In November 2012 a mob of ewes and lambs were yarded for drenching and weaning. The unweaned lambs were two to three months old (July /August drop).One thousand one hundred lambs were drafted from the ewes prior to drenching.
A recently released drench was used. The active ingredients were a three way combination of organophosphate, benzimidazole and macrocyclic lactone.
Eleven lambs died within 12 hours of drenching. Five lambs died during the day, as drenching was being undertaken. When death was observed, the producer reported lambs twitching and collapsing with spasms, frothing at the mouth and dying rapidly. Most deaths were not observed.
Six more lambs died overnight and these were available for autopsy the following day. Deaths totalled 11 out of 1100 drenched.
The previous week the producer had drenched 1700 lambs at weaning (aged 2-3 months old, July/August drop) and lost five using the same drench and technique. Eight hundred older weaned lambs (March/April drop) suffered no mortalities at that previous drenching operation, when drenched in the same manner with the same drench and at the same time.
The lambs in the current mob were 25-35 kg bodyweight and were all dosed for 35kg bodyweight. They were drenched as soon as they were drafted from their mothers. A Clostridial 5 in 1 vaccination had been given 6 weeks previously at marking. They were walked no more than 2km to the yards. Conditions were not unusually hot or severe, being around 24-27C. The operators were experienced in drenching lambs and used one power dose drench gun and one normal drenching gun.
The lambs that had died overnight were in a small clean holding paddock with feed and water available to them. The weaners were released into this area from the yards on dusk, immediately after the drafting/weaning/drenching operation was completed. They were not examined again until the next morning when the deaths were discovered. There were no toxic plants identified in the holding paddock.
The six weaner lambs presented as dead, with distended rumens in all 6, and pink froth at the nostrils from four of the six lambs. At autopsy all lambs had a congested anterior carcass (jugular veins and throat area) and serosanguinous fluid in the thoracic cavity. Four lambs examined had no trauma to the back of the throat (two lambs were not examined for this lesion).
Lungs showed degrees of mottled colour change from dark pink to purple. The tracheas had dark red stained mucosal lining ventrally. There was no visible drench residue down into bronchi. There was no fibrin or fibrinous clots in either the pericardium or within the thorax and there was no splash haemorrhages in the chest cavity.
Five of the six lambs that were autopsied had lungs with consolidation patches of varying size ranging from 10% to 60% of the anterior right ventral lung lobes, and in the ventral right central (apical) lobe. Amongst the dark hepatised areas were irregular squarish paler pink patches raised above the lung surface. The whole lungs failed to collapse but felt spongy caudally and dorsally compared to the right cranial ventral lobes which felt firmer.
Photographs were taken of lung from two lambs by the representative of the company involved in supplying the drench. The right cranial ventral lobes were sampled and sent to the NSW State Veterinary Diagnostic Laboratory for histopathology examination.
The abdomen in three lambs was opened and the rumen found to be distended with gas, but no foam. Overall the contents of the abdomen appeared a little pale. Overall, the digestive tract was pale to normal with some petechial haemorrhage seen on one kidney. The spleen was small and pale. The liver was a normal size and pale khaki colour.
The autopsies of the six lambs showed remarkably similar lesions. The lungs could be described as grossly having localised changes in the right anterior lobe in all cases, consistent with an aspiration aetiology.
Seven sections were examined. The report documented:
"There is severe diffuse congestion with haemorrhages. Many alveoli and bronchioli contain pale eosinophilic fluid, which is also expanding interlobular septae. There are marked autolytic changes, advanced in some areas, with numerous bacilli, and detachment of bronchial and bronchiolar epithelium; these changes make interpretation difficult.
There are mild multifocal accumulations of neutrophils in airways, interstitium or vessels; it is often difficult to determine their location.Bronchi show loss or flattening of epithelium and congestion of the lamina propria with moderate multifocal neutrophilic infiltrates. In one section, in a better preserved area, rare basophilic spheroidal almost crystalline particles, about 50 um diameter, are noted in small airways and interstitium".
The pathologist made the following comments in the report:
"Moderate acute multifocal suppurative bronchitis. Mild to moderate acute multifocal suppurative pneumonia. Pulmonary congestion, haemorrhage and oedema. Some of the oedema fluid may be due to post mortem vascular leakage.
Autolytic changes could potentially mask small lesions. A very small amount of basophilic material was found, nature and significance of this is uncertain; any aspirated liquid could have been washed out during histoprocessing.
The changes are not specific enough for an aetiological diagnosis but are consistent with aspiration pneumonia."
With any new drench there is a heightened awareness that post drenching mortalities could be attributed to the new formulation. The producer had not experienced this level of fatalities during previous weaning/drenching operations using other drenches, and so had raised concerns about this event.
In this case, the label instructions were followed, but an additional sheet supplied by the drug company at point of sale recommended against the use of a power dosing drench gun8. Both a power dose gun and normal drench gun were used in the process at the same time (the operators did about half each).There is no way of knowing whether the mortalities were associated with either technique.
The label instructions recommend avoiding stress. Environmental conditions of the day and distance walked by the lambs appear unlikely to have caused the stress described on the label.7
A toxicity assessment of this drench describes the drench as having moderate acute inhalation toxicity.6 The lesions seen in the lungs are consistent with inhalation of material into the lungs.
The active ingredient associated historically with toxicity problems is organophosphate5, in this case naphthalophos. The symptoms of organophosphate toxicity can be varied and include respiratory distress, collapse and death in acute poisoning9, and need to be differentiated from a severe inflammatory tissue reaction of an acute aspiration event.3
The toxicity of the drench by oral administration was also assessed prior to registration. One study in adult sheep described some loose faeces in trial sheep dosed at 3 times the recommended dose rate and 2 sheep displaying signs of OP toxicity at 5 times the recommended dose rate. 6 These 2 sheep recovered with treatment. In a trial with 2 month old lambs some loose faeces was noted at 3 and 5 times the recommended label rate.6 None of the dead lambs examined in this current incident showed signs of diarrhoea.
In trial work carried out in 1996, to examine the efficacy and safety of naphthalophos combinations, there appeared to be several syndromes associated with mortality. Three /5000 sheep (ewes) died within a day of treatment, and 8 lambs died 3-4 days later. On another property deaths in 10 weaners was reported to occur within 48-72 hours of drenching and was associated with poor body condition and scouring in the young sheep. There were no reports of pulmonary lesions in those sheep autopsied in this study.2
Aspiration pneumonia can take several days to cause death after the aspiration event.9 The timing of the deaths within 12 hours of drenching would suggest that the ingredients of the drench could have triggered the pathology, but the toxicity studies done prior to registration of the drench would suggest that death was not likely to be due to an overdose of an active ingredient in the formulation. However, absorption from the lungs can be very rapid and effects of the compound seen very quickly.1
Symptoms of sudden collapse, convulsions, and rapid death were described when carbon tetrachloride and paraffin drenches are deliberately administered into the trachea or mouth rather than by the correct route in an attempt to provoke aspiration of some of the compound.4 Aspiration of oil into the lungs can provoke an aspiration pneumonia.1
Clinical signs of an animal dying from an acute drench aspiration event could be expected to appear similar, regardless of what compound is used and could be presumed to relate to the severity of pulmonary compromise and pulmonary pathology as well as the absorption or action of an active pharmaceutical compound. A chemical pneumonia as described in human references, can present within a few minutes to a few hours of inhalation with respiratory distress, rapid breathing and cough with pink or frothy sputum, and is caused by the pulmonary inflammatory cellular reaction in response to potent cytokinins.3
The distended rumens and congestion seen in the dead lambs is considered to have been a post mortem change rather than indicating primary bloat. The owner did not comment that the acutely dead lambs showed any signs of bloat. Post mortem change is also considered to have caused some of the generalised lung discolouration and fluid congestion. The level of post mortem autolysis could be consistent with deaths occurring very soon after drenching was completed, making the sampling time 12-18 hours post mortem.
Instructions are also supplied by the drench manufacturer about correct positioning of the head while administering the drench8. In this limited sample, mortalities did seem to occur in mobs of lambs that were being weaned, rather than in the mob of older, already weaned lambs. Factors that may favoured drench being delivered into the lungs could include the lighter bodyweight of younger lambs making positioning more difficult and the tendency for lambs to vocalise at weaning.
The consistency of changes in the post mortem examinations would suggest that all lambs died from the same pathological process. The timing of deaths observed by the producer, and the pathology seen, support the diagnosis of an acute pathological process associated with the drenching operation.
The location of the lesions occurring consistently in the right apical lung supports the diagnosis of a primary aspiration event leading to an acute fatality.
In this case the pathology supports the diagnosis of acute aspiration pneumonia but autolysis of the samples prevents the drawing of further conclusions, and prevents any differentiation between a chemical pneumonia induced inflammatory reaction and a toxicosis.
My thanks to the producer and the drench manufacturer for their assistance in investigating this case.
Thank you also to those skilled pathologists NSW State Veterinary Diagnostic Laboratory pathologists for a comprehensive report.