A review of some modern equine anthelmintics

Thiabendazole was the first of several benzimidazole anthelmintics and was superior to previously available drugs in both-efficiency and safety. Of the “second generation” of benzimidazoles, mebendazole and cambendazole are widely used inhorses and provide wider efficacy spectra and lowerdose rates compared with thiabendazole. Thiabendazole has proven activity against larval strongyles, but requires high dose rates. Two organophosphates, dichlorvos and haloxon have been formulated as horse anthelmintics. Pyrantel and its analogue morantel, are reported as efficient equine anthelmintics, but only in-feed and pasteformulations are recommended by the manufacturer as suitable for horses. Strains of small strongyles tolerant to benzimidazoles have been reported in U.S.A. and U.K. The addition of a piperazine salt to approximately half recommended dose rate, or the use of pyrantel, removed the tolerant nematodes.     

The prevalence of anthelmintic resistance of horse strongyles in The Netherlands.

A survey to determine the prevalence of anthelmintic resistance of horse strongyles was carried out with 616 horses on 22 farms. The tested drugs were cambendazole, pyrantel pamaote and ivermectin. Based on egg count reduction tests the efficacy of cambendazole varied from 0% to 93% and of pyrantel from 93% to 100%. Ivermectin treatments were 100% effective on all farms. Larval cultures after cambendazole treatments revealed exclusively cyathostome larvae. After pyrantel treatments besides cyathostome larvae other types of larvae were also found. After ivermectin treatments only a few cyathostome larvae were observed. It can be concluded that benzimidazoleresistance of cyathostomes is very common and widespread in the Netherlands. This means that benzimidazoles and pro-benzimidazoles should be excluded for strategic use in horses.     

Resistance of population-B equine strongyles to thiabendazole, oxfendazole, and phenothiazine (1981 to 1987)

Critical tests were completed on foals (n = 15) naturally infected with benzimidazole (BZ)-resistant population-B strongyles during the period between 1981 and 1987. Thiabendazole at a dosage of 44 mg/kg was tested in 8 foals, oxfendazole at 10 mg/kg was tested in 4 foals, and phenothiazine at 55 mg/kg, cambendazole at 20 mg/kg, and fenbendazole at 5 mg/kg were tested in 1 foal each. Efficacies of thiabendazole, cambendazole, and fenbendazole against the 5 species of BZ-resistant small strongyles (Cyathostomum catinatum, Cyathostomum coronatum, Cylicocylus nassatus, Cylicostephanus goldi, and Cylicostephanus longibursatus) were partial. Removals in the aggregate averaged 48%, 52%, and 68%, respectively, indicating continued resistance of the 5 species of small strongyles to thiabendazole, cambendazole, and fenbendazole. In contrast, oxfendazole was efficacious, removing an aggregate average of 95% of the 5 BZ-resistant species of small strongyles in the 4 foals. This apparent reversion to susceptibility to oxfendazole may be attributable to paucity of reference data (1 test foal) done in 1976. All 5 species of the BZ-resistant small strongyles had cross resistance to phenothiazine (38% aggregate removal), whereas 9 of the BZ-susceptible species were effectively (99%) removed. This suggests a similar mode of action between phenothiaznie and the BZ compounds.     

Effect of cambendazole on swine kidneyworm,Stephanurus dentatus

Two trials were conducted to determine the effect of cambendazole against natural infections of the swine kidneyworm, Stephanurus dentatus, in sows. In the first trial, nine sows were given a single dose of 20 mg cambendazole/kg body weight, in the feed, and eight sows were not treated. In the second trial, five sows were given 40 mg cambendazole/kg body weight and four were untreated. Urine volume, S. dentatus eggs per milliliter of urine, egg hatchability, and larval survival to the third stage were determined pre and post treatment. Adult kidneyworms were counted at necropsy, 14 days after treatments. Only a temporary decline in egg hatchability was observed on the day after treatment in each trial, and cambendazole was not found to be effective against adults of S. dentatus.     

The anthelmintic activity of some benzimidazole derivatives against Fasciola hepatica

Micronised mebendazole has been shown to have anthelmintic activity against Fasciola hepatica in rats and sheep. Activity is higher against non-egg-producing F. hepatica in bile ducts than against the migrating larval stages. Parbendazole, cambendazole and thiabendazole have been shown to be much less active, or devoid of activity, against mature and immature F. hepatica in rats, at elevated dose rates.

Reasons for the differences, in terms of molecular structure, are briefly discussed and the pitfalls of structure/activity analyses are considered.     

The antiparasitic activity of ivermectin in horses

Parenteral administration of ivermectin (22,23-dihydroavermectin B₁) significantly reduced the numbers of adult large and small strongyles, the immature stages of small strongyles, pinworm and ascarid, the microfilariae of Onchocerca cervicalis and gastrophilid bots from naturally infected horses. Strongylus vulgaris, S. edentatus and S. equinus were effectively removed by 0.02 mg/kg. Adult small strongyles, Cyathostomum pateratum, C. catinatum, Cylicocyclus nassatus, C. leptostomus, Cyliostephanus minutus, C. longibursatus and C. goldi, were effectively removed by 0.1 mg/kg. Fourth stage small strongyles (cyathostomes), 4th stage Oxyuris equi, 5th stage Parascaris equorum and the microfilarie of Onchocerca cervicalis were significantly reduced by 0.1 mg/kg also. The stomach bots, Gastrophilus intestinalis and G. nasalis, were effectively removed by 0.02 mg of ivermectin/kg. Analysis of the dose response curves obtained for the nematode and larval dipteran parasites found in these naturally infected horses suggests that a parenteral dose of 0.2 mg/kg ivermectin would produce 95% or more removal of these parasites. The antiparasitic efficacies observed for ivermectin in this controlled trial were equivalent to the efficacies found in an abbreviated critical trial contained within the controlled trial. However, it was calculated that the man—day effort required for data collection from one critical trial horse was the same as for 6 controlled-trial horses.     

Benzimidazole resistance of equine stronygles--critical tests of six compounds against population B

Critical tests were conducted on eight horses naturally infected with several species of large and small strongyles from population B. Tested were six benzimidazoles, including thiabendazole (2 lots) (44 mg/kg of body weight); mebendazole (8.8 mg/kg); cambendazole (two formulations) (20 mg/kg); fenbendazole (10 mg/kg); oxibendazole (10 mg/kg); and oxfendazole (10 mg/kg). All compounds were administered by stomach tube except one of the two cambendazole formulations which was an intraoral paste. Removal of large strongyles (when present), Strongylus vulgaris and Strongylus edentatus, was 100% by each drug. In general, five species of small strongyles (Cyathostomum catinatum, Cyathostomum coronatum, Cylicocyclus nassatus, Cylicostephanus goldi, and Cylicostephanus longibursatus) exhibited varying degrees of resistance (% removal) to all of the drugs except oxibendazole. A total of 19 other species of small strongyles from seven genera, including the three described earlier were about 100% removed by the six benzimidazoles. Poor removal of immature (fourth-stage larvae) forms was also characteristic of the six drugs.     

A field evaluation of oxibendazole in horses infected with benzimidazole resistant small strongyles

Horses with a history of frequent benzimidazole (BZD) treatment were used in a trial to assess the effectiveness of oxibendazole (OBZ). Initial investigations established that these animals were infected with small strongyles resistant to thiabendazole (TBZ), mebendazole (MBZ), cambendazole (CBZ), oxfendazole (OXF) and fenbendazole (FBZ).The herd was subsequently divided into four groups and received TBZ, CBZ, OBZ, or no treatment. OBZ effectly reduced fecal egg counts. Similar reductions were not observed with TBZ or CBZ.     

Benzimidazole resistance of equine strongyles: critical tests of several classes of compounds against population B strongyles from 1977 to 1981

From 1977 to 1981, critical tests were conducted on 10 horses naturally infected with population B strongyles. Drugs tested were: oxibendazole (OBZ), 10 mg/kg of body weight (n = 1); albendazole, 10 mg/kg (n = 1); a mixture of thiabendazole (TBZ), 44 mg/kg and trichlorfon, 40 mg/kg (n = 1); a mixture of TBZ at 44 mg/kg with piperazine (PPZ) at 55 mg of base/kg (n = 1); febantel (FBT), 6 mg/kg (n = 3), 12 mg/kg (n = 1), or 24 mg/kg (n = 1); and pyrantel (PRT) pamoate, 6.6 mg of base/kg (n = 1). Large strongyles, Strongylus vulgaris (9 horses) and S edentatus (5 horses), were effectively removed (100%) by each compound and mixture. Five species of small strongyles (Cyathostomum catinatum, Cyathostomum coronatum, Cylicocyclus nassatus, Cylicostephanus goldi, and Cylicostephanus longibursatus), previously singled out in this population as resistant to 5 benzimidazoles (TBZ, mebendazole, cambendazole, fenbendazole, and oxfendazole), but not OBZ, were efficaciously removed by OBZ, albendazole, the mixture of TBZ plus PPZ, FBT (24 mg/kg), or PRT. These 5 small strongyle species were resistant to FBT (6 mg/kg) in 3 foals and Cylicostephanus minutus was also resistant in 2 of 3 foals to FBT (6 mg/kg). Doubling the dose of FBT to 12 mg/kg increased the average removal of the 5 basic species plus Cylicostephanus minutus to 88%. The mixture of TBZ and trichlorfon was relatively ineffective against 3 species (C catinatum, C coronatum, and Cylicostephanus longibursatus), but unexpectedly efficacious (86% to 99%) for 2 species (Cylicocyclus nassatus and Cylicostephanus goldi).(ABSTRACT TRUNCATED AT 250 WORDS)     

The Prevalence and Intensity of Helminth and Coccidial Infections in Dairy Cattle in Central Kenya

A survey of gastrointestinal parasite infections of young (<6 months old), immature (6–12 months old) and adult (>12 months old) dairy cattle on 16 farms in Kiambu District, Kenya was conducted during a dry season (September 1991 to January 1992) and during a wet season (March to July 1992). The survey was based on monthly coproparasitological examination of cohorts and worm counts in tracer calves. The effects of age, sex, farm and season on the prevalence and intensity of helminth and coccidial infections were determined. Faecal egg and oocyst counts revealed that the overall prevalences were: strongyles (including trichostrongyles) (85.5%), liver flukes (Fasciola gigantica) (34.0%), coccidia (30.9%) and tapeworms (9.6%). Eight species of the protozoan Eimeria were identified, the most prevalent species being E. bovis and E. zuernii. The most prevalent nematode genera were Haemonchus, Cooperia, Oesophagostomum and Trichostrongylus. Season, farm and age of the animals had a significant (p<0.05) influence on the intensity of infection with strongyles, liver flukes and coccidia, whereas the sex of the animals had no significant (p>0.05) effect on the prevalence or intensity of infections. A higher intensity of infection with strongyles and coccidia was found in the wet season than in the dry season (p<0.05). The age-specific intensity was in the following order: for strongyles, immature animals of 6–12 months of age had the highest egg counts, followed by young calves and adults. Calves had significantly (p<0.05) higher oocyst counts than immatures or adults. Liver fluke egg counts did not differ significant (p>0.05) between immatures and adult cattle.     

Efficacy of Ivermectin Pour-on Against Nematodes Infecting Foals on Pasture: Coprological and Biochemical Analysis

The efficacy of topical ivermectin (IVM) on foals naturally infected by parasitic nematodes was evaluated. Two dosages of IVM were applied pour-on (F-Nor0.5; 0.5 mg/kg body weight [BW] and F-Nor1; 1 mg/kg BW) and results compared with the oral administration (F-Eq0.2; 0.2 mg/kg BW of IVM). The efficacy was measured by estimating the reduction in the fecal egg counts (fecal egg count reduction) and in the numbers of horses shedding parasite eggs (positive horse reduction). Several biochemical and enzymatic serum parameters were measured in the groups F-Eq0.2 and F-Nor1. Before the deworming of the horses, eggs of Parascaris equorum, Cyathostomum, Gyalocephalus spp, and Oxyuris equi were identified. In all the treated groups, the excretion of ascarid eggs ended 4 days after the treatment. The orally administered IVM suppressed the egg output of strongyles and pinworms 4 days after the treatment, whereas for the F-Nor1 group this occurred 8 days after the treatment. Eggs of strongyles were detected in the F-Nor0.5 group throughout the study. The levels of blood urea nitrogen, creatinine, total proteins, albumin, globulins, and lactate dehydrogenase (LDH) reduced significantly after the administration of IVM, but values not within the normal range were only achieved for LDH. A significant positive correlation between the fecal egg output of cyathostomins and the LDH was investigated. Clinically, no adverse reactions in the horses receiving the topical IVM were observed. It was concluded that the pour-on administration of 1 mg/kg BW IVM provides similar results to the oral administration, and offers a very useful tool to control infestation by the intestinal nematodes affecting wild grazing horses.     

Helminths of sheep and goats in desert areas of south-west Mauritania (Trarza)

Faecal samples were obtained from sheep and goats before, during and after the rainy season at three locations in south-west Mauritania. Several animals were also necropsied at the same time.Haemonchus contortus was the most prevalent worm. Infection by digestive-tract strongyles andStrongyloides papillosus was always very light (prevalence less than 20%). Sheep were more heavily infected than goats but animals under 1 year of age were not infected by digestive-tract strongyles. It is likely that young small ruminants became infected during the rainy season and that the parasites so acquired are inhibited in their development and/or survive nearly one year as adults.     

Impaired efficacy of ivermectin against Parascaris equorum, and both ivermectin and pyrantel against strongyle infections in trotter foals in Finland

In order to assess the resistance situation against macrocyclic lactones in Parascaris equorum and against tetrahydropyrimidine derivatives in strongyles in Finnish trotter horses, 112 foals on 18 farms, mostly 1 year old, were examined for these parasites with a modified McMaster faecal flotation method. P. equorum positive foals (n=24) were given ivermectin orally at a dose of 200 μg/kg b.w., while strongyle positive but P. equorum negative foals (n=38) received pyrantel embonate orally at a dose of 19 mg/kg. Sixteen P. equorum infected foals, treated with ivermectin, also harboured strongyles. During the anthelmintic treatment visit to the farm, Faecal Egg Count Reduction Test (FECRT) reference (first) samples were collected. Fourteen days later, the second sampling (reduction samples) was done. The FECR was calculated for each foal/parasite combination. The reduction efficacies of ivermectin against P. equorum (mean 52%, calculated from the individual egg count reductions) and pyrantel against strongyles (43%) were strongly indicative of widespread resistance. Also indication of ivermectin resistance among strongyles was seen. The widespread use of anthelmintics for Finnish horses obviously has resulted in resistance, as has happened elsewhere, too.     

Ovine Johne's disease in New Zealand

Abstract

Extract

Cambendazole, isopropy1 2-(4-thiazoly1)-5-benzimidazolecarbamate, has been reported to be a highly efficient anthelmintic against gastro-intestinal nematodes of cattle (Egerton et al., 1970 Egerton, J. R., Eary, C. H., Lanza, G. R., Wombolt, T. H. and Campbell, W. C. 1970. The efficacy of cambendazole against gastro-intestinal nematodes of cattle. Res. vet. Sci., 11: 495–499.  [Google Scholar]; Baker and Walters, 1971 Baker, N. P. and Walters, G. T. 1971. Anthelmintic efficacy of cambendazole in cattle. Ant. J. vet. Res., 14: 29–33.  [Google Scholar]; Ciordia and McCampbell, 1971 Ciordia, J. and McCampbell, H. C. 1971. Anthelmintic efficacy of four dose levels of cambendazole in cattle. Proc. helm. Soc. Wash., 38: 40–42.  [Google Scholar]; Benz, 1971a Benz, G. W. 1971a. Anthelmintic activities of cambendazole in calves. Am. J. vet. Res., 32: 399–403.  [Google Scholar], b Benz, G. W. 1971b. Activity of cambendazole against gastro-intestinal nematodes of calves: Single vs. two therapeutic treatments. J. Parasit., 57: 286–288.  [Google Scholar]; Restani, 1971 Restani, R. 1971. Research on the anthelmintic activity of cambendazole against some nematodes of cattle. Vet. Italiana, 22: 137–139.  [Google Scholar]). Efficacy against the cattle lungworm, Dictyocaulus viviparus, has also been reported as high (Rubin, 1972 Rubin, R. 1972. Efficacy of cambendazole against lungworm (Dictyocaulus vivipams) of cattle. Am. J. vet. Res., 33: 425–426.  [Google Scholar]; Gibbs and Gupta, 1972 Gibbs, H. C. and Gupta, R. P. 1972. The anthelmintic activity of cambendazole in calves and lambs. Can. J. comp. Med., 36: 108–115.  [Google Scholar]; Baker et al., 1972 Baker, N. F., Walters, G. T., Hjerp, G. A. and Fisk, R. A. 1972. Experimental therapy of Dictyocaulus viviparis infection in cattle with cambendazole. Am. J. vet. Res., 33: 1127–1130.  [Google Scholar]). This paperreports the results of four controlled critical efficacy trials with cambendazole against naturally acquired nematode infections in cattle.     

Efficacy of Daily Pyrantel Tartrate (Strongid C) against Strongyles in Ponies on Pasture

A clinical trial was conducted with 2- to 3-year-old ponies to determine the effectiveness against strongyles of 2.64 mg pyrantel tartrate/kg body weight administered in the daily ration throughout a pasture season in Canada. Ten ponies were given the anthelmintic, and 10 were not treated and served as controls. Each group of ponies was on a separate pasture. The mean strongyle eggs/g of feces for each group, before treatment and turnout to pasture, was greater than 2,200. Thereafter, the mean eggs/g feces for the untreated group remained high (1,405−2,294) and those for the treated group decreased markedly to, and remained at, very low levels (0.2−16.8). Strongyle larval counts for the pasture with the untreated ponies rose to 26,790 larvae/kg dry herbage in August, whereas that for the treated group was 610 larvae/kg dry herbage. At the end of the season, two ponies from each group were isolated for 6 weeks and necropsied. The mean number of strongyles in the untreated and treated ponies was 69,288 and 8,452.5, respectively. In the untreated ponies, 21 species of strongyles were found, and approximately 84% of them were from eight species of cyathostomes. In the treated ponies, 14 species of strongyles were found, and approximately 77% were from one species, Cylicostephanus minutus (52.0%), and immature cythostomes (25%). Adverse reactions were not observed in any of the treated ponies. Pyrantel tartrate was highly effective in significantly reducing the strongyle egg and pasture larval counts and the transmission of strongyles during a pasture season.     

A comparison of the bioequivalence of 0.5% fenbendazole top dress pellets or 10% fenbendazole oral suspension against a spectrum of equine parasites.

A controlled test was conducted to assess the efficacy bioequivalence of a single dose of 0.5% fenbendazole (FBZ) top dress pellets to a 10% FBZ suspension formulation (Panacur suspension 10%, Hoechst Roussel Vet). Thirty horses with naturally-acquired parasite infections, in replicates of three, were used. Strongyle egg per gram counts were not significantly different (P>0.1) between groups pretreatment, but FBZ treated groups were significantly different from the control group post-treatment. At necropsy, which occurred seven to nine days post-treatment, two methods of nematode recovery were compared to assess whether a small aliquot can be used in a control test to determine efficacy against large as well as small strongyles. Both post mortem worm recovery techniques revealed similar efficacies of both formulations (>95%) against small and large strongyles, but large differences in the number of worms recovered. Six species of small strongyles comprised 96% of all the small strongyles recovered: Coronocyclus coronatus, Cylicocyclus insigne, Cylicostephanus longibursatus, Cylicocyclus brevicapsulatus, Cylicocyclus nassatus, and Cyathostomum catinatum. The results of this study demonstrated therapeutic bioequivalence between FBZ formulations and also the need to sample at least a 10% aliquot to accurately estimate number of large strongyles. No adverse reactions to treatment were detected.     

Coprological prevalence and intensity of helminth infection in working horses in Lesotho

This study aimed to (1) estimate infection prevalence of strongyle, Oxyuris equi and Parascaris equorum species and the intensity of infection with strongyles in working horses in lowland Lesotho and (2) investigate associations between infection and horse age, sex and owner-reported use of anthelmintics. In a cross-sectional survey, fresh faecal samples were obtained from 305 randomly selected horses and worm egg counts performed using a validated field laboratory kit. Details of anthelmintic use were collected using a standardised face-to-face owner questionnaire. Infection prevalence estimates for each species were calculated, as were infection intensity estimates for strongyle species. Logistic regression was used to investigate associations between exposure variables and infection status/intensity. Prevalence of strongyle infection was 88.2%; 11.8% of horses were not infected and infection intensity was low (1–500 eggs per gram (epg)) in 19.7%, medium (501–1,000 epg) in 19.7%) and high (>1,001 epg) in 48.8%. Decreasing strongyle infection intensity was associated with the use of proprietary equine anthelmintic products (OR 0.18, 95%CI 0.11–0.30, p < 0.0001). Prevalence of O. equi infection was 6.2%; the odds of infection with this parasite decreased with increasing horse age (OR 0.84, 95%CI 0.72–0.97, p = 0.02). P. equorum infection prevalence was 21.6%; no statistically significant associations with the investigated exposure variables were found. In conclusion, strongyle infection is endemic in working horses in lowland Lesotho, but proprietary equine anthelmintics assist in managing infection. The apparent lack of age-acquired immunity to P. equorum infection may deserve further investigation. Although O. equi infection is less widespread, measures to protect younger animals may be appropriate.     

Kinetics of natural expulsion of some equine parasites during a critical test

An experiment was conducted to determine the rate(s) of natural elimination of some equine parasites from nine nontreated horses during the interim of a critical test. During the 7-day period 0.08% of the small strongyles and 0.4% of the Gastrophilus (bot) populations were concluded that natural elimination of large strongyles, small strongyles, and Gastrophilus larvae during the interim of the critical test, would not have biased the efficacy of an anthelmintic or boticide.     

Use of oxibendazole for control of cambendazole-resistant small strongyles in a band of ponies: a six-year study

Oxibendazole (OBZ; 10 mg/kg of body weight) was administered to ponies at 8-week intervals to control strongylosis in a breeding band of Shetland-type ponies (n = 29 to 50) from October 1978 through September 1984. A similar use of cambendazole (CBZ; 20 mg/kg of body weight) in this band of ponies during the preceding 4-year period resulted in the survival of a CBZ-resistant population (S) of small strongyles. Effectiveness of OBZ treatments was monitored by pre- and posttreatment counts of the number of strongyle eggs per gram of feces (epg) and of the number of strongyle larvae per gram of feces (lpg). For the first 4 years of the 6-year period, epg and lpg counts were determined for 3 to 5 of the OBZ treatments; during the last 2 years, counts were determined for each treatment. For the 1st year, the mean reduction in epg was 96%. During the 2nd and 3rd years, mean reductions in epg were 80% and 81%, respectively. For the 4th and 5th years, mean reductions in epg were 69% and 43%, respectively. For the 6th year, the mean reduction in epg was 37%. Statistical analyses of the epg data, using the linear plateau method, indicated a significant increase in residual (surviving) strongyle infections after the periodic OBZ treatments, with a mean annual increase in survival of 10.3% for the 6 years. Changes in lpg were variable, but an overall loss of effectiveness of the OBZ treatments was evident. Only infective larvae of small strongyles were observed in the cultures; larvae of 2 species of large strongyles, Strongylus vulgaris and Strongylus edentatus, were conspicuously absent.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of dose and diet on the pharmacokinetics of omeprazole in the horse

This study aimed to investigate the effect of diet and dose on the pharmacokinetics of omeprazole in the horse. Six horses received two doses (1 and 4 mg/kg) of omeprazole orally once daily for 5 days. Each dose was evaluated during feeding either a high‐grain/low‐fibre (HG/LF) diet or an ad libitum hay (HAY) diet in a four‐way crossover design. Plasma samples were collected for pharmacokinetic analysis on days 1 and 5. Plasma omeprazole concentrations were determined by ultra‐high pressure liquid chromatography–mass spectrometry. In horses being fed the HG/LF diet, on day 1, the area under the curve (AUC) and maximal plasma concentration (C_max) were higher on the 4 mg/kg dose than on the 1 mg/kg dose. The AUC was higher on day 5 compared to day 1 with the 4 mg/kg dose on the HG/LF diet. On days 1 and 5, the AUC and C_max were higher in horses being fed the HG/LF diet and receiving the 4 mg/kg dose than in horses being fed the HAY diet and receiving the 1 mg/kg dose. These findings suggest that both dose and diet may affect pharmacokinetic variables of omeprazole in the horse.