• Abstract and Figures
• Public Full-text

Becskei et al. Parasites Vectors (2020) 13:64 https://doi.org/10.1186/s13071-020-3948-z Parasites & Vectors RESEARCH Open Access Efcacy of orally administered combination of moxidectin, sarolaner and pyrantel (Simparica Trio™) for the prevention of experimental Angiostrongylus vasorum infection in dogs Csilla Becskei1*, Mirjan Thys1, Padraig Doherty2 and Sean P. Mahabir3 Abstract Background: Infection with Angiostrongylus vasorum may cause severe clinical disease, even death in dogs, however, due to the often non-specifc clinical signs, diagnosis is not always straightforward. Regular prophylactic treatment may ofer a safe means to protect dogs against infection. The efcacy of a novel oral endectocide containing mox- idectin, sarolaner and pyrantel was investigated for the prevention of angiostrongylosis in dogs in three placebo- controlled, randomized, masked studies. The initial study (Study 1) determined the efcacious dosage of moxidectin in the combination product by evaluating three diferent dose levels, and two follow-up studies (Studies 2 and 3) confrmed the efcacy of the selected moxidectin dose. Methods: Animals were infected orally with 200 infective third-stage larvae (L3) of A. vasorum and were treated 28 days later with the combination product or with placebo. Timing of dosing relative to infection allowed for efcacy to be evaluated against the immature adult (L5) stage. Dogs in Study 1 received treatments with oral tablets to deliver 3, 12 or 24 µg/kg moxidectin in combination with 2 mg/kg sarolaner and 5.0 mg/kg pyrantel (as pamoate salt) or placebo. In Studies 2 and 3, Simparica Trio™ tablets were administered to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Efcacy of the combination product was calculated as the percent reduction in adult worm counts at necropsy relative to placebo. Results: In Study 1, the 3, 12 and 24 µg/kg moxidectin dosage in the combination product provided 7.2%, 54.5% and 94.7% efcacy against the immature adult stages of A. vasorum, respectively. Studies 2 and 3 confrmed that the efcacy of 24 µg/kg moxidectin combined with 1.2 mg/kg sarolaner and 5 mg/kg pyrantel in Simparica Trio™ was 92.9%. All three studies established that a single oral administration of 24 µg/kg moxidectin in the combination product≥ provided efective prophylactic treatment for angiostrongylosis, reduced L1 production and fecal excretion and minimized the tissue damage to the lungs. Conclusions: A single oral treatment of dogs with Simparica Trio™ providing moxidectin at a minimum dose of 24 µg/kg was efcacious in the prevention of angiostrongylosis. Keywords: Angiostrongylosis, Endectocide, French heartworm, Lungworm, Prevention Background Infections with nematodes that in their adult stages *Correspondence: [email protected] 1 Zoetis, Veterinary Medicine Research and Development, Mercuriusstraat reside in the cardiopulmonary system may have serious 20, 1930 Zaventem, Belgium impact on the health of their fnal host. Angiostrongy- Full list of author information is available at the end of the article lus vasorum (French heartworm or fox lungworm) and © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Becskei et al. Parasites Vectors (2020) 13:64 Page 2 of 7 Diroflaria immitis are two important species infecting of angiostrongylosis in experimentally infected dogs after dogs worldwide that may cause severe disease and, in a single oral administration. One of the studies aimed to some cases, even death [1, 2]. Both species have an indi- determine the efcacious dose of moxidectin in the com- rect life-cycle. bination product; therefore, three diferent dose levels of Angiostrongylus vasorum is a metastrongyloid nema- moxidectin were tested simultaneously. Te other two tode that develops from the L1 stage to infective L3 in studies were conducted to confrm the efcacy of the snails, slugs and frogs as intermediate hosts [2, 3]. Te selected moxidectin dose in the combination product. fnal hosts are canids [dogs, foxes (Vulpes vulpes, Dusi- cyon vetulus), coyotes (Canis latrans) etc.] that become Methods infected by ingesting the intermediate hosts or taking Tree placebo-controlled, masked, randomized labo- up the L3 excreted by the intermediate hosts from the ratory studies were conducted according to the World environment, e.g. by eating grass, chewing on sticks or Association for the Advancement of Veterinary Parasi- drinking from puddles [2, 4]. Additionally, canids may be tology (WAAVP) guidelines for evaluating the efcacy infected by ingesting paratenic hosts, such amphibians of anthelmintics for dogs and cats [16]. Study personnel and birds [3, 5]. In the fnal host, L3 undergo two molts, who made assessments of efcacy or safety were masked the frst one occurring in the abdominal lymph nodes to the treatment assignments of the dogs. within one week post-infection (pi) [6]. Following a sec- ond molt, the L5s reach the right ventricle and pulmo- Design nary arteries after about 10 days pi, where they develop Te study designs were based on the life-cycle of A. vaso- into adults [6]. Eggs laid by the adult females hatch in the rum and previously published studies [14, 17, 18]. respiratory vessels and the L1 will be passed in the feces Study 1 was a dose determination study that aimed usually within 2 months pi. Infected dogs may excrete L1 to identify the minimum efective dose of moxidectin for extended periods, but shedding may be intermittent in the combination product against the immature adult or at a low level even in heavily infected dogs, making the (L5) stage of A. vasorum. In this study, four groups of diagnosis difcult [7]. eight dogs each received oral treatment with either pla- Clinical diagnosis of canine angiostrongylosis is chal- cebo or with the combination product that delivered an lenging because of the wide spectrum of clinical signs the exact dose of 3, 12 or 24 µg/kg moxidectin. Two addi- infected dogs may present with and because subclinical tional studies (Studies 2 and 3) confrmed the efcacy of infections also occur [2, 8]. Respiratory signs are most the selected 24 µg/kg minimum moxidectin dose in the frequently reported, while infected dogs may also present combination product against the L5 stage of A. vasorum. with coagulopathies, cardiovascular, ophthalmological, Te study design of Studies 2 and 3 were identical, except gastrointestinal and neurological signs [8–10]. In rare for the origin of the A. vasorum isolates used for infec- cases sudden death may also occur [9, 11]. tion. In each of these studies, two groups of eight dogs For the treatment of angiostrongylosis, topically admin- each received oral treatment of placebo or the combina- istered moxidectin (in combination with imidacloprid; tion product. one or two monthly treatments) and oral milbemycin In all three studies, dogs were infected orally with the oxime (as monovalent or part of a combination prod- L3 stage of A. vasorum on Day-28, received the study uct; once a week for four weeks) are licensed options in treatments on Day 0, at the time when the L3 stages Europe [12–14]. Of label use of fenbendazole (daily oral were expected to have developed to immature adults treatment for several weeks) and ivermectin (weekly sub- (L5), and were necropsied once patency was confrmed cutaneous injections) has been also reported to be ef- in the placebo-treated dogs by fecal excretion of the L1 cacious [9, 13, 15]. Due to the potentially severe disease stage (28–42 days after treatment). Te timing between in infected dogs and the difculties in diagnosing angi- the inoculation and the treatment of dogs (28 days) was ostrongylosis, regular preventative treatment is a good determined based on the life-cycle of the parasite and option for dogs living in endemic regions. Licensed pro- previous study designs, in order to target the L5 stage at phylactic medications belong to the macrocyclic lactones the time of treatment administration [14, 17, 18]. (topical moxidectin in combination with imidacloprid and oral milbemycin oxime in combination products) Animals and have activity against the L4 and/or L5 stages [12]. Adult, purpose-bred Beagle dogs were used in all studies. Here, the results of three studies are presented that Tirty-two dogs were enrolled in Study 1 in two cohorts evaluated the efcacy of a novel chewable tablet contain- (9 males and 7 females in cohort 1 and 8 males and 8 ing sarolaner, moxidectin and pyrantel pamoate (Simpar- females in cohort 2). Sixteen dogs were used in both of ica Trio™, Zoetis, Parsipanny, NJ, USA) in the prevention Studies 2 and 3 (7 males and 9 females in each). Te age Becskei et al. Parasites Vectors (2020) 13:64 Page 3 of 7 of the dogs ranged between 11–45 months at enrolment In all studies, 28 days after the experimental infections and the body weights ranged between 10.2–18.5 kg at dogs were dosed with either placebo tablets or with the treatment administration.

Load more

  7

Copy Link