EPRINOMECTIN RESISTANCE in veterinary parasites: heartworms, roundworms, ticks

Eprinomectin is a macrocyclic lactone that was introduced in the 1990s, about 10 years later than ivermectin, the first macrocyclic lactone that came to market. Since then, several veterinary parasites have developed resistance or tolerance to these molecules. Most resistance cases to eprinomectin were "caused" by excessive use of ivermectin, with cross-resistance to all other macrocyclic lactones. The most relevant resistant species are:

See below for DETAILS.

There are reports on other parasites that have developed resistance to macrocyclic lactones, but so far, such cases remain restricted to limited regions and/or do not represent a global threat for domestic animals yet, and thus are not particularly analyzed in this article. Recommended measures to handle these cases are more or less the same as for the most critical ones: Rotation to chemical classes with different modes of action that remain effective and/or Integrated Pest Management. The following cases relevant to eprinomectin can be mentioned :

Multiresistance is spreading. In 2010 one sheep property was reported in Brazil where gastrointestinal roundworms were simultaneously resistant to 7 different chemical classes (levamisole, benzimidazoles, macrocyclic lactones, nitroxinil, disophenol, trichlorfon and closantel). In 2021 a study in cattle farms in Brazil reported multiresistance of gastrointestinal roundworms to 4 chemical classes of anthelmintics in 95% of the twenty farms investigated: macrocyclic lactones, levamisole, benzimidazoles, and closantel. 

Eprinomectin is used moderately used in cattle; very scarcely in sheep, goats, and cats; and not at all in dogs, horses, and pigs. It is mostly available as an injectable or as a pour-on. There are numerous generic brands available. It is also used in cats as a spot-on.

It is a general rule that compounds that belong to the same chemical class show so-called cross-resistance among them, i.e., if a parasite develops resistance to one compound, it will be more or less resistant to other compounds of the same chemical class.

Parasites with resistance to eprinomectin

  • Gastrointestinal roundworms in catte, sheep and goats

  • Cattle ticks: Rhipicephalus (Boophilus) spp.

    • OCCURRENCE. Resistance of R. microplus to ivermectin has been reported in most countries in Latin America (e.g. in Argentina, Brazil, Mexico and Uruguay) and also in India. For other related species resistance to ivermectin has been reported e.g. in Egypt (R. annulatus) and South Africa (R. decoloratus). The problem seems to be just beginning. To our knowledge no ivermectin resistance has been reported yet for R. australis in Australia or other parts of Asia. Cross-resistance with all other macrocyclic lactones used in livestock must be assumed (abamectin, doramectin, eprinomectin, moxidectin).
    • OUTLOOK. Problems are likely to worsen everywhere. Resistance will continue to spread and to strengthen, particularly where macrocyclic lactones are massively used to control these ticks. 
    • RECOMMENDED MEASURES. The most reasonable measure is to switch to Integrated Pest Management (IPM) and/or to implement whatever preventative measures that reduce the use of any chemicals (see the article on Rhipicephalus (Boophilus) in this site). Where alternative chemicals of another chemical classes are still working against these ticks, rotation is usually a good option, i.e. to stop using macrocyclic lactones and to use other products with active ingredients of those still effective chemical classes during several years.
    • ALTERNATIVE PARASITICIDES for ROTATION. There are several chemical classes of parasiticides that are effective for the control of cattle ticks. However, most of them are ectoparasiticides that will not control gastrointestinal roundworms, and they are not available for drench or injectable administration, but only for topical use (dipping, pour-on, spraying, etc.).
      • Amitraz. Amitraz is only available for dipping or spraying. However, resistance of cattle ticks to amitraz is already quite frequent worldwide  and spreading, following its increased use as an alternative to synthetic pyrethroids. It controls only ticks as well as lice and mites to some extent. It does not control flies or gastrointestinal roundworms.
      • Fipronil. Fipronil is approved for the control of cattle ticks in some countries (e.g. Latin America and India) but in others not (e.g. Australia, USA). It is available only as a pour-on. Usually it has a very long withholding period of at least 12 weeks. It does not control gastrointestinal roundworms. However, resistance of cattle ticks to fipronil has also been reported in Latin America and is likely to develop elsewhere, where fipronil is used against cattle ticks.
      • Fluazuron. Fluazuron is available for cattle tick control in most countries where these ticks are a problem. However, it is very specific for ticks and does not control other external parasites or gastrointestinal roundworms. It is available only as a pour-on. Some cases of resistance of cattle ticks to fluazuron have been already reported in Brazil.
      • Organophosphates (chlorpyrifos, coumaphos, diazinon, ethion, dichlorvos, etc.). In the past (up to the 1990s) organophosphates were used a lot worldwide for tick control. They were progressively abandoned for safety reasons when less toxic compounds were introduced. Availability today is strongly reduced because many products have been banned by the authorities or discontinued by the manufacturers. Organophosphates are used mainly for dipping or spraying. Most organophosphates are also effective against external parasites other than ticks (lice, mites, flies, etc.). Used topically they are not effective against gastrointestinal roundworms. Resistance of cattle ticks to organophosphates was well established before they were replaced and it must be assumed that it remains present in many regions.
      • Synthetic pyrethroids (e.g. cypermethrin, deltamethrin, permethrin, etc.). Synthetic pyrethroids are only available for topical use (dipping, spraying, pour-on). They control numerous external parasites (ticks, mites, lice, flies, etc.), but are ineffective against gastrointestinal roundworms. Following their massive use worldwide from the 1980s onwards, resistance of cattle ticks and other external parasites to synthetic pyrethroids is strongly established worldwide and is often extremely high, making them completely useless.

Where available, follow national or regional recommendations for delaying resistance development or for handling already confirmed cases.

In the context of resistance management it must also be considered that innovation in the field of livestock parasiticides has strongly decreased in the last decades.

This means that the likelihood that new chemical classes with new modes of action against resistant parasites become available is quite slim. The reason is that, in the last decades, almost all animal health companies have focused their R&D investments in the much more profitable business of pet parasiticides. As a consequence, regarding resistance management in livestock and horses, almost nothing really new (i.e. with a new mode of action) has been introduced in the last decades: all new products (mostly new formulations or mixtures) have been basically "more of the same".

If you want to learn more about resistance, read one of the following articles in this site:

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Parasiticides