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Antihelmintic use in farm animals

by
01 July 2011, at 1:00am

WILLIAM FITZGERALD of Bimeda reviews the classes of anthelmintics for cattle and sheep and their modes of action and ways of avoiding resistance

FARM stock have been back on pasture again for some time and the perennial issue of picking a suitable anthelmintic has come sharply back into focus for most herd or flock owners.  

There are a number of categories of anthelmintic available for use in cattle and sheep. Some of these include the avermectins (including ivermectin, doramectin and abamectin), the macrocyclic lactones (moxidectin), the benzimadazoles (including fenbendazole, albendazole and triclabendazole), the imidathiazoles (levamisole) and the more recently developed amino-acetonitrile derivatives (montepantel), the benzenesulphonamides (clorsulon) and the salicylanilides (closantel). 

Each of these individual compound classes has a slightly different range of activity and mode of action due to its chemical structure. 

Macrocyclic lactones and their derivatives the avermectins block the transmittance of electrical activity in nerves and muscle cells by stimulating the release and binding of gammaaminobutyric acid (GABA) at nerve endings. This causes an influx of chloride ions into the cells leading to hyperpolarisation and subsequent paralysis of the neuromuscular systems. 

They are active against many immature nematodes (including hypobiotic larvae) and arthropods. Ivermectin does not readily cross the blood brain barrier in mammals at therapeutic doses, the notable example being Collies, Shelties and their cross breeds. 

Benzimidazoles are used to treat nematode and trematode infections in domestic animals. However, with the widespread development of resistance and the availability of more efficient and easier to administer compounds, their use is rapidly decreasing. 

They are characterised by a broad spectrum of activity against roundworms (nematodes), an ovicidal effect, and a wide safety margin. Benzimadazoles cause degenerative alterations in the tegument and intestinal cells of the parasite by binding to the tubulin, thus inhibiting its assembly into microtubules. 

The loss of microtubules leads to impaired uptake of glucose by the larval and adult stages of the susceptible parasites, and depletes their glycogen stores. Due to diminished energy production, the parasite is immobilised and eventually dies. In recent years, the issue of benzimadazole resistance has emerged as a genuine threat to farmed animals all over the world. 

Benzimadazoles vary from drug to drug on their range of effect. Albendazole has both fluke and worm activity, being effective against all stages of roundworms, adult liver fluke and liver fluke eggs. Triclabendazole is effective against liver fluke eggs, immature liver fluke and adult liver fluke. Triclabendazole, however, has been particularly affected by the presence of resistant strains of liver fluke. This is due to overuse and overdependence on this drug, coupled with the increasing intensity with which sheep are farmed worldwide. 

Levamisole acts as a nicotinic receptor agonist and eliminates them by causing muscle paralysis. It has no activity against flukes and tapeworms and is not ovicidal. Resistance to levamisole appears to be associated with a loss of cholinergic receptors. 

Amino-acetonitrile derivatives (AADs) or “orange drenches” are the most recent addition to the farm animal wormer range. Monepantel is the active constituent seen from this range and blocks part of a receptor, the nicotinic acetylcholine receptor specific to nematodes. 

Monepantel is effective against nematodes resistant to other anthelmintics. As a result of this application, extremely judicious use of products within this category is advisable lest overuse develop to a situation leading to widespread resistance to this compound also. 

Clorsulon inhibits enzymes that are intrinsic to the glycolytic pathway within flukes, it blocks the oxidation of glucose to acetate and proprionate and depresses levels of adenosine triphosphate. It is ineffective against immature flukes and fluke eggs but is an adult flukicidal drug. 

Closantel is an antiparasitic agent used against several species and developmental stages of trematodes, nematodes (Haemonchus contortus) and arthropods. The anti-trematode activity of closantel is mainly used against liver fluke. Closantel is described as a hydrogen ionophore resulting in the uncoupling of electron transport mechanisms within the parasite. 

Resistance to anthelmintics has very much moved to the fore in recent years. Although clear anthelmintic resistance is seen in relation to a small number of products, the possibility of its occurrence can never be disregarded. 

Several strategies have been suggested to reduce the potential incidence of anthelmintic resistance. One of the more widely accepted, refugia, involves the purposeful omission of batches of animals, on a rotated basis, from the de-worming process. The principle for this is that by doing so we will allow contamination of the pasture with parasites that are susceptible to anthelmintics. It must be remembered, however, that this process must be closely monitored to avoid disastrous outcomes. 

Accurate worming patterns and worming programmes are to be advised. Recent EU directives have narrowed the spectrum of anthelmintics that can be used in lactating dairy cows. Endospec SC, which contains albendazole at 2.5% and 10% can be used in such cases, allowing short return to milk for sale (60 hours) and with short meat withdrawals (14 days cattle/four days sheep). 

For the beef farmer, Bimeda has recently added Bimectin Plus to its Bimectin range (Bimectin Injectable and Bimectin Pour On). Bimectin Plus contains ivermectin and clorsulon, with a meat withdrawal of 66 days, and it is subject to the same restriction as similar products in the UK.  

Endofluke is yet another of the Bimeda family: it contains 10% triclabendazole and affects all stages of the liver fluke (where resistance to triclabendazole is not suspected).