viable infestations throughout the study. Following infestation, live tick and flea counts for dogs treated with fipronil-permethrin compared with untreated dogs were rapidly and significantly reduced with efficacy apparent at 0.5h after infestation. Flea efficacies (arithmetic mean counts) at 0.5h after infestation on Day 7 (Day 28) were significantly greater for fipronil-permethrin, 70% (34%) compared with 8% (18%) for afoxolaner (P≤0.05). Tick efficacies at 2h on Day 7 (Day 28) were 74% (63%) for fipronil-permethrin compared with 10% (0%) for afoxolaner (P≤0.05). Efficacies for tick repellency as indicated by counts of ticks off the dogs at 2h on Day 7 (Day 28) were greater for fipronil-permethrin, 32% (22%) compared with afoxolaner, 0% (0%) (P≤0.05). Anti-attachment efficacies at 12h were greater for fipronil-permethrin compared with afoxolaner. Tick efficacies at 24h, based on arithmetic (geometric) means, were significantly greater on Day 28 for fipronil-permethrin compared with afoxolaner (P≤0.05), 74% (87%) and 45% (60%), respectively, and were similar (P >0.05) on Days 7, 14 and 21. Flea efficacies, 24h after infestation were >98% and similar for both treated groups on all infestation days (P >0.05). The topically applied fipronil-permethrin containing ectoparasiticide Effitix offers rapid efficacy against R. sanguineus and C. felis which persists for one month after a single administration in dogs. Afoxolaner is also effective although speed of kill is slower. The rapid and sustained speed of kill of both parasites by fipronil-permethrin should contribute to effective management not only of these parasites and their direct adverse effects including irritancy and allergy, but also to reducing the risk of transmitting infections.
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http://dx.doi.org/10.1016/j.vetpar.2017.06.011DOI Listing
August 2017

Synergy between dinotefuran and fipronil against the cat flea (Ctenocephalides felis): improved onset of action and residual speed of kill in adult cats.

Parasit Vectors 2017 Jul 19;10(1):341. Epub 2017 Jul 19.

Ceva Santé Animale, 10 avenue de la Ballastière, 33500, Libourne, France.

Background: The cat flea, Ctenocephalides felis felis (C. felis), is a cosmopolitan hematophagous ectoparasite, and is considered to be the most prevalent flea species in both Europe and the USA. Clinical signs frequently associated with flea bites include pruritus, dermatitis and in severe cases even pyodermatitis and alopecia. Ctenocephalides felis is also a vector for several pathogens and is an intermediate host for the cestode Dipylidium caninum. Treatment of cats with a fast-acting pulicide, that is persistently effective in protecting the animal against re-infestation, is therefore imperative to their health. In addition, a rapid onset of activity ("speed of kill") may also reduce the risks of disease transmission and flea allergic dermatitis. The aim of this study was to evaluate the in vitro insecticidal activity and potential synergism between dinotefuran and fipronil against C. felis. A further aim was to evaluate the onset of activity and residual speed of kill of the combination in vivo on cats artificially infested with C. felis.

Methods: In the first study, the insecticidal activity of dinotefuran and fipronil separately and dinotefuran/fipronil (DF) in combination, at a fixed ratio (2:1), was evaluated using an in vitro coated-vial bioassay. In the second study, the onset of activity against existing flea infestations and residual speed of kill of DF against artificial flea infestations on cats was assessed in vivo. Onset of activity against existing flea infestations was assessed in terms of knock-down effect within 2 h post-treatment and onset of speed of kill assessed at 3 h, 6 h and 12 h post-treatment. Residual speed of kill was evaluated 6 h and 48 h after infestation, over a period of six weeks post-treatment.

Results: In vitro results revealed that the DF combination was synergistic and more potent against fleas than either compound alone. The combination also proved effective when tested in vivo. Efficacy was > 97% [geometric mean (GM) and arithmetic mean (AM)] at 3 h after treatment, and ≥ 99.8% (GM and AM) at 6 h and 12 h post-treatment. At 6 h after flea re-infestations, the efficacy of DF remained ≥ 90.8% (GM and AM) for up to 28 days, and at 42 days post-treatment persistent efficacy was still ≥ 54.3% (GM and AM). At 48 h after flea re-infestations, DF remained almost fully effective for up to 28 days, with efficacies ≥ 99.4% (GM and AM) and was persistently ≥ 93.0% (GM and AM) effective for up to 42 days post-treatment.

Conclusions: The combination of dinotefuran and fipronil in a single formulation exhibited strong synergistic insecticidal activity against C. felis in vitro, and also proved effective on artificially infested cats. This activity had a rapid onset that persisted for 6 weeks against re-infestations of C. felis on cats. The rapid curative insecticidal effect was observed as early as 3 h after treatment, and as early as 6 h after re-infestations for up to 6 weeks post-treatment. The insecticidal activity profile of DF makes it an optimal candidate for the protection of cats against flea infestations, and possibly also associated diseases.
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http://dx.doi.org/10.1186/s13071-017-2272-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517796PMC
July 2017

Comparative efficacy of a new spot-on combination product containing selamectin and sarolaner (Stronghold®Plus) versus fluralaner (Bravecto®) against induced infestations with Ixodes ricinus ticks on cats.

Parasit Vectors 2017 Jun 29;10(1):319. Epub 2017 Jun 29.

Clinvet, PO Box 11186, Universitas Bloemfontein, 9321, South Africa.

Background: Ticks are increasingly reported on cats worldwide, with Ixodes ricinus being a relevant species across Europe and in near by areas of North Africa and the Middle East. Yet there are few acaracidal products with proven efficacy approved for use in cats. The objective of this study was to compare the efficacy of a new spot-on formulation containing selamectin and sarolaner with a topical application of fluralaner (Bravecto®) against Ixodes ricinus ticks on cats. To that end, twenty-four (24) cats were randomly allocated to one of three treatment groups. The cats in the control group remained untreated. Cats in group 2 were treated with selamectin/sarolaner (Stronghold®Plus; Zoetis) at the minimum recommended dose of 1.0 mg/kg sarolaner and 6.0 mg/kg selamectin on Days 0, 30 and 60. The cats in group 3 received a fluralaner treatment (Bravecto®spot-on solution for cats, MSD) at the minimum recommended dose of 40.0 mg/kg on Day 0. Cats were infested with 50 (± 4) viable, adult, unfed I. ricinus ticks on Days 26, 54, 82 and 89 and ticks were removed for counting 48 h (± 2 h) later.

Results: Three monthly treatments with selamectin/sarolaner provided high and consistent efficacy against I. ricinus for the entire duration of the study period. In contrast, the efficacy of fluralaner declined in the second month after treatment and was below the efficacy threshold of 90% on Days 56, 84 and 91. The percentage efficacy against I. ricinus was numerically higher in the selemectin/sarolaner treated group than in the fluralaner-treated group on Days 56, 84 and 91. Furthermore, greasiness and spiking of the hair, as well as white deposits were frequently observed in the fluralaner-treated cats.

Conclusion: The results of the present study confirm the high and consistent efficacy of a new spot-on combination product containing selamectin and sarolaner against I. ricinus in cats, and indicate a decline in fluralaner efficacy during the 91 day period after treatment.
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http://dx.doi.org/10.1186/s13071-017-2259-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492925PMC
June 2017

Assessment of the efficacy of a topical combination of fipronil-permethrin (Frontline Tri-Act/Frontect) against egg laying and adult emergence of the cat flea (Ctenocephalides felis) in dogs.

Parasite 2016 19;23:57. Epub 2016 Dec 19.

ClinVet International (Pty) Ltd., Uitsig Road, Bainsvlei, 9321 Bloemfontein, South Africa.

This study was conducted to assess the prevention of egg laying and the inhibition of the emergence of the cat flea (Ctenocephalides felis) resulting from the application of a combination of fipronil and permethrin (Frontline Tri-Act/Frontect, Merial) on dogs. Sixteen healthy dogs were included after pre-treatment live flea counts and randomly allocated to two groups. Eight dogs served as untreated controls and 8 dogs were treated on Day 0 and Day 30 with topical application of fipronil/permethrin at the minimum dose of 6.76 mg/kg fipronil and 50.48 mg/kg permethrin. On days -2, 7, 21, 28, 42 and 56, each dog was infested with 100 fleas. Flea eggs were collected from each dog in individual trays from 12 to 36 h after treatment or each flea re-infestation. All fleas were removed by combing and counted 36 h after treatment or infestations. The collected eggs were counted and incubated for 28 days for larval development and adult emergence assessment. The curative efficacy of Frontline Tri-Act/Frontect against adult fleas 36 h after treatment was 95.3% and the efficacy remained 100% after subsequent flea infestations for 8 weeks. Compared to the control group, the treatment reduced egg laying by 84.5% within 36 h after first treatment and was 99.9%, 100%, 100%, 100%, 100% on collection days 7, 21, 29, 43 and 57, respectively. Frontline Tri-Act/Frontect reduced by 28.7% the emergence of new adult fleas from eggs laid during the 48 h of pre-treatment infestation. The inhibition of adult emergence from incubated flea eggs could not be assessed after flea re-infestation in the treated group as no eggs were collected.
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http://dx.doi.org/10.1051/parasite/2016068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5178383PMC
August 2017

Efficacy of fluralaner administered either orally or topically for the treatment of naturally acquired Sarcoptes scabiei var. canis infestation in dogs.

Parasit Vectors 2016 07 7;9(1):392. Epub 2016 Jul 7.

MSD Animal Health Innovation GmbH, Zur Propstei, Schwabenheim, 55270, Germany.

Background: The efficacy of fluralaner, formulated as a chewable tablet (Bravecto™) or topical solution (Bravecto™ Spot-on Solution), was evaluated against naturally acquired Sarcoptes scabiei var. canis infestation in dogs.

Methods: The study was performed in privately-owned dogs naturally infested with S. scabiei var. canis. All dogs living in the same household as the infested dog were enrolled into one of 3 groups (2 fluralaner treated and 1 negative control). All dogs within one household were administered the same treatment, with one dog per household included in further observations and assessments. In total, 29 dogs confirmed positive for sarcoptic mange were included. On Day 0, all dogs in group 1 (n = 9) were treated once orally with fluralaner at a minimum dose of 25 mg/kg body weight; all dogs in group 2 (n = 11) were treated once topically with fluralaner at a dose of 25 mg/kg body weight; and dogs in group 3 (n = 9) were treated once topically with saline solution. Sarcoptes scabiei var. canis mites on each dog were counted before treatment and at 4 weeks after treatment in deep skin scrapings (~4 cm(2)) from 5 different body areas. Clinical signs of infestation (i.e. erythematous papules; casts, scales and crusts; body areas with hair loss) and pruritus were recorded at the same time points.

Results: Single oral or topical treatment with fluralaner resulted in a 100 % reduction in mite counts post-treatment (group 1: P = 0.0009 and group 2: P = 0.0011). Resolution of clinical signs at four weeks post-treatment was variable, with improvement observed for erythematous papules, casts and crusts, and pruritus. All fluralaner treated dogs showed an improvement in overall hair re-growth compared with pre-treatment observations.

Conclusion: Fluralaner administered either orally or topically to naturally infested dogs eliminates Sarcoptes scabiei var. canis mites and improves clinical signs over a 4-week observation period.
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http://dx.doi.org/10.1186/s13071-016-1670-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937584PMC
July 2016

Efficacy of afoxolaner in a clinical field study in dogs naturally infested with Sarcoptes scabiei.

Parasite 2016 17;23:26. Epub 2016 Jun 17.

Clinvet International (Pty) Ltd, PO Box 11186, 9321 Universitas, South Africa.

The acaricidal efficacy of afoxolaner (NexGard(®), Merial) was evaluated against Sarcoptes scabiei var. canis in a field efficacy study, when administered orally at a minimum dose of 2.5 mg/kg to dogs naturally infested with the mites. Twenty mixed-breed dogs of either sex (6 males and 14 females), aged over 6 months and weighing 4-18 kg, were studied in this randomised controlled field efficacy trial. Dogs, naturally infested with Sarcoptes scabiei var. canis confirmed by skin scrapings collected prior to allocation, were randomly divided into two equal groups. Dogs in Group 1 were not treated. Dogs in Group 2 were treated on Days 0 and 28. On Days 0 (pre-treatment), 28 (pre-treatment) and 56, five skin scrapings of similar size were taken from different sites with lesions suggestive of sarcoptic mange. The extent of lesions was also recorded on Days 0, 28 and 56, and photographs were taken. Dogs treated orally with afoxolaner had significantly (p < 0.001) lower mite counts than untreated control animals at Days 28 and 56 with no mites recovered from treated dogs at these times (100% efficacy based on mite counts). In addition, dogs treated with NexGard had significantly (p < 0.05) better lesion resolution at Day 56 than Day 0; no treated dog showed pruritus compared to 7/10 dogs in the control group, 1/9 treated dogs had crusts compared to 5/10 controls and 8/9 dogs recovered 90% of hairs on lesions compared to 0/10 control dogs.
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http://dx.doi.org/10.1051/parasite/2016026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912682PMC
August 2017

Efficacy of fluralaner spot-on solution against induced infestations with Rhipicephalus sanguineus on dogs.

Parasit Vectors 2016 05 31;9(1):276. Epub 2016 May 31.

MSD Animal Health Innovation GmbH, Zur Propstei, 55270, Schwabenheim, Germany.

Background: The efficacy of fluralaner spot-on solution administered once topically against induced infestations with Rhipicephalus sanguineus was evaluated in dogs over a 12-week post-treatment period.

Methods: Six negative-controlled studies were conducted, involving a total of 112 adult dogs (57 mixed breed, 47 Beagles, eight Labradors). In each study, dogs were randomized to two groups of eight to ten dogs each. On day 0, dogs in each treated group were topically administered fluralaner spot-on solution once at a dose of 25 mg/kg body weight, while dogs in each control group were not treated. Two days before treatment, and on days 28, 56 and 84 after treatment, all dogs were infested with approximately 50 unfed, adult Rh. sanguineus ticks (sex ratio 1:1). Ticks were removed and counted on days 2, 30 (4 weeks), 58 (8 weeks), and 86 (12 weeks) after treatment to assess efficacy.

Results: Efficacy against ticks 2 days after treatment was 91.1 % (study 1), 98.4 % (study 2), 100 % (study 3), 97.6 % (study 4), 99.6 % (study 5), and 99.8 % (study 6). At all other assessment time points, tick efficacy was 95.4-100 %. Tick reduction in all treatment groups was significant at all assessment time points (P < 0.0001).

Conclusions: A single topical administration of fluralaner spot-on solution provides a high level of therapeutic and persistent efficacy against Rh. sanguineus ticks over the subsequent 12 weeks.
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http://dx.doi.org/10.1186/s13071-016-1523-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886405PMC
May 2016

Prevention of transmission of Babesia canis by Dermacentor reticulatus ticks to dogs after topical administration of fluralaner spot-on solution.

Parasit Vectors 2016 05 31;9(1):234. Epub 2016 May 31.

MSD Animal Health Innovation GmbH, ZurPropstei, 55270, Schwabenheim, Germany.

Background: The preventive effect of fluralaner spot-on solution against transmission of Babesia canis by Dermacentor reticulatus ticks was evaluated.

Findings: Sixteen dogs, tested negative for B. canis by polymerase chain reaction (PCR) and immunofluorescence assay test (IFAT), were allocated to two study groups. On day 0, dogs in one group (n = 8) were treated once topically with fluralaner spot-on solution (Bravecto™ Spot-on Solution) according to label recommendations and dogs in the control group (n = 8) remained untreated. On days 2, 28, 56, 70 and 84, all dogs were infested with 50 (±4) D. reticulatus ticks harbouring B. canis, with tick in situ thumb counts 48 ± 4 h after each infestation. On day 90, ticks were removed from all dogs and counted. Prior to each infestation, the presence of B. canis in the respective tick batch was confirmed by PCR, and 12-16 % of ticks were found to be infected with B. canis. Efficacy against ticks was 99.5 and 99.3 % on days 4 and 58 after treatment, respectively and 100 % on all other days. Replacement dogs were included for any B. canis infected control dog (in total 19). All control dogs (n = 27) became infected with B. canis, as confirmed by PCR, performed every 7 days, and by IFAT, performed every 14 days after treatment. None of the eight treated dogs became infected with B. canis, as they were tested negative by PCR and IFAT throughout the study until day 112. By comparing infected dogs in the treated group with infected dogs in the untreated control group, a 100 % preventive effect against B. canis transmission was demonstrated.

Conclusions: A single topical administration of fluralaner spot-on solution effectively prevented the transmission of B. canis by infected D. reticulatus ticks over a 12-week period.
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http://dx.doi.org/10.1186/s13071-016-1481-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886439PMC
May 2016

Efficacy of a novel oral formulation of sarolaner (Simparica™) against four common tick species infesting dogs in Europe.

Vet Parasitol 2016 May 1;222:33-6. Epub 2016 Apr 1.

Zoetis, Veterinary Medicine Research and Development, 333 Portage St., Kalamazoo, MI 49007 USA.

The efficacy of single oral treatment of sarolaner (Simparica™, Zoetis), a novel isoxazoline compound, was evaluated against four tick species known to commonly infest dogs in Europe. Eight laboratory studies were conducted using adult purpose-bred Beagle dogs. In each study, 16 animals were randomly allocated to one of two treatment groups based on pre-treatment host-suitability tick counts. Dogs were infested with 50 unfed adult Dermacentor reticulatus (two studies), Ixodes hexagonus (three studies), Ixodes ricinus (two studies) or Rhipicephalus sanguineus (one study) ticks on Days -2, 5, 12, 19, 26 and 33. On Day 0, dogs were treated orally with placebo or sarolaner tablets providing the minimum dose of 2.0mg/kg bodyweight and tick counts were conducted 48h after treatment and after each subsequent weekly re-infestation. There were no treatment-related adverse reactions in any of the studies. Dogs in the placebo-treated group maintained tick infestations throughout the studies. Geometric mean live tick counts were significantly (P≤0.0001) lower in the sarolaner-treated group compared to the tick counts in the placebo group at all time-points. A single oral administration of sarolaner resulted in 100% efficacy against existing infestations of all tick species except R. sanguineus, for which the efficacy was 99.7%, within 48h. Efficacy against weekly re-infestations was ≥97.5% for all tick species for 35 days. Thus, a single dose of sarolaner administered orally at the minimum dosage of 2 mg/kg, resulted in ≥99.7% efficacy within 48h against existing tick infestations, and in ≥97.5% efficacy against weekly re-infestations, for at least 35 days after treatment. These studies confirmed that administration of the minimum dose of sarolaner will provide treatment of existing infestations and give at least one month of control against re-infestation by the common tick species affecting dogs in Europe.
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http://dx.doi.org/10.1016/j.vetpar.2016.03.024DOI Listing
May 2016

Comparative speed of kill of oral treatments with Simparica™ (sarolaner) and Bravecto®(fluralaner) against induced infestations of Rhipicephalus sanguineus on dogs.

Parasit Vectors 2016 Feb 24;9:103. Epub 2016 Feb 24.

Zoetis, Veterinary Medicine Research and Development, 333 Portage St., Kalamazoo, MI, 49007, USA.

Background: Rhipicephalus sanguineus is the most widely distributed tick species infesting dogs worldwide, which may cause discomfort to the host and transmit diseases. Acaricides with a rapid and sustained speed of kill are thus important to prevent infestation and to reduce the risk of disease transmission. In this study, the speed of kill of a monthly administered Simparica™ (sarolaner) treatment against induced infestations with R. sanguineus on dogs was evaluated and compared with a single dose of Bravecto®(fluralaner) for 95 days after the initial treatment.

Methods: Twenty four dogs were randomly allocated to treatment and were treated with either placebo or sarolaner (at 2 to 4 mg/kg) on Days 0, 30 and 60 or with fluralaner (at 25 to 56 mg/kg) once on Day 0. Tick counts were performed in situ 8 and 12 h and with removal of the ticks 24 h after treatment and subsequent re-infestations on Days 14, 28, 44, 56, 74, 90 and 95. Acaricidal efficacy was determined at each time point relative to the placebo group.

Results: Both products significantly reduced live ticks within 8 h after treatment against an existing infestation with R. sanguineus, and killed all ticks on all dogs within 24 h. After re-infestation, sarolaner provided ≥98.5 % reduction within 24 h on all days except Days 74 and 95 (P < 0.0001), compared to fluralaner which provided ≥95.5 % reduction until Day 44. Geometric mean live tick counts for sarolaner were significantly lower (P ≤ 0.0415) at 24 h than those for fluralaner on all days, except on Days 0, 14 and 28 (P ≥ 0.0678). There were no treatment-related adverse reactions observed during the study.

Conclusions: When dosed at monthly intervals for 3 consecutive months, Simparica™ has a faster and more consistent speed of kill against R. sanguineus than a single oral dose of Bravecto® for which efficacy decreased after Day 44.
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http://dx.doi.org/10.1186/s13071-016-1376-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765226PMC
February 2016

Comparative speed of kill of sarolaner (Simparica and fluralaner (Bravecto) against induced infestations of Ctenocephalides felis on dogs.

Parasit Vectors 2016 Feb 19;9:92. Epub 2016 Feb 19.

Zoetis, Veterinary Medicine Research and Development, 333 Portage St., Kalamazoo, MI, 49007, USA.

Background: Fleas are the most common ectoparasite infesting dogs globally and cause direct discomfort, induce allergic reactions, and transmit pathogenic agents. Rapid speed of kill is an important characteristic for a parasiticide in order to alleviate the direct deleterious effects of fleas, reduce the impact of allergic responses, and break the flea life cycle. In this study, the speed of kill of a novel, orally administered isoxazoline parasiticide, sarolaner (Simparica), against fleas on dogs was evaluated and compared with fluralaner (Bravecto) over a 3-month period.

Methods: Based on pretreatment flea counts, 24 dogs were randomly allocated to treatment with oral sarolaner at the label rate (2 to 4 mg/kg), once a month for 3 months, or oral fluralaner (25 to 50 mg/kg), once per label directions, or placebo. Dogs were combed and live fleas counted at 8, 12, and 24 h after treatment and subsequent re-infestations on Days 14, 29, 44, 59, 74 and 90. Efficacy was determined at each time point relative to counts for placebo dogs.

Results: There were no adverse reactions to treatment. Three monthly doses of sarolaner provided ≥97.6 % efficacy (based on arithmetic means) within 8 h of treatment or subsequent weekly re-infestations of fleas for 3 months. By 12 h, fleas were eradicated from all dogs (100 % efficacy). Significantly greater numbers of live fleas were recovered from fluralaner-treated dogs at 8 h on Days 74 and 90 (P ≤ 0.0043) when efficacy (based on arithmetic means) was only 80.7 and 72.6 %, respectively.

Conclusions: In this controlled laboratory evaluation, sarolaner had a significantly faster speed of kill against fleas than fluralaner at the end of its claimed treatment period. The rapid and consistent kill of fleas within 8 to 12 h after monthly oral doses of sarolaner indicates that this treatment will provide rapid and highly effective control of flea infestations, and suggests that it will provide relief for dogs suffering from flea allergy dermatitis, and should reduce the risk of flea-borne pathogen transmission.
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http://dx.doi.org/10.1186/s13071-016-1373-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761176PMC
February 2016

Comparative speed of kill of sarolaner (Simparica) and afoxolaner (NexGard) against induced infestations of Ctenocephalides felis on dogs.

Parasit Vectors 2016 Feb 19;9:90. Epub 2016 Feb 19.

Zoetis, Veterinary Medicine Research and Development, 333 Portage St., Kalamazoo, MI, 49007, USA.

Background: Fleas are the most common ectoparasite infesting dogs globally. The many possible sequellae of infestation include: direct discomfort; allergic reactions; and the transmission of pathogens. Rapid speed of kill is an important characteristic for a parasiticide in order to alleviate the direct deleterious effects of fleas, reduce the impact of allergic responses, and break the flea infestation cycle. In this study, the speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner (Simparica) against fleas on dogs was evaluated and compared with afoxolaner (NexGard) for 5 weeks after a single oral dose.

Methods: Twenty-four dogs were randomly allocated to treatment with a single oral dose at label rate of either sarolaner (2 to 4 mg/kg) or afoxolaner (2.5 to 6.8 mg/kg) or placebo, based on pretreatment flea counts. Dogs were combed and live fleas counted at 8, 12 and 24 h after treatment and subsequent re-infestations on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for placebo dogs.

Results: There were no adverse reactions to treatment. A single oral dose of sarolaner provided ≥98.8% efficacy (based on geometric means) within 8 h of treatment or subsequent weekly re-infestations of fleas to Day 35. By 12 h, fleas were virtually eradicated from all dogs, with only two fleas recovered from a single sarolaner-treated dog on Day 7; efficacy was 100% at all other time points. Significantly greater numbers of live fleas were recovered from afoxolaner-treated dogs at 8 h on all days and at 12 h on Days 28 and 35 (P < 0.05).

Conclusions: In this controlled laboratory evaluation, sarolaner had a significantly faster speed of kill against fleas than afoxolaner. This was noticeably more evident towards the end of the treatment period. The rapid and consistent kill of fleas within 8 to 12 h after a single oral dose of sarolaner over 35 days indicates that this treatment will provide highly effective control of flea infestations, relief for dogs afflicted with flea allergy dermatitis, and should reduce the risk of flea-borne pathogen transmission.
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http://dx.doi.org/10.1186/s13071-016-1372-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759729PMC
February 2016

Assessment of the prophylactic speed of kill of Frontline Tri-Act(®) against ticks (Ixodes ricinus and Rhipicephalus sanguineus) on dogs.

Parasite 2016 21;23. Epub 2016 Jan 21.

ClinVet International (Pty) Ltd, PO Box 11186, 9321 Universitas, South Africa.

The objective of the study was to assess the speed of kill of a single topical treatment with a combination of fipronil and permethrin (Frontline Tri-Act(®)/Frontect(®)) against experimental infestations of Ixodes ricinus and Rhipicephalus sanguineus ticks on dogs. In this parallel group designed, randomised, single centre, controlled efficacy study, 16 healthy adult dogs were allocated to two groups: 8 dogs were treated with the topical combination on Day 0 and the other 8 dogs served as untreated controls. Each dog was exposed in a crate to 100 I. ricinus (50 females, 50 males) and 50 R. sanguineus (25 males, 25 females) on Days 2, 7, 14, 21 and 28. Ticks were counted in situ at 6 and 12 h after exposure and removed at 24 h after exposure. Frontline Tri-Act(®) was effective (≥90%) against both R. sanguineus and I. ricinus tick infestations at 6, 12 and 24 h after exposure, from 2 to 28 days after treatment. This is the first time that a topical ectoparasiticide has demonstrated a preventive killing effect against these two tick species in 6 h for a full month.
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http://dx.doi.org/10.1051/parasite/2016002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722230PMC
October 2016

Repellency and acaricidal efficacy of a new combination of fipronil and permethrin against Ixodes ricinus and Rhipicephalus sanguineus ticks on dogs.

Parasit Vectors 2015 Oct 13;8:531. Epub 2015 Oct 13.

Merial Limited, 3239 Satellite Blvd., Duluth, GA, 30096, USA.

Background: A blinded, controlled laboratory study was conducted to assess the repellency and acaricidal activity of a topical spot on formulation, a combination of fipronil and permethrin, against Ixodes ricinus and Rhipicephalus sanguineus ticks on dogs.

Methods: A group of 16 adult mixed breed dogs were randomly divided into treatment and control groups based on pre-treatment live tick counts. On Day 0, the topical spot on formulation of fipronil + permethrin (commercialized under the name Frontline Tri-Act®/Frontect®) was administered to dogs in the treatment group at the minimum recommended dose of 0.1 mL/kg, corresponding to 6.76 mg fipronil/kg and 50.48 mg/kg permethrin. Tick infestations were performed with I. ricinus (50 females, 50 males) and R. sanguineus (25 females, 25 males) on each dog on Days 2, 7, 14, 21, and 28. Dogs were sedated prior to exposure and confined to crates for approximately 4 h following tick challenge. Ticks were released next to the sedated dogs and tick counts were performed at 4 h and 24 h after the start of exposure for tick counts and removal.

Results: Repellency at 4 h against I. ricinus was 72.6, 96.3, 92.8, 89.0, and 88.7 % on Days 2, 7, 14, 21, and 28, respectively. Repellency was 100 % 24 h after exposures on Days 2, 7, and 14 and 99.6 % after exposures on Days 21 and 28. For R. sanguineus, repellency at 4 h was 78.0, 96.8, 91.5, 88.0, and 56.8 % on Days 2, 7, 14, 21, and 28, respectively. Repellency at 24 h was 98.6, 100, 98.7, 96.1, and 95.1 % for exposures on Days 2, 7, 14, 21, and 28, respectively. For I. ricinus, acaricidal efficacy recorded at 4 h was ≥ 91.1 % during the full month and was ≥ 99.5 % for the full month when counted at 24 h. Acaricidal efficacy against R. sanguineus was ≥ 94.7 % at 4 h from Day 2 to Day 21 and was 71.4 % on Day 28. Acaricidal efficacy at 24 h, was > 97.7 % during the month. Tick counts were statistically significantly reduced in treated dogs at all time-points during the study.

Conclusions: A combination of fipronil and permethrin was highly effective at rapidly repelling and killing both I. ricinus and R. sanguineus ticks on dogs for at least 4 weeks, with a significant effect at 4 and 24 h after tick exposure.
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http://dx.doi.org/10.1186/s13071-015-1150-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605137PMC
October 2015

Prevention of transmission of Babesia canis by Dermacentor reticulatus ticks to dogs treated orally with fluralaner chewable tablets (Bravecto™).

Parasit Vectors 2015 Jun 4;8:305. Epub 2015 Jun 4.

MSD Animal Health Innovation GmbH, Zur Propstei, 55270, Schwabenheim, Germany.

Background: The preventive effect of fluralaner chewable tablets (Bravecto™) against transmission of Babesia canis by Dermacentor reticulatus ticks was evaluated.

Methods: Sixteen dogs, tested negative for B. canis by PCR and IFAT, were allocated to two study groups. On day 0, dogs in one group (n = 8) were treated once orally with a fluralaner chewable tablet according to label recommendations and dogs in the control group (n = 8) remained untreated. On days 2, 28, 56, 70 and 84, dogs were infested with 50 (±4) B. canis infected D. reticulatus ticks with tick in situ thumb counts 48 ± 4 h post-infestation. Prior to each infestation, the D. reticulatus ticks were confirmed to harbour B. canis by PCR analysis. On day 90, ticks were counted and removed from all dogs. Efficacy against ticks was calculated for each assessment time point. After treatment, all dogs were physically examined in conjunction with blood collection for PCR every 7 days, blood samples for IFAT were collected every 14 days and the dog's rectal body temperature was measured thrice weekly. From dogs displaying symptoms of babesiosis or were PCR positive, a blood smear was taken, and, if positive, dogs were rescue treated and replaced with a replacement dog. The preventive effect was evaluated by comparing infected dogs in the treated group with infected dogs in the untreated control group.

Results: All control dogs became infected with B. canis, as confirmed by PCR and IFAT. None of the 8 treated dogs became infected with B. canis, as IFAT and PCR were negative throughout the study until day 112. Fluralaner chewable tablet was 100 % effective against ticks on days 4, 30, 58, and 90 and an efficacy of 99.6 % and 99.2 % was achieved on day 72 and day 86 after treatment, respectively. Over the 12-week study duration, a 100 % preventive effect against B. canis transmission was demonstrated.

Conclusions: A single oral administration of fluralaner chewable tablets effectively prevented the transmission of B. canis by infected D. reticulatus ticks over a 12-week period.
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http://dx.doi.org/10.1186/s13071-015-0923-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465614PMC
June 2015

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

Parasit Vectors 2015 Mar 28;8:187. Epub 2015 Mar 28.

MSD Animal Health Innovation SAS, 49071, Beaucouzé Cedex, France.

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 cm(2)) 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.
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http://dx.doi.org/10.1186/s13071-015-0775-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394402PMC
March 2015

Comparative efficacy of two oral treatments for dogs containing either afoxolaner or fluralaner against Rhipicephalus sanguineus sensu lato and Dermacentor reticulatus.

Vet Parasitol 2015 Apr 12;209(1-2):142-5. Epub 2015 Feb 12.

Merial S.A.S., 29 Av Tony Garnier, 69007 Lyon, France.

The present study compares the efficacy of two recent oral ectoparasiticides containing isoxazolines (NexGard(®), containing afoxolaner and administered at a monthly regimen, and Bravecto™ containing fluralaner and administered at a tri-monthly regimen) against Rhipicephalus sanguineus sensu lato and Dermacentor reticulatus ticks on dogs. 24 dogs were randomly allocated to untreated control, NexGard(®) treated, and Bravecto™ treated groups. The treatments were administered on Days 0, 28 and 56 for afoxolaner and on Day 0 for fluralaner. Tick infestations were performed weekly with 50 unfed adult ticks per each species on each dog from Days 30 to 84 (with the exception of R. sanguineus on Day 63). Ticks were counted at 24h post-infestation. The dogs from both treated groups had statistically significantly (p<0.05) less R. sanguineus and D. reticulatus ticks compared to the untreated dogs on all assessment days. Percent efficacy against R. sanguineus ranged from 86.4% to 99.5% at 24h post-infestation for NexGard(®) and from 65.7% to 100% for Bravecto™. Statistically significantly (p<0.05) less R. sanguineus ticks were recorded for NexGard(®) treated dogs compared to Bravecto™ treated dogs on Day 78. Percent efficacy against D. reticulatus ranged from 85.2% to 99.6% at 24h post-infestation for NexGard(®) and from 63.4% to 99.1% for Bravecto™. Statistically significantly (p<0.05) less D. reticulatus ticks were recorded for NexGard(®) treated dogs compared to Bravecto™ treated dogs on Days 71, 78 and 85.
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http://dx.doi.org/10.1016/j.vetpar.2015.02.002DOI Listing
April 2015

Comparative speed of efficacy against Ctenocephalides felis of two oral treatments for dogs containing either afoxolaner or fluralaner.

Vet Parasitol 2015 Jan 19;207(3-4):297-301. Epub 2014 Dec 19.

Merial S.A.S., 29 Av Tony Garnier, 69007 Lyon, France.

A study was designed to compare the efficacy of NexGard(®) and Bravecto™, 2 recently introduced oral ectoparasiticides containing isoxazolines, against fleas (Ctenocephalides felis) on dogs. Twenty-four healthy dogs, weighing 9.2 kg to 28.6 kg, were included in this parallel group design, randomized, and controlled efficacy study. On Day -1, the 24 dogs were allocated to 3 study groups: untreated control; Nexgard(®) treated and Bravecto™ treated. The treatments were administered on Days 0, 28 and 56 for Nexgard(®) (labelled for monthly administration), and once on Day 0 for Bravecto™ (labelled for a 12 week use). Flea infestations were performed weekly with 100 adult unfed C. felis on each dog from Days 42 to 84. Fleas were counted and re-applied at 6 and 12 h post-infestation and removed and counted 24 h post-infestation. The arithmetic mean flea count for the untreated group ranged from 62.9 to 77.6 at 24 h post-infestation, indicating vigorous flea challenges on all assessment days. Both the Nexgard(®) and Bravecto™ treated groups had statistically significantly (p<0.05) less fleas compared to the untreated group on all assessment time points and days. Significantly fewer fleas were recorded for NexGard(®) treated dogs compared to Bravecto™ treated dogs at 6 h post-infestation on Day 56, 63, 70, 77 and 84 and at 12 h post-infestation on Days 70 and 84. No statistically significant (p<0.05) differences were recorded between the treated groups at 24 h post-infestation. Efficacies recorded 6 h post-infestation for Nexgard(®) ranged from 62.8% (Day 49) to 97.3% (Day 56), and efficacies ranged from 94.1% (Day 49) to 100% (Days 42, 56, 70 and 84) at 12 h post-infestation. Efficacies recorded for Bravecto™ ranged from 45.1% (Day 84) to 97.8% (Day 42) at 6 h post-infestation, and from 64.7% (Day 84) to 100% (Days 42 and 56) at 12 h post-infestation. Efficacies observed at 24 h were 100% for both products during the study except 99.6% on Day 84 for Bravecto™.
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http://dx.doi.org/10.1016/j.vetpar.2014.12.007DOI Listing
January 2015

Afoxolaner against fleas: immediate efficacy and resultant mortality after short exposure on dogs.

Parasite 2014 25;21:42. Epub 2014 Aug 25.

ClinVet International, Universitas, 9301 Bloemfontein, Free State, South Africa.

The speed of efficacy of afoxolaner (NexGard) against Ctenocephalides felis fleas was evaluated in two studies. Study A assessed the efficacy against existing fleas whereas study B assessed the efficacy against new infesting fleas. In study A, 12 dogs were allocated to the untreated group and 20 dogs to the treated group. All dogs were infested by 100 fleas each at Day -1, treated at Day 0 and flea combed at 2 h or at 6 h post treatment. In study B, 6 dogs were allocated to the untreated group and 10 to the treated group. They were infested with 100 fleas each on Days 2, 7, 14, 21 and 28. Fleas were removed and counted at 6 h post-infestation. Immediate and persistent efficacies were evaluated by counting fleas on the dogs. To evaluate induced mortality after exposure on dogs, fleas collected alive were placed in an insectarium for 24 h and assessed for viability. The immediate efficacy on dogs was significant at 6 h with 100%. The induced death of the fleas collected live from dogs 2 h after exposure was 99.7%. Concerning new infesting fleas, the observed efficacy at 6 h and the induced mortality were significantly different (p < 0.05) from the control at all time-points. At 6 h, the prophylactic efficacy was > 97% at Day 2 and Day 8 and > 90% at Day 14. The induced mortality after 6 h of exposure on dogs varied between 73.3% and 100% for the whole study.
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http://dx.doi.org/10.1051/parasite/2014045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141545PMC
May 2015

The effects of a pour-on formulation of fluazuron 2.5 % and flumethrin 1 % on populations of Rhipicephalus decoloratus and Rhipicephalus microplus both on and off bovine (Bonsmara breed) hosts.

Parasitol Res 2013 Aug;112 Suppl 1:67-79

ClinVet International, Universitas, South Africa.

The present study demonstrated the efficacy of a pour-on formulation of fluazuron 2.5 % and flumethrin 1 % (Drastic Deadline eXtreme®) against Rhipicephalus decoloratus and Rhipicephalus microplus on cattle on pasture previously grazed by experimentally infested animals. Six tick-free cattle were placed on the pasture and treated 7 days later (Day 0) with the pour-on. They were retreated on Days 63, 126 and 189 and monthly tick counts were done. Mean numbers of adult R. decoloratus and/or R. microplus decreased from 53 and 14 on Days 56 and 112 respectively to 2 or less on all other occasions including Day 254. Compared to the numbers of R. decoloratus and/or R. microplus larvae collected from vegetation in the previous year, larval numbers declined by 40.7 % on Day 28, and thereafter reduction remained between 84 % and 100 %. Pairs of tracer calves placed on the pasture for 7 days each month were then held in pens and adult ticks that detached collected. Reduction in the numbers of R. decoloratus collected from tracer animals was 75 % on Day 56 and remained above 93 % except for Day 224 when it temporarily decreased to 78.5 %. Reduction in the numbers of R. microplus was 97.5 % on Day 28 and remained above 98 % until the conclusion of the study on Day 254. Treatment with the pour-on formulation of fluazuron and flumethrin resulted in a marked decrease in the numbers of R. decoloratus and/or R. microplus on treated cattle followed by a reduction in the numbers of larvae questing on the vegetation and ticks picked up by tracer calves. No other potential host species for R. decoloratus and/or R. microplus were present in the camps.
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http://dx.doi.org/10.1007/s00436-013-3282-xDOI Listing
August 2013