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CASE NOTES

Importance of Nitroxynil for control of liver fluke and barber's pole worm in Australian beef cattle

Matt Ball, Virbac Australia

Posted Flock and Herd July 2023

Key Points:

Nitroxynil

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

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 recognised5-8. 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 adequately10,13. 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.

Conclusion

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.

References

  1. Riviere & Papich (2018) Veterinary Pharmacology and Therapeutics 10th Edition
  2. Chambers M (2013) Determination of the efficacy against liver fluke of an injectable nitroxynil/clorsulon formulation in cattle. Veterinary Health Research Pty Ltd, Virbac Data on File
  3. Refer to registered labels for Nitrofluke (APVMA No. 70184), Nitromec (APVMA No. 59844), Flukazole C (APVMA No. 52899) and Cydectin Platinum (APVMA No. 88072)
  4. Virbac Australia (2013) Fluke Kill Liver Fluke Control Manual Available on request
  5. Alvarez LI, Solana HD, Mottier ML, Virkel GL, Fairweather I and Lanusse CE (2005) Altered drug influx/efflux and enhanced metabolic activity in triclabendazole-resistant liver flukes. Parasitology 2005 Oct 131(4):501-10
  6. Overend and Bowen (1995) Resistance of Fasciola hepatica to triclabendazole, Australian Veterinary Journal
  7. Fairweather I (2005) Triclabendazole: new skills to unravel an old(ish) enigma Journal of Helminthology 2005 Sep 79(3):227-34
  8. Brockwell YM, Elliott TP, Anderson GR, Spithill TW and Sangster NC (2014) Confirmation of Fasciola hepatica resistant to triclabendazole in naturally infected Australian beef and dairy cattle International Journal for Parasitology: Drugs and Drug Resistance 4 Issue 1, April 2014, pp 48-54
  9. Hutchinson G et al. (2009) Efficacy of an injectable combination anthelmintic (nitroxynil+clorsulon+ivermectin) against early immature Fasciola hepatica compared to triclabendazole combination flukicides given orally or topically to cattle Veterinary Parasitology Jun 10; 162(3-4):278-84
  10. NSW DPI/LLS (2020) Duck Creek Endoparasite Trial (Virbac data on file)
  11. Ball M and Gibbison W (2021) Resistance pattern to avermectin and milbemycins in current strains of cattle nematodes The Australian Cattle Veterinarian 101
  12. JCU (2020) Comparative efficacy and productivity of pour on endectocides (Virbac data on file)
  13. Virbac Study 620/21 Comparative efficacy and productivity of Cydectin Platinum Dual Active LV Pour On against field infestations of the cattle tick, Rhipicephalus australis (microplus) - Data on file
  14. NSW DPI/LLS (2021) Pearces Creek Efficacy and Production Response to injectable drenches - Virbac data on file
  15. Prichard R and Geary (2019) Perspectives on the utility of moxidectin for the control of parasitic nematodes in the face of developing anthelmintic resistance International Journal for Parasitology - Drugs and Drug Resistance 10:69-83
  16. Boray JC(1996) Synergistic anthelmintic composition www.google.ch
  17. Boray J (1999) Liver Fluke Disease in Sheep and Cattle. Agfact AO.9.5.7, NSW Agriculture
  18. Wellington AC (1978) Nitroxynil: Anthelmintic activity in cattle following subcutaneous injection. Journal of the South African Veterinary Association ISSN: 1019-9128, 1978 Jul; 49(2):125-6

 

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