Multiple lethal effects induced by a benzimidazole anthelmintic in the anterior intestine of the nematode Haemonchus contortus

A mechanism of benzimidazole efficacy against parasitic nematodes is postul ated to involve inhibition of intestinal secretory vesicle transport via de polymerization of microtubules. We show that fenbendazole (FBZ) treatment o f lambs causes pathology localized to the anterior intestine in the parasit ic nematode Haemonchus contortus. The pathology included gross disintegrati on of the anterior intestine, DNA fragmentation in anterior intestinal nucl ei with characteristics of an apoptosis-like process, and inhibition of hos t erythrocyte digestion. These lethal effects were associated with inhibite d transport of apical secretory vesicles in the anterior intestine, and the n generalized dispersal of these vesicles-contents throughout the intestina l cytoplasm and worm body. Cytoplasmic accumulation of secretory vesicles a nd undigested erythrocytes preceded DNA fragmentation and vesicle-content d ispersal. Both DNA fragmentation and vesicle-content dispersal were detecte d in disintegrated intestine and intestine that had not yet undergone disin tegration. These pathologic effects in the anterior intestine appear suffic ient to explain the efficacy of FBZ against adult H. contortus. The results implicate mechanisms in the anterior intestine that govern dispersal of ap ical secretory vesicle contents, DNA fragmentation and tissue disintegratio n as effecters of this pathology. (C) 2000 Published by Elsevier Science B. V. All rights reserved.