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Efficacy of Imidacloprid 10%/Moxidectin 1% Spot-On

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Efficacy of Imidacloprid 10%/Moxidectin 1% Spot-On Heuer et al. Parasites Vectors (2020) 13:65 https://doi.org/10.1186/s13071-020-3937-2 Parasites & Vectors RESEARCH Open Access Efcacy of imidacloprid 10%/moxidectin 1% spot-on formulation (Advocate®) in the prevention and treatment of feline aelurostrongylosis Lea Heuer1, Gabriele Petry1, Matthias Pollmeier1, Roland Schaper1, Katrin Deuster1, Holger Schmidt2, Katrin Blazejak3, Christina Strube3, Angela Di Cesare4, Donato Traversa4, Manuela Schnyder5, Janina McKay‑Demeler6,7, Georg von Samson‑Himmelstjerna6, Sandra Mangold‑Gehring1* and Claudia Böhm1 Abstract Background: In three randomized, controlled laboratory efcacy studies, the efcacy in the prevention of patent infections of a topical combination of imidacloprid 10%/moxidectin 1% (Advocate® spot‑on formulation for cats, Bayer Animal Health GmbH) against larval stages and immature adults of Aelurostrongylus abstrusus, as well as the treatment efcacy of a single or three monthly treatments against adult A. abstrusus, were evaluated. Methods: Cats were experimentally inoculated with 300–800 third‑stage larvae (L3). Each group comprised 8 animals and the treatment dose was 10 mg/kg bodyweight (bw) imidacloprid and 1 mg/kg bw moxidectin in each study. Prevention of the establishment of patent infections was evaluated by two treatments at a monthly interval at three diferent time points before and after challenge infection. Curative efcacy was tested by one or three treat‑ ments after the onset of patency. Worm counts at necropsy were used for efcacy calculations. Results: In Study 1, the control group had a geometric mean (GM) of 28.8 adult nematodes and the single treatment group had a GM of 3.4 (efcacy 88.3%). In Study 2, the control group had a GM of 14.3, the prevention group had a GM of 0 (efcacy 100%), while the treatment group had a GM of 0.1 (efcacy 99.4%). In Study 3, the GM worm burden in the control group was 32.6 compared to 0 in all three prevention groups (efcacy 100% for all of those groups). Conclusions: The monthly administration of Advocate® reliably eliminated early larval stages and thereby prevented lung damage from and patent infections with A. abstrusus in cats. Regarding treatment, a single application of Advo‑ cate® reduced the worm burden, but it did not sufciently clear the infection. In contrast, three monthly treatments were safe and highly efcacious against A. abstrusus. Keywords: Aelurostrongylus abstrusus, Moxidectin, Feline lungworm, Prevention, Treatment Background risen worldwide, particularly across mainland Europe. Parasitic respiratory diseases are of increasing impor- Concerning parasitic helminths of the feline respira- tance in feline clinical practice [1]. Over recent years, tory tract, such as Oslerus rostratus, Troglostrongylus the number of reports of feline lungworm infections has spp. or Capillaria aerophila, Aelurostrongylus abstrusus remains the most important of the feline lungworms in *Correspondence: [email protected] both clinical and epidemiological terms [1, 2]. Tis nema- 1 Bayer Animal Health GmbH, Leverkusen, Germany tode is distributed worldwide with varying prevalence Full list of author information is available at the end of the article rates in cats, e.g. 1.7% in the UK [3], 5.1% in the USA © 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. Heuer et al. Parasites Vectors (2020) 13:65 Page 2 of 10 [4], approximately 8% in Denmark [5] or Greece [6], and a comparable efcacy, i.e. 99.4%, to the oral fenbendazole between 10 and 38.3% in Italy [7]. Te parasite may infect treatment in terms of larval shedding [25]. Te emodep- domestic cats and occasionally wild felids, e.g. European side formulation has been evaluated further in two ran- wildcats or lions [2, 8, 9]. domized, placebo-controlled experimental studies. Two Generally, the risk of infection is higher for stray or spot-on administrations at a two-week interval showed a free-roaming cats in endemic areas [10–12]. Infections 99.2% reduction of worm counts in the lung tissue [26]. ® may be acquired by ingestion of either the intermedi- Profender is therefore licensed for the treatment of ate hosts (mollusks) or paratenic hosts, such as birds, adult stages of A. abstrusus in cats with this treatment rodents, amphibians or reptiles [13–16]. Besides the regimen [27]. Another product licensed for the treatment adult nematodes, which reside mainly in the bronchi- of A. abstrusus (L3, L4 and adults) is a topical formula- oles, alveolar ducts and lung parenchyma, egg production tion containing fpronil 8.3% w/v, (S)-methoprene 10% and migrating larvae can also cause infammatory lung w/v, eprinomectin 0.4% w/v and praziquantel 8.3% w/v ® lesions, depending on the infective dosage [17]. Infec- (Broadline , Merial, Hallbergmoos, Germany), which tions can range from subclinical or severe to fatal. Clini- had an efcacy of 99.6% against adult A. abstrusus [28, cal manifestations include non-specifc signs compatible 29]. Knaus et al. [28] also demonstrated an efcacy with with a systemic disease, such as apathy, depression and this formulation of 98.9%, 99.3% and 91.6% against L3, L4 weight loss, as well as respiratory alterations, e.g. dysp- and immature adults of A. abstrusus, respectively, show- nea, panting, coughing, sneezing and nasal discharge [15, ing the preventive potential against patent A. abstrusus 18, 19]. Concerning bronchoscopy fndings, bronchiecta- infections. sis and mucus accumulation were found in cats infected Because of its longer half-life and its good safety with A. abstrusus [20]. Cardiac presentations, such as profle, moxidectin has been suggested as another right-sided cardiomegaly, heart murmurs and pulmonary potential option for the chemoprevention of aeluro- hypertension, have also been described in kittens [21]. strongylosis. Tis drug remains detectable in plasma Furthermore, spontaneous death during anesthesia has samples for weeks and consistent monthly administra- also been associated with lungworm disease in cats [22]. tions of topical moxidectin can induce elevated and sus- Severe cardiopulmonary disease or fatalities can be the tained steady-state plasma concentrations in dogs and result of a late diagnosis and treatment of aelurostrongy- cats [30–32]. Furthermore, moxidectin has proven to be losis [1]. highly efective against patent A. abstrusus infections: in Ideally, infections should be prevented or treated at an a feld study, a spot-on formulation containing 10% imi- ® early stage with adequate actives. Routine deworming is dacloprid and 1% moxidectin (Advocate ; Bayer Animal therefore advisable, especially in free-roaming cats with Health GmbH) showed 100% efcacy in reducing larval respiratory signs. Data on the efcacy of treatments are shedding and resolving clinical signs after a single treat- ® available from clinical studies and case reports, but infor- ment [24]. Tis formulation (Advocate , Bayer Animal mation on preventive properties of the licensed prod- Health GmbH) is licensed in some markets (e.g. New ucts is limited. Use of an oral formulation of milbemycin Zealand, Australia) for the treatment and control of A. oxime and praziquantel (Milbemax®, Elanco Europe, abstrusus in cats [33, 34]. Bad Homburg, Germany) stopped larval shedding and Te controlled laboratory studies reported here were resolved clinical signs in a single case after two applica- conducted to investigate the efcacy of this formulation tions two weeks apart [21]. Selamectin 45 mg spot-on in the treatment and prevention of patency in cats exper- formulation (Stronghold®, Zoetis, Berlin, Germany; dose imentally infected with A. abstrusus. range 2.6–7.5 kg body weight, bw) was used twice 23 days apart in naturally infected cats and stopped larval shed- Methods ding in 9 out of 10 cats [23]. Of the benzimidazoles, an Study design oral paste with 18.75% fenbendazole (Panacur®; MSD To evaluate imidacloprid 10%/moxidectin 1% spot-on Animal Health, Unterschleißheim, Germany) is licensed formulation for the prevention (against L3 and L4 larvae) in the UK, among other countries, for the treatment of and treatment (adults) of patent experimental A. abstru- feline aelurostrongylosis. In two feld studies [24, 25], an sus infections in cats, three studies were conducted. An efcacy of 99.3% has been reported with the oral treat- overview is given in Fig. 1 and Table 1. ment of 50 mg/kg bw daily for 3 consecutive days. In Studies were conducted in accordance with VICH these feld studies, a single application of an emodepside/ Guideline 9, “Good Clinical Practice” (July 2001) [35], praziquantel (Profender®, Bayer Animal Health GmbH, VICH Guideline 7, “Efcacy of anthelmintics: general Leverkusen, Germany) spot-on formulation at a dosage of requirements” [36] and VICH Guideline 20, “Efcacy of 3 mg/kg emodepside and 12 mg/kg praziquantel showed anthelmintics: specifc recommendations for felines” [37]. Heuer et al. Parasites Vectors (2020) 13:65 Page 3 of 10 // // // // // // // Study Day (SD) -43 -36 -20 -10 -4 0 7 14 18 21 24 28 32 34 36 48 53 81 109 136 Event 800 Study No.
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