title: Efficacy against nematode infections and safety of afoxolaner plus milbemycin oxime chewable tablets in domestic dogs under field conditions in Europe.
abstract: Afoxolaner (AFX) plus milbemycin oxime (MO) combination chewable tablets (NexGard Spectra®, Merial) were evaluated for safety and efficacy against naturally acquired nematode infections in domestic dogs in a multi-centre, positive control, blinded field study using a randomized block design based on the order of presentation for allocation. In total, 408 dogs confirmed positive for naturally acquired infections of intestinal nematodes by pre-treatment faecal examination were studied in ten countries in Europe (Albania, Austria, Bulgaria, France, Germany, Hungary, Italy, Lithuania, Romania and Slovakia). Pre-treatment faecal examination revealed Toxocara, Toxascaris, hookworm, Trichuris and/or Capillaria nematode infections in 134, 30, 223, 155 and 14 dogs, respectively. Dogs were allocated to one of two treatment groups in a ratio of 1, AFX + MO chewables (≥2.5 mg AFX + ≥0.5 mg MO per kg body weight, according to dose bands; 207 dogs), and 1, MO plus praziquantel (PRZ) chewables (Milbemax®, Novartis; ≥0.5 mg MO + ≥5 mg PRZ per kg body weight, according to the manufacturer's instructions; 201 dogs) and treated once. For evaluation of efficacy based on reduction of faecal nematode egg counts, two faecal samples, one collected prior to treatment and one collected 9 to 21 days after treatment, were examined using modified McMaster techniques. For evaluation of systemic safety, dogs were examined by a veterinarian before treatment administration and at study end, and dog owners observed the health status of their dogs until the end of the study and reported any abnormal observation. For dogs treated with AFX + MO chewables, the efficacy was 99.7, 99.7, 97.2, 99.7 and 99.7 % for Toxocara, Toxascaris, hookworm, Trichuris and Capillaria, respectively; and the efficacy was 99.5, 99.4, 94.3, 99.9 and 98.0 %, respectively, for the MO + PRZ-treated dogs (p ≤ 0.002 for all nematodes and both treatments). For Toxocara, hookworm and Trichuris, non-inferiority analysis demonstrated that the efficacy of AFX + MO chewable tablets was equal to or better than that of MO + PRZ. In spite that both treatments were ≥98 % efficacious against Toxascaris and Capillaria, a hypothesis of non-inferiority for both genera could not be established due to the low number of dogs infected with these parasites. No treatment-related adverse experiences were observed throughout the study. For both treatments, all dogs were given a systemic safety score of 'excellent' apart from one dog in each treatment group which received a score of 'acceptable'. AFX + MO combination chewables were shown to be safe and demonstrated a high level of efficacy when administered once to dogs infected with a broad range of parasitic nematodes under field conditions.
authors: Merial GmbH, Kathrinenhof Research Center, Walchenseestr. 8-12, 83101, Rohrdorf, Germany. steffen.rehbein@merial.com.
authors: Steffen
authors: http://orcid.org/0000-0002-8496-8355
authors: S
authors: Rehbein
authors: Merial GmbH, Kathrinenhof Research Center, Walchenseestr. 8-12, 83101, Rohrdorf, Germany.
authors: Martin
authors: M
authors: Knaus
authors: Merial S.A.S., Centre de Recherche de Saint-Vulbas, 1 allée des Cyprès, 01150, Saint-Vulbas, France.
authors: Yasmina
authors: Y
authors: Mallouk
authors: Tierarztpraxis Breiltgens, Lärchenstr. 4, 82166, Gräfelfing, Germany.
authors: Tatjana
authors: T
authors: Breiltgens
authors: Dipartimento di Scienze Veterinarie, Università degli Studi di Messina, Polo Universitario dell'Annunziata, 98168, Messina, Italy.
authors: Emanuele
authors: E
authors: Brianti
authors: Kapriol Bt., Vároldal ut. 5, 8330, Sümeg, Hungary.
authors: Balázs
authors: B
authors: Capári
authors: Dipartimento di Sanità Pubblica e Zootecnia, Università degli Studi di Bari, Animali Facoltà di Medicina Veterinaria, Valenzano, Bari, 70010, Italy.|Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, 50740465, Recife, Brazil.
authors: Filipe
authors: F
authors: Dantas-Torres
authors: Clinique Vétérinaire, Le Sialat les Hauts, 81100, Castres, France.
authors: Michel
authors: M
authors: Gau
authors: Institute of Parasitology, University of Veterinary Medicine, Veterinärplatz 1, 1210, Vienna, Austria.
authors: Anja
authors: A
authors: Joachim
authors: Tierarztpraxis Hofmann, Schulstr. 8, 38875, Elbingerode, Germany.
authors: Karl-Heinz
authors: KH
authors: Kaulfuß
authors: Department of Parasitology, Faculty of Veterinary Medicine, Trakia University, Student Campus, 6000, Stara Zagora, Bulgaria.
authors: Zvezdelina
authors: Z
authors: Kirkova
authors: Tierärztliche Klinik Nürnberg, Wertachstr. 1, 90451, Nürnberg, Germany.
authors: Joerg
authors: J
authors: Lechner
authors: Department of Parasitology and Parasitic Diseases, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3-5, Cluj-Napoca, 400372, Romania.
authors: Andrei D
authors: AD
authors: Mihalca
authors: Ambulatorio Medico Veterinario "Peloro", Via Consolare Pompea 2077 - Granatari, 98165, Messina, Italy.
authors: Rosamaria
authors: R
authors: Mirabito
authors: Department of Infectious Diseases, Lithuanian University of Health Sciences, Veterinary Academy, Tilzes str. 18, 47181, Kaunas, Lithuania.
authors: Saulius
authors: S
authors: Petkevičius
authors: Fakulteti i Mjekësisë Veterinare, Universiteti Bujqësor, Kodër, Kamëz, Tirana, Albania.
authors: Dhimitër
authors: D
authors: Rapti
authors: Fakulteti i Mjekësisë Veterinare, Universiteti Bujqësor, Kodër, Kamëz, Tirana, Albania.
authors: Enstela
authors: E
authors: Shukullari
authors: Clinique Vétérinaire des 3 Vallées, 44, avenue Pechiney, 09400, Tarascon sur Ariège, France.
authors: Michel
authors: M
authors: Sedeilhan
authors: Merial GmbH, Kathrinenhof Research Center, Walchenseestr. 8-12, 83101, Rohrdorf, Germany.
authors: Doris
authors: D
authors: Dollhofer
authors: Merial GmbH, Kathrinenhof Research Center, Walchenseestr. 8-12, 83101, Rohrdorf, Germany.
authors: Katrin
authors: K
authors: Kley
authors: Merial S.A.S., Centre de Recherche de Saint-Vulbas, 1 allée des Cyprès, 01150, Saint-Vulbas, France.
authors: Wilfried
authors: W
authors: Lebon
authors: Merial GmbH, Kathrinenhof Research Center, Walchenseestr. 8-12, 83101, Rohrdorf, Germany.
authors: Martin
authors: M
authors: Visser
authors: Merial S.A.S., Centre de Recherche de Saint-Vulbas, 1 allée des Cyprès, 01150, Saint-Vulbas, France.
authors: Philippe
authors: P
authors: Jeannin
mesh_terms: D000818:Animals; D000969:Antinematodal Agents / Q000008:administration & dosage*; D004283:Dog Diseases / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology*; D004285:Dogs; D005060:Europe / Q000453:epidemiology; D005243:Feces / Q000469:parasitology; D007555:Isoxazoles / Q000008:administration & dosage*; D018942:Macrolides / Q000008:administration & dosage*; D009281:Naphthalenes / Q000008:administration & dosage*; D009348:Nematoda / Q000187:drug effects* / Q000502:physiology; D009349:Nematode Infections / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary*; D011223:Praziquantel / Q000627:therapeutic use; D013607:Tablets / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000969:Antinematodal Agents; D007555:Isoxazoles; D018942:Macrolides; D009281:Naphthalenes; D013607:Tablets; C000589002:afoxolaner; C078973:milbemycin oxime; D011223:Praziquantel
keywords: Afoxolaner; Dogs; Efficacy; Milbemycin oxime; Nematodes; Safety