In cattle, conceptus-derived interferon tau (IFNT) is the pregnancy recognition (PR) signal. Our previous studies showed that non-cytopathic bovine viral diarrhoea virus (ncpBVDV) infection inhibited ...IFNT-induced interferon stimulated gene (ISG) expression, potentially causing early embryonic death. This study investigated the effect of bovine viral diarrhoea virus (BVDV) infection on upstream regulatory pathways of ISG production using an established PR model. Uterine endometrial cells from 10 apparently healthy and BVDV free cows were cultured and treated with 0 or 100 ng/mL IFNT for 24 h in the presence or absence of ncpBVDV infection. Microarray and pathway analysis were used to determine the IFNT-induced upstream regulators. Expression of the genes associated with the identified pathways were quantified with qPCR. IFNT challenge activated the signalling pathways associated with IFN receptors, JAK1/TYK2, IRFs and STATs and ncpBVDV infection inhibited the activation of IFNT on this pathway. Inhibition of this upstream signalling pathway may thus reduce ISG production to disrupt maternal PR. In addition, the reduction of uterine immunity by ncpBVDV infection may predispose the animals to uterine infection, which in turn impairs their reproductive performance. This provides a mechanism of how BVDV infection leads to early pregnancy failure in cows.
Since 2008, the Swiss veterinary service has been running a mandatory eradication program for Bovine Viral Diarrhea (BVD) that is focused on detecting and eliminating persistently infected (PI) ...animals. Detection was initially based on antigen testing from ear tag samples of the entire cattle population, followed by antigen testing of all newborn calves until 2012. Since then, bulk milk serology (dairy herds) and blood sample serology (beef herds) have been used for the surveillance of disease-free herds. From 2008 to 2012, the proportion of newborn PI calves decreased from 1.4% to less than 0.02%. However, this success was associated with substantial expenditures.
The aim of this study was to conduct an economic evaluation of the BVD eradication program in the Swiss dairy sector. The situation before the start of the program (herd-level prevalence: 20%) served as a baseline scenario. Production models for three dairy farm types were used to estimate gross margins as well as net production losses and expenditures caused by BVD. The total economic benefit was estimated as the difference in disease costs between the baseline scenario and the implemented eradication program and was compared to the total eradication costs in a benefit-cost analysis. Data on the impact of BVD virus (BVDV) infection on animal health, fertility and production parameters were obtained empirically in a retrospective epidemiological case-control study in Swiss dairy herds and complemented by literature. Economic and additional production parameters were based on benchmarking data and published agricultural statistics. The eradication costs comprised the cumulative expenses for sampling and diagnostics. The economic model consisted of a stochastic simulation in @Risk for Excel with 20,000 iterations and was conducted for a time period of 14 years (2008–2021).
The estimated annual financial losses in BVDV infected herds were CHF 85–89 per dairy cow and CHF 1337–2535 for an average farm, depending on the production type. The median net present value (NPV) was estimated at CHF 44.9 million (90% central range: CHF 13.4 million–69.4 million) and the break-even point to have been reached in 2015. Overall, the outcomes demonstrate that the Swiss BVD eradication program results in a net benefit for the dairy sector. These findings are relevant for planning similar BVD control programs in other countries.
A national eradication programme was designed with the aim of achieving total freedom from bovine viral diarrhea virus (BVDV) infection in the Swiss cattle population. The eradication programme ...consisted of testing every Swiss bovine for antigen, culling virus-positive animals and applying movement restrictions. Starting in 2008, the campaign achieved the goal of reducing the proportion of newborn calves that were virus-positive from 1.8% to under 0.2% within two years (situation in September 2010). Both good data flow between the parties involved as well as speed and efficiency (e.g. concerning the application of tests, movement restrictions and slaughter) are central to the success of the programme. Since the beginning of the programme 2.85 million cattle have been tested for bovine viral diarrhea virus (BVDV).
The BVD-prevalence in cattle at the individual and herd levels following the implementation of the eradication programme was assessed. Using data collected during this campaign a risk factor analysis was conducted in order to identify factors associated with the appearance of virus positive newborn calves in herds where BVD had not previously been detected; these risk factors would allow targeting of future surveillance. Herd size, early death rate (i.e. the number of animals that either die before 15 days of age or are stillborn per number of newborns per year), buying in stock, using communal summer grazing, production type, age structure and management strategy were factors associated with the appearance of new cases of infection. Testing of newborn calves for antigen will continue to be conducted until the end of 2011, this is combined with outbreak investigation of newly infected herds (consisting of re-testing dams of virus-positive calves and if necessary all cattle on or that recently left the farm). This process is done to identify infected animals that may have been missed during prior testing (false negatives), it also serves to identify other factors that may be responsible for the introduction of BVDV onto the farm. Since October 2009, testing of calves for antigen combined with outbreak investigation has led to the detection of 55 infected animals that had tested negative (presumably false negative) during previous rounds of testing.
The success of bovine viral diarrhoea virus (BVDV) eradication campaigns can be undermined by spread through local transmission pathways and poor farmer compliance with biosecurity recommendations. ...This work combines recent survey data with cattle movement data to explore the issues likely to impact on the success of BVDV control in Scotland. In this analysis, data from 249 beef suckler herds and 185 dairy herds in Scotland were studied retrospectively to determine the relative influence of cattle movements, local spread, and biosecurity on BVDV seropositivity. Multivariable logistic regression models revealed that cattle movement risk factors had approximately 3 times greater explanatory power than risk factors for local spread amongst beef suckler herds, but approximately the same explanatory power as risk factors for local spread amongst dairy herds. These findings are most likely related to differences in cattle husbandry practices and suggest that where financial prioritization is required, focusing on reducing movement-based risk is likely to be of greatest benefit when applied to beef suckler herds. The reported use of biosecurity measures such as purchasing cattle from BVDV accredited herds only, performing diagnostic screening at the time of sale, implementing isolation periods for purchased cattle, and installing double fencing on shared field boundaries had minimal impact on the risk of beef or dairy herds being seropositive for BVDV. Only 28% of beef farmers and 24% of dairy farmers with seropositive herds recognized that their cattle were affected by BVDV and those that did perceive a problem were no less likely to sell animals as replacement breeding stock and no more likely to implement biosecurity measures against local spread than farmers with no perceived problems. In relation to the current legislative framework for BVDV control in Scotland, these findings emphasize the importance of requiring infected herds take appropriate biosecurity measures to prevent further disease transmission and conducting adequate follow-up to ensure that biosecurity measures are being implemented correctly in the field.
Classical swine fever (CSF) is endemic in large parts of the world and it is a major threat to the pig industry in general. Vaccination and stamping out have been the most successful tools for the ...control and elimination of the disease. The systematic use of modified live vaccines (MLV), which are very efficacious and safe, has often preceded the elimination of CSF from regions or countries. Oral vaccination using MLV is a powerful tool for the elimination of CSF from wild boar populations. Bovine virus diarrhea (BVD) is endemic in bovine populations worldwide and programs for its control are only slowly gaining ground. With two genotypes BVD virus (BVDV) is genetically more diverse than CSF virus (CSFV). BVDV crosses the placenta of pregnant cattle resulting in the birth of persistently infected (PI) calves. PI animals shed enormous amounts of virus for the rest of their lives and they are the reservoir for the spread of BVDV in cattle populations. They are the main reason for the failure of conventional control strategies based on vaccination only. In Europe two different approaches for the successful control of BVD are being used: Elimination of PI animals without or with the optional use of vaccines, respectively.
•The prevalence of BVDV-1 PI animals entering Australian feedlots was 0.24%.•BVDV-1 was detected by qPCR in 59% of feedlot pens.•BVDV-1 in the pen modestly increased the risk of BRD amongst animals ...in the pen.•A single qPCR test was useful in differentiating PI from TI animals.
Viruses play a key role in the complex aetiology of bovine respiratory disease (BRD). Bovine viral diarrhoea virus 1 (BVDV-1) is widespread in Australia and has been shown to contribute to BRD occurrence. As part of a prospective longitudinal study on BRD, effects of exposure to BVDV-1 on risk of BRD in Australian feedlot cattle were investigated. A total of 35,160 animals were enrolled at induction (when animals were identified and characteristics recorded), held in feedlot pens with other cattle (cohorts) and monitored for occurrence of BRD over the first 50days following induction. Biological samples collected from all animals were tested to determine which animals were persistently infected (PI) with BVDV-1. Data obtained from the Australian National Livestock Identification System database were used to determine which groups of animals that were together at the farm of origin and at 28days prior to induction (and were enrolled in the study) contained a PI animal and hence to identify animals that had probably been exposed to a PI animal prior to induction. Multi-level Bayesian logistic regression models were fitted to estimate the effects of exposure to BVDV-1 on the risk of occurrence of BRD.
Although only a total of 85 study animals (0.24%) were identified as being PI with BVDV-1, BVDV-1 was detected on quantitative polymerase chain reaction in 59% of cohorts. The PI animals were at moderately increased risk of BRD (OR 1.9; 95% credible interval 1.0–3.2). Exposure to BVDV-1 in the cohort was also associated with a moderately increased risk of BRD (OR 1.7; 95% credible interval 1.1–2.5) regardless of whether or not a PI animal was identified within the cohort. Additional analyses indicated that a single quantitative real-time PCR test is useful for distinguishing PI animals from transiently infected animals.
The results of the study suggest that removal of PI animals and/or vaccination, both before feedlot entry, would reduce the impact of BVDV-1 on BRD risk in cattle in Australian feedlots. Economic assessment of these strategies under Australian conditions is required.
In a cross-sectional field study involving 51 cattle herds in Belgium, 3159 serum samples and 557 individual milk samples were collected and tested by four different commercial antibody (Ab) ELISAs ...on serum and two Ab ELISAs on milk. A virus neutralization test (VNT) was performed on serum samples with discording ELISA results and on all samples from non-vaccinating herds. An epidemiological survey was carried out in the same herds to collect information about herd characteristics, management practices, BVD vaccination and BVD infection status. The objective of the study was to evaluate the performances of the Ab ELISAs relatively to the VNT, to assess the possibility of using pooled samples and to give recommendations regarding serological monitoring of BVD-free herds in the context of the Belgian national BVD eradication program which started early 2015. Depending on the assays, for ELISAs on serum, the diagnostic sensitivity (DSe) was estimated to be between 93.0 and 98.7% and the diagnostic specificity (DSp) between 94.3% and 99.1%. For the two ELISAs on milk, the DSe were 91.3% and 96.7% and the DSp 94.0% and 100% respectively and the Cohen’s agreement coefficients between serum and milk samples were 0.75 and 0.85. Positive serum and milk samples diluted in negative samples to mimic different pool sizes were not detected by all ELISAs at dilutions above 1:5 or 1:10, leading to the conclusion that the testing of pooled samples should be used cautiously for serological monitoring and only with ELISAs with high sensitivity. The epidemiological analysis and the seroprevalence study, based on a general estimating equation model, showed that several factors had a significant influence on overall animal seroprevalence and within-herd seroprevalence such as age class, herd size, BVD herd infection status, BVD vaccination of young and/or adult cattle and the number of stables in the farm. This study showed that the best performances obtained with commercial Ab ELISAs are observed on individual serum samples, which should therefore be the preferred matrix to monitor BVD-free herds in the context of the Belgian eradication program. By regularly testing a limited number of samples from young (6–18 months) unvaccinated cattle it is possible to confirm the BVD-free herd status or to detect a recent infection.
Bovine viral diarrhea virus (BVDV) is a single stranded RNA virus in the family Flaviviridae that causes a form of persistent infection. If a fetus is infected in utero during the first 120days of ...gestation the resulting calf will be immunotolerant to the infecting strain and maintain the virus for life. These animals are epidemiologically important in maintaining BVDV on farms, but also present a unique opportunity to study quasispecies in vivo in the absence of significant selection by the host adaptive immune response. We used deep sequencing and novel analytical methods to characterize the viral populations within the mesenteric lymph nodes of 10 persistently infected animals. Our results indicate that the pattern of variability across the viral genome from animal to animal is very consistent within BVDV subgenotypes. However, the individual mutations that constitute this variation are not necessarily the same in each animal. Even in the absence of significant immune selection the structural genes of BVDV vary more extensively than the non-structural genes. These findings could be useful for future vaccine design against BVDV as well as for measuring and understanding patterns of variation in other ssRNA viruses, especially those that belong to the family Flaviviridae.
•BVDV is a rapidly evolving, ssRNA virus.•Persistently infected hosts harbor large numbers of viral variants.•Structural genes in the viral genome are more variable than non-structural ones.•Conserved sites in the viral genome present promising, novel vaccine targets.•These methods are applicable to other rapidly evolving viruses.
Infection of bulls with bovine viral diarrhoea virus (BVDV) can result in the development of virus persistence, confined to the reproductive tract. These bulls develop a normal immune response with ...high neutralizing antibody titres. However, BVDV can be excreted in the semen for a prolonged period. Although relatively rare, in this study we describe six separate cases in bulls being prepared for admission to artificial breeding centres. Semen samples were tested in a pan-Pestivirus-reactive real-time PCR assay and viral RNA was detected in semen from five of the bulls for three to eight months after infection. In one bull, virus was detected at low levels for more than five years. This bull was found to have one small testis. When slaughtered, virus was only detected in the abnormal testis. The low levels of BVDV in the semen of these bulls were only intermittently detected by virus isolation in cell culture. This virus-contaminated semen presents a biosecurity risk and confirms the need to screen all batches of semen from bulls that have been previously infected with BVDV. The use of real-time PCR is recommended as the preferred laboratory assay for this purpose.
Bovine viral diarrhea virus (BVDV) is endemic in many parts of the world, and multiple countries have implemented surveillance activities for disease control or eradication. In such control programs, ...the disease-free status can be compromised by factors that pose risks for introduction or persistence of the virus. The aim of the present study was to gain a comprehensive overview of possible risk factors for BVDV infection in cattle herds in Europe and to assess their importance. Papers that considered risk factors for BVDV infection in cattle were identified through a systematic search. Further selection of papers eligible for quantitative analysis was performed using a predefined checklist, including (1) appropriate region (i.e., studies performed in Europe), (2) representativeness of the study population, (3) quality of statistical analysis, and (4) availability of sufficient quantitative data. In total, 18 observational studies were selected. Data were analyzed by a random-effects meta-analysis to obtain pooled estimates of the odds of BVDV infection. Meta-analyses were performed on 6 risk factors: herd type, herd size, participation in shows or markets, introduction of cattle, grazing, and contact with other cattle herds on pasture. Significant higher odds were found for dairy herds (odds ratio, OR = 1.63, 95% confidence interval, CI: 1.06–2.50) compared with beef herds, for larger herds (OR = 1.04 for every 10 extra animals in the herd, 95% CI: 1.02–1.06), for herds that participate in shows or markets (OR = 1.45, 95% CI: 1.10–1.91), for herds that introduced cattle into the herd (OR = 1.41, 95% CI: 1.18–1.69), and for herds that share pasture or have direct contact with cattle of other herds at pasture (OR = 1.32, 95% CI: 1.07–1.63). These pooled values must be interpreted with care, as there was a high level of heterogeneity between studies. However, they do give an indication of the importance of the most frequently studied risk factors and can therefore assist in the development, evaluation, and optimization of BVDV control programs.