Anthelmintic drug development: an evolving landscape in the face of evolving resistance

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Helminths – parasitic flatworms and roundworms – are a leading cause of morbidity both to livestock and to billions of humans in the developing world. Like other infectious diseases, helminths have a remarkable and alarming ability to adapt to changes in their environment, including the development of resistance to chemotherapy. In the animal health (AH) sector, particularly for small ruminants such as sheep, multi-drug resistance to the three main anthelmintic classes (benzimidazoles, imidazothiazoles and the macrocyclic lactones) is now established in Australia and parts of Europe.

Multi-drug resistance is the consequence of intense usage or misusage of drugs and, ultimately, a result of the limited number of chemistries available. This dire situation is leading to a complete rethink of disease-management strategies; including developing refugia (dilution) approaches to limit the number of drug-resistant worms in any worm population, in addition to the more focused and scientifically rational use of chemotherapy (www.ema.europa.eu/docs/en_GB/document_library/…/04/WC500226288.pdf). Both approaches will be critical to keeping livestock infections in check, but the development of new therapies must also be included in a comprehensive strategy.

For helmintic diseases of humans, it is important to recognize and understand the evolution of resistance to anthelmintics used in the AH sector as it has been responsible for all of the essential, and still vital, medicines that have been eventually translated to treat human helminthiases. It follows that the multi-drug resistance seen in AH may yet occur in the medical arena. Disconcertingly, and although there is increased trans-national political will to eliminate and eradicate the ‘neglected’ diseases of poverty (http://unitingtocombatntds.org/), the strategy relies heavily on handing out tablets of the same few drugs to which resistance has long since emerged in the AH sector. Also, many of these drugs lack the complete efficacy necessary to actually ‘cure’ the targeted infestations. One can’t help but have the sense that we are simply asking for resistance to emerge and establish in human populations.

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