Selection for drug-resistant nematodes during and following extended exposure to anthelmintic

Five groups of ten 7-month-old Romney lambs were challenged twice-weekly (2 x 3,000) with either Ostertagia circumcincta (Groups 1-3) or Trichostrongylus colubrifornzis (Groups 4 and 5) infective-stage larvae (L3) following administration of controlled release capsules (CRC) containing either albendazole (ABZ-CRC) (Groups 2 and 5) or ivermectin (IVM-CRC) (Group 3). Larval challenge comprised a mixture of equal numbers of drug-susceptible and -resistant L3 (OR/TR:OS/TS) during the 14-week period of drug release. Positive faecal egg counts (FEC) were recorded in each group during this period. Eggs recovered from faeces were used in an egg hatch assay (EHA) utilizing different concentrations of ABZ. O. circumcincta eggs from Groups 2 and 3 had significantly higher LC50 values than Group 1; eggs of T. colubriformis from the ABZ-CRC treated Group 5 had a higher LC50 than control Group 4. Following the exhaustion of drug release, larval challenge was changed to consist of only susceptible parasites and EHA performed wveekly to determine whether LC50 declined, which would indicate dilution or replacement of drench survivors. In those animals challenged with O. circumcincta, LC50 values were still significantly higher in Groups 2 and 3 at week 19 than in the previously untreated Group 1. For T. colubriformis, LC50 values declined steadily following exhaustion of drug release and were not significantly different between Groups 4 and 5 by week 20. This decline in LC50, and corresponding rise in FEC, was largely the result of 3 animals which dominated with high FEC. The remaining 6 animals showed little decline in LC50 or rise in FEC. The results demonstrate the ability of persistent drugs to screen for resistant parasites and establish that the period of selective advantage for drug-resistant parasites of both species is significantly longer than the period of drug release from CRCs.