Control Tools

• Diagnostics availability

• Commercial diagnostic kits available worldwide

  Several commercial real-time RT-PCR kits have been developed targeting different regions of the CSFV genome. Real-time RT-PCR has been found to be the most sensitive method for detection of CSFV. For viral antigen detection, capture ELISA kits (E^rns detection) are available but have lower sensitivity than real-time RT-PCR methods and are only suitable for screening at the herd level. Several commercial tests based on detection of anti-E2 antibodies are on the market and routinely used for many years now. In addition, ELISA kits for detection of anti-E^rns antibodies are available. Advantage of these E^rns based assays is the detection of antibodies at an early stage of infection and a possible application in conjunction with marker vaccines (DIVA concept).Commercially available monoclonal antibodies and conjugates can be used for different staining techniques.Furthermore, easy-to perform lateral flow devices for the combined detection of CSFV- and ASFV-directed antibodies have been developed.Evaluation of oral fluid sampling at the individual and group level for ELISA and RT-PCR has been reported. Oral fluid sampling has also been used to detect anti-E^rns antibodies.

  List of commercially available diagnostics (Diagnostics for Animals)

  GAPS :

  Quality of diagnostic products varies, availability of certain test kits may be problematic. Improved CSFV antigen ELISAs for use in resource poor settings where large scale RT-PCR are not yet easily accessible.Easy-to perform pen-side tests for the detection of CSFV-specific antibodies are lacking in terms of sensitivity.Occasionally non-specific reactions in antibody ELISAs still require confirmation by comparative neutralising assays.

• Diagnostic kits validated by International, European or National Standards

  Routine methods are described in both the WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals as well as in the Manual of Diagnostic Tests for Detection of CSF of the EURL for CSF (available at the homepage of the EURL for CSF). Batch release is performed by national reference laboratories within the EU and by other national reference laboratories.

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

  Routine methods are described in both the WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals as well as in the Manual of Diagnostic Tests for Detection of CSF, available at the homepage of the EURL for CSF.

  GAPS :

  See section “New developments for diagnostic tests”.

• Commercial potential for diagnostic kits worldwide

  Compared to other veterinary pathogens there is only a limited market for diagnostics for exotic diseases. Thus, the incentive for the development of new diagnostic kits is not very high. In addition, CSF is a notifiable disease, hence National and International Regulations may limit the use of new products like pen side tests. Among other things cost-efficient production depends on high production volumes. CSF outbreaks are difficult to predict which makes product forecasts vulnerable to high variations. Customers ask for a large number of ELISA and real-time RT-PCR tests ready for use in case of a contingency, but usually only a few tests are sold in peacetime.

  GAPS :

  Low commercial incentives to develop new tests, improve existing tests or even maintain the current fully validated kits.

• DIVA tests required and/or available

  A live DIVA vaccine is available. Two differential diagnostic E^RNS antibody ELISA tests are on the market. Real-time RT-PCR methods are available which can discriminate between C-strain vaccine and CSFV genotype 2 field strains or between DIVA vaccine CP7_E2alf and CSFV.

  GAPS :

  Limited specificity of current DIVA ELISAs make a reliable differentiation difficult. Lack of efforts and strategies to overcome this problem.

• Vaccines availability

• Commercial vaccines availability (globally)

  Different variants of the C-strain live vaccine are available worldwide. Live vaccines are widely used for domestic pigs as injection vaccines and for wild boars as oral vaccines.Local vaccines of undefined quality are available in some countries. Vaccine banks for emergency use are maintained in the EU and some other disease-free countries.

  GAPS :

  Due to financial and political restraints, availability of vaccines is limited in some countries resulting in insufficient vaccine coverage. Standard control protocols are not universally applied. No obligatory quality control for vaccines in some countries.Limited number of suppliers and formulations for oral bait vaccine for use in different wild boar populations.

• Marker vaccines available worldwide

  Live DIVA vaccines and E2-based subunit vaccines are available and used in some countries. Recently, novel Live DIVA vaccine candidates providing a reliable differentiation from infected animals were developed.

  GAPS :

  See section “Commercial Vaccines authorised in Europe”.

• Effectiveness of vaccines / Main shortcomings of current vaccines

  Animals vaccinated with conventional live vaccines cannot be differentiated serologically from infected animals. Pigs vaccinated with marker vaccines and infected by ruminant pestiviruses may test positive in the discriminatory test due to cross-reaction/lack of test specificity (this will be the fact even if they have not been vaccinated previously).

  Live vaccines are effective even when vaccination takes place only a few days before infection. In general, most MLV (e.g. C-strain vaccines) are reported as highly efficacious after a single oral or parenteral vaccine application and the onset of protection starts very shortly (few days) after vaccination. Several experimental studies suggest that the live DIVA vaccine CP7_E2alf is equally protective.

  GAPS :

  Understanding the mechanism of early protection after vaccination with MLV (C-strain) and new DIVA live vaccines.As numerous suppliers of MLV vaccines exist globally and variation in efficacy has been reported, it is important to perform a quality control of vaccines from different suppliers on a regular basis. In some countries several manufacturers still produce C-strain vaccines in rabbits despite concerns in terms of standardization and safety. In addition, ethical reasons argue for a replacement by production of C-strain vaccines in cell culture.

  Further understanding of the impact of maternally derived antibodies on vaccination efficacy in endemic situations.

• Commercial potential for vaccines

  Commercial potential exists in endemic countries outside Europe. Within Europe limited commercial potential exists for vaccine banks for emergency vaccination of domestic pigs or wild boar.

  GAPS :

  Commercial incentives for development and licensing of DIVA live vaccines are limited.

• Regulatory and/or policy challenges to approval

  Use of genetically modified vaccines might be problematic in some countries.

  GAPS :

  It is unclear whether GMOs as vaccines will be accepted by market and consumers.The current licensing process does not include a formal link between DIVA vaccine and discriminating test.

• Commercial feasibility (e.g manufacturing)

  GAPS :

  Development and production of “new” type of bait vaccines for wild boar with improved heat stability and degradable blisters are needed.

• Opportunity for barrier protection

  In principle, it is possible to use vaccination as a measure to prevent entry or spread of CSF (cordon sanitaire vaccination). However, direct or indirect contacts may occur to non-vaccinated pigs outside this area due to increased mobility (personnel, pig transports, meat).

• Pharmaceutical availability

• Current therapy (curative and preventive)

  There is no therapy for CSFV and in Europe any treatment is forbidden by EC legislation.

• Future therapy

  Antiviral substances might be potential candidates for treatment.

  GAPS :

  Knowledge on use of antivirals is yet scarce. So far, no antivirals are commercially available.

• Commercial potential for pharmaceuticals

  Antiviral substances which prevent or diminish the shedding of CSFV by infected pigs, and or prevent infection might become commercially interesting in the future.

• Regulatory and/or policy challenges to approval

  In Europe any treatment is forbidden by EC legislation.

  GAPS :

  Minimal requirements with regard to safety and efficacy of antiviral substances have been not defined so far.

• Commercial feasibility (e.g manufacturing)

  Unknown.

• New developments for diagnostic tests

• Requirements for diagnostics development

  In general, sensitive, specific, and robust laboratory diagnostic tests are available. There is a continuous need for the improvement of diagnostic tests in terms of sensitivity, specificity, costs, practicability, and robustness.To improve comparability of sensitivity of CSF E2 antibody ELISA batches, a standard serum reference panel was established at the EU and WOAH Reference Laboratory for CSF and is available upon request.Pen side tests could be interesting tools; however, their role in the control of notifiable diseases is discussed controversially.

  GAPS :

  Reliable pen-side tests are not commercially available although some lateral flow devices have demonstrated to be promising. A consensus on the use of pen-side tests for the detection of CSF is needed.More robust serological tests for feral pigs are needed, i.e. tests which tolerate highly haemolysed samples without problems.While there are general guidelines for validation of diagnostic tests (e.g. WOAH), there are no standardized procedures for validation of specific tests. The criteria for test validation have not been defined.Tools to differentiate CSFV infection from other pestivirus infections should be improved.

• Time to develop new or improved diagnostics

  In general, the development of tests is much faster and less expensive compared to vaccine development. Time and costs depend on the nature of the test. Still several years elapse until a test becomes available as diagnostic tool and even longer until it is commercially marketed.

  GAPS :

  Low disease incidence means limited availability of positive field samples for test validation, necessitating use of samples from experimental infections in high containment facilities.

• Cost of developing new or improved diagnostics and their validation

  Developing and validating new diagnostic tests is a time- and labour consuming task, which is rather costly. Costs cannot be specified exactly as they depend on the nature of the test. Cooperation between diagnostic/research lab with expertise in diagnostic techniques and commercial companies with expertise in licensing and marketing such products is useful.

  GAPS :

  There are limited incentives for commercial companies to license and market new products.There are limited incentives for commercial companies to license and market new products.

• Research requirements for new or improved diagnostics

  Cooperation and serious involvement of labs with a combination of research and diagnostic expertise is necessary.

  GAPS :

  Testing of samples derived from national domestic pig herds (negative samples collected for other purposes) for test validation might cause legal problems in some countries.A stronger involvement of industry would be advantageous.

• Technology to determine virus freedom in animals

  Freedom from virus in individual domestic animals can be certified by repeated real-time RT-PCR analyses of the same animal within a certain time frame, while it is kept in quarantine in the meantime. Certification of virus freedom on herd level and in wildlife populations is limited and statistical methods have to be included.Ab ELISA can be used in parallel to check the absence of seroconversion at herd level.

  GAPS :

  Modern improved techniques can provide a very good diagnosis with a minimum error rate. However, it is impossible to guarantee 100% freedom of disease for any population.Minimum requirements for monitoring have not been defined in all countries.Evaluation of surveillance strategies in backyard pig and wild boar populations is needed.Validation of oral fluid based sampling needs to be evaluated.

• New developments for vaccines

• Requirements for vaccines development / main characteristics for improved vaccines

  There is a licensed live DIVA vaccine (Suvaxyn CSF Marker) and an accompanying serological tests based on detection of E^rns induced antibodies available. However, the BVDV backbone in this vaccine impedes a reliable differentiation of vaccinated from infected animals on individual level. Improved combinations of DIVA vaccine candidates and accompanying diagnostic tests have been developed.

  GAPS :

  Whereas the European Pharmacopeia only deals with drugs and vaccines, there is no formal link between the marker vaccine and the accompanying diagnostic (marker) assays.

• Time to develop new or improved vaccines

  A period of 5-10 years for the development, clinical trials and licensing is realistic.

  GAPS :

  Commercial incentives are lacking in disease free areas.

• Cost of developing new or improved vaccines and their validation

  Very expensive and a small probability of a large market in Europe. However, outside Europe there could be a substantial market for live DIVA vaccines.

  GAPS :

  Currently there is no substantial funding of research activities by non-commercial bodies in Europe and only limited funding in some countries outside Europe (e.g. Japan).

• Research requirements for new or improved vaccines

  Cooperation and serious involvement of labs with a combination of research and diagnostic is necessary. Especially for the subsequent test of vaccinated and/or infected animals.The limited market potential in Europe for improved vaccines is a critical factor.

  GAPS :

  Closer cooperation and contact between European and Non-EU laboratories needs to be established and maintained.Development of improved vaccines would be enhanced by an improved understanding of what host responses are required to improve efficacy of subunit DIVA vaccines and minimise impact of infections with immunosuppressive agents.

• New developments for pharmaceuticals

• Requirements for pharmaceuticals development

  There is no therapy for CSFV and in Europe any treatment is forbidden by EC legislation. Currently there are no promising and efficacious substances for antiviral treatment. However, the potential of antiviral substances could be further elucidated.

  GAPS :

  Lack of commercial incentives

  Establish criteria for :

  -registration of antivirals

  -acceptance of meat from treated animals

• Time to develop new or improved pharmaceuticals

  Five to ten years seems to be a realistic time frame.

  GAPS :

  See section “Time to develop new or improved vaccines and their validation”.

• Cost of developing new or improved pharmaceuticals and their validation

  Unknown.

  GAPS :

  See section “Time to develop new or improved vaccines and their validation”.

• Research requirements for new or improved pharmaceuticals

  N/A

Disease details

• Description and characteristics

• Pathogen

  Classical Swine Fever Virus (CSFV), Pestivirus, Flaviviridae. Lipid-enveloped RNA virus.Closely related to the ruminant pestiviruses that cause bovine viral diarrhoea and border disease.

  GAPS :

  Infection of pigs with ruminant pestiviruses closely related to CSFV complicates CSFV diagnosis.

  Biological significance of cross-reactive antibodies induced by other pestiviruses and recombination potential with other porcine and ruminant pestiviruses unknown.

• Variability of the disease

  The virus has only one serotype, although some minor antigenic and genomic variability between strains can be shown (genotypes). Variability in virulence: acute (high mortality – up to 100%), sub-acute (lower morbidity and mortality rates), chronic (few animals affected – always fatal), some subclinical cases. Piglets are more severely affected with higher mortality than in adults. The virus is able to cross the placental barrier and can induce persistent infections. The outcome of the disease is influenced by the infecting virus isolate as well as age class and immune status of the infected pig. The only natural hosts known are members of the family Suidae.

  GAPS :

  Virulence factors and host factors, which influence the outcome of the disease.Prevalence of chronically infected animals for different CSF viruses in the population – high percentage versus low percentage and the arising implications.Effect of genetic and antigenic variation on maintenance of circulation of field virus within vaccinated populations. Effect of this on long term efficacy of existing and new vaccines.The antigenic mismatch between the field strain and the vaccine strain may be serious in piglets that only have maternal antibodies.

• Stability of the agent/pathogen in the environment

  Moderately fragile and does not persist in the environment. Sensitive to drying and ultraviolet light. Survives well in pens during cold conditions (up to 4 weeks in winter). Survives 3 days at 50°C and 7-15 days at 37°C. Survives in meat during salt curing and smoking for 17 to >180 days depending on the process used. Virus persists 3–4 days in decomposing organs and 15 days in decomposing blood and bone marrow.Stable at pH 5-10. Rapidly inactivated at pH <3.0 or pH >11.0. (source: WOAH technical disease card).

  GAPS :

  Data on the survival of CSFV in cured meat products is variable. Level of certainty of estimated survival times in these products is therefore low.

• Species involved

• Animal infected/carrier/disease

  For CSFV, only porcine species are involved (pig, swine, wild boar).Serological cross-reaction with ruminant pestiviruses.Chronically and persistently infected (PI) animals may occur. Experimental transmission to ruminants and rabbits is possible.

  GAPS :

  Transmissibility of CSFV to ruminants – sheep, goat, cattle under field conditions.Longevity and prevalene of PI wild boar piglets is unclear.Chronic infections and the factors leading to it are far from being understood.

• Human infected/disease

  None.

• Vector cyclical/non-cyclical

  No known vectors.

• Reservoir (animal, environment)

  Infected pigs and wild boar are the only reservoirs in Europe.

  GAPS :

  Population dynamics of CSFV in wild boar.

  Role and prevalence of persistently infected wild boar.

  Differences of CSFV-transmission dynamics in differently structured wild boar populations.

  Impact of ASF infected wild boar populations on prevalence and geographical spread of CSF.

• Description of infection & disease in natural hosts

• Transmissibility

  Ingestion of virus, direct (oronasal, sperm) and indirect contact (orofecal, contaminated equipment, clothes, vehicles, rodents, uncooked meat products). Infected wild boar are risk factors for domestic pigs and vice versa.

  GAPS :

  Causes of neighbourhood transmissions in densely populated areas.

  Role of aerogenic spread and indirect contact.

  Modelling/ retrospective studies on dynamics of transmission in backyard pig populations and transfer to commercial pig holdings and wild boar (determination of source of introduction and contact rate).

• Signs/Morbidity

  Fever and haemorrhagic disease with immunosuppression as leucocytes almost disappear. Moribund pigs may also suffer from CNS signs. Clinical signs are similar in wild boar, though rarely seen, as they hide.

  Febrile, multisystemic disease with extremely variable, age and virus dependent clinical signs. Acute, chronic, and prenatal courses. Signs include gastrointestinal, respiratory, central nervous, and reproductive disorders (huddling, dullness, high fever, anorexia, erythema, cyanosis, petechiae, staggering, weakness, convulsions and poor reproductive performances, swollen lymph nodes, conjunctivitis).Secondary infections due to immunological impairment.

  GAPS :

  Host and viral factors determining the clinical outcome of infection and manifestation of distinct signs.

• Incubation period

  2 to 12 days, mainly 3-8 days (Depends on virulence of strain and host factors).

  GAPS :

  Incubation period after infection via artificial insemination.

• Mortality

  Depending on virulence of the infecting virus isolate, presence of other primary/secondary pathogens and age class of animals the case fatality rate (the number of clinically affected animals that die from the disease) of the acute form of CSF may reach 70 to 95 % especially in young animals. It may be lower in breeding sows and boars. Chronically and persistently infected animals will all ultimately die after variable time of being infected.

  GAPS :

  Factors determining the mortality rate in host populations, particularly in wild boar.

• Shedding kinetic patterns

  Chronically infected pigs and congenitally infected piglets (persistently infected animals) shed the virus for months or until death.

  GAPS :

  Period of virus shedding (survival of chronic/ persistently infected pigs).

• Mechanism of pathogenicity

  As a consequence of its destructive effects on the lymphoid system CSFV is known to be immunosuppressive. The virus causes depletion of T- and B-lymphocytes, lymphoid follicles disintegration, as well as a thymus and bone marrow atrophy. Animals severely affected by the disease do not develop neutralizing antibodies before 2-4 weeks.Since CSFV is noncytopathic in vitro, and surviving piglets infected early in gestation may show few, if any clinical signs or lesions beyond thymic atrophy it has been suspected that the serious lesions seen in vivo following acute infection were linked to immunopathological damages induced by a reaction of the host to the virus infection. A basis for this is the high affinity of CSFV for the immune system with infection of leukocytes, macrophages, endothelial cells and dendritic cells. For this infection, the viral N^pro protein which inhibits the release of IFN-α and -β from macrophages, endothelial cells and conventional dendritic cells, is important. In vitro data also suggests that N^pro inhibits apoptosis. However, the infection is associated with a high systemic IFN type I response as well as a local inflammatory cytokine responses within primary and secondary lymphoid tissue. While macrophages are involved in secretion of pro-inflammatory cytokines, plasmacytoid dendritic cells are the only cell type “resistant” to the effect of N^pro and therefore able to produce large quantities of IFN type 1. The latter represent a most prominent and early response, and likely to represent a key event in immunopathogenesis. It is proposed that lymphopenia, destruction of lymphoid structures and leukocyte apoptosis is a consequence of a virus-induced “cytokine storm”.Also the changes in the haemostatic balance typical for the disease, inducing thrombocytopenia and disseminated haemorrhages, are thought to be triggered by overproduction of pro-inflammatory and antiviral factors. Virus-induced activation of endothelial cells could play a role in disease pathogenesis, by production of pro-coagulant factors and pro-inflammatory cytokines, as well as in facilitating virus dissemination by attracting monocytic cells. CSFV could also use dendritic cells as a vehicle to different sites in the body, especially to lymphoid tissues.In chronic infection, immune complex deposition may play an additional role.

  GAPS :

  The viral elements of importance for pathogenesis are largely unknown and their identification will be critically important for a rational vaccine design as well to understand viral epidemiology considering the wide range of virulence. This suggests a spectrum of interactions with the host response, exhibited to different degrees by different strains of the virus. To this end it is important to identify the viral factors (viral proteins and cis-acting RNA elements) involved in cell tropism and the various steps of the viral life cycle (invasion, translation and processing of viral proteins, RNA replication, assembly, and release) that determine the virulence of a particular CSFV isolate. These are likely to determine the capacity of the virus to replicate and persist in its primary target cells within the immune system.On the host side, it will be important to determine the sequence of events in immune-pathogenesis, the role of individual cell types, and their interaction to understand disease pathogenesis. To identify the cellular receptor(s) and factors involved in attachment and entry of CSFV will also be crucial to understand viral tropism and pathogenesis. Such knowledge will be crucial for development of better vaccines and novel interventions such as disease resistant gene edited animals.

• Zoonotic potential

• Reported incidence in humans

  None.

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

  None.

• Symptoms described in humans

  None.

• Likelihood of spread in humans

  None.

• Impact on animal welfare and biodiversity

• Both disease and prevention/control measures related

  Clinical CSF is a severe welfare problem. However, animal welfare problems in farms are few given that the diagnosis is determined fast and the herd culled. In case of an outbreak severe welfare problems may arise among pigs in healthy farms in restriction zones, because of the imposed quarantine measures and transport stand stills. Long lasting courses with pneumonia, fever, lameness and wasting are very bad for animal welfare.

  GAPS :

  Reliability and safety of alternative eradication strategies e.g. emergency vaccination to live using conventional or marker vaccines. Design and reliability of suitable testing strategies.Adequate culling techniques to ensure safe and animal welfare friendly culling on the farm. Encourage pig industry to establish strategies to minimise the impact of movement restrictions on animal welfare.

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

  In Europe, no endangered wild species. Some rare wild pig breeds in Asia might be affected by CSF outbreaks.

• Slaughter necessity according to EU rules or other regions

  Yes.

• Geographical distribution and spread

• Current occurence/distribution

  Occasionally outbreaks recurring in highly industrialised countries. Endemic in parts of Asia, Africa, Southern America, Eastern Europe, recurrent relapses in areas with infected wild boar.

  Further information:

  1. WOAH animal disease information (WAHID) database https://www.woah.org/en/disease/classical-swine-fever/#ui-id-2

  2. EU: Animal Disease Information System (ADIS) http://ec.europa.eu/food/animals/animal-diseases/not-system_en

  GAPS :

  Information is not always up to date. While in the EU reporting of disease outbreaks is obligatory, many other countries do not report to the WOAH or no testing is performed. The disease status of such countries remains unknown.

• Epizootic/endemic- if epidemic frequency of outbreaks

  It is known that the disease is endemic in much of Asia, Central and South America, and parts of Eastern Europe. A list of WOAH members and zones recognized as free from CSF is provided at the WOAH web page:

  https://www.woah.org/en/disease/classical-swine-fever/#ui-id-2

  GAPS :

  Continuous monitoring and overview global CSF situation.

• Speed of spatial spread during an outbreak

  Numerous studies have been conducted on spatial spread and dynamics in domestic pigs and wild boar. It is greatly influenced by human activities such as transport and pig density. As soon as an outbreak is detected, the implementations of control measures will contribute to interrupt the spread.

  GAPS :

  Comparison of field and modelling studies on the spatial spread during different control measures, in particular vaccination.

• Transboundary potential of the disease

  International trade of pigs, wild boar crossing borders, legal and illegal import of infected meat, waste management, rendering, safe disposal and illegal swill feeding may be the reasons for introduction of CSF into a free country.

  GAPS :

  Lack of awareness with respect to global trade and travel, biosecurity, e.g. illegal swill feeding and waste management.

• Route of Transmission

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

  Direct and indirect contacts, movement and contact with infected pigs (domestic and backyard pigs as well as wild boar), swill feeding of contaminated meat products.

  GAPS :

  Quantification of direct and indirect contacts between herds as well as wild boar and probability of transmission related to specific contacts.

• Occasional mode of transmission

  Mechanical vectors (vehicles and implements), persons, semen, (aerosols), rodents, arthropods.

• Conditions that favour spread

  Late diagnosis and reporting, non-appropriate control and eradication measures, poor hygiene and bad management, high pig density within holding or geographical region, dense wild boar population. Close contact between domestic pigs and wild boars.

  GAPS :

  Role of infectious carcasses/ viscera in the wild.

  Education and awareness of hunters, producers, and veterinary staff.

  Contingency plans.

• Detection and Immune response to infection

• Mechanism of host response

  Immunosuppressive disease, in severe cases the animals die before seroconversion. Pigs infected with less virulent strains recover and as antibody positive animals they are protected from recurring infections, also from highly virulent CSFV strains.Reconvalescent animals develop neutralising antibodies with long-lasting solid protection. Maternal derived antibodies are transmitted to litter from immune sows and can persist for many years. Chronically and persistently infected pigs fail to develop an effective immune response.Infection with CSFV leads to leukopenia and thrombocytopenia through mainly apoptotic pathways and thus depresses the immune system.

  GAPS :

  Role of cellular immunity, mechanisms of immune suppression, innate immune response and role in pathogenesis. Additional factors that confer very early protection upon vaccination.

  Role of cytokines (Interferons, TNFα and others) in the cytokine storm following infection.

  Improved understanding of host factors contributing to pathogenesis, resistance against or recovery from disease will be important for interventions, which may include gene-edited animals, that may help combat the impact of CSF disease.

• Immunological basis of diagnosis

  Antibodies against the virus are used for diagnostic tests (ELISA, VNT). Antibodies usually appear after the second week post-infection. Cross-reactions occur between CSFV antibodies and antibodies raised against ruminant pestiviruses.

  GAPS :

  Currently, the ability to differentiate antibodies to CSF from those to ruminant pestiviruses is complex, time consuming and can be unreliable, particularly at individual animal level.

• Main means of prevention, detection and control

• Sanitary measures

  • State of the art farm biosecurity and hygiene including protection against wild boar.
  • Strict import policy for live pigs, semen, and fresh and cured pig meat.
  • Quarantine of pigs before admission into herd.
  • Efficient prohibition of waste food fed to pigs.
  • Efficient control of rendering plants and disposal sites.
  • Strict regulations for destruction, burial of infected carcasses.
  • Strict sanitary measures on infected premises, cleansing and disinfection, rodent control.
  • Structured serological surveillance targeted to breeding sows and boars.
  • Effective pig identification and recording system.
  • Effective disease reporting system.
  • Effective communication between veterinary authorities, veterinary practitioners and pig farmers.
  • Regular hunting and monitoring of wild boar population.
  • Training of veterinary services.

  GAPS :

  Development of models of alternative eradication strategies (with and without emergency vaccination; vaccination to live scenario) including economic, social and ethical aspects, technical and political requirements for such approaches.Interaction between vaccination and other disease control measures.Standardisation of methodologies for treatment of spray-dried blood and plasma used as feed additives.Assessment of potential risk for dry-cured meat products from various countries/ local regions to contain viable CSFV. Standardisation of methodology for treatment of bristles.

• Mechanical and biological control

  • Slaughter of all pigs on affected farms
  • Safe disposal of carcasses
  • Thorough disinfection
  • Detailed epidemiological investigation, with tracing of possible sources (up-stream) and possible spread (down-stream) of infection.

• Prevention through breeding

  GAPS :

  Potential for, and regulatory and market approval of gene edited pigs with resistance or resilience to CSFV disease is unclear.

• Diagnostic tools

  Diagnostic tests for detection of CSF are described in Manual of Diagnostic Tests for Detection of CSF of the EURL for CSF and WOAH-Manual of Diagnostic tests and Vaccines for terrestrial animals, 2022.

  1. Nucleic Acid Detection Tests:
     1. Real-time RT-PCR
     2. Gel based RT-PCR
     3. Partial sequencing
  2. Virus and Viral Antigen Detection Tests:
     1. Virus isolation using susceptible cells
     2. Immunoperoxidase assay
     3. Immunofluorescence assay
     4. Fluorescent antibody test (FAT) using organ sections
     5. Antigen ELISA
  3. Antibody Detection Tests:
     1. Antibody ELISA
     2. Neutralizing peroxidase-linked assay (NPLA)
     3. Fluorescence antibody virus neutralization assay (FAVN)
     4. Lateral flow devices

  Public accessible commercial tests are available for CSFV genome (RT-PCR), antigen (ELISA) and antibody (ELISA) detection (see Section “Commercial diagnostic kits available worldwide”). Penside tests for the combined serological diagnosis for CSFV and ASFV specific antibodies have been developed.

  GAPS :

  Availability and quality of specific and sensitive marker ELISAs that correspond to available marker vaccines to distinguish infected from vaccinated animals; current DIVA systems not reliable for individual animal testing.Appropriate validation of newly developed diagnostic tests prior to implementation in routine diagnosis.Commercially available penside tests, which combine the CSFV and ASFV serological analyses, frequently provide only limited sensitivity for CSF antibodies and should be improved.Discrimination between ruminant pestiviruses and CSFV antibodies remains difficult due to cross reactivity (e.g. in ELISA for antibody detection).FAT on organ sections has poor specificity, often confounded by non-specific staining.Lack of international, non-infectious molecular standards.

• Vaccines

  Vaccination with modified live virus strains is effective and safe in preventing losses and eradication of the disease, provided the vaccines are carefully manufactured, controlled and applied. It is important that vaccination is always accompanied by control measures. In countries which are free of disease, or where eradication is in progress, vaccination is usually prohibited. Currently two types of live CSFV-vaccines are registered in Europe: live attenuated (modified live vaccine = MLV; C-strain) and a chimeric marker vaccine (genetically modified MLV; CP7_E2alf). While the C-strain vaccines are licensed or authorised by national authorities, CP7_E2alf was registered by EMA.

  In addition, CSFV E2 subunit vaccines are widely used in China, but not on the market in the EU. The subunit vaccines are 2-shot vaccines, have a much longer onset of immunity and are less effective than attenuated live vaccines.

  According to EU legislation, marker vaccines could be used for emergency vaccination to live, i.e. free marketing of products of marker-vaccinated animals. However, this option has never been used so far.

  GAPS :

  Accompanying diagnostic tests for (Live) marker vaccines.

  Development/ availability of improved (Live and subunit) marker vaccines for both domestic and free-living animals.

  Consequences of marker vaccination with the goal of free marketing of products of vaccinated animals, i.e. reaction/ acceptance of EU Member States, Third Countries, trade partners, other stake holders, and consumers.

• Therapeutics

  Treatment is neither allowed nor possible. Affected pigs must be slaughtered and the carcasses buried or destroyed in rendering plants. Nevertheless, antivirals have been discussed as supplementary tool and some were tested in pilot trials.

• Biosecurity measures effective as a preventive measure

  Security clearance for staff entry to the laboratory.

• Border/trade/movement control sufficient for control

  In case of outbreaks designation of infected zone, with control of pig movements.Import of pigs and meat from affected countries is prohibited; similar rules apply for personal consumable goods of international travellers.

  GAPS :

  Legislation is not always fully enforced.Appropriate extent of control and surveillance zones in case of domestic pigs and wild boar CSF outbreaks.Registration of all Suidae (pet, backyard etc) throughout all countries.

• Prevention tools

  Strict rules for importation of food and feed.

  Effective controls at border inspection posts including airports, harbours.

  High biosafety measures on pig holdings.

  Swill feeding prohibited.

  GAPS :

  In some countries swill feeding is not prohibited. In other countries prohibition of swill feeding is not fully enforced (conflict of prohibition of swill feeding with sustainable pig husbandry).

• Surveillance

  Surveillance of infected zone, and the surrounding area.

  Surveillance of areas with CSF in wild boar.

  GAPS :

  Surveillance strategies in countries with a high proportion of backyard pigs.

  Surveillance taking into account limited resources and local conditions in domestic pig and wild boar populations (particular in resource poor countries).

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

  Several large outbreaks in Member States of the EU have resulted in implementation of effective control and eradication strategies.

• Costs of above measures

  In The Netherlands 1997: 11 million pigs were killed and destroyed also for animal welfare reasons, estimated costs of 2 Billion USD.

  GAPS :

  There is a need for an EU harmonized format/framework for the cost estimation, to enable transparent comparison of the economic impact of (1) different control strategies, and (2) between EU member states.

• Disease information from the WOAH

• Disease notifiable to the WOAH

  Yes

• WOAH disease card available

  Direct link to the WOAH

• WOAH Terrestrial Animal Health Code

  Direct link to the WOAH

• WOAH Terrestrial Manual

  Direct link to the WOAH

• Socio-economic impact

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

  Not applicable.

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

  Not applicable.

• Direct impact (a) on production

  Impact on production because of mortality, infertility and other health effects.Impact due to depopulation and restriction measures.

  GAPS :

  Compensation schemes are not emphasizing preventive measures.

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

  Costs of vaccination.Cost of depopulation, costs of re-population, costs of transport restrictions, costs of surveillance post outbreak.

  GAPS :

  More information needed in particular for free global marketing and market acceptance of meat and products from DIVA vaccinated animals.

• Indirect impact

  Loss of import and export markets: pigs and pork products.High economic impact especially in areas with high pig density and export rates due to movement and trade restrictions.Loss of genetically valuable animals, such as rare breeds.For countries with backyard pig production, losses resulting from CSF outbreaks can also impact on poor communities, where pigs are used to supplement income.

  GAPS :

  Evaluation of the cost of control measures e. g. in a tourist area:Most compensation schemes do only compensate direct losses and not consequential losses of an outbreak.Impact on the increased premium costs for self-insured pork producers.

• Trade implications

• Impact on international trade/exports from the EU

  In case of an outbreak quarantine measures and transport stand stills are imposed on infected areas. Once a region is declared free of CSFV trade may be resumed again. This usually takes a few months or longer, particularly in the case of third countries.

  GAPS :

  Impact on trade of DIVA vaccinated and tested animals is unclear (see section “Direct impact (b)”).Market acceptance of product from DIVA vaccinated animals.Inadequate incentives to ensure risk preventive behaviour (transport).

• Impact on EU intra-community trade

  See section “Impact on international trade”.

  GAPS :

  See section “Impact on international trade/exports from the EU.

• Impact on national trade

  See section “Impact on international trade”.

  GAPS :

  See section “Impact on international trade/exports from the EU.

• Links to climate

  Seasonal cycle linked to climate

  Indirect transmission reduced due to higher temperatures in summer, cold and moist conditions support the survival and spread of virus (fall -> spring season).

• Distribution of disease or vector linked to climate

  No.

• Outbreaks linked to extreme weather

  No.

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

  Significant climate and land use changes may affect geography and density of some wild boar populations and thereby may alter some potential for CSF distribution.

• Main perceived obstacles for effective prevention and control

  Difficulties in clinical diagnosis in domestic pigs due to variability of signs, coinciding with emergence of other diseases with similar clinical presentation (PDNS, PRRS, ASF), reluctance of veterinarians to include CSF in the list of differential diagnoses (due to severe consequences), lack of managerial skills and practice, endemically infected wild boar, lack of biosecurity, illegal swill feeding. Illegal import of meat from infected areas due to imperfect control measures on global trade.The occurrence of low virulent strains in recent years has made the diagnosis more problematic.Lack of awareness by farmers and veterinarians especially in countries free of the disease. Wild boar, difficult diagnosis in domestic pigs, materials for analysis obtained from already dead pigs, and illegal import of meat from infected areas. Traditional methods of dry-curing to produce local delicacies, also without need for refrigeration. Swill feeding of material originating from wild boar.

  GAPS :

  Improvement of early detection of CSF outbreaks (shorten high risk period, systems to increase awareness and reporting)Lack of efforts to improve cooperation between farmers, practitioners and veterinary authorities with respect to early detection of disease outbreaks.Lack of awareness and deficiencies in application of control strategies in wild boar. Lack of awareness among hunters. Acceptance of alternative sampling methods has to be discussed.

  Lack of awareness of veterinary services and farming community.No permanent, obligatory education of swine practitioners in CSF diagnosis based on epidemiology of the disease, and clinical and pathological changes as well.

• Main perceived facilitators for effective prevention and control

  Implementation and use of modern diagnostic techniques. Awareness, fast and robust diagnosis without need for movement restrictions, if suspicion not overt but applied as a precaution.Risk based targeted surveillance strategies.

  GAPS :

  Further development and implementation of computerised systems for early detection of CSF primary outbreaks where applicable.Adoption of surveillance strategies in countries with a high proportion of backyard holdings. Lowering the obstacles to send samples for exclusion diagnostics, use of pragmatic sampling and testing approaches.

Global challenges

• Antimicrobial resistance (AMR)

• Mechanism of action

  N/A.

• Conditions that reduce need for antimicrobials

  N/A.

• Alternatives to antimicrobials

  N/A.

• Impact of AMR on disease control

  N/A.

• Established links with AMR in humans

  N/A.

• Digital health

• Precision technologies available/needed

  Precision technologies (sound analyzers, image-detection techniques, sweat and salivary sensing, serodiagnosis, and others) are available and can improve animal health control.

  GAPS :

  Implementation of precision technologies to monitor animal health is limited. There is a need to integrate the available sensors and establish an efficient online monitoring system.

• Data requirements

  Available.

• Data availability

  Available.

• Data standardisation

  Limited.

• Climate change

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

  High standard of disease control including biosecurity results in reduced number of animals required for production of the same amount of pork demanded and a reduction of greenhouse gas emissions and pollutions can be expected.

• Preparedness

• Syndromic surveillance

  Routine surveillance strategies are implemented in the EU and other countries to minimize the high risk period after re-introduction of the disease.

  GAPS :

  Surveillance strategies in resource poor countries with a high proportion of backyard pigs can be improved.Evaluation of surveillance strategies in backyard pig and wild boar populations is needed.

• Diagnostic platforms

  Modern diagnostic techniques/kits are commercially available. High standard and quality of diagnostic tests applied at National reference laboratories for CSF in the EU. and several other countries ensure fast and robust diagnosis of CSF.

  GAPS :

  Outside the EU and associated countries, the range of available international laboratory comparative tests for CSF diagnosis is very limited and should be expanded.

• Mathematical modelling

  Mathematical models using spatio-temporal simulation tools have been developed and used to investigate the efficiency of surveillance and control protocols, which are predetermined by the regulations implemented for CSF control.

• Intervention platforms

  Platforms collecting information about major animal diseases are available. These include the Animal Disease Information System (ADIS) in the EU, which is linked to the World Animal Health Information System (WAHIS) of the WOAH.

  GAPS :

  Several countries outside the EU are not connected to a standardized animal disease notification and information system and/or do not report animal disease outbreaks to the WOAH.

• Communication strategies

  Communication strategies including disease notification and information systems (see above) are available. In the EU, ADIS was implemented to ensure immediate notification of alert messages and detailed information about outbreaks of the most important animal diseases in the countries that are connected to the application.

  GAPS :

  Several countries outside the EU are not connected to a standardized animal disease notification and information system and/or do not report animal disease outbreaks to the WOAH. In such countries, establishment of intervention platforms may improve preparedness for CSF outbreaks.

Main critical gaps

• 1. Improvement of early detection of CSF outbreaks (shorten high risk period, systems to increase awareness and reporting)
  2. Lack of efforts to improve cooperation between farmers, practitioners and veterinary authorities with respect to early detection of disease outbreaks.
  3. Lack of awareness and deficiencies in application of control strategies in wild boar. Lack of awareness among hunters. Acceptance of alternative sampling methods has to be discussed.
  4. Lack of awareness of veterinary services and farming community: no permanent, obligatory education of swine practitioners in CSF diagnosis based on epidemiology of the disease as well as clinical and pathological changes.
  5. Further development and implementation of computerised systems for early detection of CSF primary outbreaks where applicable.
  6. Adoption of surveillance strategies in countries with a high proportion of backyard holdings. Lowering the obstacles to send samples for exclusion diagnostics, use of pragmatic sampling and testing approaches.
  7. In the present epidemiological situation, there are no significant CSF research networks and also no continuous funding for development of CSF vaccines and diagnostics.

Conclusion

• CSF remains a major health and trade problem for the pig industry. In endemic countries or those with a wild boar reservoir, CSF remains a priority for Veterinary Services. Surveillance as well as stamping out and/or vaccination remain principle tools of prevention and control, depending on the context. Vaccines and diagnostic tests are available in Europe and worldwide. Technological advances in both domains have been made in recent years. Further improvements should be promoted by external funding. However, in the present epidemiological situation, there are no significant CSF research networks and also no continuous funding for development of CSF vaccines and diagnostics.

Sources of information

• Expert group composition

  Paul Becher, EU & WOAH Reference Laboratory for CSF, Institute of Virology, University of Veterinary Medicine Hannover, Germany - [Leader]

  Sandra Blome, National Reference Laboratory for CSF, Federal Research Institute for Animal Health, Greifswald – Insel Riems, Germany

  Helen Crooke WOAH CSF Reference Laboratory Animal and Plant Health Agency, Weybridge, New Haw, UK

  Ad de Groof, Department Discovery & Technology, MSD Animal Health, Boxmeer, The Netherlands

  Oliver Gomez-Duran, Technical Service Lead, Global Strategic Marketing, Boehringer-Ingelheim Vetmedica GmbH, Ingelheim am Rhein, Germany

  Denise Meyer, EU & WOAH Reference Laboratory for CSF, Institute of Virology, University of Veterinary Medicine Hannover, Germany

  Alexander Postel, EU & WOAH Reference Laboratory for CSF, Institute of Virology, University of Veterinary Medicine Hannover, Germany

  Yoshihiro Sakoda, Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan

• Date of submission by expert group

  24.07.2023

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