Drug Resistance

Anthelmintic resistance is an extremely serious problem for controlling parasitic nematodes of sheep and goats, where resistance to the three major classes of anthelmintics is widespread (Kaplan and Vidyashankarb, 2012). Parasitic nematode populations tend to be large and genetically diverse, and this diversity is an essential factor for the parasite to avoid susceptibility to drugs. Resistance to anthelmintics appears very rapidly, so far within 10 years of each new drug being licensed for use. Alarmingly, once resistance has occurred, it appears to be irreversible.

Anthelmintic resistance is defined as the genetically transmitted loss of sensitivity in worm populations that were previously sensitive to the same drug. In this process, the anthelmintic drug selectively removes individual susceptible worms from a genetically diverse population leading to an increase in individual worms carrying genes conferring drug resistance that are passed to the offspring.

What is the molecular mechanism of drug resistance?

There are several possibilities:

(1) a change in a gene encoding a drug receptor that results in weaker drug binding

(2) a change in gene expression that leads to an increased production of the drug target

(3) a change resulting in enhanced detoxification to inactivate or remove the drug. This type of change can potentially give rise to multi-drug resistance.

Most of the known examples of anthelmintic resistance fall into one of the categories listed above.

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