Abstract
Background
Otodectic mange is one of the most common ectoparasitic diseases in cats and the most common cause of feline otitis externa. It is particularly prevalent in young cats between 3 and 6 mo of age and is a veterinary concern, especially in catteries, due to its highly contagious nature. Although there is a risk of overdiagnosis if based solely on cerumen, it is not difficult to identify Otodectes cynotis if there is a clinical suspicion in a young cat. Considering the variety of available acaricidal molecules, as well as the need to use the most effective treatment, the present article reviews evidence comparing various types of systemic treatment for otodectic mange in cats.
Results
Isoxazolines (sarolaner, fluralaner, or esafoxolaner) or similar molecules such as tigolaner (a bispyrazole) and macrocyclic lactones (selamectin, eprinomectin, or moxidectin) can lead to parasitological cure and improvement of clinical signs associated with otodectic mange in cats, with rare, mainly cutaneous side effects with mild, autoresolving lesions.
Conclusion
Similarities in the clinical and parasitological efficacy of these substances highlight the need for comparative studies that could allow identification of the most efficacious product.
RÉSUMÉ
Le traitement systémique le plus efficace contre la gale otodectique chez les chats : un sujet évalué de manière critique
Contexte
La gale otodectique est l’une des maladies ectoparasitaires les plus courantes chez les chats et la cause la plus fréquente d’otite externe féline. Elle est particulièrement répandue chez les jeunes chats âgés de 3 à 6 mois et constitue une préoccupation vétérinaire, en particulier dans les chatteries, en raison de sa nature hautement contagieuse. Bien qu’il y ait un risque de surdiagnostic si l’on se base uniquement sur le cérumen, il n’est pas difficile d’identifier Otodectes cynotis en cas de suspicion clinique chez un jeune chat. Compte tenu de la variété des molécules acaricides disponibles, ainsi que de la nécessité d’utiliser le traitement le plus efficace, le présent article passe en revue les études comparant les différents types de traitements systémiques de la gale otodectique chez le chat.
Résultats
Les isoxazolines (sarolaner, fluralaner ou esafoxolaner) ou des molécules similaires comme le tigolaner (un bispyrazole) et aussi les lactones macrocycliques (selamectine, eprinomectine ou moxidectine) peuvent conduire à une guérison parasitologique et à une amélioration des signes cliniques associés à la gale otodectique chez le chat, avec de rares effets secondaires, principalement cutanés, avec des lésions peu graves et autorésolutives.
Conclusion
Les similitudes dans l’efficacité clinique et parasitologique de ces substances soulignent la nécessité d’études comparatives qui pourraient permettre d’identifier le produit le plus efficace.
(Traduit par les auteurs)
BACKGROUND
Otodectic mange is one of the most common ectoparasitic diseases in cats. It is caused by Otodectes cynotis, a psoroptidae, and is particularly common in young cats between 3 and 6 mo of age (1). Many terms such as otoacariasis, otoacariosis, ear mite infestation, or otodectic mange are used to describe this condition. In this article, the term “otodectic mange” is used.
Otodectes cynotis are non-burrowing mites with complete development in the external acoustic meatus of cats, dogs, foxes, ferrets, and humans (2,3). The total life cycle lasts ~13 to 15 d in warmer months and up to 21 d in colder months. The female mite lays eggs in the external acoustic meatus. After 4 d of incubation, eggs hatch into larvae (4). These mites feed on the surface of the skin and on the cerumen in the external acoustic meatus (5).
This parasitic otitis is highly contagious, with mites transmitted directly between animals (6,7). Mites can also be transmitted via grooming equipment, bedding, or other shared items (8). In the environment, O. cynotis can survive for up to 12 d at temperatures between 12.3 and 14.2°C (9).
Ear mites are not host-specific and multiple pets can be infested in a household (10). This lack of host specificity means that all mammals in contact with an infested cat should be treated to limit cross- and reinfestation (11). In a Greek survey, cats were common carriers of ear mites: 25.5% of domestic cats were infested with O. cynotis, with a higher prevalence in catteries, especially kittens, which are most commonly infected through contact with their mothers (7). Ear mites are the most common cause of otitis externa in cats. Prevalence of otodectic mange can range from 50 to 80% (12,13).
Clinical signs are characterized by large amounts of dry, dark-brown, coffee-ground-like, ceruminous otic exudate in the external acoustic meatus, erythema of the pinnae, head shaking, and pruritus (6). Secondary bacterial (staphylococci) and fungal (Malassezia spp.) infections are common, and clinicians should adapt their management approaches according to the importance of the cytological findings (14).
Diagnosis is based on history and clinical presentation and is confirmed by demonstrating the presence of mites at various stages (adults, larvae, and eggs) in cerumen observed under a stereomicroscope (15). Differential diagnosis includes bacterial or fungal erythematous and ceruminous otitis of various origins: allergic otitis, otic masses, foreign body otitis.
Historically, treatment of otodectic mange was based on topical preparations instilled into the external acoustic meatus. However, compliance with these treatments can be difficult, leading to the use of systemic medications.
Since the early 2000s, topical systemic acaricides (selamectin, eprinomectin, and moxidectin) with excellent efficacy have been developed (16–20). More recently, new systemic molecules (fluralaner, sarolaner, afoxolaner, lotilaner, and tigolaner) with rapid and excellent efficacy have been developed for oral or topical administration (21–29).
For this article, we critically reviewed the literature on systemic treatments for otodectic mange in cats and used the available evidence to determine the most effective therapy according to the relevant literature identified. The format chosen was “critically appraised topic.”
CLINICAL SCENARIO
The patient is a 5-month-old domestic shorthair cat presented with bilateral severe ear pruritus. Dermatological examination reveals pinnae erythema and a dark-brown, coffee-ground-like, ceruminous exudate. Microscopic examination of the exudate collected by ear swab reveals O. cynotis mites in various stages (adults, larvae, and eggs). Otodectic mange is therefore diagnosed.
CLINICAL QUESTION
A population, intervention, comparison, outcome (PICO) question was formulated: What are the most effective and safest systemic treatments for cats with otodectic mange?
| P (population) | = | cats with otodectic mange. |
| I (intervention) | = | systemic treatment. |
| C (comparison) | = | various molecules. |
| O (outcome) | = | clinical and parasitic resolution without side effects. |
| Preferred study type | = | clinical trials. |
SEARCH STRATEGY
A literature review was conducted to identify types of treatment, using the following search terms: [(cats OR feline) AND (otodectic mange OR otacariosis OR otacariasis OR Otodectes cynotis) AND (treatment OR systemic treatment)]. Two electronic databases were searched (PubMed and), with no time limit, with date up to February 17, 2024. Reporting was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) updated guideline for systematic reviews (30).
QUANTITY AND QUALITY OF EVIDENCE
The search yielded 42 results in PubMed and 51 in ScienceDirect. Articles in languages other than English were excluded. Among the potentially eligible full-text articles, only 18 met the eligibility criteria, including relevance to our PICO question and inclusion of multiple animals. Case reports and case series were excluded (Figure 1). The keyword string search system was much less efficient on ScienceDirect than on PubMed. On ScienceDirect, the number of results increased to almost 300. The same search, after excluding book chapters, encyclopedias, review articles or conference abstracts, yielded ~50 results.
FIGURE 1.
Search strategy and selection process flowchart.
Quality of the evidence, including journal names, types of study, and numbers of subjects enrolled, is summarized in Table 1, whereas main results of all the studies are summarized in Table 2. All articles included were published in international, peer-reviewed journals, but quality of the evidence varied considerably. Factors responsible for this variability were the type of study and the number of cases included. However, the quality of all included studies was considered sufficient to contribute to the PICO conclusion.
TABLE 1.
Summary of the quality of evidence for systemic treatments in cats with otodectic mange.
| Journal/publication year | Type of study | Number of subjects | Reference |
|---|---|---|---|
| Veterinary Parasitology/2017 | 2 prospective, placebo-controlled, randomized, blinded studies; multicenter | 30 (14 and 16 for Studies 1 and 2, respectively) | Becskei et al, 2017 (21) |
| BMC Vet Research/2019 | Prospective, no control group, multicenter | 39 | Bosco et al, 2019 (22) |
| Parasites & Vectors/2017 | Prospective, placebo-controlled, randomized, blinded study; single center | 16 | Taenzler et al, 2017 (23) |
| Parasites & Vectors/2018 | Prospective, placebo-controlled randomized, blinded study; single center | 16 | Taenzler et al, 2018 (24) |
| Veterinary Parasitology/2018 | Prospective, randomized, including control group, single center | 16 | Machado et al, 2018 (25) |
| Parasite/2021 | 3 prospective, placebo-controlled randomized, multicenter studies | 50: 8 in Lab Study 1, 10 in Lab Study 2, 32 in Field Study | Tielemans et al, 2021 (26) |
| Current Research in Parasitology & Vector-borne Diseases/2023 | Prospective, positive-controlled, blinded, randomized, multicenter study Naturally infested cats |
78 treated 70 positive control |
Blazejak et al, 2023 (27) |
| Pathogens/2021 | Prospective, negative-controlled, blinded, randomized, single-center study | 10 treated | Campos et al, 2021 (28) |
| Veterinary Parasitology/2019 | 2 prospective, positive-controlled, single-masked randomized, multicenter studies | 124: 74 in Study 1, 50 in Study 2 | Vatta et al, 2019 (29) |
| Veterinary Parasitology/2003 | Prospective, no controls, single-center study | 30 | Blot et al, 2003 (16) |
| Veterinary Parasitology/2000 | 2 prospective, negative-controlled, randomized, blinded, multicenter studies | 32: 10 in Study 1 (USA), 6 in Study 2 (Italy) | Shanks et al, 2000 (17) |
| Veterinary Parasitology/2000 | Prospective, positive-controlled, randomized, blinded, multicenter study | 144: 57 (USA), 87 (UK/France) | Six et al, 2000 (18) |
| Parasite/2014 | Preventive efficacy, prospective, negative-controlled, randomized, single-center study | 6 treated 6 control |
Beugnet et al, 2014 (19) |
| Parasitology Research/2003 | Prospective, placebo-controlled, randomized, blinded, single-center study | 10 treated twice (Day 0 and Day 28) 10 placebo 10 treated only on Day 0 |
Fourie et al, 2003 (20) |
| Current Research in Parasitology & Vector-borne Diseases/2023 | 3, prospective, negative-controlled, randomized, blinded, single-center studies Artificially infested cats |
48: 3 groups of 8 (+ 8 negative controls per group) | Blazejak et al, 2023 (34) |
| Canadian Veterinary Journal/2012 | Prospective, positive-controlled, randomized, blinded, single-center study | 12 treated 12 positive control |
Roy et al, 2012 (31) |
| Veterinary World/2011 | Prospective, noncontrolled, non-randomized, non-blinded, single-center study | 60: 30 in Group 1 (selamectin), 30 in Group 2 (doramectin) | Salib and Baraka, 2011 (32) |
| Assiut Veterinary Medical Journal/2015 | Prospective, randomized, single-center study | 17 | Wally et al, 2015 (33) |
TABLE 2.
Analysis of relevant publications regarding systemic treatments in cats with otodectic mange.
| Tested medications | Patients | Study design | Outcomes and key results | Study weaknesses | Reference |
|---|---|---|---|---|---|
| Selamectin + sarolaner versus placebo | 30 cats, DSH, 15 males, 15 females Age: 4 mo to 8 y 2 groups: 15 cats in treated group, 15 cats in placebo group Induced infestation (interaural transfer of mites from naturally infested cats) |
Confirmed infestation before enrollment (direct or otoscopic examination of both ears), inclusion if > 5 live mites Cats were separated into 2 groups Study 1: n = 14 Study 2: n = 16 At D0, cats were randomly and blindly allocated to treated group [selamectin (6 mg/kg) + sarolaner (1 mg/kg)] or placebo-treated group (excipients) Otoscopy on D14 semiquantitative assessment/total ear count under sedation on D30 with a stereomicroscope (flushing with 5% aqueous solution of docusate sodium and saline solution until ear ducts were clean and counting live mites in recovered material) |
Efficacy based on reduction in mites count in treated versus placebo groups on D30: Study 1 (n = 7): 99.2% (P = 0.0003) Study 2 (n = 8): 99.3% (P = 0.0021) At D14: 2 cats with live mites in the treated group (n = 15), 14 cats with live mites in the placebo-treated group (n = 15) |
Medium or limited number of cats No evaluation of clinical signs |
Becskei et al, 2017 (21) |
| Fluralaner | 39 cats, DSH, 18 males, 21 females 14 stray cats 25 owned cats Age: 1 to 8 y Weight: 1.8 to 8.5 kg Naturally infested cats |
Confirm infestation before enrollment (direct or otoscopic examination of both ears) Cats were separated into 2 groups Study 1: stray cats Study 2: owned cats At D0, semiquantitative assessment of ear mite infestation: 1 to 5, 6 to 20, or > 20 live mites Application of 40 mg/kg of fluralaner D7, D14, D28, D56, D84: clinical, otoscopic, and cytological examination of ears + clinical scoring D28, D56, D84: sedation and ear flushing, with recovered material filtered through a sieve and ear mites (adults and immatures) counted |
Study 1 (stray cats): Efficacy D0 to D84: 100% (P < 0.0001) Study 2 (owned cats): Efficacy D0 to D84: 100% (P < 0.0001) D7: No live mites observed in ear canals in either study |
Absence of controls Medium or limited number of cats |
Bosco et al, 2019 (22) |
| Fluralaner versus placebo | 16 cats, DSH, 6 males, 10 females Age: 10 wk to 5 y Weight: 2.3 to 4.7 kg Induced infestation (interaural transfer of mites from naturally infested cats) with 50 to 100 live mites 1 mo before start |
Infestation confirmed before enrollment (otoscopic examination of both ears) Inclusion in study if > 10 live mites per ear at D0 At D0, cats were randomly and blindingly allocated to treated group (40 mg/kg of fluralaner) or saline (placebo-treated group) At D0, D14 and D28: Otoscopic semiquantitative infestation assessment (0, 1 to 4, 5 to 10, or > 10 live mites) and amount of debris/cerumen per ear canal (no, slight, moderate, or severe) On D28, sedate, flush with 5% aqueous solution of docusate sodium and saline solution until ear ducts were clean; filter material (38-micrometer sieve) and count (stereomicroscope) live mites |
No visible mites on D14 or D28 in all cats in treated group Reduced cerumen/debris at D14 and D28 in treated group Efficacy based on 100% reduction (P < 0.0001) in mite counts in treated versus placebo groups on D28 |
Limited number of cats | Taenzler et al, 2017 (23) |
| Fluralaner + moxidectin versus placebo | 16 cats, DSH, 7 neutered males, 9 intact females Age: 1 to 7 y Weight: 2.3 to 4.3 kg Induced infestation (interaural transfer of mites from naturally infested cats) with 50 to 100 live mites 1 mo before start |
Infestation confirmed before enrollment (otoscopic examination of both ears) Inclusion in study if > 10 live mites in each ear at D0 At D0, cats randomly and blindingly allocated to treated group (n = 8) (40 mg/kg of fluralaner + 2 mg/kg moxidectin) or saline solution (placebo-treated group) At D0, D14, and D28, otoscopic semi quantitative infestation assessment (0, 1 to 4, 5 to 10, and > 10 live mites) and amount of debris/cerumen per ear canal (no, slight, moderate, or severe) At D28, sedate, flush with 5% aqueous solution of docusate sodium and saline solution until ear ducts were clean; filter (38-micrometer sieve) material and count live mites |
No visible mites on D14 or D28 in all cats in treated group Decreased amount of cerumen/debris at D14 and D28 in treated group Efficacy based on reduced mite counts in treated versus placebo groups on D28: 100% (P < 0.0059) |
Limited number of cats | Taenzler et al, 2018 (24) |
| Afoxolaner | 16 cats, DSH, Age: 1 to 6 y Weight: 2.6 to 4.7 kg Naturally infested cats |
Infestation confirmed before enrollment (video-otoscopic examination of both ears) Semiquantitative assessment of ear mite infestation (< 5, 5 to 10, and > 10 live mites for Scores 1, 2, and 3, respectively) At D0, cats were randomly allocated to treated group (2.5 mg/kg of oral afoxolaner) or control group (untreated) Mean of treated group: 2.0 Mean of control group: 2.3 Assessment at H4 and D7, D14, D21, D28, and D35 |
No visible mites at D2 in all cats of treated group Mean of control group: 2 to 3 from D7 to D14, and 1 to 3 from D14 to D35 No mites for treated group at D35 No reinfestation at D65 for treated group |
Limited number of cats No evaluation of clinical signs |
Machado et al, 2018 (25) |
| Esafoxolaner + eprinomectin/praziquantel versus placebo | 3 studies: Lab study 1: 8 cats with induced infestation (interaural transfer of 100 live mites per ear) Lab study 2: 10 cats with natural infestation Field study: 32 cats with natural infestation |
Infestation confirmed before enrollment (otoscopic examination of both ears) On D0, cats randomly allocated to treated or placebo group Lab study 1: D0: treated group (1.44 mg/kg esafoxolaner + 0.48 mg/kg eprinomectin + 10.0 mg/kg praziquantel), placebo group (0.12 mL/kg mineral oil) Otoscopic examination on D0, D7, D14, and D28 for semiquantitative assessment of ear mite infestation and pruritus/clinical scoring D28: quantitative assessment of ear mites under sedation (swabbing and flushing) Lab study 2: D0: same treatment as in Lab study 1 D32: quantitative assessment of ear mites under sedation (swabbing and flushing) Field study: D0: treated group [0.3 mL NexGard combo (Boehringer Ingelheim) if weight 0.8 to 2.5 kg, 0.9 mL if weight 2.5 to 7.5 kg], placebo group (mineral oil 0.3 mL if weight 0.8 to 2.5 kg or 0.9 mL if weight 2.5 to 7.5 kg) Otoscopic examination on D0, D30 for pruritus/clinical scoring D30: quantitative assessment of ear mites under sedation (swabbing and flushing) |
Lab study 1: Efficacy based on reduction in mite count in treated group versus placebo on D28: 97.7% (P < 0.001) Reduction of otoscopic score of live mites and debris/cerumen on D7, D14, D21, and D28 Lab study 2: Efficacy based on reduction in mite count in treated group versus placebo on D28: 99.9% (P < 0.0001) Field study: Reduction of debris/cerumen in majority of cats (28/32), cleared in 1/3 (10/32) Improvement of pruritus for majority (27/32), cleared in 1/2 (17/32) Efficacy based on reduction in mite count in treated group versus placebo on D30: 97.4% (P < 0.0001) |
Medium or limited number of cats | Tielmans et al, 2021 (26) |
| Tigolaner + emodepside/praziquantel versus sarolaner + selamectin | 78 cats in treated group: 5 purebred, 73 non-purebred 44 females, 34 males Age: 2.5 to 180 mo Weight: 1.3 to 7.9 kg 70 cats in positive control group: 6 purebred, 64 non-purebred 41 females, 29 males Age: 2.8 to 180 mo Weight: 1.3 to 6.3 kg Naturally infested cats Client-owned cats Not treated for ≥ 3 mo |
Confirmation of infestation before enrollment (otoscopic examination and microscopic examination of both ears) Inclusion in the study if > 3 live mites per ear at D0 At D0, cats were randomly allocated to treated or positive control group Treated group: 14.4 mg/kg tigolaner + 3 mg/kg emodepside + 12 mg/kg praziquantel Positive control group: 6 mg/kg selamectin + 1 mg/kg sarolaner Otoscopic examination and microscopic examination of both ears at D14 and D28 Clinical scoring at D0, D14, D28: head shaking, pruritus, trauma/alopecia at the pinnae, erythema, or debris in ear canal Assess presence of ear mites at D0 and D28 |
Clinical improvement in treated group and in positive control group at D14 and D28 Efficacy based on number of mite-free cats: In treated group: At D14 (70/78: 89.7%) At D28 (78/78: 100%) In positive control group: At D14 (62/70: 88.6%) At D28 (70/70: 100%) |
No data on ear mite assessment/flushing for evaluation of efficacy | Blazejak et al, 2023 (27) |
| Sarolaner | 10 Brazilian mixed-breed 6 males, 4 females Age: 1 to 6 y Weight: 2.9 to 5.15 kg Naturally infested cats |
Cats included in the study if presence of clinical signs compatible with otitis externa and confirmation of infestation (video otoscopic examination) at D5 and D2 Semiquantitative assessment of ear mite infestation: 0, 1, 2, and 3 for 0, < 5, 5 to 10, and > 10, respectively At D0, cats randomly allocated to treated group (sarolaner 2 to 4 mg/kg) or negative control group Video otoscopic examination and semiquantitative assessment at D0 + 2 h, 4 h, 12 h, D1, D2, D7, D14, D21, and D28 At D28, sedate, flush with 5% aqueous solution of docusate sodium and saline solution until ear ducts were clean; filter (38-micrometer sieve) material and count live mites |
Reduction of average semiquantitative scoring: 2.6 at D0, 1.2 at D1, 0 at D48 Efficacy based on reduction in mite count in treated group versus control: 100% at D28 (P < 0.0001) |
Limited number of cats No evaluation of clinical signs |
Campos et al, 2021 (28) |
| Selamectin + sarolaner versus imidacloprid + moxidectin | 124 mixed-breed cats (81.5% DSH) 62 males, 62 females Age: mean 2.7 y (9 wk to 14 y) Weight: 3.6 kg, 1.3 to 9.8 kg Client-owned cats Naturally infested cats |
Infestation confirmed before infestation (bilateral otoscopic examination) and examination of aural secretions, exudates, or debris if no direct observation of ear mites by otoscopy at D1, D0 Enrolled if > 5 live mites At D0, cats randomly allocated to treated group (6 to 12 mg/kg selamectin + 1 to 2 mg/kg sarolaner) or positive control group (10 mg/kg imidacloprid + 1 mg/kg moxidectin) Video otoscopic examination and qualitative assessment at D14 and D30 |
In treated group: Efficacy based on number of mite-free cats At D14 (n = 55): 87.3% At D30 (n = 54): 94.4% In positive control group: At D14 (n = 25): 64% At D30 (n = 25): 72% D14: P = 0.018 D30: P = 0.013 Significantly more cats with no mites in treated versus positive control group on D14 and D30 |
No data on ear mite counting/flushing No evaluation of clinical signs |
Vatta et al, 2019 (29) |
| Selamectin | 30 mixed-breed cats from a cattery of 120 cats with endemic infestation 5 males, 16 neutered males, 8 females, 1 neutered female Age: 1.5 to 9 y Naturally infested cats No treatment for ≥ 6 wk before study |
Infestation confirmed before enrollment (otoscopic examination/microscopic examination) D0: cats treated with 6 mg/kg selamectin Clinical scoring (erythema, ulcers, pruritus, cerumen, head shaking, scratch reflex) 2×/wk (D0, D3, D7, D10, D14, D17, D21, D24, and D28) Video otoscopic examination and qualitative assessment on D0 and D30 |
At D30: Efficacy based on number of mite-free cats: 100% (n = 30) Absence of live adult mites in all cats (n = 30), D3 to D30 Rapid improvement of clinical scoring (no more cerumen at D21) |
Absence of control group No statistical analysis |
Blot et al, 2003 (16) |
| Selamectin versus placebo | 32 DSH cats from cattery, 2 labs (USA and Italy) 14 males, 18 females Age: 4 mo to 5 y Weight: 1.2 to 4.6 kg Naturally infested cats |
Confirmation of infestation before enrollment (otoscopic examination/microscopic examination) on D-3 D0: treated group (6 mg/kg selamectin), negative control group (vehicle alone) D30 quantitative assessment (swabbing and flushing under anesthesia in 1 study and dissection of ear after euthanasia in other study) |
Efficacy based on reduction in mite count in treated group versus control group: USA group (treated n = 10): 100% (P = 0.0006) Italy group (treated n = 6): 100% (P = 0.0010) |
Limited number of cats No evaluation of clinical signs |
Shanks et al, 2000 (17) |
| Selamectin versus Otomite (Virbac) versus GAC (Arnold Veterinary Products) versus Oridermyl (Vetoquinol) | 144 DSH cats in treated group: 57 in USA 87 in UK/France 84 males, 75 females Age: 6 wk to 16 y Weight: 0.5 to 8.2 kg 61 positive-control group Client-owned cats Naturally infested cats No antiparasitic treatment at least 1 to 2 mo before study |
Infestation confirmed before enrollment (otoscopic examination/microscopic examination of cerumen if no mites were observed by direct examination) Enrollment if live mites D0: treated group (6 mg/kg selamectin), positive control group (Otomite or GAC or Oridermyl) Video otoscopic examination and qualitative assessment at D0, D14, and D30 in USA study group and at D0 and D30 in UK/France study group Clinical scoring: head shaking, pruritus/ear scratching, trauma or alopecia of the pinnae, erythema, ulceration or debris in ear canals |
Efficacy based on number of mite-free cats: USA study group: At D14, 59/62: 95.2% (P < 0.0001 compared to D0, P > 0.05 compared to control) At D30, 60/60: 100% (P < 0.0001 compared to D0, P > 0.05 compared to control) UK/France study group: At D30, 82/87: 94.3% (P < 0.0001 compared to D0, P > 0.05 compared to control) |
No data on flushing | Six et al, 2000 (18) |
| Fipronil + (S)- methoprene-eprinomectin-praziquantel | 6 treated cats 6 non-treated cats Age: > 6 mo Weight: > 2 kg Naturally infested for the chronically infested cats |
Preventive efficacy Confirmation of infestation of chronically infested cats at D1 and D28 Group 1: 6 non-treated cats housed with 3 chronically infested cats in a room (20 m2) for 1 mo Group 2: 6 treated cats housed with 3 chronically infested cats in a room (20 m2) for 1 mo D7, D0: randomly allocate the 12 naive cats to Groups 1 or 2 D1: clinical scoring for cats in both groups D0: Group 2 given 0.3 mL if < 2.5 kg [fipronil 8.3%, (S)-methoprene 10%, eprinomectin 0.4%, praziquantel 8.3%], 0.9 mL if > 2.5 to 7.5 kg D28: clinical scoring (ear pruritus: 0 to 3, cerumen: 0 to 3) and complete ear mite counts by flushing |
Efficacy based on number of mites after D28 in both groups: Group 1 (untreated): 129 live mites Group 2 (treated): 5 live mites % preventive efficacy: 96.12% (P = 0.003) Increase in clinical scores for Group 1 (untreated) between D1 and D28 (P = 0.00026), not significant for Group 2 (treated) (P = 0.30) Difference in cerumen scoring between groups at D28 (P = 0.00026) |
Limited number of cats | Beugnet et al, 2014 (19) |
| Imidacloprid 10% + moxidectin 1% versus placebo | 30 DSH cats No data on sex ratio, age, or body weight Naturally infested cats |
D3: swabbed both ears for mite assessment before enrollment D1: random allocation in 3 groups: 10 cats for negative placebo group, 10 cats treated once at D0 with imidacloprid/moxidectin and at D28 with a placebo, 10 cats treated twice (D0 and D28) with imidacloprid/moxidectin Qualitative (presence of mites or not) assessment (by swabbing) at D8, D22, D36, and D50 |
Efficacy based on number of mite-free cats: Group 2: treated once (D0): 90% on D22, 80% on D50 Group 3: treated twice (D0 and D28): 100% on D22, 100% on D50 |
Limited number of cats No data on sex ratio, age, or body weight No evaluation of clinical signs |
Fourie et al, 2003 (20) |
| Tigolaner + emodepside + praziquantel, Felpreva (Vetoquinol) versus tigolaner versus emodepside + praziquantel, Profender (Vetoquinol) versus placebo | 80 DSH cats No data on sex ratio Age: 8 to 172 mo Weight: 2.2 to 5.9 kg Induced infestation 1 mo before inclusion by South Africa Otodectes origin in Studies 1 and 2 (80 to 100 live mites by ear canal) USA Otodectes origin for Study 3 (> 10 live mites by ear canal) |
Confirmation of infestation before enrollment (video otoscopic examination) on D6 to D2 Semiquantitative assessment: 0: no mites, 1: < 5, 2: 5 to 10, 3: > 10 live mites Inclusion in the study if > 10 live mites in 1 ear for Studies 1 and 2 If > 5 live mites in 1 ear in Study 3 Random allocation in 3 studies and groups: Study 1: treated group (Felpreva) or placebo group (Solketal) Study 2: treated Group 1 (Felpreva) or treated Group 2 [tigolaner alone (14.5 mg/kg)], placebo group (Solketal) Study 3: treated Group 1 (Felpreva) or treated Group 2 [tigolaner alone (14.5 mg/kg)] or treated Group 3 (Profender) or placebo group (mineral oil) In Studies 1 and 2 at D14 and D28: otoscopic semiquantitative infestation assessment (0 live mites, 1 to 4 live mites, 5 to 10 live mites, > 10 live mites) and recording of debris/cerumen amount in each ear canal (0: no, 1: slight, 2: moderate, 3: severe) On D28 (Studies 1 and 2), D30 (Study 3), sedate, flush with 5% aqueous solution of docusate sodium and saline solution until ear ducts were clean; filter (38-micrometer sieve) material and count live mites |
Study 1: efficacy = 100% (n = 8) (P < 0.0001) Study 2: Group 1 Felpreva: efficacy = 99.6% (n = 8) (P < 0.0001) Group 2 Tigolaner alone: efficacy = 99.9% (n = 8) (P < 0.0001) Group 3 Profender: efficacy = 31.6% (n = 8) (P = 0.4621) Study 3: Group 1 Felpreva: efficacy = 100% (n = 8) (P < 0.0001) Group 2 Tigolaner alone: efficacy = 100% (n = 8) (P < 0.0001) Group 3 Profender: efficacy = 36% (n = 8) (not determined) No significant difference between Profender and control group Improvement in cerumen/debris scoring in Felpreva group in Studies 1 and 2 on D14 and D28 Improvement of mite count for Tigolaner and Felpreva group in Studies 1 and 2 on D14 |
Limited number of cats | Blazejak et al, 2023 (34) |
| Selamectin versus neomycin + nystatin + triamcinolone + permethrin, Oridermyl | 24 DSH cats from a cattery 14 males, 10 females No data on age or body weight Naturally infested cats |
Confirmation of infestation before enrollment (otoscopic examination/microscopic examination) on D1 At D0, cats were randomly and blindly allocated to treated group [selamectin (6 mg/kg)] or positive control group [Oridermyl (0.3 mL)] in each ear canal, q24h for 9 d Otoscopic examination on D0, D2, D3, D4, D6, D8, D10 Semiquantitative infestation assessment (0: no mites, 1: < 5 live mites, 2: 5 to 10 live mites, 3: > 10 live mites) Clinical scoring (erythema, pruritus, amount of secretions, pain) for each cat |
Efficacy based on reduction in mite count at D10 Treated group: 100% (n = 12) Positive control group: 100% (n = 12) Rapid acaricidal effect (no live mites at D4) Total otoscopic scoring (pain, erythema, pruritus, secretions, visible mites) significantly lower in positive control group (Oridermyl) than in treated group (selamectin) from D2 to D10 (P < 0.001) |
Limited number of cats | Roy et al, 2012 (31) |
| Selamectin or doramectin (subcutaneous) | 60 DSH cats No data on sex ratio, age, or body weight Naturally infested cats |
Confirmation of infestation before enrollment (ear swabbing and counting) Group 1: 30 cats, treated on D0 with 6 mg/kg selamectin Group 2: 30 cats, treated on D0 with 1 mL/50 kg subcutaneous doramectin On D14, ear swabbing and counting each ear for every cat |
Efficacy based on number of mite-free cats on D14: Group 1 (selamectin): 96.6% (n = 30) Group 2 (doramectin): 90% (n = 30) |
Absence of comparison between groups/no control group | Salib and Baraka, 2011 (32) |
| Ivermectin versus fipronil versus fusidic acid + framycetin + nystatin, Canaural (Leo Pharmaceutical) | 17 client-owned cats 10 Persian, 7 Angora 9 males, 8 females Age: 2 to 72 mo Body weight not recorded Naturally infested cats |
Enrollment if suggestive clinical signs of infestation and otoscopic observation of ear mites D0: cats randomly allocated to treated groups Group 1: ivermectin subcutaneous injections, 2 to 4× at 1-week intervals (no data on dosage) Group 2: topical fipronil (skin) 1× per month Group 3: otic application of Canaural, q12h for 21 d On D7, D14, D21, and D30, response to treatment and owner satisfaction were recorded; assessment of ear mites in each ear canal/aural debris; qualitative assessment (absent/mild/moderate/severe) of clinical signs: head shaking, pruritus/ear scratching, trauma or alopecia of the pinnae, erythema/ulceration/debris in ear canals |
Efficacy based on number of mite-free cats at D30: Group 1 (ivermectin): 75% (n = 7) Group 2 (fipronil): 60% (n = 5) Group 3 (Canaural): 100% (n = 5) Absence of significant difference among the 3 treatments (P = 0.409) |
Limited number of cats | Wally et al, 2015 (33) |
D — Day; DSH — Domestic shorthair; H — Hour.
RESULTS AND DISCUSSION
Tested molecules and combinations
From the 18 studies included in our review, 6 products containing only a macrocyclic lactone (selamectin, doramectin, or ivermectin) administered topically or subcutaneously were tested (16–18,31–33). Isoxazolines alone (fluralaner, afoxolaner, or sarolaner) were used in 4 studies (22,23,25,28).
In 4 studies, macrocyclic lactones (selamectin, moxidectin, eprinomectin) were combined with isoxazolines (sarolaner, fluralaner, esafoxolaner) to enhance the ectoparasiticidal effect (21,24,26,29). Tigolaner, a newly developed molecule belonging to the chemical class of bispyrazoles with an antagonist effect on GABA-regulated chloride channels, has also been tested in some studies, sometimes as a positive control molecule (27,34). This molecule is not an isoxazoline as its name suggests, but its mechanism of action is very similar. In 2 studies, macrocyclic lactones (eprinomectin, moxidectin) were tested in combination with other molecules such as fipronil, (S)-methoprene, praziquantel, or imidacloprid, to enhance the ectoparasiticidal effect or to extend the spectrum to endoparasites (19,20).
The efficacy of tigolaner compared to a macrocyclic lactone (selamectin) associated with an isoxazoline (sarolaner) was tested in a study (27). In another study, the same combination (selamectin/sarolaner) was compared to a macrocyclic lactone (moxidectin) (29).
Study design
Eleven of the 18 studies were based on a natural infestation model in which infestation was confirmed before enrolment by direct observation of ear mites (by otoscopy or video otoscopy) or by observation of live mites on an ear swab or ear debris under a stereomicroscope (16–18,20,22,25,27–29,31,32). Four studies used an artificial infestation model with intra-aural transfer of live mites from donors (21,23,24,34). One study used a mixed model with natural and artificial ear mite infestation, depending on the group studied (26).
Most studies used positive controls (18,27,29,31,33,34), but 3 of the 18 studies had no control group (16,22,32). In 6 studies, treated groups were compared to placebo groups (16,19,21,23,24,26); however, in the last 3 studies, treated groups were compared to untreated groups (19,25,28).
Various studies were conducted to assess the efficacy of the compounds tested. Six of the 18 studies evaluated treatment efficacy by looking only at the reduction in mite counts (17,19,26,28,31,34). Seven of the 18 studies evaluated the efficacy of the treatment not by analyzing reduction in number of mites in treated cats but by analyzing the proportion of cats with no mites (16,18,20,27,29,32,33). Five studies used both designs — reductions in mite counts in treated cats and number of mite-free cats — to assess treatment efficacy (21–25). Assessment of changes in ear-mite counts were variable and included quantitative, semiquantitative, or qualitative approaches. Three of the 18 studies used a quantitative assessment of ear mite development in treated cats (17,20,26), 3 used a semiquantitative assessment (25,28,31), 5 used both semiquantitative and quantitative assessments (21–24,34), and 7 used only a qualitative assessment (16,18,20,27,29,32,33). Some studies also evaluated the development of a clinical score for ear pruritus, head shaking, ulcers in the external auditory canal, or amount of cerumen (16,18,19,22–24,26,27,31,33,34).
In 16 of the 18 studies, only 1 treatment was given at the start of the protocol on Day 0 (D0) (16–19,21–29,31, 32,34). Only 2 studies reported multiple treatments. Fourie et al used moxidectin in combination with imidacloprid, given 2 times, 28 d apart in 1 group, compared to a single treatment at D0 (20). Waly et al compared 3 groups, one of which received 2 to 4 courses of ivermectin injected subcutaneously, 1 wk apart (33).
Safety results
Almost all trials evaluated the safety of the various molecules (16–18,21,23–29,31,34). In most cases, no side effects were reported, regardless of the family of molecules used (isooxazolines, macrocyclic lactones, or bispyrazoles), apart from a few transient cosmetological disorders (greasiness, matting, and spikiness of the hairs) that were observed in some cats. Five of 18 studies did not analyze the potential side effects associated with using the treatments (19,20,22,32,33).
Side effects were reported in 2 studies with the combination of selamectin and sarolaner (21,29). Most adverse reactions reported were moderate skin lesions (alopecia, erythema, squamosis, dermatitis) that were rarely observed (< 4% of cats studied) and autoresolving (29). In very rare cases, systemic effects were reported (salivation, depression, anorexia, vomiting). As with the skin lesions, no treatments were required to resolve these side effects (21).
Efficacy results
Most molecules tested in the studies produced good improvements in clinical signs associated with ear-mite infestation, as well as reductions in the number of mites, or even complete elimination of mites. Cats were declared microscopically clear in 12 of 18 studies. Most of the molecules associated with complete microscopical cure belonged to the isoxazoline family or molecules with similar mechanisms of action, such as tigolaner. Indeed, 6 of those studies used isoxazoline alone or in combination with other molecules (sarolaner, afoxolaner, fluralaner, or fluralaner + moxidectin) (22–25,28), and a positive control using isoxazoline in combination with a macrocyclic lactone (sarolaner/selamectin) also achieved complete microscopic treatment (27). Some studies used isoxazolines alone or in combination with other molecules (sarolaner/selamectin or esafoxolaner/eprinomectin) with a result < 100%, unlike the studies cited previously. In all cases, results were still very good, with efficacy rates ranging from 94 to > 99% (21,26,29).
Two studies used tigolaner in combination with emodepside and praziquantel. The efficacy of this molecule was very good, with between 99.6 and 100% of cats mite-free 1 mo after treatment (27,34). In 2 studies, isoxazolines (afoxolaner and sarolaner) produced a very quick parasitological cure, with total disappearance of mites in 48 h (25,28). In studies using isoxazolines or tigolaner, the complete microscopical cure was systematically achieved with a single treatment over the study period (usually 1 mo) (22–25,27,28,34). In 1 study, a single treatment with oral afoxolaner provided rapid and total healing in 48 h, with no reinfestation observed up to 65 d post-treatment (25).
Macrocyclic lactones (selamectin or moxidectin) can also lead to a complete cure. Five studies using those molecules reported a complete microscopic cure (16–18,20,31). In one of these studies, topical moxidectin 10% had to be applied twice with a 28-day interval to achieve full efficacy after 50 d, whereas the group treated once achieved only 80% efficacy after 50 d of follow-up (20). In 4 of 5 studies, the macrocyclic lactone molecule used was selamectin 6%, one of the most widely used molecules for treatment of otodectic mange in cats since the early 2000s (16–18,31). In those 4 studies, the acaricidal effect was observed rapidly, with 2 studies reporting the absence of larvae on otoscopic examination 4 d after application of selamectin (16,31), and 3 studies confirming 100% efficacy 30 d after treatment (16–18). Roy et al (31) conducted a count at 10 d post-treatment and reported complete efficacy of selamectin at a dose of 6%.
Macrocyclic lactones can also be administered off label via the subcutaneous route. Two studies in our review used this route. In one, doramectin (off label) was injected once, at 0.2 mg/kg, and its efficacy was measured at 90% after 14 d by evaluating the number of mite-free cats. However, no comparison was made with the other study group treated with selamectin 6% (32). The other study used ivermectin (off label) injected 2 to 4× with a 1-week interval; dosage data were not provided. Efficacy was measured after 30 d by evaluating the number of mite-free cats. Only 75% of cats were mite free after 1 mo, with no significant difference between the positive control group treated with topical fipronil on the skin or with a combination of fusidic acid, framycetin, nystatin, and prednisolone applied q12h for 21 d (33).
In 1 study, moxidectin at 10% in combination with imidacloprid (which has no acaricidal properties, only insecticidal properties) was used as a positive control with a single application. The result was limited, with a rate of treated cats of < 75% at 30 d (29).
One study investigated the preventive effect of a macrocyclic lactone (eprinomectin) in combination with fipronil (an insecticide), (S)-methoprene (an insect growth regulator with ovicidal and larvicidal activity), and praziquantel (an anthelmintic) in healthy cats housed with cats chronically infected with O. cynotis. After 28 d of cohabitation, all cats in the untreated control group were infected. In the group treated with the combination of molecules, only 3 cats were infected with a low number of mites (< 3 live mites were detected in the flushing product material). Efficacy at 28 d was assessed as 96.12% (P = 0.003) (19).
Oral afoxolaner and sarolaner were assessed in 2 studies. Although these molecules are not currently available for cats, they have interesting properties and can provide a rapid and complete cure. After 48 h, cats treated orally with a dose of 2.5 mg/kg of afoxolaner had no live mites, and reinfestation was successfully prevented for up to 65 d (25). Similarly, a single oral dose of 2 to 4 mg/kg of sarolaner resulted in a complete cure in 24 to 48 h, with no reinfestation over the 1-month study period (28).
CONCLUSIONS AND IMPLICATIONS FOR PRACTITIONERS
Based on scientific evidence, isoxazolines (sarolaner, fluralaner, esafoxolaner) or similar molecules such as tigolaner (a bispyrazole) as well as macrocyclic lactones (selamectin, eprinomectin, or moxidectin) can all lead to parasitological cure and improvement in clinical signs associated with otodectic mange in cats. Side effects are rare and mainly cutaneous with mild, autoresolving lesions. Oral afoxolaner and sarolaner appeared to be effective and safe but are not available on the market. No studies are available on other isoxazolines such as lotilaner, an oral antiparasitic treatment available for cats.
In conclusion, a single dose of topical fluralaner, esafoxolaner, or sarolaner, alone or in combination with moxidectin or selamectin, was the most effective and safest systemic treatment for cats with otodectic mange. Isoxazolines provided the fastest and most complete parasitological cure; between 2 and 7 d after treatment, most cats treated with these molecules were free of ear mites. However, these data should be interpreted with caution. Because daily posttreatment checks were not consistently done across studies, it is difficult to determine which of these molecules was the most rapidly effective. Because of the similar parasitological and clinical efficacy of the molecules discussed, comparative studies of similar design are needed to identify the most effective product. Other criteria may require consideration when deciding which product to use. These include frequency of application, spectrum of activity against other parasites, availability, owner acceptance of the product price, and potential ecotoxicity. CVJ
Footnotes
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