Diseases

Nematodes

Download as PDF Download as XLS Download summary

Chapter select

Control Tools

  • Diagnostics availability

  • Commercial diagnostic kits available worldwide

    Coprological (microscopical) tests and pepsinogen assays are available in the established veterinary laboratories across Europe. These tests are based on in-house protocols and are not standardized.

    Commercially available kits and materials include:

    •  McMaster-slides, FLOTAC®,Mini-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.
    • Svanovir®- A. suum-Ab for detection of antibodies against Ascaris in fattening pigs.

    GAPS: 

      • There is a need for standardisation of available diagnostic methods to qualify and quantify parasite burdens or their consequences.
      • Novel tests for the early detection of anthelmintic resistance and the interpretation of results
      • Multi-parasite species low cost diagnostic tests
      • Pen-side diagnostic tests
      • Diagnostic systems based on the principle of identifying those animals that can cope with parasite infections without anthelmintic intervention, and to select individuals that require treatment.
      • Commercial diagnostic kits available in Europe

        Same as above
      • 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 in Europe

        Moderate. Large for anthelmintic resistance management strategies.

      • DIVA tests required and/or available

        Not applicable.

      • Opportunities for new developments

          • Further development of existing tests to make them suitable for high-throughput platforms
          • Development of pen-side tests for user friendly (low input) on-farm monitoring and rapid detection of parasitic infections.

            GAP:

            Multipathogen diagnosis, clinical disease indicators for health surveillance.

          • Vaccines availability

          • Commercial vaccines availability (globally)

            Barbervax, vaccine against Haemonchus contortus in sheep is available in Australia.

            GAP:

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

          • Commercial vaccines authorised in Europe

            None.

            GAP:

            Development of effective vaccines and registration guidelines for helminth vaccines.

          • Marker vaccines available worldwide

            None.

          • Marker vaccines authorised in Europe

            None.

          • Effectiveness of vaccines / Main shortcomings of current vaccines

            Barbervax (vaccine against Haemonchus contortus) reduce worm numbers and worm egg output by > 90%, but repeated (monthly) administration is required

            Prototype vaccines against Ostertagia ostertagi and Cooperia oncophora reduce worm egg output by 60-98% during a two-month challenge period. Main shortcomings include lack of cross-protection against other important nematodes and possible need for repeated administrations.

            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.
            • Multivalent vaccines 
          • Commercial potential for vaccines in Europe

            Native 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 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.

            GAP:

            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 Southern Hemisphere countries).

            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.

              • Opportunity for new developments

                No vaccines yet.

              • Pharmaceutical availability

              • Current therapy (curative and preventive)

                See section [Main means of prevention, detection and control - therapeutics]

                GAPS:

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

              • 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 animal requiring treatment.

                GAPS:

                  • Short term – (1) Introduction of anthelmintic combinations and/or novel formulations.; (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 in Europe

                    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.

                    GAP:

                    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.

                  • Opportunities for new developments

                    Current priority research targets for antiparasitics are orientated towards the companion animal market. Spin offs may lead to novel production animal (and human) anthelmintics e.g. cyclooctadepsipeptides.

                    Opportunities for novel therapeutics may arise from developing genome technologies e.g. dietary interventions which may influence parasite gene promotors directly and switch off key proteins.

                    GAP:

                    Research into the control of parasite gene expression.

                  • New developments for diagnostic tests

                  • Requirements for diagnostics development

                    Identification of:

                    • specific proteins or sequences for species differentiation of eggs, larvae or adults
                    • novel  biomarkers  and molecular 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 diagnostics

                    GAPS:

                      • Need for high throughput novel and affordable diagnostics for the farming and research communities.
                      • Novel target proteins and morbidity markers.
                      • 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 moderate to low.

                        GAP:

                        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 [Requirements for diagnostic development]GAP:

                        Funding for research laboratories capable of discovering novel parasite diagnostics.

                        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 vaccines

                            GAPS: 

                            For most GI nematodes:

                            • improved knowledge of protective immune responses
                            • 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.

                            GAP:

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

                          • Research requirements for new or improved vaccines

                            See section [Requirements 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.GAP:A leaner regulatory framework for the combinations of existing classes of anthelmintics.

                          • Time to develop new or improved pharmaceuticals

                            Around 10 years for new chemistry.

                          • 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 30-50 million euro.

                            GAP:

                            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.

                          • 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 and pigs are considered (Trichinella excluded). Large number of genera and species. Most important GI nematodes are:

                            • Cattle -  Ostertagia ostertagi, Cooperia oncophora, Nematodirus helvetianus
                            • Small ruminants – Teladorsagia circumcincta, Haemonchus contortus, Trichostrongylus colubriformis, T. vitrinus, Nematodirus spp.
                            • Swine – Ascaris suum, Trichuris suis, Oesophagostomum spp.

                            GAPS:

                            • Variations in biology of nematodes
                            • Interspecies interactions 
                          • Variability of the disease

                            Agent types: Some GI nematode species are more pathogenic than others (e.g. Ostertagia ostertagi is more pathogenic in cattle than Cooperia spp. and Haemonchus contortus is more pathogenic in sheep/goats than Trichostrongylus spp.) 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 (latter has mainly been described in small ruminants, to a lesser extent in cattle/swine) and within breeds between age classes (younger animals more susceptible), physiological status (pregnancy, lactation, level of production) 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: Important differences in the prevalence, abundance and importance of parasite species according to regions (sub-arctic, temperate & Mediterranean regions). For example, in Northern Europe Teladorsagia circumcincta is the most important GI nematode in sheep, while in temperate & Mediterranean regions Haemonchus contortus is more important.

                            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 in general and to AR in particular.
                              • Currently, very few genetic markers are available to identify resistant vs. susceptible host individuals 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.
                              • 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.
                              • Stability of the agent/pathogen in the environment

                                Environmentally very stable. Infectious 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) can survive for several years on pasture or in stables

                                GAPS:

                                  • Agents killing infectious eggs.
                                  • 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
                                  • 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.GAP:
                                    • 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, see annex 1) can infect humans and it is closely linked and perhaps identical to Ascaris lumbricoides, the species infecting humans and primates

                                  • Vector cyclical/non-cyclical

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

                                  • Reservoir (animal, environment)

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

                                    GAP:

                                    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 soil and earth worms as reservoir for 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 (free living L3 or L1/2/3 in ovo). The host is infected by oral ingestion of the infectious stages.

                                    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). 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.
                                    • 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.

                                  • 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.

                                    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 animals graze on pasture (ruminants) or are kept in infected housing (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. Individuals vary in level of egg excretion.

                                    GAP:

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

                                  • Mechanism of pathogenicity

                                    All GI nematodes 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).

                                    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

                                    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 under reporting.

                                    GAP:

                                    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).

                                    GAP:

                                    Need to assess symptoms in humans.

                                  • Estimated level of under-reporting in humans

                                    Ascaris suum – limited reporting at all so unknown if under-reporting. But presumable serious under-reporting

                                    GAP:

                                    Severe under reporting. Need to inform medical doctors.

                                  • 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. However, the therapeutic use of effective anthelmintics in the face of clinical disease generally is rapidly effective. Grazing and nutritional management, supported by the tactical/strategic use of anthelmintics 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.

                                    GAP:

                                    Consequences of low input and organic farming practices on infection outcomes and 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, and could in theory have negative impacts on their populations and those of species at higher trophic levels.

                                    GAP:

                                    True impact of anthelmintics on invertebrates at population level is 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. 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.

                                    GAPS:For some parasite species little or no representative data on GI nematode prevalence.

                                    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.

                                  • Epizootic/endemic- if epidemic frequency of outbreaks

                                    Infections with GI nematodes are endemic.

                                  • Seasonality

                                    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.

                                    GAP:

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

                                  • Speed of spatial spread during an outbreak

                                    Not applicable.

                                  • Transboundary potential of the disease

                                    No, ubiquitous.

                                  • Seasonal cycle linked to climate

                                    Yes.

                                  • Distribution of disease or vector linked to climate

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

                                  • 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 and management, and this could impact indirectly on nematode epidemiology.

                                    GAP:

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

                                  • 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).

                                    Potential for increasing drug resistance problems e.g. in a dry summer, the population in refugia may be affected.

                                    GAPS: 

                                      Relative significance of certain GI nematodes and levels of exposure may change.

                                      Effect of refugia on drug resistance selection under temperate climate conditions and expected climate change scenarios.
                                      • 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.

                                        GAP:

                                        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. Furthermore this may also result in infection in housed animals.

                                        GAP:

                                        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)..

                                      • Conditions that favour spread

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

                                        GAP:

                                        Improved predictive understanding of conditions that favour increased infection pressure and impact (e.g. see section [Seasonal cycle] and [Sensitivity of disease or vectors to the effects of climate change])

                                      • 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.

                                        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

                                        Antibodies and antigens (in blood, milk, faeces and meat juice) can be used to detect nematode infections

                                        GAP:

                                        • 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.GAP:

                                        Increased use of sanitary measures may benefit animal health but negatively impact general farm economics. Increased knowledge of this trade-off is required.

                                        The potential for nematodes to evolve in response to alternative (non-chemical) means of control is unknown.
                                      • 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.
                                          • Technical solutions for delivery of nematophagous fungi, and research into cost-effective and GMP accredited production for the nematophagous fungi
                                          • Impact on non target organisms.
                                          • Development of other biological control methods.
                                          • Regulatory framework for approval for this type of product.
                                          • Diagnostic tools

                                            Ruminants

                                            1) 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.

                                            Pigs

                                            1) 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.

                                            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.
                                              • 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.

                                                GAP:

                                                • Anthelmintics with a new mode of action or combinations of products belonging to the current classes would greatly assist in managing anthelmintic resistance.  However, a gap is a regulatory environment favouring the development of such 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?) and refine the message.
                                                  • Updated 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 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.
                                                      • 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 OIE

                                                      • Disease notifiable to the OIE

                                                        None of these nematodes are among the notifiable diseases.

                                                      • OIE disease card available

                                                        No.

                                                      • OIE Terrestrial Animal Health Code

                                                        None.

                                                      • OIE Terrestrial Manual

                                                        None.

                                                      • Socio-economic impact

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

                                                        Ascaris suum infections do impact humans.

                                                        Knowledge gained in controlling GI nematode infections in animals may provide invaluable models for Soil Transmitted Helminth (STH) infections in humans.

                                                        The issue of drug resistance for human helminthiases may be of public health concern, particularly in view of growing drug pressure in the era of ‘preventive chemotherapy’, which is the large-scale application of anthelminthic drugs to at-risk populations (e.g., school-aged children) in developing countries.

                                                        Due to their impact on animal productivity, control of GI nematodes is a significant topic in the discussions regarding food security.

                                                        GAPS: 

                                                          • Assessing impact of Ascaris suum infections in humans
                                                          • One-Health approach - Better interactions between veterinary and human parasitologists which for example could lead to improved guidelines for evaluating the efficacy of anthelmintics in humans, especially against STH.
                                                          • Quantifying the impact of GI nematodes on animal productivity and hence food security and malnutrition in less developed countries.
                                                          • Zoonosis: cost of treatment and control of the disease in humans

                                                            Not available.

                                                          • Direct impact (a) on production

                                                            Varies considerably between animal species, geographic area, farm, etc. Most losses within the EU are caused by effects on productivity

                                                            Ruminant nematodes -  In growing animals subclinical infections can lead to reduced weight gains by 10 to 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.

                                                            GAPS:

                                                            More information is required on:

                                                            • Effects on susceptibility to other diseases (bacterial, viral infections and metabolic diseases) and vaccination responses.
                                                            • Effects on production parameters (growth, milk yield, milk quality, fertility parameters,culling, carcass weight/quality) in different husbandry scenario’s.at individual and group levels
                                                            Pig nematodes – a need for  a suitable model to assess the impact on-farm
                                                          • 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 (the bulk of which in the major livestock producing regions of Europe, USA and Australasia).

                                                            GAP:

                                                            The cost of disease on the farm level has been poorly described. Studies are needed in order to define the room for investment for the farmer to prevent production losses.

                                                          • Indirect impact

                                                            According to FAO, the demand for food is expected to continue to grow as a result both of population growth and rising incomes. Annual meat production will have to grow by over 200 million tonnes to reach a total of 470 million tonnes in 2050; annual milk production is projected to increase from 580 to 1047 million tones. Reaching these targets will require an increase in the efficiency of production. Both milk and meat production from cattle and pigs are the most important sectors in animal farming in the EU. GI nematode infections cause among the highest productivity and economical losses in livestock. Combatting these infections is indispensable to increase efficiency of production.

                                                            GAPS:

                                                            Need for economic and socio-psychological analyses of:

                                                            • The impact of GI nematodes on the quantity and quality of livestock products (impact on food security)
                                                            • The effect of ineffective helminth control on livestock production and the sustainability 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.

                                                          • Impact on EU intra-community trade

                                                            None.

                                                          • Impact on national trade

                                                            None.

                                                          • Main perceived obstacles for effective prevention and control

                                                            The persistence of infectious stages in the environment (see 1.3) limits the application of environmental control on pasture and in housing. A balance between the development of immunity and the limitation of impact is the key for controling GIN.

                                                            Ruminants

                                                            Control currently is largely centred on the use of anthelmintics and dependence is not without risk. An emerging problem threatening worm control today is the spread of anthelmintic resistance (AR). The prevalence of resistance varies geographically, depending on the livestock species involved and the drugs used.

                                                            Benzimidazole-resistant and Macrocyclic lactones-resistant nematodes are widely reported in sheep/goats of several temperate European countries. Resistance to levamisole is present in sheep and goat parasites, though at a lower level.

                                                            In cattle AR has been reported, however, until now it is mainly limited to Macrocyclic lactones resistance to Cooperia spp.

                                                            Pigs

                                                            AR has been demonstrated for Oesophagostomum spp. in Denmark and Germany (pyrantel, levamisole, benzimidazoles), and may be an overlooked problem.

                                                            GAPS:

                                                            Overall

                                                            There is a lack of standardized techniques for the diagnosis of infection, the early detection of AR and the absence of systematic large-scale surveys to assess the importance of AR for ruminants in Europe.

                                                            Ruminants

                                                            Much of the research on non-pharmaceutical approaches has not yet been successfully transferred from the research environment to the field.

                                                            In the long run, vaccines may provide complementary measures for control, but their efficacy and value under commercial farming conditions is only just beginning (in Australia).

                                                            Farmers and veterinarians like simple, empirical solutions to diseases and their control: the control of parasitism with anthelmintics is still viewed like this and a major initiative is required to change these habits to those that are more attuned to local topography, weather, management etc. The concept of Integrated Pest Management involving a global approach for controlling GIN infection has not reached the technicians, the vets, the farmers.

                                                            Pigs

                                                            Lack of means to remove the constant high infection pressure on permanently used premises. Also a high level of protection and associated low levels of immunity in early life, often results in major problems with liver condemnation due to late infections and a lot of milk spots.
                                                          • Main perceived facilitators for effective prevention and control

                                                            Demonstrating and understanding the benefits of control measures in terms of profitability of the production system is the most important facilitator to implement effective control measures.

                                                            GAPS:

                                                              • Effective knowledge transfer mechanisms are poorly understood due to the lack of inclusion of socio-psychological science.
                                                              • Finding effective methods for enhancing uptake of best practices by farmers and veterinarians.

                                                              Risk

                                                              • Livestock welfare and production (both meat and dairy) are negatively affected by GI nematode infections, which are one of the main constraints to efficient livestock production worldwide. Changing climate is likely to exacerbate parasitoses by increasing the level and duration of pasture infectivity.

                                                                Failure to optimise anthelmintic usage could lead to loss of effective worm control.

                                                                GAPS: 

                                                                  • Improved communication and implementation of holistic control strategies using improved diagnostics, approaches for routine parasite-directed herd health surveillance, host genetics, nutrition and pasture management to reduce the reliance upon anthelmintics.
                                                                  • Introduction of additional control measures, e.g. vaccines, bio-active forages, nutraceuticals, ovicidals.

                                                                  Main critical gaps

                                                                  Conclusion

                                                                  • Failure to implement sustainable control threatens animal welfare and productivity and, in the long term, food security.

                                                                  Sources of information

                                                                  • Expert group composition

                                                                    Expert group members are included where permission has been given Jozef Vercruysse - Ghent University, Belgium - [Leader]

                                                                    Johannes Charlier, Ghent University, Belgium

                                                                    Christophe Chartier, Oniris, France

                                                                    Edwin Claerebout, Ghent University, Belgium

                                                                    Thomas Geurden, Zoetis, Belgium

                                                                    Eric Morgan, University of Bristol, UK

                                                                    Laura Rinaldi , UNIVERSITA’ DEGLI STUDI DI NAPOLI “FEDERICO II”, Italy

                                                                    Georg von Samson-Himmelstjerna, Freie Universität Berlin, Germany

                                                                  • Reviewed by

                                                                    Project Management Board

                                                                  • Date of submission by expert group

                                                                    11th of February 2015

                                                                  • References

                                                                    Discontools nematode expert group e-meeting, 6th of February 2015.