Control Tools

• Diagnostics availability

• Commercial diagnostic kits available worldwide

  Coprological (microscopical and molecular) as well as serological (direct and indirect) tests are available in established veterinary laboratories across Europe. The availability differs greatly between host species and laboratories as well as are not always standardized and commercialized.Commercially available kits and materials include:

  • McMaster-slides, FLOTAC, Mini-FLOTAC, Fill-FLOTAC and FECPAK for microscopical examination of faecal samples (faecal egg counts)
  • Svanovir®-O. ostertagi-Ab for detection of antibodies against gastrointestinal nematodes in bovine milk (and serum) samples.
  • FECPAK^G2 and Parasight automated egg counting systems are now available for use in sheep and cattle
  • Svanovir®- A. suum-Ab for detection of antibodies against Ascaris in fattening pigs.

  List of commercial diagnostic kits (Diagnostics for Animals)

  GAPS :

  There is a need for standardisation of available diagnostic methods to qualify and quantify parasite burdens or their consequences (i.their contribution to environmental contamination).

  Novel tests for the early detection of anthelmintic resistance and the interpretation of results have seldom been tested in the context of realistic systems of production.

  Sampling strategies and multi-parasite species rapid (pen-side) and low-cost diagnostic tests need to be evaluated out on farms.

  Diagnostic systems based on the principle of identifying those animals that can cope with parasite infections (i.e. resilient) without the need for anthelmintic intervention must be developed.

  Non-invasive sampling protocols?

  Include goats in the validation of automated egg counting systems and any other diagnostic tool.

• Diagnostic kits validated by International, European or National Standards

  None.

• Diagnostic method(s) described by International, European or National standards

  None.

• Commercial potential for diagnostic kits worldwide

  Moderate.

• DIVA tests required and/or available

  Not applicable.

• Vaccines availability

• Commercial vaccines availability (globally)

  Barbervax, vaccine against Haemonchus contortus in sheep is available in Australia, South Africa and the UK.

  GAPS :

  Vaccines for all the important gastrointestinal nematodes – in some cases (Haemonchus, Ostertagia) might have a market place as monovalent vaccines but the ambition should be polyvalent vaccines.

• Marker vaccines available worldwide

  None.

• Effectiveness of vaccines / Main shortcomings of current vaccines

  Barbervax (vaccine against Haemonchus contortus) reduces worm numbers and worm egg output by > 90%, but repeated administration is required (3 primary immunisations and 6-weekly vaccination boosts).Prototype vaccines against Ostertagia ostertagi and Cooperia oncophora reduce worm egg output by 40-98% during a two-month challenge period. An experimental recombinant vaccine against H. contortus reduced faecal egg counts by 43-80% and worm counts by up to 80%. Main shortcomings include lack of cross-protection against other important nematodes and possible need for repeated administrations.

  No prototype vaccines are available in chicken. Ascaridia significantly increase local mRNA expression of IL-4 and IL-13 and significantly decreased TGF-b4 expression in the jejunum two weeks after infection. However, immunity to A. galli develops slowly and the level of protection is partial.

  GAPS :

  Required efficacy has been defined for some species by experimental infection and/or by modelling. There is a requirement to define efficacy in the field, probably at the level required to reduce or eliminate the economic impact of the disease, and in different climate and management settings.

  Multivalent vaccines.

  In laying hens traditional vaccination strategies based on boosting aquired immunity seems to be an unrealistic alternative due to the short production cycles.

• Commercial potential for vaccines

  Native and recombinant protein “prototype” vaccines are under development for Haemonchus, Ostertagia and Cooperia with support from the commercial sector.(Cocktails of) different recombinant proteins have given useful levels of protection against Ostertagia, Haemonchus and Teladorsagia in recent housed trials.

  GAPS :

  Effective recombinant vaccines to allow mass production are required.Effective means of delivery.

• Regulatory and/or policy challenges to approval

  This whole area is undefined. How will the regulators treat a monovalent vaccine with 60% protection? Vaccines seem to be entirely in line with policy at a national, European and global level.

  GAPS :

  Helminth vaccine registration guidelines. We need to interact with the regulators to ensure the targets are acceptable.

• Commercial feasibility (e.g manufacturing)

  Recombinant vaccines can be produced on an industrial scale. The current native protein vaccines are not commercially feasible, except for specific niche markets (e.g., a native Haemonchus contortus vaccine in countries where H. contortus is the predominant species).

  GAPS :

  Development of affordable large-scale expression systems that can produce recombinant helminth proteins with the same conformational and protective properties as the native antigens.Concerted interaction between researchers, the commercial sector and end-users is required.

• Opportunity for barrier protection

  Not applicable.

  GAPS :

  Not applicable.

• Pharmaceutical availability

• Current therapy (curative and preventive)

  Anthelmintics (see Section “Main means of detection, prevention, control/Therapeutics").

  GAPS :

  Means of optimising anthelmintic usage to both control nematodes and maintain efficacy across all livestock.

  A better understanding of pharmacokenetics, how it is influenced by routes of administration and how it affects the concentration of active entering target worms. Similarly, effects of host condition, diet and age needs to be explored in more detail.

• Future therapy

  The difficulties and cost of discovering new actives, can be compensated for in part through the introduction of novel mixtures, formulations and delivery systems.Instead of blanket treatments future treatment strategies could benefit from selective treatment of only those animals requiring treatment or in targeted groups at time points when treatments are most efficient.

  GAPS :

  Short term – (1) Introduction of anthelmintic combinations and/or novel formulations.; revisiting actives which were never released due to inadequate broad-spectrum efficacy but which may be effective if combined with other similar drugs; Combining existing anthelmintics with resistance inhibiting molecules which render resistant worms susceptible (2) Development of sustainable treatment regimes with the currently available anthelmintic classes.Long term – Development of in vivo parasite gene silencing technology (e.g. RNAi).

• Commercial potential for pharmaceuticals

  Large – based on current anthelmintic market.Also, meat consumption predicted to continue increasing globally until 2050. Therefore, more pressure on grazing, increased intensification where feasible.

  GAPS :

  Statistics difficult to obtain because of different routes of distribution (e.g. vet/non-vet) and some generic companies do not submit figures.

• Regulatory and/or policy challenges to approval

  Safety studies and their interpretation, particularly in terms of tissue residues/withholding periods and environmental impact assessments.

  GAPS :

  Knowledge transfer and exchange with policy makers and commerce to ensure global standardisation of regulatory requirements.

• Commercial feasibility (e.g manufacturing)

  Existing technology is adequate.

• New developments for diagnostic tests

• Requirements for diagnostics development

  The core needs are improved diagnostics for the identification of parasites, quantitation of infection intensities and of resistance to different anthelmintics, assessment of disease and production impacts. To achieve this the following are needed:

  • specific proteins, peptides, metabolites or nucleic acid sequences for species differentiation of eggs, larvae or adults ;
  • novel biomarkers and molecular genetic markers for anthelmintic resistance ;
  • novel genetic markers associated with host resistance/resilience.

  Improvement and refinement of:

  • non-invasive and automated sampling (e.g. milk, meat-juice, automated body condition scoring and weight determination) ;
  • pen-side (direct and indirect) diagnostics ;
  • quantitative diagnostic tests.

  GAPS :

  Need for high throughput novel and affordable diagnostics for the farming and research communities.

  Novel target proteins and morbidity markers.

  Development of ‘risk’ models capable of predicting when disease outbreaks are NOT going to occur – enabling users to safely reframe from prophylactic treatments.

  Development of improved sampling strategies (invasive and non-invasive) that can assist in targeted or targeted selective treatment strategies. What kind of diagnostic samples are required to reflect the levels of infection or environmental contamination, e.g. when and how are these samples collected? Note one solution does not fit all as the requirements can differ between livestock (i.e ruminants and monogastrics) and herd/flock management.

• Time to develop new or improved diagnostics

  From short (1-2 years) to evaluate prototype test and improve standardization to long (4 years or more) to develop more specific methods suitable for high-throughput platforms.

• Cost of developing new or improved diagnostics and their validation

  Requires research and costs will be relatively high. Return on investment is potentially high based on improved effectiveness and sustainability of control.

  GAPS :

  Develop a better understanding of the cost the farmer is prepared to pay for diagnosis at farm level and individual animal level.

• Research requirements for new or improved diagnostics

  See section “New developments of diagnostic tests/Requirements and/or opportunities for diagnostics development”.

  GAPS :

  Funding for research laboratories capable of discovering novel parasite diagnostic markers, methodologies and platforms.Technologies allowing pen-side diagnosis against a wider range of pathogens.

• Technology to determine virus freedom in animals

  Not applicable.

• New developments for vaccines

• Requirements for vaccines development / main characteristics for improved vaccines

  Requirements :

  • knowledge of protective immune responses ;
  • protective worm antigens ;
  • large-scale expression systems ;
  • effective antigen delivery systems ;
  • definition of the efficacy required for vaccines².

  GAPS :

  For most livestock GI nematodes:

  • improved knowledge of protective immune responses in different species and breeds/crosses ;
  • identification of protective worm antigens ;
  • development of affordable large-scale expression systems that can produce recombinant helminth proteins with the same conformational and protective properties as the native antigens ;
  • development of improved antigen delivery systems ;
  • knowledge on required vaccine efficacies ;
  • regulatory framework.

• Time to develop new or improved vaccines

  5 to 20 years.

• Cost of developing new or improved vaccines and their validation

  Lower than the cost for development of conventional anthelmintics.

  GAPS :

  Funding is needed to bridge the gap between lab research and commercialisation.

• Research requirements for new or improved vaccines

  See section “Requirements or opportunities for vaccines development/ main characteristics for improved vaccines”.

• New developments for pharmaceuticals

• Requirements for pharmaceuticals development

  Anthelmintics with new mode of actions.Combinations of existing classes of anthelmintics.Current anthelmintics have a high broad-spectrum efficacy against most nematodes.Low or nil effect of a number of anthelmintics against Trichuris – for pigs/humans.

  GAPS :

  A regulatory framework for the combinations of existing classes of anthelmintics. There is no regulatory framework for the development of pharmaceuticals with efficacy against resistant strains of nematodes in the EU, or with the ability to prevent the development of AR.

  Long term regulatory impact of environmental safety concerns. Currently there is increased scrutiny on environmental safety, both for new products and for existing products. Existing products (>25 years on market) have been subject to additional questions regarding environmental safety with an increased risk that these products will be taken off the market.This has an impact on the attractiveness to develop new products.The PFAS guideline that is currently being developed may have an impact on existing products and future product development.There needs to be a clearer definition of what will be acceptable in future in terms of benefit-risk assessment and a clearer definition of what will not be acceptable as a risk in terms of environmental safety.

• Time to develop new or improved pharmaceuticals

  Greater than or equal to 10 years for new chemical entity.

• Cost of developing new or improved pharmaceuticals and their validation

  The costs of the discovery phase are highly variable and difficult to estimate.The development cost for compounds/antigens that have successfully resulted from the discovery phase is typically around 50 million euro.

• Research requirements for new or improved pharmaceuticals

  Additional screens to identify novel targets (e.g. parasite genes).

Disease details

• Description and characteristics

• Pathogen

  Only Nematoda of the gastrointestinal tract of ruminants as well as of poultry and pigs are considered (Trichinella excluded). Large number of genera and species (annex1). Most important GI nematodes are :Cattle - Ostertagia ostertagi, Cooperia oncophora, Nematodirus helvetianus ;Small ruminants - Teladorsagia circumcincta, Haemonchus contortus, Trichostrongylus colubriformis, T. vitrinus, Nematodirus spp ;Poultry - Ascaridia spp. and Heterakis gallinarum ;Pigs - Ascaris suum, Trichuris suis, Oesophagostomum spp.

  GAPS :

  Variations in biology of nematodes.

  Knowledge of how nematode parasites are affected by the occurrence of or protection to other pathogens (viruses and bacteria) is virtually non-existent.

• Variability of the disease

  Agent types: In each host, GI nematodes often occur as mixed infections but some species are more pathogenic than others (e.g. Ostertagia ostertagi in cattle and Haemonchus contortus in sheep/goats). Similarly in poultry Ascaridia is more important than Heterakis. Within nematode species, no clearly documented differences in pathogenicity between strains or regional isolates. Heritable mutations that confer drug resistance comprise key agent variation in all major species.

  Host range: Differences in host susceptibility to GI nematodes occur between animal species and breeds/crosses (latter has mainly been described in small ruminants, to a lesser extent in cattle/swine/poultry) and within breeds between age classes (younger animals more susceptible), physiological status (pregnancy, lactation, level of production), nutritional status (protein) and genetics to the level of the individual.

  Temporal variability: In ruminants, parasitic gastroenteritis mainly occurs during the grazing period and will vary geographically. Environmental, climatic and management conditions (e.g. access to pastures, turn-out and housing periods) will determine infection levels. Selective control agents may suppress certain nematode species and allow others to flourish. As an example long acting macrocyclic lactones can suppress e.g. Teladorsagia or Ostertagia, and may allow e.g. Cooperia and Trichostrongylus to flourish, as a result of differences in drug efficacy across species as well as biological differences such as generation time.

  Spatial variability: There are differences in the prevalence, abundance and importance of parasite species according to regions (sub-arctic, temperate & Mediterranean regions) or local environmental factors. For example, in Northern Europe Teladorsagia circumcincta is the most important GI nematode in sheep, while in temperate & Mediterranean regions Haemonchus contortus used to be more important, although now it is very common also in the north, possibly due to climatic changes.

  Poultry ascarids has reemerged in laying hens since the Pan-European ban of the traditional wire cages.

  GAPS :

  Parasite genetic variation and virulence.Genetic mutations for drug resistance: the nature, mechanism, detection, distribution and management of such mutations are key knowledge gaps and crucial for sustainable control. Fitness in relation to strains, anthelmintic resistance and host resistance (including interactions) needs to be explored further. Although well known, variations in susceptibility/resilience are underexploited as a control strategy.

  In-depth knowledge is required about the mutations that cause anthelmintic resistance. Note that the level of knowledge is extremely varied. For example, while it is relatively well developed for strongylids (i.e. Haemonchus contortus and some other clade V nematodes), it is more or less non-existent for the ascarids. Both to develop molecular tests and to predict/evaluate risks of resistance development, basic knowledge about the mechanisms involved must be in place.

  Currently, very few genetic markers are available to identify host resistance and resilience and few studies describe functional genomics.

  Deeper insights are required into the effect of climatic, environmental and management conditions on the availability of infective stages and abundance of parasitic stages within the host. These insights are expected to lead to predictive models of disease and better adaptive management. Control procedures, based on epidemiological principles, have seldom been tested in the context of realistic systems of production.

  Better georeferenced data are needed for parasite occurrence and genotypes in order to appreciate their spatial distribution and future changes.

  The relative roles of livestock movement and other aspects of farm management in the spread of parasites and drug resistance alleles.

  The use of connected/automatic devices for remote monitoring of ruminants (geolocalisation, animal activity) linked to grazing management software has to be developed and evaluated.

  Basic knowledge of the biology of worms is relatively well known. On the other hand, information on how ascarids are spread both geographically and between flocks within the same production site is lacking.

• Stability of the agent/pathogen in the environment

  Environmentally very stable. Infective L3 larvae can commonly survive up to one year on pasture and at low levels into subsequent years (depending on climate and worm species); infectious eggs (Ascaris, Trichuris, Nematodirus, Ascaridia) can survive for several years on pasture or in stables.

  GAPS :

  Knowledge about agents killing infectious eggs under field conditions are missing.Larvicidal compounds/management on pasture.Characterisation of mortality rates to determine ‘safe’ pasture for grazing management.Influence of pasture composition and larval development and survival.Effects of severe drought/rainfall periods on GIN epidemiology. Quantitative molecular methods have not been sufficiently adapted for estimation of the level of pasture contamination and infectivity. Methods for estimating residual environment parasite challenge should be developed and modernized (eDNA technologies). This also includes the sampling methods that needs to be reviewed.

  Protocols for increased biosecurity should be improved. This is important not least to prevent the spread of resistant between farms, but also to prevent local spread (eg. Ascaridia) between flocks on the same farm.

• Species involved

• Animal infected/carrier/disease

  Nematode species are typically host-specific, but there are species overlaps in sheep and goats for example and some parasite species of sheep and goats can infect cattle and vice versa (see annex 1). Only one species (Trichostrongylus axei) may infect ruminants, pigs and horses.Most animals are asymptomatic carriers.

  GAPS :

  Shifts in host specificity, e.g. adaptation to multiple hosts under rotational grazing regimes.Pathogenic aspects of crossed infections (e.g. for Cooperia species between SR and cattle or O. ostertagi for goats).

• Human infected/disease

  Ascaris suum (and Trichuris spp. and occasionally other nematodes) can infect humans and it is closely linked and perhaps identical to Ascaris lumbricoides, the species infecting humans and primates. In principle also some ruminant GINs (e.g. H. contortus, T. circumcincta or Trichostrongylus spp.) can infect humans. However, this occurs only very rarely.

  GAPS :

  Although unlikely and difficult to study, the possibility that Ascaridia galli, like other closely related roundworms, is a zoonosis has never been investigated.

• Vector cyclical/non-cyclical

  No vectors for the most important species (some minor genera have insect vectors).

  GAPS :

  The importance of flying insects and rodents as mechanical vectors for nematodes is unexplored (eg. on poultry farms).

• Reservoir (animal, environment)

  Wild ruminants and wild boars (see comments on species specificity above).

  GAPS :

  The identification of wild-life as a potential reservoir of parasites, and their role in the spatial spread of parasites and resistance alleles; or, conversely, as refugia for drug-susceptible genotypes.Role of invertebrates such as beetles, soil and earth worms as reservoir for nematode larvae in respect with climatic changes.

• Description of infection & disease in natural hosts

• Transmissibility

  Eggs excreted by the host need first to develop to an infectious stage (L3 that is free living or in ovo). The host is infected by oral ingestion.Speed of development to the infectious stage is mainly determined by temperature and varies between a single to multiple weeks. Faeces act as egg/larvae reservoirs (large differences between cattle and small ruminants as well as poultry). Moisture (rainfall) is important in facilitating the release of infective stages from the faeces onto pasture. Temperature and moisture also affect survival of infective stages and therefore pasture infectivity.

  GAPS :

  Better understanding of parasite fitness (from egg to L3) as a key of general epidemiology.The role of host immunity in influencing fitness / transmission of free-living stages.

  Better understanding of climatic influences in order to predict occurrence of disease, and to support control through evasive grazing and strategic targeting of treatment.

• Pathogenic life cycle stages

  Developing stages and adults.

  GAPS :

  See above (Section “Transmissibility).

• Signs/Morbidity

  Anorexia, diarrhoea, anaemia, cachexia, production losses (weight, milk, wool, feed conversion). Very high morbidity (i.e. production losses) in ruminants but lower in pigs.

  In laying hens the magnitude of the harmful effects on the host such as reduced growth, increased feed consumption, decreased egg production, anaemia, and diarrhoea, grows with increased worm burden. Concurrent bacterial infection can lead to a greater adverse impact on the host.

  GAPS :

  Deeper insights into the morbidity and actual production (qualitative and quantitative) losses caused by GI nematodes. This is of high relevance given the high pressure on food prices and the need to decrease the ecological footprint of intensive farming systems.Consequences for morbidity of mixed-species infections including the impact of nematode infections on the occurrence of secondary (viral, bacterial, protozoal) infections and heterologous vaccine efficacies as well as the interactions with the gut-microflora.Potential for changes to morbidity and production impact as a result of management change, e.g. increasing outdoor pig production, lengthening grazing seasons in ruminants.

• Incubation period

  Varies from weeks to months; most infections are chronic.Infection is generally continuous when/if animals are on pasture (ruminants and poultry) and/or are kept in infected housing (poultry and pigs).On pasture, infection may be subject to seasonal variations.

• Mortality

  In the absence of control measures, mortality can be high, particularly with the more pathogenic species such as Haemonchus contortus, Nematodirus battus, Teladorsagia circumcincta & Ostertagia ostertagi.

• Shedding kinetic patterns

  Infected animals can excrete eggs more-or-less continuously. Level of egg excretion can fluctuate, e.g. increasing in ewes following parturition or season. Individuals vary in level of egg excretion/output.

  GAPS :

  Why are some animals excreting a high number of eggs, can we develop tools to identify these?

  What determines emergence of arrested stages, for example, termination of hypobiosis in gastrointestinal nematodes in ruminants or the end of the mucosal phase of ascarids in poultry.

• Mechanism of pathogenicity

  All GI nematodes in ruminants induce anorexia and impair nutrient utilisation. Infections with nematodes are likely to have a higher impact in animals suffering from concurrent diseases,under-nutrition or in high-producing animals that have higher nutritional requirements.A key characteristic of GI nematode infections is that pathogenicity is burden-dependent, i.e. increases with increasing burdens, hence can be negligible, subclinical or severe in different individual hosts infected with the same nematode species, even within the same herd or flock.Pathogenicity varies according to the nematode genus (species) and includes the following:Ostertagia/Teladorsagi/Trichostrongylus influence protein digestion and utilisation and can cause diarrhoea.Haemonchus – blood sucking worm inducing anaemia ;Nematodirus – principle effect on water balance resulting in diarrhoea ;Ascaris – nutrient malabsorption, intestinal occlusion, pulmonary dysfunction, secondary bacterial infections in the lungs, possibly negative interactions with certain pathogens and vaccines ;Trichuris - hemorrhagic diarrhoea (dysentery) ;Ascaridia - larvae dig into the the mucosa (enteritis) which results in decreased food intake and reduced weight gain. Massive adult worm burdens can obstruct the intestine leading to reduced egg production ;Heterakis - relatively harmless but can transmit Histomonas (blackhead).

  GAPS :

  Different elements of importance for pathogenesis are still unknown and their identification may be important to better understand rationale of production losses and for vaccine development.Pathogenic interactions during multi-pathogen infections are incompletely understood.Processes leading to overdispersion in parasite burdens and hence differential pathogenic impacts within a flock or herd.Impact of infection on immune response/balance towards other pathogens.Mechanisms involved in resilient/non resilient animals i.e. beyond the simple consideration on worm burden control (resistance aspect).

• Zoonotic potential

• Reported incidence in humans

  Trichostrongylus spp. and some other GINs which are primarily parasites of ruminants can occasionally infect other animals and humans, especially in those living in close proximity with livestock. Most infections in humans are asymptomatic. Heavy infections can cause gastrointestinal problems (abdominal pain, diarrhoea, anorexia), headache, fatigue, anemia and eosinophilia.Ascaris suum/A. lumbricoides – Only in Denmark (DK) the incidence has been studied: 3.0 per 10,000 children living in the urban area and 27.8 per 10,000 children in the rural population. Estimated 200-500 cases/5 mill./year in DK but severe underreporting.

  GAPS :

  Studies required to assess prevalence of zoonotic nematodes in humans.

• Risk of occurence in humans, populations at risk, specific risk factors

  Ascaris suum - mainly children, farm environments and often related to use of pig slurry as fertiliser. A. suum in humans has been observed mainly in developed countries where A. lumbricoides is no longer common. In developing countries mainly A. lumbricoides is present in humans.

• Symptoms described in humans

  Ascaris suum - no recorded pathogenicity, but A. lumbricoides cause retarded growth and cognitive impairment, pneumonitis, abdominal pain (e.g. bile duct infections).

  GAPS :

  Need to assess symptoms in humans.

• Likelihood of spread in humans

  Ascaris suum – low.

• Impact on animal welfare and biodiversity

• Both disease and prevention/control measures related

  Clinical parasitic gastroenteritis (PGE) is a severe welfare problem across all hosts.The therapeutic use of effective anthelmintics in the face of clinical disease generally is rapidly effective.The presence of anthelmintic resistant GI nematode populations threatens drug efficacy globally and is leading to treatment failure.Biosecurity measures as well as pasture and nutritional management, supported by the selective use of anthelmintics within a tactical or strategic protocol can control diseases and thus maintain high levels of welfare.In some regions, mainly on small farms and in marginal areas, prevention/control measures are not regularly practised.

  GAPS :

  Recent studies have shown that some animals are resilient to GI nematodes and require no anthelmintic treatment. A proportion of infected animals show no sign of morbidity, production loss or disease. It is necessary to generate data across different species, breeds and production systems, to define the level of GI nematode infection that affects productivity and welfare of animals.Consequences of low input and organic farming practices on infection outcomes and welfare are ill defined.Consequences of low efficacy of anthelmintic treatments due to drug resistance on infection outcomes and animal welfare are ill defined.Translate novel insights on the impact of management into high intensity farming systems.

• Endangered wild species affected or not (estimation for Europe / worldwide)

  No specific threat to endangered species.GI nematodes are known to regulate wildlife populations and infections could be a factor in reduced fitness and decline of vulnerable populations.Antiparasitic drugs can negatively affect invertebrates, especially dung-breeding insects, fresh water fish and other aquatic organisms, and could in theory have negative impacts on their populations and those of species at higher trophic levels.

  GAPS :

  True impact of anthelmintics on invertebrates, fresh water organisms in general, at population level, is unknown. The consequences on animal species at higher trophic levels are also unknown.

• Slaughter necessity according to EU rules or other regions

  No.

• Geographical distribution and spread

• Current occurence/distribution

  For ruminants, nematodes have a worldwide distribution, with regional differences in specific occurrence. All grazing/outdoor reared animals are exposed to infection with trichostrongyles. Ruminants reared indoors can sporadically be infected, e.g. with Trichuris spp. or other species when they are fed fresh grass at stable.In pigs reared indoors, individual prevalence varies between 0-50% in Ascaris suum, 0-5% in Trichuris suis, and 0-100% for Oesophagostomum spp. depending on age groups and management. In pigs, outdoor systems are associated with significantly higher GI nematodes infection rates.

  In poultry, Ascaridia galli and Heterakis gallinarum has increased within the past decade in laying hens on both conventional and organic commercial farms due to the European Union (EU) ban on non-enriched battery cages.

  GAPS :

  For some parasite species, regions or eco-systems little or no representative data on GI nematode prevalence is available.

  Poor knowledge of temporal changes and the causal factors in parasite abundance. Longitudinal studies on sentinel farms to better understand the dynamics of GI nematode infections over years (including the impact of climate change), will help to define management measures.

  In most countries, there are no standard programmes in place to monitor the prevalence, infection intensity and evolution of GI nematode infections.

  There is no systematic monitoring of the occurrence and spread of anthelmintic resistant GI nematode populations resulting from intensive use of anthelmintic drugs, or from the movement of animals between farms.

• Epizootic/endemic- if epidemic frequency of outbreaks

  Infections with GI nematodes are endemic.

• Speed of spatial spread during an outbreak

  Not applicable.

• Transboundary potential of the disease

  No, ubiquitous.

• Route of Transmission

• Usual mode of transmission (introduction, means of spread)

  All livestock reared outdoors are, to some extent, infected and most animals excrete eggs; infection is direct by the faeco-oral route after development in the environment. Introduction or spread of infection between farms or regions generally occurs via the movement of animals.

  GAPS :

  Importance of animal movements (including wildlife) on spread of anthelmintic resistance. (trade, transhumance, gathering...).

• Occasional mode of transmission

  Nematode eggs and larvae may be transported by e.g. contaminated machinery, human beings (clothes, boot), slurry, forage, on insects. This mode of transmission may be important for the introduction of species to a previously non-infected herd/flock.Furthermore this may also result in infection in housed animals.

  GAPS :

  Importance of atypical modes of transmission, including in management systems assumed to be at low risk (e.g. deep-litter pig and ruminant housing, ‘zero’-grazed systems with some access to pasture as requested in some quality labels).

  Factors related to the spread of asacrids between farms as well as between flocks within the same farm is poorly known.

• Conditions that favour spread

  Favourable climate (warm and humid weather), host stocking density, pasture quality.

  GAPS :

  Improved predictive understanding of conditions that favour increased infection pressure and impact (see section “Links to climate”).

• Detection and Immune response to infection

• Mechanism of host response

  In general, a T helper-2 type immune response is generated against GI nematode infections.Ruminants - While this response seems to be effective against some nematode species (rapid development of some level of protective immunity against Cooperia oncophora and Nematodirus), other nematode species are affected to a lesser extent and can persist in older animals (e.g. Ostertagia).Pigs - Immunity to reinfection with Ascaris suum but adults stay for prolonged time (concomitant immunity). Trichuris suis: all expelled and solid immunity after 7 to 8 weeks - but 5% may be low responders – continue to excrete eggs. Oesophagostomum spp.: cause life-long infections due to low protective immunity.Poultry - Infection levels in laying hens usually gradually build up during the egg productions cycle (up to ≈85 weeks of age) indicating poor/slow development of aquired protective immunity.

  GAPS :

  Many aspects of the innate and acquired immune responses are not clearly defined e.g. molecular pattern recognition, Th1/Th2 balance, cells and pathways involved in the early stages of the immune response, defining essential components of the protective host immune response, and influence of host genotype and nutrition.The development and maintenance of an immune response against nematodes may be an important component of the induced production losses.Consequences on other antigenic stimulation (pathogens, vaccines).

• Immunological basis of diagnosis

  In cattle antibodies and antigens (in blood, milk, faeces and meat juice) can be used to detect nematode infections. In infected poultry antibodies in the hens eggs are able to detect the infection before parasite eggs appear in the faeces.

  GAPS :

  Standardised and widely available diagnostic techniques required.Improved understanding and interpretation.

• Main means of prevention, detection and control

• Sanitary measures

  Grazing management (e.g. by rotational grazing, reduced grazing density, mixed grazing of different host species, pasture resting) can reduce pasture infection levels. Implementation of these practices is limited by the availability of labour, and/or suitable pastures and livestock.Dung removal and removal of deep litter bedding in animal houses (or using slatted floors without bedding material) will reduce the contamination of the environment.In poultry (practising all in all out) the empty houses are cleaned/disinfected before the new flock is introduced.

  GAPS :

  Increased use of sanitary measures may benefit animal health but negatively impact general farm economics. Increased knowledge of this trade-off is required, including in relation to optimal grazing rotation periods for grass growth and utilisation versus pasture infectivity.The potential for nematodes to evolve in response to alternative (non-chemical) means of control is unknown.The viability of re-introducing anthelmintic-susceptible isolates to replace anthelmintic-resistant populations should be investigated for different ecosystems, farming systems and ruminant species.Reasons why and how parasite eggs often survive sanitation is unclear.

• Mechanical and biological control

  Currently not practised on a large scale. Bioactive forages can deliver parasitological and nutritional benefits. Biological control with nematophagous fungi is effective under experimental conditions.

  GAPS :

  Practical agronomics of bioactive forages needs further applied research.Knowledge of active compounds in bioactive forages and their variability within a plant, within a season (plant growth stage) and between seasons is limited. Strategies for the implementation of bioactive forages in the field together with other control tools is lacking.Development of efficacy evaluation framework for bioactive forages to promote standardisation and regulation.

  Technical solutions for delivery of nematophagous fungi, and research into cost-effective and GMP accredited production for the nematophagous fungiImpact on non-target organisms, especially in relation to invertebrates important to nutrient cycling and carbon sequestration.Development of other biological control methods.Regulatory framework for approval for this type of product.Efficient application of expensive alternatives, e.g. through targeted (selective) treatment.

• Prevention through breeding

  Breeding livestock that are more resistant (i.e., have enhanced immune responses leading to lower infection levels) or resilient (i.e., perform well in the face of infection pressure) is feasible and has resulted in breed improvements especially in sheep. These reduce reliance on anthelmintic treatment.

  Indigenous GIN resistant breeds are being substituted for introduced breeds that are supposedly more productive.

  GAPS :

  Sustainability of this approach at scale (e.g. using estimated breeding values) when not in subsidised programmes.Field evaluation of GI nematode resistant ram selection in several breeds on other parameters (other parasites, productivity traits) in different epidemiological situations.Harmonisation of phenotypic markers for selection, especially for resilience, which is by definition context-sensitive.Progress in species other than sheep.Are the genetic markers for GI nematode resistance the same for different breeds? Do resistant breeds use different immune mechanisms than non-resistant breeds?

• Diagnostic tools

  Ruminants1) Coprological methods :These methods can be used for all gastrointestinal nematodes and all hosts. Coprology can be used to identify and quantify eggs and coproculture to identify L3. Molecular techniques for species identification and quantification are available, but they are currently not cost-effective for routine use.2) Serological methods :Serum pepsinogen levels are used to assess the degree of damage/extent of exposure to abomasal nematode infections.Antibody levels against crude extract of Ostertagia ostertagi in bulk-tank milk or serum are used to assess nematode exposure in adult cows.3) Morbidity markers :Morbidity markers have been mostly described in sheep.An estimation of the level of anaemia (FAMACHA©), diarrhoea index (DISCO), body condition scoring (BODCON) and use of automated weighing (LIVGAIN) are means of identifying individual animals that may benefit from treatment.

  Pigs1) Liver condemnation in abattoir :Pig nematodes are mainly diagnosed by reports from abattoir of milk spots in the liver, only indicative of recent Ascaris suum exposure. Elimination of worms observed by farmer reassures him/her of necessity to treat.

  2) Coprological methods :Pig nematodes can also be diagnosed by faecal examination for eggs.

  3) Serological methods :Since 2014, an ELISA is available based on a haemoglobin antigen to detect exposure of piglets to A. suum.

  Poultry1) Worms found at necropsy or in droppings.2) Faecal parasite egg counts/detection.3) Genotyping (required to distinguish between Ascaridia and Heterakis).4) Antibodies in table eggs.

  GAPS :

  Conventional diagnosis of nematode infections is laborious and expensive, and often not informative in providing a decision on whether to treat or not. A key problem is to identify those animals requiring treatment in order to avoid unnecessary use of anthelmintics, those animals being either the most infected ones (the less resistant) or the less able to cope the infection (the less resilient). Tools are to be developed on the consequences of GIN infection rather than on the level of GIN infection.Tools for differential diagnosis. Morbidity markers (FAMACHA©, PCV) and resilience markers (BODCON and LIVGAIN) may be heavily influenced by other factors than parasite infection.

  Standardised, cost-efficient, control-relevant diagnostic tools are needed, both at group and individual level.Value of morbidity markers needs to be further assessed in multicentre field trials.

• Vaccines

  The only vaccine against GI nematodes currently on the market is a subunit vaccine for Haemonchus in sheep, available in Australia.

  GAPS :

  For most GI nematodes:

  • identification of protective worm antigens ;
  • development of affordable large-scale expression systems that can produce recombinant helminth proteins with the same conformational and protective properties as the native antigens ;
  • development of improved antigen delivery systems ;
  • improved knowledge of protective immune responses ;
  • knowledge on required vaccine efficacies for meaningful epidemiological and production impact regulatory framework for parasite vaccines.

• Therapeutics

  Control of GI nematodes in Europe relies largely on anthelmintics. The three current major families of anthelmintics are the benzimidazoles (BZ), macrocyclic lactones (ML) and imidazothiazoles & tetrahydropyrimidines (which include levamisole - LEV & pyrantel - PYR). Two new classes for sheep have been marketed in some European countries since 2011: (i) amino- acetonitrile derivative or AAD and ii) spiroindoles (used in a combination product with abamectin).All anthelmintics used in livestock are very effective, reducing susceptible worm burdens (all parasitic stages) by at least 90% (BZ, PYR & LEV) up to 99% (ML, AAD).Possible drawbacks of the use of anthelmintics may include: (a) the increasing incidence of anthelmintic resistance (AR); (b) reduced development of natural immunity against nematodes; and (c) consumer concerns regarding drug residues in food products and in the environment.Nematodes in pigs are mainly controlled by application of anthelmintics (as above), cleaning of pens/change of bedding and pasture shifts between farrowings. MLs are widely used due to combined effect on sarcoptic mange.Only one drug class formulation (BZs in the drinking water) is currently registered for laying hens.

  GAPS :

  Anthelmintics with a new mode of action or combinations of products belonging to the current classes would greatly assist in managing anthelmintic resistance. New anthelmintics for dairy animals are an urgent need to be able to alternate classes of molecules. However, a gap is a regulatory environment favouring the development or authorisation of such products.

  Potential to repurpose existing drugs or those with lesser efficacy into effective combination formulations.

  Sound scientific approach to evaluate the benefits and risks of anthelmintic combination products.

  Develop comprehensive benefit-risk models to evaluate anthelmintic combination products.

  Clear field evidence to underpin recommendations for targeted drug use in the interests of sustainable efficacy, and the economic implications of such approaches.

• Biosecurity measures effective as a preventive measure

  Quarantine strategies can be useful in minimising the transmission of drug resistant parasite populations in animals.

  GAPS :

  Despite the evidence that quarantine strategies are effective in reducing the spread of anthelmintic resistance, implementation by farmers is poor. There is a need to understand why (management constraints, increased labour costs?) and refine the message.Need to integrate sociological considerations (perception of risk, knowledge, paradigm).

• Border/trade/movement control sufficient for control

  Animal products with anthelmintic residues above the minimum acceptable level cannot be traded.

• Prevention tools

  Chemoprophylaxis – strategic use of anthelmintics based on nematode epidemiology.The impact of parasitism can be mitigated using grazing management, optimised nutrition and selection of appropriate host genetics.

  GAPS :

  Vaccines.Improved anthelmintic treatment strategies. Targeted (selective) treatment strategies should be developed and evaluated, to treat only those groups or individuals that require treatment in terms of control, health, welfare and/or production. This would limit selection pressure for anthelmintic resistance and reduce treatment costs.

  In general, preventive farm management is poorly adopted and implemented. There is a need to understand why (management constraints, increased labour costs, complexity of recommendations?) and refine the message.

  Updated site-specific epidemiological information to reflect recent changes in management and the impact of climate and land use changes.

• Surveillance

  Little or no routine surveillance exists for endemic GI nematode infections.

  GAPS :

  Need for national capacity to undertake surveillance of nematode infections e.g. national reference laboratory and national epidemiological observatory.Routine procedures to direct control strategies and to monitor their efficacy.Routine procedures to implement targeted selective treatment schemes to protect anthelmintic efficacy in all farms.Routine procedures to monitor anthelmintic efficacy.

• Past experiences on success (and failures) of prevention, control, eradication in regions outside Europe

  Failure of anthelmintic-based control strategies for GI nematode infections in the southern hemisphere to remain sustainable.Eradication is not a feasible option under all circumstances.Anthelmintic resistant parasite substitution has been achieved in South Africa and should be attempted in other regions.

  GAPS :

  Identify and produce drug susceptible populations to test different parasite substitution protocols in different ecosystems, with careful evaluation of biosecurity and animal welfare.

• Costs of above measures

  Costs of GI nematode infections and their control are among the highest of all enzootic endemic production limiting diseases.

  GAPS :

  Appropriate cost-benefit analyses of preventive and therapeutic measures in order to support economic control measures.

• Disease information from the WOAH

• Disease notifiable to the WOAH

  None of these nematodes are among the notifiable diseases.

• WOAH disease card available

  Not available.

• WOAH Terrestrial Animal Health Code

  Not available.

• WOAH Terrestrial Manual

  Not available.

• Socio-economic impact

• Zoonosis: impact on affected individuals and/or aggregated DALY figures

  Not available.

• Zoonosis: cost of treatment and control of the disease in humans

  Not available.

• Direct impact (a) on production

  The cost of GI nematode infections in the ruminant livestock sector (cattle, sheep and goats) in 18 European countries in 2017 was estimated at € 825 million per year. Approximately 80% of these costs are due to production losses, and the other 20% to treatment costs. The cost of AR in ruminants was estimated at € 38 million per year.There are considerable variations between impacts by production sector, geographic area :Ruminant nematodes - In growing animals subclinical infections can lead do reduced weight gains by 10 tot 30%. In adult animals infections can result in milk yield losses (5 to 10% in cattle and up to 40% in small ruminants). Other losses include lower conception rates, poor carcass quality, reduced wool yields.Pig nematodes - Largely unknown, some older reports on marked reduced reproductive performance and weight gain but several other studies have failed to show an impact. Liver condemnations up to 20 % in certain countries.Poultry nematodes - Associated with decreased egg production and altered feed consumption. In addition, immature and adult can migrate from the intestine to the oviduct where they can be enclosed within the egg shell. Therefore, all eggs are transilluminated. If the parasite is detected they will be discarded before they reach the consumer stage.

  GAPS :

  There are many data gaps hampering accurate quantification of economic impact of livestock disease and GI nematode infetions at national, European and global level:

  • granular and harmonized reporting methods on livestock numbers ;
  • granular data on pasture access by animals ;
  • regular programmes to monitor prevalence of GI nematodes and AR at national level ;
  • studies assessing impact on production in different production systems and regions ;
  • standardized monitoring of anthelmintic drug consumption.

  Pig nematodes – a need for a suitable model to assess the impact on-farm.

  Poultry nematodes - information of the current socio-economic impact of GIN in laying hens is missing.

• Direct impact (b) cost of private and public control measures

  Costs for control measures are borne by the farmer with no public financial support.Control of GI nematodes is largely dependent on the use of anthelmintics, with an estimated €2.8 billion spent on anthelmintics globally.

  GAPS :

  Economic models to define the room for investment and how to prevent production losses at farm level.

• Indirect impact

  According to FAO, global meat and milk production is expected to increase by 30 and 50% production by 2050, even under sustainability scenario’s where animal protein consumption is mitigated in high income countries. Increasing efficiency is regarded a sustainable way to reach these targets. GI nematode infections cause among the highest productivity and economical losses in livestock. Combatting these infections in a sustainable way is indispensable to increase efficiency of production.

  GAPS :

  Need for socio-economic studies on sustainable control practices to increase the resilience of rural communities.

  Effective knowledge transfer mechanisms to understand the current constraints in uptake of current recommendations.

• Trade implications

• Impact on international trade/exports from the EU

  Animal products with anthelmintic residue limits above the minimum acceptable level cannot be traded.

  GAPS :

  Accumulation and safety of compounds from bioactive forages in meat/milk.Relationship between environmental concerns, welfare concerns and trade barriers.

• Impact on EU intra-community trade

  None.

• Impact on national trade

  None.

• Links to climate

• Seasonal cycle linked to climate

  Pasture infectivity varies markedly during a season, according to latitude (climatic patterns) and management.In pigs, infections occur all year round (in-door production); outdoors, development does not take place in winter.

  GAPS :

  Influence of climatic and management change on the seasonality of infection and the effectiveness of control strategies based on assumed seasonality.

• Distribution of disease or vector linked to climate

  No, ubiquitous (although regional differences in species spectrum). No vectors.

  GAPS :

  Role of climate in the spatial distribution of anthelmintic resistance (gaps in georeferenced data and understanding of mechanisms).

• Outbreaks linked to extreme weather

  Possible as climate will influence the development and survival of pre-parasitic stages. Host might also be affected by extreme weather through changes in physiology, resilience, food availability and quantity and management, and this impacts indirectly on nematode epidemiology.

  GAPS :

  Integration of GI nematodes into broader-based measures of risks to animal health and welfare from extreme weather.

  Severe drought periods followed by heavy rainfall are becoming the new normal and this is profoundly changing GI nematode epidemiology. The effects on GI nematode epidemiology need to be studied to define new control strategies, including their effects on anthelmintic resistance.

• Sensitivity of disease or vectors to the effects of global climate change (climate/environment/land use)

  Very important. Nematode diseases found previously in sub-tropical regions are now causing problems in temperate regions (e.g. haemonchosis in northern Europe).Predictive models exist to evaluate future changes in transmission potential of climate-sensitive species (e.g. Haemonchus).Potential for increasing drug resistance problems e.g. in a dry summer, the population in refugia may be affected (e.g., as in Western Australia).

  GAPS :

  Relative significance of certain GI nematodes and levels of exposure may change.Unequal effects of climate change on different species could affect coinfection and disease consequences.Effect of refugia on drug resistance selection under temperate climate conditions and expected climate change scenarios.Feedback effects of infection impacts on greenhouse gas emissions and hence potential for co-benefits of improved nematode control.

• Main perceived obstacles for effective prevention and control

  Anthelmintic resistance present the main obstacle to current methods of control.Alternative and complementary methods are likely to require co-ordinated use for best effect.Tools to identify animals that require anthelmintic treatment in targeted selective or targeted treatment schemes are difficult to implement in practice for most farmers.Lack of knowledge on the presence and risk of anthelmintic resistance.

  GAPS :

  Mechanisms of resistance across anthelmintic groups.The real risk of multi-drug resistant nematodes adapting more rapidly to new chemical compounds.Robust and practical diagnostics for drug resistance across anthelmintic groups.Optimisation of complementary control methods especially when used together, in different contexts.

• Main perceived facilitators for effective prevention and control

  Improving awareness and knowledge on the often hidden topic of nematode control and anthelmintic resistance is the first required step towards better and sustainable control.Appropriate diagnostics remain a key tool to underpin evidence based control approaches. The digital revolution creates a new momentum to drive forward the development of new diagnostics and their increased uptake. This includes both the potential for automated nematode diagnosis as well as improved record keeping of animals leading to optimized decision making.It will be key to continuously monitor epidemiological situation, the applied control approaches in the field and to study human behaviour to promote sustainable control approaches.

Global challenges

• Antimicrobial resistance (AMR)

• Mechanism of action

  Anthelmintic resistance develops when individual worms are able to survive drug treatment and pass on their resistance genes to subsequent generations. There can be multiple different molecular mechanisms that confer resistance, even within a single nematode species and drug class. Only mechanisms to BZ resistance are relatively well understood (alteration of Beta-tubulin genes). Genomic and transcriptomic analyses are also increasingly elucidating the mechanisms of resistance against various molecules in Haemonchus contortus.

  GAPS :

  The (epi)genetic mechanisms of anthelmintic resistance are poorly understood. Vast more basic research is needed to define the multitude of underlying mechanisms for different anthelmintics and different parasite species in order to inform the development of diagnostic tests for AR and novel drug design.

• Conditions that reduce need for antimicrobials

  Use of appropriate diagnostics can aid to better target and reduce anthelmintic use.Preventive pasture/grazing management can avoiding that animals get excessively infected with infective larvae on pasture.Indigenous breeds are often more resistant to GI nematodes reducing the need for anthelmintics. In addition, breeding for GI nematode resistant livestock is possible.Use of bio-active forages, e.g. containing condensed tannins, often based on local plants, can be a part of integrated parasite control, reducing the need for anthelmintics.Promising advances are made in vaccine research against GI nematodes, and successful.Nematode infections in cattle, pigs, and poultry can predispose to secondary bacterial infection in the gastrointestinal tract and alter immune responses to bacterial and viral pathogens in general and can also interfere with vaccination to other pathogens. Prevention of nematode infections could improve general health conditions of livestock, lowering the need for antimicrobial use.Daily feeding of spores of nematophageous fungi (e.g. Duddingtonia flagrans) has been developed into a commercial product (BioWorma) in Australia. It aims at reduction of pasture infectivity in combination with anthelmintic worm management strategy.

  GAPS :

  Scientific advances are needed for all the conditions that reduce need for anthelmintics:- development of better diagnostics ;- pasture management ;- breeding for resistance ;- bio-active forages ;- vaccines.

  Research towards behaviour change and the uptake of new outputs from these fields is essential and remains a major challenge.More research is needed on immunological modulation and its effects on co-infections as drivers of antibiotic use.

• Alternatives to antimicrobials

  All the above options can reduce the need for anthelmintics but are not an alternative. Effective anthelmintics remain needed and will remain essential to control nematode infections and their impacts on animal health, welfare and productivity.

  GAPS :

  Research on sustainable treatment strategies that maintain the efficacy of current anthelmintics and prevent negative consequences for the environment.

• Impact of AMR on disease control

  In some cases, multi-drug resistance develops to anthelmintics, leaving no options for effective control. There are some reports where this has necessitated farmers to stop their business.

  GAPS :

  How does multi-drug resistance develop? Can we reverse resistance development and make the parasite population on a farm susceptible again?

• Established links with AMR in humans

  Soil transmitted helminths are a major neglected tropical disease in the tropics. These infections are controlled via mass drug administration campaigns, mainly in school aged children. There is a huge threat of resistance development through the repeated use of anthelmintics.

  GAPS :

  There is much to learn from both human and veterinary side on how they control infection, monitor efficacy of control programmes and on the research towards molecular anthelmintic resistance mechanism. Need to set-up One Health projects focused on overcoming the challenges in nematode control in humans and animals.

• Digital health

• Precision technologies available/needed

  Well-designed precision livestock farming (PLF) systems enable farmers to manage larger herds in a more time-efficient manner. In cattle, automated systems already exist to monitor behavioural activities for the detection of lameness and oestrus. PLF systems will have to be developed for other important health events, including the management of parasitic disease, and integrated into a single management system for farmers. These systems will make use of advanced technologies like microfluidics, sound analysers, image-detection techniques, sweat and salivary sensing, serodiagnosis, and others.

  GAPS :

  Important advances are being made and should be further supported in the field of:

  - Automated faecal egg count methods (where the sample processing as well as egg recognition is automated).- Point-of-care diagnostic tests, including sequencing devices, isothermal DNA amplification and biomarker detection.- Automated weighing of animals and body condition scoring to take treatment decisions.

  Further impetus in research is needed in the use of sensors for precision parasite control :

  - Activity monitors (pedometers, accelerometers, GPS, ruminal and resting behaviour …) to detect animals suffering from nematode infection.- Sensor networks to monitor weather and environmental parameters on pasture and predict the nematode infection risk.- Sensors implanted in the animals to detect biomarkers and nematode disease.

• Data requirements

  Validation of precision technology data as a predictor for parasite infections or absence thereof is required.

  GAPS :

  More and better data are needed for parasite population modelling, including from experimental studies to estimate key parameters in mechanistic models, and field data to validate such models in farm settings. Empirical models also rely on strong field data to infer drivers of infection.

• Data availability

  Limited.

  GAPS :

  High resolution weather data at farm level could greatly enhance the prediction of nematode infection risk via mathematical modelling.Opening and standardizing fractionated data on environmental parameters obtained a.o. via satellite imagery.

• Data standardisation

  Need for coordination of evaluation protocols of precision technologies.

• Climate change

• Role of disease control for climate adaptation

  Climate change is profoundly changing nematode epidemiology leading to different periods of high pasture infectivity and different disease patterns. This in turns influences refugia and can thus impact on the development of anthelmintic resistance.

  GAPS :

  Research to understand the changing epidemiology of nematode infections as a direct consequence of climate change as well as of changing farming practices in response to climate change.

  Influence of climate change on the development of resistance to drugs.

• Effect of disease (control) on resource use

  Parasitic nematode infections are ubiquitous and a major cause of inefficient resource use in livestock farming. If uncontrolled, the infections may lead to efficiency losses over 30%. The control of these infections in a sustainable way is paramount in the challenge to feed a growing world population from a shrinking natural resource base.

  GAPS :

  Importance of nematode control in sustainable pasture based livestock systems.Effect of nematode control on water use on farms.

• Effect of disease (control) on emissions and pollution (greenhouse gases, phosphate, nitrate, …)

  While the effects of climate change on the distribution and severity of infectious diseases are widely recognized, the inverse, how infectious agents contribute to climate change, is rarely considered. However, a recent letter showed how in theory the combined effect of poor animal health and the influence of climate change on disease burden can fuel a positive feedback loop between climate change, disease and atmospheric GHG emissions. This is particularly the case for GI nematode infections which are heavily influenced by climatic conditions because a large part of their life cycle takes place outside the host.

  GAPS :

  Empirical data to investigate the theoretical positive feedback mechanisms between disease burden, climate change and GHG emissions.

  Development of climate impact models that take into account animal health in general as well as specific diseases such as GI nematodes.

• Preparedness

• Syndromic surveillance

  GI nematode infections can lead to general health detoriation and should be considered/ruled out in any deviating pattern (drop in milk yield, increased mortality, decreased egg production, increased food consumption…) detected via syndromic surveillance.

  GAPS :

  Linking datasets on GI nematode epidemiology/cases with syndromic surveillance datasets.

• Diagnostic platforms

  There is a move towards the development of automated diagnostic systems (e.g. automated faecal egg counts) as well as multiplex systems quantifying different key species or the whole nematode species composition at once. Artificial intelligence is expected to facilitate diagnostic work flow and automatization.

  GAPS :

  Automated and multiplex systems are still in research phase and more research and development is needed in order to :- Automate sample preparation.- Improve image recognition.- Reduce overall diagnostic cost.- Improve interpretation of diagnostic test results.This can drive higher uptake of diagnostic methods than is the case today.

• Mathematical modelling

  Several mathematical models are published and accessible to the research community. These models are critical to :

  • Understand GI nematode epidemiology and control options under various scenarios (climate change, animal husbandry changes, alternative control options, exploring the combination of different control approaches when anthelmintics fail).
  • Predict potential infection levels and necessity for veterinary intervention given the current climate or farm management conditions.

  GAPS :

  Extend mathematical models to integrate new principles of sustainable parasite control (targeted selective treatment, use of bio-active forages, vaccination, …) and take into account farm-specific conditions such as specific pasture management, local weather conditions.

  New modelling approaches are needed to understand the complexities of interacting climate and management factors, especially on mixed species infections and on selection for resistance against anthelmintics and other interventions, and will be supported by improved diagnostic tools. Transforming insights from models into strategic and farm-level tactical decision support also requires significant new research.

• Intervention platforms

  See above.

• Communication strategies

  There is an increasing body of sociologic research on the factors influencing the adoption of sustainable worm control practices. The insights of these studies offer handles to develop effective communication strategies and other incentives to promote sustainable behaviour in nematode control. So far, these studies have focused on the adoption of diagnostic approaches by farmers in a limited number of countries. Moreover so far mainly the behaviour intention has been studied (through quantitative and qualitative research methods). There is a need for studies that cover the gap between behaviour intention and actual behaviour, the role of the veterinarian and other advisors in adopting sustainable control approaches and geographical variation.

  GAPS :

  Study other components of sustainable worm control beyond diagnostics (treatment approaches, non-chemoprophylactic control approaches).Study behaviour and role of veterinarian in sustainable nematode control.Extend studies to European/international level and compare results between countries and regions.Develop methods to study the gap between behaviour intention and actual behaviour in nematode control.Turn insights of sociologic studies into effective and adapted communication strategies and other incentives to promote sustainable behaviour.

Main critical gaps

• 1. Improved diagnostic tools :

  • Validated sampling strategies.
  • Molecular tests for detecting anthelmintic resistance against all major drug classes in the helminth species of importance.
  • Pen-side tests.
  • Decision support systems that inform on the level of infection and morbidity.

  2. Improved therapeutic responses :

  • Improving therapeutic responses for existing anthelmintics via enhancing drug exposure, drug combinations and use of bio-active forages.
  • Novel active pharmaceutical/phytochemical ingredients with alternative mode of action and/or expanded therapeutic response.

  3. Vaccines :

  • Improved knowledge of the immune mechanisms associated with natural and vaccine induced protection.
  • Flexible, modifiable expression systems for various antigen conformations and secondary modifications.

  4. Integrated parasite control :

  • Establishment of regional/national/international centres of expertise
  • Improved risk assessments, modelling and decision support tools
  • Working out integrated control approaches making smart, combined use of a “Basket of control options” and reducing reliance on anthelmintic drugs.

Conclusion

• Sustainable nematode control in livestock including poultry significantly contributes to improved livestock welfare, health, and productivity, but is compounded by an altering epidemiology due to climate and husbandry changes as well as due to the escalating spread of anthelmintic resistance. Sustainable nematode control is a must to deliver on the planet’s growing needs for animal based proteins from a shrinking resource base and different advancements have been made towards its achievement. These advancements are in different stages of development and promise solutions on the immediate, medium and long term.

  Immediate impact can be achieved by taking advantage of the new diagnostic tools including for the detection of anthelmintic resistance, and insights that have been developed within several multinational research projects (impact of nutrition, farm management, weather and climate, impact on production and economic returns). We now have access to a wide range of tools that, if used correctly, can assist in the optimal and selective use of anthelmintics in ruminants, the monitoring of anthelmintic efficacy and the detection of anthelmintic resistance. However, they are rarely used in practice. Therefore, these diagnostics should now be demonstrated and validated in large scale on farms in varying contexts and sectors. This should go together with the development of sampling protocols, interpretation recommendations (when, where and how to use the diagnostics?), economic feasibility studies and socio-psychological research identifying the barriers for uptake. On the medium term, impact can be expected from the further development of bioactive forages and biological control as complementary control options next to anthelmintics and grazing management. For the long term, continual research is also needed to fill the gap of practical, but realistic control options through vaccination and genetic selection.

  Parallel to the research needs, there is a great need to strengthen capacities in integrated nematode control and diagnosis of anthelmintic resistance through (i) stronger integration of the topic in curricula of animal production and veterinary curricula during higher education and (ii) the establishment of local, national and international reference centres that play an essential role in maintaining susceptible nematode isolates, confirm diagnostic results obtained from the field through molecular methods and play an essential role in establishment and dissemination of evidence-based sustainable nematode control strategies.

Sources of information

• Expert group composition

  Johannes Charlier, Kreavet, Belgium – [Leader]

  Andrew Greer, Lincoln University, New Zealand

  Christophe Chartier, Oniris, France

  Dave Leathwick, Ag Research, New Zealand

  Edwin Claerebout, Ghent University, Belgium

  Eric Morgan, Queen’s University of Belfast, UK

  Felipe Torres-Acosta, Autonomous University of Yucatan, Mexico

  Georg von Samson-Himmelstjerna, Freie Universität Berlin, Germany

  Johan Höglund, Swedish university of agricultural sciences, Sweden

  John S. Gilleard, University of Calgary, Canada

  Jozef Vercruysse, Ghent University, Belgium

  Laura Rinaldi, Università Federico II, Napoli, Italy

  Thomas Geurden, Zoetis.

• Date of submission by expert group

  January 2023

• References

  Helminth infection control in farmed ruminants. Key priority research needs 2020. Link.

  Test, don’t guess! (Video)

  Best practice for diagnosis of anthelmintic resistance: from the field to the lab (Video).

  Charlier J., Bartley D.J., Sotiraki S., Martinez-Valladares M., Claerebout E., von Samson-Himmelstjerna G., Thamsborg S.M., Hoste H., Morgan E.R., Rinaldi L., 2022. Anthelmintic resistance in ruminants: challenges and solutions. Advances in Parasitology 115, 171-227. https://doi.org/10.1016/bs.apar.2021.12.002

  Charlier J., Thamsborg S.M., Bartley D.J., Skuce P.J., Geurden T., Hoste H., Williams A.R., Sotiraki S., Höglund J., Chartier C., Geldhof P., van Dijk J., Rinaldi L., Morgan E.R., von Samson-Himmelstjerna G., Vercruysse J., Claerebout E., 2018. Mind the gaps in research on the control of gastrointestinal nematodes of farmed ruminants and pigs. Transboundary and Emerging Diseases 65(Suppl.1), 217-234. https://doi.org/10.1111/tbed.12707

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