Treatment of rabbit cheyletiellosis with selamectin or ivermectin: a retrospective case study

Parasite infestation with Cheyletiella species is reported worldwide. The condition is highly contagious, with three species, C. parasitivorax, C. blakei and C. yasguri normally infesting rabbits, cats and dogs respectively [1–3]. Cheyletiella mites belong to the order prostigmata and the family Cheyletiellidae. The mites are large (270–540 μm) and very mobile. Adult mites have four pairs of legs with distal combs instead of claws. The mouthpart (palpi) has a pair of curved claws characteristic of the mite Cheyletiella. The three species can be separated morphologically only by the shape of a sensory organ in genu 1 on the first pair of legs. The entire lifecycle of approximately 21 days is spent on the host, where they feed on surface epithelia, debris and lymph. Adult Cheyletiella mites can survive a month without feeding in cool temperatures [2, 3]. Eggs that fall off the host can be a source of re-infestation.

Cheyletiellosis is a zoonosis, causing papular, pruritic dermatitis in humans [1, 2]. Experimental studies transferring C. yasguri between dogs and rabbits suggest a low host specificity of the mite [1]. Cheyletiellosis in the rabbit is common and clinical signs consist of varying degrees of pruritus, alopecia, dry to oily seborrhoea with crusts and sometimes erythema (figure 1) [1]. Lesions mainly affect the withers but sometimes extend to the back and ventral abdomen. In some cases lesions are seen only in the face. The severity of clinical signs ranges from asymptomatic to moderate, although widespread lesions can be seen in immunocompromised rabbits [1–3].

Diagnosis of Cheyletiella infestation is made by demonstration of the mite or eggs in superficial skin scrapings, transparent tape preparations or by flea combing.

A variety of antiparasitic treatment protocols have been successfully used for ectoparasitic mite infestation in small animal veterinary practice. In the literature there is evidence of efficacy using fipronil [3, 4], ivermectin [5–8] and selamectin [9, 10] in the treatment of cheyletiellosis in the dog and cat. Use of ectoparasiticides in the rabbit has been reported in the treatment of Psoroptes cuniculi and Sarcoptes scabei with ivermectin [11–13], ivermectin and fipronil combination [14], moxidectin [15], eprinomectin [16], selamectin [17, 18] and doramectin [19]. Although ivermectin, selamectin and moxidectin have been advocated for treatment of cheyletiellosis in rabbits in textbooks and proceedings [2, 20, 21], no studies to our knowledge, have been published to support the recommendation. In the view of evidence-based medicine, it is important that primary references are available to substantiate textbook statement and clinical practice. The objective of the present study was therefore to evaluate the efficacy and safety of selamectin and ivermectin in the treatment of Cheyletiella mite infestation in rabbits in clinical practice.

This study indicates that all treatment protocols seemed to be sufficiently effective and safe and that cheyletiellosis in rabbits can be successfully treated using ivermectin or selamectin in clinical practice. Neither ivermectin or selamectin is currently approved for use in rabbits in Sweden. In the UK however a topical spot-on preparation containing ivermectin (Xeno 450, Genitrix) has just recently been initiated for use in rabbits, guinea pigs and ferrets.

Ivermectin and selamectin both belong to the macrocyclic lactones. All macrocyclic lactones have the same primary mode of action, namely to affect the chloride ion channel activity in the nervous system of nematodes and arthropods. Nerotoxicity however has been described in mammals, mainly in cases of ivermectin use in collies (and collie related breeds) and young animals or after overdosing [6, 7].

The doses of ivermectin recommended for cheyletiellosis in dogs and cats are oral or injectable formulas at 200–300 μgkg^-1, at a 10–14 day interval during 6–8 weeks [8]. Studies in rabbits suffering from Psoroptes infestation have concluded that ivermectin at the doses of 100–200 μgkg^-1 twice, with a 2 week interval, and of 400 μgkg^-1 once subcutaneously, are effective in eliminating the mite [12, 13].

Selamectin has been shown to have persistent efficacy against fleas after topical administration in dogs and cats for at least 28 days after application [24]. Cheyletiellosis in a multi-cat household and in three canine breeding colonies was successfully treated with selamectin (6–15 mgkg^-1), using 3–4 topical treatments at 2–4 week intervals [9, 10]. Rabbits infested with psoroptes or sarcoptes and treated with selamectin (6–18 mgkg^-1) spot-on applications at one or two occasions at 2–4 week intervals had a complete recovery [17, 18].

The results from this field study may have been affected by uncontrolled events and factors. For example the chance that the treated rabbits in this study were asymptomatic carriers of Cheyletiella mites after treatment cannot be excluded, as the response to treatment was assessed as clinical cure and not parasitical cure, except in a few cases. Treatment results were therefore graded as in remission only if no relapse was seen during the entire follow-up time and as relapses if the rabbit experienced recurrence of clinical signs during the follow-up time.

There may be several explanations as to why the combination of injection and oral administration of ivermectin (Group 2) has a tendency to be less effective, independent of treatment length. It is possible for example that oral bioavailability of ivermectin is not high enough in rabbits, explaining the higher number of rabbits experiencing relapse or treatment failure. Lower efficacy and shorter duration of action from orally administered ivermectin have been documented, for instance in cats where most of the drug is eliminated from plasma at 5 days [5, 7]. The doses used in Group 2 were very high but this factor does not seem to affect the treatment results, perhaps reinforcing the theory that the oral bioavailability of ivermectin is low in rabbits. In contrast subcutaneous injections of ivermectin have been shown to elicit high concentrations in plasma for at least 13 days in rabbits [13]. Another cause could be compliance-related due to owner difficulties when medicating the rabbits orally at home, or that the ivermectin was not stored under the right conditions (e.g. UV protection).

Why some rabbits still experienced clinical signs or relapsed even when living in single-rabbit households remains unanswered. Insufficient cleaning of the environment and in-contact dogs and cats not treated against Cheyletiella may be a source of re-infestation. Most owners were urged to clean the cages, although this cleaning could only be verified in a few cases (8/53). Five of the rabbits in Group 1 were also concurrently bathed. These treatments were made both in the treatment failure groups and in the remission group. Other diseases could possibly also influence the incidence of relapse or lack of treatment success. In 13 of the total 53 rabbits concurrent health issues were recorded and 12 were overweight. Rabbits with concurrent disease or overweight however were seen in both treatment failure and remission groups. Time to relapse varied from a few weeks to several years. Five of the rabbits with relapse were living in single-rabbit households. The mean follow-up time in Group 3 was shorter (8.2 months) compared to the two ivermectin groups (13.7–18.0 months). A study with a longer follow-up time in all groups with clinical and microscopically examination at revisit is needed to further validate the results of this study. Such a study should also include a control group. The outcome of larger groups in such a study might result in statistical significance between the different treatment groups.

Possible side effects were only recorded in two cases, both in Group 1, the group receiving ivermectin injections. One rabbit experienced pain after the ivermectin injection and one developed ataxia at the second treatment. It could not be excluded that the symptoms were correlated to the ivermectin injection. The rabbit experiencing a short episode of ataxia at the second injection died a few months after the last treatment, without having had any relapses of neurological signs. No autopsy was performed. The almost total absence of neurotoxicity is remarkable, since the doses used in Group 2 (ivermectin injection and oral administration) were very high, up to 2732 μgkg^-1, which is many times the dosage recommended by the manufacturer for treating ruminants and horses. In ruminants the toxicity dosage (4 mg kg^-1) is 20 times the recommended dosage, given as injections, and in horses the toxicity dosage (2 mg kg ^-1, given twice in two days, orally) is 10 times the recommended dosage. Teratogenic studies in rabbits performed by the manufacturers concluded that ivermectin orally administrated daily to pregnant rabbits at the dose 6 mg kg^-1 resulted in signs of toxicity after 7 days.

Results of this retrospective study suggest that both ivermectin and selamectin are effective and safe for clearance of clinical signs of cheyletiellosis in rabbits. In the group including oral administration of ivermectin (Group 2) a tendency towards a lower efficacy was registered, as compared to Groups 1 (ivermectin injections) and 3 (selamectin spot-on), although not statistically significant. Controlled prospective studies including larger groups are needed to further evaluate efficacy of the treatment protocols.