Effects of the benzimidazole anthelmintics on murine toxocariasis
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Description
A specific therapy for visceral larva migrans is not yet available. Although thiabendazole is being used in the treatment of human and animal infections with Toxocara canis, there is no evidence that it has a specific anthelmintic action against the larvae. Treatment of human toxocariasis with thiabendazole is reported to produce clinical improvement, however, this is apparently due to a non-specific effect of the drug and this action is not fully understood. Structural modifications of the thiabendazole molecule have produced a new class of anthelmintics: the benzimidazoles. These compounds have not yet been evaluated under standard conditions for their effects on toxocariasis. The aim of the present study was to assess the specific and non-specific effects of the benzimidazole anthelmintics on toxocariasis, taking murine toxocariasis as a model. Using thiabendazole as a prototype for the newer benzimidazole anthelmintics, its effects on murine toxocariasis were studied in more detail. Screening of the newer benzimidazoles was then done on the basis of the findings with thiabendazole. The effects of thiabendazole on the survival and the migratory behavior of T. canis larvae in mice were studied. Larval migration was assessed in relation to the dose level of thiabendazole, the method of administration of the drug, the duration of treatment and the route of inoculation of the infective eggs. The effect of thiabendazole on the histopathology of toxocariasis was studied in mice treated with thiabendazole during the migratory phase of infection. Peripheral blood eosinophilia was followed in treated and untreated mice that were infected with T. canis eggs by oral inoculation and mice that were injected intravenously with killed eggs. In vitro tests were done to study the effect of thiabendazole on production of antigenic metabolites by T. canis larvae as measured by amounts of precipitates formed around larvae in immune serum. The newer benzimidazole anthelmintics: fenbendazole, flubendazole, cambendazole, mebendazole, oxfendazole, oxibendazole, parbendazole and albendazole, were compared with thiabendazole for their larvicidal actions and their effects on larval migration. Thiabendazole was found to have a weak larvicidal effect but produced a reversible inhibition of larval migration. Inhibition of larval migration required administration of the drug in medicated diet, and was correlated with the concentration of thiabendazole in the diet. T. canis larvae were arrested in the liver after oral inoculation and in the lungs after intravenous inoculation of the infective eggs. As treatment with thiabendazole was prolonged, the effect of thiabendazole on larval migration became less reversible after treatment was terminated. Thiabendazole treatment had a suppressive effect on the pathology induced by the larvae during the migratory phase of infection. The in vitro production of precipitates by T. canis larvae in immune serum was inhibited by the presence of 100 mcg/ml of thiabendazole, which indicates that the drug may inhibit production of antigenic metabolites by the larvae. The course of peripheral blood eosinophilia was not affected by thiabendazole treatment in infected mice but was slightly inhibited in mice injected with killed eggs. All of the newer benzimidazoles tested had significant effects on larval migration but significant larvicidal effects were observed only in mice treated with albendazole, oxfendazole and cambendazole. It was concluded that the non-specific effect of thiabendazole in toxocariasis is mainly due to the inhibition of larval migration. The newer benzimidazole anthelmintics have high efficacy in causing temporary arrest of larval migration but they varied in the permanent damage they inflict on the larvae