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combed and examined for fleas, flea feces,mites, and their developmental stages.Clinical signs had subsided by Day 14 in allrabbits and no signs of recurrence wereapparent in the following weeks. No fleas ormites, including developmental stages, werecaptured and no flea feces were found onDays 14, 28, and 42. No adverse reactionswere observed. Under the conditions of ourstudy, topical formulation of imidaclopridand permethrin was a practical and well-tol-erated means of treatment for flea infesta-tion in rabbits.

INTRODUCTIONFlea and mite infestations are a commoncause of skin disorders and reason for con-sultation in small animal practices. Fleasand mites cause irritation in rabbits as wellas dogs and cats. Rabbits can be readily

Efficacy of a FormulationContaining Imidacloprid andPermethrin Against NaturallyAcquired Ectoparasite Infestations(Ctenocephalides felis, Cheyletiellaparasitovorax, and Listrophorus gib-bus) in RabbitsOlaf Hansen, DVM, MBA, PhD1

Norbert Mencke, DiplEVPC, PhD1

Kurt Pfister, DiplEVPC, PhD2

Wieland Beck, DiplEVPC, PhD2

1Bayer HealthCare AG, Animal Health DivisionLeverkusen, Germany2Institute for Comparative Tropical Medicine and ParasitologyFaculty of Veterinary MedicineLudwig-Maximilians-University MunichMunich, Germany

KEY WORDS: imidacloprid, permethrin,rabbit, Ctenocephalides felis, Cheyletiellaparasitovorax, Listrophorus gibbus

ABSTRACTThe purpose of this study was to evaluatethe efficacy of a topical formulation con-taining imidacloprid and permethrin foreradication of a patent flea(Ctenocephalides felis) and mite(Cheyletiella parasitovorax andListrophorus gibbus) infestation in rabbits.Sixteen adult rabbits from a rabbit hus-bandry were enrolled in the study. Rabbitswere treated with 40 mg imidacloprid and200 mg permethrin dermally as spot-on onDay 0. No other treatment or environmentaldecontamination was performed during thetrial. Prior to treatment followed by 14, 28,and 42 days post treatment, all rabbits were

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infested by the cat flea Ctenocephalidesfelis from dogs and cats; by Spilopsylluscuniculi after contact with wild rabbits1,2;and also by Pulex irritans, Echidnophagagallinaceum, or Nosopsyllus fasciatus.3

Clinical features vary from asymptomatic tosevere hypersensitivity reactions with rest-lessness, alopecia from scratching and bitingresulting in a pruritic papular dermatitis.3,4

Cheyletiella parasitovorax and Listrophorusgibbus are commonly found on rabbits andare thought to be a normal commensal.3,5

The responsibility for the care of com-panion animals including exotic pets otherthan dogs and cats also falls to the animalpractitioner, and while dogs and cats remainthe main pets throughout Europe and NorthAmerica, there is an increase in ownershipof pets other than canine or feline. Sincethere are few substances licensed for use onexotic pets, veterinary surgeons often turn tooff-label use of products that are availablefor the treatment of other species.6

A new dermal product has been devel-oped containing imidacloprid and perme-thrin (Advantix®, Bayer AG, Germany),which is administered as a topical applica-tion to the skin at a single site on dogs. Noinformation is available on the efficacy ofthis preparation to control rabbit flea infes-tation. The present clinical study was con-ducted to evaluate the efficacy and toleranceof a spot-on formulation with imidaclopridand permethrin in the treatment of rabbitsnaturally infested with C. felis, C. para-sitovorax, and L. gibbus.

MATERIALS AND METHODSSixteen adult rabbits (14 female, 2 male) ofthe breed "Sachsengold" with a natural C.felis, C. parasitovorax, and L. gibbus infes-tation were enrolled in this clinical study.All rabbits were from the same rabbit hus-bandry in Rodgau/Jugesheim nearFrankfurt/Main (Germany) and kept in anenclosure outdoors during the day and incages indoors over night and during thetreatment period. Ages ranged from 6months to 1 year with a mean age of 9

months. On Day 0, all animals wereweighed individually. Body weight (BW) ofthe rabbits ranged from 2.4 to 4 kg BW witha mean BW of 2.9 kg.

TreatmentEach rabbit received one spot-on treatmenton study Day 0. Dermal application wasperformed using 0.4 mL of a topical solu-tion containing 40 mg imidacloprid and 200mg permethrin (Advantix®, Bayer AG,Germany) at the base of the neck. Due toanimal welfare within this clinical field trialwith heavily flea- and mite-infested animals,a placebo treatment group was not enrolled.Because of the comparatively small numberof patients and in order to achieve more rep-resentative results, a positive control treatedwith another insecticide/acaricide was notincluded. No other treatment or environ-mental decontamination was performed dur-ing the trial. The success of the therapy wasassessed by clinical as well as parasitologi-cal examination.

Clinical ExaminationGeneral health of all treated animals wasobserved daily by the husbandry ownerfrom Day 0 for the duration of the study,except for Days 14, 28, and 42 when adetailed clinical check-up was conducted bythe veterinarian. At these particular assess-ment dates, the general condition of thehaircoat with respect to appearance of scal-ing and crusting or flea feces was judged foreach rabbit. During the course of the trial,evaluations of the current state and observedside effects were recorded.

Parasitological ExaminationOn Days 0, 14, 28, and 42, all rabbits werethoroughly combed craniocaudal with astainless steel fine-toothed flea comb (12points/cm) 4 times (2 times each right andleft paramedian sight) on the dorsal and onthe ventral trunk, respectively. The combwas pulled through the haircoat from theneck until the origin of the tail dorsally, andfrom the neck until the inguinal region ven-trally. Captured specimens were counted

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and afterwards collected in small plasticcontainers and preserved frozen until micro-scopic examination and identification. Theflea species determination was based onmicroscopic examination; the nomenclatureof Peus (1938)7 and Pospischil (2002)8 wereused for identifying flea species. By comb-ing, obtained hair and skin samples wereexamined microscopically for detection andquantification of mites and their develop-mental stages. Detected fleas and miteswere evaluated for each patient by scoringfrom absent (-), 1-3 specimens (+), 4-6specimens (++), or >6 specimens (+++) onDays 0, 14, 28, and 42. With respect toappearance of flea feces in the hair coat, thiswas recorded by scoring from absent (-),few (+), moderate (++), or plenty (+++) onDays 0, 14, 28, and 42.

RESULTSOwners reported about reduced appetenceand increasing restlessness in their animalhusbandry over the last weeks. Furthermore,a number of adult fleas and small crumbs offlea feces in the hair coat of some rabbitswere observed. All fleas sampled from therabbit's haircoat in this trial were C. felis.The rabbits showed mild scaling and crust-ing on the whole body; 2 rabbits exhibitedventral alopecia and 1 rabbit exhibited dor-sal alopecia on Day 0 (Figure 1). On Day14, the owners reported that the generalcondition of all rabbits (Figure 2) improved

remarkably. Moreover, the appetencereturned for all treated animals. Clinicalsigns were absent by Day 14 in all 16 rab-bits and no signs of recurrence were appar-ent on assessment Days 28, 42, and in thefollowing weeks. The animals showed abright haircoat without any scaling andcrusting or crumbs of flea feces startingfrom Day 14. No fleas or mites, includingtheir developmental stages, were capturedand no flea feces were found on combingDays 14, 28, and 42, which appeared to cor-relate with clinical improvement.

The number of fleas, flea feces, andmites recovered from the rabbit's haircoatwere documented for each patient on theassessment days (0, 14, 28, and 42). Foreach assessment day within the study, theparasitological status was assessed in orderto specify the efficacy of the used parasiti-cide (Tables 1 and 2). As shown in Table 1,fleas were found in all animals (7/16: +,2/16: ++, 7/16: +++) on Day 0, but haddeclined on Day 14. Seven of 16 rabbitsharbored few fleas right from the start, andall showed flea feces; also, mites werefound in their hair coat. All 16 rabbits wereparasitized by fur mites (+ to +++), L. gib-bus, in conjunction with their numerouseggs fixed on the hairs. On 1 rabbit, a C.parasitovorax infestation (Figure 3) wasobserved. The check-up for Psoroptes cuni-culi by collecting epidermal debris fromboth auricular areas and the external ear

Figure 1. Dorsal alopecia of breeding rabbitsnaturally infested with Ctenocephalides felisprior to treatment.

Figure 2. Cured rabbits from Figure 1 on trialDay 42 after topical application of the imida-cloprid/permethin spot-on combination.

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canal for microscopic examinationproceed negative. Neither fleas (deador alive) nor flea feces in any rabbitwere detected on assessment Days 14,28, and 42. All mites (L. gibbus andC. parasitovorax) as well as theirdevelopmental stages were absent onDays 14, 28, and 42. Thus, efficacyof the imidacloprid/permethrin spot-on formulation rated 100% at thesepoints of time, accordingly. The spot-on was well tolerated systemicallyand locally. Administration regionsfor the spot-on compound on the baseof the animal's neck did not show anyerythematous or pruritic irritations.

DISCUSSIONFleas and mites can infest rabbitswhether or not the rabbits share thehousehold or environment with otherpets, such as dogs and cats. Exceptfor wild rabbits parasitized from S.cuniculi, flea infestation is seen pre-dominantly in large agricultural orbreeding rabbit husbandries than insingle pet rabbits. However, fleainfestation in pet rabbits is recordedfrequently in cases of multi-pethouseholds, when rabbits and cats or

dogs share a household. Mite infestationsnormally occur in any rabbits irrespective oftheir kind of husbandry. Although our studydoes not allow us to conclude how the fleainfestation is usually acquired, the fact thatseveral stray cats are frequently found in theneighborhood near the husbandry may beseen as a constant source of infestation withcat fleas. After capturing 3 of those roamingcats, detailed examinations revealed asevere flea infestation with C. felis in allcases. Therefore, insecticidal treatment ofcats in the environment is essential for ulti-mate solution of this ectoparasitic problem.The investigations by Beck et al9 confirmthe results from previous studies that C. felisis the predominant flea species found ondogs and cats during all seasons of the year.The reason for more cats being infested by

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Table 1. Parasitological Examination of Rabbits WithNaturally Acquired Ectoparasite Infestation Before andAfter Treatment With an Imidacloprid/PermethrinCombination With Respect to Appearance of FleaFeces.

Evaluation of FleaFeces in theRabbit's Haircoat

Number of Rabbits With or WithoutFlea Feces*

Day 0 Day 14 Day 28 Day 42Absent (-) 0 16 16 16Few (+) 11 0 0 0Moderate (++) 1 0 0 0Plenty (+++) 4 0 0 0

*Treatment (Day 0) and assessment days (Days 14, 28, and 42).

Table 2. Parasitological Examination of Rabbits WithNaturally Acquired Ectoparasite Infestation Before andAfter Treatment With an Imidacloprid/PermethrinCombination With Respect to Appearance of AdultFleas and Mites (flea and mite counts are summarized)

Flea andMite Counts

Number of Rabbits With or Without FleaFeces and Mites*

Day 0 Day 14 Day 28 Day 420 (-) — 16 16 161–3 (+) 7 — — —4–6 (++) 2 — — —> 6 (+++) 7 — — —Efficacy (%) — 16/16 (100) 16/16 (100) 16/16 (100)

*Treatment (Day 0) and assessment days (Days 14, 28, and 42).

Figure 3. Cheyletiella parasitovorax from oneof the multiparasite-infested rabbits.

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cat fleas than dogs is not resolved by thedata, but may be due to different behaviorsbetween dogs and cats. A possible explana-tion is that felines usually roam more freelythan dogs and may therefore have moreopportunities to interact with other cats orother free-living animals, including rabbits.Moreover, cats frequently have restingplaces away from their permanent homes,where external parasites may persist.10 Theclimatic and environmental conditions inhouseholds,11 orchards, and the open coun-tryside are important for the dynamics offlea populations. Some authors quantifiedthe probability of transmission of fleas fromthe environment to the animal and empha-sized its fundamental importance for thedesign and implementation of effective con-trol strategies.12-14 Infestations with S. cuni-culi appear where there is contact with wildrabbits.1,2 According to Wall and Shearer,3

Pulex irritans, Echidnophaga gallinaceum,and Nosopsyllus fasciatus can infest rabbitsas well. The flea infestations in the presentfield study were accompanied by fur mite(L. gibbus) infestations in all 16 rabbits.Listrophorus gibbus is thought to be a com-mensal ectoparasite, asymptomatic in nor-mal healthy adult animals. However, whenheavy infestations occur or where there isan underlying disease, alopecia, moist der-matitis, mild scurf, and pruritus may devel-op.5 Furthermore, 1 patient harbored C.parasitovorax. A common clinical descrip-tion of Cheyletiella is "walking dandruff,"describing the effect of the migration of therelative large mites amongst the numerousskin debris into the coat resulting from aheavy infestation. Other signs are variableand include pruritic dermatitis and alope-cia.15 Listrophorus gibbus and C. para-sitovorax are considered to be speciesspecific. The appearance of the studied 3different arthropod species observed in ahusbandry of breeding rabbits demonstratesthe need for effective ectoparasite control tomaintain the animal's well-being.

In this trial, the spot-on formulation con-taining imidacloprid and permethrin was100% effective from the beginning against

naturally acquired infestations of C. felis, C. parasitovorax, and L. gibbus in rabbits.Although there was no control group, thetreatment regimen appeared effective andtolerable in the clinical control of flea andmite infestations. A lack of licensed antipar-asiticides for this indication in rabbits inmost countries requires an off-label use ofadequate pharmaceuticals. The simple dos-ing protocol used, with a topically adminis-tered spot-on formulation at the base of therabbit's neck, facilitates owner compliancewith the treatment protocol. The spot-onapplication is in contrast to traditional routesof administration, like bathing or powder-ing. The latter require more applications anda higher incidence of recurrence of thoseadministrations are much more time-con-suming and laborious; thus, owner compli-ance favors spot-on applications. The resultsfrom Hutchinson et al16 indicate that imida-cloprid as mono-substance is a good alterna-tive for the flea control in artificiallyinfested rabbits. After topical administrationof the substance, imidacloprid is rapidly dis-tributed over the animal's skin within 1 dayafter application. Imidacloprid was safewhen used on rabbits and eliminated resi-dent flea populations. The 0.4-mL dose washighly effective and gave substantial protec-tion. This is in accordance to the results ofJacobs et al,1 who evaluated efficacy of imi-dacloprid on rabbits naturally and experi-mentally infested with the cat flea. In theUK, imidacloprid (Advantage®, Bayer AG,Germany) with a dosage of 10 mg/kg BW isofficially licensed for flea control in rabbits,except for animals younger than 10 weeks.Results of another study17 revealed that asingle topical application of imidaclopridcan completely eliminate fleas from domes-tic rabbits naturally infested with C. feliswithin 2 days. In addition, a high residualimpact for at least 1 week post treatmentwas observed. Corresponding to anotherreport,18 a single spot-on treatment ofselamectin at a dose rate of 18 mg/kg BW isrecommended for flea treatment in rabbitswith a repeat therapy in 30 days if required.Hughes2 recommends therapy with 15 mg

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selamectin for rabbits weighing less than 2.3kg and 45 mg for those weighing more than2.3 kg, with a second application after 1month to kill emerging larvae of C. para-sitovorax, and L. gibbus. The use of fipronilagainst fleas or mites on rabbits has neverbeen recommended or approved by themanufacturer. In the literature, reports ofadverse reactions including deaths due tofipronil are given when applied to rabbits.19

Under the conditions of our trial, thetopical formulation containing imidaclopridand permethrin resulted in a completereduction in the prevalence of clinical signsassociated with flea and mite infestation inthe treated rabbits. Advantix® was well-tol-erated by all infested rabbits without anyside effects. The results indicate that imida-cloprid plus permethrin at a single dosage of40 and 200 mg/kg BW, respectively, topicalapplied is an effective and appropriatechoice for the ectoparasite control in rabbits.

REFERENCES1. Jacobs DE, Hutchinson MJ, Fusake T, Hansen O:

Efficacy of imidacloprid (Advantage®) on rabbitsnaturally or experimentally infested with the catflea (Ctenocephalides felis). January 13-17, 2001,Orlando, Florida. NAVC Small Animal & ExoticProc 2001;15:485-486.

2. Hughes JE: Diagnosis and treatment of selectedrabbit dermatologic disorders. EXOTIC DVM2004;5.6:18-20.

3. Wall R, Shearer D: The diagnosis and control ofectoparasitic infestation. In: VeterinaryEctoparasites: Biology, Pathology & Control. 2nded. Oxford, London, Edinburgh: Blackwell;2001:179-242.

4. Timm KI: Pruritus in rabbits, rodents and ferrets.Vet Clin North Am: Small Anim Pract1988;18(5):1077-1091.

5. Kirwan AP, Middleton B, McGarry JW:Diagnosis and prevalence of Leporacarus gibbusin the fur of domestic rabbits in the UK. Vet Rec1998;142:20-21.

6. Kuenzel F, Schmerold I: Drug therapy of rabbitand rodent diseases. Wien Tierärztl Mschr2001;88:153-168.

7. Peus F: Die Flöhe: Hygienische Zoologie No. 5.1938; Verlag Dr. P. Schöps, Leipzig.

8. Pospischil R: Bestimmungsschlüssel häufigerFloharten. Prakt Schädlingsbek 2002;54:20-24.

9. Beck W, Boch K, Mackensen H, Wiegand B,Pfister K: Qualitative and quantitative observa-tions on the flea population dynamics of dogs andcats in several areas of Germany. Vet Parasitol2006;137:130-136.

10. Williams B: The cat flea C. felis (Bouché): itsbreeding biology and its larval anatomy comparedwith that of two ceratophyllid larvae. Dphil.Thesis: University of Oxford; 1983.

11. Beugnet F, Porphyre T, Sabatier P, Chalvet-Monfray K: Use of a mathematical model to studythe dynamics of Ctenocephalides felis populationsin the home environment and the impact of vari-ous control measures. Parasite 2004;11:387-399.

12. Chesney CJ: Species of flea found on cats anddogs in south west England: further evidence oftheir polyxenous state and implications for fleacontrol. Vet Rec 1995;136:356-358.

13. Koutinas AF, Papazahariadou MG, Rallis TS,Tzivara NH, Himonas CA: Flea species fromdogs and cats in northern Greece: environmentaland clinical implications. Vet Parasitol1995;58:109-115.

14. Beck W, Pfister K: Recent investigations on thepopulation dynamics of cat fleas (Ctenocephalidesfelis) and the concept of integrated flea control.Prakt Tierarzt 2004;85:555-563.

15. Beck W: Common ectoparasitic diseases and der-matophytes in small mammals, birds and reptiles.Prakt Tierarzt 2003;84:752-762.

16. Hutchinson MJ, Jacobs DE, Bell GD, Mencke N:Evaluation of imidacloprid for the treatment andprevention of cat flea (Ctenocephalides felis felis)infestations on rabbits. Vet Rec 2001;148(22):695-696.

17. Fukase T, Stanneck D, Mencke N: Efficacy andsafety of an imidacloprid spot-on formulation fortreating flea infestations in domestic rabbits. ProcWSAVA-FECAVA Congr. Amsterdam, 25-29April 2000 (abstract).

18. Beck W: Common ectoparasites in rabbits andtheir control. Kleintiermed 2004;7:6-14.

19. Beck W: Efficacy of fipronil (FRONTLINE®)against ectoparasites: application against lice,mites, mallophages in diverse small animals.Tierärztl Umschau 2000;55:244-250.

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