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This article was published in 1981
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Levamisole Toxicity in Lambs
S.J. Whittaker, B.V.Sc., Veterinary Inspector, Glen Innes/Inverell
CASE REPORT:
In this incident 150, 3-8 week old crossbred lambs were injected at marking time with 3.5ml. 'Nilvax Gold' (I.C.I. containing 100 g/1 levamisole phosphate).
It was intended by the owner to inject a further 400 lambs with the 'Nilvax Gold' but after vaccinating the first 150 it was realised that it 'something was wrong!'
CLINICAL SIGNS
The owner reports that 5 - 6 lambs had shown some reaction within minutes of being vaccinated,
* described as 'frothing at the mouth', muscle trembling, going down and then getting up again and running off within a few minutes.
Approximately one hour after marking had commenced a quick check around the small paddock into which the marked lambs had been released showed 6 lambs to be dead with a further 6 - 7 showing the following clinical signs:-
* staggery or abnormal gait; generalised muscular fibrillation; salivation; increased respiratory rate and cyanosis.
* lateral recumbency and death followed in some cases and others 'went down' when chased or stressed.
In the literature the signs of levamisole overdosage in sheep have been described by Baker and others, (1) Forsyth (3) Philip & Shone (6), Waletzky and Rohrbacher (7), and Walley (8), whose findings in a large number of animals over a wide range of climatic and husbandry conditions are in very close agreement.
The signs comprise head shaking, lip licking, some salivation, and muscle tremors particularly about the head and neck. At higher doses,muscle tremors become more extensive. There is slight ataxia, anxiety, and marked hyperaesthesia with definite periods of irritability. There is some increase in the frequency of defaecation. Severely affected animals show still more extensive muscle tremors, marked ataxia, and, when disturbed, walk with short jumping steps. Collapse and prostration follow, with very rapid respiration, dyspnoea and convulsions.
Death, when it occurs, follows the acute collapse, and is considered to be due to heart failure.
The signs are rapid in onset, usually five to 20 minutes after dosing. Death, after very high doses usually occurs within 12 hours.
High or low protein diet, rich or poor pasture, starvation or dehydration, or stress due to prolonged driving do not appear to reduce the safety of the drug.
Forsyth (3) points out that the signs of overdosage with tetramisole are in many ways similar to those seen following overdosage with organophosphorus compounds.
PATHOLOGY
Post-mortem examinations carried out on the lambs that had died in this case consistently revealed the following general findings:-
namely lung congestion and myocardial petechiation; pale renal cortex and liver parenchyma.
These findings are in contrast to those of Baker (2) who examined the tissues of two sheep three days after a single dose of 80 mg/kg of dl-tetramisole and of two sheep seven days after dosing. No gross or histological changes attributed to the drug could be found in the mucosa of the alimentary canal, heart, kidney, adrenals, bladder, bone marrow, brain, eyes, gonads, lung lymph nodes, mammary gland, pancreas, spleen or thyroid.
TOXICOLOGY
I.C.I. 'Nilvax Gold' is a combination of a 5 in 1 vaccine and a levamisole injectable drench designed specifically for use in ewes prior to lambing and in other sheep in excess of 35 kg body weight.
Walley in his work showed that the minimum lethal dose of tetramisole hydrochloride given by subcutaneous injection for adult sheep was 60 mg/kg.
'Nilvax Gold' contains 100g/l levamisole phosphate corresponding to 68 g/l levamisole base, i.e. a 3.5 ml dose of 'Nilvax Gold' contains 353 mgs of levamisole phosphate (the equivalent amount of levamisole base being contained in 280 mg of tetramisole hydrochloride).
Thus a lamb weighing 4.7 kg (280 divided by 60) that received 3.5 ml 'Nilvax Gold' would receive the minimum lethal dose.
Although no actual data is available on the subject it is felt that levamisole is more toxic in younger animals.
However, young lambs such as those which were affected in this incident are not normally drenched with 'Nilvax Gold' and this case obviously represents a gross misuse of the product.
TREATMENT
Three affected lambs (one of which was in a moribund condition) were given 2 mgs I/V dexamethasone. All three lambs recovered completely within 2 hours of treatment (or, in spite of it!)
REFERENCES
I.C.I. (Aust.) supplied much of the reference material contained in this article and this material was extracted from the following references:
1. BAKER, N.F. et al. (1970) American Journal of Veterinary Research 31, 977 USA (file ref. 3.11-213)
2. BAKER, S.B. de C., (1965) ICI Pharm Div. Res. Dept. Rept. UK (file ref. 1.211-3)
3. FORSYTH, B.A, (1966) Aust. vet. J. 42, 412 AUSTRALIA (file ref. 3.11-3)
4. FORSYTH, B.A. (1968) Aust. Vet. J. 44, 395 AUSTRALIA (file ref. 3.16-5)
5. JANSSEN PHARMACEUTICA (1974) Res. Prod. Inf. Serv. BELGUIM (file ref. 4500391)
6. PHILIP, J.R. & SHONE, D.K. (1967); J. S. Afr. vet. med. Ass. 38, 287 SOUTH AFRICA (file ref. 3.11-55)
7. WALETZKY, D. & ROHRBACKER, G.H. (1966) Amer. Cyanamid Document USA (file ref. 1.221-2)
8. WALLEY, J.K. (1966) Vet. Rec., 78, 406 UK (file ref. 3.11-6)