Closantel was introduced as an anthelmintic in the 1970s. Since then, a few resistance cases have been reported in several countries in sheep and cattle farms.

So far, the problem is much less widespread and severe than resistance of gastrointestinal roundworms to benzimidazoles, macrocyclic lactones or levamisole.

The most relevant resistant species are:

• In CATTLE and SHEEP:
  • Gastrointestinal roundworms, mainly Haemonchus spp
  • Liver flukes (Fasciola hepatica)

See below for DETAILS.

Closantel is a narrow-spectrum anthelmintic belonging to the chemical class of the salicylanilides. It is effective against some gastrointestinal roundworms (e.g. Bunostomum, Haemonchus, Oesophagostomum, Ostertagia - Teladorsagia, Strongyloides, Trichostrongylus), liver flukes and some external parasites of cattle and sheep (e.g. sheep nasal bots, cattle grubs). It is not effective against tapeworms.

Closantel was broadly used in ruminants before more effective compounds came to market in the 1980s that vastly replaced it (benzimidazoles, macrocyclic lactones, etc.). In the last decade usage of closantel has increased considerably along with the exacerbation of resistance problems to other chemical classes in many countries. Nowadays usage is still growing.

Closantel is available mostly in the form of oral drenches, injectables and topical pour-ons (only for cattle), often in combination with other compounds. There are dozens of generic products available in numerous countries. It is not used in horses, pigs, dogs or cats.

Other veterinary salicylanilides are: niclosamide, oxyclozanide, and rafoxanide. They are much less used than closantel.

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 closantel

Cattle, sheep and goats:

• Gastrointestinal roundworms, mainly Haemonchus spp
  
  • OCCURRENCE. Resistance to closantel has been reported in numerous sheep farms in Uruguay, Argentina and Brazil, mainly in sheep but also in cattle. In many cases affected roundworm populations were multiresistant, i.e. simultaneously resistant to several chemical classes. 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. 
  • OUTLOOK. Problems are likely to worsen everywhere, along with the predictable use increase of closantel in the desperate effort to control multiresistant gastrointestinal roundworm populations.
  • 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 closantel 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 other chemical classes that still work can make sense. However, those worm species that have developed resistance to closantel are often already resistant to these other chemical classes. Other chemicals or chemical classes that control gastrointestinal roundworms of livestock to some extent are the following:
    • Benzimidazoles (e.g. febantel, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, etc.). Resistance of gastrointestinal roundworms to benzimidazoles is already very frequent worldwide, can be very high, and multiresistant worm populations are spreading.
    • Macrocyclic lactones (abamectin, doramectin, eprinomectin, ivermectin and moxidectin). Unfortunately, resistance of gastrointestinal worms to macrocyclic lactones has already developed worldwide, is very frequent as well and can also be very strong.
    • Levamisole (imidazothiazoles). Resistance of gastrointestinal roundworms to levamisole is less frequent than to benzimidazoles and macrocyclic lactones, but it is also spreading and strengthening because it is increasingly used in livestock due to resistance to other chemical classes. Multiresistant worm populations that are also resistant to levamisole have been already reported.
    • Tetrahydropyrimidines (e.g. pyrantel, morantel, etc.). Are not effective against some important gastrointestinal worm 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 yet an issue.
    • 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.).
• Liver flukes (Fasciola hepatica)
  • OCCURRENCE. Resistance of Fasciola hepatica to closantel was already reported in sheep and cattle farms in Australia in the 1980s, but it does not seem to be a current problem nowadays. More recently resistance has been reported in cattle farms in Sweden (2015) and in sheep farms in Iraq (2019). Cases of resistance to other salicylanilides with probable cross-resistance to closantel have been also reported, e.g. to rafoxanide in cattle farms in 2008 in Turkey
    
  • OUTLOOK. Problems are likely to spread and worsen, perhaps not too fast, as usage of closantel and other salicylanilides increases in order to handle resistance of Fasciola hepatica to albendazole and triclabendazole.
  • 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. Whatever measures that keep the pastures dry will reduce level of infestation of the pastures with liver flukes, since they need snails as intermediate hosts. Read also the article on liver flukes in this site. Where alternative chemicals of other chemical classes are still working against these worms, rotation is usually a good option, i.e. to stop using benzimidazoles and to use other products of still effective chemical classes during several years.
  • ALTERNATIVE PARASITICIDES for ROTATION.
    • Benzimidazoles (only albendazole and triclabendazole). However, resistance of Fasciola hepatica to benzimidazoles is much more frequent and strong than to closantel.
      
    • Clorsulon. It is a narrow-spectrum anthelmintic effective against several fluke species, also against liver fluke There are a few reports on liver fluke resistance to clorsulon, but it is certainly not a big issue yet. Clorsulon is almost always used as an injectable in mixture with  ivermectin, also against liver flukes and a few gastrointestinal roundworms. Resistance of Fasciola hepatica to clorsulon was reported in a few sheep farms in Spain in 2013-14.
    • Nitroxinil. It is a narrow-spectrum anthelmintic effective against liver flukes and a few gastrointestinal roundworms (e.g. Bunostomum spp, Haemonchus spp, Oesophagostomum spp. There are a few reports on liver fluke resistance to nitroxinil as cross-resistance with other flukicides, but it is certainly not a big issue yet. Nitroxinil is usually administered as an injectable.

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.