Treating simultaneously with 2 drugs from different anthelmintic classes is one method of preventing the development of anthelmintic resistance. A computer based model has documented that if this strategy is used when the drugs are first introduced, before there is any selection for resistance to either drug, appreciable resistance will not develop for over 20 years. However, once resistance alleles accumulate in worm populations, this strategy will probably not be successful. Compared with individual drug effects, anthelmintics of different chemical classes administered together induce a synergistic effect, resulting in clinically relevant increases in the efficacy of treatment. This synergistic effect is most pronounced when the level of resistance is low. Once high-level resistance to both drugs is present, the synergistic effect is unlikely to produce acceptable levels of efficacy. In contrast, the same model indicated that rotating drugs with each treatment, using annual rotation or a 5- or 10-year rotation resulted in high-level resistance within 15 to 20 years (38). Thus, the common recommendation of annual rotation must be challenged. Rotation of drugs was originally suggested on the basis of the hypothesis that reversion to susceptibility (or at least substantial decrease in resistance gene allele frequency) might occur if resistant worms were less fit than were susceptible worms, and counter selection was applied via treatment with a drug from a distinct chemical class. However, evidence that resistant worms are any less fit or that true reversion occurs in the field is scant. Despite this, the concept of rotation is often viewed as a bona fide resistance prevention scheme, which it is not. Therefore, some leading small ruminant parasitologists are now calling for an end to the practice of rotation (27). It is suggested that a drug should be used until it is no longer effective, then a different drug should be used. The main rationale behind this recommendation is that: 1) the arsenal of effective drugs is limited, making it difficult to institute a true rotation on many farms; and 2) progressive development of resistance will make it easier to monitor the resistance problem on a farm
