Characterization of moxidectin resistant Trichostrongylus colubriformis and Haemonchus contortus
Introduction
Until recently, what was known about macrocyclic lactone (ML) resistance was restricted to studies on resistance that had developed against the first generation ML, ivermectin (IVM) (Gill and Lacey, 1998). IVM resistance provided protection against IVM either as a drench or delivered in a sustained release device. In field-selected strains, IVM resistance (IVM-R) was inherited as an autosomal, major effect gene (Le Jambre et al., 2000). IVM-R provided limited side resistance to the more potent second generation ML, moxidectin (MOX) (Barnes et al., 2001). In IVM-R Haemonchus contortus MOX was equally effective against both heterozygote and homozygote worms, while in IVM-R Ostertagia circumcincta the homozygote resistant worms were more likely to survive MOX than the heterozygotes. As well as this potency, MOX also has a persistent activity against Haemonchus and Ostertagia. However, in this case IVM-R worms can re-establish during the period that the persistent activity prevents susceptible worms from establishing.
Now, however, MOX resistant strains of H. contortus are being reported in Australia (Love et al., 2003) and a MOX resistant strain of O. circumcincta has been reported from New Zealand (Sutherland et al., 1999). These strains can survive the initial exposure to MOX as well as the persistent activity. Therefore, during MOX exposure, MOX resistant (MOX-R) worms in contrast to the IVM-R worms continue to lay eggs through the entire period when MOX treatment is killing MOX susceptible worms.
Present drenching recommendations as well as simulation model outputs (e.g. Le Jambre et al., 1999, Barnes et al., 2001) are based on what is known about IVM resistance and not MOX resistance. Consequently, the debate on whether high potency against resident worms is or is not offset by selection during the persistent phase is biased by the lack of knowledge about MOX resistance. If, as it appears, resident MOX-R worms are unaffected by MOX, then the persistency of the drug would leave these worms unaffected by competition for at least 35 days (Shoop et al., 1997). Likewise, it needs to be determined whether MOX is more effective against the heterozygotes carrying the MOX-R gene(s) than against the homozygotes. Abamectin (ABA), a ML more potent than IVM but without the persistency of MOX, should also be tested against MOX-R homozygotes and heterozygotes. It is urgent that these questions regarding the MOX resistance phenotype be answered so that the information provided to industry by veterinary consultants on parasite control is up-to-date and of the highest quality. Consequently, when goat faeces sent to the Department of Primary Industries, Queensland (DPI, Queensland) were found to be positive for trichostrongylid eggs following treatment with MOX we decided to isolate these parasites and characterize their MOX resistance phenotype.
Section snippets
Resistant strains
A goat farm where MOX was putatively failing to remove resident adult worms located on the Gold Coast hinterland was the source of the resistant strains. The drenching record for this property indicated that some age groups of goats were being drenched eight times per year with MOX. IVM drenches had not been used for the past two years when it was noticed that they were failing to control parasites. At that time MOX became the ML of choice.
Faeces sent in to the DPI, Queensland for faecal egg
Faecal egg counts and larval differentials
FECs were done on all sheep 10 days after anthelmintic treatment. In the HcMOX-R heterozygotes the mean percentage reduction of ML anthelmintics ranged from 66% with MOX treatment to 9% reduction with a 2× dose of ABA (Table 1). Based on FEC, it would appear that MOX had an effect against the heterozygous resistant parasites. It is unlikely that a double dose of ABA would have less effect on FEC than a single dose and that the difference between the two ABA dose levels was within the margin of
Discussion
Both NAP and LEV are effective options for the control of HcMOX-R. Combinations of drenches containing these anthelmintics would appear to be a good method of regaining control of the strain.
The TcMOX-R strain is one of the first, if not the first, MOX resistant strain of this parasite to be described. The existence of this strain proves that Australian T. colubriformis has sufficient genetic variability to develop MOX resistance. It is also a more difficult species of parasite to control than
Acknowledgements
The assistance of Dominic Niemeyer, Callum Mack and Kerri Tyrrell with sheep care and parasitology was greatly valued.
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