Strategies for overcoming resistance in parasites

Tim Nickel - Bovine Technical Services Veterinarian, Boehringer Ingelheim Animal Health Canada Inc.

Article Summary:

• Given the limited number of products available today to treat internal and external parasites, preserving the efficacy of the ones we have now is important.
• Development of resistance can be delayed by using management strategies to reduce parasite levels in the animals and the environment, reducing the need for treatment. When treatment is necessary, avoid under-dosing animals as this increases the risk of resistance developing. Combination treatment (use of two different drugs) may be beneficial but do so only under the advice of a veterinarian.
• Refugia is another tool that is available to help slow down the development of resistance. It involves making the decision to only treat certain groups or a portion of animals within the herd – for example 90% – leaving the remaining animals untreated and reducing the build-up of resistant parasites in the animals and the environment.

When it comes to treating parasites, there are a limited number of products with different modes of action, whether it is for external or internal parasites. It can take many years to develop a new product and bring it to market. As a result, it is very important to preserve the effectiveness of the products we have now rather than hope that a new treatment will replace the ones currently available.

To do this, it is important to understand the concept of resistance and how it relates to parasites. Resistance is defined as a demonstrated reduction in effectiveness of a drug against the target parasite. This reduction in effectiveness is a result of a genetic difference in the parasite that allows it to survive treatment, and this resistance can be passed on to subsequent generations.

Every time we treat, we are selecting for resistant parasites. In other words, the treatment kills the susceptible parasites but those that already have resistance survive. This is known as selection pressure. The more frequently we treat with a drug, the more we select for these resistant parasites and the proportion of resistant parasites builds in the population. As a result, our treatments become less and less effective.

There are things that can be done to help slow down the development of resistance to a drug.

The obvious answer is to reduce the number of treatments, since this is one of the biggest drivers of resistance development. Management strategies like reduced stocking density, pasture management and good animal nutrition can be used to reduce the number of treatments required. When treatment is necessary, target individuals or groups rather than doing blanket treatment of the whole herd, if possible.

Under-dosing also increases the risk of resistance developing. For this reason, it is critically important to ensure every animal that receives a treatment gets a full dose. Use accurate weights when calculating the dose and ensure the product is applied correctly. Timing of treatment is also important. If treatment occurs too early before parasites are present and active, they may wind up getting exposed to subtherapeutic concentrations as drug levels are declining.

Combination treatment is another option to consider, where two drugs with different modes of action are administered at the same time. It is based on the premise that there will be very few parasites in a population that have resistance against both drugs. Parasites with resistance to one drug can still be eliminated by the other drug. Using both together improves the overall effectiveness.

It is important to be aware that this method may delay the onset of resistance, but over time, combination treatment can lead to parasites with resistance to both drugs. It is important to discuss combination treatment options with your veterinarian before using on animals, as some drugs may be incompatible with others and the potential of seeing an adverse reaction may increase.

Refugia is a strategy that can also help slow down the development of resistance. It is defined as the population of parasites that is not exposed to the drug.

The population not exposed to the drug generally consists of two sub-populations:

1. those parasites that are in the environment at the time of treatment, rather than in or on the animal; and
2. those parasites that are in or on animals that have not received a treatment.

As an example, with gastrointestinal worms, the first group would include the larval stages that are on the pasture prior to treatments; these larvae would not have been exposed to the drug and as a result have no selection pressure for resistance. The second group would be represented by animals that were not treated, such as a cow-calf herd where calves and heifer replacements are treated but the cows are not.

This strategy works based on the principle of dilution – by having a group of worms that have not been exposed to a drug, the relative proportion of resistance genes in the population should remain low, as no selection pressure has occurred in this group. This population will dilute the resistance genes that have been selected for in the treated animals.

Different strategies have been suggested to select which animals can be left untreated. The cow-calf example above is straightforward. In a group of similar animals, such as grass yearlings, one could leave a portion of animals untreated. The more animals that can be left untreated the better, but it is a balance between minimizing the impact parasites are having on performance and health with trying to preserve the efficacy of the drug for as long as possible. A suggested target would be to leave at least 10% of animals untreated. Based on specific conditions on the farm this may need adjustment.

As always, have a discussion with your veterinarian to build a parasite management program that addresses the specific conditions of your operation, including what options may be considered to reduce selection pressure for resistance.