Acta Veterinaria Scandinavica 2008, 50:1 http://www.actavetscand.com/content/50/1/1 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 arthro- pods. Nerotoxicity however has been described in mam- mals, mainly in cases of ivermectin use in collies (and collie related breeds) and young animals or after overdos- ing [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 sub- cutaneously, 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 col- onies was successfully treated with selamectin (6–15 mgkg-1), using 3–4 topical treatments at 2–4 week inter- vals [9,10]. Rabbits infested with psoroptes or sarcoptes and treated with selamectin (6–18 mgkg-1) spot-on appli- cations 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 combina- tion 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 rab- bits, 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 reinforc- ing the theory that the oral bioavailability of ivermectin is low in rabbits. In contrast subcutaneous injections of iver- mectin 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 environ- ment 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. Rab- bits 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 house- holds. 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 exam- ination 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 treat- ment 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 epi- sode 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 manufac- turer 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 dos- age (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 ivermec- tin orally administrated daily to pregnant rabbits at the dose 6 mg kg-1 resulted in signs of toxicity after 7 days. Page 5 of 6 (page number not for citation purposes)