Fenbendazole was introduced in the 1970s. Since then, its massive use as a livestock anthelmintic has led to resistance to fenbendazole (and other benzimidazoles) in numerous species of roundworms of livestock and horses.
The most relevant resistant species are:
- In CATTLE, SHEEP and GOATS:
- In HORSES
- Cyathostomins = small strongyles = small red worms, a group of about 50 species of gastrointestinal roundworms
See below for DETAILS.
There are reports on other parasites that have developed resistance to benzimidazoles 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 cases can be mentioned:
- Dogs: Dog hookworms (Ancylostoma caninum). Resistance of Ancylostoma caninum to fenbendazole was reported in the USA in 2019. Little is now yet about how many dogs are affected by such resistance in the concerned regions.
- Pigs: Oesophagostomum dentatum. Resistance of O. dentatum to benzimidazoles was reported in Germany in the early 2000s. However, since then it has not become a generalized problem in most other countries.
Multiresistance is spreading. In an FAO survey in the early 2000s 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 chemical classes of anthelmintics in 95% of the twenty farms investigated: macrocyclic lactones, levamisole, benzimidazoles, and closantel.
Fenbendazole is a broad-spectrum anthelmintic belonging to the chemical class of the benzimidazoles. It is effective against many veterinary helminths of livestock and pets, including roundworms, as well as several species of tapeworms. It is ineffective against flukes.
Fenbendazole is available mainly for oral administration: in the form of drenches, feed additives, and a few slow-release devices for livestock, in oral pastes & gels for horses, and in tablets or pills for pets, often in combination with other compounds. Fenbendazole is massively used in livestock and horses, abundantly in pigs and poultry, less in pets.
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 fenbendazole
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 all benzimidazoles has been reported worldwide, it is very frequent in all types of livestock operations, and can be very high, making treatments completely useless against gastrointestinal roundworms. The problem is particularly dramatic in sheep and goats, less in cattle. Prevalence studies during a FAO survey run in the early 2000s in numerous countries in sheep properties found that more or less strong resistance of gastrointestinal roundworms to benzimidazoles was present in 97% of the properties investigated in Uruguay, 90% in Australia and Brazil, 83% in Paraguay and France, 64% in Scotland, 50% in Mexico and 45% 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, levamisole, 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 benzimidazoles 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 benzimidazoles 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.
- 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 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.).
Gastrointestinal roundworms in horses
- Cyathostomins = small strongyles = small red worms, a group of about 50 species of gastrointestinal roundworms that affect horses, donkeys and other equids worldwide.
- Horse roundworm (Parascaris equorum).
- OCCURRENCE. Resistance of cyathostomins to benzimidazoles is found worldwide, is very frequent and can be very strong. In a survey from 2009 resistance to benzimidazoles was confirmed in >80% of the investigated yards in UK and Germany. It is known to be also frequent in the US, Australia and in many other countries, including Latin America. So far, resistance of Parascaris equorum to benzimidazoles seems to be less frequent than to macrocyclic lactones. Cross-resistance among all other benzimidazoles used in horses (mainly flubendazole, mebendazole, oxfendazole, oxibendazole) must be assumed.
- OUTLOOK. 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.
- 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 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. However, these worms have already developed resistance to some of the alternative chemical classes as well.
- ALTERNATIVE PARASITICIDES for ROTATION.
- Macrocyclic lactones (abamectin, doramectin, ivermectin and moxidectin). Tolerance of cyathostomins to macrocyclic lactones (e.g. ivermectin, moxidectin), manifested as a low but significant worm egg output after treatment (determined after fecal egg counts) is not yet widespread, but has been already reported in Europe (e.g. in the UK, Germany, Italy), the USA, and Brazil. Resistance of Parascaris equorum to macrocyclic lactones has also been reported in numerous countries. Cross-resistance with all other macrocyclic lactones used in horses mainly (abamectin, doramectin, moxidectin) must be assumed.
- Tetrahydropyrimidines (mainly pyrantel). They are not effective against some important gastrointestinal worm species (narrow spectrum of activity). Cases of resistance of cyathostomins to pyrantel have been reported in Europe and the USA, but so far it is much less frequent and severe than resistance to benzimidazoles. Cases of resistance of Parascaris spp to pyrantel have been reported in Sweden (2018). For the time being resistance of these horse parasites to pyrantel seems not to be an issue in most regions.
- Piperazine derivatives. Piperazine is a narrow-spectrum anthelmintic used in pets and livestock effective against some gastrointestinal roundworms (particularly against ascarids, e.g. Parascaris equorum).
- Other anthelmintics such as levamisole and closantel that may still control these worms are not available for horses in most countries.
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.