Effect of benzimidazole under-dosing on the resistant allele frequency in Teladorsagia circumcincta (Nematoda)

This experiment was designed to determine the effects of under-dosing on th e frequency of benzimidazole resistant allele in the nematode Teladorsagia circumcincta. Fenbendazole (FBZ) was tested at 1/32, 1/16, 1/8 and 1/4 of t he recommended dose for sheep (5 mg/kg body weight). The fraction of the su sceptible homozygote (SS), susceptible heterozygote (RS) and resistant homo zygote (RR) genotypes were compared among FBZ dose groups to evaluate diffe rences between SS and RS genotype selective advantage. Almost all SS genoty pe worms were eliminated by 1/4 of the FBZ recommended dose, whereas a sign ificant fraction of the RS genotype worms survived treatment. The selective advantage was 4.5 times higher for the RS genotype. This selective advanta ge was determined at 1/4 of the manufacturer's recommended dose of FBZ. Thi s value should be taken as an indictor of the selective advantage of RS ove r the SS genotype when lambs are underdosed. A computer simulation was used to study the putative spread of anthelmintic resistance over a range of RS selective advantages (2, 4.5 and 10-fold), with two average sizes of indiv idual host worm population (20 or 2000 worms/host) and two initial R allele frequencies (0.1% or 1%) all situations, the lowest selective advantage of the RS genotype over the SS genotype was sufficient to promote the spread of resistance in susceptible populations. When the RS genotype had no selec tive advantage over the SS genotype, genetic drift almost always led to the loss of the R allele, except in the largest populations (average size = 20 00 worms).