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    Ecological genetics of anthelmintic resistance in nematode parasites of sheep
    Martin, Paul John. (University of Melbourne, 1989)
    Ecological and genetic studies were conducted on anthelmintic resistance in Ostertagia spp. and Trichostrongylus spp., two economically important nematode parasites of sheep. Benzimidazole resistance developed rapidly under field conditions. The selection pressure for resistance related primarily to the efficiency of the anthelmintic and to stock management. These factors determined the relative genetic contribution made, by the survivors of the anthelmintic, to future generations of worms, compared to that made by the free-living sub-population on pasture at the time of treatment. Benzimidazole resistance in Trichostrongylus spp. and Ostertagia spp. was found to be under polygenic control and inherited as an incompletely recessive character with strong maternal influence. Levamisole resistance in the strain of Trichostrongylus spp. studied, was mainly inherited as a sex-linked recessive gene or gene complex although there was some evidence of polygenic influences. The recessive nature of resistance supported the concept of using high dose rates of anthelmintics to delay the onset of resistance. High dose rates increase recessiveness with respect to fitness in the presence of the anthelmintic and remove resistance alleles which are present in heterozygous worms. Reductions in the degree of benzimidazole resistance in Ostertagia spp. occurred too slowly to re-introduce benzimidazoles for parasite control. This occurred under natural selection or counter-selection with levamisole in both field and laboratory studies. Therefore, from a practical perspective, resistance is a problem to avoid rather than manage. As an alternative means of using anthelmintics with a view to preventing resistance, selection studies were conducted using anthelmintics individually or in combination (mixture). Resistance in Trichostrongylus spp. and Ostertagia spp. developed rapidly where a benzimidazole or levamisole anthelmintic was used alone but no resistance developed where the recommended dose rate of both anthelmintics was administered in combination. Furthermore, a combination of a benzimidazole and levamisole, or either with naphthalophos, was found to offer high efficiency (>97%) against field strains of Ostertagia spp. showing resistance to either compound when used alone. The results provide an ecological and genetic understanding of anthelmintic resistance necessary for the strategic implementation of anthelmintics in sustainable worm control programs. The genetic analysis provides the background necessary for simulation models of parasite population dynamics incorporating the development of resistance.