Nitroxynil is a unique narrow spectrum anthelmintic classified as a nitrophenolic compound. It was developed in the late 1960s but has not been used extensively in Australian cattle, making it useful against parasites overexposed to other actives. Nitroxynil has long been recognised as an effective flukicide and is also known to be useful to control macrocyclic lactone (ML) resistant barber's pole worm1,18. Oral formulations are destroyed by ruminal microflora so only injectable forms are used. Injected nitroxynil is absorbed rapidly and binds almost completely (>97%) to plasma proteins. Concentrations in blood are substantially higher than in the tissues. Unchanged nitroxynil is excreted through the liver leading to high concentrations in the bile ducts, the preferential sites of adult liver flukes. It is then metabolised to a metabolite that acts against late immature flukes (6-8 weeks old) migrating through the liver tissue. Metabolism is slow, taking about 30 days to be completed, and occurs mainly in the liver with excretion through urine and faeces. Nitroxynil produces a rapid spastic paralysis in susceptible parasites by uncoupling oxidative phosphorylation in the cell mitochondria. This disturbs the production of ATP, (energy-carrying molecule found in the cells of all living things) and impairs parasite motility. Used on its own nitroxynil is effective against adult and late immature liver flukes (6-8 weeks old), Haemonchus spp, Bunostomum and Oesophagostomum spp.1. When nitroxynil and clorsulon are combined into one injection they provide a synergistic highly effective flukicide against both adult and early immature fluke (2 - 5 weeks old)2,3. When a ML is also added, the spectrum of activity against worms is widened, to include Ostertagia3. Nitroxynil, due to its slow elimination, has a residual effect, i.e. it not only kills the parasites present in the host at the time of treatment, but protects against re-infestation for a period of time (up to several weeks)1. Nitroxynil is not effective against stomach flukes, lungworms or tapeworms. The standard dose rate of nitroxynil in cattle is 10mg/kg. The drug is well tolerated but side effects can occur at high dose levels, especially in young cattle. A dose of 40mg/kg may be lethal to cattle. Nitroxynil stains hair yellow so care should be taken to avoid spilling1.
Liver fluke (Fasciola hepatica) is a trematode parasite with immature stages that damage liver tissue during migration and adult stages that suck blood within bile ducts. Over 6 million Australian cattle graze at-risk pastures. Both young and adult cattle are susceptible. Studies have shown that it is beneficial to remove liver fluke at the earliest possible stage, reducing liver damage and minimising pasture contamination with fluke eggs4. Strategic liver fluke programs incorporate two core treatments: an all-stage treatment in late Autumn/early Winter and a treatment in early Spring, with additional treatment during Summer when the fluke challenge is high17.
Oral triclabendazole (in products such as Fasinex®, Fasimec®, Flukare C®, Flukamec® and Flukazole C®) has been crucial in liver fluke control due to efficacy against both immature and mature liver fluke. Flukazole C is the only product in this group that also includes oxfendazole, which has a synergy effect with triclabendazole and improves efficacy to control early immature 2-week stage fluke3,16. Resistance to triclabendazole is now well recognised 5-8. Oxyclozanide (Nilzan®) and Clorsulon (Virbamec Plus®) only control adult liver fluke so are not suitable for the main flukicide in a control program. Injectable products containing both nitroxynil and clorsulon (Nitromec or Nitrofluke) can be used in beef cattle to provide an effective alternative which also control early immature fluke2,9. A trial undertaken in Armidale, NSW involved infesting 42 beef cattle with liver fluke strains known to be triclabendazole resistant. Fasinex had no efficacy against these liver fluke while Nitrofluke was 100% effective based on assessing fluke burdens 84 days after treatment, at slaughter2. Products containing nitroxynil should be used in rotation or combination with triclabendazole on all liver fluke properties to manage and/or prevent resistance. They are critical components of quarantine treatments when purchasing cattle from a liver fluke region. Same day use with a macrocyclic lactone/levamisole combination (For example, Cydectin Platinum) provides multiple actives against both worms and liver fluke. An on-farm liver fluke program can be designed to include different products in different classes of stock. For example, Flukazole C, which has a shorter ESI, may be used in growing stock while NitroFluke or Nitromec, with longer ESI, are ideal for replacement heifers and adult breeders3
Barber's Pole Worm
Haemonchus placei is a bloodsucking nematode living in the abomasum of cattle. It is found in most cattle regions of Australia. Young cattle are most susceptible to infestation with an age-related immunity developing by 18 months of age. Uncontrolled burdens in young cattle can lead to anaemia and death. Subclinical production losses in weaners and yearlings can be significant with trials showing a loss of 8-33kg over a few months if burdens are not removed adequately 10,13. Haemonchus spp are well known to readily develop resistance to anthelmintics and the over-reliance on ML drenches has led to widespread ML resistant barber's pole worm10-14. On some properties, drench actives such as ivermectin and doramectin, may have an efficacy close to zero against barber's pole worm. Moxidectin has been demonstrated to have a higher efficacy against ML resistant barber's pole worm, but resistance has also been detected15. In response to the challenge of resistant barber's pole worms ML/Levamisole combination drenches, such as Cydectin Platinum3, have been developed and registered. Combination drenches are considered the new standard for cattle anthelmintics and are important to use at induction, weaning and in young breeders. Programs against barber's pole worm can also consider nitroxynil products because it has a different mechanism of action to both MLs and levamisole and can play an important role to treat and prevent drench resistance. A trial by NSW DPI and LLS in 2021 showed Nitrofluke had 100% efficacy against ML resistant barber's pole worm14. The use of a nitroxynil containing product can be a valuable component of quarantine protocols to remove ML resistant barber's pole worms when introducing new cattle. Nitroxynil-containing products can also be used as an alternative to ML/Levamisole combinations when barber's pole worms have been identified as the main threat. Designing a program that includes both ML/Lev and nitroxynil products can help prolong the useful life of all available actives against cattle barber's pole worms.
The anthelmintic nitroxynil has an important role in Australian beef cattle to both treat and prevent triclabendazole resistant liver fluke and ML resistant barber's pole worm.