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tions were observed. Under the conditionsof our study, topical formulation of imida-cloprid and moxidectin was a practical andwell-tolerated means of treatment for earmange in rabbits.

INTRODUCTIONAstigmated P s o r o p t e s mites are cosmopoli-tan external parasites of mammalian hostsand are of economic significance as theagents of mange in several domesticatedanimals, particularly with regard to thepsoroptic mange of sheep caused byPsoroptes ovis ( H e r i n g ) .1 – 3 Another ear mite,Otodectes cynotis (Hering), causing otoacar-iosis, is an obligate parasite that inhabits thevertical and horizontal ear canals of dogsand cats,4 although other species such as fer-rets may become infested.5 A fairly frequentspecies of veterinary importance isPsoroptes cuniculi (Delafond) responsiblefor otoacariasis in different farm animals,mainly affecting rabbits, goats, horses,

Efficacy of a FormulationContaining Imidacloprid andMoxidectin Against NaturallyAcquired Ear Mite Infestations(Psoroptes cuniculi) in RabbitsOlaf Hansen, DVM, PhD1

Yvonne Gall, PhD2

Kurt Pfister, DiplEVPC, PhD 2

Wieland Beck, DiplEVPC, PhD2

1Bayer Vital GmbHLeverkusen, Germany2Institute for Comparative Tropical Medicine and Parasitology, Faculty of Veterinary MedicineLudwig-Maximilians-University MunichLeopoldstrasse, Munich, Germany

KEY WORDS: imidacloprid, moxidectin,rabbit, mites, Psoroptes cuniculi

ABSTRACTThe purpose of this study was to evaluatethe efficacy of a topical formulation con-taining imidacloprid and moxidectin foreradication of Psoroptes cuniculi in rabbits.Fourteen adult rabbits from a rabbit hus-bandry were enrolled in the study. Rabbitswere treated with 40 mg imidacloprid and 4mg moxidectin monthly as spot-on on Days0, 30, and 60. No other treatment or envi-ronmental decontamination was performedduring the trial. On Days 0, 30, 60, and 90,all rabbits were examined, and epidermaldebris was collected from both auricularareas and the external ear canal for micro-scopic examination. Clinical signs had sub-sided by Day 30 in 13/14 rabbits and almostno signs of recurrence were apparent in thefollowing weeks. All epidermal sampleswere negative by Day 90. No adverse reac-

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antelopes, cattle, and sheep.6 – 9 The ear miteis mainly found in the external auricularmeatus of the ear and inside the ear pinnae;it is common to discover that only one ear isaffected. Psoroptes cuniculi infestations indomestic rabbits are recognized in 2 clinicalpictures: characteristic psoroptic “earcanker” causing puff pastry-like crusts,excoriations, massive pruritus, and occa-sionally aural hematomas due to intensehead shaking or scratching1 0 , 1 1; and “extra-auricular” mange extensively described byRibbeck and Ilchmann1 2 and Guilhon.1 3

C u t l e r1 4 reported an ectopic P. cuniculiinfestation in a pet rabbit, with severelesions on the skin of the caudoventralabdomen. Bates3 observed the ectopic formin 5% of all P. cuniculi-infested rabbits ofhis study, showing lesions extending to thebase of the ears, the cheeks, dewlap, face,and between the digits of both hind feet.

A new dermal product has been devel-oped containing imidacloprid and mox-idectin (Advocate®, Bayer) that isadministered as a viable topical applicationto the skin at a single site on dogs and cats.No information is available on the efficacyof this preparation in rabbit “ear canker.”There are currently no licensed veterinaryproducts specifically indicated for the thera-py of ectoparasites in rabbits. Thus, veteri-narians need to rededicate pharmaceuticalsnormally used for other animal species. Thepresent clinical study was conducted toevaluate the efficacy and tolerance of aspot-on formulation with imidacloprid andmoxidectin in the treatment of P. cuniculimange in naturally infested rabbits.

MATERIALS AND METHODSFourteen adult rabbits with a naturallyoccurring P. cuniculi infestation wereenrolled in this field study. All rabbits werefrom the same rabbit husbandry in the west-ern Bodensee area (Baden-Wuerttemberg)and kept exclusively in cages indoors duringthe treatment period. Ages ranged from 6months to 1 year with a mean age of 9months. On Day 0, all animals were individ-

ually weighed. Body weight of the meas-ured rabbits ranged from 2.1 to 3.7 kg witha mean body weight of 2.65 kg. In thecourse of this study, one female was preg-nant. Owners reported about reduced appe-tence and increasing restlessness in theiranimal husbandry over the last weeks.Moreover, remarkable crusts in the pinnaewere observed.

TreatmentEach rabbit received 3 spot-on treatments30 days apart on study Days 0, 30, and 60.Dermal application was performed using a40-mg imidacloprid and 4-mg moxidectintopical solution (Advocate®, Bayer) at thebase of the neck. Due to the animal welfarewithin this field trial of heavily mite-infest-ed animals, a placebo treatment group wasnot enrolled. No other treatment or environ-mental decontamination was performed dur-ing the trial. The success of the treatmentwas assessed by clinical as well as parasito-logical examination.

Clinical ExaminationGeneral health of all treated animals wasobserved daily by the farm owners fromDay 0 for the duration of the study, exceptfor Days 30, 60, and 90 when a detailedclinical check-up was conducted by the vet-erinarian. At these particular assessmentdates, ear lesions were judged for each rab-bit. During the course of the trial, ear lesionevaluations and observed side effects wererecorded. Clinical signs were evaluated byscoring from absent (–), mild (+), moderate-ly (++), or profoundly (+++) on Days 0, 30,60, and 90 with respect to appearance ofscaling and crusting in the pinnae and in theexternal auricular meatus.

Parasitological ExaminationOn Days 0, 30, 60, and 90, all rabbits wereexamined, and epidermal debris was collect-ed from both auricular areas and the exter-nal ear canal for microscopic examination.The ear canal swabs sampled were exam-ined for mites, their eggs, and other devel-opmental stages each time by at least 2 ofthe following methods: (1) stereomicro-

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scope: epidermal debris and hairs wereplaced in a petri dish and examined at 25×magnification; (2) epidermal debris andhairs from one sample, respectively, werediluted in ~1 mL of a 10% KOH solutionand heated for 20 minutes to maceratescales and hairs. The mixture was stirred,centrifuged, and the supernatant discarded.A concentrated sucrose solution was thenadded to the sediment, a cover slip wasapplied to the surface of the solution, thesamples were again centrifuged, and, final-ly, the cover slip was transferred to a slideand inspected under a microscope at 40×magnification; or (3) direct check up underthe microscope: epidermal debris and hairswere applied directly onto a microscopeslide, covered with a few drops of mineraloil and a cover slip, then inspected at 40×magnification. The KOH and flotation tech-nique was used in all rabbits on Day 0,because a relatively large portion of patternmaterial was collected with a sharp spoon.

RESULTSOn Days 30, 60, and 90, the quantity of earcanal swaps sampled was generally muchless than on Day 0, which appeared to cor-relate with clinical improvement. Clinicalsigns were absent by Day 30 in 13/14 rab-bits, and no signs of recurrence were appar-ent in the following weeks (Figures 1 and2). Thus, for all further examinations per-formed on Days 30, 60, and 90, the stere-

omicroscope and direct microscopic proce-dure were the only techniques used.

The eggs and mites recovered from theears were documented for each rabbit toproduce geometric mean egg and mitecounts on each assessment day (0, 30, 60,and 90). For each treatment and/or assess-ment day within the study, the number ofrabbits with or without eggs/mites in theskin scrapings was established in order tospecify the efficacy of the used antiparasiti-cide (Table 1). Live mites and eggs werenumerous in all animals on Day 0, but haddeclined on Day 30 prior to the secondtreatment. A moderate recurrence of meanmite counts was observed from Day 30 toDay 60 despite repeated treatment. Only4/14 rabbits still harbored eggs and/or miteson Day 30 and Day 60. Thus the evaluatedefficacy of the imidacloprid/moxidectincombination was 71.4%. No eggs or mites(dead or alive) in any rabbit were detectedon assessment Day 90. Efficacy of the imi-dacloprid/moxidectin spot-on formulationrated 100% at this point of time, according-ly. Clinical signs of the rabbits during thestudy are summarized in Table 2. Therewere no adverse drug experiences or treat-ment-related mortalities during the trial.

DISCUSSIONAlthough our study does not allow us toconclude where the mite infestation is usu-ally acquired, the fact that new rabbits are

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Figure 1. Mild scaling/crusting in the pinnaedue to P. cuniculi infestation in a rabbit priorto treatment with the imidacloprid/mox-idectin combination.

Figure 2. Rabbit from Figure 1 on Day 90 ofthe trial.

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purchased permanently in this husbandrymay be seen as a constant source of infesta-tion with P. cuniculi mites. Twelve of the14 rabbits showed a mild form of “earcanker” accompanying moderate pruritusand head shaking. There had been no evi-dence for ectopic ear mite infestation. Theskin lesions were margined to the pinnaeand the external ear canal. All animals suf-fered from bilateral otitis externa parasitaria.On Day 0, all 14 rabbits showed a clinicalpicture compatible with “ear canker.”Pruritus, which was present in 14/14 rabbits,was considered mild to moderate in 12 rab-bits and severe in 2 rabbits. Fourteen rabbitspresented mild to moderate ear scaling andcrusting. Alopecia, excoriations, orhematomas were not detectable. On Day 30,a great clinical improvement was noted.Only one rabbit still exhibited mild scaling.Pruritus and head shaking had resolved inall of the small mammals. On Day 60, withthe exception of 2 rabbits, all clinical signsdisappeared, even though a total of 4 rabbitsstill harboured eggs and mites on this day.On Day 90, all rabbits were free from clini-

cal signs and mites or developmental stages.Significantly increased mite counts fromDay 30 to Day 60 may be due to reinfesta-tion from the contaminated environment.This might be supported by the ability of P .c u n i c u l i to survive off the host for 4 to 21days at relative humidities between 20%and 99% and temperatures between 5˚C and3 0 ̊ C .1 5 Smith and colleagues1 6 quantified theprobability of transmission of psoropticmites from the environment to the animaland emphasized its fundamental importancefor the design and implementation of effec-tive control strategies.

In this trial, the spot-on formulationcontaining imidacloprid and moxidectinwas 100% effective against naturallyacquired aural infestations of P. cuniculimites in rabbits. Although there was nocontrol group, the treatment regimenappeared effective and tolerable in the clin-ical control of ear mite infestations. A lackof licensed antiparasiticides for this indica-tion in rabbits requires an off-label use ofadequate pharmaceuticals.17 The simpledosing protocol used here, with a spot-on

Table 1. Parasitological Examination of Rabbits With Naturally Acquired P. cuniculi Infection Before andAfter Treatment With an Imidacloprid/Moxidectin Combination.

Treatment* and Assessment DaysDay 0* Day 30* Day 60* Day 90

Geometric mean mite counts 10.4 4.5 15.5 0Geometric mean egg counts 7.5 4 4 0Number of rabbits with mites

and eggs in the ear swabs 14 4 4 0Efficacy (%) — 71.4 71.4 100

*Days of treatment.

Table 2. Clinical Efficacy of an Imidacloprid/Moxidectin Combination Against Naturally AcquiredInfestations by P. cuniculi in Rabbits: Clinical Signs of Mite Infestation Before and After Treatment.

Number of Rabbits With Particular Scaling/Crusting (+, ++, +++)Clinical Signs Day 0 Day 30 Day 60 Day 90

S c a l i n g / c r u s t i n gAbsent (-) — 1 3 1 2 1 4Mild (+) 1 2 1 2 —Moderate (++) 2 — — —Profound (+++) — — — —

Clinical efficacy (%) 0 (0/14) 92.9 (13/14) 85.7 (12/14) 100 (14/14)

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formulation topically administered at thebase of the rabbit’s neck, facilitates ownercompliance with the treatment protocol.“Ear canker” is seen predominantly in largeagricultural rabbit husbandries. It is in con-trast to the otic preparations currently avail-able for the therapy of ear mites thatdemand applications into the external auric-ular meatus once or twice daily for up to 4weeks. Because of more applications and ahigher incidence of recurrence, topicaladministration into the ear canal is muchmore time-consuming and laborious. Theoff-label use of another macrocyclic lactoneof the avermectin subclass, ivermectin,administered subcutaneously, has beenreported to be successful in the control ofP. cuniculi in rabbits.18–22 Although there aretopical and injectable acaricidial productsavailable for the treatment of psoropticmange in rabbits, most of them require fre-quent and careful application to control oreradicate the mites. Several authors reportthat efficacy of injections with the preferredivermectin appears to vary with severalpopulations of P. cuniculi in rabbits.According to Wilkins and colleagues23 inTexas, USA, and Pandey19 in the UK, a sin-gle injection of ivermectin (200 µg/kg bodyweight) eliminated all P. cuniculi mites.Animals studied by Wright and Riner18

required injections at a higher dose rate of400 µg/kg body weight to cure psoroptic“ear canker.” In a German trial, neither 200nor 400 µg/kg body weight failed to eradi-cate P. cuniculi completely.24 Moreover, theinjection route seems to be a determiningfactor. Rabbits infested with P. ovis and P.cuniculi were injected intramuscularly (IM)or subcutaneously (SC) with ivermectin. Asingle application of 200 µg/kg bodyweight either IM or SC was inadequate toeliminate all mites in the ears of the rabbits.However, a single injection of 400 µg/kgbody weight, regardless of the route ofapplication, eradicated all P. cuniculi mites,but eliminated P. ovis in only 50% of therabbits.18 Results of a study from McTierand colleagues25 suggest that a single topi-cal application of selamectin at a dose of 6

or 18 mg/kg body weight can completelyeliminate mites from rabbits naturallyinfested with P. cuniculi. Wagner andWendlberger26 treated rabbits with psoropticmites with moxidectin 0.2 mg/kg bodyweight SC and orally twice 10 days apart,respectively. After this period, neitherexcessive cerumen nor mites could be iden-tified in the external ear canal. All rabbitswere cured and did not show clinical signsduring the next 6 months. No side effectsoccurred in any of these rabbits. Fourie andcolleagues4 figured out that a single therapywith an imidacloprid/moxidectin solutionapplied at a dosage of 0.1 mL/kg bodyweight resulted in a treatment success rateof 80% as assessed 50 days after applica-tion in O. cynotis-infested cats. Two treat-ments with the imidacloprid/moxidectincombination 4 weeks apart and at the samedosage was efficacious in curing all catsfrom the ear mites as assessed 22 days afterthe second application (Day +50). Pulliumand colleagues27 found that in mice infestedby Myocoptes musculinus, there was a totaleradication of mites without any toxiceffect or clinical signs of illness in thepatients after one topical treatment withmoxidectin 0.5%. Avermectins are not cur-rently approved for use in rabbits inGermany or elsewhere in the world. Interestis developing in the use of biocompatibleproducts such as lavender oil for the thera-py of external parasites in rabbits.28

Macchioni and colleagues29 tested acaricidi-al activity of aqueous extracts of camomileflowers against P. cuniculi and showed itsefficacy.

CONCLUSIONSUnder the conditions of our trial, topicalformulation containing imidacloprid andmoxidectin was a practical and well-tolerat-ed means of treatment for ear mite infesta-tion in rabbits. The results indicate thatimidacloprid in addition to moxidectin at adosage of 10 and 12 mg/kg body weight,respectively, percutaneously thrice 4 weeksapart is effective and a good alternative forthe control of “ear canker” in rabbits.

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