Levamisole was introduced in the 1960s as a veterinary anthelmintic. Since then, its massive use in livestock has led to resistance in numerous species of gastrointestinal roundworms of cattle, sheep, and goats.

The most relevant resistant species are:

• In CATTLE, SHEEP and GOATS:
  • Gastrointestinal roundworms, mainly Haemonchus spp, Cooperia spp, Nematodirus spp, Trichostrongylus spp, Teladorsagia spp, Oesophagostomum spp.

See below for DETAILS.

There are reports on other parasites that have developed resistance to levamisole as well, 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 case can be mentioned:

• Pigs: Oesophagostomum dentatum. Resistance of O. dentatum to levamisole was reported in Germany in 1990s. However, since then it has not become a generalized problem in most other countries.

Multiresistance is spreading. In a FAO survey in 2004 it was found that simultaneous resistance to benzimidazoles and levamisole was present in 73% of the sheep properties investigated in Brazil, 60% in Australia, and 8% in New Zealand. 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 different chemical classes of anthelmintics in 95% of the twenty farms investigated: macrocyclic lactones, levamisole, benzimidazoles, and closantel. 

Levamisole is only effective against roundworms (in the digestive system and elsewhere). It is ineffective against tapeworms or flukes.

Levamisole is available mainly for both oral and injectable administration to livestock (ruminants, pigs, swine, poultry): in contrast with benzimidazoles it is soluble in water. A few pour-ons alre also available for ruminants in some countries. There are hundreds of generic levamisole products in most countries.

For oral administration to livestock it is used mainly in drenches and feed or water additives, often in combination with other compounds. For dogs and cats it is available mainly in tablets or pills, but use in pets is scarce. It is not used in horses.

Parasites with resistance to levamisole

• Gastrointestinal roundworms in catte, sheep and goats

  • OCCURRENCE. Resistance of these gastrointestinal roundworms (mainly Haemonchus spp, Cooperia spp, Nematodirus spp, Trichostrongylus spp, Teladorsagia spp, Oesophagostomum spp, Chabertia spp.) to levamisole has been reported worldwide, it is quite frequent in all types of livestock operations, and can be rather high. The problem is more extended in sheep and goats, than in cattle. Prevalence studies during a FAO survey run in the 2000s in numerous countries in sheep properties found that more or less strong resistance of gastrointestinal roundworms to levamisole was present in 84% of the properties investigated in Brazil, 82% in Uruguay, 80% in Australia, 71% in Paraguay, 50% in France, 35% in Spain, 25% in Argentina, and 24% in New Zealand. Since than the problem has certainly not improved but worsened.
  • OUTLOOK. Problems will worsen everywhere. Resistance will continue to spread and to strengthen, because little is done in most regions to reduce their use and to encourage non-chemical control and prevention. In fact, it is the biggest and most threatening resistance problem in livestock parasites. Also because such parasites are often multiresistant, i.e. they can be simultaneously resistant to nematicides of other chemical classes e.g. macrocyclic lactones, benzimidazoles, etc.
  • RECOMMENDED MEASURES. The most recommended measure is to switch to Integrated Pest Management (IPM) and/or to implement whatever preventative measures that reduce the use of any chemicals. Where alternative chemicals of another chemical classes are still working against these worms, rotation is usually a good option, i.e. to stop using levamisole and to use other products with actives of those still effective chemical classes during several years.
  • ALTERNATIVE PARASITICIDES for ROTATION. There are various chemical classes that control gastrointestinal roundworms too, and rotation with those chemical classes that still work can make sense. However, those worm species that have developed resistance to levamisole are often also resistant to these other chemical classes. Other chemicals or chemical classes that control gastrointestinal worms of livestock to some extent are the following:
    
    • Macrocyclic lactones (abamectin, doramectin, eprinomectin, ivermectin and moxidectin). Unfortunately, gastrointestinal roundworms have already developed resistance to macrocyclic lactones worldwide, which is very frequent and can also be very strong.
    • Benzimidazoles (e.g. febantel, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, etc.). Resistance of gastrointestinal roundworms to benzimidazoles is already very frequent and high as well, and multiresistant worm populations are spreading.
    • Tetrahydropyrimidines (e.g. pyrantel, morantel, etc.). Are not effective against some important gastrointestinal roundworm species (narrow spectrum of activity), and there are rather few products available for livestock. Resistance of gastrointestinal worms to this chemical class in livestock is not an issue.
    • Salicylanilides (e.g. closantel, rafoxanide). Are not effective against some gastrointestinal roundworm species (narrow spectrum of activity), and there are rather few products available for livestock in some countries. Resistance of gastrointestinal roundworms to this chemical class in livestock is not an issue, although some cases have been reported (Haemonchus contortus).
    • Monepantel. It is available for sheep and goats. For cattle available in combination with abamectin in some countries. Resistance of several gastrointestinal roundworms (Haemonchus, Trichostrongylus, Teladorsagia ) to monepantel has already been reported in several countries in sheep and goats but it is still not very frequent.
    • Derquantel. It is only available for sheep in combination with abamectin. A few cases of reduced efficacy to the derquantel and abamectin mixture have been reported in Argentina and Australia.
    • Nitroxinil. It is a narrow-spectrum anthelmintic effective against liver flukes and a few gastrointestinal roundworms (e.g. Bunostomum spp, Haemonchus spp, Oesophagostomum spp. Nitroxinil is usually administered as an injectable.
    • Organophosphates (e.g. naphtalophos, trichlorfon). Organophosphates were used as nematicides in the 1960s, before more effective and less toxic compounds became available. By the 1980s they were mostly abandoned for this purpose. However, the strong increase in resistance of gastrointestinal nematodes to almost all modern anthelmintics has led to the re-introduction of some of these compounds for sheep in certain countries (e.g. Australia, Uruguay, etc.).

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

To evaluate resistance problems it must also be considered that innovation in the field of livestock parasiticides has strongly decreased in the last decades.

• The last "new" chemical class of nematicides for cattle and horses (macrocyclic lactones) was introduced in the 1980s, for sheep and goats in the early 2000s (monepantel, derquantel).
• The last "new" tickicide for cattle (fluazuron belonging to the benzoylphenyl ureas) was introduced in the 1990s.
• The last "new" ectoparasiticides for sheep (dicyclanil, spinosad) were introduced in the 1990s.
• The last "new" flukicide for cattle and sheep (triclabendazole) was introduced in the 1970s.

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:

• Resistance Basics: what is resistance, types of resistance, etc.
• Resistance Development: how does resistance develop and what drives it.
• Resistance Diagnosis: how to find out whether a product failure is due to resistance or not.
• Resistance Prevention and Management: how to prevent, delay or manage resistance.
• Integrated Pest Management (IPM): A global approach to parasite control without relying only on chemicals.

Cick here to get to the section on RESISTANCE in this site.