Levamisole resistance in Haemonchus contortus selected at different stages of infection. 1995

N C Sangster, and H Bjorn
Department of Veterinary Pathology, University of Sydney, N.S.W., Australia.

Resistance to the anthelmintic levamisole is common amongst most genera of trichostrongylid nematodes of sheep, but is relatively rare in the species Haemonchus contortus. The level of resistance in at least one strain of this species varies during the life cycle. Investigation of this phenomenon, especially in parasitic stages of the parasite may reveal information on resistance mechanisms and factors affecting the selection of resistance. Compared with adult worms of the same resistant strain, immature worms are more susceptible to levamisole both in in vitro contraction assays and an in vivo efficacy experiment. To ascertain if immature parasitic worms of a susceptible strain could be selected for resistance, 3 lines of worms were selected with levamisole for 9 generations. Lines were selected with the same dose rate (2 mg kg-1) at the 4th and 24th day of infection. In addition, because levamisole is less active against immature worms a further line was selected at the 4th day with a higher dose (8 mg kg-1) but similar efficacy to the selection at day 24. In in vitro assays the line selected at day 4 with the lower dose of levamisole showed no resistance compared with an unselected line. The other 2 lines developed high levels of resistance indicating that resistance can develop after selection at either stage. In addition these data directly show that selection pressure is important in determining the rate of development of resistance.

UI MeSH Term Description Entries
D007978 Levamisole An antihelminthic drug that has been tried experimentally in rheumatic disorders where it apparently restores the immune response by increasing macrophage chemotaxis and T-lymphocyte function. Paradoxically, this immune enhancement appears to be beneficial in rheumatoid arthritis where dermatitis, leukopenia, and thrombocytopenia, and nausea and vomiting have been reported as side effects. (From Smith and Reynard, Textbook of Pharmacology, 1991, p435-6) L-Tetramisole,Levotetramisole,Decaris,Dekaris,Levamisole Hydrochloride,Solaskil,Hydrochloride, Levamisole
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D011950 Receptors, Cholinergic Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology. ACh Receptor,Acetylcholine Receptor,Acetylcholine Receptors,Cholinergic Receptor,Cholinergic Receptors,Cholinoceptive Sites,Cholinoceptor,Cholinoceptors,Receptors, Acetylcholine,ACh Receptors,Receptors, ACh,Receptor, ACh,Receptor, Acetylcholine,Receptor, Cholinergic,Sites, Cholinoceptive
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D005260 Female Females
D006188 Haemonchiasis Infection with nematodes of the genus HAEMONCHUS, characterized by digestive abnormalities and anemia similar to that from hookworm infestation. Haemonchiases
D006189 Haemonchus A genus of parasitic nematode worms which infest the duodenum and stomach of domestic and wild herbivores, which ingest it with the grasses (POACEAE) they eat. Infestation of man is accidental. Hemonchus
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012641 Selection, Genetic Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population. Natural Selection,Genetic Selection,Selection, Natural
D012756 Sheep Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS. Ovis,Sheep, Dall,Dall Sheep,Ovis dalli

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