Efficacy of Afoxolaner Plus Milbemycin Oxime in the Treatment of Canine Demodicosis Camilo Romero-Núñeza Linda Guiliana Bautista-Gómeza Galia Sheinbergb Alberto Martínc Anahí Romerod Ariadna Floresa Rafael Herediaa Laura Mirandaa aCentro Universitario UAEM Amecameca, Universidad Autónoma del Estado de México, Km. 2.5 Carretera Amecameca-Ayapango, 56900, Amecameca de Juárez, Estado de México, México bCentro Veterinario México, Calle Cincinnati #22, Benito Juárez, Cd de los Deportes, 03710 Ciudad de México, México cVeterinaria Dermatología Veterinaria Especializada, Argentina No. 690, Colonia Moderna, Guadalajara, 44190 Jalisco México. dMaestría en Medicina Veterinaria, Av. Universidad 3000, Edificio A, Delegación Coyoacán, Col. Ciudad Universitaria, Cd. Universitaria, 04510 Ciudad de México, CDMX Corresponding Author: Linda Guiliana Bautista Gómez, Centro Universitario UAEM Amecameca, Universidad Autónoma del Estado de México, Carretera Amecameca-Ayapango Km 2.5, Amecameca de Juárez, 56900 Estado de México, Mexico. E-mail: [email protected] KEY WORDS: Efficacy, afoxolaner, plus milbemycin oxime in the treatment of milbemycin oxime, treatment, dog, generalized canine demodicosis. Sixty-eight demodicosis dogs diagnosed with generalized demodico- sis were included. From each dog, three skin ABSTRACT scrapings and hair samples were obtained. Demodicosis is a canine dermatosis pro- Dogs were treated with an oral dose of duced by the Demodex sp. mite; the local- 2.50–5.36 mg/kg of afoxolaner in combina- ized form can become generalized and have tion with 0.50–1.07 mg/kg of milbemycin bacterial complications, making it difficult oxime. Evaluations were made on days 7, to effectively treat. The objective was to 14, and 28 post-treatment through a lesion evaluate the efficacy of the use of afoxolaner visualization and positive samples to mites. Intern J Appl Res Vet Med • Vol. 17, No. 1, 2019. 35 After a single oral dose of afoxolaner It typically occurs in young dogs (between with milbemycin oxime, the number of 3 months and 1 year), although there are positive animals according to skin scrapings reports in dogs from two weeks of age6 and was reduced from 100% on day 1 to 17.6% in dogs older than one year, these cases tend on day 28 (P < 0.05). The resolution of the to be occasional3 or secondary to another lesions after treatment was variable, with a underlying pathology.7 significant decrease for the first 7 days. This Canine demodicosis is a common, parameter continued to decrease until the non-contagious parasitic dermatosis8 that end of the study on day 28, when a decrease can be divided into two clinical manifesta- of 94.68% was observed. An association tions: localized and generalized. Localized between the presence of Demodex sp. and demodicosis appears as small alopecic the area of the head was observed (Chi- and erythematous areas, which can regress square = 14.65, P = 0.0001). Oral adminis- spontaneously without the administration of tration of a single dose of 2.50–5.36 mg/kg treatment. Generalized demodicosis is more of afoxolaner in combination with 0.50–1.07 variable and is characterized by five or more mg/kg of milbemycin oxime is effective in affected areas or lesions that cover an entire the treatment of generalised demodicosis in region of the body, and/or pododemodicosis dogs, with a decrease in lesions in the first that involves two or more legs; the affected days of treatment. areas are erythematous, with comedones, INTRODUCTION alopecia, follicular pustules or papules and scales.9 It can be fatal in severe chronic Demodex mites are considered to be part of 10 the cutaneous microbiota of dogs. It is be- cases with secondary bacterial infection and progression of the disease is associated lieved that all dogs have a small population 2 of Demodex spp. mites in their skin,1 but with lymphadenopathy, lethargy, and fever. the manifestation of the disease is limited Diagnosis of demodicosis is usually to some animals. Under normal conditions, based on clinical signs, and is confirmed by they seem to live as commensals, feeding the presence of mites on deep skin scrap- 2 on the tallow of their hosts, thus acting as a ings, allowing for identification at different 3 pathogenic opportunists. They are transmit- stages of mite development. The manage- ted from the bitch to her puppies during the ment of canine demodicosis includes multi- 8 first days of life2 and are commonly found in modal treatment, in addition to an effective the pilosebaceous follicles.3 acaricide therapy. Demodicosis is the result of an excessive The treatment of internal parasitism is proliferation of the Demodex spp. mite. One suggested to maximize the potential of a 2 of the causes of this process is concurrent successful treatment. The currently avail- immunosuppressive conditions (specific he- able therapeutic options include: reditary immunodeficiency ofDemodex spp. • Amitraz2,4 or acquired immunosuppression). Studies • Ivermectina11 have identified the induction of demodicosis • Imidacloprid-moxidectin12,13 or by the suppression of the immune response • Doramectin14 and observed the development of the disease in strains of immunodeficient rats, in addi- Regardless of the antiparasitic drug chosen, tion to numerous clinical occurrences in im- several months of treatment, with last- munosuppressed humans and animals. These ing from three months or more, are often 15 studies have shown that immunosuppression required to achieve a clinical resolution. For all therapy options, the benefits and risks is directly associated with the development associated with the treatment must be con- of the disease, which is frequently found in dogs and rarely found in cats, resulting in sidered. For example, poor safety or toxicity from the amitraz and and environmental skin lesions consistent with demodicosis.4,5 36 Vol. 17, No.1, 2019 • Intern J Appl Res Vet Med. contamination problems are particularly as- means of a permission letter sociated with avermectins.16 ANIMALS Isoxazolines have opened a new avenue Inclusion criteria were: animals with a mini- in the therapeutic treatment of demodicosis. mum age of 8 weeks and weighing more Afoxolaner is an isoxazoline that has both than 2 kg with parasitic evidence of at least insecticidal and acaricidal activity, acting four live Demodex spp. mites (immature on GABA/glutamate receptors to inhibit or adults), confirmed by positive deep skin chloride ion channels, producing irreversible scrapings and observation of hair samples neuronal hyperexcitability and the death of under a microscope. These are in addition to arthropods.17,18 Afoxolaner has been evalu- clinical evidence of demodicosis such as: ated in dogs with generalised demodicosis using monthly oral administration. It has • Alopecia been shown to effectively reduce live mites • Erythema compared to control groups, as assessed • Comedones through skin scrapings and clinical improve- • Papules ment in dermatological lesions, without • Pustules any adverse effects,15,19 thus achieving a • Scales, or high level of efficacy for the control of this dermatosis. Currently, there is an oral • Scabs. chewable tablet formulation15 that combines Generalized demodicosis was defined the insecticidal-acaricidal compound of as a complete body region or five or more afoxolaner with the nematocidal compound localized lesions (diameter > 2.5 cm) or of milbemycin oxime (NexGard Spectra®, pododemodicosis that involved two or more 2 Boehringer Ingelheim)20,21 to provide treat- limbs. Exclusion criteria were: pregnant ment and control of endo- and ectoparasites or lactating bitches, animals undergoing in dogs.22 immunosuppressive therapy, or having been In addition, milbemycin oxime has also treated with an ectoparasitic with residual been shown to be useful for the treatment efficacy againstDemodex spp. of generalized canine demodicosis at doses Treatment Protocol of 0.5 to 2 mg/kg orally once a day.4 Due Day 1 (time of positive skin scrapings), to its ease of use, safety and efficacy, it can dogs were treated orally with 2.50–5.36 mg/ be used in all dog breeds, including Collies kg of afoxolaner and 0.50–1.07 mg/kg of and Shetland Sheepdogs.23 However, there milbemycin oxime (NexGard Spectra®). are no reports on the use of this isoxazoline The tablets were administered directly into combined with milbemycin oxime for the the oral cavity 10 minutes after eating. Skin treatment of dogs with demodicosis. There- scrapings were repeated on days 7, 14, and fore, the aim of this study was to evaluate 28. Data were recorded as the presence or the efficacy of the use of afoxolaner plus absence of live mites and a dermatological milbemycin oxime in the treatment of gen- lesion score. eralised canine demodicosis after 28 days of Diagnostic Tests treatment. Three surface scrapings (5 x 5 cm) and hair MATERIALS AND METHODS samples, and four scrapes of deep skin (1 x 1 This study protocol was approved by the cm) were taken from the most affected areas. Ethics Committee of the Amecameca Uni- During the procedure, pressure was applied versity Center of the Autonomous University to the area to be sampled to bring the mites of the State of Mexico (UAEM). Sixty-eight to the surface. Areas with primary lesions, dogs from the State of Mexico, Mexico City, such as papules and follicular pustules, were and Guadalajara, Mexico, were included, chosen. Sampling in ulcerated areas was with the prior consent of the owner, by avoided. A scalpel blade was used to collect Intern J Appl Res Vet Med • Vol. 17, No. 1, 2019. 37 Table 1. Comparison of the decrease in the presence of Demodex canis (as assessed by skin scapings) and number of lesions, after treatment with afoxolaner plus milbemycin oxime Day 1 Day 7 Day 14 Day 28 CV MEE Positive samples (%) 68 (100)a 37 (54.4)b 13 (19.1)c 12 (17.6)c 104.70 0.03 Lesions 177.37a 74.10b 33.43bc 9.47c 158.16 7.05 abc Means with different letters within a row represent a significant difference, P < 0.05 the samples.