The speed of kill of fluralaner (Bravecto™) against Ixodes ricinus ticks on dogs

Particle and Fibre Toxicology

Anja R Heckeroth¹  Rainer KA Roepke¹  Judith Langenstein²  Andreas Moritz²  Eva Zschiesche¹  Heike Williams¹  Christina Wengenmayer¹ 

[1] MSD Animal Health Innovation GmbH, Zur Propstei, Schwabenheim, 55270, Germany;Department of Veterinary Clinical Sciences, Clinical Pathophysiology and Clinical Pathology, Justus-Liebig-University Giessen, Giessen, Germany

关键词: Efficacy;    Tick-borne diseases;    Ixodes ricinus;    Tick;    Dog;    Speed of kill;    Fluralaner;    Bravecto¿ chewable tablets;   

Others  :  1149293
DOI  :  10.1186/s13071-014-0525-3

 received in 2014-07-25, accepted in 2014-11-05,  发布年份 2014

【 摘 要 】

Background

Pathogens that are transmitted by ticks to dogs, such as Anaplasma phagocytophilum, Babesia spp., Borrelia burgdorferi sensu latu, and Ehrlichia canis, are an increasing problem in the world. One method to prevent pathogen transmission to dogs is to kill the ticks before transmission occurs. Fluralaner (Bravecto¿) is a novel isoxazoline insecticide and acaricide that provides long persistent antiparasitic activity following systemic administration. This study investigated the speed of kill of fluralaner against Ixodes ricinus ticks on dogs.

Methods

A total of 48 dogs were randomized to 8 groups of 6 dogs and each dog was infested with 50 female and 10 male I. ricinus ticks. Two days later (day 0), 4 groups received a single treatment of 25 mg fluralaner/kg body weight as Bravecto¿ chewable tablets; the dogs in the other 4 groups were left untreated. Separate control and treatment groups were paired at each time point (4, 8, 12, or 24 hours after treatment) for assessment of tick-killing efficacy. At 4, 8, and 12 weeks after treatment, all dogs were re-infested with 50 female I. ricinus ticks and subsequently assessed for live or dead ticks at either 4, 8, 12, or 24 hours after re-infestation. Efficacy was calculated for each assessment time point by comparison of the treatment group with the respective control group.

Results

Tick-killing efficacy was 89.6% at 4 hours, 97.9% at 8 hours, and 100% at 12 and 24 hours after treatment. Eight hours after re-infestation, efficacy was 96.8%, 83.5%, and 45.8% at 4, 8, and 12 weeks after treatment, respectively. At least 98.1% tick-killing efficacy was demonstrated 12 and 24 hours after re-infestation over the entire 12 week study period.

Conclusions

Fluralaner kills ticks rapidly after treatment at 4 hours, and over its entire 12-week period of efficacy, it achieves an almost complete killing effect within 12 hours after tick infestation. The rapid tick-killing effect together with the long duration of efficacy enables fluralaner to aid in the prevention of tick borne diseases.

【 授权许可】

   
2014 Wengenmayer et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Chomel B: Tick-borne infections in dogs-an emerging infectious threat. Vet Parasitol 2011, 179:294-301.
• [2]Little SE: Changing paradigms in understanding transmission of canine tick-borne diseases: the role of interrupted feeding and intrastadial transmission. In 2nd Canine Vector-Borne Disease (CVBD) Symposium. ?, Mazara del Vallo, Sicily, Italy; 2007:30-34.
• [3]Dantas-Torres F, Chomel BB, Otranto D: Ticks and tick-borne diseases: a One health perspective. Trends Parasitol 2012, 28:437-446.
• [4]Piesman J, Eisen L: Prevention of tick-borne diseases. Annu Rev Entomol 2008, 53:323-343.
• [5]Irwin PJ: It shouldn't happen to a dog ¿ or a veterinarian: clinical paradigms for canine vector-borne diseases. Trends Parasitol 2014, 30:104-112.
• [6]Otranto D, Dantas-Torres F, Breitschwerdt EB: Managing canine vector-borne diseases of zoonotic concern: part two. Trends Parasitol 2009, 25:228-235.
• [7]Jongejan F, Fourie JJ, Chester ST, Manavella C, Mallouk Y, Pollmeier MG, Baggott D: The prevention of transmission of Babesia canis canis by Dermacentor reticulatus ticks to dogs using a novel combination of fipronil, amitraz and (S)-methoprene. Vet Parasitol 2011, 179:343-350.
• [8]Fourie JJ, Luus HG, Stanneck D, Jongejan F: The efficacy of Advantix to prevent transmission of Ehrlichia canis to dogs by Rhipicephalus sanguineus ticks. Parasite 2013, 20:36.
• [9]Fourie JJ, Stanneck D, Luus HG, Beugnet F, Wijnveld M, Jongejan F: Transmission of Ehrlichia canis by Rhipicephalus sanguineus ticks feeding on dogs and on artificial membranes. Vet Parasitol 2013, 197:595-603.
• [10]Gassel M, Wolf C, Noack S, Williams H, Ilg T: The novel isoxazoline ectoparasiticide fluralaner: selective inhibition of arthropod gamma-aminobutyric acid- and L-glutamate-gated chloride channels and insecticidal/acaricidal activity. Insect Biochem Mol Biol 2014, 45:111-124.
• [11][http:/ / www.ema.europa.eu/ docs/ en_GB/ document_library/ EPAR_-_Summary_for_the_public/ veterinary/ 002526/ WC500163861.pdf] webcite Bravecto EPAR summary for the public.European Medicines Agency .
• [12]Ozoe Y, Asahi M, Ozoe F, Nakahira K, Mita T: The antiparasitic isoxazoline A1443 is a potent blocker of insect ligand-gated chloride channels. Biochem Biophys Res Commun 2010, 391:744-749.
• [13]Walther FM, Allan MJ, Roepke RK, Nuernberger MC: Safety of fluralaner chewable tablets (Bravecto), a novel systemic antiparasitic drug, in dogs after oral administration. Parasit Vectors 2014, 7:87. BioMed Central Full Text
• [14]Walther FM, Paul AJ, Allan MJ, Roepke RK, Nuernberger MC: Safety of fluralaner, a novel systemic antiparasitic drug, in MDR1(?/?) Collies after oral administration. Parasit Vectors 2014, 7:86. BioMed Central Full Text
• [15]Kilp S, Ramirez D, Allan MJ, Roepke RK, Nuernberger MC: Pharmacokinetics of fluralaner in dogs following a single oral or intravenous administration. Parasit Vectors 2014, 7:85. BioMed Central Full Text
• [16]Rohdich N, Roepke RK, Zschiesche E: A randomized, blinded, controlled and multi-centered field study comparing the efficacy and safety of Bravecto (fluralaner) against Frontline (fipronil) in flea- and tick-infested dogs. Parasit Vectors 2014, 7:83. BioMed Central Full Text
• [17]Stanek G, Wormser GP, Gray J, Strle F: Lyme borreliosis. Lancet 2012, 379:461-473.
• [18]Kidd L, Breitschwerdt EB: Tranmission times and prevention of tick-borne diseases in dogs. Compend Contin Educ Pract Vet 2003, 10:742-751.
• [19]Heile CH, Hoffmann-Köhler P, Weimann A, Schein E: Uebertragungszeiten von durch Zecken übertragenen Erregern beim Hund: Borrelien, Anaplasmen/Ehrlichien und Babesien. Praktischer Tierarzt 2007, 88:584-590.
• [20]des Vignes F, Piesman J, Heffernan R, Schulze TL, Stafford KC III, Fish D: Effect of tick removal on transmission of Borrelia burgdorferi and Ehrlichia phagocytophila by Ixodes scapularis nymphs. J Infect Dis 2001, 183:773-778.
• [21]Crippa M, Rais O, Gern L: Investigations on the mode and dynamics of transmission and infectivity of Borrelia burgdorferi sensu stricto and Borrelia afzelii in Ixodes ricinus ticks. Vector Borne Zoonotic Dis 2002, 2:3-9.
• [22]Prullage JB, Hair JA, Everett WR, Yoon SS, Cramer LG, Franke S, Cornelison K, Hunter JS 3rd: The prevention of attachment and the detachment effects of a novel combination of fipronil, amitraz and (S)-methoprene for Rhipicephalus sanguineus and Dermacentor variabilis on dogs. Vet Parasitol 2011, 179:311-317.
• [23]Davoust B, Marie JL, Mercier S, Boni M, Vandeweghe A, Parzy D, Beugnet F: Assay of fipronil efficacy to prevent canine monocytic ehrlichiosis in endemic areas. Vet Parasitol 2003, 112:91-100.
• [24]Fourie JJ, Ollagnier C, Beugnet F, Luus HG, Jongejan F: Prevention of transmission of Ehrlichia canis by Rhipicephalus sanguineus ticks to dogs treated with a combination of fipronil, amitraz and (S)-methoprene (CERTIFECT(R)). Vet Parasitol 2013, 193:223-228.
• [25]Otranto D, Paradies P, Testini G, Latrofa MS, Weigl S, Cantacessi C, Mencke N, de Caprariis D, Parisi A, Capelli G, Stanneck D: Application of 10% imidacloprid/50% permethrin to prevent Ehrlichia canis exposure in dogs under natural conditions. Vet Parasitol 2008, 153:320-328.
• [26]Blagburn BL, Spencer JA, Butler JM, Land TM, Billeter SA, Dykstra CC, Stafford KC, Pough MB, Levy SA, Endrizzi M, Hostetler J: Prevention of transmission of Borrelia burgdorferi and Anaplasma phagoyctophilum from ticks to dogs using K9 Advantix and Frontline Plus applied 25 days before exposure to infected ticks. Intern J Appl Res Vet Med 2005, 3:69-75.
• [27]McCall JW, Baker CF, Mather TN, Chester ST, McCall SD, Irwin JP, Young SL, Cramer LG, Pollmeier MG: The ability of a topical novel combination of fipronil, amitraz and (S)-methoprene to protect dogs from Borrelia burgdorferi and Anaplasma phagocytophilum infections transmitted by Ixodes scapularis. Vet Parasitol 2011, 179:335-342.
• [28]Fourie JJ, Beugnet F, Ollagnier C, Pollmeier MG: Study of the sustained speed of kill of the combination of fipronil/amitraz/(S)-methoprene and the combination of imidacloprid/permethrin against Dermacentor reticulatus, the European dog tick. Parasite 2011, 18:319-323.
• [29]Kunkle BN, Everett WR, Yoon SS, Beugnet F, Pollmeier M: Study of the sustained speed of kill of the combination fipronil/amitraz/(S)-methoprene and the combination imidacloprid/permethrin against newly acquired Dermacentor variabilis (American Dog Tick). Intern J Appl Res Vet Med 2012, 10:42-47.
• [30]Hunter JS 3rd, Baggott D, Everett WR, Fourie JJ, Cramer LG, Yoon SS, Collidor N, Mallouk Y, Lee L, Blair J, Prullage JB: Efficacy of a novel topical combination of fipronil, amitraz and (S)-methoprene for treatment and control of induced infestations of brown dog ticks (Rhipicephalus sanguineus) on dogs. Vet Parasitol 2011, 179:318-323.
• [31]Baker CF, Hunter JS 3rd, McCall JW, Young DR, Hair JA, Everett WR, Yoon SS, Irwin JP, Young SL, Cramer LG, Pollmeier MG, Prullage JB: Efficacy of a novel topical combination of fipronil, amitraz and (S)-methoprene for treatment and control of induced infestations with four North American tick species (Dermacentor variabilis, Ixodes scapularis, Amblyomma americanum and Amblyomma maculatum) on dogs. Vet Parasitol 2011, 179:324-329.
• [32]Beck S, Schein E, Baldermann C, von Samson-Himmelstjerna G, Kohn B: [Tick infestation and tick prophylaxis in dogs in the area of Berlin/Brandenburg¿results of a questionnaire study]. Berl Munch Tierarztl Wochenschr 2013, 126:69-76.
• [33]Mencke N: Future challenges for parasitology: vector control and 'One health' in Europe: the veterinary medicinal view on CVBDs such as tick borreliosis, rickettsiosis and canine leishmaniosis. Vet Parasitol 2013, 195:256-271.
• [34]Leschnik M, Feiler A, Duscher GG, Joachim A: Effect of owner-controlled acaricidal treatment on tick infestation and immune response to tick-borne pathogens in naturally infested dogs from Eastern Austria. Parasit Vectors 2013, 6:62. BioMed Central Full Text