Control Tools

• Diagnostics availability

• Commercial diagnostic kits available worldwide

  For virus detection, isolation is the gold standard. However, antigen capture ELISA (NS3, E^rns) and real-time RT-PCR are used more routinely. Both are used for testing of blood and ear notch samples in standard screening. Many real-time RT-PCR kits are widely available from commercial suppliers.For exposure, VNT is the gold standard for diagnostics, however, routinely blocking ELISAs (NS2-3, or E^rns) or indirect ELISAs (total antibodies) are used for serum, plasma and milk.

  List of commercial diagnostic kits (Diagnostics for Animals).

  GAPS :

  • Validation of kits to detect/differentiate antibodies/antigen/RNA pestiviral species that infect ruminants.
  • Validation of kits to detect antigen or antibodies for use with pooled samples in serum, blood, or milk
  • Lack of serological assays (and vaccines) with DIVA capability.
  • Lack of affordable and practical diagnostic methods for identify dams carrying PI foetuses.

• Diagnostic kits validated by International, European or National Standards

  Kit release testing according to national regulations in some European countries (eg Germany, Belgium, Ireland, Switzerland, France). Work is ongoing in Europe through CEN (www.cencenelec.eu) to develop standards in animal health diagnostics.

  GAPS :

  Lack of central co-ordination of approval of test kits and batch release certification results in duplication of efforts between countries.

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

  Yes, chapter available on BVD in the terrestrial manual from WOAH (chapter 3.4.7).

• Commercial potential for diagnostic kits in Europe

  Ongoing and newly started national and regional control programmes means there is a huge market for commercial diagnostic kits. However the market for NEW kits with similar performance may be limited.

• DIVA tests required and/or available

  Currently not available.

  GAPS :

  • A DIVA strategy lacking. Could be helpful to combine eradication and surveillance with vaccination (protection of a naïve population), although eradication can be achieved without vaccination.
  • Also useful to facilitate introduction of serological testing in programmes which began with tissue tag testing.

• Vaccines availability

• Commercial vaccines availability (globally)

  MLV (based on noncytopathic viruses or double deleted mutant virus) and inactivated vaccines are available.

  Projects involving RNA vaccines are underway but cost is likely to be an impediment in the immediate future.

  GAPS :

  • DIVA vaccines are not available.
  • Cross protection and duration of immunity for heterologous field strains largely unknown for most vaccines.
  • Questions regarding need for vaccine components to reflect subgenotypes and genotypes in circulation in different geographic regions.
  • Evaluation of the efficacy/cost-efficiency of different vaccines/vaccination strategies under field conditions.
  • Efficacy and safety still an issue.

• Marker vaccines available worldwide

  Currently no marker vaccines available.

• Effectiveness of vaccines / Main shortcomings of current vaccines

  MLV and inactivated vaccines are available globally. The prevention of establishment of persistent infection is the major goal with vaccination, and close to 100% efficacy would be required for efficient BVD control. The efficacy of most vaccines under various field conditions is less than 100%.

  GAPS :

  • Evaluation of the efficacy/cost-efficiency/duration of immunity provided by different vaccines/vaccination strategies under field conditions and in the presence or absence of (maternal) antibodies is missing.
  • More extensive information on the level and duration of cross protection and efficacy of existing vaccines against HoBi-like strains and different BVDV1 (Pestivirus A) and BVDV2 (Pestivirus B) sub genotypes, particularly under field conditions.

• Commercial potential for vaccines in Europe

  Very high in the short term until control programmes prohibit their use.

  GAPS :

  Agreement on what will be an acceptable marker antibody for detection in bulk milk and/or serum. Broader cross-reactivity against more recent field subtypes. The goal should be to develop vaccines demonstrating 100% foetal protection.

• Regulatory and/or policy challenges to approval

  Currently none.

• Commercial feasibility (e.g manufacturing)

  All current vaccines are prepared using conventional cell lines. Production is amenable to scale up using bioreactors.

  GAPS :

  Alternative production cell lines may be needed to emerging bovine pestiviruses to the titers required for vaccine production.Alternative platforms for vaccine production (mRNA, DNA, vector vaccines, recombinants proteins etc.) might be envisaged.

• Opportunity for barrier protection

  Currently none.

• Pharmaceutical availability

• Current therapy (curative and preventive)

  No pharmaceutical therapy available commercially to treat acute transient infections. Prototypes are available (tested for related human viruses as well as for CSFV). Treatment of PI animals not realistic.

• Future therapy

  Unlikely.

• Commercial potential for pharmaceuticals in Europe

  No.

• Regulatory and/or policy challenges to approval

  No.

• Commercial feasibility (e.g manufacturing)

  Not considered applicable.

• New developments for diagnostic tests

• Requirements for diagnostics development

  Yes.

  GAPS :

  International standards for test validation, test registration and batch release testing need to be established. Tests should be validated against all pestivirus species that have been isolated from cattle and domestic, especially border disease virus (wich can circulate between ovine and bovine population) and free ranging ruminants that may be in contact with domestic cattle and against subgenotypes of species in circulation in the geographic region from which samples will be collected.

• Time to develop new or improved diagnostics

  Development and registration of diagnostic tests needs 1 – 3 years in general. The veterinary diagnostics market errs on the side of conservatism and new concepts/technologies may need longer time for market penetration.

• Cost of developing new or improved diagnostics and their validation

  In many countries there is a close collaboration between industry and research institutes as well as regulatory bodies that facilitates test development and evaluation.

  GAPS :

  The availability of standard pestivirus-positive reference material with low and high viral loads (e.g. semen, serum, milk) is a limiting factor in test validation and test comparison.

• Research requirements for new or improved diagnostics

  GAPS :

  Currently no tests licensed for differential diagnosis between the different ruminant pestiviruses.Rapid, reasonably priced on-site diagnostic tests that allow timely identification of PI animals would be of great benefit to control efforts.

• Technology to determine virus freedom in animals

  RT-PCR is recognized as the most sensitive method for virus detection. Repeated testing by RT-PCR within a specified time frame provides information about the animal status. Freedom from virus in a population can only be guaranteed in terms of statistical probability.

  GAPS :

  The high sensitivity of RT-PCR sometimes yields results that are difficult to interpret, as transient infections are detected as well. In addition, there are PI animals with a high Ct (>30), and transiently infected animals with a low Ct (<25).

• New developments for vaccines

• Requirements for vaccines development / main characteristics for improved vaccines

  Vaccines have been shown to reduce the incidence of acute infections and persistent infections.

  GAPS :

  No vaccine tested to date has been 100% effective in preventing virus from crossing the placenta and establishing a persistent infection in the fetus. Reducing but not eliminating the number of PI’s conpromises control by vaccination alone.

• Time to develop new or improved vaccines

  Prototypes exist (all are Npro-deletion mutants).Estimation of a time frame: 5 years.

  GAPS :

  Other mutants or double mutants might be helpful, as Npro is not a good marker for DIVA vaccines.

• Cost of developing new or improved vaccines and their validation

  Could be considerable as the model for evaluating efficacy requires the use of cattle. Cattle are expensive, naïve cattle are difficult to acquire and cattle housing is expensive.

• Research requirements for new or improved vaccines

  Better understanding of transplacental transmission of ncp BVDV, in order to provide improved means of blocking virus passage across the placenta. Better understanding of impact of passive antibodies on efficacy of vaccination.

• New developments for pharmaceuticals

• Requirements for pharmaceuticals development

  Unlikely to be any means of pharmaceutical treatment.

• Time to develop new or improved pharmaceuticals

  N/A.

• Cost of developing new or improved pharmaceuticals and their validation

  N/A.

• Research requirements for new or improved pharmaceuticals

  NA.

Disease details

• Description and characteristics

• Pathogen

  Three main species of pathogens in cattle, Bovine viral diarrhea virus (BVDV) type 1 (BVDV1) (Pestivirus A), BVDV type 2 (Pestivirus B) and Hobi-like (Pestivirus H) viruses (previously referred to as BVDV3 and atypical bovine pestivirus) are associated with the group of clinical presentations known as bovine viral diarrhea (BVD). All three species are classified in the genus Pestivirus of the family Flaviviridae. They are single stranded, enveloped RNA viruses similar to Classical swine fever virus (hog cholera virus; Pestivirus C) and Border disease virus (Pestivirus D) of sheep. All three species can be grouped, based on phylogenetic analysis, into subgroups (subgenotypes). While it appears that there are differences between subgenotypes in geographic distribution and antigenic cross reactivity, the criteria for differentiating subgenotypes has not been defined.Viruses in all three species may exist as one of two biotypes, cytopathic and noncytopathic, based on their activity in cell cultures. Regardless of species, the noncytopathic biotype predominates in nature, as only this biotype is able to induce persistence.In addition, several other emerging pestivirus viruses originating from non-bovine species have been described during recent years (e.g. “Antelope” and “Atypical porcine pestivirus). However, the host tropism of these emerging viruses has not been established and it is not known if they infect bovines and cause clinical presentations similar to those seen with BVD.

  GAPS :

  • There is a need of further investigations of the host tropism, geographical distribution and clinical importance of recognised and emerging pestiviruses in both ruminant and non-ruminant species, and the potential reservoir role of wildlife species. Similarly the geographic distribution, antigenic relationship and clinical importance of subgenotypes is largely undefined. Systematic screening and characterisation of pestiviruses globally should be carried out, with particular focus on areas that have been poorly investigated and that may have a major influence on other parts of the world, e.g. due to export of fetal bovine serum (FBS) or semen.
  • The capacity of diagnostic methods to satisfactorily detect and/or differentiate between virus species and subgenotypes, and of current vaccines to adequately cross protect against different species and subspecies, needs to be kept under review.
  • There is a need for vaccine specific to Border Disease Virus (BDV) for the ovine population, since the BVDV vaccine is used with a relative success in this species.
  • There is also a need for diagnostic kits (serology) specific to BDV.

• Variability of the disease

  Virus isolates from the main species exhibit considerable antigenic and biological diversity. The three species may be differentiated from each other and from other pestiviral species by monoclonal antibodies directed against the E2 and E^rns major glycoproteins, differential PCR amplification or by phylogenetic analysis. Relative prevalence of the three varies by geographic location. BVDV-1 and BVDV-2 viruses are more geographically dispersed than HoBi-like viruses. BVDV1 viruses are prevalent in Europe, South America and North America. BVDV2 viruses are found at higher rates in North America and South America than in Europe. Hobi-like viruses thus far have only been reported in South America, Europe and Asia. Regardless of species or geographic location, the non-cytopathogenic biotype predominates in the field. While both BVDV1 and BVDV2 have been isolated following outbreaks of severe acute disease associated with haemorrhage in the field, severe acute disease has only been reproduced under controlled conditions with BVDV2 strains. It should be noted that highly virulent BVDV2 strains are in the minority in nature and that the majority of BVDV2 strains are no more virulent thanBVDV1 or HoBi-like virus strains.

  The genomes of all three species consist of 1 long open reading frame (ORF) flanked by two non-translated regions. The ORF is translated into one long polypeptide, which is subsequently cleaved into the individual viral proteins by viral and cellular proteases. Recombination events, resulting in genomic insertions, have been observed with all three species. These insertions might be associated with changes in biotype and in some cases virulence.

  GAPS :

  • There is a need of further investigations of the host range, geographical distribution and clinical importance of recognised and emerging pestiviruses, both in ruminant and non-ruminant species, and the potential reservoir role of wildlife species. Systematic screening and characterisation of pestiviruses globally should be carried out, with particular focus on areas that have been poorly investigated and that may have a major influence on other parts of the world, e.g. due to export of FCS or semen. The capacity of diagnostic methods to satisfactorily detect and/or differentiate between virus species, and of current vaccines to adequately protect against all three species, needs to be keep under review.
  • Gaps remain in the understanding of virulence factors, the role of many of the pestivirus proteins and the mechanism of adaptation of viruses to different hosts (important in determining impact of wildlife infections on control programs and infections with Border disease virus in cattle).
  • Better data is needed on the drivers and rate of evolution, the impact of management factors on evolution and how different population factors such as contact structures shape evolution.
  • The real impact from a production and welfare point of view is still not clear. The impact of infection on the developing bovine immune system is poorly understood as is the interaction of these viruses with other pathogens in the development of the bovine respiratory disease complex. Although it is widely recognized that BVD is important and relevant, there is the need to convince both the producers and the authorities in some countries to take it seriously.

• Stability of the agent/pathogen in the environment

  BVDV does normally not survive in the environment for more than two weeks; although it has been shown that virus may survive for a longer period of time under wet and cold conditions (winter snows).

  Virus may also survive and remain infective for longer periods in hair samples, desiccated tissues, fomites and beddings.BVDV is susceptible to common disinfectants.

  GAPS :

  • The practical importance of prolonged survival of the virus under cold wet conditions, and in hair, desiccated tissues, beddings and fomites on equipment used to house, handle, process and transport animals and the risk of mechanical transmission (e.g. via flies) are unknown.
  • The risk of spread of BVDV from contaminated vaccines, semen, pooled colostrum and materials used in embryo transplant has been demonstrated, but the stability of the virus in such media is unknown.
  • Further work on environmental stability (half life) under different conditions (e.g. temperature, humidity, matrix) is required.
  • Little information is available regarding the contamination rates of personnel, vehicles, and equipment after visiting BVD positive farms.
  • The effectiveness of common disinfection practices in a variety of matrices (slurry, manure, straw, lochia, etc.) in reducing contamination is unknown.

• Species involved

• Animal infected/carrier/disease

  Persistently infected (PI) cattle are the main carriers. Their role in the epidemiology of the disease cannot be overestimated.

  Acutely infected cattle are transient carriers. The length of transmission following acute infection may vary based on health, stress level, age and presence of other pathogens.

  Small ruminants and other domestic and wild even toed ungulates are potential carriers.

  Some studies have described evidence of infection/susceptibility to infection in rabbits and European hares.

  GAPS :

  • The epidemiological importance of virus presence in other populations besides cattle (small ruminants and other domestic and wild even toed ungulates, e.g. water buffalo, alpaca, deer, chamois) is not fully understood. The impact of ruminant pestivirus infections in countries with large and dense populations of small domestic ruminants needs further investigation. Particularly in production systems where co-grazing of species (e.g. sheep and beef) is practiced.
  • The susceptibility of non-ruminant species e.g. lagomorphs to infection, and their role in the epidemiology of the disease, needs to be clarified.
  • The contribution of pregnant, non-PI cattle carrying PI foetuses (Trojan dams) in the spread of infection between herds under different management systems requires further investigation.
  • The importance and role of chronically infected animals and of long-term virus shedding after acute infection, e.g. recrudescence of disease after steroid treatment in seropositive animals with prolonged viral survival in ovaries, need further investigation. The ability of the virus to circulate in herds for extended periods in the absence of PI animals also needs clarification. Especially in “naïve populations” this transfer mechanism might have a high impact (comparison to CSFV).
  • New-born calves infected early in life appear to be a possible problem. Virus in serum might may be detectable for a prolonged time even in the presence of maternal antibodies (by RT-PCR, often with high Ct values). These animals are not PI, but in field situation, such a farm is often restricted until clear negative results are available. But whether they really can transmit the virus is unknown. Prepubescently infected, non-PI cattle may develop chronic infection in reproductive tissues. In some cases infectious virus can be isolated while in others virus is only detectable by PCR. The risk of transmission of virus by these animals is largely unknown.
  • A vaccine failure with, at least, one live attenuated vaccine has been described in two countries. When this vaccine is misused (vaccination of the dam after the insemination) a persistence of BVDV nucleic acids is seen on the newborn calf (during its early live).

• Human infected/disease

  No.

  GAPS :

  While there is no direct evidence that any of the three species cause clinical disease in humans, human vaccines have been demonstrated to be contaminated with BVDV. Given the plasticity of pestiviruses and their ability to rapidly adapt to new hosts, more effort should be exercised in reducing human exposure to pestiviruses by eliminating BVDV contamination of vaccines and determining how effective food processing protocols are in eliminating/reducing BVDV contamination of milk and meat.

• Vector cyclical/non-cyclical

  Insects may carry the virus passively.Passive vectors like vehicles and veterinarians etc can play a significant role in transmission.

  GAPS :

  The importance of vectors (flies) for passive transmission of BVDV not well understood. Risk estimates needed.

• Reservoir (animal, environment)

  Persistently Infected (PI) animals including cattle, other domestic ruminants and wildlife are the major reservoirs.

  Minor sources of infection include transiently infected animals, semen of infected cattle, frozen colostrum, transplanted embryos, contaminated live vaccines and cell lines and other biologicals produced using contaminated fetal bovine serum (FBS).

  GAPS :

  The ability of small and wild ruminants (independent of contact with cattle or otherwise) and of non-ruminant species to serve as reservoirs of infection, and the potential impact of this on control and eradication programmes, needs further investigation.

• Description of infection & disease in natural hosts

• Transmissibility

  Spread is mainly by direct contact with infected animals or bodily fluids from infected animals, in particular by contact with PI cattle. Vertical transmission plays an important role in its epidemiology and pathogenesis. Viruses may be transmitted across the placenta from dam to fetus.

  Semen from persistently and acutely infected animals and, rarely, recovered animals may be suspect.

  The general use of FBS in embryo transfer and in vaccine production is a risk factor for long distance/high impact transmission.

  GAPS :

  • Transmission parameters poorly understood, including required infectious dose, cell type initially infected upon various routes of infection, role of mucosal immunity in protection, systemic spread of virus to reach reproductive organs or the fetus, etc.
  • Risk of spread of virus between domestic and wildlife species in different geographic areas needs to be assessed.
  • Risk of spreading virus via embryo transplant due to use of contaminated FBS is well recognised This should not be occurring and there are guidelines that indicate FBS is unsuitable for embryo freezing.
  • The potential risk of spreading ruminant viruses through natural insemination from infected bulls is not clear. The virus load in semen can vary from very low (that will result in transmission to a small number of recipients) to levels approaching those of PI animals where a much higher proportion will be infected. The production of a PI animal by insemination with virus containing semen (artificial or natural insemination) is possible, but appears to be inefficient. However, even with low efficiency, it is only necessary to infect a single animal in a susceptible herd to establish a transmission cycle.
  • Risk of spreading virus via modified live vaccination (against various pathogens in cattle) due to use of contaminated FBS in manufacturing process needs to be assessed. This risk is not limited to vaccines against BVD, but applies to any vaccine produced using ruminant pestivirus-contaminated FBS.
  • Transmission parameters poorly understood with regards to interspecies transmission and transmission by vehicles, equipment and people (influence of contact rates, infectious dose etc.) as described in Section “Species Involved”.
  • How quickly virus spreads within individual herds and role of level of herd immunity in promoting self-clearance of BVDV.

• Pathogenic life cycle stages

  Not relevant.

• Signs/Morbidity

  BVD manifests itself as different clinical presentations depending on among other things virus strain, age and immunophysiological status of the animal when first infected:

  • Naïve calves – from subclinical to severe clinical signs (haemorrhagic syndrome, including fatalities). Acutely infected calves are prone to secondary infections due to immunosuppression.
  • Naïve adult cows – from subclinical to severe clinical signs (haemorrhagic syndrome, including fatalities).
  • Foetal infection – -Early gestation – foetal loss (embryonic death or abortion), congenital defects in calf, birth of PI calf (if infected before day 125 in gestation) -Late gestation– congenital infection with or without clinical consequences.
  • PI animals – from no clinical signs to fatal mucosal disease. Predisposed to secondary infections due to immunosuppression.

  GAPS :

  • The role of chronic or prolonged infections (associated with stress or presence of secondary pathogens) not well understood.
  • Impact and mechanism of synergy between BVDV and other pathogens due to immunosuppression, that results in reduced production (milk, growth) and/or clinical disease is not fully understood.
  • Host factors determining course of disease in transiently infected animals.
  • The effect of congenital infections, that do not result in persistent infection, on calf development (especially subsequent immune health) and production has not been well studied and quantified.
  • Longitudinal studies on the effect on production in endemically infected herds needed on population level. Focus not only on reproductive parameters but also on general calf health, including long term impact of transient infections in neonates on endocrine and immune tissues (particularly thymus tissues).
  • Role of BVD in increasing susceptibility to other pathogens and quantification of veterinary treatments, particularly antimicrobials, and costs to manage secondary infections.

• Incubation period

  Generally 6 to 12 days post infection although this period may be shorter following infection with high virulence strains.

• Mortality

  Mortality due to acute uncomplicated BVD is generally considered low, however this is strain dependent and for strains inducing haemorrhagic syndrome, mortality can exceed 50%. During outbreaks with bovine respiratory disease complex (BRDC), in which BVDV interacts with other pathogens, and/or at various stress conditions, mortality may also be significant, and a certain post-natal mortality in calves infected in late gestation (non-PI), can be expected. In addition, infection can result in abortion.In PI animals the mortality is significantly higher than in acutely infected animals, and reaches 100% in those that develop mucosal disease.

  GAPS :

  • The direct and indirect contribution of BVD to mortality (through immunosuppression/co-infections) needs further investigation.
  • The contribution and quantification of the role of BVD to bovine abortions needs further investigation.

• Shedding kinetic patterns

  Persistent infection: Every excretion with high titers of up to 10⁷ TCID50 per ml (exception: during colostral immunity).Acute infection: typically low to medium titers (10² to 10⁴ TCID50 per ml). However infection with high virulence strains associated with hemorrhagic syndrome can result in higher titers.

  GAPS :

  • The extent of shedding in PI animals under the influence of maternal antibodies and its influence on the within-herd transmission is poorly understood.
  • The importance of shed hair from PI animals as a source of infection unknown.
  • The survival of these viruses on equipment and in the environment is largely unknown. The risk of sharing grazing lands is largely unknown.
  • Risk quantification needed.
  • The role of shedding of virus from acutely infected animals in maintaining infection within a population (herd) in the absence of PI animals needs further investigation. Transient shedding can also occur when an acutely infected pregnant animal loses a foetus (the foetus represents the transient occurrence of a PI animal).

• Mechanism of pathogenicity

  Ruminant pestiviruses can cross the placenta and infect the fetus resulting in congenital defects (including persistent infections).Mucosal disease (MD) occurs when a PI animal, persistently infected with a noncytopathic strain, is superinfected with a cytopathic strain. The immunosuppression accompanying acute infections can foster secondary infections.Ruminant pestiviruses can interact directly with secondary pathogens to increase severity of disease.Some viral strains cause hemorrhagic syndrome in acute, uncomplicated infections.

  GAPS :

  • The role of immunopathogenicity/immunoreactivity has to be investigated. PI-animals are often healthy, even if the strain induces severe clinical signs during acute infection.
  • Mechanism(s) of immune suppression and mechanism(s) associated with pathogen synergy that results in increased virulence of other pathogens in the presence of BVDV not fully understood.
  • Role of host cell factors during infection, tissue specific host cell factors, in vivo immunopathogenesis (sequence of events in different tissues) role of innate immune response, role of different virus receptors.
  • Delayed immune response in newborn calves in the presence and absence of maternal antibodies not sufficiently understood.
  • The significance of low levels of RNA detection for prolonged periods following acute infection, particularly infection of reproductive tissues, is not known.
  • The ability of these viruses to cross the placenta and cause reproductive disorders is a major mechanism of pathogenicity – and the role of humoral vs cellular immunity in preventing this is not well understood.
  • The host contribution to susceptibility (heritability of susceptibility/production of PI calves) needs further investigation.

• Zoonotic potential

• Reported incidence in humans

  None (one old report without convincing or reproduced data).

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

  Unknown, likely none.

• Symptoms described in humans

  None.

• Likelihood of spread in humans

  Low, although contamination of human vaccines with bovine pestiviruses is a potential route by which humans could be exposed to BVDV where normal immune defence mechanisms are circumvented.

  GAPS :

  Risk of spread to human population through contaminated vaccines unknown. Impact and consequence of potential spread unknown.

• Impact on animal welfare and biodiversity

• Both disease and prevention/control measures related

  1) Impact due to disease:

  The animal welfare impact of BVD is hard to estimate. However, given the worldwide spread of the disease and its immunosuppressive effects, resulting in general impaired health in affected herds, the global impact is huge.

  2) Impact due to control:

  The impact on animal welfare associated with the implementation of effective control measures is low. Control measures do not require any pre-emptive culling. Only PI animals need to be removed from the herd.

  GAPS :

  • Calf health is often severely impaired in infected herds but the impact of this for farm economy, animal welfare etc is poorly quantified. To date, much focus has been on reproductive disorders instead of overall productive and reproductive efficiency (also including young stock survival and replacement). The impact of the disease in different production settings is poorly understood. The impact of respiratory and gastrointestinal signs, often observed in production settings, on productive efficiency (e.g. delayed weight gain, reduced milk production etc) is unknown and most probably underestimated.
  • The impact of immunosuppression on herd health leading to increased use of antibiotics is largely unexplored.

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

  BVD infection could have an impact on biodiversity if it is present in herds with endangered cattle breeds (including the preservation of semen from these breeds), zoos, game parks, and free ranging ruminant populations due to the disease itself or indirectly due to control efforts.

  GAPS :

  Extent of problem in captive (zoos, parks and preserves) and free ranging wildlife (e.g. chamois, mountain goats) needs further investigations.

• Slaughter necessity according to EU rules or other regions

  PI animals should be slaughtered to reduce transmission.

• Geographical distribution and spread

• Current occurence/distribution

  BVDV1 strains are found in all continents that support domestic or wild ruminant herds. BVDV2 strains have a similar distribution with the exception of its apparent absence in Australia and perhaps New Zealand. Hobi-like viruses have thus far been only reported in South America, Asia and Europe.

  GAPS :

  • Systematic screening and characterisation of pestiviruses globally should be carried out, with particular focus on areas that have been poorly investigated and that may have a major influence on other parts of the world, e.g. due to export of FBS or semen.
  • Less advanced countries rate BVD very low on priority list compared to the control of other diseases such as FMD, mostly due to unperceived economic impact and less focus on animal welfare.

• Epizootic/endemic- if epidemic frequency of outbreaks

  Introduction or reintroduction of ruminant pestiviral species into naïve population can have epidemic characteristics.

  GAPS :

  Vaccination. The role of vaccines of less than 100% efficacy in disease outbreaks in a BVD-free country is unknown (e.g. can disease-free state be maintained with the aid of currently available vaccines?).

• Speed of spatial spread during an outbreak

  Virus may be shed, based on virus isolation, in body secretions and excretions from days 4 to 15 post-transient (acute) infection. Bulls with persistent testicular infections can shed virus in semen for many months. Horizontal transmission to seronegative cattle has been shown to occur after only one hour of direct contact with a PI animal.

  GAPS :

  • Rate of between-herd transmission through movements/contacts with different types of infectious animals/materials poorly understood.
  • The importance of virus shedding after resolution of acute infection, e.g. recrudescence of disease after steroid treatment in seropositive animals with prolonged viral survival in ovaries, need further investigation.
  • The importance of shedding of infectious virus in young animals (<6 months) in the presence and absence of maternal antibodies after acute infection, which might remain positive by RT-PCR for weeks to months, is unclear.

• Transboundary potential of the disease

  High via global trade with potentially infected semen, and embryos, or the trade of PI animals or dams carrying PI foetuses (so called PI-carriers).

  The global trade with potentially infected FBS, or biological products based on FBS (incl. cell cultures and live-attenuated vaccines) has further implications on the potential for transboundary spread.

  GAPS :

  • The global distribution pattern of potentially infected FBS needs further investigations. Many labs worldwide work with pestivirus-contaminated cells without knowing it.
  • The movement of untested livestock needs to be controlled.
  • Import protocols are not always sufficient to prevent movement of PI animals due to a poor understanding of selection and use of appropriate diagnostic tests. Deliberate falsification of certificates is difficult to detect and track.

• Route of Transmission

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

  Horizontally via contact with excretions or secretions of PI animals and vertically by foetal infection during early pregnancy – generally thought to be before 125 days of pregnancy. Common modes of between-herd transmission, apart from over-the-fence contacts and contacts during co-pasturing etc is through trade with PI animals or dams pregnant with PI foetuses. Indirect contacts through animals, feed, people, carriers, etc.

  GAPS :

  • Quantification of the importance of different transmission routes to individual farms and in various herd management systems to make more specific biosecurity recommendations.
  • There are knowledge gaps in terms of survival in environment and the role of TIs in transmitting infection.

• Occasional mode of transmission

  Contaminated embryos, semen and biological products based on FBS such as vaccines.Iatrogenic, ET, other indirect means such as fomites, bedding, slurry, lochia, afterbirth, flies, contamination of equipment used to handle, process and transport animals.

  GAPS :

  • Quantification of the role/impact of different means of indirect transmission in a large scale control context is lacking. The risk of transmission by contaminated vehicles, equipment and people is largely unknown.
  • Impact / extent of transmission of BVDV and related ruminant pestiviruses from small ruminants is largely unknown.

• Conditions that favour spread

  Conditions that FAVOUR spread include animal trade (purchase of PIs or pregnant animals, potentially carrying PI foetuses), common pasturing (including cattle and domestic small ruminants), grouping of animals from different sources (such as in sale barns and feedlots), contact between domestic and wild species, and other cattle management strategies that increases the likelihood of between-herd contacts.Inadequate attention to bioexclusion to address indirect transmission pathways between herds. Survival of the virus in biologicals favours spread through indirect means.

  Generally, inapparent clinical signs of the disease make early detection difficult.

  GAPS :

  • Relative effects of different intervention strategies at the population level needs further investigation.
  • The type, frequency and quality of surveillance required to detect PI animals, in a timely manner, in various control schemes and diverse herd management practices is largely unknown. The speed of detection and removal of a PI animal are the crucial factors for successful control/eradication, especially in the absence of vaccination.

• Detection and Immune response to infection

• Mechanism of host response

  In non-PI animals infection elicits a serological antibody response and a T cell response; in PI animals, a humoral (serological) and cellular immune response is not seen unless the infecting virus is sufficiently heterologous.A reduction in circulating WBC is observed following acute infection and is probably associated with immune suppression.

  GAPS :

  • Role of innate and cellular immunity, in vivo suppression of immune response is not fully understood.
  • The role of neutralising antibodies vs cell-mediated immunity in fetal protection is not fully understood.
  • The impact of acute infection on immune development and endocrine function, particularly in neonates, is not fully understood.

• Immunological basis of diagnosis

  To date, immunological based tests cannot differentiate between exposed and vaccinated animals. In the absence of vaccination, antibodies may be detected via ELISA or serum neutralisation test (SNT) using paired serum samples taken 21 days apart (but this is rarely done). At the herd level, more commonly used, antibody detection in bulk milk or spot samples may be used as the basis for diagnosis regarding the likely presence or absence of the infection.

  GAPS :

  • Availability of vaccines and companion diagnostic kits capable of differentiating infected and vaccinated animals.
  • Diagnostic methods able to reliably identify seropositive dams carrying PI foetuses.
  • Impact/importance of interference of maternal antibodies with antigen testing in the serum of calves.
  • ELISA tests able to differentiate antibodies to different ruminant pestiviruses.

• Main means of prevention, detection and control

• Sanitary measures

  Identification and removal of PI animals is a prerequisite for further sanitary measures aimed at removing the infection. The use of a closed herd policy with strict control of semen (and embryos in herds where embryo transfer is used) should be implemented. The effectiveness of a closed herd policy will be a function of prevalence in the neighbourhood and in the market, and the compliance with biosecurity measures such as pre-introduction testing or sourcing animals from herds confirmed to be free from BVDV. In non-closed herds, adequate biosecurity measures to avoid introduction via added PI animals, dams carrying PI foetuses or transiently infected animals are required. In both circumstances, additional bioexclusion measures to prevent introduction by other direct or indirect transmission pathways (e.g. boundary contacts, personnel) are required. Serological testing will not identify PI animals so virus testing would be required to eliminate these animals. Pre-introduction testing is less efficient in identifying dams carrying PI foetuses (although quarantine and testing with negative serological results can help exclude the possibility of such animals being introduced) and introduction of these are best prevented by control at the herd of origin.

  GAPS :

  • Effectiveness of standard procedures for cleaning in-vitro produced embryos not fully established. There seems to be virus strain differences in the adherence to zona pellucida.
  • Good and cheap substitutes for FBS lacking.
  • Best practices guidelines for serological testing/screening. For example, seronegative results in a pregnant animal at a single time point is not sufficient to exclude a "Trojan dam".

• Mechanical and biological control

  So far only strategies using improved biosecurity and elimination of PI animals have been shown to be successful.Non-systematic vaccination strategies have been widely used in many settings, so far with no proof of sustainable decrease in disease prevalence or impact.Various BVD control programmes based on improved biosecurity and elimination of PI animal, and either with or without permitted use of vaccines, are underway in a number of countries and regions.

• Diagnostic tools

  Virus isolation (gold standard) using multiple sample types, most commonly whole blood, serum, buffy coat and spleen. In routine practice methods more commonly used include antigen capture ELISAs (ACE) (in blood, milk, semen and ear notches), RT-PCR (in blood, milk, semen and ear notches) and immunohistochemistry (fixed tissue samples, particularly ear notches).Serological based tests are useful in determining exposure but only in the absence of vaccination.

  GAPS :

  • Need tests that simultaneously detect and differentiate between all three viral species and other ruminant pestiviruses. Current tests for the presence of virus may not be equally efficacious in detecting all three ruminant pestiviral species and do not differentiate between the viral species. Similarly, current ELISAs cannot differentiate between exposure to different viral species and thus, tedious cross-SNT needs to be performed. Differentiation is important for control regulations and in tracking and controlling the introduction of pestivirus species into new geographic regions.
  • Marker (DIVA) tests in conjunction with marker vaccines to protect animals in BVDV free areas and run surveillance programmes.
  • Diagnostic tools for detection of PI fetuses carried by non-PI dams.
  • Systematic monitoring and characterisation of existing viruses in geographic regions to assess appropriateness of diagnostics/vaccines used needs to be carried out regularly.
  • Sensitivity of herd-level tests where the within-herd prevalence of the target is expected to be low, or where there is a low level of the analyte in the specimen, e.g. RT-PCR on bulk tank milk, needs further assessment.
  • Interference of maternal antibodies with calf antigen testing in serum to determine PI status.
  • The common practice of pooling samples has not been appropriately vetted in many of the laboratories that offer testing of pooled samples. Proper vetting would include use of multiple strains of viral species and subspecies for sensitivity testing and the use of large sample of negative tissues to determine the presence of inhibition.

• Vaccines

  Conventional MLVs, double deleted live vaccine and inactivated vaccines are available.Efficacy, safety and duration remain issues.Non-systematic vaccination strategies have been widely used in many settings, so far with no proof of sustainable decrease in disease prevalence or impact.Various BVDV control programmes based on improved biosecurity and elimination of PI animal, and either with or without permitted use of vaccines, are successfully underway in a number of countries and regions.

  GAPS :

  • Evaluation of the efficacy/cost-efficiency of different vaccines/vaccination strategies under field conditions is missing, in particular one that also incorporates compliance.
  • Understanding compliance: Behavioural changes (e.g. attitudes to risk taking) as a result of the implementation of different control strategies has not been investigated.
  • DIVA vaccines and accompanying assays missing.

• Therapeutics

  There are no therapeutic treatments available. Prophylactic treatments may be used and antibiotics may be used to treat secondary infections, but their overuse should be avoided.Prototypes (NS5b polymerase blocking pharmaceuticals) have been tested in vitro (from HCV research).

  GAPS :

  Impact of overuse of antimicrobials in PI animals and cohorts of PI animals has been largely unaddressed.

• Biosecurity measures effective as a preventive measure

  See Section “Sanitary measures”. Most important biosecurity measure for herd prevention is to prevent contact with/introduction of PI animals/PI carriers. Most important biosecurity measure to control the infection at the herd level is to identify and remove PI animals, and using quarantine measures for new animals to avoid introduction of the virus via transiently infected animals.Several studies have shown that herd biosecurity measures alone can lead to free herds in many cases through self-clearance. This is probably particularly true in small-size herds, but is also commonly seen in larger herds.

  GAPS :

  Impact of timing/frequency of PI screening and removal on effectiveness of within-herd control measures. Recognition of common production practices that decrease effectiveness of testing and control strategies.

• Border/trade/movement control sufficient for control

  BVDV1 (Pestivirus A) and BVDV2 (Pestivirus B) are not currently a significant barrier to international trade. Countries with national or regional control programmes may have certain regulations for affiliated farmers that effectively restrict trade with animals of unknown BVDV status. AI stations are under regulatory control and there are requirements for the testing of both bulls and semen.Within the European Union, under the new Animal Health Law (REGULATION (EU) 2016/429 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 9 March 2016 on transmissible animal diseases and amending and repealing certain acts in the area of animal health (‘Animal Health Law’)), countries or regions may apply for either approval of eradication programmes or recognition of freedom, according to the requirements of COMMISSION DELEGATED REGULATION (EU) 2020/689. Where such approval or recognition is granted, specific requirements and/or prohibitions are put in place regarding the introduction of animals from other herds and Member Sates (COMMISSION DELEGATED REGULATION (EU) 2020/688).

  GAPS :

  • While no current policies are in place regarding HoBi-like viruses, the more limited geographic distribution of this species may lead to discussion on trade barriers.
  • Current BVD eradication programs focus on detection and removal of animals persistently infected with either BVDV1 or BVDV2 strains. Legal regulations need to be adapted to handle cases of animals persistently infected with other ruminant pestiviruses, especially border diseases virus. Herd with mixed population (ovine-bovine, caprine-bovine) must be particularly monitored because of the circulation of BVDV in the listed species.

• Prevention tools

  The primary target for BVDV prevention is usually the herd. Biosecurity measures and vaccination may be used as strategies for prevention.

• Surveillance

  Wide variation in practices across the globe.May be done by testing for antibodies in bulk milk or on a small sample of individuals (spot tests) and/or by bulk tank milk (BTM) or individual testing for viral RNA or antigen using RT-PCR or antigen capture ELISA, respectively. BTM testing using RT-PCR alone is NOT recommended.

  GAPS :

  • Efficient, sensitive, timely, and at the same time cost-effective methods and strategies for PI surveillance are missing, particularly for RT-PCR realize on bulk tank milk.
  • Effective diagnostic tools for identification of pregnant dams carrying PI foetuses (PI carriers) are missing.
  • Role of molecular epidemiology as a potential contact tracing tool to assist surveillance and control efforts.
  • Surveillance strategies for post-eradication period to rapidly identify re-introductions.

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

  Several European countries have experience with systematic large scale BVD programmes aimed at eradication or control on a regional basis in other countries. Despite different pre-conditions in terms of initial prevalence, herd density, regulatory support etc these have all proven to be successful in eliminating or strongly reducing the prevalence of infection. Strategies aimed at elimination have also proven to be cost-efficient. National/regional systematic strategies that permit vaccination as an additional biosecurity tool are included in some of these European programs, while in others use of vaccine is prohibited in order not to interfere with serological surveillance.Non-systematic vaccination strategies have been widely used in many settings, so far with no proof of sustainable decrease in disease prevalence or impact.

  GAPS :

  • Publication of ex-post cost-benefit assessments in production setting outside the EU.
  • Formal means of review and comparison of success rates for different control/eradication strategies over time would be helpful to design of new BVD control programs.

• Costs of above measures

  Costs will vary by geographic region and type of production. For an overview please see:

  https://www.frontiersin.org/articles/10.3389/fvets.2021.688078/full

  GAPS :

  • Publication of ex-post cost-benefit assessments needed. This needs to be done in more detail within different eradication schemes, as the economic benefit of BVDV eradication is there but is not as obvious as initially expected.
  • Publications relating to efficiency calculations, in particular at national and regional level, are rare.Publications of the benefits of such measures on the market are missing.
  • Separating costs of BVDV for herds from other concurrent animal health problems (i.e. there could be many reasons why a herd has poor reproductive performance besides BVDV so may underestimate how much effect controlling for BVDV will have on improving herd performance).

• Disease information from the WOAH

• Disease notifiable to the WOAH

  Yes.

• WOAH disease card available

  Yes. Direct link.

• WOAH Terrestrial Animal Health Code

  Terrestrial Animal Health Code - 28/06/2019.

  Collection and processing of bovine, small ruminant and porcine semen.

  Collection and processing of oocytes and in vitro produced embryos from livestock and horses.

• WOAH Terrestrial Manual

  Chapter 3.4.7 Bovine Viral Diarrhoea

• Socio-economic impact

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

  Minimal except in the case of increased resistance.

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

  Not applicable.

• Direct impact (a) on production

  Direct losses between and within countries were largely heterogeneous with respect to the monetary level.For an overview of the worldwide production losses please see Richter et al., 2017. The Veterinary Journal.https://www.sciencedirect.com/science/article/pii/S1090023317300102?via%3Dihub

  GAPS :

  • Good estimates of the impact in endemically infected populations lacking.
  • A better understanding of the economic impact under different farming conditions is needed.
  • More studies are needed, which analyse the impact of BVDV such as between case and control herds or within herds before and after the eradication.
  • The relative importance of different motivators in making farmers engage in BVDV control – economic aspects are not the only ones not well understood.
  • The benefits of eradication in terms of e.g. reduced calf mortality, morbidity, antimicrobial usage, contribution to reduced emissions of greenhouse gases per unit of production, and increase in animal welfare need further investigation. How to incorporate variability in farm level impacts into design of national control programmes (i.e. is it more cost effective to develop individual farm-based recommendations rather than one-size-fits-all national control policies).

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

  See Section “Main means of prevention, detection and control – costs of above measures” and “Direct impact on production.

  GAPS :

  • Good estimates of impact lacking.
  • A better understanding of the economic impact under different farming conditions is needed.
  • The relative importance of different motivators in making farmers engage in BVDV control – economic aspects are only one not well understood.

• Indirect impact

  Difficult to calculate (country, control programs, number of PI animals, vaccination etc.).

  GAPS :

  • A better understanding of the economic impact under different farming conditions.
  • Better economic methods and data are needed to analyse the indirect impacts such as trade effects on the cattle market.

• Trade implications

• Impact on international trade/exports from the EU

  Currently no or very low impact on trade from EU. Many external trading partners have specific health requirements relating to vaccination or testing for BVD in relation to live exports.

• Impact on EU intra-community trade

  Within the European Union, under the new Animal Health Law (REGULATION (EU) 2016/429 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 9 March 2016 on transmissible animal diseases and amending and repealing certain acts in the area of animal health (‘Animal Health Law’)), countries or regions may apply for either approval of eradication programmes or recognition of freedom, according to the requirements of COMMISSION DELEGATED REGULATION (EU) 2020/689. Where such approval or recognition is granted, specific requirements and/or prohibitions are put in place regarding the introduction of animals from other herds and Member Sates (COMMISSION DELEGATED REGULATION (EU) 2020/688).On the other hand, countries with national control programmes may have regulations regarding importation of animals equal to those regarding purchase of animals of unknown BVDV status. Such measures do not require national legislation but have the same potential function with regards to international trade.

  GAPS :

  Good studies on impact on trade, involving economists and political scientist needed.

• Impact on national trade

  Initially high in countries with control programs, when there is a need for a market that can handle animals from herds with different statuses, and when there is still an additional market value for BVDV free animals. Both these impacts decrease as the majority of herds become free.No impact in other countries.

  GAPS :

  The relationship between national animal policies (e.g. declaring herd status and/or requiring pre-movement testing) to mitigate BVD risk and the impact on national trade is largely unexplored. Assessment required to calculate the costs and impact of trade restrictions on the one hand, and the costs for surveillance and risk for re-introduction of BVD on the other hand have not been completed for most control programs. There is a trade-off between reducing trade restrictions for farmers to avoid unnecessary losses, and the risk detecting a PI animal too late for efficient control and finally eradication.

• Links to climate

• Seasonal cycle linked to climate

  No.

• Distribution of disease or vector linked to climate

  No.

• Outbreaks linked to extreme weather

  Has been described as a consequence of flooding, leading to emergency movement of cattle (crowding and exposure to multiple herds).Climate flux can lead to changes in migratory routes or grazing ranges of free ranging wildlife populations that result in greater contact between domestic and free ranging species.

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

  None recognised.

• Main perceived obstacles for effective prevention and control

  Obstacles are not on the tool side. Rather, the main obstacles can be found in the attitudes and priorities of influential individuals/groups within the industry, academia and authorities.There is often lack of awareness among farmers and veterinarians, and because in many countries the producers will bear the cost of BVD control, the producer “buy-in” is critical.A trustful relationship between farmers, practitioners and governmental authorities is a prerequisite, and commitment of all involved parties is necessary.

  GAPS :

  • Poor understanding of drivers and constraints for implementing BVD control (in whatever format) under different settings – will be different between countries, and different among stakeholders. Poor understanding of how to use the drivers to create change. Well-designed socio-economic studies needed.
  • Reliable cost benefit studies and risk analysis for re-infection needed.
  • Reassessment should be performed several years after the start of an eradication program accounting for waning enthusiasm of producers and increased impact of infection as control programs result in naïve herds that are fully susceptible.
  • Establishing consistent national protocols strictly avoiding regional fragmentation for the different testing and vaccination procedures. Individual farmers and veterinarians often have their own different protocols, which can be confusing.

• Main perceived facilitators for effective prevention and control

  A cooperative and nation-wide farming industry, efficient interface between industry and academia, good and trustful collaboration between authorities and industry, a well-founded communication strategy. An integrated national database to facilitate co-ordination at national level, processing large volumes of data and used to control movements and assign statuses in more or less real-time at animal- and herd-levels.

  GAPS :

  • Poor understanding of drivers and constraints for implementing BVDV control (in whatever format) under different settings – will be different between countries, and different among different important stakeholders! Poor understanding of how to use the drivers to create change. Well-designed socio-economic studies needed.
  • Good animal movement database/control appears is required for an efficient control program. Without this, the speed of detection of PI animals and tracing back chains of infection will not be successful. In addition, access rights and severe consequences for deliberate false entries into the databases need to be defined in advance.

Global challenges

• Antimicrobial resistance (AMR)

• Mechanism of action

  Control or eradication of BVD is recognised to confer advantages in wider animal health, particularly in calves and therefore to reduce antimicrobial usage, which in turn contributes to reducing the development of AMR.

  GAPS :

  Specific studies quantifying impact of BVD control and eradication on AMU and ultimately on development of AMR.

• Conditions that reduce need for antimicrobials

  NA.

• Alternatives to antimicrobials

  NA.

• Impact of AMR on disease control

  NA.

• Established links with AMR in humans

  NA.

• Digital health

• Precision technologies available/needed

  NA.

• Data requirements

  NA.

• Data availability

  NA.

• Data standardisation

  NA.

• Climate change

• Role of disease control for climate adaptation

  NA.

• Effect of disease (control) on resource use

  NA.

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

  BVD is recognised to reduce the efficiency of dairy and beef production. Control and eradication will therefore reduce the emissions per unit of output (kg of beef or litre of milk). If accompanied by a reduction in animal numbers while maintaining the same level of output, this will also deliver absolute reductions in emissions.

  GAPS :

  • Specific studies to quantify the levels of efficiencies and mitigations that can be achieved in different production systems.
  • Valid measures/estimates of impact of pestivirus infection on the parameters to include in such studies.

• Preparedness

• Syndromic surveillance

  NA.

• Diagnostic platforms

  NA.

• Mathematical modelling

  Mathematical models have been developed to inform decision making in several European countries, including Ireland, France and Germany.

• Intervention platforms

  NA.

• Communication strategies

  NA.

Main critical gaps

• • Poor understanding of drivers and constraints for implementing BVD control (in whatever format) under different settings – will be different between countries, and different among stakeholders. Poor understanding of how to use the drivers to create change. Well-designed socio-economic studies needed.
  • Reliable cost benefit studies and risk analysis for re-infection needed.
  • Reassessment should be performed several years after the start of an eradication program accounting for waning enthusiasm of producers and increased impact of infection as control programs result in naïve herds that are fully susceptible.
  • Establishing consistent national protocols strictly avoiding regional fragmentation for the different testing and vaccination procedures. Individual farmers and veterinarians often have their own different protocols, which can be confusing.

Conclusion

• Cattle of all ages are susceptible to BVD and the viruses which cause BVD are endemic worldwide. Clinical signs range from sub-clinical to fatal (mucosal disease and haemorrhagic syndrome). Acute infections may result in transient clinical disease with non-specific signs (respiratory tract, intestinal tract, fever, leukopenia). The virus spreads mainly by contact between cattle or via indirect contact, but vertical transmission plays the major role in its epidemiology and pathogenesis. Infections of the bovine foetus may result in abortions, stillbirths, teratogenic effects or persistent infection of the neonatal calf. Persistently infected (viraemic) animals (PI) may be born as weak, unthrifty calves or very often appear as normal healthy calves and be unrecognised clinically. Antibody positive pregnant cattle carrying persistently infected calves are important transmitters of the disease. There is some degree of cross protection seen. Currently the only restriction placed on the market is in the sale of semen from infected bulls.

Sources of information

• Expert group composition

  Julia Ridpath, Ridpath consulting LLC, USA – [Leader].

  Matheus Nunes Weber, Universidade Feevale, Porto Alegre, Brazil.

  David Graham, Animal Health Ireland, Ireland.

  Maria Guelbenzu, Animal Health Ireland, Ireland.

  Matthias Schweizer, Vetsuisse Faculty, University of Bern, Switzerland.

  Beate Conrady, University of Copenhagen, Denmark.

  Matt Yarnall, Boehringer Ingelheim Vetmedica.

  Peter Kirkland, Elizabeth Macarthur Agriculture Institute, Australia.

  Nicola Decaro, University of Bari, Italy.

  Carolyn Gates, Maasey University, New Zealand.

• Date of submission by expert group

  15/05/2023

• References

  https://www.woah.org/fileadmin/Home/fr/Health_standards/tahm/3.04.07_BVD.pdf.Regulation (EU) 2016/429 on transmissible animal diseases.

  Overview of Cattle Diseases Listed Under Category C, D or E in the Animal Health Law for Which Control Programmes Are in Place Within Europe.

  Jaka Jakob Hodnik, Žaklin Acinger-Rogić, Mentor Alishani, Tiina Autio, Ana Balseiro, John Berezowski, Luís Pedro Carmo, Ilias Chaligiannis, Beate Conrady, Lina Costa, Iskra Cvetkovikj, Ivana Davidov, Marc Dispas, Igor Djadjovski, Elsa Leclerc Duarte, Céline Faverjon, Christine Fourichon, Jenny Frössling, Anton Gerilovych, Jörn Gethmann, Jacinto Gomes, David Graham, Maria Guelbenzu, George J. Gunn, Madeleine K. Henry, Petter Hopp, Hans Houe, Elena Irimia, Jožica Ježek, Ramon A. Juste, Emmanouil Kalaitzakis, Jasmeet Kaler, Selcuk Kaplan, Polychronis Kostoulas, Kaspars Kovalenko, Nada Kneževič, Tanja Knific, Xhelil Koleci, Aurélien Madouasse, Alvydas Malakauskas, Rene Mandelik, Eleftherios Meletis, Madalina Mincu, Kerli Mõtus, Violeta Muñoz-Gómez, Mihaela Niculae, Jelena Nikitović, Matjaž Ocepek, Marie Tangen-Opsal, László Ózsvári, Dimitrios Papadopoulos, Theofilos Papadopoulos, Sinikka Pelkonen, Miroslaw Pawel Polak, Nicola Pozzato, Eglé Rapaliuté, Stefaan Ribbens, João Niza-Ribeiro, Franz-Ferdinand Roch, Liza Rosenbaum Nielsen, Jose Luis Saez, Søren Saxmose Nielsen, Gerdien van Schaik, Ebba Schwan, Blagica Sekovska, Jože Starič, Sam Strain, Petr Šatran, Sabina Šerić-Haračić, Lena-Mari Tamminen, Hans-Hermann Thulke, Ivan Toplak, Erja Tuunainen, Sharon Verner, Štefan Vilček, Ramazan Yildiz, Inge M. G. A. Santman-Berends. Front Vet Sci. 2021; 8: 688078. Published online 2021 Jul 30. doi: 10.3389/fvets.2021.688078

  Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): bovine viral diarrhoea (BVD). EFSA Panel on Animal Health and Welfare (AHAW); More S, Bøtner A, Butterworth A, Calistri P, Depner K, Edwards S, Garin-Bastuji B, Good M, Gortázar Schmidt C, Michel V, Miranda MA, Nielsen SS, Raj M, Sihvonen L, Spoolder H, Stegeman JA, Thulke HH, Velarde A, Willeberg P, Winckler C, Baldinelli F, Broglia A, Dhollander S, Beltrán-Beck B, Kohnle L, Bicout D. EFSA J. 2017 Aug 4;15(8):e04952. doi: 10.2903/j.efsa.2017.4952. PMID: 32625618; PMCID: PMC7009957.

  Moennig V, Yarnall MJ. The Long Journey to BVD Eradication. Pathogens. 2021 Oct 7;10(10):1292.. doi: 10.3390/pathogens10101292. PMID: 34684241; PMCID: PMC8539298.