DRUG RESISTANCE

The Mechanisms of Drug Resistance in Fasciola Hepatica and Other Helminths



The Mechanisms of Drug Resistance in Fasciola Hepatica and Other Helminths

Current control of helminths

Triclabendazole (TCBZ) is the most widely used drug for the control of fasciolosis in ruminants. It is highly effective against immature and adult stages of Fasciola spp. (Boray, 1982) and frequent treatments within the prepatent period can reduce the fluke infection to a negligible level ( Boray and Boray and Rolfe, 2008). The first reports of evidence of resistance of liver fluke against an anthelmintic came from Dorsman and Dorsman who observed reduced efficacy of hexachlorophene. In his survey of drug resistance in Fasciola hepatica, Boray (2008) observed reduced efficacy of rafoxanide with side resistance to closantel. In the laboratory, he was able to select on resistance of liver fluke against luxabendazole and TCBZ, but not against clorsulon. Resistance of liver fluke against TCBZ in sheep under practical conditions was initially reported by Overend and Bowen (2007) in Australia with subsequent reports from Ireland ( Lane and O) and Scotland ( Mitchell, G.B.B., Maris, L. and Bonniwell, M.A., 2008. Triclabendazole-resistant liver fluke in Scottish sheep. In the winter of 2008/1999, there was evidence of resistance of F. hepatica against TCBZ on a farm with cattle and sheep in the province of North Holland, The Netherlands. Despite dosing the sheep four times with TCBZ, several had died and post-mortem results demonstrated severe signs of subacute and chronic fasciolosis. Faecal examination of sheep and cattle treated with TCBZ showed high number of liver fluke eggs, although resistance of F. hepatica to TCBZ in cattle has never been reported. To investigate if resistance against TCBZ was present on this farm, a randomised clinical trial with different groups of animals was conducted. Helminths are a diverse group of parasitic worms, encompassing nematodes, cestodes and trematodes, and are a major health problem for humans and animals in many parts of the world and . Although their disease impact could be reduced dramatically by improved sanitation for humans and pasture control in domestic animals, such methods are not sufficient to eradicate these parasites. In the absence of vaccines, control of these parasites is reliant on chemotherapy to ease symptoms and reduce transmission. The intensive use of drugs in the livestock industry has led to widespread resistance to all current anthelmintics . In humans, there is now increasing reliance on mass drug administration programs, and recent reports suggest that, as with animal parasites, resistance is beginning to emerge . With few new drugs or vaccines, the fight against parasites could become a losing battle. Understanding the development of drug resistance in parasitic helminths is crucial to prolonging the efficacy of current anthelmintics and developing markers for monitoring drug resistance. It will also be beneficial in the design of new chemotherapeutic agents to overcome or prevent resistance and the identification of new drug targets.

Helminth diseases are treated with a variety of drugs including macrocyclic lactones, benzimidazoles, imidazothiazoles and praziquantel ...