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Evidence of multiple mechanisms of avermectin resistance in haemonchus contortus--comparison of selection protocols
J H Gill1, C A Kerr, W L Shoop
1Microbial Screening Technologies, Kemps Creek, NSW, Australia. jhgill@mst.aust.com
Abstract:
Three isolates of Haemonchus contortus selected for avermectin resistance in sheep were compared in three in vitro pharmacological tests previously shown to discriminate between field isolates of H. contortus resistant and susceptible to the avermectins. Two isolates, F7-A and IVC, were selected for avermectin resistance in the laboratory from a reference susceptible isolate using suboptimal doses of ivermectin (LD95) for 7 and 16 generations, respectively. In these isolates avermectin resistance was not associated with a decreased sensitivity to avermectin inhibition of larval development or L3 motility but was associated with an increased sensitivity to paraherquamide. The third isolate, Warren, was derived from an overwhelmingly avermectin-susceptible, mixed species field isolate in a single generation by propagating the small number of survivors of a 0.2 mg/kg ivermectin treatment (i.e. 10 x LD95). This isolate, like previously characterised avermectin-resistant H. contortus isolates derived from the field in South Africa and Australia, showed a markedly reduced sensitivity to avermectin inhibition of larval development and L3 motility, as well as an increased sensitivity to paraherquamide. These results suggest that avermectin resistance can manifest itself in different ways and that the two selection protocols used to generate the F7-A, IVC and Warren isolates have resulted in the selection of different resistance phenotypes.
Insights
Avermectin resistance in Haemonchus contortus presents diverse phenotypes. Laboratory selection yielded isolates with altered drug sensitivities, suggesting varied resistance mechanisms in sheep parasites.
Area of Science:
- Veterinary Parasitology
- Molecular Pharmacology
- Antiparasitic Drug Resistance
Background:
- Haemonchus contortus is a major gastrointestinal nematode parasite of small ruminants.
- Avermectin resistance in H. contortus poses a significant threat to livestock health and productivity.
- Understanding the mechanisms of avermectin resistance is crucial for developing effective control strategies.
Purpose of the Study:
- To characterize the pharmacological phenotypes of Haemonchus contortus isolates selected for avermectin resistance.
- To compare in vitro responses to avermectins and paraherquamide in laboratory-selected and field-derived resistant isolates.
- To investigate the diverse manifestations of avermectin resistance in H. contortus.
Main Methods:
- In vitro pharmacological testing of three H. contortus isolates (F7-A, IVC, Warren) selected for avermectin resistance.
- Assessment of avermectin inhibition on larval development and L3 motility.
- Evaluation of sensitivity to paraherquamide.
- Comparison with previously characterized resistant isolates from field populations.
Main Results:
- Two laboratory-selected isolates (F7-A, IVC) showed resistance not linked to reduced sensitivity to avermectin's effects on larval development or motility, but increased sensitivity to paraherquamide.
- A third isolate (Warren), selected from a field population, exhibited reduced sensitivity to avermectin's effects on larval development and motility, and increased sensitivity to paraherquamide.
- The selection protocols resulted in distinct resistance phenotypes, differing from each other and from previously identified field isolates.
Conclusions:
- Avermectin resistance in Haemonchus contortus can manifest through different pharmacological phenotypes.
- Laboratory selection methods can generate distinct resistance profiles, highlighting the complexity of avermectin resistance.
- These findings underscore the need for nuanced approaches to managing avermectin resistance in parasitic nematodes.
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