The Significance of Triclabendazole Resistance

Triclabendazole is the best fasciolicide available with activity against very young fluke. But there are increasing numbers of reports of resistance including failure of therapy in humans. Determining the resistance status on ‘fluky’ farms is essential as high mortality of sheep can occur if it is not realised resistance is present. The options for control are confined to other less effective products and failure of closantel as well could lead to the closure of some sheep farms in the UK. Preventing fluke infections though pasture management is difficult or may be impossible so development of a vaccine is urgently required. The pathology of fasciolosis is well known and occurs as two main forms, the acute infection resulting from the migration of large numbers of immature fluke through the liver and chronic infection caused by adult fluke in the bile ducts and loss of blood giving rise to sub mandibular oedema (bottle jaw) and lost production. Acute fluke, which can be fatal, is largely confined to sheep and lambs due to the smaller size of their livers compared with those of cattle. The introduction of triclabendazole revolutionised the control of fasciolosis due to its activity against fluke as young as one week of age making it the most effective fasciolicide. The result was the over reliance on one product (monotherapy) that had the almost inevitable consequence of the selection of triclabendazole resistant fluke. The first reportof resistance to triclabendazole came from Australia in 1995 [1]. Other reports followed and are summarised in (Table 1). Apart from the obvious implication for animal health, triclabendazole is used in treatment of human infections with F. hepatica and failure of triclabendazole has been reported in infected patients in Peru [2]. The implications of triclabendazole resistance can be severe when its presence has not been recognised. In central Wales a farmer informed his veterinary surgeon that he had used triclabendazole in September and in November his sheep were sick. Treatment with triclabendazole was recommended with faecal egg counts after 3 weeks. As triclabendazole had not worked treatment with closantel was given but it was too late and 60% of the flock died [3]. For a long time sheep farmers have been advised to establish the anthelmintic resistant status of nematodes on their farms due to the widespread occurrence of anthelmintic resistant nematodes, but so far this has not been adopted widely [4]. Now a similar recommendation must be made for all farms where liver fluke infections are known to occur especially where triclabendazole is used. A recent survey in Northern Ireland fortunately suggests fluke control practices are beginning to change [5]. It is also important that the effectiveness of other fasciolicides is established as resistance has been described to some alternative therapies (Table 2). The biggest concern is that resistance will be described to closantel, the other product used in sheep. Closantel, which is only effective against immature fluke from about six weeks of age, is more toxic and less effective than triclabendazole. Another uncoupler, nitroxynil, is used in cattle as it can be injected whilst triclabendazole is usually given orally to sheep. However, Novobilsky et al. [6], described the failure of closantel pour-on on cattle in Sweden. If due to resistance it could be of considerable concern as no therapy would be left for immature fluke in sheep. However, some veterinary Table 1: Reports of triclabendazole resistance in Fasciola hepatica. Date Place Reference 1955 Australia 1 2000 Wales 17 2000 Ireland 8 2001 The Netherlands 18 2006 Spain 19 2008 Brazil 2