Linking phenotype to genotype: a study of antibody responses to bovine respiratory virus vaccines in a crossbred cattle population

Vaccination is central to prevention of infectious disease in modern livestock production systems. Accurate assessment of the many factors controlling immune responses to vaccination is crucial to maximising their effectiveness. Identification of the genetic component of those immune responses is a prelude to selection for disease resistance. Assignment of those effects at a molecular level should lead to a more complete understanding of the complex processes underlying immunity. The overall aim of this study was to evaluate the IgG antibody responses induced by vaccination in a juvenile, fully pedigreed bovine population of Holstein-Charolais crossbred animals. Vaccines against bovine respiratory syncytial virus (BRSV), bovine parainfluenza 3 virus (PIV3) and bovine herpesvirus 1 (BHVl) were administered to 463 calves, aged 60 to 167 days old. Antibody responses to field infections against bovine coronavirus (BCV) were also examined. The experimental population comprised second-cross Holstein-Charolais F2, Holstein-backcross and Charolais-backcross animals with a daily-type calf-rearing scheme employed for females and a beef-type calf-rearing method for males. All datasets were extensively investigated using Residual Maximum Likelihood (REML) procedures. Across the population, there was a broad spectrum of antibody responses to vaccination. Mean antibody half-lifes were estimated as -24 days for total BRSV-IgG, -72 days for BRSV-IgG2, -32 days for total PIV3 IgG and -26 days for total BHVl-IgG. Although PIV3 and BHVl are both components of a multivalent intranasal vaccine, the BHVl-IgG response was poor while the PIV3-IgG response was substantial. Sex, year-of-birth, cross-breeding, animal age, and levels of pre existing antibody were significant sources of variation for levels of IgG antibodies against all viruses in this population. Although the effect is confounded by management, female calves had higher levels of BRSV-IgG and PIV3-IgG. Despite year-of-birth effect, including seasonality in climate, environment, wild-type infections and management, it accounted for a lower order of the observed variation than sex. Pre-vaccination, calves from dams with higher percentages of the Holstein breed had higher levels of BRSV-IgG and PIV3-IgG. Dam-age was also positively correlated with pre-vaccination levels of BRSV-IgG, the effect plateauing at about 4 years old. Although calf-age was a significant pre-vaccination determinant, its effect on post-vaccination levels of IgG was much less pronounced. The inhibitory effect of pre-existing BRSV-IgG and PIV3-IgG on vaccine response was analysed using logistic regression and respective relative optical density thresholds of -26% and -35% established. Pre-vaccination IgG above these levels meant a positive antibody response was less likely than a negative one. Pre-vaccination, maternal heritable effects dominated total phenotypic variance but postvaccination, additive heritable effects became more important. Estimates of heritability (+/-se) peaked at 0.29 (+/-0.17) for total BRSV-IgG (Day 35); 0.52 (+/-0.26) for the deviation in BRSV-IgG levels between Day 0 and Day 35; 0.47 (+/-0.28; Day 28) and 0.51 (+/-0.31; Day 42) for total PIV3-IgG in the male and female calves, respectively. Much lower values were recorded for BHVl and BCV IgG responses. All calves underwent genotyping and were mapped for 139 microsatellite markers with an average marker interval of 15. centiMorgans (cM). Interval analysis for quantitative trait loci (QTL) using the above antibody phenotypes revealed a large number of loci (positions in cM) influencing levels of IgG. Quantitative trait loci on BTAl (59 cM), BTA2 (108 cM), BTA7 (29 cM), BTA8 (41 cM), BTAIO (55 cM), BTAl2 (84 cM), BTA24 (44 cM) and BTA28 (2 cM) proved significant for one or more of the BRSV-, PIV3- and BHVl-IgG antibody traits. Although the QTL for antibody phenotype identified here are preliminary, they could plausibly be incorporated into breeding programmes to influence antibody response to vaccination. Further, they could act as a basis for further QTL research in this area leading to precise isolation of the relevant genes involved, to a molecular level. However most of all, these results prove that antibody production in cattle is under quantitative genetic control and this influential element should not be disregarded in the future

Economics of Cattle Production Systems Post CAP Reform.

End of Project ReportThe radical reform of the Common Agricultural Policy (CAP) in the early 1990’s impacted directly and indirectly on most of the farm enterprises in Ireland. The direct focus of the reform was largely confined to the cereal and beef enterprises. The reforms consisted of: • A phased reduction in the institutional support prices for cereals and beef of the order of 30 per cent • A phased switch to a direct payment system of farm income support to compensate for the product price reductions. Most farms in Ireland have a cattle enterprise, either alone or in combination with other land using enterprises. Therefore, the reforms of the CAP affected almost all the farms in the country either directly or indirectly. For cattle farmers, the potential consequencee of these changes could be far reaching in terms of their magnitude and their permeation into the details of the husbandry practices of the production system(s) themselves. These changes clearly impact on the economic efficiency of beef systems without necessarily affecting technical efficiency of the systems. The economic optimum cattle production systems would thus be achieved by using the best mix of feed resource costs, carcass values and direct payments. The purpose of the study was to: • determine the economic impact on the cattle enterprise of the switch to: • lower EU prices for beef • lower EU prices for cereals and as a consequence a lower price for concentrate feeds • the direct payment system of income support • identify the economic optimum cattle production system(s) that would arise from these changes • quantify the sensitivity of the economic optimum system to key policy, economic and technical production variables

A survey of antibodies to pestivirus in sheep in the Republic of Ireland

<p/> <p>Sera from 1,448 adult ewes in 91 flocks, representing all 26 counties in the Republic of Ireland, were examined for pestivirus antibodies using a commercially available ELISA which detected IgG₁antibody to border disease virus. Eighty-one sheep (5.6%) in 42 flocks (46.0%) were antibody-positive. Within infected flocks, the mean seroprevalence level was 11.4% with a range of 6.3% to 30.0%. The highest antibody prevalence was detected in sheep from central lowland counties of Ireland. Comparative neutralisation testing of 42 ELISA-positive sera detected geometric mean antibody titres of 136 to the NADL strain of bovine viral diarrhoea virus (BVDV), 92 to the Moredun strain of border disease virus and 21 to the 137/4 strain of border disease virus. These results suggest that BVDV may be the major ruminant pestivirus infecting sheep in Ireland. Although there are high numbers of infected flocks, many sheep within such flocks remain antibody-negative and are at risk of giving birth to lambs with congenital border disease.</p

The bovine paranasal sinuses: Bacterial flora, epithelial expression of nitric oxide and potential role in the in-herd persistence of respiratory disease pathogens

peer-reviewedThe bovine paranasal sinuses are a group of complex cavernous air-filled spaces, lined by respiratory epithelium, the exact function of which is unclear. While lesions affecting these sinuses are occasionally reported in cattle, their microbial flora has not been defined. Furthermore, given that the various bacterial and viral pathogens causing bovine respiratory disease (BRD) persist within herds, we speculated that the paranasal sinuses may serve as a refuge for such infectious agents. The paranasal sinuses of clinically normal cattle (n = 99) and of cattle submitted for post-mortem examination (PME: n = 34) were examined by microbial culture, PCR and serology to include bacterial and viral pathogens typically associated with BRD: Mycoplasma bovis, Histophilus somni, Mannheimia haemolytica and Pasteurella multocida, bovine respiratory syncytial virus (BRSV) and bovine parainfluenza-3 virus (BPIV-3). Overall, the paranasal sinuses were either predominantly sterile or did not contain detectable microbes (83.5%: 94.9% of clinically normal and 50.0% of cattle submitted for PME). Bacteria, including BRD causing pathogens, were identified in relatively small numbers of cattle (<10%). While serology indicated widespread exposure of both clinically normal and cattle submitted for PME to BPIV-3 and BRSV (seroprevalences of 91.6% and 84.7%, respectively), PCR identified BPIV-3 in only one animal. To further explore these findings we investigated the potential role of the antimicrobial molecule nitric oxide (NO) within paranasal sinus epithelium using immunohistochemistry. Expression of the enzyme responsible for NO synthesis, inducible nitric oxide synthase (iNOS), was detected to varying degrees in 76.5% of a sub-sample of animals suggesting production of this compound plays a similar protective role in the bovine sinus as it does in humans

Risk factors associated with exposure to bovine respiratory disease pathogens during the peri-weaning period in dairy bull calves

peer-reviewedBackground Bovine respiratory disease (BRD) remains among the leading causes of death of cattle internationally. The objective of this study was to identify risk factors associated with exposure to BRD pathogens during the peri-weaning period (day (d)-14 to d 14 relative to weaning at 0) in dairy bull calves using serological responses to these pathogens as surrogate markers of exposure. Clinically normal Holstein-Friesian and Jersey breed bull calves (n = 72) were group housed in 4 pens using a factorial design with calves of different breeds and planes of nutrition in each pen. Intrinsic, management and clinical data were collected during the pre-weaning (d − 56 to d − 14) period. Calves were gradually weaned over 14 days (d − 14 to d 0). Serological analysis for antibodies against key BRD pathogens (BRSV, BPI3V, BHV-1, BHV-4, BCoV, BVDV and H. somni) was undertaken at d − 14 and d 14. Linear regression models (for BVDV, BPI3V, BHV-1, BHV-4, BCoV and H. somni) and a single mixed effect random variable model (for BRSV) were used to identify risk factors for changes in antibody levels to these pathogens. Results BRSV was the only pathogen which demonstrated clustering by pen. Jersey calves experienced significantly lower changes in BVDV S/P than Holstein-Friesian calves. Animals with a high maximum respiratory score (≥8) recorded significant increases in H. somni S/P during the peri-weaning period when compared to those with respiratory scores of ≤3. Haptoglobin levels of between 1.32 and 1.60 mg/ml at d − 14 were significantly associated with decreases in BHV-1 S/N during the peri-weaning period. Higher BVDV S/P ratios at d − 14 were significantly correlated with increased changes in serological responses to BHV-4 over the peri-weaning period. Conclusions Haptoglobin may have potential as a predictor of exposure to BHV-1. BRSV would appear to play a more significant role at the ‘group’ rather than ‘individual animal’ level. The significant associations between the pre-weaning levels of antibodies to certain BRD pathogens and changes in the levels of antibodies to the various pathogens during the peri-weaning period may reflect a cohort of possibly genetically linked ‘better responders’ among the study population

Quantitative Trait Loci Associated with the Immune Response to a Bovine Respiratory Syncytial Virus Vaccine

Infectious disease is an important problem for animal breeders, farmers and governments worldwide. One approach to reducing disease is to breed for resistance. This linkage study used a Charolais-Holstein F2 cattle cross population (n = 501) which was genotyped for 165 microsatellite markers (covering all autosomes) to search for associations with phenotypes for Bovine Respiratory Syncytial Virus (BRSV) specific total-IgG, IgG1 and IgG2 concentrations at several time-points pre- and post-BRSV vaccination. Regions of the bovine genome which influenced the immune response induced by BRSV vaccination were identified, as well as regions associated with the clearance of maternally derived BRSV specific antibodies. Significant positive correlations were detected within traits across time, with negative correlations between the pre- and post-vaccination time points. The whole genome scan identified 27 Quantitative Trait Loci (QTL) on 13 autosomes. Many QTL were associated with the Thymus Helper 1 linked IgG2 response, especially at week 2 following vaccination. However the most significant QTL, which reached 5% genome-wide significance, was on BTA 17 for IgG1, also 2 weeks following vaccination. All animals had declining maternally derived BRSV specific antibodies prior to vaccination and the levels of BRSV specific antibody prior to vaccination were found to be under polygenic control with several QTL detected

Methicillin-resistant Staphylococcus aureus Clones, Western Australia

The emergence of multiple multidrug-resistant Panton-Valentine leukocidin–positive MRSA clones in the community is a major public health concern

Defining Disease Phenotypes in Primary Care Electronic Health Records by a Machine Learning Approach: A Case Study in Identifying Rheumatoid Arthritis.

OBJECTIVES: 1) To use data-driven method to examine clinical codes (risk factors) of a medical condition in primary care electronic health records (EHRs) that can accurately predict a diagnosis of the condition in secondary care EHRs. 2) To develop and validate a disease phenotyping algorithm for rheumatoid arthritis using primary care EHRs. METHODS: This study linked routine primary and secondary care EHRs in Wales, UK. A machine learning based scheme was used to identify patients with rheumatoid arthritis from primary care EHRs via the following steps: i) selection of variables by comparing relative frequencies of Read codes in the primary care dataset associated with disease case compared to non-disease control (disease/non-disease based on the secondary care diagnosis); ii) reduction of predictors/associated variables using a Random Forest method, iii) induction of decision rules from decision tree model. The proposed method was then extensively validated on an independent dataset, and compared for performance with two existing deterministic algorithms for RA which had been developed using expert clinical knowledge. RESULTS: Primary care EHRs were available for 2,238,360 patients over the age of 16 and of these 20,667 were also linked in the secondary care rheumatology clinical system. In the linked dataset, 900 predictors (out of a total of 43,100 variables) in the primary care record were discovered more frequently in those with versus those without RA. These variables were reduced to 37 groups of related clinical codes, which were used to develop a decision tree model. The final algorithm identified 8 predictors related to diagnostic codes for RA, medication codes, such as those for disease modifying anti-rheumatic drugs, and absence of alternative diagnoses such as psoriatic arthritis. The proposed data-driven method performed as well as the expert clinical knowledge based methods. CONCLUSION: Data-driven scheme, such as ensemble machine learning methods, has the potential of identifying the most informative predictors in a cost-effective and rapid way to accurately and reliably classify rheumatoid arthritis or other complex medical conditions in primary care EHRs