Comparative efficacy of flubendazole chewable tablets and a tablet combination of febantel, pyrantel embonate and praziquantel against Trichuris vulpis in experimentally infected dogs

Fourteen of 23 dogs developing patent Trichuris vulpis infections by 120 days p.i. with 5000 embryonated eggs were allocated into three groups. One group was treated with flubendazole 220 mg chewable tablets (Flubenol) at the recommended dose regimen once daily for 3 days. The second group was given the recommended single treatment with a tablet containing 150 mg febantel, 144 mg pyrantel embonate and 50 mg praziquantel in combination (Drontal Plus). The third group remained untreated. All dogs were necropsied for worm counts 10 or 11 days after (first) treatment. No worms were recovered from the flubendazole treated dogs resulting in a significant worm count reduction of 100%. In contrast, 2 of 5 animals treated with the combination of febantel, pyrantel embonate and praziquantel remained infected; the geometric mean worm burden was reduced by 99.4% as compared to the control group but did not differ significantly from those of the controls.     

Efficacy of a combination of febantel, pyrantel, and praziquantel for the treatment of kittens experimentally infected with Giardia species

This study evaluated the effect of two combination products containing febantel, pyrantel, and praziquantel (FPP) for the treatment of Giardia species in experimentally infected kittens. In experiment 1, five kittens were administered the United States (US) formulation of FPP at doses of 37.8 mg/kg, 7.56 mg/kg, and 7.56 mg/kg, respectively, PO, q24h, for 5 days and four kittens remained as controls. In experiment 2, five kittens were administered the European formulation of FPP at the doses of 12.5 mg/kg, 12 mg/kg, and 4.16 mg/kg, respectively, PO, q24h, for 5 days and four kittens remained as controls. In experiment 3, six kittens were administered the US formulation of FPP at 56.5 mg/kg, 11.3 mg/kg, 11.3 mg/kg, respectively, PO, q24h, for 5 days and five kittens remained as controls. Thirteen days after treatment, kittens testing negative for Giardia species cysts were administered 20 mg/kg methylprednisolone acetate, IM, weekly for a maximum of two injections. Feces were analyzed for Giardia species cysts using a direct immunofluorescence test. After experiment 3, four of the six treated kittens, but no control kittens, remained negative for Giardia species after the administration of methylprednisolone acetate.     

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.     

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.     

Anthelmintic efficacy of febantel combined with praziquantel in dogs

Ninety-four dogs were randomly assigned to 1 of 6 groups (5 treated and 1 untreated control) for evaluation of anthelmintic efficacy. Three anthelmintic formulations were studied: a febantel paste, a praziquantel paste, and a combination paste containing both active ingredients. Treated dogs were dosed once daily for 3 days. The minimal effective dosages in combination were established as 10 mg of febantel and 1 mg of praziquantel/kg of body weight. At those dosages for the combination, 99.5% to 100% of the major nematodes and cestodes identified (ie, Ancylostoma caninum, Trichuris vulpis, Toxocara canis, Dipylidium caninum, and Taenia pisiformis) were eliminated. Febantel paste (10 mg/kg) alone was ineffective against cestodes (14.2% elimination of Dipylidium caninum) and praziquantel paste (1 mg/kg) alone was ineffective (0% to 2.4% elimination) against nematodes.     

Efficacy of a combined paste formulation of praziquantel/febantel against immature Echinococcus granulosus and immature Echinococcus multilocularis

A combined paste formulation of praziquantel (1 mg/kg of body wt)/febantel (10 mg/kg) given for 3 consecutive days gave 100% clearance of immature Echinococcus granulosus and E multilocularis in experimentally infected dogs. The formulation was extremely convenient to administer. Adverse reactions were not noted in the treated animals.     

Evaluation of praziquantel against induced Nanophyetus salmincola infections in coyotes and dogs

Efficacy of praziquantel against Nanophyetus salmincola, the trematode vector of salmon poisoning disease, was determined in coyotes (n = 29) and dogs (n = 25). The 10- to 14-week-old animals were fed fish or fish kidneys that contained metacercariae of N salmincola. To prevent salmon poisoning disease, all animals were treated with tetracycline on days 8 and 9 after they were fed fish. Ten days after ingestion of infected fish, 19 coyotes and 12 dogs were treated once with praziquantel, administered SC or IM, at dosages between 6.68 and 38.73 mg/kg of body weight. Within 8 days after treatment, the numbers of trematode eggs in feces and trematodes recovered from the small intestine were reduced by greater than 99% when compared with untreated controls. Signs of drug toxicosis were not observed. On the basis of these results, praziquantel at doses approved for use in dogs against cestodes was highly effective against N salmincola in coyotes and dogs.     

Field efficacy of ivermectin, fenbendazole and pyrantel embonate paste anthelmintics in horses

Three anthelmintic pastes were compared in terms of their ability to suppress the output of parasite eggs in the faeces of 108 grazing horses at four sites in Britain; the horses were treated once with either ivermectin, fenbendazole or pyrantel. At each site, the horses grazed together throughout the trials which took place during the summers of 1985 and 1986. The median periods before parasite eggs reappeared in faeces were 70 days for ivermectin, 14 days for fenbendazole and 39 days for pyrantel embonate. Geometric mean faecal egg counts in the groups treated with ivermectin and pyrantel were significantly less (P less than 0.05) than in the fenbendazole group on days 21, 28, 35 and 42 after treatment. On days 49, 56, 63 and 70 the mean egg counts in the ivermectin group were significantly lower (P less than 0.05) than those in either of the other groups. The results indicated that in order to ensure minimal contamination of pastures, grazing horses treated with ivermectin paste would have required a second treatment approximately 10 weeks after the first, and to achieve similar control with fenbendazole or pyrantel embonate, a second treatment would have been required after approximately two weeks and six weeks, respectively.     

Evaluation of a beef-based chewable formulation of pyrantel pamoate against induced and natural infections of hookworms and ascarids in dogs.

Pyrantel pamoate, formulated in a beef-based chewable tablet, was evaluated for efficacy in dogs against induced and natural infections of Toxocara canis, Toxascaris leonina, Ancylostoma caninum and Uncinaria stenocephala. Dose titration trials were conducted in Canada, the UK and Germany in dogs treated with pyrantel (as pamoate salt) at 0, 2.5, 5 or 10 mg kg-1 body weight. These studies showed that a dose rate of 2.5 mg kg-1, the efficacy of pyrantel against adult T. canis, T. leonina, U. stenocephala and A. caninum was 76.1, 85.6, 100 and 87.9%, respectively. Efficacy at 5 mg kg-1 against the same parasites was 94.2, 92.0, 93.5 and 93.8%, respectively, and at 10 mg kg-1 efficacy was 91.2, 97.6, 98.7 and 91.3%, respectively. No adverse effects due to treatment were seen in any of these trials.     

Comparative efficacies of ivermectin, febantel, fenbendazole, and mebendazole against helminth parasites of gray foxes

Anthelmintic efficacies of ivermectin, febantel, fenbendazole, and mebendazole were compared in 45 adult gray foxes (Urocyon cinereoargenteus) naturally infected with helminth parasites. Fecal specimens were examined one week before treatment and one week and 3 weeks after treatment with each anthelmintic, using a sucrose flotation technique. Compared with pretreatment, fewer foxes in all groups were infected with helminths one week and 3 weeks after treatment. Ivermectin, febantel, and fenbendazole more effectively eliminated helminths than did mebendazole. Parasites found were Ancylostoma sp, Capillaria aerophila, and Aelurostrongylus abstrusus and/or Filaroides osleri.     

Efficacy of febantel against abomasal nematodes and lungworms in cattle

The efficacy of febantel at a dosage of 5 mg/kg (45.5% paste formulation) against inhibited early 4th-stage larvae (EL4) of Ostertagia ostertagi, other nematodes of the abomasum, and Dictyocaulus viviparus was investigated in 4- to 6-month-old Holstein calves that grazed on pasture heavily contaminated with parasites from February 24 to April 1, 1986 (36 days). In Louisiana, this is the first month of a 3-month period in which increasing numbers of inhibition-prone O ostertagi larvae are acquired, and infection risk with D viviparus may remain high. Three of 4 calves that died of lungworm infection during the pasture-exposure period were necropsied. Large numbers of abomasal nematodes, including inhibited O ostertagi larvae, and large numbers of D viviparus were recovered. Twenty-five calves were randomly allotted by equal distribution of body weight to 2 groups and treated on April 4: placebo-treated calves (n = 13) and febantel-treated calves (n = 12). Equal numbers of treated and control calves were killed at 6 and 7 days, respectively, after treatment. Mean numbers of O ostertagi in control cattle were: adults, 4,931; developing 4th-stage larvae (DL4), 1,119; and inhibited EL4, 3,410. Ostertagia lyrata, Trichostrongylus axei, Haemonchus sp, and D viviparus were well distributed in nearly all control calves. Percentage reduction of O ostertagi in treated calves, when compared with controls, was: adults, 83.6%; DL4, 57.8%; and inhibited EL4, 34.8%. Percentage reductions of other species were: O lyrata, 92.6%; T axei adults, 99.3% and 4th-stage larvae (L4), 100%; Haemonchus sp adults, 66.7%, and L4, 64%; D viviparus adults 90.6%, and immature forms, 97.1%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of epsiprantel against Echinococcus granulosus infections in dogs

Dogs with 41-day-old experimental infections of Echinococcus granulosus were treated orally with epsiprantel. Single doses of 2.5 mg kg-1, 5.0 mg kg-1 or 7.5 mg kg-1 were effective in removing more than 99 per cent of these parasites, but total clearances of worms only occurred in dogs given the highest dose.     

Comparison of febantel tablets and Vercom paste against gastrointestinal nematodes of dogs.

Thirty adult dogs with naturally acquired gastrointestinal nematode infections were assigned at random to ten replicates and treated daily for 3 days with either a combination febantel/praziquantel (Vercom) paste, febantel tablets or placebo tablets. Numbers of hookworm and whipworm eggs after treatment were reduced similarly for both drug formulations when compared with pretreatment egg counts, whereas these counts increased in the controls. Vercom paste reduced the hookworm egg count by 99.9% and the whipworm egg count by 99.6%. The febantel tablet decreased the hookworm egg count by 99.9% and the whipworm egg count by 100%. As determined at necropsy, the controlled test efficacy against adult hookworms and whipworms was similar for the Vercom paste and the febantel tablets. The controlled test efficacies of Vercom paste against Ancylostoma caninum, Ancylostoma braziliense, and Trichuris vulpis were, respectively, 99.7%, 100% and 95.8% and those of febantel tablets were 98.2%, 100% and 99.7%. These results indicate that the nematocidal efficacy of febantel against these nematodes remains unchanged in these two formulations. No adverse reactions to either febantel tablets or to Vercom paste were observed.     

Evaluation of the efficacy of an epsiprantel/pyrantel combination against gastrointestinal helminths of dogs

Trials were conducted to evaluate the anthelmintic effect of a combination of epsiprantel at a dose rate of 5-5 mg/kg bodyweight and pyrantel pamoate at 5 mg pyrantel base/kg against Toxocara canis in prenatally infected unweaned greyhound pups, Toxascaris leonina, Uncinaria stenocephala, Trichuris vulpis and Dipylidium caninum in naturally infected adolescent greyhounds and Ancylostoma caninum, U stenocephala. Taenia hydatigena and Taenia pisiformis in artificially infected laboratory beagles. The product was well accepted and produced no obvious side effects. Percentage efficacy values based on post mortem worm counts were: T hydatigena 100; T pisiformis 100; D caninum 100; adult T canis 84-0; adult T leonina 96-5; immature T leonina 99-8; U stenocephala 99-0 and 87-7; A caninum 92-7; and T vulpis 43-3.     

Comparison of anthelmintic activity of pyrantel, praziquantel, and nitazoxanide against Anoplocephala perfoliata in Horses

Three anthelmintics were compared for efficacy in reducing the egg production of Anoplocephala perfoliata in a herd of central Texas horses. Two trials were run, 1 in mares and the other in weanlings that were diagnosed as being infected with Anoplocephala by recovery of eggs in 5 g of feces with sugar centrifugation. Each animal was evaluated twice before treatment and again twice following treatment (at weeks 2 and 4 after treatment). The criteria for infection were the recovery of eggs on at least 1 occasion before treatment and the finding of eggs on 1 day following treatment. The mares were treated 1 time with either pyrantel pamoate at 13.2 mg/kg, nitazoxanide at 100 mg/kg, praziquantel at 1.23 mg/kg or remained as untreated controls. The weanlings were treated with pyrantel at 13.7 mg/kg nitazoxanide at 100 mg/kg or remained as untreated controls. The percentage reduction of patient infection in mares after treatment with pyrantel was 83%, with nitazoxanide was 78%, and with praziquantel was 83% and in controls was 17%. There was a 75% reduction of patient weanlings treated with pyrantel or nitazoxanide and a 17% reduction in untreated controls. The reduction of infection in all horses treated with any drug was significantly different from controls. All of the drugs were somewhat effective in the control of Anoplocephala, and there were no differences among the drugs in their effectiveness.

Introduction

Anoplocephala perfoliata, the lappeted tapeworm, is an inhabitant of the intestine of equids. Adult tapeworms attach to the intestinal mucosa at the ileocaecal valve and, when present in large numbers, cause edema and hypertrophy of the ileum. The disease manifest by this infection may be inapparent or may give rise to colic (abdominal pain) in the horse apparently from mechanical obstruction or intussusception of the small intestine into the caecocolon.^{1, 2, 3, 4, 5, 6, 7 and 8} The prevalence of infection is geographically variable^{9, 10, 11, 12 and 13} but appears to be increasing,¹⁴ with a much higher rate of infection found with necropsy as opposed to fecal observations. Horses become infected by the ingestion of infected orbatid mites in pastures. Orbatid mites, the intermediate hosts, are predatory and are found in decaying organic material, such as leaf litter. Horses of all ages are infected, but there are lower numbers of clinical cases in horses older than 4 years of age.⁴ The intensity of infection is highest in the late summer and autumn.^{8 and 12} Anthelmintics with reported efficacy against A perfoliata include pyrantel pamoate at 13.2 mg/kg,¹⁰ pyrantel tartrate at 2.6 mg/kg for 30 days,¹⁵ pyrantel embonate at 38 mg/kg,¹⁶ and praziquantel at 1 to 2 mg/kg.^{17 and 18} Nitazoxanide has not been evaluated for Anoplocephala but was included in the trial because of its effects against nematodes and tapeworms in humans.¹⁹ Because Anoplocephala infections may cause disease and there is a perception that current anthelmintics may not be as effective as in the past, a study was done to compare anthelmintics to lower the intensity of fecal egg counts in a herd of horses in central Texas.

Materials and methods

Quarter horse mares and weanlings from a single herd were evaluated with 5 g of feces with a sucrose double centrifugation test to determine whether eggs of Anoplocephala were present.²⁰ Feces from each individual horse were evaluated twice, once approximately 2 weeks before treatment and again on the day of treatment. If Anoplocephala eggs were found on either date, the horse was considered to have positive results. Within each group (mares or weanlings), the treatment selection was randomly allocated as the horses were restrained for treatment. Fecal samples were again evaluated at 14 and 28 days after treatment for the presence or absence of eggs on either day.The dose for each individual horse was determined by chest girth weight tape at the time of treatment. The treatments were as follows: pyrantel pamoate (Strongid-T, Pfizer Animal Health, Exton, Pa) at 13.7 mg/kg via nasogastric intubation (12 mares, 8 weanlings), nitazoxanide oral paste (Nitazoxanide, Idexx Laboratories, Westbrook, Me) at 100 mg/kg (9 mares, 8 weanlings), praziquantel (Droncet injectable, Bayer Corp, Shawnee Mission, Kan) at 1.23 mg/kg via nasogastric intubation (6 mares), and untreated controls (6 mares, 6 weanlings). A 1-tailed Fisher exact test was used to compare rates of infection before and after treatment. If a mare or foal did not have positive results before treatment, it was not evaluated in this study.

Results and discussion

No abnormal clinical signs were seen after treatment with any of the products. Treatment was administered to several additional animals with each product, but they were not included in the analysis if they did not have positive results on 1 of the 2 evaluations before treatment, hence, the different numbers of horses in treatment groups.None of the horses in the trial exhibited clinical signs associated with the infection of A perfoliata. However, before the trial, a mare from the infected herd exhibited signs of colic and Anoplocephala eggs were detected in the feces. Examination of the remainder of the herd gave impetus to the study.Mean egg counts before and after treatment are given in the Table.The presence of strongylate and Parascaris eggs in weanlings served as a control of the methodology of evaluation. The difficulty of finding Anoplocephala eggs has been recognized by several authors,^{5, 8, 13, 14 and 21} but the authors also recognize that when there were greater numbers of parasites there was increased egg production. Therefore, finding of eggs with fecal flotation indicated that there were 20 worms or more. However, there appears to be no correlation between the number of worms and egg counts once the detection threshold is reached,²² so the criterion for evaluation was the presence of eggs in the feces before treatment compared with after treatment. Although mean egg counts were not compared, the number of eggs in each infected horse was less after treatment in all groups compared with untreated controls (Table). The method of evaluation used in this study cannot be equated to those of critical^{10 and 16} or control¹⁴ studies in which horses are killed so that all worms are detected. However, the use of clinical studies to compare compounds is useful in detecting which anthelmintics are likely to be of value against geographically distinct populations of worms. Admittedly, more sampling may have increased the number of horses with positive results, both before and after treatment.