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 commonly used anthelmintic in veterinary medicine that has recently been found to have anticancer effects in humans. On the other hand, few studies have examined the anti-inflammatory effects of FBZ, and its mechanism is unknown. In this study, mouse bone marrow cells (BMs) were treated with lipopolysaccharide (LPS), a representative inflammation-inducing substance, to generate a situation similar to osteomyelitis in vitro. The effect of FBZ on inflammatory BMs was examined by measuring the metabolic activity, surface marker expression, cell nuclear morphology, and mitochondrial membrane potential (MMP) of BMs. FBZ decreased the metabolic activity and MMP of LPS-treated BMs. Annexin Ⅴ-fluorescein isothiocyanate/propidium iodide staining and Hoechst 33342 staining showed that FBZ reduced the number of viable cells and induced the cell death of inflammatory BMs. In addition, FBZ reduced the proportion of granulocytes more than B lymphocytes in LPS-treated BMs. Overall, FBZ induces cell death by destabilizing the MMP of LPS-induced inflammatory BMs. FBZ can play a role as an anthelmintic and anticancer agent and an anti-inflammatory agent.

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.

The possible development of type-1 hypersensitivity reactions in the abomasal mucosa caused by soluble L3 products of Ostertagia ostertagi was studied in 4-month-old calves sensitized by repeated exposure to L3 over a 50-day period followed by anthelmintic treatment. Four groups each of 4 calves were used. Group 1 served as nonsensitized controls and group 2 as sensitized controls, group 3 was challenge exposed at 2-week intervals beginning at week 10 with a soluble L3 product (OAG), and group 4 was challenge exposed at 2-week intervals with an oral dose of L3, followed by anthelmintic treatment 3 days later. All calves infected with L3 became sensitized, as indicated by a positive reaction to an intradermal skin test. However, a passive cutaneous anaphylaxis was only partly effective in indicating the presence of homocytotropic antibody in the infected calves. Sensitized calves had significantly (P < 0.05) higher eosinophil counts and plasma pepsinogen values for the entire 14 weeks than uninfected controls. Globule leukocyte and mast cell counts from the abomasal mucosa were also significantly (P < 0.05) higher. Studies for possible immunomodulation revealed that lymphocyte counts decreased between every 2-week challenge-exposure period for groups-3 and -4 calves. A transient depression of blood lymphocyte (BL) responses to phytohemagglutinin (PHA), a T-cell mitogen, was observed over the first 8 weeks in the infected calves. Increases in BL responses to OAG were also observed. Differences were not observed in BL responses to pokeweed mitogen, a T- and B-cell mitogen. Blood lymphocyte responses to PHA in group-3 calves were low following the initial challenge exposure with OAG. The sensitized calf lymphocytes did not have suppressive activity on the response of control calf lymphocytes to PHA. Differences were not observed in lymphocyte responses to PHA in a suppressive assay done on abomasal lymph node lymphocytes. Increases in abomasal lymph node mass and lymphocyte responses to PHA, pokeweed mitogen, and OAG were observed in all sensitized calves. Histologic examination of abomasal lymph node sections from challenge-exposed calves revealed increased mitotic activity in germinal centers. Plasma pepsinogen values in groups 3 and 4 increased between each challenge exposure, which further suggested that type-1 hypersensitivity reactions had occurred in the abomasal mucosa, resulting in increased permeability and leakage of macromolecules.

Bunostomum phlebotomum experimental infection of beef calves superimposed upon naturally occurring gastrointestinal nematode infections, fenbendazole anthelmintic efficacy tested

Strongylus vulgaris, pony foals (nat. and exper.), effectiveness of fenbendazole against later fourth stage larvae assessed by larval motility and studies of cranial mesenteric, ileocolic, and celiac arteries

Efficacy of fenbendazole at 2 dosages for treating naturally acquired giardiasis in dogs was assessed. Giardia cysts were not detected in the feces of 6 of 6 group-1 dogs (as determined by use of the zinc sulfate concentration technique) after fenbendazole treatment (50 mg/kg of body weight, PO, q 24 h, for 3 doses). Cysts were not detected in the feces of 6 of 6 group-2 dogs after fenbendazole treatment (50 mg/ kg of body weight, PO, q 8 h, for 3 days). However, cysts were not detected in the feces of only 1 of 6 group-3 (nontreated control) dogs. Signs of toxicosis were not observed in any dog. These results indicate that the current label dosage (for the treatment of Toxocara canis, Toxascaris leonina, Ancylostoma caninum, Uncinaria stenocephala, Trichuris vulpis, and Taenia pisiformis, but not Giardia spp) of fenbendazole (50 mg/kg, PO, q 24 h, for 3 doses) is also effective for treating giardiasis in dogs.

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.

The efficacy, safety, and compatibility of fenbendazole (FBZ) and clorsulon (CLN) were tested after oral administration of label recommended and of higher (5 x) dosage rates to calves naturally infected with gastrointestinal nematodes and Fasciola hepatica. Results for 42 calves allotted to 4 treatment groups indicated a similar efficacy against mature F hepatica by FBZ (5 mg/kg of body weight) and CLN (7 mg/kg) in a combined oral suspension, compared with CLN (7 mg/kg) alone (100 vs 99% reduction). A lesser efficacy was observed against immature flukes (88.6 and 84.9% reduction, respectively). Calves given 25 mg of FBZ/kg and 35 mg of CLN/kg had nearly complete reduction of both mature (99.6%) and immature flukes (99.1%). Fasciola egg counts were reduced by > 99.5% in all treated groups. Against Ostertagia ostertagi, the percentage of efficacy of the combined FBZ (5 mg/kg) and CLN (7 mg/kg) treatment was 94.3% against adults and 81.3% against inhibited larvae. Efficacy against all other nematodes was 100%, except against Cooperia spp adults (98.3%) and immature Oesaphagostomum radiatum (88.0%). At 5 x dosage rates for FBZ and CLN, percentage of removal of adults and inhibited larvae of O ostertagi was 99.3 and 99.0%, respectively, and 99 to 100% for other nematodes. Results indicate that FBZ and CLN are compatible when mixed together and administered as an oral suspension to cattle and that the efficacy is similar to that of the drugs individually. On the basis of further results, we suggest that summer treatment may be superior in preventive value for gastrointestinal nematodes and F hepatica, compared with spring treatment, because of seasonal infection dynamics of the major cattle parasites in Louisiana.