5 Jun 2023

Alternative treatment and control of GI nematodes in ruminants

Charlie Farrer, Hany Elsheikha

Job Title



Alternative treatment and control of GI nematodes in ruminants

Image © sara_winter / Adobe Stock

ABSTRACT

The responsible use of anthelmintic drugs in animal production has been promoted for many years to slow the emergence of anthelmintic-resistant parasites and prevent the spread of drug-resistant strains. The results emerging from the literature show that the application of alternative gastrointestinal nematode (GIN) control methods can significantly reduce development of anthelmintic resistance.

Given the current reliance on synthetic anthelmintics and the barriers to application of alternative treatments, it is unlikely that mass replacement of synthetic anthelmintics will occur. However, reduction of anthelmintics by use of complementary methods can be attractive to farmers and preserve the efficacy of anthelmintics.

In this article, the authors summarise the main alternative methods of GIN control, with emphasis on their potential efficacy and challenges, as well as the opportunities these methods can bring to the livestock industry.

Gastrointestinal nematodes (GINs) are globally recognised as one of the largest challenges in maintaining livestock health and welfare.

GIN infection in ruminants is linked to feed inappetence, and changes in gastric function and protein metabolism (Fox, 1997), resulting in loss of animal productivity and reduction in carcase quality (Figure 1).

Figure 1. Sheep infected with gastrointestinal nematode parasites spend more time idling in the pasture rather than grazing, which leads to less productivity and weight loss.
Figure 1. Sheep infected with gastrointestinal nematode parasites spend more time idling in the pasture rather than grazing, which leads to less productivity and weight loss.

This is an issue of animal welfare and causes great economic loss for farmers. In Europe, the estimated cost of GIN infection is in the billions of pounds, the majority of this being due to loss of production (Charlier et al, 2018). Additional costs are accumulated due to anthelmintic resistance (AR), which makes anthelmintics less effective.

Due to the heavy use of synthetic anthelmintics (Domke et al, 2011), high levels of AR to many common classes of anthelmintics have become widespread throughout Europe (Mickiewicz et al, 2021), posing a barrier to effective control of GINs. Even relatively new anthelmintics – for example, monepantel – are beginning to experience resistance (Höglund et al, 2020).

The global issue of AR indicates a need to identify and utilise alternative or complementary treatments that do not select for resistance. More sustainable and effective methods of worm control need to be identified, tested and applied to farms with the help of veterinarians, to ensure reduction of AR development.

These methods include using plants and plant-derived compounds, nematophagous fungi, selective breeding, vaccination, grazing management and targeted selective treatment.

Implementation of alternative treatment and control methods may find a key role on organic farms, which seek to reduce use of synthetic drugs (Silva et al, 2020).

Efficacy of different alternative approaches

Plants and plant-derived compounds

Plant secondary metabolites (PSM) with proven anthelmintic properties include condensed tannins (CTs), saponins and flavonoids (Oliveira Santos et al, 2019).

A plethora of research shows that a wide variety of plant extracts have strong efficacy against GINs. Tannin-rich legumes have been associated with three main anthelmintic effects: decreased rate of infective larva establishment, decreased egg excretion (either by reduced worm burden or reduced adult female fertility), and delayed development of infective larvae from nematode eggs (also reduced larval motility; Hoste et al, 2012).

Tannins have protein-binding abilities that prevent protein degradation in the rumen and increase protein flow to the small intestine for uptake (Hajaji et al, 2018). Increased protein intake is especially important for animals infected with GINs due to the reduced feed intake and changes in protein metabolism they experience. Negative effects of small ruminant consumption of tannin-rich forage do exist; however, GIN-infected goats will choose to consume these plants when the positive anthelmintic effects outweigh the negative effects, as a form of self-medication (Kearney et al, 2016).

A study into the anthelmintic efficacy of aqueous pomegranate extracts found significant ovicidal effects in egg hatching tests, with efficacy comparable to thiabendazole (Castagna et al, 2020). This is an example of an accessible plant, which is already used in ethnoveterinary practice, showing promising anthelmintic efficacy in vitro.

This result highlights extracts for development into pharmaceuticals, and provides knowledge of accessible plants for GIN control in communities where synthetic anthelmintics are not accessible.

However, large variations in PSM exist. Investigation of the plant Lotus corniculatus found no significant difference in faecal egg counts (FECs), or worm burdens when lambs were supplemented with this crop (Bernes et al, 2000). This may be due to low CT content resulting from environmental factors.

A study into the effects of aqueous extract of sisal waste (AESW) on GINs in goats found that it was significantly effective in reducing FECs and infective larvae; however, it could not be described as an anthelmintic (Botura et al, 2011). It was also suggested that AESW may interfere with the ruminal microbiota by altering pH.

This shows a variety of PSM contained within many plants with a large variety of effects. These PSM need to be isolated and tested in vitro and in vivo to ensure they are effective, and their side effects are identified.

The possibility of GIN strains with reduced susceptibility to CTs in regions where animals consume high levels of tannin-rich browse is also possible (Hoste et al, 2012). This indicates AR development towards anthelmintic plant compounds, despite little industrial use.

Papaya latex is a highly effective anthelmintic against Haemonchus contortus due to the active enzyme cysteine proteinase (Buttle et al, 2011). Resistance to this enzyme has been documented in human GINs (Kearney et al, 2016).

Investigation of sainfoin as a nutraceutical found significant improvement in packed cell volume; however, it also found lower efficacy of ivermectin when sainfoin was fed (Gaudin et al, 2016).

It is essential this is evaluated properly, as different tannin-rich plants may interact with ivermectin in different ways, and this needs to be quantified.

It is possible to identify useful PSM within plants that can be isolated and applied as anthelmintics in the future (Delgado-Núñez et al, 2020). Furthermore, it is reasonable to suggest that incorporation of anthelmintic plants into livestock diets would be effective (Váradyová et al, 2018).

However, many barriers to this application still exist, including cost, awareness of these control methods, and variation in PSM within plants. Further research is required on isolated bioactive plant compounds to establish their anthelmintic modes of action (Karonen et al, 2020).

We can then maximise efficacy, and ensure no issues with toxicity or antagonism with other parasite control methods.

The variety in PSM, resulting in variety in efficacy, indicates that more research is required to fully understand the necessary conditions in which tannin-rich forage is best grown to maximise efficacy (Mederos et al, 2012). In vivo research, which is lacking, will be needed to fully understand efficacy of plant-derived compounds.

Nematophagous fungi

Many fungi have been investigated for their nematode-trapping abilities; however, the majority are not able to survive in the gastrointestinal tract (GIT).

One fungus that has been effective at reducing the number of larvae in ruminants and on pasture when fed as a daily supplement is Duddingtonia flagrans (Larsen, 2000). This is due to its unique intercalary chlamydospores, which allow it to survive in the ruminant GIT and germinate in the faeces, thereby trapping the infective larvae stage and preventing spread on pasture (Waller et al, 2006). This means decreased pasture contamination and reduced GIN infection.

Daily supplementation of D flagrans significantly improves lamb liveweights and reduces worm burden (Waller et al, 2004). Feeding this supplement is of no inconvenience to farmers, who can add it to the daily supplementary feed of lactating ewes. Furthermore, farmers who participated in the study were pleased with the effects of using D flagrans on lamb performance.

In a recent study, the possible effects of feeding D flagrans and the tannin-rich plant, Calluna vulgaris, were analysed (Maurer et al, 2022). No antagonistic effects were found; however, no synergistic effects were discovered either. More research into synergistic uses of D flagrans with different dosages of tannin-rich forage may prove to be effective.

An alternative administration method for daily supplementation of D flagrans is desired (Waller et al, 2004) and more on-farm trials are required to confirm its efficacy (Waller et al, 2006).

Selective breeding

Selective breeding has long been used by farmers to select for production-related traits. It may be beneficial to also include genetic traits for resistance (suppressed FEC and worm burdens), and resilience (sustained production in diseased state) to GIN infection in selective breeding programmes (Woolaston and Baker, 1996).

Selective breeding for resistance and resilience is attractive to many farmers, with farmers in England showing a high preference for this practice (Moore et al, 2016).

A study aiming to assess selective breeding for H contortus resistance and susceptibility in sheep found that resistant sheep maintained consistently lower FECs (Gowane et al, 2020). This suggests that selective breeding could mean reduced use of anthelmintics, resulting in lower costs and reduced development of AR in the long term. It is important for specific indicators of resistance and resilience to be identified, so these traits are correctly selected for.

Using genetic markers rather than pathophysiological indicators would save time, costs, and effort (Casu et al, 2022).

Selection within the herd/flock, and introducing sires with high resistance, can be effective in reducing FECs (Sánchez et al, 2021). However, drawbacks are associated with this, including possible reduction in production traits, high costs with little short-term gain, and big changes to management required in herds/flocks with high infection.

Selective breeding programmes are effective in reducing pasture contamination by selecting for resistance (Sweeney et al, 2016). It would also take a long time for changes in anthelmintic treatment to be possible with these programmes. They may be possible for some farmers and should be encouraged if so, but they are largely not an accessible control method.

It is essential to ensure that selection is not decreasing important traits relating to production or increasing inbreeding, as risks of this have been suggested (Sánchez et al, 2021).

Vaccination

Native antigen vaccines have been shown to reduce FEC, anaemia and mortality rates in both sheep and cattle infected with Haemonchus species (Bassetto and Amarante, 2015). This could mean reduced anthelmintic use, pasture contamination and production loss.

These native antigens are the major components of one of the only current GIN vaccines, Barbervax (used to vaccinate against H contortus in sheep), which is available in the UK, Australia and South Africa.

It is suggested that recombinant antigen vaccinations are needed to ensure a commercially viable and affordable vaccination option against GINs (Charlier et al, 2018). Vaccines have shown a high percentage reduction in FECs, and evidence of maternal antibody transfer exists (Teixeira et al, 2019). However, development is still challenging, and more research is required to ensure the vaccine is effective in all environments.

Research has been conducted into the efficacy of administration of Barbervax pre-lambing and at lamb marking (Kebeta et al, 2020). Lambs that received a Barbervax booster vaccination (and administration of an anthelmintic) had reduced FECs when compared to lambs that only received an anthelmintic.

A recent study investigating the efficacy of a recombinant sub-unit vaccine against Teladorsagia circumcincta in different sheep breeds found high efficacy with several specific immunoglobulin levels against recombinant antigens significantly higher in vaccinated sheep serum (Machín et al, 2021). However, this article also found high levels of individual variability due to many factors, including breed, age, genetic resistance, and parasite factors.

Investigation of the antigen HcADRM1 as a means of generating protective immunity against H contortus in goats found decreased worm burden and FECs, and suggested effective immune applications with recombinant versions of this antigen (Lu et al, 2021).

In regions of the world where vaccines are available, application should be encouraged and used alongside effective anthelmintic use. However, current vaccines are limited in the countries they are licensed for use in, and the species and ages of the animals they can be administered to (Kearney et al, 2016). Future research focusing on recombinant sub-unit vaccines will present effective and affordable options, as promising results are presented in research (Lu et al, 2021).

A need exists to reduce the number of immunogens involved in recombinant sub-unit vaccines, thereby simplifying these vaccines, and making them affordable, as well as investigating differences in immunity related to factors such as breed and age (Machín et al, 2021).

Focus should also be placed on ensuring currently existing vaccines are licensed for use in other age groups and species.

Cows on pasture

Grazing management

The term “grazing management” encompasses many effective methods of reducing pasture contamination, GIN infection rates, and anthelmintic use on farms.

Promising outcomes including reduction in death rate, and increases in growth rate and liveweight in lambs, have been reported (Mahieu et al, 2015). These findings can be distributed to inform farmers of best grazing systems.

One of the biggest barriers to GIN-reductive grazing systems is lack of pasture. Not all farmers have the pasture space or resources to clear their pastures in rotational grazing programmes. For these farmers, rotational grazing systems with other species may be a better option (Kearney et al, 2016).

Common grazing management practices exist that were introduced to reduce GIN infection, but have since been discovered to increase selection for AR. The “dose and move” strategy is a grazing management method, which has been shown to be effective at reducing GIN infection (Laurenson et al, 2012); however, since it involves moving dewormed stock on to pastures with a lack of refugia, it strongly selects for resistance in the GIN population (Falzon et al, 2014). A study conducted in Norway found that 33.2% of sheep farms used the “dose and move” strategy (Domke et al, 2011). Lack of refugia is already an issue in colder countries like Norway, as the cold winters remove refugia from pastures, creating selection pressure.

Preserving refugia is essential for maintaining a susceptible population of GINs; therefore, all grazing management systems must incorporate this concept to slow AR development.

Improved grazing management techniques are always being developed, and these need to be tested and implemented into farms to decrease GIN infection (Mahieu et al, 2015).

Targeted selective treatment

An issue on many farms is blanket use of anthelmintics, rather than selective treatment of specific animals, contributing to increasing presence of AR. Targeted selective treatment (TST) is shown to reduce selection for AR based on the concept of refugia.

GIN infection is overdispersed, with most animals having few worms and subclinical signs, but a few are “shedders”, which have high worm burdens and contribute to pasture contamination (Coppieters et al, 2009). TST focuses on identifying the shedders and treating them.

This provides a source of worms in refugia throughout a treatment programme to reduce anthelmintic use and maintain susceptibility to anthelmintics, while effectively treating infection (Kenyon et al, 2009).

An effective and efficient indicator is essential for the development of TST schemes. Investigation of pathophysiological indicators in TST schemes found that FAMACHA (anaemia scoring system) and DISCO (diarrhoea score) were both strongly related to egg per gram of faeces, while body condition score (BCS) was not (Ouzir et al, 2011).

BCS was not effective in identifying animals with high infection in this study; however, combined with FAMACHA, it could help us to detect animals for treatment. Use of DISCO resulted in a significant reduction of treatments, whereas FAMACHA did not.

It is important for use of TST to result in lower treatment frequency, as treatment frequency is a major risk for AR development (Falzon et al, 2014), and determines cost for farmers.

It is recommended that larger studies be conducted into the correlation of FAMACHA and packed cell volume (Walker et al, 2015), as well as comparison of FAMACHA with individual egg counts to assess FAMACHA as an indicator for treatment.

Geographic information system mapping technology could help to predict exposure risks and map infection patterns in relation to environmental factors (Beck et al, 2015). This could be a useful tool in applying TST – especially as climate change alters current infection patterns.

Random treatment (RT) may be as effective as TST at reducing anthelmintic use while controlling GIN infection.

One of the key benefits of RT is that it does not require identification of highly infected individuals, which can be costly. RT has been found to outperform TST in reducing AR selection (Gaba et al, 2012), although TST was better at reducing infection intensity.

RT could be a good method of GIN control while reducing AR selection and costs of anthelmintics and identification, but a specific random selection technique is needed to be implemented.

A recommended indicator should be identified for TST, so farmers can be informed of how best to identify heavily infected individuals (Ouzir et al, 2011).

Further research may also be required into the use of random treatment (Gaba et al, 2012).

Challenges and opportunities

Many barriers to application of alternative treatments on to farms exist. For example, 41% of English sheep farmers feel that cost is the most influential factor in setting up a new control method (Moore et al, 2016).

This survey also found that although a relatively high level of awareness of alternative methods existed, so too did a slow uptake of such methods, as well as a disconnection between GIN control practices and AR.

A possible connection was identified between higher numbers of staff on the farm that were family members, and an unwillingness to learn about and implement new effective practices. Although more research will need to be undertaken to fully understand this, it is important that unique factors be identified through research and considered when producing educational programmes and giving direct advice to encourage farmers to implement alternative control measures.

Goats are considerably different to sheep physiologically, but this is often not considered, leading to incorrect control of GINs in goats.

Goats do not have a developed immunity against infective larval stage as sheep do (Costa-Junior et al, 2021). They do, however, naturally browse rather than graze, which leads to them avoiding larvae on pasture. This browsing behaviour also allows selection of plants with anthelmintic properties.

In many farming systems, goats are forced to graze on pasture (Zanzani et al, 2014) for convenience of farmers and are not offered the wide range of plants to graze on that they need to maintain their health.

Furthermore, many anthelmintics used by farmers will incorrectly recommend using a sheep dose for goats, even though goats metabolise anthelmintics twice as fast as sheep do (Mohammedsalih et al, 2019). This leads to chronic underdosing of goats, strongly selecting for AR.

Improvement of goat farming systems may mean inclusion of more browsing opportunities where available, higher dosing of goats, and a push to license more anthelmintics for goat use.

Incorrect use of anthelmintics and other control techniques is common on farms, which indicates a lack of education as a major barrier to application of alternative control. On 57.4% of Norwegian sheep farms, timing and frequency of treatment were based on established routines, with triggering factors being primarily weather and climate conditions, rather than any evidence (Domke et al, 2011).

Furthermore, no selective treatment was used, and on most farms, anthelmintic dose was determined by visual appraisal, not by accurate weighing of animals.

A survey on Norwegian cattle farms found that very few farmers used diagnostic techniques, and many reported not being encouraged to do so (Opsal et al, 2021).

In total, 58% of English sheep farms stated that they had not considered planting bioactive forage for dietary supplement, with 20% of these saying that they were unaware of this as a GIN control method (Moore et al, 2016).

This shows a lack of awareness of alternative control methods, and a need for educational programmes and specific veterinarian advice relating to anthelmintic usage, and alternative methods of control to allow for integration on to farms.

Application of control programmes involving TST and grazing management schemes is dependent on many on-farm factors. TST is a good option for reduction of anthelmintics, but requires monitoring of stock with indicators like FAMACHA, BCS, DISCO and FECs. Many farmers do not see this as financially viable (Naeem et al, 2020).

Random treatment may be a better option in many cases – especially in countries where labour costs are high (Gaba et al, 2012), as in the UK. Grazing management schemes have also shown to be effective (Bailey et al, 2009) and educational programmes informing both vets and farmers of new schemes that show high efficacy would be valuable.

International perspective

Both international research into alternative control methods and treatments, and a wide variety of practices used in the international farming community, can help us to learn about effective control methods that could be applied in the UK, as well as other European countries.

An investigation that aimed to gain information about ethnoveterinary use of medicinal plants – particularly in remote and nomad communities in Asia – identified 73 medicinal plants used to treat livestock in these communities (Aziz et al, 2018). This shows long-term, effective use of plants as anthelmintics.

Gaining knowledge from international communities on their use of plants and plant compounds could be very useful to the global community.

Goats fed the CT-rich plant Mimosa caesalpiniifolia had significantly fewer H contortus worms at postmortem analysis compared to the control group (Brito et al, 2018). In Brazil, M caesalpiniifolia is an accessible, drought-resistant, high in protein, fast-growing plant, which can be supplemented to reduce worm burden and promote protein intake.

The flavonoid, isorhamnetin, from the plant Prosopis laevigata, resulted in strong ovicidal activity and significant structural differences, and loss of architectural structure in larvae and eggs (Delgado-Núñez et al, 2020). P laevigata is used in home remedies in Mexico and has ethnoveterinary uses in Venezuela. These promising results support the use of plant-derived compounds as natural anthelmintics.

Grazing management and selective treatment programmes have also been investigated and trialled internationally.

Three grazing management types were investigated in ewes in Australia (Bailey et al, 2009). This included the industry-standard practice of continuous grazing with sheep (CS), as compared to continuous grazing with cattle (CC) and smart graze summer rainfall (SGSR). FECs were significantly lower on CC and SGSR pastures compared to CS pastures.

CS ewes and lambs also required more anthelmintic treatments compared to the other two groups, and the CC, and SGSR ewes and lambs were significantly heavier at weaning. This supports the testing and implementation of new effective grazing systems.

Cell grazing systems have been identified as a good control method for farmers in temperate countries in which larval survival period and risk of losing valuable crops on pasture prevents rotational grazing (Naeem et al, 2020). This technique has shown to be equally effective to rotational grazing systems.

A study conducted in Botswana showed that use of TST was as effective at reducing FAMACHA scores as blanket treatment (Walker et al, 2015). Farmers in these villages had to travel long distances for anthelmintics that they often could not afford, so use of TST means effective GIN control where it otherwise might not be possible.

It is important to consider that many resource-poor farmers may not be able to attempt grazing management schemes due to communal grazing (Walker et al, 2015). However, the cited study also suggests that TST could be a great community-led option for reducing anthelmintic use and effectively treating livestock in areas where anthelmintics are unaffordable and inaccessible.

Conclusion

Responsible use of anthelmintics – particularly the relatively new ones (for example, monepantel) – is key to preserve susceptibility (Sager et al, 2010). This can be achieved by improving education on the correct use of anthelmintics, as well as use of alternative methods to reduce anthelmintic use where possible.

Many alternative treatments exist that are effective in controlling GIN infection in ruminants while reducing development of AR.

Plant-derived compounds, nematophagous fungi, selective treatment schemes and grazing management all have high efficacy, and can help farmers to manage GIN infection in their livestock while limiting AR development.

These different methods should be applied carefully wherever possible, as every farm is different, and many farmers face unique challenges to application of alternative GIN control methods.

Many combinations of alternative treatment and control methods could work effectively to reduce anthelmintic use on the farms, while ensuring healthy livestock and low selection for AR (Waller et al, 2004). For example, a farm incorporating bioactive forage into the diet of their livestock could use a TST programme to reduce use of new anthelmintics such as monepantel, and a mixed rotational grazing system.

Climate change may alter current GIN infection patterns, possibly causing earlier GIN exposure in the spring, and higher exposure in areas that previously had limited GIN infection (Opsal et al, 2021).

It is essential to take this into account when planning and implementing parasite control practices in specific regions (Geurden et al, 2014). Improved diagnosis and surveillance are required to assist these adaptations (Zanzani et al, 2014).

Educational programmes to share information on correct practices would also be useful to promote this.

More research is required – especially regarding vaccine development and selective breeding – so that these control methods can be developed and applied on farms.

  • Use of some of the drugs in this article is under the veterinary medicine cascade.

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