Control Tools

• Diagnostics availability

• Commercial diagnostic kits available worldwide

  Commercially available antibody detection ELISA (cattle)

  Commercially available copro-antigen detection ELISA that can be used in any host species

  Faecal egg count kits are available.

  Bulk tank tests are available for dairy cattle.

  GAPS:

  Antibody detection detects evidence of exposure not necessarily current infection. Little information is available about how quickly antibody levels drop in response to treatment or loss of infection.

  Coproantigen tests have not been fully evaluated in the field

  There are no commercial antibody detection tests for sheep

  Faecal egg counts (FEC) are a useful indicator of infection but need validation for composite samples

  Rumen flukes (paramphistomes) are becoming an increasing problem in some countries – but diagnostics to differentiate between rumen fluke and liver fluke are not available.

  Most tests are validated for F. hepatica – less known about F. gigantica (found in the tropics)

  Diagnosis of human fasciolosis is problematic. Lack of point-of-care/pen-side tests will impact targeted treatment or mass drug administration campaigns.

• Commercial diagnostic kits available in Europe

  Commercially available antibody detection ELISA (cattle)

  Commercially available copro-antigen detection

• Diagnostic kits validated by International, European or National Standards

  No.

  GAP: Limited number of kits available and are not validated. Some tests that are not necessarily commercially available are validated and that validation is published.

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

  No.

  GAP: FEC, in particular composite FECs, require validation for herd/flock level diagnosis, butalso if they are to be used for the detection of drug resistance via faecal egg count reduction tests (FECRT).

• Commercial potential for diagnostic kits in Europe

  There could be commercial potential assuming that the kits were reliable and the cost of performing the test was significantly less than the cost of prophylaxis with anthelmintics.

  GAP: More information/details required on farmer motivations behind treatment decisions and the use of diagnostics prior to treatment.

• DIVA tests required and/or available

  No

  GAP: Vaccines are under development – DIVA based vaccines are important to reduce unnecessary immunisations; thusdiagnostic tests to discriminate between vaccinated and infected animals are required.

• Opportunities for new developments

  There is a lack of sensitive and specific, fully evaluated diagnostics for sheep, cattle and humans. The following areas are identified to be addressed:

  ·rapid diagnosis especially for acute infection in sheep

  ·good diagnostics for new/recent infection

  ·pen-side tests

  ·herd level tests to identify heavily infected herds

  ·tests that can discriminate between different species and/or hybrids of Fasciola.

  GAPS:

  Identification of commercial partners

  More information/details required on farmer motivations behind treatment decisions and the use of diagnostics prior to treatment, including financial considerations

• Vaccines availability

• Commercial vaccines availability (globally)

  No.

  GAP

  Sub-unit vaccines under development through most recently EU project PARAVAC and PARAGONE. Vaccine trials evaluating potential antigens are underway. Work is required on efficacy of these vaccine antigens and identification of other antigens using new methods such as reverse vaccinology.

• Commercial vaccines authorised in Europe

  No. Major pharma companies are interested in potential vaccines and would be involved in licensing in Europe and worldwide.

• Marker vaccines available worldwide

  No.

  GAP: Required

• Marker vaccines authorised in Europe

  No.

  GAP: Required

• Effectiveness of vaccines / Main shortcomings of current vaccines

  Not applicable.

• Commercial potential for vaccines in Europe

  There is commercial potential for effective vaccines especially as this could minimise the risk of increased resistance to anthelmintics.

  GAP: Research is required into how efficacious vaccines should be to have an effect in the field either on reducing transmission or generating sufficient immunity to protect the individual against disease.

• Regulatory and/or policy challenges to approval

  None.

• Commercial feasibility (e.g manufacturing)

  Commercial feasibility would be a factor in progression through the product pipeline and non-viable products discarded.

• Opportunity for barrier protection

  No

• Opportunity for new developments

  A number of developments are required.

  GAPS: The following areas need to be addressed:

  • Different approaches to identification of vaccine antigens
  • Reverse vaccinology
  • Need to develop new delivery and adjuvant systems to improve level of protection
  • Need to understand the level of protection required to be commercially viable
  • Need to understand the nature of fluke mediated immuno-modulation on delivery of fluke vaccines and also other vaccines
  • Need to understand the immune responses to fluke (innate and adaptive; protective and suppressive) in naturally exposed animals.

• Pharmaceutical availability

• Current therapy (curative and preventive)

  Current therapy relies on anthelmintics. Nitrophenols (oxyclozanide and nitroxynil); Benzimadazoles (triclabendazole, albendazole, netobimin), closantel and clorsulon are available.

  No preventive therapy available.

  GAP: Other than triclabendazole there are no drugs effective against young juvenile stages of the parasite; juveniles are the cause of death in acute disease and pathology in animals challenged with a high burden.

• Future therapy

  Treatment will still probably rely on anthelmintics for the foreseeable future.

  GAPS:

  Resistance in fluke populations to triclabendazole has been reported in many countries (Australia, Europe and S. America).

  Research into strategic treatment regimens reducing reliance on anthelmintics is required.

• Commercial potential for pharmaceuticals in Europe

  New anthelmintic products would compete in the market with the generic compounds already available and would therefore need to be of comparable cost.

• Regulatory and/or policy challenges to approval

  Use of flukicides except albendazole, no longer licensed for use in milking cows. This is under review by EMA.

• Commercial feasibility (e.g manufacturing)

  Feasible.

• Opportunities for new developments

  Yes. The following areas need to be addressed:

  • Development of new flukicides will depend on commercial feasibility and size of market.
  • Different delivery systems, particularly those which impact on MRLs will enhance use of flukicides.
  • Need for more research on triclabendazole resistance to extend the life of this drug.

• New developments for diagnostic tests

• Requirements for diagnostics development

  Any new diagnostic test would need to be cheap and preferably able to distinguish the level of infestation which may mean that treatments can be targeted at those most in need in order to minimise the risk of development of anthelmintic resistance.

  GAPS:

  Antibody detection detects evidence of exposure not necessarily current infection. Little information is available about how quickly antibody levels drop in response to treatment or loss of infection.

  Faecal egg counts are a useful indicator of infection but need further validation for composite samples in cattle.

  Coproantigen tests have not been fully evaluated in the field.

  There are no commercial antibody detection tests for sheep

  Rumen flukes (paramphistomes) are becoming an increasing problem in some countries – but other than faecal egg counts, diagnostics to differentiate between rumen fluke and liver fluke are not available. Information about antigenic cross reaction between trematodes needed.

  Most tests are validated for F. hepatica – less known about F. gigantica (found in the tropics).

  Diagnosis of human fasciolosis needs improvement, WHO already aware.

  For all tests information is needed concerning the ability of existing tests to differentiate between heavy infections vs light infections in individual animals.

• Time to develop new or improved diagnostics

  This could be significant.

  GAP: Potential new diagnostic targets need to be developed that relate specifically to life stage or to severity of infection/disease. This in combination with host biomarkers may aid in developing a diagnostic approach to assessing disease severity.

• Cost of developing new or improved diagnostics and their validation

  This could be significant.

• Research requirements for new or improved diagnostics

  There is a lack of sensitive and specific, fully evaluated diagnostics for sheep, cattle and humans.

  GAPS: The following areas should be addressed:

  • rapid diagnosis especially for acute infection in sheep
  • diagnostics for new/recent infection
  • pen-side tests
  • herd level tests to identify heavily infected herds
  • tests that can discriminate between different species and/or hybrids of Fasciola spp and Paramphistomes

• Technology to determine virus freedom in animals

  Not applicable.

• New developments for vaccines

• Requirements for vaccines development / main characteristics for improved vaccines

  Research in the past has focused on development of vaccines against secretory proteins and these are under validation in current trials. Infestation with flukes does not produces a transient immune response possibly because of the immunomodulation mediated by fluke or potentially due to host directed efforts at minimising immunopathology. It would be informative to determine if the course of natural immune responses can be altered during infection to elicit parasite killing and thus aiding the identification of future vaccine targets.

  GAPS:

  Field studies of naturally exposed animals to evaluate their immune responses, likelihood of reinfection and if there is development of protection over time are required.

  Greater knowledge of the immune response to natural infection and that involved in protection, where evidence exists that it occurs, are required.

• Time to develop new or improved vaccines

  Some basic research into the immune response to infestation may be required before the development of new vaccines can be contemplated; e.g. the protective mechanisms required to kill adult flukes.

  Time to development of vaccines is likely to be significant.

  GAPS:

  Little is known about immune responses to F. hepatica in naturally infected cattle and sheep.

  More information is needed on the immunomodulation caused by fluke infection to determine if fluke infection can impede vaccine responses to fluke itself but also to other pathogens (BDVD, Lepto, respiratory disease, tetanus etc).

• Cost of developing new or improved vaccines and their validation

  Significant.

• Research requirements for new or improved vaccines

  A range of requirements exist.

  GAPS:

  The following areas need to be addressed:

  • Field trials of existing vaccine candidates to determine if they confer sufficient protection to be commercially viable
  • Identification of new vaccine candidates such as through a reverse vaccinology approach.
  • Investigation into adjuvants and appropriate delivery systems
  • Understanding of the nature of protection to allow vaccines to be delivered in such a way as to induce the right type of response
  • Studies to assess the level of protection required to protect individual animals or reduce transmission.

• New developments for pharmaceuticals

• Requirements for pharmaceuticals development

  The modification of current anthelmintic compounds to make them more effective, possibly by increasing their concentration in the liver or searching for other chemicals that have activity against the fluke may be investigated.

  The only compound licensed for use in milking cattle (with a 60hour withdrawal period) is albendazole. There is a need for new products or different formulations of existing products that can be used in milking cattle with no residues in milk.

  GAPS:

  Mode of action of current flukicides is not well understood. More work is required to investigate their modes of action.

  Few compounds are fully effective against the immature stages of the parasite. These are the most pathogenic stages, particularly for sheep.

• Time to develop new or improved pharmaceuticals

  Significant

• Cost of developing new or improved pharmaceuticals and their validation

  Significant.

• Research requirements for new or improved pharmaceuticals

  Requirements as indicated in the gaps section

  GAPS:

  The following areas need to be addressed:

  • New flukicidal compounds that target immature stages
  • New application methods for existing products
  • More information about flukicidal resistance – prevalence and extent of TBCZ resistance and evidence of resistance to closantel
  • Need for flukicides that can be used in milking cattle

Disease details

• Description and characteristics

• Pathogen

  Members of the Fasciola Family – mainly Fasciola hepatica in temperate areas and Fasciola gigantica in the hot humid tropics. In humans a range of trematode infections have been identified that are considered to be components of the WHO classification of Neglected Tropical Diseases. These include F. hepatica, Clonorchis sinensis Opisthorchis, Paragonimus, Fasciolopsis.

  GAPS:

  Is Fasciola gigantica a human pathogen?

  In areas where F. hepatica and F. gigantica co-exist and where fasciolosis in humans occurs, what species is responsible?

  Genome mapping should be a priority area of research to develop tools for diagnosis, differentiating between species, identification of drug resistant isolates and improving our understanding of drug resistance to different flukicides.

  The prevalence and epidemiology of human trematode infections is lacking.

• Variability of the disease

  The severity of the disease in herbivores depends to some extent on host susceptibility and principally on the number of flukes present. It is not clear if different isolates of fluke have differing degrees of pathogenicity but some evidence exists that some isolates are more virulent in snails and the number of cercariae is variable between different isolates. Disease incidence also varies according to the availability of the intermediate host the freshwater snail from the FamilyLymnaeidae. Both temperature and rainfall and other environmental and physical factors have a profound effect on the incidence.

  GAPS:

  More information is required about infection in species other than ruminants – for example horses and also wild life species. More information is required about snail vectors – which are permissible hosts in different parts of the world and in different ecosystems.

  The species of Fasciola found in Europe is F. hepatica and F. gigantica is found principally in the tropics. In some parts of the world these two species overlap and it is not clear how the two species interact. There is evidence of triploidy and introgression of F. gigantica DNA into F. hepatica and vice versa. How this genetic complexity affects spread of drug resistance is not clear and warrants further work. Does horizitonal gene transfer occur?

• Stability of the agent/pathogen in the environment

  Temperature and moisture affect the development of eggs in the environment. Eggs hatch into miracidia which must find a snail host within 24 hours of hatching or they will die. The parasite develops in the snail host through a series of different stages ending up as the cercaria which are shed from the snail over a period of several days and encyst on nearby plant material to form metacercariae which remain viable for several months. During winter or periods of drought the snail can survive buried in mud and re-emerge when suitable conditions return.

  GAP: More information is required about the survival of environmental stages including the egg, metacercariae and infected snails, given different environmental conditions. In particular more information is required about the predicted effects of climate and environmental change may have on survival of these different stages.

• Species involved

• Animal infected/carrier/disease

  Herbivores, typically cattle, goats, and sheep.

  GAP: Scant detail on wild life reservoirs in Europe or worldwide.

• Human infected/disease

  Humans can be infected but not directly from meat consumption. Commonly infection is caused by eating encysted metacercariae on water cress or similar food stuff .

  GAP: Human infection is sporadic in Europe. However, in other parts of the world there are foci of human disease (S. America, Iran, Egypt, Vietnam). There are gaps in our knowledge about the epidemiology of human fasciolosis in these parts of the world and particularly in newly emerging foci.

• Vector cyclical/non-cyclical

  Members of the Lymnaeides family are cyclical vectors for the liver fluke.

• Reservoir (animal, environment)

  Herbivores (including wild herbivores such as deer and hares) together with the intermediate hosts - snails of the family Lymnaeidae together with eggs on pasture and encysted metacercariae on vegetation act as a reservoir.

  GAP: Impact of environmental change on development and survival of eggs, snails, parasite stages within snails and metacercariae on pasture.

• Description of infection & disease in natural hosts

• Transmissibility

  Direct transmission between animals is not possible since completion of the life cycle is dependent on the snail. However, infected animals shed eggs which develop and infect lymnaeid snails which results in production of cercariae which encyst on pasture. These are the infective stage for domestic and wild life hosts.

  GAP: Capacity for local geographical spread of the vector is unknown.

• Pathogenic life cycle stages

  In the herbivores it is the immature and mature stages of the fluke that cause disease.

• Signs/Morbidity

  Fluke disease occurs in three forms – acute, sub-acute and chronic.

  Acute – This occurs when massive numbers of infective cysts are ingested from herbage over a short period. The simultaneous migration of large numbers of immature fluke through the liver can cause severe tissue damage and can lead to sudden death.

  Sub-acute – Cysts are ingested over a longer period and the liver contains immature and adult flukes.

  Chronic – This is associated with a prolonged intake of moderate numbers of infective cysts and the accumulation of adult flukes in the bile ducts.

• Incubation period

  From ingestion by a herbivore to adult flukes in the bile duct takes approximately 6 to 10 weeks.

• Mortality

  Acute disease may lead to sudden death. This is common in sheep but less common in Europe in cattle.

• Shedding kinetic patterns

  Adult flukes are hermaphrodite and each can produce up to 4,000 eggs per day which are flushed from the bile duct and released into the environment via the faeces.

• Mechanism of pathogenicity

  Clinical signs usually occur as a result of the immature fluke feeding on liver tissue causing damage to the parenchyma, anaemia and fibrosis. The adult flukes in the bile ducts feed on blood causing anaemia, cholangitis and weight loss.

• Zoonotic potential

• Reported incidence in humans

  Human fascioliasis is very rare in Europe but in some parts of the world the disease is a major public health issue. Human trematodiases are prevalent in SE Asia and is estimated to infect 30,000,000 people. The incidence of human infection with Fasciola hepatica is estimated at 2.4 million with 180 million people at risk.

  GAP: Active surveillance of human cases required.

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

  The acute phase of infection in humans is characterised by the migration of immature worms through the liver; haemorrhage and inflammation of the liver can be severe, including fever, abdominal pain, respiratory disturbances and skin rashes. Chronic infections can lead to biliary cirrhosis.

• Symptoms described in humans

  In high risk areas the level of reporting is anticipated to be well below the actual infection level.

• Estimated level of under-reporting in humans

  The risk of occurrence in humans is geographically distinct being greatest in areas including the Altiplano of South America, Egypt, Iran, SE Asia.

  GAP: Diagnosis in humans is difficult and poor communities are most at risk. Therefore human infection is probably significantly under reported.

• Likelihood of spread in humans

  In high risk areas the likelihood of spread is high although spread is dependent on presence of the intermediate snail host.

  GAP: There is some evidence that Fasciola adapts to different hosts. It is therefore important to establish if strains of Fasciola exist that cycle from human to human or if domestic animals are the principle reservoir.

• Impact on animal welfare and biodiversity

• Both disease and prevention/control measures related

  Herbivores with the disease require treatment with a flukicide to minimise the loss of production and potential anaemia that can result. The presence of liver fluke may also predispose animals to other infections. Treatment with a flukicide is recommended but resistance to the anthelmintics used is also being reported.

  No assessment of the impact on wild herbivore species in terms morbidity/mortality.

  GAPS: More information is required about prevalence of resistance to triclabendazole (the one drug that has proven efficacy against young immature stages of Fasciola and the drug used to treat human fasciolosis). There is little evidence at this stage of resistance to other flukicides.

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

  Any herbivore is susceptible to liver fluke.

• Slaughter necessity according to EU rules or other regions

  Generally speaking slaughter is only considered if the animal involved is suffering badly due to either a chronic or an acute infestation. It is not a policy decision.

• Geographical distribution and spread

• Current occurence/distribution

  Liver fluke disease is found on every continent but is particularly prevalent in areas of high rainfall and temperatures above 10^oC where the intermediate snail host is abundant. The life cycle is seasonal, occurring in the winter in Mediterranean countries when conditions are suitable for development and in the summer in northern climes where the winter is too cold. In other areas such as S. America, although day/night temperatures have a large range, transmission probably occurs all year round, or depends on rainfall since mean temperature remains suitable for development.

• Epizootic/endemic- if epidemic frequency of outbreaks

  Endemic.

• Seasonality

  Liver fluke disease is seasonal, but the season when the greatest load of infection occurs depends on the climatic conditions within each ecological zone. Development of both the parasite and the intermediate host requires a temperature of over 10 °C. Where there areseasonal rains the greatest, development occurs during the rainy season provided the temperature is above 10 °C.

• Speed of spatial spread during an outbreak

  Spatial spread depends on risk factors in the environment and animal movement.

• Transboundary potential of the disease

  The spread of the disease is not only related to the herbivores but also to the distribution of the intermediate host snail therefore there is potential for the disease to cross boundaries.

• Route of Transmission

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

  Infection is by ingestion of metacercariae contaminating herbage.

• Occasional mode of transmission

  No other known mode of transmission.

• Conditions that favour spread

  Warm and wet environments favour intermediate host population expansion.

• Detection and Immune response to infection

• Mechanism of host response

  Flukes can accumulate in the liver. They do not induce sterile protective immune responses.

  GAP: We need more information about the host-parasite interactions, particularly in cattle in terms of their susceptibility to infection, to re-infection and whether self-cure occurs.

• Immunological basis of diagnosis

  Antigen-capture ELISAs are available based on the detection of species specific antibodies from serum.

• Main means of prevention, detection and control

• Sanitary measures

  Drainage of wet lands will reduce the numbers of the intermediary host snails and this method can be quite effective in reducing the incidence. It is not always a practical proposition however, especially where land availability is limited and wet areas extensive.

  EU agri-environmental schemes and Payment for Ecosystem Service schemes may preclude drainage.

  GAPS:

  There are environmental reasons why drainage schemes are not always advocated. Fencing off contaminated areas is not always an option because of cost and scale of the affected area.

  Research into better management methods to improve control not relying on either drug prophylaxis or drainage alone.

• Mechanical and biological control

  The alternative to drainage is to restrict animals grazing to dryer areas although again this is not always a practical proposition.

  GAP: See Section above “Sanitary measures”. Biological control of snail vectors requires more research.

• Diagnostic tools

  A range of diagnostic tools to detect infection are available but few are used to detect disease – this is especially true in acute infections where treatment is advocated as early as possible for animal welfare reasons – death is very rapid in heavily infected animals.

  GAP: Need for better diagnostics for diagnosing early and acute infections.

• Vaccines

  There are no vaccines currently available.

• Therapeutics

  There are a number of anthelmintics available, triclabendazole being the anthelmintic of choice because of its effect against immature fluke. Resistance can be problematical.

  GAP: More research needed into mechanisms of action of flukicides and extent of drug resistance.

• Biosecurity measures effective as a preventive measure

  There is a need to avoid the introduction of fluke, particularly resistant fluke, onto uninfected farms. The use of closed herds/flocks and avoidance of purchasing animals from known fluke infested areas is good practice. Quarentine of newly purchased animals while a diagnostic outcome is best practice.

• Border/trade/movement control sufficient for control

  There are no specific border or movement controls on animals as the disease is endemic worldwide.

• Prevention tools

  Drainage of wet land and keeping animals away from wet grazing are the most effective prevention tools.

  GAP: More work is required to determine what management factors can be used to control infection including when and how frequently to administer flukicidal treatment strategically.

• Surveillance

  There are no specific surveillance measures.

  GAP: As current models predict prolongation of liver fluke transmission season in many regions across Europe due to climatic change, there is a need to set up standardised surveillance systems to detect changes in parasite challenge on pasture and disease intensity.

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

  Liver fluke disease is endemic throughout the world and eradication is unlikely to be a possibility.

• Costs of above measures

  The cost of preventive measures and prophylaxis can be significant. Treatment and the loss of production from infested animals is also significant.

  GAP: No recent figures are available as to the true costs and impact on productivity and animal welfare.

• Disease information from the WOAH

• Disease notifiable to the WOAH

  Liver fluke disease is not an OIE notifiable disease.

• WOAH disease card available

  No.

• WOAH Terrestrial Animal Health Code

  Not applicable.

• WOAH Terrestrial Manual

  Not applicable.

• Socio-economic impact

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

  Haemorrhage and inflammation of the liver can be severe including fever, abdominal pain, respiratory disturbances and skin rashes. WHO are collecting DALY figures but these relate to food borne trematode diseases in general.

  GAP: Making use of current MDA or targeted drug administration programs to evaluate patient outcomes.

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

  Significant but currently no accurate data on results of treatment in humans or outcomes in terms of morbidity data.

  GAP: More research needed into diagnosis of human fasciolosis; highly relevant given the use of TCBZ [only effective veterinary drug] in human infection. There is little information about problems of resistance in fluke populations affecting animals spilling over into humans, but case reports suggest it can occur.

• Direct impact (a) on production

  Acute cases suffer higher mortality rates, while chronic and sub-acute diseases affect production capacity leading to reduced yields or premature culling.

  GAP: The industry requires accurate information about cost of controlling disease, impact on milk production, time to reach slaughter weight and a number of other key production indicators. Including how accurate treatment/diagnosis will affect these outcomes.

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

  Regular treatment and prophylaxis with anthelmintics will be undertaken at significant cost. Frequent use of anthelmintics will result in anthelmintic resistance thus giving declining cost/benefit ratios.

• Indirect impact

  This is likely to be significant.

  GAP: Quantification of indirect costs is required

• Trade implications

• Impact on international trade/exports from the EU

  Liver fluke disease is not anticipated to impact international trade.

• Impact on EU intra-community trade

  Liver fluke disease is not anticipated to impact intra-community trade.

• Impact on national trade

  There may be reluctance on behalf of farmers to buy animals from a recognised fluke infested area.

  GAP: Fluke is known to modulate the immune system such that fluke infected animals may be more susceptible to some infectious agents and also less likely to be diagnosed with bovine TB. While further work is required on the motivation/decisions of farmers itmay deter some from buying cattle from fluke endemic areas across the UK in fear of undiagnosed bovine TB in those cattle. This is particularly significant with regards export of animals to TB free areas.

• Main perceived obstacles for effective prevention and control

  Control of the intermediate snail host;

  Good diagnostics for infected animals;

  Good control programmes that do not rely solely on use of anthelmintic prophylaxis because of problems with drug resistance;

  Lack of drugs that are effective against the young immature stages of the parasite;

  Lack of vaccines.

  GAPS:

  Control cannot rely solely on vector control. We lack data to give informed advice on other methods of reducing burden of infection.

  Proven benefits of integrated diagnostics/treatment remain to be widely taken up by stakeholders.

• Main perceived facilitators for effective prevention and control

  The prophylactic use of anthelmintics is currently the main method for prevention and control.

  GAP: More research is required to investigate whether strategic worming programmes will be adopted by farmers if information can be provided on intensity of infection in individual animals.

• Links to climate

  Seasonal cycle linked to climate

  Yes in that as warmer and wetter seasons become more apparent the incidence of the disease is spreading to areas not previously associated with the disease. The seasonality of disease outbreaks may change and geographical distribution of infection may increase.

• Distribution of disease or vector linked to climate

  The presence of the intermediate snail host is required for transmission. Snails can be transported accidentally via a variety of routes (e.g. on wild birds). But movement of infected domestic stock is most likely to be responsible for introduction of infection into new areas.

• Outbreaks linked to extreme weather

  No.

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

  The geographical distribution of the vector will be dependent on the effects of climate change.

  GAP: More information is required about the possible impact of climate change on seasonality, prevalence and spatial distribution of fluke infection and fasciolosis.

Risk

• Currently the most urgent risk is in relation to the development of resistance to the current pharmaceutical products. The predicted effects of climate change may also significantly increase the risk of infection and subsequent disease. Change in geographical patterns of disease amongst herbivores also has the potential to increase risk of disease for human populations.

Main critical gaps

Conclusion

• The use of anthelmintics as a prophylactic treatment is common among conventional farms in fluke endemic areas. However the use of anthelmintics is problematic for organic farmers and therefore other methods of control need to be applied. These should include better management methods to reduce exposure to infection and biological control of the intermediate host. The impact of fluke on its host’s immune system needs further work especially the effect of increasing susceptibility to other pathogens leading to increased disease and diagnosis of some infections such as bovine TB. This should be a priority area for more research.

Sources of information

• Expert group composition

  Expert group members are included where permission has been given

  Diana Williams, University of Liverpool, UK - [Leader]

  Robin Flynn, University of Liverpool, UK

• Date of submission by expert group

  30 November 2017

• References

  Review paper based on this gap analysis:

  Beesley et al., 2017. Transbound Emerg Dis, 1-18.

• Name of reviewers

  Project Management Board

STAR-IDAZ Research Road Maps

• Development of candidate vaccines (Liver fluke)

  Development of control strategies (Liver fluke)

  Development of therapeutics (Helminths)

  Development of diagnostic tests (Helminths)