Ivermectin selection and characterization of the life history traits of Heligmosomoides polygyrus (Nematoda)

A stock "parent" (S) strain of the mouse parasite Heligmosomoides polygyrus was exposed to increasing levels of ivermectin at the L4 stage for 15 generations. A Passage line was also developed from the parent strain parallel with the ivermectin selected line to control for the effects of rapid passage of the parasite from host to host during drug selection. A dose titration trial indicated 1.5 fold resistance had developed in the ivermectin selected strain at the 8th generation (IVM-8) both at the L4 and adult stage. A higher dose of drug was required to kill the L4 stage compared to the adults at generation 8. Additional selection pressure for 7 generations (IVM-15) did not change the resistance status of adult worms. The Passage strains (P-8 and P-15) remained susceptible to drug. The life history traits of the parent strain (S), the ivermectin selected (IVM-8 and IVM-15) and the Passage (P-8 and P-15) strains were then compared. Eight generations of selection with ivermectin (IVM-8) resulted in an increase in establishment 8 days post-infection (pi) but decreased egg output and worm burden over 4 months compared with strain S. However these effects were not seen after 15 generations of drug selection. The ivermectin selected strain (IVM-15) had similar establishment, egg production and worm burden as the parent strain (S). Establishment in strain P-8 was intermediate and not different from S or IVM-8 however 15 generations of passage (strain P-15) resulted in higher establishment and more rapid development to adult. This was also reflected in the net egg output and worm burden during the first month of infection. There were no differences in per capita fecundity among the five strains. Environmental pressure exerted by passage of H. polygyrus from host to host rather than ivermectin selection caused shifts in some life history traits of this nematode