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:
Moderate. Large for anthelmintic resistance management strategies.
Multipathogen diagnosis, clinical disease indicators for health surveillance.
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.
Development of effective vaccines and registration guidelines for helminth 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.
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
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.
Helminth vaccine registration guidelines. We need to interact with the regulators to ensure the targets are acceptable.
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).
No vaccines yet.
Means of optimising anthelmintic usage to both control nematodes and maintain efficacy.
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.
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.
Statistics difficult to obtain because of different routes of distribution (e.g. vet/non-vet) and some generic companies do not submit figures.
Safety studies and their interpretation, particularly in terms of tissue residues/withholding periods and environmental impact assessments.
Knowledge transfer and exchange with policy makers and commerce to ensure global standardisation of regulatory requirements.
Existing technology is adequate.
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.
Research into the control of parasite gene expression.
Improvement and refinement of:
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.
Requires research and costs will be relatively high. Return on investment moderate to low.
Develop a better understanding of the cost the farmer is prepared to pay for diagnosis at farm level and individual animal level.
Funding for research laboratories capable of discovering novel parasite diagnostics.Technologies allowing pen-side diagnosis against a wider range of pathogens.
For most GI nematodes:
5 to 20 years
Lower than the cost for development of conventional anthelmintics.
Funding is needed to bridge the gap between lab research and commercialisation.
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.
Around 10 years for new chemistry.
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.
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.
Additional screens to identify novel targets (e.g. parasite genes).
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:
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.
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
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:
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
No vectors for the most important species (some minor genera have insect vectors).
Wild ruminants and wild boars (see comments on species specificity above)
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
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.
Developing stages and adults.
Anorexia, diarrhoea, anaemia, cachexia, production losses (weight, milk, wool, feed conversion). Very high morbidity (i.e. production losses) in ruminants but lower in pigs.
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.
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.
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.
Why are some animals excreting a high number of eggs, can we develop tools to identify these?
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:
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)
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.
Studies required to assess prevalence of zoonotic nematodes in humans.
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.
Ascaris suum - no recorded pathogenicity, but A. lumbricoides cause retarded growth and cognitive impairment, pneumonitis, abdominal pain (e.g. bile duct infections).
Need to assess symptoms in humans.
Ascaris suum – limited reporting at all so unknown if under-reporting. But presumable serious under-reporting
Severe under reporting. Need to inform medical doctors.
Ascaris suum – low
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.
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..
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.
True impact of anthelmintics on invertebrates at population level is unknown.
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.
Infections with GI nematodes are endemic.
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.
Influence of climatic and management change on the seasonality of infection and the effectiveness of control strategies based on assumed seasonality.
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.
Importance of animal movements (including wildlife) on spread of anthelmintic resistance.(trade, transhumance, gathering...)
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.
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)..
Favourable climate (warm and humid weather), host density, pasture quality.
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])
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.
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).
Antibodies and antigens (in blood, milk, faeces and meat juice) can be used to detect nematode infections
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.
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.
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.
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 methodsSince 2014, an ELISA is available based on a haemoglobin antigen to detect exposure of piglets to A. suum.
The only vaccine against GI nematodes currently on the market is a subunit vaccine for Haemonchus in sheep, available in Australia.
For most GI nematodes:
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.
Quarantine strategies can be useful in minimising the transmission of drug resistant parasite populations in animals.
Animal products with anthelmintic residues above the minimum acceptable level cannot be traded.
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.
Little or no routine surveillance exists for endemic GI nematode infections.
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 GI nematode infections and their control are among the highest of all enzootic endemic production limiting diseases.
Appropriate cost-benefit analyses of preventive and therapeutic measures in order to support economic control measures.
None of these nematodes are among the notifiable diseases.
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.
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 yieldsPig 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.
More information is required on:
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).
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.
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.
Need for economic and socio-psychological analyses of:
Animal products with anthelmintic residue limits above the minimum acceptable level cannot be traded.
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.
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.
AR has been demonstrated for Oesophagostomum spp. in Denmark and Germany (pyrantel, levamisole, benzimidazoles), and may be an overlooked problem.
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.
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.
PigsLack 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.
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.
No, ubiquitous (although regional differences in species spectrum). No vectors.
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.
Integration of GI nematodes into broader-based measures of risks to animal health and welfare from extreme weather.
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.
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.
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.
Failure to implement sustainable control threatens animal welfare and productivity and, in the long term, food security.
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
Project Management Board
11th of February 2015
Discontools nematode expert group e-meeting, 6th of February 2015.