Validating a drug resistance marker for a globally important ruminant parasite

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BBSRC : Christopher Wray : BB/T008776/1Parasitic worm infections are an extremely common issue on livestock farms worldwide, costing farmers and economies billions in production losses. One particularly important species is the barber pole worm, named for its distinctive red and white spiral pattern similar to those seen outside a barbershop. Adult parasites live in an animal's gut, releasing thousands of eggs daily, feeding on the blood of the host. Eggs hatch to larval worms on pasture, and are ingested by another host animal, normally sheep, goat or cattle, spreading the infection. Symptoms of infection include anemia, fluid buildup, reduced growth/milk production and sudden death. Infection is difficult to diagnose before the appearance of these symptoms, with sudden death often the first sign. Thus, farmers periodically apply chemical treatments when concerned about barber-pole worm. This selects for drug-resistant worms; barber-pole worm populations have quickly developed resistance to all of the drugs to which they have been exposed, often with a few years of a new drug's introduction. Thus, monitoring drug-resistance in worm populations (on different farms) is vitally important. Currently, this is done by counting the number of eggs in faeces before and after treatment, with the expectation being that if the worm is susceptible to the drug, there will be fewer eggs present after treatment while in resistant parasites, the number of eggs will remain stable. This technique is unfortunately unreliable due to inconsistent egg numbers being counted in samples, differences in number of eggs counted based on the analyst doing the counting, and a number of other confounding factors. Thus, novel methods for monitoring drug susceptibility are needed. Recent work has identified a genetic mutation within the worm that may be linked to resistance to levamisole, one of the most commonly used drugs against the barber pole worm. In this project, we will compare how common this mutation is between two different worm populations - one which has been exposed to levamisole, and one which has not. We hypothesize that the mutation will be significantly more common in the worm populations that have been regularly exposed to levamisole and so this work will validate this mutation as a marker of resistance to levamisole. This will lead to the development of a test that could be used directly on farms to test for the presence of this mutation. If the test is positive, farmers will know they need to use different drugs. Without this kind of testing, farmers cannot know if the parasite populations on their farms are drug-resistant and thus will continue to apply these drugs, wasting money on drugs that will not improve the health of their animals.