TREATMENT AND PROPHYLAXIS - REVIEW A systematic review of moxidectin as a treatment for parasitic infections in mammalian species Andrea L. Schraven 1 & Hayley J. Stannard 2 & Julie M. Old 1 Received: 29 November 2020 /Accepted: 16 February 2021 # Crown 2021 Abstract Moxidectin (MOX) is a macrocyclic lactone approved worldwide for the treatment of both endo- and ecto-parasites in many mammalian species. The aim of this study was to assess the efficacy of MOX as a treatment against parasites in a range of mammalian species. An electronic literature search was performed for publications to the 1 st September 2020. A total of 205 papers were retrieved and screened against all required criteria; hence, 35 were papers were reviewed in this study. The level of evidence and methodological quality was analysed, where a total of 13 publications were categorised as a ‘randomised control trial’, seven were categorised as a ‘non-randomised control trial’ and 15 as an ‘experimental control trial’. The overall method- ological quality of the publications was considered low, low to moderate, moderate, moderate to high and high in ten, four, twelve, five and a further four, respectively. We assessed the treatment and possible toxicity of MOX in 13 mammalian species, six investigations reported adverse effects to MOX in a small percentage of individuals. The authors reported observed reactions that were typically mild symptoms that did not require additional therapies, and/or resolved themselves. Further studies are needed to assess the efficacy of MOX treatment in a larger number of species, particularly in wildlife. Keywords Sarcoptic mange . Treatment . Parasites . Mite Introduction Moxidectin (MOX) is a macrocyclic lactone belonging to the milbemycin chemical family, and is approved and marketed worldwide for the treatment for both endo- and ecto-parasites in a number of species (Vercruysse and Rew 2002). MOX is a semi-synthetic methoxime derived from nemadectin and pro- duced by a combination of the fermentation and chemical syn- thesis of Streptomyces cyaneogriseus (Plumb 1999). It has a similar molecular structure to ivermectin (IVM), a member of the avermectin family; however, MOX differs from IVM be- cause IVM has a disaccharide side chain at C-13, whereas MOX has a methoxime at C-23 and an unsaturated side chain at C-25 (Hayes 1994). These structural differences have a sig- nificant impact on the physical and physiological properties of these two drugs. As a result, MOX has a higher lipophilicity which appears to result in a longer residence time in the body (Alvinerie et al. 1996; Lanusse et al. 1997). MOX binds to the receptors of chloride ions, increasing the membrane permeabil- ity, and in turn affects the chloride ion channel activity in the nervous system of parasites (Wagner and Wendlberger 2000). It has the ability to inhibit the electrical activity of the muscle cells in arthropods and the nerve cells in nematodes, hindering parasites by paralysis, resulting in death (Plumb 1999). MOX efficacy has been reviewed previously by Vercruysse and Rew (2002); however, due to the increasing interest in treating sarcoptic mange in a wider number of spe- cies, including wildlife (Death et al. 2011; Ruykys et al. 2013; Cypher et al. 2017; Van Wick and Hashem 2019), we thought it timely to review the efficacy of MOX given the nearly two decades since its last review. Methods Search strategy and selection A systematic review was conducted to identify and analyse peer-review publications investigating the usage of MOX in a Handling Editor: Una Ryan * Julie M. Old j.old@westernsydney.edu.au 1 School of Science, Western Sydney University, Hawkesbury, NSW, Australia 2 School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW, Australia Parasitology Research https://doi.org/10.1007/s00436-021-07092-0