Safety of albendazole in developing bovine fetuses.

Albendazole, administered orally at a dose rate of 25 mg/kg of body weight to presumed pregnant cows or heifers on days 21, 31, 41, 51, and 61 of gestation, did not induce toxicosis in embryos or fetuses, and all calves born were structurally normal. Albendazole administration at a rate of 25 mg/kg to cows at 7 and/or 14 days of gestation decreased the apparent conception rate (ie, embryolethality), but did not have a teratogenic effect. Apparent embryolethality was greater in cows administered 25 mg/kg only on day 14, compared with those administered the drug only on day 7. Single dosage of 25 mg/kg given in the final 3 months of gestation did not induce abortion. There were no adverse effects of albendazole at a dosage of 10 or 15 mg/kg on developing embryos or fetuses when administered to presumed pregnant cows at various times in early gestation.

The metabolism of benzimidazole anthelmintics.

The benzimidazole carbamates are important broad-spectrum drugs for the control of helminth parasites in mammals. David Gottschall, Vassilios Theodorides and Richard Wang explain that the metabolism of these compounds depends heavily on the substituent present on carbon-5 of the benzimidazole nucleus and involves a wide variety of reactions. Work in vitro has shown that two major enzyme systems, the cytochrome P-450 family and the microsomal flavin monooxygenases are primarily responsible for these biotransformations. The parent compound is generally short-lived and its metabolites predominate in the tissues and excreta of treated animals. The metabolic pathways can be exploited therapeutically to overcome the problems of poor water solubility and adsorbtion of benzimidazoles by the development and use of more soluble prodrugs.

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of anthelmintics in swine.

As a follow-up to a previous guideline publication on efficacy evaluation of anthelmintics in ruminants, an expert group of the World Association for the Advancement of Veterinary Parasitology presents similar guidelines for the testing of anthelmintics in swine. The goal of the guidelines is to develop uniform testing standards and registration requirements. Data obtained from investigations according to the guidelines should be internationally accepted in the registering of drugs. Further, the use of the guidelines may contribute towards reducing costs, labor and the number of experimental animals used for drug testing.

In vitro delayed hypersensitivity granuloma formation: development of an antigen-coated bead model.

Previously, we have described an in vitro model of granulomatous hypersensitivity around Schistosoma mansoni eggs in both the murine model of schistosomiasis and in human schistosomiasis. These studies describe a new model of in vitro granuloma formation that complexes soluble egg antigen from S. mansoni eggs, a partially purified protein derivative of Mycobacterium tuberculosis (PPD), or bovine serum albumin to carrier beads. Ultrastructural and morphologic evaluations demonstrate that there are initial macrophage interactions, followed by the recruitment of antigen-specific T cells that interact with and recruit macrophages, lymphocytes, granulocytes, and fibroblasts. Finally, there is a stage of granulomatous organization involving fibroblast proliferation and collagen deposition. The in vitro reactivity, defined by a quantitative granuloma index, correlates with in vivo granulomas around S. mansoni eggs in the livers of infected cell donor animals. In vitro granuloma formation against PPD-coated beads correlated with delayed cutaneous hypersensitivity against PPD, which was judged by footpad swelling. The reactions demonstrate antigenic specificity and were intrinsically modulated in a manner that is analogous to that previously shown with the in vitro egg granuloma model. This model of in vitro granuloma formation promises to be a useful tool for elucidating mechanisms of cellular immunity and regulation.

Equine verminous arteritis; efficiency and speed of larvicidal acitivty as influenced by dosage of albendazole.

Albendazole was effective in destroying Strongylus vulgaris larvae in verminous lesions of the cranial mesenteric artery when administered as a 20% suspension by stomach tube to ponies. Fifty mg/kg body weight administered twice a day for 2 days caused death and gradual disintegration of larvae over a period of 3 to 6 weeks with mild toxic signs appearing in 3 of 11 ponies. Higher total doses of albendazole (50 mg/kg twice a day for 4 days and 25 mg/kg three times a day for 5 days) lead to more rapid disintegration of the larvae but fatal toxicity was observed in 3 of 6 ponies so treated. In all cases, resolution of verminous arterial lesions was delayed until larva remains had disappeared from the lesions. A non-parametric analysis was applied to combined radiographic, pathologic and parasitologic observations and data for testing their statistical significance

Efficacy of albendazole against Fasciola hepatica in cattle.

Albendazole in drench formulation was administered to calves 16 weeks after infection with 400 metacercariae of Fasciola hepatica. In separate experiments, albendazole at dose levels of 10 or 15 mg/kg reduced the fluke burden by 92.84 per cent and 95.0 per cent, respectively. In another experiment, a dose level of 7.5 mg/kg given once, twice with a two-week interval, or twice with a three-week interval reduced the mean fluke burden by 43.75 per cent, 72.29 per cent and 90 per cent, respectively.

Equine verminous arteritis. An arteriographic evaluation of the larvicidal activity of albendazole.

Albendazole was an effective larvicidal anthelmintic against the fourth stage Strongylus vulgaris larvae as late as one month post-infection. The drug was administered at a dose rate of 25 mg/kg three times daily for 5 days. Diarrhoea occurred in 3 of 4 foals treated and of these one died during belated intravenous therapy for dehydration. Arteriography allowed for an in vivo assessment of the development and regression of lesions in infected-treated foals compared to the continued development of lesions in infected-untreated foals. The arteriographic findings were confirmed at necropsy.

Transmission and control of Filaroides hirthi lungworm infection in dogs.

Transmission of Filaroides hirthi among cagemate pups was demonstrated to occur through the ingestion of first-stage larvae in recently passed feces. It was suggested that coprophagia is the principal mechanism of transmission of F hirthi and that transmission from brood bitches to their litters occurs by this mechanism during and after the fourth or fifth week of the nursing period. Medication of 15 infected brood bitches with two courses of albendazole at a dosage rate of 50 mg/kg of body weight twice each day for 5 days resulted in complete absence of F hirthi infection among all 21 of their progeny, whereas 16 of 19 progeny (84%) from 14 nontreated infected dams harbored F hirthi worms.

Effect of albendazole on the metacestodes of Taenia saginata in calves.

Albendazole, a benzimadazole-carbamate anthelmintic, has been shown to effectively cause destruction of the metacestodes of Taenia saginata in calves.

Anthelmintic activity of albendazole against Filaroides hirthi lungworms in dogs.

Albendazole given at a dosage rate of 25 to 50 mg/kg twice daily for 5 days killed all but a small proportion and sterilized the few surviving Filaroides hirthi worms in artificially infected Beagle pups. Extensive tissue reaction around the dead worms persisted for an undetermined length of time. However, albendazole treatment of mature stock should prove useful in preventing transmission of F hirthi infection to their offspring and thus provide an efficient means of control.

Toxicologic and teratologic studies of oxibendazole in ruminants and laboratory animals.

Acute toxicity of oxibendazole was assessed with single oral doses given to mice (4 to 32 g/kg of body weight), sheep (230 to 600 mg/kg), and cattle (600 mg/kg); there were no ill effects. Subacute toxicity did not occur with multiple doses given 5 days to cattle (30 to 75 mg/kg/day) and to sheep (10 to 50 mg/kg/day). Chronic effects did not occur with daily doses of 3 to 30 mg/kg given 98 days to rats and dogs. Teratogenicity of the compound was studied in mice, rats, and sheep medicated at a dose level of 30 mg of oxibendazole/kg and in cattle given 75 mg/kg on selected dates during pregnancy. Microscopically, rodent fetuses seemed normal, and on gross physical examination, lambs and calves were free of malformations and ossification variations.

Efficacy of albendazole against Haemonchus, Nematodirus, Dictyocaulus, and Monieza of sheep.

Albendazole was highly efficacious in the removal of monospecific and mixed infection of Haemonchus contortus, Nematodirus spathiger, and Dictyocaulus filaria from sheep. A dose level of 5 mg/kg removed nearly all gastrointestinal nematodes, and 10 mg/kg removed all lungworms. Tapeworms of the genus Moniezia were completely removed by a dose level of 10 hg/kg.

Efficacy of albendazole against gastrointestinal nematodes of cattle.

Forty-five calves with artificial and pasture-acquired nematode infections were medicated with albendazole at dose levels of 0, 2.5, 5.0, or 10 mg/kg of body weight. A dose level of 2.5 mg/kg removed at least 99% of adult Trichostrongylus axei, Trichostrongylus colubriformis, Cooperia oncophora, and Bunostomum phlebotomum. Burdens of Haemonchus contortus, Strongyloides papillosus, and Ostertagia ostertagi were reduced 79, 88, and 97%, respectively. At a dose level of 5.0 mg/kg, at least 95% of all adult nematodes were removed; at 10 mg/kg, at least 97% were removed. At least 99% of 4th-stage larvae of O ostertagi, T axei, C oncophora and T colubriformis and 96% of H contortus were expelled at a dose level of 2.5 mg/kg. At 5.0 and 10 mg/kg, 99 to 100% of all species of larvae were removed. Trichuris spp adults were slightly susceptible at all dose levels; larvae were susceptible (83%) only at 10 mg/kg.

Efficacy of oxibendazole against gastrointestinal nematodes of cattle.

In 3 separate studies, oxibendazole in drench and premix formulation was shown efficacious against larvae and adults of the genera Haemonchus, Ostertagia, Trichostrongylus, Strongyloides, Nematodirus, Cooperia, Bunostomum, Capillaria, Oesophagostomum, and Trichuris. In the first study, artificially infected calves were cleared of virtually all histotrophic larvae and adult parasites after medication with oxibendazole drench at a dose level of 10 mg/kg of body weight. Smaller doses (7.5 and 5.0 mg/kg) expelled 84 to 100% of the parasites. Oxibendazole at a dose level of 15 mg/kg in premix form was given to artificially infected calves 3, 7, or 42 days after infection in a 2nd study. Third stage and 4th stage Cooperia oncophora larvae were, respectively, 92 and 98% susceptible to the drug at day 3 and day 7 after infection; neither larval stages of Ostertagia ostertagi and of Oesophagostomum radiatum were susceptible. Premix given on day 42 after infection removed 83 to 100% of adult O ostertagi, Nematodirus spp, C oncophora, O radiatum, and Trichuris spp. In a 3rd study, calves harboring a mixture of parasitic stages from artificial and pasture-acquired infections were medicated with oxibendazole at a dose of 15 mg/kg in premix form. The burdens of larvae from the abomasum and small intestines were reduced 93 to 95%, respectively; the burdens of adults of 11 species of worms were reduced 87 to 100%.