BVDV - available
Control ToolsDiagnostics availabilitySNT is gold standard for diagnostics, however, routinely blocking ELISAs (NS3, ERNS) or indirect ELISAs are used for serum, plasma and milk. All ELISAs are commercially available. For virus detection, isolation is the gold standard. However, routinely antigen capture ELISA (NS3, ERNS) and real-time RT-PCR are used. Both are used for blood and ear notch samples. Many real-time PCR kits are commercially available (Blood and ear notch samples or bulk milk). SNT is gold standard for diagnostics, however, routinely blocking ELISAs (NS3, ERNS) or indirect ELISAs are used for serum, plasma and milk. All ELISAs are commercially available. For virus detection, isolation is the gold standard. However, routinely antigen capture ELISA (NS3, ERNS) and real-time RT-PCR are used. Both are used for blood and ear notch samples. Many real-time PCR kits are commercially available (Blood and ear notch samples or bulk milk). Kit release testing according to national regulations in some European countries (eg Germany). No international standards available. Yes, chapter available on BVD in the terrestrial manual from OIE (chapter 2.4.8). Ongoing and newly started national control programmes means there is a huge market for commercial diagnostic kits. – however the market for NEW kits with similar performance may be limited. Currently no. GAP: A DIVA strategy lacking. Could be helpful to combine eradication and surveillance with vaccination (protection of a naïve population), although eradication can be acquired also without vaccination. Opportunities for future test developments are linked to the different eradication/control programmes applied. Ban of vaccination after BVDV eradication may lead to development of antibody detection tests with higher sensitivity (bulk milk testing). Protection of BVDV free herds by vaccination may trigger development of DIVA systems (marker vaccine plus corresponding antibody detection test). On-site tests might be helpful to create awareness for BVDV and support activities leading to eradication/control programmes. Highly sensitive but robust pathogen detection systems are needed for different diagnostic specimen (ear notch, blood, semen, milk etc.), which are suitable for sample pooling. Test systems which allow multiplexing of samples in one test run may facilitate running different progammes at the same time (cost savings). Vaccines availabilityMLV and inactivated vaccines are available globally. Efficacy and safety still an issue. GAPS:
MLV and inactivated vaccines are available globally. Efficacy and safety still an issue. GAPS:
Currently no marker vaccines available. Currently no marker vaccines available. MLV and inactivated vaccines are available globally. Efficacy and safety still an issue. The prevention of PI animals by protecting the foetus is the major goal with vaccination, and close to 100% efficacy would be required for efficient BVD control. Today this cannot be achieved.
GAPS:
Very high in the short term until control programmes either outlaw their use unless marked. Only vaccines with proven 100% foetal protection should be used. 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. Currently none. All current vaccines grown to high titre on conventional bovine kidney cell lines. GAP: Alternative production cell lines. Currently none. High quality combination vaccines with 100% foetal protection. Negatively-marked vaccines with 100% foetal protection. Pharmaceutical availabilityNo pharmaceutical therapy available commercially. Prototypes are available (tested for related human viruses as well as for CSFV). Unlikely. No. No. Not considered applicable. siRNA; new antivirals; resistant animals? New developments for diagnostic testsDefinition of design requirements for test development should be based on customer’s requirements and needs continuous adjustment. Test validation has to be standardized according to the “fitness for purpose” approach. The broad genetic variability of pestiviruses has to be addressed during test development. International standards for test validation, test registration and batch release testing might be helpful to increase quality of diagnostic testing. Development and registration of diagnostic tests needs 1 – 3 years in general, if the commercial potential is evident. The veterinary diagnostics market errs on the side of conservatism and new concepts/technologies may need longer time for market penetration. Close collaboration between industry and research institutes as well as regulatory bodies facilitate test development and reduce time and costs needed to bring new tests to the market.
PCR is recognized as the most sensitive method for virus detection. Repeated testing by 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. New developments for vaccinesAgreement on negative marker to use. Prototypes are existing (all are Npro-deletion mutants). Estimation of a time frame: 5 years. Could be considerable. Better understanding of transplacental transmission on ncp BVDV. New developments for pharmaceuticalsUnlikely to be any means of pharmaceutical treatment. N/A N/A Comments NA Disease detailsDescription and characteristics.Bovine Viral Diarrhoea Viruses (BVDV) are classified in the genus Pestivirus in the family Flaviviridae. They are single stranded, enveloped RNA viruses similar to classical swine fever virus (Hog Cholera virus) and Border Disease Virus of sheep. BVDV has been grouped into 2 species, Type 1 and Type 2 (BVDV-1 and -2). These species can be sub-divided into subtypes (subgenotypes) and thus far, 12 BVDV-1 subgenotypes (a-l) and 2 BVDV-2 subgenotypes (a and b) have been identified. Viruses in each of the two species may exist as one of two biotypes, cytopathic and noncytopathic, based on their activity in cell cultures. Recently atypical BVDV-like pestiviruses have been described, detected in fetal calf sera (FCS) as well as in sera from live cattle and buffaloes. These so called “HoBi-like” viruses have been suggested to belong to a new third species of BVDV, BVDV type 3 (BVDV-3). In addition several other emerging pestivirus viruses originating form non-bovine species have been described during recent years (e.g. “Bungowanah” and “Antilope”). GAPS: There is a need of further investigations of the host range, geographical distribution and clinical importance of BVDV-3 (as well as other emerging pestivirus 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. Virus isolates from the main species exhibit considerable antigenic and biological diversity. The two species may be differentiated from each other and from other pestiviruses by monoclonal antibodies directed against the E2 and Erns major glycoproteins or by genetic analysis. Multiplex PCR enables virus typing direct from blood samples. BVDV-1 viruses are generally more common and it is usually the non-cytopathogenic biotype that circulates in cattle populations. BVDV-2 viruses are normally non-cytopathogenic and have been associated with outbreaks of severe acute infection and a haemorrhagic syndrome. The genomes of BVDV consist of 1 long open reading frame (ORF) flanked by two untranslated regions. The ORF is translated into one long polypeptide, which is subsequently cleaved into the individual viral proteins by viral and cellular proteases. Pestiviral recombination events have been well characterised in BVDV. GAPS:
BVDV does normally not stay in the environment past 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 survive and remain infective for longer periods in hair samples, dessicated tissues, fomites and beddings. BVDV is susceptible to common disinfectants. GAPS:
Species involvedPersistently infected (PI) cattle are the main carriers. Their role in the epidemiology of the disease cannot be overestimated. Acutely infected cattle are transient carriers. Small ruminants and other domestic and wild even toed ungulates are potential carriers. GAPS:
No. Insects may carry the virus passively. GAP: The importance of vectors (flies) for passive transmission of BVDV not well understood. Risk estimates needed. Persistently Infected (PI) cattle, and semen of infected cattle. Frozen colostrum, embryos, FCS, contaminated live vaccines and cell lines and other biologicals based on FCS. Description of infection & disease in natural hostsBVDV spreads mainly by direct contact between cattle, in particular by contact with PI cattle. Vertical transmission plays an important role in its epidemiology and pathogenesis. Semen from persistently and acutely infected animals and, rarely, recovered animals may be suspect. The general use of FCS in embryo transfer and in vaccine production is a risk factor for long distance/high impact transmission. GAPS:
Not relevant.
-Early gestation – fetal 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 clincal consequences
GAPS:
Generally 6 to 12 days post infection. Mortality due to acute uncomplicated BVDV infection generally considered low, however this is strain dependent and for strains inducing hemorrhagic syndrome, mortality can be up to 50%. During outbreaks with bovine respiratory disease complex (BRDC), in which BVDV interacts with other pathogens, mortality may also be significant, and a certain mortality in calves infected in late gestation (non-PI), can be expected. In PI animals the mortality is significantly higher than in acutely infected, and reaches 100% in those that develop mucosal disease. GAPS: The direct+indirect contribution of BVDV to mortality (through immunosuppression/co-infections) hard to estimate. Persistent infection: Every excretion with high titers of up to 107 per ml (exception: during colostral immunity). Acute infection: low to medium titers (102 to 104 per ml). GAPS:
An internal protein cleavage site results in additional production of the p80 (NS3) protein, and this protein is associated with cytopathogenicity in cell culture. When this mutation occurs in an animal PI with ncpBVDV a population of mutated (cp) viruses expands so that both cp and ncp biotypes of the same virus are present. This scenario results in Mucosal Disease, which is invariably lethal. Leucopenia is generally seen post infection. GAPS:
Zoonotic potentialNone (one old report without convincing or reproduced data). Unknown. None. None. 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. GAP: Risk of spread to human population through contaminated vaccines unknown. Impact and consequence of potential spread unknown. Impact on animal welfare and biodiversityImpact 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. Impact du to control: The impact on animal welfare due to control is low. Control measures do not include 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 described/discussed/understood. Too much focus on reproductive disorders instead of overall reproductive efficiency (also including young stock survival and replacement). The impact of the disease in different production settings is poorly understood. BVDV infection could have an impact on biodiversity if it is present in zoos, game parks, herds with endangered cattle breeds, preservation of semen from rare breeds, due to the disease itself or indirectly due to control efforts. GAP: Extent of problem in captive (zoos, parks and preserves) and free ranging wildlife (e.g. Chamois) needs further investigations. PI animals should be slaughtered to reduce transmission. Geographical distribution and spreadWorldwide distribution (known exceptions are Iceland and Norway and regionally in other parts of Europe.). GAP: 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. Endemic appearance on population level, can have epidemic characteristics at herd level, but also in population level in free populations in the future. Highly seasonal in many countries due to management (grazing seasons, stable seasons). Virus may be shed in body secretions and excretions from days 4 to 15 post infection. Horizontal transmission to seronegative cattle has been shown to occur after only one hour of direct contact with a PI animal. GAPS:
High via global trade with potentially infected semen, and embryos, or the trade of PI animals or dams carrying PI fetuses (so called PI-carriers). The global trade with potentially infected FCS, or biological products based on FCS has further implications on the potential for transboundary spread. GAP: The global distribution pattern of potentially infected FCS needs further investigations. No. No. Has been described as a consequence of flooding, leading to emergency movements of cattle. None. Route of TransmissionHorizontally via contact with excretions or secretions of PI animals, via semen or vertically by fetal infection during early pregnancy – generally thought to be before 125 days of pregnancy for PI animals. 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. Contaminated embryos, semen and biological products based on FCS. Iatrogenic, ET, other indirect means such as fomites, bedding flies. GAP: Quantification of the role/impact of different means of indirect transmission in a large scale control context is lacking. Conditions that favour spread is e.g. animal trade (purchase of PIs or pregnant animals, potentially carrying PI fetuses), common pasturing, grouping of animals from different sources (such as in sale barns and feedlots), and other cattle management strategies that increases the likelihood of between-herd contacts. Survival of the virus in biologicals favours spread through indirect means. Generally inapparent clinical signs of the disease make early detection difficult. GAP: Relative effect of different intervention strategies at the population level needs further investigations. Detection and Immune response to infectionIn non-PI animals infection elicits a serological antibody response and a T cell response; in PI animals, a serological response is not seen unless the infecting virus is sufficiently heterologous. A reduction in circulating WBC is observed following acute infection (probably associated with immune suppression). GAPS:
At the individual level, 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. Direct detection of PIs is done by antigen capture ELISA or genome detection. Main means of prevention, detection and controlIdentification 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 on 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. 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 (but is possible using quantitative serological assays in non-vaccinated populations) and introduction of these are best prevented by control at the herd of origin. GAPS:
So far only strategies using improved biosecurity and elimination of PI animals have 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. BVDV control programmes including systematic vaccination besides improved biosecurity and elimination of PI animal, underway in a number of countries and regions. Virus isolation (gold standard), but in routine more common with antigen capture ELISAs or PCR on blood or milk samples (individual/bulk), antibody detection utilising SNT or ELISA (on blood or milk). PCR also on semen and ear notches. GAPS:
MLV and inactivated vaccines are available. Efficacy and safety still an issue. Non-systematic vaccination strategies have been widely used in many settings, so far with no proof of sustainable decrease in disease prevalence or impact. BVDV control programmes including systematic vaccination besides improved biosecurity and elimination of PI animal, underway in a number of countries and regions. GAPS:
There are no therapeutic treatments available. Prophylactic treatments may be used and antibiotics may be used to treat secondary infections. Prototypes (NS5b polymerse blocking pharmaceuticals) are tested in vitro (from HCV research). 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. Several studies have shown that herd biosecurity measures alone will 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. BVD is 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 semen from bulls that test positive may not be traded. This point is becoming more and more important since more and more countries are starting eradication programs (e.g. Germany on the 01.01.2011). Therefore, EU-wide guaranties (like written in 64/432/EWG for other diseases) will be an important issue in the future. The primary target for BVDV prevention is usually the herd. Biosecurity measures and vaccination may be used as strategies for prevention. GAP: Effective diagnostic tools for identification of pregnant dams carrying PI fetuses (PI carriers) are missing. Depends on the country! May be done by testing for antibodies in bulk milk or on a small sample of individuals (spot tests) and/or by bulk milk or individual testing using PCR. BTM testing using PCR alone is NOT recommendable. GAPS:
Several European countries (e.g. Denmark, Finland, Sweden, Norway, Austria) have experience with systematic large scale BVDV control aimed at eradication, and new programmes are being started in e.g. Germany and Switzerland. 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 introducing vaccination as an additional biosecurity tool are underway. 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:
Estimates available for the 10 first years of the Norwegian BVD control scheme. The annual net benefits over the 10 years of BVD control were discounted to net present value (NPV) estimated at 130 million NOK (≈15 million €) (Valle et al., 2005) The cost of BVDV infection to an infected average-sized dairy herd in New Zealand was estimated to be NZ$11,334 (or NZ$35.19 per cow) per annum, and NZ$48,311 over 10 years. Based on these calculations, the estimate of the annual cost of BVDV infection to the dairy industry in New Zealand was in excess of NZ$23 million per annum. While all of the control options required financial input, the rate of return compared with the cost of BVD, when viewed over a 10-year term, was as high as 123% (Reichel et al., 2008) GAP: Publication of ex-post cost-benefit assessments needed. Disease information from the OIENo. No. No. No. Socio-economic impactMinimal except in the case of increased resistance. Not applicable. Total annual losses due to a low-virulent BVDV strain have been estimated as US$ 20 million per million calvings when modelling the losses. Using the same model, losses due to a high-virulent BVDV strain were estimated as US$ 57 million per million calvings (Houe, 1999). The cost of BVDV infection to an infected average-sized dairy herd in New Zealand was estimated to be NZ$11,334 (or NZ$35.19 per cow) per annum, and NZ$48,311 over 10 years. Based on these calculations, the estimate of the annual cost of BVDV infection to the dairy industry in New Zealand was in excess of NZ$23 million per annum (Reichel et al, 2008) GAPS:
Estimates available for the 10 first years of the Norwegian BVD control scheme. The annual net benefits over the 10 years of BVD control were discounted to net present value (NPV) estimated at 130 million NOK (≈15 million €) (Valle et al., 2005) The cost of BVDV infection to an infected average-sized dairy herd in New Zealand was estimated to be NZ$11,334 (or NZ$35.19 per cow) per annum, and NZ$48,311 over 10 years. Based on these calculations, the estimate of the annual cost of BVDV infection to the dairy industry in New Zealand was in excess of NZ$23 million per annum. While all of the control options required financial input, the rate of return compared with the cost of BVD, when viewed over a 10-year term, was as high as 123% (Reichel et al., 2008) Difficult to calculate (country, control programs, number of PI animals, vaccination etc.). GAP: A better understanding of the economic impact under different farming conditions. Trade implicationsCurrently no or very low impact on trade from EU. Potentially high if BVD free countries are declared, and if BVDV will be part of 64/432/EWG (Article 9 or 10 status!). However at this stage it is unlikely that BVDV will become a disease for which additional guarantees regarding intra-community trade can be granted. On the other hand, countries with national control programmes 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. GAP: Good studies on impact on trade, involving economists and political scientist needed. Initially high countries with control programs, when there is a need for a market that can handle animals from herds with different status, and when there is still an additional market value for BVDV free animals. Both these impacts decrease as a majority of herds become free. No impact in other countries. Main perceived obstacles for effective prevention and controlObstacles 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 BVDV 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:
Main perceived facilitators for effective prevention and controlA 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. GAP: 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. RiskThe disease results in huge economic losses for the cattle industry worldwide. Reproductive effects are the most prominent (abortions, deformed offspring, PI animals) but significant financial losses occur also through a general impaired health in endemically infected herds, due to the immunosuppressive effect of the virus and death of affected animals. PI animals are the most serious risk for any herd. ConclusionCattle of all ages are susceptible to infection with BVDV and the virus is endemic worldwide. Clinical signs range from sub-clinical to fatal (Mucosal disease and hemorrhagic syndrome ). Acute infections may result in transient clinical disease with unspecific symptoms (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. |
