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Understanding anthelmintic resistance

What is anthelmintic resistance?

Resistance is the ability of worms in a population to survive treatments that are generally effective against the same species and stage of infection¹. Anthelmintic resistance requires resistant genes to be present in a worm population. How quickly this resistance develops depends on how many worms survive anthelmintic treatment to pass these resistant genes on to the next generation. The resistant worms continue to reproduce, ensuring that more and more worms in the population have the resistant gene. Eventually the population of worms with the resistant gene becomes so large that the anthelmintic treatment fails.

How does anthelmintic resistance occur?

Several factors can influence how quickly resistance to a particular anthelmintic will develop. They include:

  • Lifecycle – The shorter the lifecycle of the parasite, the more quickly resistance will develop. For example, resistance has developed more rapidly in cyathostomes with a lifecycle of six weeks, than in large strongyles with a lifecycle of six months1.

  • Egg production – Parasites that produce numerous eggs will develop resistance faster than those that produce fewer eggs.

  • Horse immunity – Resistance will develop more rapidly if the horse is unable to produce an adequate immune response to the worm’s presence i.e. the worm can evade the horse’s internal defence mechanisms.

  • Frequency of worming treatment – High frequency dosing (generally more frequently than every six to eight weeks) is an important risk of selection for resistance. Treating too frequently will ensure only resistant worms survive, and no susceptible worms are able to reach maturity, so do not contribute to and dilute the parasite population 1,2,3.

  • Dosing and efficacy of treatment – Under-dosing or using an ineffective anthelmintic will increase the development of resistance. By doing this, only the most susceptible worms are killed, leaving the resistant worms to reproduce 4,5. Under-dosing is most commonly caused by incorrect weight estimation, incorrect method of administration, spitting out of the product and splitting of doses between horses.

  • Refugia population – (In refugia) literally means “taking refuge” or “hiding” and refers to the population of worms not exposed to or affected by treatment. Worms in refugia remain susceptible to a worming treatment. This means that the higher the proportion of worms in refugia is, the more slowly resistance will develop. The population of worm larvae living on pasture is in refugia. Resistance will develop faster if worming treatments are given when there are only very low numbers of larvae on the pasture. Refugia generally refers to the worms in the external environment (i.e. on the pasture). However, in the case of cyathostomes, the refugia also includes the larval stage of cyathostomes that encysts in the intestinal wall of the horse because the majority of anthelmintics can’t kill these larvae. Thus, in cases of anthelmintics which have some efficacy against encysted larvae, for example moxidectin, the proportion of cyathostomes in refugia would be smaller and thus the risk to induce resistance would be higher1. Experts recommend that moxidectin use should be limited to a single annual treatment when required to remove encysted cyathostome larvae6.
  • Overgrazing and overstocking – This can contribute to an increase in the number of resistant worms on a property. Worm larvae hatch from eggs passed in the horse’s manure. The larvae don’t move very far from where they have hatched, and horses don’t like to graze close to the manure. This helps horses avoid inadvertently swallowing the larvae with the grass they are eating. However, if grass is scarce or paddocks are overstocked, horses are forced to graze close to their manure and therefore consume more larvae. In this way overgrazing and overstocking can cause a rapid increase of resistant worms in the horse7. It’s a good idea to change paddocks, pick up all manure or clean the stable two to three days after administering an anthelmintic treatment. This will help to remove as many worm eggs as possible which will help to greatly reduce the risk of re-infection, and therefore minimise the worm burden.

Anthelmintic resistance in Australiaascarids

In Australia, cyathostomes, or small strongyles, is one species of worm in which anthelmintic resistance has been proven. It is generally accepted that cyathostomes are resistant to the benzimidazole (BZ) class of anthelmintics.

Horses under the age of two years are at risk of ascarid (roundworm) infections. There is concern that ascarids may develop resistance to the other major class of anthelmintic, the macrocyclic lactones (mectins).

Ascarid resistance to mectins has recently been documented in Australia. Previously mectin resistance in ascarids has been documented in several countries overseas and some studies site failures of multiple types of mectins. In almost all the studies, pyrantel was used effectively to control the worms.

1 Sangster NC, (1999). Pharmacology of anthelmintic resistance in cyathostomes: will it occur with the avermectin/milbemycins? Vet. Parasitol., 85: 189-204. 2 Martin PJ, (1987). Development and control of resistance to anthelmintics. Int. J. Parasitol., 17, 2, 493-501. 3 Herd RP, Willardson KL, Gabell AA (1985). Epidemiological approach to the control of horse strongyles. Equine Vet. J., 17, 3, 202-207. 4 Comer KC, Hillyer MH, Coles GC, (2006). Anthelmintic use and resistance on thoroughbred training yards in the UK. Vet Rec., 158 (17): 596-598. 5 Matthee S (2003). Anthelmintic treatment in horses: the extra-label use of products and the danger of under-dosing. J. S. Afr. Vet. Assoc., 74 (2): 53-56. 6 Coles GC, Eysker M, Hodgkinson J, Matthews JB, Kaplan RM, Klei TR, Sangster NC, (2003). Anthelmintic resistance and use of anthelmintics in horses. Vet. Rec., 153 (20): 636. 7 Herd RP and Coles GC, (1995). Slowing the spread of anthelmintic resistant nematodes of horses in the United Kingdom. Vet. Rec., 136 (19) 481-485

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