Roundworms are costing UK sheep farmers £84 million a year, and drug resistance is now so severe that some farms have shut down entirely. The problem is that the same few drugs have been used for decades, and the parasites have evolved to survive them—much like bacteria evolving antibiotic resistance. No one knows exactly how this resistance spreads through worm populations on a farm, and current tests for detecting it are too slow and insensitive to catch it early. This project will use the recently sequenced genome of *Haemonchus contortus* (the Barber’s pole worm) to find the genetic markers of drug resistance. The team will also study *Teladorsagia circumcincta*, the most common sheep parasite in the UK. By tracking genetic changes in worms exposed to drugs, they aim to understand how resistance arises and spreads, and to model how different treatment schedules—combined with climate change—affect that spread. In the longer term, the genome data will help identify which worm proteins are most likely to trigger a sheep’s immune response, providing a rational basis for vaccine development where previous attempts have failed. If successful, this research could give farmers practical tools to slow resistance and keep existing drugs working longer. The findings will also apply to parasites in cattle, horses, and pigs, and to human roundworm infections that use the same drugs.
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Most food-producing animals are infected with a variety of different roundworms, or nematodes, many of which live in the digestive tract. These parasites cause a range of disease in their hosts, from diarrhoea and anaemia, to death, in severe cases. They are a major welfare issue and cause significant economic losses to farmers, in terms of reduced production and treatment. It is estimated that these worms cost the UK sheep industry a conservative £84 million per annum. At the present time these parasites are controlled using drugs known as anthelmintics, but many of these chemicals no longer work effectively because the parasites have developed resistance to them, analogous to antibiotic resistance in bacteria. How anthelmintic resistance arises and spreads throughout the worms on a farm is not known. The problem has become so serious in the UK that some sheep-farming enterprises have had to close because the worms can no longer be controlled. Our project will investigate ways of ensuring that the existing drugs are managed to minimise the occurrence and spread of resistance and will also study novel approaches to vaccine development. The current methods for detecting resistant parasites are labour intensive and insensitive, making early detection impossible and analysis of the extent of the problem difficult. This makes it hard to evaluate strategies aimed at reducing the spread of resistance. We need to develop more sensitive methods to detect resistant parasites and so must understand the genetic changes in the parasites that lead to resistance. We have recently sequenced the genome of one of these parasites called Haemonchus contortus (the Barber's pole worm) and found it to be large and complex, containing a similar number of genes to the human genome. Studying this genome will identify novel ways of controlling nematode infections and our research is aimed at using new technologies to ensure that farmers can continue to produce livestock effectively. We plan to use information from the genome to identify markers of drug resistance in Haemonchus and in a closely related worm called Teladorsagia circumcincta, which is the most prevalent parasite found in the UK sheep population. By identifying the genetic changes in worms exposed to anthelmintics, we aim to understand how resistance arises and to develop markers to identify resistant worms on sheep farms. This information will be used to help model how resistance spreads and to investigate how different treatment schedules affect the development of resistance, taking into account climate change scenarios. In the longer term, we would like to develop vaccines against these worms. Although many attempts have been made to do this, most have not been successful, as we have no way of assessing whether the antigens tested to date are the most effective at stimulating a host immune response. However, our project will provide the basis for identifying genes that are under selection by the sheep immune system and therefore likely to be antigenic. We will combine results from this study with knowledge of where and when specific antigens are expressed in the worm to optimise the selection of potential vaccine candidates. Finally, the results from this project will be used to design sustainable control strategies for sheep parasites in the face of anthelmintic resistance and climate change. We have robust plans to engage with the farming community through workshops and publications to ensure that the implications of our work are translated into good farming practice. While this project focuses on parasites of sheep, we anticipate that much of what we learn about anthelmintic resistance will be directly applicable to parasites of cows, horses and pigs where anthelmintic resistance is an emerging problem. Moreover, as the same drugs are increasingly used to control related worms in humans, our work will also impact on human health.
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