BACKGROUND: During the last two decades, anthelmintic drugs have been increasingly applied against gastrointestinal parasites of sheep in Iran. OBJECTIVES: For this purpose, drug resistance to albendazole (Alb) and fenbendazole (Feb) in gastrointestinal nematodes in sheep of Saqez multiplicity was assessed. METHODS: In in-vivo experiment, a total number of 90 sheep in three groups (30 sheep/group) with EPG≤150 were examined for nematode resistance to Alb and Feb. They were treated with Alb and Feb or untreated (as a control group). RESULTS: There was significant difference between Alb and Feb treated groups and control group. The EPG in Alb, Feb and control groups was 59.8±1.93, 18.8±1.258 and 204.07±4.81, respectively. There was drug resistance against Alb in compassion with control group (R=71%). There was suspicion drug resistance for Feb in comparison with control group (R=90.66%). CONCLUSIONS: From the results of the present study, it was concluded that there was absolute and suspected drug resistance against Alb and Feb in sheep of Saqez municipality, Iran, respectively.

Fenbendazole (FBZ) is a benzimidazole anthelmintic widely used to treat parasitic infections. The anticancer effect of FBZ has been recently highlighted leading to its consideration as a potential anticancer agent. Although previous studies have demonstrated the effect of FBZ on cancer cells, there is a paucity of studies on the effect of FBZ on lymphoma cells and normal immune cells. Herein, we investigated the effects of FBZ on a mouse lymphoma cell line, EL-4 cells, and spleen cells, using vincristine as a positive control. The cellular metabolic activity of EL-4 cells was decreased by FBZ, but that of the spleen cells was not decreased. Moreover, FBZ reduced the mitochondrial membrane potential and induced reactive oxygen species production in EL-4 cells, but not in spleen cells. FBZ induced G2/M phase arrest and increased the sub G0/G1 phase ratio, indicating apoptosis. Furthermore, compared to the control cells, the reactivity of spleen cells pretreated with FBZ to lipopolysaccharide was maintained. In summary, FBZ is cytotoxic to EL-4 cells, but not to spleen cells. This study provides experimental evidence that FBZ exerts an anticancer effect, and less cytotoxic effects and functional damage to normal spleen cells.

Nematodes resistant to anthelmintics are of increasing concern to sheep farms in Malaysia. Thus to ascertain the degree of anthelmintic resistance in the sheep population, faecal egg count reduction (FECR) trials were conducted on sheep in the Veterinary Institute, Kluang. A total of 60 weaned sheep were selected and divided into six (6) equivalent groups. Group A was treated with ivermectin, Group B with Closantel, Group C with Fenbendazole, Group D with Levamisole, Group E with Cydectin and the remaining 10 were untreated controls. Faecal samples were collected from each sheep before treatment and repeated on day 14, 30, 45 and 60 post treatment. The worm egg counts were estimated by using McMaster’s method. The population of worm was classified as resistant if the adjusted percentage reduction was less than 90%. It is concluded that only levamisole can be used for helminthiasis control. The results showed that worms at the Sheep Unit of the Veterinary Institute, Kluang was suspected to be resistant to Ivermectin, Closantel and Cydectin. The worm population showed total resistance to fenbendazole. The strongyle population is mainly made up of 80% Haemonchus contortus and 20% of species were Oesophagostomum and Bunostomum.

Ten controlled tests were done between 1972 and 1989, in lambs on pasture, evaluating activity of fenbendazole (FBZ; 5 mg/kg of body weight), oxfendazole (OFZ; 3.5 and 10 mg/kg), oxibendazole (OBZ; 10 mg/kg), pyrantel pamoate (PRT; 25 mg of base/kg), and thiabendazole (TBZ; 44 and 50 mg/kg) against natural infections of helminths, with emphasis on 2 strains (A and B) of Haemonchus contortus. Strain A was phenothiazine-susceptible and strain B was phenothiazine-resistant when isolated in 1955. For approximately 10 years prior to these tests, sheep infected with both strains had been treated periodically each year with several compounds, including thiabendazole, which was used many more times than the other drugs. For this study, 4 (FBZ, OFZ, OBZ, and PRT) of the 5 compounds were evaluated in either 1 or 2 controlled tests. The fifth compound, TBZ, was used for 5 tests. Strain A H contortus was resistant to TBZ for all years tested, but more susceptible to FBZ, OFZ, OBZ, and PRT. Overall, strain B was susceptible to TBZ (with a few exceptions), and also to FBZ, OFZ, OBZ (activity less on immature forms), and PRT. Other abomasal parasites (2 species of Ostertagia and 3 of Trichostrongylus) were found in low numbers, but removal overall was good for the compounds tested. Trichostrongylus axei, found in higher numbers than species of Ostertagia and other species of Trichostrongylus, were effectively removed by all compounds in most cases. Activities of TBZ and PRT were also evaluated against several species of intestinal helminths, most of which were found in low numbers. Cooperia curticei were inconsistently removed by TBZ, but activity of PRT was effective. Both compounds were active on mature Nematodirus spathiger, but TBZ had variable activity on immature forms. Strongyloides papillosus were effectively removed by TBZ. Other parasites found in lower numbers than the aforementioned 3 species were Capillaria spp, Trichuris spp, and Oesophagostomum columbianum; removal was variable for both drugs.

fenbendazole safety tested in pigs, significant gross or histopathologic lesions not found

Strongylus spp. and other parasites of equids (natural infections), controlled tests with fenbendazole in multiple doses at two dose levels

Change in β-tubulin nucleic acid and protein sequences was the only known difference between Haemonchus contortus fenbendazole (FBZ)-resistant and -susceptible isolates. This change was sufficient to determine the pathologic effect induced by FBZ treatment. This research was initiated to investigate further differences from these two isolates. Since β-tubulin is involved in formation of microtubule, which has functions in secretory vesicle transport, DNase activities from excretory/secretory products (ESP) of the two isolates were compared, based on pH, sensitivity to DNase inhibitors, molecular masses and production of 3'-OH.

Antiparasitic activity of several compounds was evaluated over a long period (about 25 years) in the same flock of sheep. Haemonchus contortus was of special interest, including its relation to drug resistance, especially to thiabendazole and other benzimidazoles, in addition to phenothiazine. Eleven compounds were evaluated in 15 controlled tests, done between 1966 and 1989 in naturally infected lambs (n = 145) born and raised on the same pasture. Sheep were first placed on the pasture in 1962, and a few more were added thereafter. Internal parasites in these sheep were classified in 3 general categories: indeterminate exposure to parasiticides; H contortus, resistant to thiabendazole; and H contortus, resistant to phenothiazine. The parasitic infections probably became more homogeneous after several years because of few introductions of outside sheep after initial establishment of the flock. Activity against naturally acquired internal helminths was evaluated for cambendazole (CBZ: dosage, 20 mg/kg of body weight), fenbendazole (FBZ: 5 or 7.5 mg/kg), mebendazole (MBZ: 10 mg/kg); oxfendazole (OFZ: 3.5 or 10 mg/kg), oxibendazole (OBZ: 10 mg/kg); parbendazole (PBZ: 15 mg/kg), phenothiazine (PTZ: 550 mg/kg); pyrantel pamoate (PRT: 25 mg base/kg), tetramizole (TET: 15 mg/kg); thiabendazole (TBZ: 30 or 44 mg/kg), and trichlorfon (TCF: 100 mg/kg). Thiabendazole was used more often (9 tests) than the other compounds. Thiabendazole was more active against mature H contortus in later years than when first used in 1966, although it was never 100% effective. Efficacy against immature H contortus for TBZ did not exceed 86%. Activity against immature and mature stages of this parasite was good overall for the other benzimidazoles. Results indicated no definite side resistance of non-TBZ benzimidazoles for this species. Removal of both stages of H contortus was generally low for PTZ. For the other nonbenzimidazoles (PRT, TET, and TCF), efficacy against immature and mature H contortus was 93 to 100%, except for 1 test with PRT (79% on mature worms) and 1 with TCF (77% on immature worms). With regard to other abomasal parasites, activity for the compounds tested against 2 species of Ostertagia was greater than or equal to 97%, with 1 exception; numbers of these parasites in nontreated lambs were less than numbers of H contortus. All compounds, except PTZ and TCF, were effective against a third species, Trichostrongylus axei. Activity against several species of intestinal parasites, most present in low numbers, was determined for 5 compounds (TCF, TBZ, CBZ, PTZ, and PRT) in 5 rests. Thiabendazole, CBZ, and PRT were highly effective against trichostrongylus, with a few exceptions. Trichlorfon and PTZ had overall less activity against trichostrongylus than did the other products. Against trichurids, PRT and TCF were highly efficacious.

To test the effect of a parasite control program for cattle, 2 groups of similar composition were grazed on separate, but equivalent, improved pastures. Cattle in 1 group were treated with fenbendazole at 5.0 mg/kg of body weight at the time they were turned out on pasture in the spring and again at midsummer, when the cattle were moved to a new pasture. The control group was not treated. Parasite egg counts were significantly (P < 0.04) lower in the treated group. Trichostrongyle-type eggs were the most prevalent throughout the, year, except in the month of May, when Strongyloides papillosus eggs were predominant. The number of worms recovered from tracer calves was lower for those on pastures where the treated group grazed than for those on- the control group's pasture. The most consistently recovered parasite was Ostertagia ostertagi, and hypobiosis was observed.

Anthelmintic efficacies of fenbendazole, ivermectin, and levamisole were evaluated against naturally acquired infections of Nematodirus battus in lambs. Four groups of 10 lambs each were used. Oral administration of 8 mg of levamisole/kg of body weight or 5 mg of fenbendazole/kg significantly (P < 0.01) reduced the degree of infection by N battus (adults) by > 99%. An oral formulation of 200 microgram of ivermectin/kg was 98% effective (P < 0.01). Numbers of other Nematodirus spp (including N filicolis and N spathiger) were significantly reduced.