Closantel Toxicity

Closantel is an athelmintic (dose) occurring as single actives in doses such as Prodose Yellow LA (Virbac) (Tri-Dose oral (MSD), Zerofluke (Afrivet) or in combination doses such as Closamectin injectin (Norbrook), Maxispec (Bayer), Maxicare (Bayer), Ovidose 4 (Kyron), Prodose Orange (Virbac), Sudox (Bayer), Valbantel (Pfizer)as examples, The updated list can be found on the website: 

https://www.angoras.co.za/page/anthelmintic_drug_list#38

Roundworm treatments containing Closantel (Group 4 and in combinations - Halogenated salicyclanalides) can potentially cause blindness and deaths in Angora goats where they are:

• Overdosed (weigh goats)
• High parasite loads (roundworm, cocci) resulting in low Albumin (blood protein) levels.
• Cachexia, goats in poor condition. Low protein levels.

It has been internationally recognised that due to roundworm anthelmintic resistance and metabolism of goats that they are commonly dosed 1.5x the sheep dose (off label).

It is important to note that Closantel is albumin bound so toxicity is more likely in goats with high roundworm or coccidiosis counts (hypoalbumineamia) or goats that are in poor condition.

Trials indicated that kids dose at 4x the therapeutic dose went blind. Kids not affected too badly recovered over 3-4 weeks. It is therefore very important that the Angora goats are weighed and dosed according to weight.

Most frequent symptoms of Closantel toxicity in Angora goats

• Loss of appetite (anorexia)
• Ataxia (uncoordinated movements)
• Weakness
• Visual disturbance
• Blindness
• Collapse, recumbency
• Paresis
• Opitothonus (hyperextension of head, neck and spine)

SEE VIDEO: dr_mackie_video.mp4

Also seen in sheep as: depression, colic, opistothonus (severe hyperextension of head, neck and spine), nystagmus (uncontrolled eye movements), mydriasis (dilatation of the pupil), loss of pupillary reflex and blindness. Fatalities can also occur.

Once blindness appears it is usually irreversible.

How fast does the toxicity occur?

Peak plasma levels are reached 10 to 48 hours after administration, both after oral or intramuscular administration

Four days after treatment up to 60% of the injected and 30% of the drenched closantel is absorbed into the blood. In the blood, unchanged closantel binds strongly and almost completely (>99%) to plasma albumins.

• In cases seen in Angora goats the symptoms started about 48 hours post dosing. This is different to Levamizole toxicity where goats may show signs before you have finished dosing in the race- 10-15 minutes and peak after 30 minutes, so much quicker. However, levamisole intoxication can also have similar symptoms, such as muscle tremors spasms, cramps, trembling and depression (cholinergic signs).

Antidote and Treatment

There is no specific antidote for closantel.

Treatment consists in supportive and symptomatic measures.

Advice is:

• Tube activated charcoal (2g/kg)
• Tube glucose/water
• Inject vitamin B

FOR REFERENCE Pathology case report: (June 2024)

History:

50 adult goats (out of flock of 360) which reported ill, 20 of which were reported as being critical. The goats were reported to fall and then be unable to stand. Some died overnight others appeared disorientated, appeared blind, tremors were observed. The goats became recumbent (lateral) and were able to lift heads. Some showed torticollis (head pulled back) before dying.

The goats started dying about 2 days after being dosed Ovidose 4. In total about 30 goats died.

Examination:

An adult recumbent kapater Angora goat was examined. Pupil size appeared normal and no nystagmus observed. It was weak, ataxic and unable to stand. Neurological clinical signs were present.

A faecal sample was checked and was clean.

Bloods were taken:

No abnormalities detected on renal and liver function, Glucose elevated (stress response) Total Protein (TP) was within normal range

• ALP 22 (5-30U/L)
• ALT 15 (11-40 U/L) BUN 11 11 (7-11 mg/dl)
• Creat 0.9 (1-2mg/dl)
• GLU 196 (45-75mg/dl)*
• TP 75 (63-73g/dl)

Post Mortem examination.

Angora kapater was reported to have been found dead in the morning.

Weight 37.6kg.

BCS 2

Macroscopic findings:  General autolysis, more bloated than expected (reported to have been found dead this morning). Gas-filled intestines, Severely congested lung, Kidney: signs of autolysis more advance than expected in time period since death. Liver: tan coloured.

Presumptive dx:  Due to rapid autolysis Clostridium (neurological form of enterotoxaemia) needed to be ruled out through histopathology and other differentials excluded to make a diagnosis of anthelmintic toxicity (levamizol, closantal, ivermectin) which was suspected.

Samples were sent to IDEXX laboratory: Brain, eye, intestine, liver, kidney, heart, abomasum, Small Intestine. The report was sent for a second opinion.

Basic summary of pathology:

• optic nerve showed areas of mild myelin vacuolization. All layers of the retina are visible.
• The cerebral samples also show mild status spongious of the white matter, but there is no sign of gliosis or myelin degeneration.

These changes are mild and non-specific, but given the history, clinical symptoms described, concern was expressed about possible halogenated salicylanilide toxicity. No other cause of acute death or infectious aetiology for the neurological signs noted could be found.

Discussion:

Taking into account the clinical history, Post Mortem findings and pathology findings the most likely differential diagnosis was the anthelmintic treatment containing Closantel.

Clinical signs occurred about 48 hours post treatmnet in this case, peak closantel plasma levels usually occur 10-48hrs post treatment. When this is compared to the development of Levamizole toxity signs, which can occur within 5-15 minutes peaking after 30 minutes after oral administration, make Levamizole less likely.

No other cause or infectious cause was detected on histopathology.

The Post Mortem Angora goat kapater weighed 37.6 Kg, had a BCS of 2 and had Total Blood Protein (TP) level of 75 g/dl. This would suggest the Post Mortem goat was not in a cachexic state

Closantel being protein (albumin) bound it would be of concern treating goats in a cachexic state or goats with high roundworm or coccidiosis counts. The faecal sample was clean but unknown at time of treatment but insufficient to have lowered the TP blood count.

The reported dose was 8ml per goat (I am obviously not in a position to confirm this) which was not significantly higher than the label dose which would have been 7.52ml for the PM goat (1ml/5kg ).

References:

PARASITIPEDIA.net CLOSANTEL: SAFETY SUMMARY for VETERINARY use in CATTLE, SHEEP and GOATS. Poisoning, intoxication, overdose, antidote

Idexx Laboratory