Article — Artikel

A study to evaluate the field efficacy of , and pamoate, with preliminary observations on the efficacy of doramectin, as in horses

J A Daviesa* and L M J Schwalbachb

tance has indicated the need for alterna- ABSTRACT tive or complementary methods of The efficacy of ivermectin, fenbendazole, pyrantel pamoate and doramectin was evaluated parasite control and additional effective under field conditions at 2 sites in the Free State Province of South Africa. The study in- drugs. An example of the more recently volved 25 horses at each site, divided into 5 groups of equal size. Ivermectin, fenbendazole developed drugs is doramectin, an and pyrantel pamoate were administered orally at doses of 0.2, 10 and 19 mg/kg respec- currently registered for use in tively. Doramectin was administered by intramuscular injection at a dose of 0.2 mg/kg. sheep, cattle and swine in South Africa Treatment efficacy was based on the mean faecal egg count reduction 14 days post treat- (Dectomax, Pfizer). Although not regis- ment. At site A a faecal egg count reduction of 100 % was found after treatment with ivermectin, fenbendazole and doramectin. A 96.1 % reduction was found after treatment tered for use in horses, doramectin is cur- with pyrantel pamoate. At site B ivermectin and doramectin produced a 100 % reduction in rently used by many horse owners who faecal egg counts, fenbendazole produced an 80.8 % reduction and pyrantel pamoate a are claiming excellent results and no 94.1 % reduction. Doramectin produced a 100 % reduction in faecal egg counts at both sites, adverse side-effects. despite not being registered for use in horses. In addition, the results indicated reduced The aim of this study was to investigate efficacy of fenbendazole at site B, which suggested resistance. Larval cul- the efficacy of the main groups of anthel- tures showed that cyathostomes accounted for between 86 and 96 % of pre-treatment para- mintics in South Africa, where limited site burdens at both sites. Other helminths identified in the faecal samples were Strongylus studies have been conducted to date, and spp. and axei. to assess the efficacy of doramectin as an Key words: , cyathostomes, doramectin, equine, fenbendazole, horse, anthelmintic for horses. ivermectin, pyrantel, resistance. Davies J A, Schwalbach L M J A study to evaluate the field efficacy of ivermectin, MATERIALS AND METHODS fenbendazole and pyrantel pamoate, with preliminary observations on the efficacy of This study involved 50 horses, 25 at each doramectin, as anthelmintics in horses. Journal of the South African Veterinary Association of 2 sites (sites A and B) in the eastern Free 71(3): 144–147 (En.). Equine Veterinary Practice, PO Box 1075, Shelbyville, KY 40066, USA. State Province. The trial was conducted between December and January, when day temperatures averaged 28 °C and there had been no rain for approximately INTRODUCTION to be restricted to the cyathostomes and 4 months. All horses included had not Intestinal parasites are important fac- most commonly involves the benzimi- received anthelmintic treatment for at tors in the aetiology of gastrointestinal dazole anthelmintics, although resistance least 3 months and had at least 100 eggs disease and are also of economic impor- to pyrantel has also been detected2,3,5,7,9,13. per gram (EPG) at the beginning of the tance in horses throughout the world. It is Anthelmintic resistance in cyathostomes trial. The horses were predominantly not yet certain to what extent immunity is of horses has become widely documented Arabians, part-bred Arabians, Appaloosas acquired either with age or exposure16,17,29, over the last 3 decades and has been and Basutho ponies. and as a result, for many years, the control reported in most countries of the world1. Site A: horses were aged from 2 to 22 of equine parasites has depended largely In South Africa only a single study in years. All horses were kept on grass on the administration of anthelmintics, to which benzimidazole resistance was although some received supplementary remove adult parasites and prevent egg reported has been documented34. concentrates. Only 4 of these horses production with a subsequent reduction Cyathostomes commonly produce received regular treatment (every 6 in infective larvae on pastures. 75–100 % of eggs passed in the faeces of months) with ivermectin (Ivomec liquid, Intensive anthelmintic usage appears to naturally infected, adult, grazing horses4. Logos Agvet), the last treatment having select for those that can In contrast to previously held beliefs, it been administered approximately 6 survive treatment. The reproduction of has now been established that cyatho- months before the study. No other these individuals and the further treat- stomes can be highly pathogenic or even method of parasite control was imple- ment of their progeny with the same type fatal10,24. Their clinical effects range from mented. The pastures were grazed only of anthelmintic progressively selects for poor performance and colic to fatal enter- by horses. resistance26. Resistance in horses appears itis5,18. They are also responsible for the Site B: horses were aged from 3 months potentially fatal larval cyathostomiasis to 33 years. Two horses were stabled at aEquine Veterinary Practice, PO Box 1075, Shelbyville, KY 40066, USA. caused by mass emergence of hypobiotic night, receiving supplementary hay and bUniversity of the Orange Free State, Department of larvae usually seen in spring. These ob- concentrates. Of the others, which were Animal Science, PO Box 339, Bloemfontein, 9300 South Africa. servations illustrate the need for effective kept on grass, some also received supple- *Author for correspondence. cyathostome control. mentary hay and/or concentrates. The Received: December 1999. Accepted: June 2000. The development of anthelmintic resis- horses received anthelmintics at fixed

144 0038-2809 Tydskr.S.Afr.vet.Ver. (2000) 71(3): 144–147 Table 1: Mean faecal egg counts (± standard deviations) and reductions for each group at sites A and B.

Site A Site B Group Arithmetic mean Arithmetic mean Mean Arithmetic mean Arithmetic mean Mean (Day 0) (Day 14) % reduction (Day 0) (Day 14) % reduction

IVM 2210 ± 1166 0** 100 1650 ± 823 0** 100 DRM 2220 ± 1324 0** 100 1580 ± 974 0** 100 FBZ 2200 ± 1226 0** 100 1510 ± 917 290* ± 139 80.8 PYR 2290 ± 1088 90** ± 49 96.1 1530 ± 884 90** ± 58 94.1 Control 2140 ± 1466 1670 ± 1105 22 1720 ± 820 1400 ± 683 18.6

*P < 0.05; **P < 0.01.

3-monthly intervals. The drugs used Statistical methods 0.01) were found between mean faecal included fenbendazole (Panacur liquid, The effects of the different anthel- egg counts on day 0 and day 14 for all Hoechst), ivermectin (Ivomec liquid, mintics were estimated using the faecal treated groups except the fenbendazole- Logos Agvet) and doramectin (Dectomax egg count reduction test. Arithmetic treated group at site B, which showed a liquid, Pfizer). No particular rotation was means of the day 0 and day 14 egg counts less significant reduction (P < 0.05). At site used. Fenbendazole (Panacur liquid, were calculated to determine the mean A, significant differences (P < 0.01) were Hoechst) was the most recent treatment percentage reductions within each found between the mean EPGs of the con- administered, having been given approx- group. Two-way analysis of variance was trol and all the treatment groups on day imately 3 months before the study. No performed to evaluate the effect of day of 14. At site B the mean EPG of the control other management practices were em- sampling and treatment administered on and the treated groups were also signifi- ployed as methods of parasite control. mean faecal egg counts. Multiple compar- cantly different on day 14 (P < 0.01, for Mixed grazing with cattle and sheep isons were then made using the ivermectin, doramectin and pyrantel occurred periodically. Tukey-HSD interval. Analysis was carried pamoate and P<0.05, for the fenben- out on logarithmic transformed data dazole-treated group). It was not appro-

Design of study (log10 faecal egg count + 1), as the sample priate to pool the results from the 2 sites Faecal samples were collected from all size was small and the data could not be for statistical analysis, as it was apparent horses and analysed the same day using a assumed to be normally distributed. that there were between-site variations in modified McMaster technique with a sen- the faecal egg count reductions in the sitivity of 50 EPG. Horses were allocated RESULTS fenbendazole-treated groups (P < 0.01). to 1 of 5 equal-sized groups according to the EPG and, where possible, sex and age. Faecal egg count reductions Larval identification Anthelmintic treatment was carried out The results of the day 0 and day 14 mean The pre-treatment larval cultures the following day. On Day 14 post treat- EPG values from both sites are presented yielded 86 % cyathostomes and 14 % ment, faecal samples were again collected in Table 1, together with the mean faecal Strongylus spp. at site A and 96 % cyatho- from each horse and faecal egg counts egg count reductions. Ivermectin and stomes, 3 % Strongylus spp. and 1 % Tri- performed. Post-treatment samples were doramectin produced 100 % reductions at chostrongylus axei at site B. processed blind so that there was no both sites. Pyrantel pamoate showed Third-stage larvae from the pyrantel knowledge of the treatment group. Be- 96.1 % efficacy at site A and 94.1 % at site pamoate-treated group at site A were fore and after treatment, bulk faecal sam- B. Fenbendazole was 100 % effective at 98 % cyathostomes and 2 % Strongylus ples from each site were kept at room site A and 80.8 % effective at site B. spp. From site B, 98 % were cyathostomes, temperature (approx. 28 °C). Third-stage On day 0 all horses had positive egg 1% Strongylus spp. and 1 % Tricho- larvae were recovered using a variation of counts with a range of 100–4000 EPG at strongylus axei. At site B larval cultures the Baermann technique and identified site A and a range of 250–3200 EPG at site from the fenbendazole-treated group according to the number of intestinal B. On day 14, at site A all horses in the showed 99 % cyathostomes and 1 % cells. control and pyrantel pamoate-treated Trichostrongylus axei. Group 1 received ivermectin (Ivomec group had positive egg counts, ranging liquid, Logos Agvet), 0.2 mg/kg; group from 50–2850 and 50–150 eggs per gram DISCUSSION 2 received doramectin (Dectomax liquid, respectively. All horses in the ivermectin-, Ivermectin produced 100 % faecal egg Pfizer), 0.2 mg/kg; group 3 received doramectin- and fenbendazole-treated count reductions at both sites. Resistance fenbendazole (Panacur liquid, Hoechst), groups had egg counts of zero. At site B all to ivermectin has not been reported in 10 mg/kg; group 4 received pyrantel horses in the control, fenbendazole- and horses to date, possibly owing to the longer pamoate (Nemex-H powder, Pfizer), pyrantel pamoate-treated groups had treatment interval compared to that in 19 mg/kg, and group 5 was an untreated positive egg counts, with a range of anthelmintic treatment programmes of control. Ivermectin (IVM), fenbendazole 450–2300, 100–400 and 50–200 eggs per sheep, where resistance to ivermectin is a (FBZ) and pyrantel (PYR) were given gram respectively. All horses treated with widespread problem33,35. Ivermectin is orally, doramectin (DRM) was given by ivermectin or doramectin had egg counts also a more recently introduced equine intramuscular injection. The body- of zero. Resistance was defined as a faecal anthelmintic than the . weights were estimated using a weigh- egg count reduction of less than 90 % after A 100 % reduction in faecal egg counts band, based on heart girth measure- anthelmintic treatment2. According to was shown at both sites after administra- ments, and the weights were rounded up this definition resistance to fenbendazole tion of doramectin by intramuscular in- to the nearest 50 kg for dose determina- was found at site B. jection. These findings indicate that tion. At both sites significant differences (P < doramectin appears to be effective

0038-2809 Jl S.Afr.vet.Ass. (2000) 71(3): 144–147 145 against adult cyathostomes, Strongylus lower percentage of Strongylus spp. mectin as an equine anthelmintic might spp. and Trichostrongylus axei in horses. Trichostrongylus axei accounted for1%of be warranted. The fact that doramectin No adverse reactions were observed and the total burden, which may result from may be administered by intramuscular no irritation or swelling was seen at the occasional mixed grazing and pasture injection ensures that no anthelmintic is injection site in any of the horses. Obvi- rotation between ruminants and horses. wasted and hence no under-dosing ously further testing with a larger sample As previously reported, the present in- occurs, providing the animals’ mass is size would be required to extend these vestigation only shows benzimidazole accurately calculated. Under-dosing has observations. resistance in cyathostomes7,13,34. The rela- been suggested as an important factor in Fenbendazole was 100 % effective at site tively short life cycle of cyathostomes, hastening the development of resistance26 A, but reduced efficacy was apparent at when compared to Strongylus spp., and and this is often a risk associated with oral site B, suggesting benzimidazole resis- the fact that cyathostomes can become dosing, as spillage frequently occurs. Sim- tance. It would be incorrect to assume that hypobiotic in the host, allows generations ilar results were, however, reported for this finding is representative of the area, of cyathostomes to be exposed to anthel- cyathostominae in horses in Brazil after or country as a whole, as the sample size mintics more frequently, thus hastening oral administration of doramectin at was small, but the fact that resistance the development of resistance4,6,28. Uncon- 0.2 mg/kg19. Doramectin is registered for appears to have developed in the parasite firmed reports have also suggested resis- prolonged activity over a broad spectrum population of these horses is likely to tance in Strongylus spp.8,31. The results of of internal and external parasites in cattle, indicate a more widespread problem. the present study do not support this. The sheep and swine. This would also make Fenbendazole was reported as being presence of Trichostrongylus axei larvae doramectin usage advantageous if such highly effective in equines in South Africa after treatment with fenbendazole and claims could be substantiated in horses. in 1979 and 1981, but since then benzi- pyrantel pamoate is to be expected, as Investigation of these claims was beyond midazole resistance has been reported in these drugs are not registered for control the scope of this study. Considerable the only similar study22,23,34. The mean fae- of this parasite. additional data would be required before cal egg count reduction of 80.8 % in the Other studies have found increased such conclusions could be drawn. present study is higher than that reported levels of benzimidazole resistance in by Van Wyk and Van Wijk in 199234. horses treated with benzimidazoles alone ACKNOWLEDGEMENTS The faecal egg count reductions of or treated with benzimidazoles and non- Many thanks to the horse owners and 96.1 % and 94.1 % recorded after adminis- benzimidazoles alternately14,15,20,32. The Mr Jacques Prinsloo for their assistance tration of pyrantel pamoate, at sites A and results of the present study were, there- and to the veterinarians for the use of B respectively, are consistent with those fore, as anticipated. Van Wyk and Van their equipment. Sincere thanks to Mrs found by other authors7,13. These results Wijk34 mentioned that Maggie Fisher for her support and help provide no evidence of resistance. had been used before the study, but with the manuscript, to Dr Helen Pyrantel pamoate is not claimed to be made no further reference to previous Moreton for her inspiration and to Mr 100 % effective against cyathostomes or anthelmintic usage or treatment strate- Mark Kennedy for his help with statistical Strongylus spp. gies, thus making comparison difficult. analyses. The slight reductions seen in the control Further and more widespread studies groups confirm that the considerably with a larger sample size are needed to REFERENCES higher reductions in the other groups ascertain the extent of benzimidazole 1. Bauer C 1993 Anthelmintic resistance in resulted from the effect of anthelmintics, resistance, as the lack of studies in South nematodes of horses. In Anthelmintic resis- tance in nematodes of farm animals, a seminar not from natural factors. 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