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Background
Closantel is a salicylanide derivative widely used in the UK for the treatment of Fasciola hepatica and Haemonchus contortus in sheep. Five products containing closantel are currently licensed in the UK, all of which carry a licence for use in pregnant ewes not producing milk for human consumption. This includes products for which closantel is the sole active ingredient as well as combination products containing ivermectin or mebendazole ( DEFRA 2014 ).
As a flukicide, closantel is effective against both mature and late immature stages. It has also been shown to delay the resumption of egg shedding by up to 13 weeks post-treatment in experimentally infected sheep ( Maes and others 1990 ), a characteristic referenced within the product information for Supaverm oral Suspension (Eli Lilly& Company Ltd) and Mebadown Super Oral suspension (Eli Lilly & Company Ltd) ( DEFRA 2014 ). This gives closantel efficacy in control of pasture contamination comparable with triclabendazole ( Maes and others 1990 ). These properties, combined with a proven efficacy against triclabendazole-resistant fluke ( Coles and others 2000 , Thomas and others 2000 , Olaechea and others 2011 ), mean that while triclabendazole remains the drug of choice in instances of acute fasciolosis, closantel may play an increasing role in fluke control in the future.
There are numerous reports of closantel toxicity in both sheep and goats ( Obwolo and others 1989 , Gill and others 1999 , Barlow and others 2002 , Tiwari and others 2007 ). However, the effects of closantel toxicity on mid gestation pregnant ewes and, furthermore, the lamb in utero have not been previously reported. Previous embryo toxicity studies carried out in ewes included the delivery of 20 or 40 mg/kg once on day 11, 17 or 23 of gestation ( Van Cauteren and others 1985 ). These ewes were observed to have equal distribution of repeat breedings and perinatal death between treated and untreated control groups. This study did not document lamb survival and production following birth.
The use of flukicides with efficacy against immature fluke has traditionally been reserved for autumn, targeting the period of greatest risk of acute fasciolosis. However, recent studies have suggested a change in the occurrence of acute fasciolosis in the UK with the majority of...