The efficacy of pour-on ivermectin in bison (Bison bison)

Abstract

To test the effectiveness of pour-on ivermectin in parasitized bison, changes in fecal parasite egg counts after treatment with ivermectin injectable or pour-on preparations were compared to a negative control group. There was no difference between the two ivermectin groups, and both forms of ivermectin were effective in reducing fecal parasite egg counts in parasitized bison.

The avermectin class of anthelmintic drugs have large margins of safety, high efficacy, and a broad range of activity which has influenced the way anthelmintics are used in livestock production (1). Their use for the treatment and prevention of intestinal and other parasites in bison is becoming routine and widespread. The avermectins include ivermectin, moxidectin, eprinomectin, and doramectin. The only one of these currently licensed for use in bison (in the USA, but not Canada) is eprinomectin (Eprinex; Mérial Canada, Baie D’Urfé, Quebec), which is a pour-on formulation that is not available in an injectable form.

Pour-on formulations are usually less labor-intensive than injections and have no injection site drug residue. Also, direct hand contact with the animal and maintaining control over a subcutaneous injection, which can be hazardous in poorly restrained bison, are unnecessary. Despite the advantages of pour-on preparations, injectable preparations such as ivermectin continue to be a preferred treatment for intestinal parasites in bison. Existing research has demonstrated the efficacy of pour-on ivermectin in bison (2) but there is a growing belief among bison producers that pour-on preparations in general, and ivermectin specifically, are clinically ineffective in bison. Our objective was therefore to compare changes in fecal parasite egg count resulting from treatments with ivermectin injectable and ivermectin pour-on preparations to changes in a negative control group.

In mid-June, 2009 a heterogeneous group of 41 bison of various ages (mean = 2.2 ± 1.9 y, range: 1 to 9 y) and body weights (mean = 249 ± 95 kg, range: 114 to 432 kg) were purchased the same day from a single source for finishing at a bison feedlot in northern Alberta, Canada. Bison entering the feedlot are routinely given anthelmintic treatment on entry but, through an evaluation of body and hair coat condition, this group in particular was identified by a veterinarian (Lewis) as likely to be parasitized and therefore suitable for this study. This was confirmed by a fecal strongyle egg count (ParaCount-EPG Fecal Analysis Kit, Chalex Corporation, Wallowa, Oregon, USA) on a pooled sample of feces, informally collected from the holding pen floor.

On the first day of the experiment animals were randomly divided into 2 treated groups and 1 untreated control group. As the bison were moved into a hydraulic restraint chute they were assigned to their group through blind selection of 1 of 3 colored balls from a bag. A pre-treatment fecal sample was obtained from the rectum of each bison. The 2 treatment groups received either subcutaneous (SC) injection [200 μg/kg body weight (BW)] (n = 15) or a pour-on aliquot (500 μg/kg BW) (n = 14) of ivermectin (Ivomec; Mérial Canada) and the control group (n = 12) received no drug. After treatment they were released into a common holding pen. Prior to the application of the pour-on treatment old hair along the dorsal midline target area of skin was pulled off so that the pour-on preparation was applied directly to the surface of the healthy hair coat. The manufacturer’s application device was touched lightly to the skin as the drug was applied along the dorsal midline from front to back. Twenty-one days later the bison were again restrained in the handling system and rectal fecal samples were obtained from each animal. As this was the end of the experiment, control animals were given injectable ivermectin (Ivomec, Mérial Canada) to treat their parasitism, but no further anthelmintic treatment was given to the previously treated groups. All animals were returned to the feedlot production cycle without illness or incident. This experimental protocol was in compliance with Canadian Council on Animal Care (CCAC) guidelines and was approved by the University of Saskatchewan Committee on Animal Care and Supply.

Fecal strongyle eggs in pre- and post-treatment fecal samples were counted on the day of collection according to the manufacturer’s directions using the ParaCount-EPG Fecal Analysis Kit, (Chalex Corporation) and recorded as eggs per gram of feces (epg). Observer bias was avoided by keeping the test operator blind to the pre- and post-treatment sample identification.

Data were entered into a database (GraphPad Prism V5; GraphPad Software, La Jolla, California, USA), summarized, and a one-way analysis of variance (ANOVA) with Bonferroni’s post hoc comparison was applied to assess differences in pre- and post-treatment strongyle egg counts between groups. In addition, a paired t-test was used to test for post-treatment change in fecal strongyle egg count in the control group. Differences between groups were considered statistically significant when P < 0.05.

There was no pre-treatment difference (P = 0.73) in mean strongyle egg count among the 3 treatment groups. However, 1 individual in the control group had a dramatic reduction in egg count, going from 100 epg to 0.0 epg over the 21-day test period. Conversely, 4 of the control group bison had pre- treatment egg counts of 0.0 epg and showed positive post control treatment counts (50, 75, 125, and 25 epg).

The ANOVA indicated a significant post-treatment difference in strongyle egg count between groups (P < 0.001). Post hoc analysis showed no significant difference in mean strongyle egg count between bison treated by the injectable and pour-on treatment methods (P > 0.05), but both methods resulted in egg counts that were lower than those of the control group (P < 0.05). Post-treatment egg counts in every bison from both ivermectin treatment groups decreased to 0.0 epg. All control bison had pre-treatment egg counts > 0.0 and there was no significant change in the mean egg count (P = 0.17) of the control group after 21 d.

The results demonstrate the effectiveness of pour-on ivermectin in bison under conditions of standard bison industry practice. There was, however, an experimental design problem to be considered. The bison treatment groups were mixed and held in the same pen over the experimental period. This allowed animal interaction and the potential for grooming behavior between animals of different treatment groups, which has been shown in cattle studies to cause transfer of drug between animals (3). Allo-grooming (licking) is part of natural bison behavior (4). In the literature much consideration has been given to the effect in cattle that licking behavior has on systemic availability and other pharmacokinetic measures of ivermectin and to the consequences for efficacy studies comparing different formulations of avermectin drugs (3).

The therapeutic effect of injectable ivermectin may have been enhanced by injected animals licking animals given pour-on treatment. In fact, the reduction in strongyle egg counts observed in 1 individual control animal may be explained by licking behavior causing the control animals to ingest therapeutic levels of pour-on product. We can be certain though, that the pour-on treated animals were not influenced in this way by either the control or the injected animals. In a practical sense, licking behavior (either self or others) after application seems not to improve the already satisfactory clinical efficacy of pour-on preparations of ivermectin. The primary research question concerning the clinical efficacy of pour-on ivermectin in bison appears to have been addressed despite the flawed experimental methodology. The results show that pour-on ivermectin has clinical efficacy in bison when measured by fecal egg count reduction and this supports the results of previous research on this question which showed the efficacy of ivermectin pour-on after artificial infection of bison with Ostertagia sp. parasites (2).

Our experiment may have involved the addition of various pour-on methodology groups to examine the effect of applying the drug preparation on top of the hair coat versus applying it directly to the skin of the bison. Regardless, the correct application of pour-on products to bison needs to be considered by the product user. In the bison industry, because of the difficulties with handling and restraining animals, it is possible that the efficacy of pour-on drug preparation is influenced more by the application method and subsequent absorption, or lack thereof, than by the formulation or pharmacologic action. The authors suspect that, for safety reasons, pour-on products are often deposited on bison in a superficial manner at convenient anatomic locations. In fact, adjustment of the manufacturer’s instructions for cattle applications may be necessary to suit the peculiarities of the bison skin and hair covering and in our experiment care was taken to ensure that the product was applied directly to growing hair and the skin surface. The differences in hair density between cattle and bison have been documented and are likely due to the evolution of bison in the extremes of the North American climate (5). It is obvious to the observer that liquids poured on to the surface of a bison hair coat are more likely to be repelled than absorbed and in our opinion this requires some modification of application technique to ensure that the product actually reaches the skin surface.

One of the consequences of using a poorly effective drug or using an effective drug in an ineffective manner such as underdosing is the development of drug resistance. The apparent lack of satisfactory results experienced by bison producers could also result from parasites with resistance to avermectins. Although this has been well-documented in parasites of small ruminant (sheep, goats) and recently in North American cattle parasites, we believe that because of the relatively small scale of the bison industry and the rarity of co-production with other ruminant species, this is unlikely to have occurred in bison as yet (1).

In summary, the results support the effectiveness of correctly applied pour-on ivermectin in treating nematode infections in bison and we suggest that therapeutic failures in the commercial bison industry are more likely to be due to the manner in which the product is administered rather than parasite resistance or poor drug efficacy. The current study used ivermectin products and the results may not necessarily be extrapolated to all pour-on avermectin products.