Closantel toxicity in lambs in Norway

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cerebral malacia was reported in kid goats in Brazil, at a dosage eight to ten times higher than the manufacturer's recommended dose (Ecco and others 2006).
Closantel toxicity in lambs in Norway 1Meling 1

S., 1Ulvund M.J.

Norwegian School of Veterinary Science, Department of Production Animal Clinical Sciences, Section for Small Ruminant Research, Kyrkjevegen 332-334, 4325 Sandnes, Norway.

Introduction A closantel-oxfendazole mixture (Duotech®, Noorbrok) was introduced into the Norwegian market during the winter of 2005 for the control and treatment of helminthiasis and fascioliasis. Closantel is a salicylanilide drug with activity against Haemonchus contortus, adult and immature Fasciola hepatica and Oestrus ovis. Closantel is highly bound to plasma proteins and its activity is restricted against those parasites that suck blood. Optic neuropathy and retinopathy due to closantel overdose have been reported previously by others (Gill and others 1999, Barlow and others 2002) and the toxicity has been associated with dosages three to ten times the recommended dose. Closantel toxicosis with hepatocellular necrosis, spongiform change in the cerebellar white matter, retinal atrophy and cerebral malacia was reported in kid goats in Brazil, at a dosage eight to ten times higher than the manufacturer’s recommended dose (Ecco and others 2006). The dosage rate recommended by the producer is 10 mg closantel per kg live weight.

Fig 1. Dosage rate were not readily visible on the container, information were added on a separate paper which can easily be misplaced after use.

Materials and methods Toxicity occurred in June 2006 in a flock of about 100 sheep (Norwegian White), three days after dosing with the mixture. In a group of 16 lambs and their dams, two lambs were found dead, and seven lambs showed signs of depression, disorientation, blindness, and weakness in their hind legs. Lambs which were showing symptoms had a rectal temperature of about 40 °C. The remaining eight lambs seemed somewhat depressed, but they were still eating and moving around freely. No other drugs were administered to this group of animals at the same time, and there were no observations of any toxic plants on the pasture. One lamb with clinical signs was admitted to our unit for examination and necropsy. Fig.2 Norwegian White ewe with lambs

Results Microscopic examination of eyes and brain revealed: Clinical examination revealed: • Rectal temperature of 39.1°C • Heart rate was 100 bpm • Respiratory rate was 100 bpm. • Appeared blind (no response to light / menace test) • Mydriasis • Depression • Lateral recumbency • Urine was flowing freely • Faeces were dark green and paste-like



• •



The lamb was euthanized with an intravenous barbiturate injection.

Post mortem examination: • Thin (16 kg) • Pale mucous membranes • Moderate amounts of serous fluid in the abdomen, thorax and pericardial sac • Pale, emphysematous and oedematous lungs



Retinal degeneration with haemorrhages and loss of nuclear layer (Fig.3) Necrosis and vacuolisation of the optic nerve at globe exit Focal necroses with perivascular vacuolisation of white matter at optic chiasm (Fig.4) Severe vacuolisation of white matter with perivascular hypertrophy of glia cells (Fig.5) Changes appearing throughout the brain tissue were in close proximity to the vascular supply of the brain

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Tissue samples of liver, kidney, both eyes and the whole brain were put on 10% formalin, routinely processed for histopathology, and stained with haematoxylin and eosin (H&E).

Discussion Traditionally, lambs are dosed according to weight estimation of the heaviest lamb in the flock (about 40 kg lwt.). This is usually safe as many anthelmintics have a low toxicity. In this case, the lightest lambs in the flock may have received up to three times the recommended dose. Farmers have also reported that viscosity of this product has caused problems with the dosing gun. Closantel toxicity in this flock may have appeared due to several factors. Weight estimation may not have been accurate, and there may have been a large gap in live weight between the heaviest and lightest lambs. In some cases it is necessary to divide the lambs into dosage groups, likewise to make sure that the dosing gun administers the correct dose. Data sheets and user guidelines should always be readily available and read by the user, and in any case, veterinarians prescribing these products should ensure that the user is aware of dosage rate and toxicity. References: Gill, P. A., Cook, R. W., Boulton, J. G., Kelly, W. R., Vanselow, B., and Reddacliff, L. A. Optic neuropathy and retinopathy in closantel toxicosis of sheep and goats. Aust.Vet.J. 1999; 77: 259-261 Barlow, A. M., Sharpe, J. A., and Kincaid, E. A. Blindness in lambs due to inadvertent closantel overdose. Vet.Rec. 2002; 151: 25-26. Ecco, R., de Barros, C. S., Graca, D. L., and Gava, A. Closantel toxicosis in kid goats. Vet.Rec. 2006; 159: 564-566. Veterinærkatalogen online (2006). www.veterinarkatalogen.no/ Accessed August 30, 2006