Flubendazole was introduced in the 1970s. Since then, the massive use of benzimidazoles as livestock and pet anthelmintics has led to resistance to all benzimidazoles (incl. flubendazole) in several species of roundworms.
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.
Flubendazole 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.
Flubendazole is available mainly for oral administration: in the form of drenches and feed additives for livestock, in oral pastes & gels for horses, and in tablets or pills for pets, often in combination with other compounds. Oxfendazole is abundantly used in pigs and poultry, much less in ruminants. Usage in horses and pets is irrelevant.
Other important benzimidazoles are: albendazole, febantel, fenbendazole, mebendazole, oxfendazole, oxibendazole, thiabendazole and triclabendazole. 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 flubendazole
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.).
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.