Efficacy of ivermectin in the treatment of induced Parascaris equorum infection in pony foals

Eighteen pony foals inoculated with 1,500 +/- 109 infective Parascaris equorum eggs were given 0.02 ml of ivermectin vehicle (liquid)/kg of body weight, PO, (control); 0.2 mg of ivermectin paste/kg, PO; or 0.2 mg ivermectin liquid/kg, PO, on postinoculation day (PID) 28. Foals were euthanatized on PID 42, and the small intestinal contents were examined for P equorum larvae. The mean number of fourth-stage P equorum larvae in foals treated with ivermectin paste and liquid were 3.5 and 6, respectively. Significantly (P less than 0.01) higher mean numbers of larvae (1,250) were detected in foals treated with ivermectin vehicle. Larvae recovered from foals treated with ivermectin vehicle were of significantly (P less than 0.002) longer mean length than those from foals treated with ivermectin paste or liquid. Gross examination of lungs and liver revealed similar pathologic changes from the migration of P equorum in all foals. Adverse reaction to treatment was not observed.     

Critical tests and clinical trials on oxibendazole in horses with special reference to removal of Parascaris equorum.

The efficacy of oxibendazole given at dose level of 10 mg/kg of body weight was determined by 10 critical tests in foals and by 2 clinical trials in 20 foals (16 treated, 4 nontreated), with special interest in the drug activity against Parascaris equorum. The drug was uniformly efficacious (100%) against P equorum in the 10 critical-test foals, each having between 22 and 236 ascarids. Posttreatment reductions of ascarid egg counts in fecal samples were also 100% in suckling foals treated with oxibendazole given as a drench. Ascarid eggs did not reappear in fecal samples until the 8th week after foals were treated. A paste formulation of oxibendazole at 10 mg/kg also eliminated ascarid eggs from feces of 12 suckling foals. Strongyle EPG were markedly reduced by oxibendazole in the 10 critical-test foals and in 16 treated sucklings in the clinical trials. Egg and larval count data on foals in both the critical tests and the clinical trials also indicated oxibendazole was active against Strongyloides westeri. Untoward effects of treatment with oxibendazole were not observed.     

Efficacy of ivermectin in the oral paste formulation against naturally acquired adult and larval stages of Parascaris equorum in pony foals

The efficacy of ivermectin in oral paste formulation at a dosage of 200 micrograms/kg of body weight was tested against naturally acquired larval and adult stages of Parascaris equorum, in a controlled study. Twenty infected pony foals 18 to 27 weeks of age were randomly allocated to 2 groups of 10 each and were placed in dry lots. Foals in 1 group were given ivermectin on day 0. Necropsies and parasite recoveries from small intestines and lung tissues were performed on 5 foals in each group at 2 weeks after treatment (WAT) and on the remaining foals at 5 WAT. Ivermectin was 100% effective against adult P equorum. At 2 WAT, ivermectin was 100% effective against lung larval stages and 91% effective against intestinal larvae of P equorum. Efficacy of ivermectin against all intestinal stages was 93%. Intestinal and lung larval populations were similar in ivermectin-treated and nontreated foals at 5 WAT, indicating that the foals had become reinfected from the contaminated drylots, with larvae repopulating in the tissues 2 to 5 WAT. Apparent increases in severity of lymphoproliferative and inflammatory tissue reactions were observed histologically in lung and liver tissues of treated foals. Clear differences in clinical conditions between foals in treated and nontreated groups were not observed. However, weight gains in foals were greatest after treatment.     

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.     

Evaluation of ivermectin for larvicidal effect in experimentally induced Parascaris equorum infections in pony foals

A controlled test was carried out on 15 pony foals inoculated with 1,500 +/- 108.8 infective Parascaris equorum eggs. The foals were assigned to 3 treatment groups. Treatments given on postinoculation day 11 included 0.2 mg of ivermectin/kg of body weight, formulated as paste (n = 5), or liquid (n = 5), or no treatment (controls; n = 5). The foals were euthanatized on postinoculation day 25, and examined for larvae in the small intestine, lungs, and liver. Larvae were not found in foals treated with ivermectin liquid or paste, whereas significantly (P less than 0.05) higher mean numbers (960.9; range, 379 to 1,736) of 4th-stage larvae were found in the controls. Histologic and gross examination of lungs and liver revealed pathologic changes attributable to P equorum migration that were similar in all foals. Adverse reactions to treatment were not observed.     

Comparison of ivermectin, oxibendazole, and pyrantel pamoate in suppressing fecal egg output in horses

Thirty resident horses at a boarding stable in Alberta were used to evaluate the relative efficacies of ivermectin, oxibendazole, and pyrantel pamoate in reducing fecal egg output in adult horses under routine management conditions during spring and early summer, and to more clearly define the duration of suppression of fecal egg production following anthelmintic treatment. Horses were blocked according to pretreatment egg counts and randomly assigned to one of three treatments: pyrantel pamoate at 6.6 mg/kg body weight; oxibendazole at 10 mg/kg body weight; or ivermectin at 200 μg/kg body weight. All treatments were administered orally as a paste on day 0.Fecal samples were collected for examination by the modified Wisconsin procedure before treatment, and then at 4-11 day intervals up to day 72.

Very few if any strongyle eggs were found in the feces of any horses up to day 35. On days 42, 50 and 57, the geometric mean egg count for the ivermectin group was significantly (p<0.05) lower than that for the oxibendazole or pyrantel pamoate groups. Based on a survival curve analysis of the data, the mean number of days for recurrence of eggs in the feces was significantly longer for the ivermectin group than for the oxibendazole and pyrantel pamoate groups.

Under conditions encountered in this study, the posttreatment interval to resumption of fecal egg out-put in horses treated with ivermectin was eight to nine weeks, compared with five to six weeks for horses treated with oxibendazole or pyrantel pamoate.

     

Macrocyclic lactone-resistant Parascaris equorum on stud farms in Canada and effectiveness of fenbendazole and pyrantel pamoate

The aims of studies in 2002 and 2003 on three farms with 76 foals naturally infected with Parascaris equorum were to (i) identify if the nematode was resistant to ivermectin and moxidectin, and (ii) confirm the effectiveness of fenbendazole and pyrantel pamoate for the parasite. Twelve clinical trials, each with a Fecal Egg Count Reduction Test, were conducted on two Thoroughbred and one Standardbred farms in southwestern Ontario, Canada. In each trial, Parascaris eggs/g feces were estimated for each foal pre- and post-treatment using the Cornell-Wisconsin double flotation and Cornell-McMaster dilution techniques. On each farm and for each trial, foals were randomized into treatment groups. Treatments were ivermectin, moxidectin, fenbendazole, pyrantel pamoate administered at the manufacturers' recommended dosages, and some foals were untreated. The overall efficacy for ivermectin was 33.5% (19 foals) and for moxidectin 47.2% (28 foals). Fenbendazole (16 foals) and pyrantel pamoate (21 foals) were highly effective for P. equorum each at 97.6%. For fenbendazole, 15 foals had 100% and for pyrantel pamoate 17 foals had >97% with 14 at 100%.     

Effects of repeated Strongylus vulgaris inoculations and concurrent ivermectin treatments on mesenteric arterial lesions in pony foals

Eight of 10 pony foals reared under helminth-free conditions were inoculated PO with 50 Strongylus vulgaris infective larvae/week for 4 weeks, at which time 1 foal died of acute verminous arteritis. Inoculation of 7 remaining foals continued at 2-week intervals for 20 weeks. Of the 7 foals, 3 were treated with ivermectin (0.2 mg/kg of body weight) in an oral paste formulation at experiment weeks 8, 16, 24; 4 foals were not treated. Two foals were not inoculated or treated and served as controls. After the first ivermectin treatment, ivermectin-treated foals had fewer days (12 +/- 2.9) with rectal temperatures greater than 38.6 C than did nontreated foals (23.3 +/- 3.8). Mean baseline rectal temperatures were 38 +/- 0.2 C. Adverse clinical reactions to ivermectin treatment were not observed in foals. Foals were euthanatized and necropsied 3 weeks after the last ivermectin treatment (week 24). Ivermectin was effective in reducing S vulgaris arterial larval and intestinal adult parasite numbers by 100% in 3 treated foals. Strongylus vulgaris arterial larvae and/or adults were recovered from all 4 nontreated inoculated foals. One nontreated inoculated foal lacked arterial larvae or active arterial lesions, indicating that protective resistance had developed in this individual. Marked gross and histopathologic lesions typical of chronic S vulgaris infection were observed in the 3 nontreated inoculated foals with arterial larvae. Repeated killing of intra-arterial S vulgaris fourth-stage larvae in ivermectin-treated foals did not exacerbate lesions associated with verminous arteritis or induce unique lesions associated with repeated destruction of arterial larvae.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence of Ivermectin Resistance by Parascaris equorum on a Texas Horse Farm

By collecting fecal samples every 2 weeks beginning at 2 months of age, 32 foals from a single Texas farm were monitored. The foals were administered ivermectin paste at the time of the first collection and again monthly. When foals had Parascaris egg counts higher 2 weeks after ivermectin treatment than at treatment, they were administered pyrantel pamoate at the manufacturer's recommended dose (6.6 mg/kg) or at twice the recommended dose (13.2 mg/ kg) when tapeworm eggs were also detected. An elevation or only minimal reduction (less than 75%) in Parascaris egg counts was seen 2 weeks after ivermectin treatment until the foals were 8 months of age, at which time there was an 85% reduction in fecal egg count after treatment. When pyrantel was administered at the manufacturer's recommended dose, a 42% to 84% reduction in egg counts occurred, but at 13.2 mg/kg there was a 98% to 100% reduction in fecal egg counts 2 weeks posttreatment. However, pyrantel failed to control strongylate egg counts even at the elevated dose, whereas ivermectin reduced strongylate fecal egg counts by greater than 99%, determined 2 weeks posttreatment. Pyrantel, but not ivermectin, lowered Parascaris egg counts. Ivermectin, but not pyrantel, lowered strongyle egg counts 2 weeks post administration. A single drug for all ages of horses approach to parasite control requires rethinking. Combinations of drugs or more careful evaluation of anthelmintics in foals may be necessary for continued parasite control.     

Identification of foals infected with Parascaris equorum apparently resistant to ivermectin

During September 2002, routine fecal examinations performed on 16 Thoroughbred foals residing on a farm outside Toronto, Ontario, Canada, revealed low to moderate numbers of Parascaris equorum eggs in feces from 9 of the 16. All foals were then treated with ivermectin at a dose of 220 to 280 microg/kg (100 to 127 microg/lb), p.o., and fecal egg counts were repeated 12 days later. Fecal P. equorum egg counts increased between the first and second fecal examination in 7 foals, were unchanged in 1, and decreased in 5. Fecal samples were collected 13 days after treatment from 21 additional foals that had been treated with ivermectin at the same dose, and P. equorum eggs were detected in 12 of the 21. For all 37 foals, high P. equorum egg counts (> or = 100 eggs/g of feces) 12 to 13 days after ivermectin treatment were significantly more likely in foals that had been regularly treated with ivermectin since birth and permanently resided on the farm, compared with foals that had been treated with other anthelmintics or had an unknown deworming history. Collectively, these data suggested that P. equorum in these foals was resistant to ivermectin administered at the recommended dose.     

Efficacy of ivermectin in oral drench and paste formulation against migrating larvae of experimentally inoculated Parascaris equorum

Twenty-one mixed-breed pony foals, reared and maintained under parasite-free conditions, were used to test the efficacy of ivermectin in oral drench and paste formulations (200 micrograms/kg) against 11-day-old migrating larvae of Parascaris equorum. Three replicates of 4 foals and 3 replicates of 3 foals were formed on the basis of age. Foals in replicates of 4 were randomly allocated to be indicators, or to receive vehicle (control) or ivermectin paste or ivermectin liquid. Foals in replicates of 3 were randomly allocated to receive vehicle or ivermectin paste or ivermectin liquid. The recovery of larvae from the lungs, liver, and small intestines of the indicator foals showed that 99.9% of the larvae were in the lungs 11 days after inoculation (day 0 of treatment). The recoveries of larvae from lungs and small intestines of controls at 25 days after inoculation indicated that all larvae had migrated to the small intestine by this time. The mean length of larvae recovered from the lungs (11 days after inoculation) was 0.87 mm the mean length of those recovered from the small intestine (25 days after inoculation) was 3.65 mm. Using larvae recovered from small intestinal contents for calculations, ivermectin in both formulations was 100% effective against 11-day P equorum (P less than 0.01, compared with control group geometric mean of 1498.4).     

Anthelmhntic effects of injectable and oral paste formulations of ivermectin against 28-day infections of parascaris equorum

Efficacy of ivermectin treatment (0.2 mg/kg) against 28-day experimental infections of Parascaris equorum was determined in 18 pony foals6–17.5 weeks old. There were 6 foals in each group: nontreated control, ivermectin injectable or oral paste. In comparison with larvae found in the nontreated controls, ivermectin injectable or paste was 96.0% and 99.9% efficacious. There was a distinct difference in drug effect against the larger (ca 26mm.) vs the smaller (13–19mm) larvae by the 2 formulations of ivermectin. There were no adverse signs related to treatment of the young foals.     

Parascaris equorum in foals and in their environment on a Swedish stud farm, with notes on treatment failure of ivermectin

Environmental contamination and the egg excretion pattern of the ascarid Parascaris equorum (Nematoda) was investigated in relation to anthelmintic treatment on a Swedish stud farm. Faecal samples from 15 foals, dewormed every 8th-week with a paste formulation of ivermectin at the standard dose rate of 0.2 mg/kg bodyweight, were collected at five sampling occasions between August and November 2006. In addition, soil samples were obtained from four paddocks used by these foals in November 2006. The number of eggs per gram (epg) was counted in both faeces and soil. Egg excretion started when the foals were 3-4 months, and reached the highest levels when they were approximately 5-month-old, and was then followed by a decline. Egg excretion seemed to be unaffected by ivermectin despite these foals were dewormed at regular intervals. In four out of five foals examined 10 days after treatment, epg actually increased. In contrast, when either fenbendazol or pyrantel embonate were used instead of ivermectin, treatments were effective. The number of eggs in soil was significantly higher in the permanent paddock compared to in the temporarily used soil paddock and in the summer paddocks.     

Evaluation of ivermectin paste in the treatment of ponies for Parascaris equorum infections

Twenty ponies less than 18 months of age and infected with Parascaris equorum were treated with either 0.2 mg of ivermectin/kg of body weight (n = 10) or a placebo (n = 10; controls). Five control and 5 ivermectin-treated ponies were euthanatized 14 and 35 days after treatment, respectively. At necropsy, the small intestinal contents, lungs, and liver were examined for larvae and/or adult P equorum. Significantly (P less than 0.02) higher mean total numbers of P equorum were found in the small intestinal contents of the controls on day 14 (51) and on day 35 (21) than in the ivermectin-treated ponies on days 14 (0) and 35 (3). The efficacy of ivermectin in removing adult and intestinal larvae of P equorum at 14 days after treatment was 100%. The efficacies of ivermectin in removing adults and intestinal larvae of P equorum at 35 days after treatment were 100% and 76.9%, respectively. Gross examination of liver and lung tissues revealed damage as a result of P equorum infections in all ponies. The Baermann technique used on liver and lung tissues did not yield any P equorum larvae. Adverse reactions attributable to treatment were not observed.     

Anthelmintic efficacy on Parascaris equorum in foals on Swedish studs

Background

In the last few years stud farms have experienced increasing problems with Parascaris equorum infections in foals despite intensive deworming programs. This has led to the question as to whether the anthelmintic drugs used against this parasite are failing. This study aimed to investigate the efficacy of ivermectin, fenbendazole and pyrantel on the faecal output of ascarid eggs of foals.

Methods

A Faecal Egg Count Reduction Test (FECRT) was performed on nine large studs in Sweden. Anthelmintic drugs were given orally and faecal samples were examined for ascarid eggs on the day of deworming and 14 days later. Faecal Egg Count Reductions (FECRs) were calculated on arithmetic means of transformed individual FECRs and on arithmetic means of individual FECRs.

Results

Seventy-nine (48%) out of a total of 165 foals sampled were positive for P. equorum eggs before deworming and 66 of these met the criteria for being used in the efficacy assessment. It was shown that there was no, or very low activity of ivermectin on the output of ascarid eggs in the majority of the foals, whereas for fenbendazole and pyrantel it was >90%.

Conclusion

Ivermectin resistance was shown in 5 out of 6 farms. Therefore, ivermectin should not be the drug of choice in the control of P. equorum infections in foals. According to the results of this study, fenbendazole or pyrantel are still effective and should be used against this parasite.     

Prevalence and control of benzimidazole-resistant small strongyles on German thoroughbred studs

The prevalence of benzimidazole-resistant small strongyles was determined in a survey, conducted on 14 thoroughbred studs, which compared the faecal egg counts of groups of horses before and after treatment with the recommended doses of cambendazole (20 mg kg-1 b.w.) or febantel (6 mg kg-1 b.w.). Benzimidazole-resistant cyathostomes were found on all farms examined. Pyrantel pamoate (19 mg kg-1 b.w.), oxibendazole (10 mg kg-1 b.w.) and ivermectin (0.2 mg kg-1 b.w.) reduced the strongyle egg counts on these studs by 97-100% at 2 weeks post-treatment. However, 6 weeks after dosing the reduction of the strongyle egg output had decreased to an average of 67.8% (8.7-97.1%) with pyrantel pamoate and 51.2% (0-95.8%) with oxibendazole, whereas ivermectin still suppressed the egg counts by 98.2% (95-100%).     

Reduced efficacy of anthelmintics in young compared with adult horses

Studies on a Thoroughbred breeding farm in Ohio from 1982 to 1988 demonstrated the value of three anthelmintic pastes (ivermectin, oxibendazole, pyrantel pamoate) in controlling benzimidazole resistant cyathostomes (small strongyles) in adult horses. However, a comparison of drug efficacy in suppressing faecal egg counts for the full period between treatments showed a significant reduction in efficacy of all drugs in yearling horses compared with adults. Mean faecal egg counts of adult horses were generally kept below 100 eggs per gram (epg) of faeces when using oxibendazole or pyrantel pamoate at four to five week intervals and ivermectin at eight week intervals. By contrast, mean counts of young horses rose as high as 655 epg (oxibendazole), 729 epg (pyrantel pamoate) and 852 epg (ivermectin) within the same time period after treatment. Individual counts of treated yearlings sometimes exceeded 3,000 epg. Three distinct mechanisms appeared to be involved in the poor results in young horses. These were 1) anthelmintic refuge, 2) anthelmintic resistance, and 3) anthelmintic avoidance.     

Efficacy of an ivermectin and pyrantel pamoate combination against adult hookworm, Ancylostoma braziliense, in dogs

A chewable tablet incorporating ivermectin and pyrantel was tested in 12 Beagle dogs for efficacy against the adult hookworm, Ancylostoma braziliense. The dogs were administered infective larvae of A braziliense orally. Twenty-one days after infection the dogs were weighed and allocated randomly to receive either an oral treatment with ivermectin and pyrantel in a beef-based chewable tablet or no treatment. The chewable tablet was a commercially available product, which was made to deliver ivermectin at 6 μg/kg and pyrantel at 5.0 mg/kg to each dog. Seven days after treatment the dogs were euthanased, necropsied, and examined for adult hookworms. At necropsy, no adult A braziliense was observed in any of the 6 treated dogs and all 6 dogs that had been left untreated were infected with adult A braziliense (range, 48 to 161). It was concluded that this combination product is 100% efficacious against adult A braziliense.     

Activity of closantel in the prevention of Gasterophilus and Strongylus vulgaris larval infections in equine foals and yearlings

Two controlled tests were conducted in equine foals and yearlings to determine the optimal oral dosage and the duration of activity of closantel for the prevention of Gasterophilus spp larval infections. Additional data were collected on the activity of closantel against Strongylus vulgaris larval infections. In experiment 1, 12 foals and 12 yearlings were equally allocated to 4 experimental groups, and were given oral treatments with closantel at dosages of 0 (nontreated controls), 2, 5, or 8 mg/kg of body weight every 2 months during bot season. The foals and yearlings were allowed to graze on open pasture throughout the experiment to provide a natural source for bot and helminth infections. All animals were euthanatized and necropsied 6 weeks after the final treatment. Closantel was highly effective (98.6% to 100%) at all doses in preventing Gasterophilus spp larval infections in the foals, but only the 8 mg/kg dose had significant (P less than 0.05) activity (99.7%) in the yearlings. This dose also significantly reduced the numbers of 4th-stage and immature adult S vulgaris (86.0%) in the mesenteric arteries as compared with nontreated controls. In experiment 2, 9 foals and 9 yearlings received a single oral treatment of 8 mg of closantel/kg of body weight; 3 foals and 3 yearlings were kept as nontreated controls. Groups of 6 treated (3 foals, 3 yearlings) and 2 control (1 foal, 1 yearling) animals were euthanatized and necropsied 1, 2, and 3 months after treatment. Closantel remained effective for 2 months in preventing infections of G intestinalis larvae in these foals and yearlings. Clinical signs of toxicosis were not observed in the treated animals of either study.     

Efficacy of ivermectin and pyrantel pamoate combined in a chewable formulation against heartworm, hookworm, and ascarid infections in dogs.

Eight trials were conducted in dogs to document the efficacy of ivermectin (6 micrograms/kg of body weight) and pyrantel pamoate (5 mg of active pyrantel/kg) in a beef-based chewable formulation against Dirofilaria immitis, Ancylostoma caninum, Uncinaria stenocephala, Toxocara canis, and Toxascaris leonina. Three studies involved induced infection with D immitis, and 5 studies involved induced or natural infection with hookworms and ascarids. In 3 intestinal parasite trials, the efficacy of the combination chewable tablet was compared with each of its components. Results indicated that 1 component did not interfere with the activity of the other. In 1 heartworm and 2 intestinal parasite trials, the efficacy of pyrantel, ivermectin/pyrantel combination, or ivermectin with pyrantel dosage of 10 mg/kg was evaluated. The ivermectin/pyrantel combination was 100% effective in preventing development of D immitis larvae. Efficacy of the combined product against T canis, Toxascaris leonina, A caninum, and U stenocephala was 90.1, 99.2, 98.5, and 98.7%, respectively. In the intestinal parasite trials, each individual component was found not to interfere with the anthelmintic action of the other. Increasing the dosage of pyrantel to 10 mg/kg (2 x that in the combination) did not interfere with the efficacy of ivermectin against heartworm or increase the activity of pyrantel against intestinal parasites.