Control Tools

• Diagnostics availability

• Commercial diagnostic kits available worldwide

  Yes

• Commercial diagnostic kits available in Europe

  Antibody detection kit for BRSV antibodies from Guildhay Limited UK, Svanova AB, Sweden. An F antibody detection ELISA is available commercially via Cedidiagnostics Lelystad, The Netherlands (Cedididagnostics BRSV strip).ELISAs for detection of both IgG or IgM in serum are available commercially in France (Iddexx, Institut Pourquier, Montpellier, France). Speed EIA assay for antigen detection in nasal sawbs (BRSV Diagnostic, Virbac, Carros, France)qRT-PCR kit also commercially available for labs (LSI, Lissieu, France)

• Diagnostic kits validated by International, European or National Standards

  No

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

  None

• Commercial potential for diagnostic kits worldwide

  If compulsory DIVA based eradication programs would start, than diagnostics would become very profitable but this seems unlikely except in some Nordic countries.

• DIVA tests required and/or available

  None available yet. However, an N based ELISA would be a good option, since all animals infected with BRSV develop Abs against this protein, whereas it is not essential for efficient vaccine preparations such as MVA based subunit vaccines.

  For a live, attenuated BRSV mutant vaccine, non-essential viral proteins like SH, M2, G, NS1 and NS2, are possibly suitable for DIVA test development, depending on their capacity to induce antibodies in the BRSV infected host.

  Research into the antibody inducing aspects of all these BRSV proteins would be the needed to be able to decide on the available options for BRSV DIVA vaccine-test combinations.

  A DIVA approach is not only interesting for eradication programs but it will also enable monitoring the vaccine efficacy.

  In addition, vaccination makes us blind regarding the monitoring of the epidemiological situation, and a DIVA will enable to get a better understanding of the epidemiological situation in vaccinated areas.

• Opportunities for new developments

  Development of DIVA diagnostic tests linked to vaccines

• Vaccines availability

• Commercial vaccines availability (globally)

  Many single and combination modified-live and killed BRSV vaccines are currently on the market for intramuscular and intranasal administration in cattle.• Freeze-dried live modified BRSV vaccine, Rispoval 4 (Pfizer) (Novartis) • Bovi- Shield: Pfizer AH, • Bovilis Bovipast, Intervet, subcutaneous application. Bayovac BRSV (Pfizer)• Triangle and Pyramid (Fort Dodge) and Hiprabovis (Hipra)

• Commercial vaccines authorised in Europe

  Amongst others:• Rispoval RS, Pfizer, Intramuscular application• Bovilis Bovipast, Intervet, subcutaneous application• Rispoval 3, Pfizer, Intramuscular application (BRSV attenuated strain different from Rispoval RS)• Rispoval RS+Pi3 Intranasal, Pfizer• Bayovac BRSV (Pfizer)• European pharmacopeia specifies the requirements for the freeze-dried BRSV vaccine (live)

• Marker vaccines available worldwide

  None

• Marker vaccines authorised in Europe

  None

• Effectiveness of vaccines / Main shortcomings of current vaccines

  • Immunity conferred by BRSV infections or vaccination is probably short lived and may only last 3 or 4 months. However, host resistance increases following repeated infection. The reason for short lived immunity in BRSV, and its human counterpart HRSV, is not known, but may explain the common occurrence of recurrent infections in vaccinated and unvaccinated individuals. Therefore, frequent vaccination may be necessary to control disease. • Some inactivated vaccines have induced exacerbated disease following BRSV infection. • As young calves are at greatest risk of severe BRSV disease, calves should be vaccinated when maternally-derived antibodies (MDA) are still present. However, MDA suppress immune responses to vaccination and infection.• Current vaccines induce poor or variable protection against viral shedding allowing the virus circulation to continue.• Intranasal vaccination with live attenuated BRSV vaccine induces rapid protective immunity, which is useful when disease occurs in very young calves (3 to 6 weeks old). However, live virus is excreted and could revert to virulence.

  GAP

  • Comment: The European Pharmacopoeia could be improved by including that all vaccines should demonstrate efficacy against clinical disease and should not induce enhanced disease. Studies should include a control vaccine that enhances clinical disease following BRSV challenge.

• Commercial potential for vaccines

  A highly effective BRSV vaccine with documented effect on calf pneumonia in general would have a good market

• Regulatory and/or policy challenges to approval

  None unless genetically manipulated vaccines which may pose a problem in some countries. Some countries may be reluctant to use live virus vaccines that may spread within the calf population.

• Commercial feasibility (e.g manufacturing)

  Feasible

• Opportunity for barrier protection

  Not applicable

• Opportunity for new developments

  Live vaccines with gene deletions and/or recombinant virus vectors.

  Vaccines able to induce a Th1 response in young cattle (adjuvants) and overcoming the inhibitory effect of maternal antibodies

• Pharmaceutical availability

• Current therapy (curative and preventive)

  As with other viruses, antibiotics have no affect on the BRSV infection. However, antibiotic treatment is indicated in attempts to control the secondary bacterial infections. As there is a need to reduce antibiotic usage, antibiotic treatment should be linked to development of diagnostic tools to show presence of bacteria in the lungs.

  Anti-inflammatory compounds are used in some countries but the effect are questionable

  GAP

  • Larger studies on clinical effect of corticosteroids, which are commonly used in BRSV outbreaks in the field

• Future therapy

  None

  GAP

  • Improvement of NSAIDs, eg. by preserving the protective effect of prostaglandin in the lung?• An increased understanding of the pathogenesis of BRSV infection would lead to the development of therapeutics that specifically target BRSV-induced pathology

• Commercial potential for pharmaceuticals

  An antiviral may have a place in future as well as other agents that have a disease mitigating effect at low cost, in combination with antibiotics or anti-inflammatories.

• Regulatory and/or policy challenges to approval

  None

• Commercial feasibility (e.g manufacturing)

  Not applicable at present

• Opportunities for new developments

  None

• New developments for diagnostic tests

• Requirements for diagnostics development

  G and F protein antibody Elisa’s are available (see above).

  Lab-based (real time) PCR’s have been described by several research groups. Real time RT-PCR kit (LSI, Lissieu, France) is available in France for vet labs

  GAP

  • Potential for a DIVA vaccine and accompanying diagnostic test.• Assays to detect multiple pathogens at the penside are needed – especially those that can distinguish bacterial from viral infections.

• Time to develop new or improved diagnostics

  Can be fast, depending on approach and availability of reagents within weeks (PCR’s) or months (ELISA

• Cost of developing new or improved diagnostics and their validation

  If enough samples for validation of tests are available, costs are low. If field experiments are necessary for sample generation development may get costly.

  Some difficulties to obtain a challenge model able to reproduce severe clinical signs of BRSV infection.

• Technology to determine virus freedom in animals

  PCR and possible antigen detection methodologies, if latent carrier animals exist & contribute to the epidemiology of BRSV

• New developments for vaccines

• Requirements for vaccines development / main characteristics for improved vaccines

  • BRSV vaccine to provide durable immunity against BRSV infection of the lower respiratory tract which prevents viral shedding and is effective in calves with maternal antibodies. • Development of an efficacious DIVA vaccine (single shot; duration of protection > 1 year in young calves) with an accompanying ELISA based diagnostic test. • Most promising approaches seem to be Vector based- and genetically modified live virus vaccines and inactivated virus/subunit with ISCOMs.• Other adjuvants (CpG , commercial adujants) could be tested for their capacity to induce a strong immune response (TH1 cell response).

• Time to develop new or improved vaccines

  Up till licensing at EMEA, 5-10 years

• Cost of developing new or improved vaccines and their validation

  Hard to estimate, but can be high, especially for GMO’s; mainly depends on safety study requirements of EMEA

  GAP

  • Vaccine efficacy will need to be evaluated on calves with MDA• Good BRSV challenge models that induce clinical disease should be used to evaluate vaccine efficacy

• Research requirements for new or improved vaccines

  The development of safe and effective RSV vaccines has been hampered by the need to induce protective immunity within the first month of life, at a time when maternal antibodies can pose a major obstacle to successful vaccination; and the observation that vaccination can exacerbate RSV disease. Since vaccine-augmented disease has been associated with

  inactivated virus, it has been proposed that a live, attenuated virus administered intranasally would make a safer and more effective vaccine.

  Recent advances in the molecular biology of negative-sense RNA viruses have provided a means to manipulate the genome of BRSV and opened the way for producing genetically stable, attenuated BRSV vaccine candidates.

  Development of gene deleted or recombinant BRSV vaccines would have the advantages of allowing the development of diagnostic kits which could differentiate infected form vaccinate cattle.

  Specific research requirements include:-

  • Effective antigen delivery systems
  • Adjuvants for inactivated vaccines or attenuated vaccine (insertion of immunomodulatory genes)
  • Combination vaccines
  • Route of administration
  • Research into mechanisms of exacerbated disease induced by some vaccines
  • Vaccines that induce durable protective immunity
  • Use of unified BRSV challenge stocks in order to compare results from different challenge studies performed in different establishments

  GAP

  • Good model to evaluate both vaccine efficacy and safety.

• New developments for pharmaceuticals

• Requirements for pharmaceuticals development

  None apart form the generic approach to antivirals for most viral disease. Most effort is currently directed at development of antivirals effective against HRSV. Such products could be validated against BRSV in calves.

  Use of antivirals could cause problems with emergence of antiviral resistance

  GAP

  • A greater understanding of the role of the host response in the pathogenesis of BRSV could lead to the development of immunomodulators to treat disease

• Time to develop new or improved pharmaceuticals

  Depends upon the nature of the product

• Cost of developing new or improved pharmaceuticals and their validation

  Depends upon the nature of the product

• Research requirements for new or improved pharmaceuticals

  A greater understanding of the role of the host response in the pathogenesis of BRSV could lead to the development of immunomodulators to treat disease

Disease details

• Description and characteristics

• Pathogen

  Bovine respiratory syncytial virus (BRSV) is an RNA virus classified as Pneumovirus in the family of Paramyxoviridae. It is a negative single-stranded, non-segmented RNA genome of about 15 kilobases. The genome encodes for two non-structural proteins NS1 and NS2 and the 8 structural proteins, N, P, M, SH, G, F, M2 and L. The G protein is the viral attachment protein, however it is dispensable for viral infection and protection. The F or fusion protein is essential for viral infection and induces neutralising antibodies and CTL’s. Virions are spherically shaped and surrounded by a lipid envelope into which the G & F are inserted.

• Variability of the disease

  BRSV exist as a single serotype, with four antigenic subtypes and six genotypes based on the G protein-coding gene, which cluster temporally and spatially. BRSV is species specific although sheep may be infected experimentally with BRSV. Natural infections of sheep and goat occur with closely related RS viruses. BRSV is also structurally and antigenically related to human (H)RSV, which is the single most important cause of bronchiolitis and pneumonia in infants. The high degree of similarity between HRSV and BRSV indicates that comparative studies of the immunobiology of these viruses will yield important insights that should benefit both man and cattle

  GAP

  • What is the role of genetic variation in calves on disease severity?• What aspects of the virus determine virulence?

• Stability of the agent/pathogen in the environment

  BRSV does not survive very long in the environment. The fragility of the virus makes it difficult to isolate in the laboratory; therefore, BRSV infection is difficult to diagnose by virus isolation. However, by the use of antigen detection (IIF, ELISA) conventional or real time RT-PCR, the virus can be detected in clinical specimens such as nasopharyngeal swabs, bronchoalveolar lung lavage or lungs.

  GAP

  • How long can BRSV persist in the environment?The survival of BRSV in the environment is not really known i.e. water, teats, even if it is probably short. Nevertheless outbreaks can occur without animal introduction suggesting that the virus is resistant enough to enable indirect transmission.

• Species involved

• Animal infected/carrier/disease

  In additional to cattle, sheep and goats can also be infected by respiratory syncytial viruses. BRSV infections associated with respiratory disease occur predominantly in young beef and dairy cattle. BRSV can be detected in cattle with mild to severe respiratory signs. Virus has been isolated from lymph nodes of calves 71 days after experimental infection. However, viral excretion from persistently infected animals has not been documented. BRSV can also be isolated from cattle without clinical signs of disease.

  GAP

  · Existence of carrier and can they excrete BRSV.

• Human infected/disease

  Although there are many similarities in antigenic epitopes, epidemiology and disease pathogenesis with HRSV, BRSV is not known to be infectious to humans. Although calves can be experimentally infected with HRSV, replication of BRSV in chimpanzees is highly restricted.

  GAP

  • Better understanding of the species barrier.

• Vector cyclical/non-cyclical

  None

• Reservoir (animal, environment)

  The virus may persist from outbreak to outbreak in a herd through subclinical or mild infections in a few infected animals that may transmit virus to younger susceptible cattle, but this has not been definitely proved. Neither can excretion by persistently infected animals be excluded. BRSV also circulates between herds, probably by indirect as well as direct transmission to susceptible animals. The existence of a wild-life reservoir cannot be excluded but has not been confirmed to play a major role in the epidemiology

  GAP

  • How long does BRSV circulate in closed herds after an outbreak?• At the individual level, how long does virus excretion persist after natural infection in animals of different age and immunity?• Do BRSV reservoirs exist?

• Description of infection & disease in natural hosts

• Transmissibility

  The transmissibility of BRSV is high: the spread of the virus between immunologically naive animals within herds and between herds is very rapid. BRSV gains entry to susceptible cattle through the respiratory tract where it replicates and causes disease

  GAP

  • How does BRSV spread? An understanding of the mode of transmission will aid the development of biosecurity measures.

• Pathogenic life cycle stages

  Not applicable

• Signs/Morbidity

  Major respiratory pathogen in young calves, causing severe bronchiolitis, pneumonia, and upper- and lower respiratory tract disease. The clinical signs range from hyperthermia +/- cough with serous nasal and ocular discharge to severe bronchopneumonia with abdominal dyspnoea, raised temperature, and death following acute respiratory distress caused directly by the virus or by bacterial superinfection.

  • Morbidity is highest in calves 1 to 6 months of age. However, the severity of the disease is variable among calves in one herd.• In feed lots, BRSV may cause severe respiratory diseases in cattle between 6 mths to 1 year, with or without superinfection by other viruses, mycoplasmas &/or bacteria. This justifies the wide range of BRSV vaccination in this type of production. • A primary infection in older cattle is also associated with high morbidity. • Re-infection of older cattle is associated with little clinical disease.

  GAP

  • What determines differences in disease severity? (HRSV disease severity in infants is influenced by host genetics)- Influence of host genetics?- Role of co-infection- Genetic background of virus

• Incubation period

  3-5 days after exposure to the virus

• Mortality

  Usually less than 5% in young calves. Deaths may result from BRSV infection alone or as a result of secondary bacterial pneumonia. However, severe outbreaks of BRSV with 15-20% mortality can be seen.

  GAP

  • What is the role of co-infections and differences in virulence of BRSV isolates in severity of disease?

• Shedding kinetic patterns

  Excretion in droplets and nasal secretions

• Mechanism of pathogenicity

  Much like HRSV, BRSV replicates predominantly in ciliated airway epithelial cells and type II pneumocytes inducing an array of pro-inflammatory chemokines and cytokines that recruit neutrophils, macrophages and lymphocytes to the respiratory tract resulting in respiratory disease. In tissue outside the respiratory tract and regional lymph nodes neither BRSV antigen nor replication of BRSV could be demonstrated.

  GAP

  • A greater understanding of the mechanisms of pathogenicity is needed.

• Zoonotic potential

• Reported incidence in humans

  Does not infect humans

  GAP

  • Better understanding of the species barrier is needed

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

  not known

• Symptoms described in humans

  none

• Estimated level of under-reporting in humans

  not known

• Likelihood of spread in humans

  Minimal

• Impact on animal welfare and biodiversity

• Both disease and prevention/control measures related

  Respiratory disease in young calves is a major animal welfare problem. BRSV is a major primary pathogen in the respiratory disease complex of calves.

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

  No

• Slaughter necessity according to EU rules or other regions

  No

• Geographical distribution and spread

• Current occurence/distribution

  Worldwide/ubiquitous-endemic character of infection in dairy and especially beef cattle

  GAP

  • Up-to-date prevalence studies based on sensitive detection methods in animals at the acute stage of disease, (when BRSV is present as primary pathogen) are needed• Although BRSV is already considered as a major pathogen in the respiratory disease complex of calves, prevalence studies based on virus isolation and chronic cases might give an underestimation of BRSV importance.

• Epizootic/endemic- if epidemic frequency of outbreaks

  Endemic

• Seasonality

  Outbreaks of the disease occur seasonally especially in autumn and winter. Although the number of clinical cases are less during summer, BRSV outbreaks are sometimes detected also in this season. This shows that at least in some areas, the virus continues to circulate the year around.

  GAP

  • Is there a relation between outbreaks of disease and the length of day light, as suggested for influenza viruses, change in environmental temperature, &/or absolute humidity?

• Speed of spatial spread during an outbreak

  Rapid within a herd. Rapid between herds with low herd immunity.

• Transboundary potential of the disease

  Can be easily spread by movement of cattle. Aerogenic transmission of BRSV has also been suggested.

• Route of Transmission

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

  Transmission from one animal to another is thought to be via aerosol droplets from the nose and throat. However, aerosol transmission has also been described. Due to the mode of transmission, the length of time for the disease to progress through an exposed herd depends upon the confinement status of the herd. In feed yards and dairies, where cattle are in close confinement, the disease can spread rapidly through the cattle in 3 to 10 days. However, in pastured cattle it may take several weeks or months to move through the entire herd. Once exposed, it requires 2-4 days for a susceptible animal to begin showing clinical signs of the disease. In susceptible herds undergoing a BRSV outbreak, you can expect 100% of the animals to become infected with the virus, 20-50% to show clinical signs, and generally less than 5% to die. Indirect transmission between herds via humans or other passive vectors is likely to occur but has never been documented. Transmissibility (and consequently disease progress) also depends on the immune status of animals, since immunity is known to reduce the nasal BRSV excretion

  GAP

  • What is the route of transmission of BRSV within and between herds? • What is the importance of passive vectors? • What are the biosecurity measures needed to prevent introduction of BRSV in herds that are closed with regard to animal introduction?

• Occasional mode of transmission

  Not applicable

• Conditions that favour spread

  Close confinement of animals and close contact between calves and older animals. Mixing of animals from multiple origins.

  GAP

  • What is the effect of specific immunity on spread?• How does vaccination influence spread?

• Detection and Immune response to infection

• Mechanism of host response

  Both cell-mediated and antibody–mediated immune responses contribute to efficient protection of animals. Antibody to the F and G proteins are important in mediating protection. However, antibody to the G protein is mainly sub-type specific. MHC class I restricted CD8+ CTL’s play an important role in clearing the virus from lungs and nasopharynx. Bovine CD8+ T cells recognise predominantly the N and P proteins, although other viral proteins are also recognised in cattle with different MHC class I haplotypes. In addition to the F and G proteins, the N protein can also induce some protection against challenge.

  There is evidence of vaccine-augmented disease, possibly related to a Th2-biased immune response.

  GAP

  • Immunological basis of vaccine-augmented disease in cattle needs clarifying further.• What is the role of the immune response in the pathogenesis of primary infection?• What is the duration of immunity?• What influences the duration of immunity?

• Immunological basis of diagnosis

  Antibody detection using paired samples. However, the high levels of maternally-derived antibodies in young calves can mask antibody response.

  GAP

  • Development of an immunological test based on detection of BRSV-specific IgM or IgA antibodies

• Main means of prevention, detection and control

• Sanitary measures

  Introduction of animals into herds through quarantine. Hygiene of visitors and material that are in contact with several herds. Keeping the density of animals and calf group size low. Ensuring adequate colostrum-intake. Separating young naive calves from older cattle is a simple management tool that can be used to reduce BRSV exposure and disease in calves that are usually most susceptible to severe BRSV infections. However, this is often not practical.

  BRSV is also diagnosed in feedlots, where it is difficult to apply sanitary policies. In the veal production industry, calves are collected at 10-14 days of age and taken to a farm where they will be fattened together with a few hundred calves. A “system innovation” instead of a technical innovation to prevent calves being brought together in a period when they are most vulnerable may reduce respiratory disease.

  GAP

  • Designing efficient and applicable biosecurity measure to limit the spread of the virus.

• Mechanical and biological control

  Vaccination

• Diagnostic tools

  The clinical and epidemiological picture in major BRSV outbreaks is quite distinctive; however, the symptoms and lesions noted are generally not specific enough for diagnostic purposes. Diagnosis must be based on laboratory findings.Virus detectionA diagnosis of BRSV requires laboratory confirmation. BRSV has proved to be a difficult virus to detect by isolation procedures. Chances of isolation may improve by sampling animals that are in the incubation or acute phase of infection (hyperthermia phase). Antigen detection enzyme immunoassay has been developed and is useful in detecting BRSV antigen and establishing an ante mortem or post-mortem diagnosis. Other procedures that have proved useful in detection of BRSV virus antigen are fluorescent antibody and immunoperoxidase staining. Furthermore, PCR-based tests are used in routine diagnostics as well as for research purposes.Identification of antibodiesPaired serum samples can be used to establish a diagnosis of BRSV infection. However, the antibody titre of animals with well-developed clinical disease may be higher in the acute sample than in the sample taken 2-3 weeks later. This is because the antibody response often develops rapidly, and clinical signs follow virus infection by up to 7-10 days. Single serum samples showing high antibody titres from a number of animals in a respiratory outbreak may be useful in making a diagnosis if coupled with clinical signs. Calves that become infected with BRSV in the presence of passively derived antibody may not seroconvert, and serum antibody titres may even decrease between sampling. . The duration of BRSV maternal antibodies in calves is usually between 3 to 6 months.

  GAP

  • Penside tests• Tests to detect multiple pathogens in a single sample• Tests to detect BRSV-specific antibody response in calves with high levels of maternally-derived serum antibodies

• Vaccines

  Inactivated single component and combination BRSV vaccines are available. These induce different responses depending upon the route of vaccination, dose and adjuvant.• Modified live virus (MLV) vaccines generally induce high virus neutralizing antibody levels. In contrast, inactivated vaccines induce significantly lower levels of virus neutralizing antibodies and some stimulate Th-2 responses, which may have a disease enhancing effect following exposure to live virus.• BRSV infections are often recurrent despite the presence of neutralizing antibodies, suggesting the importance of CTL responses in protection and/or (significant) field strain variation.• Young calves (<6 mths) are difficult to immunise effectively and maternally-derived antibodies may compromise vaccine efficacy• Young calves may need a different type of vaccine than older calves.

  GAP

  • An effective BRSV DIVA vaccine that will:- be safe and rapidly induce clinical and virological protection when administered to calves with maternal antibodies- induce a long duration of protection- require a minimum number of dose administration- enable the distinction between vaccinated and infected animals (DIVA)- be suitable for large scale production and have a cost compatible with its use in livestock production- be compatible with vaccines against other respiatory pathogens• Identification of mmune correlates of protection

• Therapeutics

  None specifically for BRSV and only the use of antibiotics to control secondary bacterial infection. In case of respiratory distress syndrome, corticoids and bronchodilators are currently used in the field. Efficacy of these treatments is not proved to date.

  The excipient some long lasting antibiotic preparations might precipitate the death.

  GAP

  • Identify efficient therapeutic to limit animal losses and impact on the welfare. Identification through a better understanding of the pathogenesis of BRSV infection?

• Biosecurity measures effective as a preventive measure

  Closed herds. However, introduction of virus into closed herds has been described.

• Border/trade/movement control sufficient for control

  None as not a listed disease

• Prevention tools

  Since disease caused by BRSV and secondary bacterial infections can be difficult to treat, especially in young calves, control of the disease should be aimed at prevention. Due to the widespread occurrence and lack of detailed knowledge of disease transmission and persistence of virus in the population, eradication is not realistic in high cattle density areas. However, eradication in such areas might be possible if a vaccine that induces full virological protection with long duration was developed and used in combination with biosecurity measures.

• Surveillance

  Serology when required

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

  Variable as BRSV is a component of Bovine respiratory disease complex caused by a wide range of viruses and bacteria. Reports exist of BRSV vaccine failure. However, it is difficult to estimate a BRSV vaccine failure as it could be either vaccine failure or failure of vaccination procedure.

• Costs of above measures

  Costs of treatment of infected animals. Costs of purchase and application of vaccine when used

• Disease information from the WOAH

• Disease notifiable to the WOAH

  No

• WOAH disease card available

  No

• WOAH Terrestrial Animal Health Code

  No

• WOAH Terrestrial Manual

  No

• Socio-economic impact

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

  None

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

  Not applicable

• Direct impact (a) on production

  BRSV is a major cause of respiratory disease in calves resulting in a substantial economic loss for the cattle industry worldwide. No specific figures are available, but must be significant given BRSV infection is the major respiratory disease in cattle below 6 months of age. Approximately 1.9 million calves in the UK affected by respiratory disease each year, at a cost of £54 million. Furthermore, approximately 160,000 calves, which have a potential market value of £100 million, die annually as a result of pneumonia and related illnesses in the U.K. BRSV is the single most important respiratory viral pathogen of calves.Worldwide infection with

  BRSV is a major contributor to the multi-pathogen disease, bovine respiratory disease complex.

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

  Costs of diagnosis and treatment

• Indirect impact

  Disruption to production and mortality of young calves with a knock on effect on livestock production

• Trade implications

• Impact on international trade/exports from the EU

  None

• Impact on EU intra-community trade

  None

• Impact on national trade

  None

• Main perceived obstacles for effective prevention and control

  • Difficulties in inducing durable protection by vaccination of calves with maternal antibodies. • Understanding how BRSV survives between periods of infection and how outbreaks occur suddenly in herds without animal exchanges. • An extensive epidemiological study is needed to determine how long the virus circulates in a herd after infection and if re-occurring infections in herds are caused by genetically identical viruses, and thus may persist in herds by carriers. • Identification of the route of introduction / transmission in a herd. • Some obstacles, such purchase and concentration of cattle from different origins, are directly linked to cattle industry (technopathy) and cannot be resolved. This underlines the importance of preventive measures such as efficacious vaccination.

• Main perceived facilitators for effective prevention and control

  • Vaccines that are efficacious in young calves with maternally-derived antibodies. • Vaccines that prevent virus shedding. • Vaccines of the DIVA type conferring longterm (> 1 year) protection. • Improved medical treatment to mitigate clinical signs.• One shot vaccine especially for young beef cattle

• Links to climate

  Seasonal cycle linked to climate

  There is some evidence that climatic conditions may affect the occurrence of BRSV infections, which tend to be more prevalent in the autumn and winter. It is speculated that BRSV outbreaks may be precipitated by changes in the weather, such as a drop in temperature or a decrease in atmospheric pressure

  GAP

  • Is there a link with day-light length, change in environmental temperature, &/or absolute humidity?

• Distribution of disease or vector linked to climate

  No

• Outbreaks linked to extreme weather

  No

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

  No

Risk

Main critical gaps

Conclusion

• BRSV is still a major cause of respiratory disease in calves and causes considerable economic losses worldwide. More effective vaccines, especially of the DIVA type, combined with biosecurity measures based on identified routes of virus introduction in herds are needed to combat the disease successfully in a well controlled manner in endemic areas.

  However, BRSV infections are not notifiable to the OIE and there is no compulsory eradication program being considered.

  Large volumes of antibiotics are used in the veal production sector to try and control respiratory disease. Governments have requested that the use of antibiotics in livestock should be reduced by 50% in the next few years, in order to reduce the risk of emergence of antibiotic resistant organisms that may spread to man.

  Increased funding for research and development is needed, as the level of funding for endemic diseases is decreasing in many EU countries.

  BRSV in calves is an excellent model for development of HRSV vaccines and pharmaceutical products.

Sources of information

• Expert group composition

  Expert group members are inlcuded where permission has been given

  Geraldine Taylor, Institute for Animal Health, Newbury. - [Leader]Sarah Hagglund, Swedish University of Agricultural Sciences, SwedenBirgit Makoschey, MSD Animal Health, The NetherlandsGilles Meyer, National Veterinary School of Toulouse, FranceJean-Francois Valarcher, Swedish University of Agricultural Sciences, Sweden Adriaan Antonis, Central Veterinary Institute of Wageningen UR, The Netherlands

• Reviewed by

• Date of submission by expert group

• References