Flukicide Treatment and Resistance in Sheep: Assessing Drug Efficacy and Managing Treatment Failure

Repeated flukicide treatment does not necessarily translate into effective liver fluke control. Sheep may continue to show signs of fasciolosis despite treatment, raising concerns about drug efficacy, incorrect administration or the development of anthelmintic resistance. 

Infection with Fasciola hepatica remains challenging to manage because sheep do not develop protective immunity, making reinfection possible^[1]. Selecting an appropriate flukicide and verifying treatment efficacy are therefore important components of clinical management. 

Triclabendazole Resistance: A Growing Clinical Concern^[1],[2],[3] 

Triclabendazole (TCBZ) is considered the drug of choice for fasciolosis because of its activity against both immature and adult flukes. However, resistance has been reported in sheep across several European countries, threatening its continued effectiveness. 

Other available flukicides include albendazole, clorsulon, closantel, oxyclosantel, nitroxynil and rafoxanide. Unlike triclabendazole, these drugs are active only against adult flukes. Resistance has also been reported against some of these alternatives. 

In cases of suspected TCBZ resistance, nitroxynil and closantel may retain their effectiveness in certain areas. However, alternative drug selection should consider the developmental stage of the parasites and the local resistance situation. 

Treatment Failure Does Not Always Mean Resistance 

Persistent clinical signs or continued detection of fluke eggs after treatment should prompt further investigation. However, these findings alone do not establish anthelmintic resistance. 

Several factors can contribute to apparent treatment failure: 

• Underdosing or incorrect dose calculation. 
• Inadequate storage of the anthelmintic. 
• Improper administration. 
• Inappropriate timing of treatment. 
• Use of diagnostic tests unsuitable for assessing treatment efficacy. 

These factors should be investigated before concluding that resistance has developed^[3]. 

Assessing Flukicide Efficacy 

The faecal egg count reduction test (FECRT) is considered the gold standard for detecting anthelmintic resistance in F. hepatica. However, its interpretation can be challenging because egg shedding is intermittent and eggs may be released from the gallbladder^[3],[4]. 

Other available methods include^[3]: 

• Coproantigen ELISA: Provides an additional approach to assessing fluke infection. 
• Fasciola egg hatch test (FEHT): An in vitro method used to investigate resistance. 

Since field-based drug trials alone may not reliably establish resistance, combining them with in vitro testing such as FEHT has been suggested to strengthen the assessment. 

Currently, there is no universally recognised standard protocol for determining flukicide efficacy or resistance. 

Strategic Treatment to Preserve Drug Efficacy^[3] 

Repeated blanket treatment has contributed to widespread resistance against triclabendazole and other flukicides. Strategic drug use is therefore preferable to routine, repeated treatment without assessing infection risk. 

The objective should be to select the appropriate drug, dose and treatment timing according to the parasite stage and local epidemiological conditions. 

Quarantine treatment is also recommended for purchased sheep to minimise pasture contamination. If fasciolosis signs persist after treatment, faecal examination should be performed three weeks later. Continued egg detection may warrant treatment with an alternative flukicide, where appropriate. 

Clinical Bottom Line 

Effective fasciolosis management requires more than administering a flukicide. Veterinarians should investigate possible causes of treatment failure, assess drug efficacy using appropriate methods and avoid unnecessary repeated treatments. Strategic drug selection and resistance monitoring remain essential to maintaining the effectiveness of available flukicides.

References:

1. Howell AK, Williams DJ. The epidemiology and control of liver flukes in cattle and sheep. Veterinary Clinics: Food Animal Practice. 2020 Mar 1;36(1):109-23. https://livrepository.liverpool.ac.uk/3081693/1/VNAC%202020%20for%20Elements.pdf
2. Beesley NJ, Williams DJ, Paterson S, Hodgkinson J. Fasciola hepatica demonstrates high levels of genetic diversity, a lack of population structure and high gene flow: possible implications for drug resistance. International journal for parasitology. 2017 Jan 1;47(1):11-20. https://www.sciencedirect.com/science/article/pii/S0020751916302569
3. Stuen S, Ersdal C. Fasciolosis—an increasing challenge in the sheep industry. Animals. 2022 Jun 8;12(12):1491. https://www.mdpi.com/2076-2615/12/12/1491
4. Novobilský A, Solis NA, Skarin M, Höglund J. Assessment of flukicide efficacy against Fasciola hepatica in sheep in Sweden in the absence of a standardised test. International Journal for Parasitology: Drugs and Drug Resistance. 2016 Dec 1;6(3):141-7. https://www.sciencedirect.com/science/article/pii/S2211320716300288