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Background: Despite decades of extensive research, bovine respiratory disease (BRD) remains the most devastating disease in beef cattle production. Establishing a clinical diagnosis often relies upon visual detection of non-specific signs, leading to low diagnostic accuracy. Thus, post-weaned beef cattle are often metaphylactically administered antimicrobials at facility arrival, which poses concerns regarding antimicrobial stewardship and resistance. Additionally, there is a lack of high-quality research that addresses the gene-by-environment interactions that underlie why some cattle that develop BRD die while others survive. Therefore, it is necessary to decipher the underlying host genomic factors associated with BRD mortality versus survival to help determine BRD risk and severity. Using transcriptomic analysis of at-arrival whole blood samples from cattle that died of BRD, as compared to those that developed signs of BRD but lived (n = 3 DEAD, n = 3 ALIVE), we identified differentially expressed genes (DEGs) and associated pathways in cattle that died of BRD. Additionally, we evaluated unmapped reads, which are often overlooked within transcriptomic experiments., Results: 69 DEGs (FDR<0.10) were identified between ALIVE and DEAD cohorts. Several DEGs possess immunological and proinflammatory function and associations with TLR4 and IL6. Biological processes, pathways, and disease phenotype associations related to type-I interferon production and antiviral defense were enriched in DEAD cattle at arrival. Unmapped reads aligned primarily to various ungulate assemblies, but failed to align to viral assemblies., Conclusion: This study further revealed increased proinflammatory immunological mechanisms in cattle that develop BRD. DEGs upregulated in DEAD cattle were predominantly involved in innate immune pathways typically associated with antiviral defense, although no viral genes were identified within unmapped reads. Our findings provide genomic targets for further analysis in cattle at highest risk of BRD, suggesting that mechanisms related to type I interferons and antiviral defense may be indicative of viral respiratory disease at arrival and contribute to eventual BRD mortality., Competing Interests: The authors have declared that no competing interests exist.

In cattle treated for respiratory disease, resolution of clinical signs has been the mainstay of determining treatment response and treatment efficacy. Through the use of calf lung ultrasound, we have found that pneumonia can persist or recur in the face of antibiotic therapy, despite improved clinical signs, leading to greater risk of clinical disease and more antibiotic use in the future. This review will discuss the pros and cons of using clinical signs to define resolution of disease and discuss how to implement lung ultrasound to improve our ability to accurately measure the impact of antibiotic therapy in cattle with respiratory disease.

Bovine respiratory disease (BRD) is one of the most common indications for antimicrobial therapy in beef cattle production and research trials demonstrate that antibiotic therapy greatly improves clinical outcome for BRD. These trials also show that BRD treatment success rates are less than 100% and that there are opportunities to optimize antimicrobial prescribing and improve clinical outcomes if the underlying cause(s) of BRD treatment failures can be identified and addressed. As the etiology of BRD in an individual animal is frequently multi-factorial in nature; it is likely that BRD treatment failures also result from complex interactions between the drug, drug administrator, animal host, pathogens, and the environment. This review will focus specifically on the pharmacological aspects, specifically the interactions between the host and the drug and the drug and the drug administrator, of BRD treatment failures and the actions that veterinary practitioners can take to investigate and mitigate therapeutic failures in future cases.

Bovine respiratory disease (BRD) treatment failure occurs when animals receiving a treatment regimen for BRD fail to directly return to health, resulting in chronic illness and a requirement for repeated treatments, sale for salvage slaughter, euthanasia or death. BRD treatment failure has both direct and indirect impacts. Direct impacts include costs to manage chronically ill animals, including those associated with BRD relapse treatment; reduced returns from animals sent for salvage slaughter, loss of the initial investment to purchase the animal and feed and other accumulated expenses to death, and costs associated with carcass disposal. Indirect impacts include costs of infrastructure requirements, and negative effects on animal welfare and employee morale.

Alternatives to antibiotics for prevention of respiratory tract infections in cattle are urgently needed given the increasing public and regulatory pressure to reduce overall antibiotic usage. Activation of local innate immune defenses in the upper respiratory tract is one strategy to induce non-specific protection against infection with the diverse array of viral and bacterial pathogens associated with bovine respiratory disease complex (BRDC), while avoiding the use of antibiotics. Our prior studies in rodent models demonstrated that intranasal administration of liposome-TLR complexes (LTC) as a non-specific immune stimulant generated high levels of protection against lethal bacterial and viral pathogens. Therefore, we conducted studies to assess LTC induction of local immune responses and protective immunity to BRDC in cattle. In vitro, LTC were shown to activate peripheral blood mononuclear cells in cattle, which was associated with secretion of INFγ and IL-6. Macrophage activation with LTC triggered intracellular killing of Mannheimia hemolytica and several other bacterial pathogens. In studies in cattle, intranasal administration of LTC demonstrated dose-dependent activation of local innate immune responses in the nasopharynx, including recruitment of monocytes and prolonged upregulation (at least 2 weeks) of innate immune cytokine gene expression by nasopharyngeal mucosal cells. In a BRDC challenge study, intranasal administration of LTC prior to pathogen exposure resulted in significant reduction in both clinical signs of infection and disease-associated euthanasia rates. These findings indicate that intranasal administration of a non-specific innate immune stimulant can be an effective method of rapidly generating generalized protection from mixed viral and bacterial respiratory tract infections in cattle., Competing Interests: SD, AC and RH hold stock options and corporate positions at LaPorte Ag Therapeutics, Inc, a Colorado State University-based startup company developing the LTC immunotherapy platform technology. WW, LC and SD are patent holders for the LTC technology. The issued US patent covering this technology is US 10,512, 687, issued Dec 24, 2019. Any commercial affiliation of the above-mentioned authors with LaPorte Ag Therapeutics, Elanco Inc. or Hunter Cattle Co. did not play a role in the study design, data interpretation, or publication decisions. Accordingly, this does not alter our adherence to PLOS ONE policies and sharing data and materials.

Treatment and control of bovine respiratory disease (BRD) is predicated on the use of two categories of antimicrobials, namely bacteriostatic drugs that inhibit bacterial growth and replication (STATIC), and bactericidal drugs that kill bacteria in in vitro culture systems (CIDAL). Recently, we reported that initial BRD treatment with a STATIC antimicrobial followed by retreatment with a CIDAL antimicrobial was associated with a higher frequency of multidrug-resistant bacteria isolated from field cases of BRD submitted to a veterinary diagnostic laboratory. The present study was conducted to test the hypothesis that calves administered the same class of antimicrobial for first and second BRD treatment (i.e., CIDAL-CIDAL or STATIC-STATIC) would have improved health and performance outcomes at the feedlot compared to calves that received a different antimicrobial class for retreatment (i.e., STATIC-CIDAL or CIDAL-STATIC). The association between antimicrobial treatments and health, performance, and carcass quality outcomes were determined by a retrospective analysis of 4,252 BRD treatment records from a commercial feedlot operation collected from 2001 to 2005. Data were compared using generalized linear mixed statistical models that included gender, season, and arrival weight as covariates. The mean (±SE) probability of BRD cases identified as requiring four or more treatments compared to three treatments was greater in calves that received STATIC-CIDAL (73.58 ± 2.38%) or STATIC-STATIC (71.32 ± 2.52%) first and second antimicrobial treatments compared to calves receiving CIDAL-CIDAL (50.35 ± 3.46%) first and second treatments (P < 0.001). Calves receiving CIDAL-CIDAL first and second treatments also had an increased average daily gain (1.11 ± 0.03 kg/d) compared to calves receiving STATIC-CIDAL (0.95 ± 0.03 kg/d) and STATIC-STATIC (0.84 ± 0.02 kg/d) treatments (P < 0.001). Furthermore, CIDAL-CIDAL-treated calves had a higher probability of a choice quality grade at slaughter (36.44 ± 4.80%) compared to STATIC-CIDAL calves (28.09 ± 3.88%) (P = 0.037). There was no effect of antimicrobial treatment combination on BRD mortality (P = 0.855) or yield grade (P = 0.240) outcomes. These observations suggest that consideration should be given to antimicrobial pharmacodynamics when selecting drugs for retreatment of BRD. These findings have implications for developing BRD treatment protocols that address both post-treatment production and antimicrobial stewardship concerns., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Mortality in preweaned dairy calves is a significant source of economic loss for dairy producers. In particular, bovine respiratory disease (BRD) is a leading cause of death in preweaned dairy calves. The objectives of this study were to investigate management practices and their effects on mortality, both that specifically attributed to BRD and overall mortality due to all causes, in preweaned dairy calves. Rates of failure of passive transfer of immunity (FPT) are also reported. The study consisted of a convenience sample of 5 dairies across California, selected based on management practices, calf records, location, and size. Trained study personnel performed comprehensive calf management surveys on every dairy at least once every season. Calves were enrolled in the study at birth and followed until weaning. Mixed-effect logistic regression models were specified for the outcomes all-cause mortality (any death before weaning) and mortality attributed to BRD. The 2 final models included a total of 11,470 calves that were born on the study dairies and followed until weaning. The study cohort's overall crude mortality was 2.8%, with crude mortality of individual dairies ranging from 1.7 to 7.2%. The proportion of mortality attributed to BRD was 19.3%, with a range of 0 to 27.1% on the study dairies. Increasing the frequency of changing maternity pen bedding was associated with a decreased risk of mortality due to BRD. Calves diagnosed with BRD in the spring had an increased risk of mortality compared with calves born in the summer; mortality in calves with fall and winter BRD diagnoses did not different significantly from that in summer. Season of mortality was not significant in either model. Feeding ≥5.7 L of milk per day per calf (vs. ≤3.7 L/d) decreased the risk of mortality in calves over 21 d of age. Twins had a 68% increased risk of all-cause mortality compared with calves born as singletons. Both mortality models showed an association between administration of a modified live vaccine in dams (targeting BRD pathogens) and a decreased risk of mortality in calves. Using a serum total protein cut-off of 5.2 g/dL, 16.8% of calves had FPT, with a mean serum total protein concentration of 5.94 ± 0.06 g/dL across all calves sampled., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

This retrospective analysis aimed to determine the effects of a maternal viral vaccination program (MVVP; Express Verified) on calf health during the feeding period. In low- and high-risk populations, calves born to dams vaccinated pre-breeding with program products had improved morbidity and mortality outcomes compared with non-program animals.

A distinct difference between veterinary and human medicine is the routine use of antimicrobial mass medications (prophylaxis, metaphylaxis) to healthy individuals. The need for antimicrobial mass medications is based on beliefs that group/s of animals will contract a bacterial disease (i.e. morbidity) and/or die (i.e. mortality). Bovine respiratory disease (BRD) represents the major indication for cattle antimicrobials worldwide. The objectives were to perform a systematic review and meta-analysis of randomised controlled clinical trials (RCTs) for naturally occurring BRD investigating antimicrobial prophylaxis/metaphylaxis to prevent morbidity/mortality. In total, 58 publications met the inclusion criteria summarizing 169 individual RCTs, spanning 50 years (1966-2016). Antimicrobial prophylaxis and metaphylaxis demonstrated moderate, yet highly variable relative risk reductions in BRD morbidity. These were dependent on the antimicrobial classes used, dependent on metaphylaxis definition, BRD attack rates and duration of the RCTs. Best relative risk reductions were from broad-spectrum critically important antimicrobials, or combinations. BRD prophylaxis/metaphylaxis represents major antimicrobial consumption for highly variable short-term gains in absolute risk reduction of morbidity/mortality. Despite widespread use of prevention products, the need for antimicrobial mass medications should be re-evaluated since the underlying problem is more likely the segmented infrastructure of the feedlot and veal calf industries compared to the disease itself., (© FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Undifferentiated fever, or bovine respiratory disease complex (BRDc), is a challenging multi-factorial health issue caused by viral/bacterial pathogens and stressors linked to the transport and mixing of cattle, negatively impacting the cattle feedlot industry. Common practice during processing at feedlots is administration of antibiotic metaphylaxis to reduce the incidence of BRDc. Nitric oxide (NO) is a naturally occurring nano-molecule with a wide range of physiological attributes. This study evaluated the metaphylactic use of intranasal NO releasing spray (NORS) to control BRDc incidence in calves at low-moderate risk of developing BRDc, arriving at a commercial feedlot as compared to conventional antibiotic metaphylaxis. One thousand and eighty crossbred, multiple-sourced, commingled, commercial, weaned beef calves were screened, enrolled, randomized and treated upon arrival. Animals appearing sick were pulled (from their pen) by blinded pen keepers then assessed for BRDc symptoms; blood samples were taken for haptoglobin quantification and the animals were rescued with an antibiotic. After 35 days both groups showed no significant difference in BRDc incidence (5.2% of animals from NORS group and 3.2% from antibiotic group). Average daily weight gain of animals at day 150 for the NORS cohort was 1.17kg compared to 1.18kg for the antibiotic group (p>0.05). There was no significant difference in mortality in the first 35 days (p=0.7552), however, general mortality over 150 days trended higher in the antibiotic cohort. NORS treatment was shown to be safe, causing neither distress nor adverse effects on the animals. This large randomized controlled study in low-moderate BRDc incidence risk calves demonstrates that NORS treatment, as compared to conventional metaphylactic antibiotics, is non-inferior based on BRDc incidence and other metrics like weight and mortality. These data justify further studies in higher BRDc incidence risk populations to evaluate NORS as an alternative strategy to reduce sub-therapeutic metaphylaxis antibiotic use in beef cattle production., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Twelve screened cases of bovine respiratory disease (BRD) in calves were enrolled. Six of the calves were treated intramuscularly with sodium ceftiofur (1 mg/kg), and six were treated with nebulised sodium ceftiofur (1 mg/kg). Comparative evaluation of the two therapeutic modalities was based on repetitive analysis of hematological profile of calves on days 0, 5, and 10 post-therapy. The mortality rate in the group of calves treated with the nebulised sodium ceftiofur was significantly (p < 0.001) lower, and their clinical and hematological parameters returned to normal significantly (p < 0.001) faster than in calves treated intramuscularly. Nebulisation of sodium ceftiofur is the most effective treatment in calves with BRD under field conditions. Nasal lavage fluid analysis indicating a high rise of neutrophil count and macrophages may be used as an alternative method to detect pulmonary inflammation in BRD-affected calves.

Bovine respiratory disease (BRD) is a multifactorial disease and the primary cause of both bovine morbidity and mortality in Ireland. The risk factors associated with a primary necropsy diagnosis of BRD among cattle in the traditional (non-feedlot) husbandry systems prevalent in Ireland have not been investigated previously. The aim of this case-control study was to investigate those risk factors among cattle of all ages over an 8 year period. A total of 3,090 BRD cases and 5,236 controls were matched by submitting veterinary practitioner. Univariable and multivariable analyses were performed to examine the association of selected animallevel, herd-level and environmental risk factors with case or control status using a conditional logistical regression model. Male cattle aged more than 31 days were significantly more likely to record a primary necropsy diagnosis of BRD than female cattle. Older cattle of both sexes were at increased odds of a BRD necropsy diagnosis than younger calves with the exception of female cattle aged greater than 165 days. The risk of a primary necropsy diagnosis of BRD increased with increasing herd size and decreased with increasing time in days since the last animal movement into the submitting herd. There were significantly reduced odds of a primary necropsy diagnosis of BRD in the summer (June to August) when compared with the autumn (September to November). These findings identify significant risk factors for a necropsy diagnosis of BRD under non-feedlot-type husbandry conditions., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A large proportion of newly arrived feedlot cattle are affected with bovine respiratory disease (BRD). Economic losses could be reduced by accurate, early detection. This review evaluates the available literature regarding BRD confirmatory diagnostic tests, early detection methods, and modalities to estimate post-therapeutic prognosis or predict unfavorable or fatal outcomes. Scientific evidence promotes the use of haptoglobin to confirm BRD status. Feeding behavior, infrared thermography, and reticulorumen boluses are promising methods. Retrospective analyses of routinely collected treatment and cohort data can be used to identify cattle at risk of unfavorable outcome. Other methods have been reviewed but require further study., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Bovine respiratory disease (BRD) is a worldwide health concern and is the number one disease of stocker, backgrounder, and feedlot cattle in North America. In feedlots in the USA, BRD accounts for 70-80% of all feedlot morbidity and 40-50% of all mortality. In 2011, the US Department of Agriculture's National Animal Health Monitoring System conducted a feedlot study that showed 16.2% of all feedlot cattle were treated for BRD. It is universally accepted that this number is distressingly high and that our industry has the tools available to reduce the incidence of BRD.

Mortality during the finishing phase in beef steers has increased over the last 13 years at a rate of 0.05% per year for cattle fed in Cactus Feeders' operations. A change in the demographics of placements has also occurred, in that heavier weight cattle are being placed as compared to previous years. Morbidity rates are lower, but higher case fatality rates are observed when compared to years when lighter weight cattle were placed. More lung lesions of varying degree are documented at necropsy of new arrivals and there is greater perception of reduced response to therapy in animals identified with respiratory disease. As placement weights have increased, mortality in the early stages of the feeding period has decreased, resulting in a greater proportion of total death loss later in the period. This shift, in conjunction with an increasing long-term trend of total death loss, can lead to the interpretation of higher 'late day mortality'. Rather than relying solely on observation and distributions of the data, Cactus Feeders believes that the development of a predictive model is better suited to address the potential of 'late day mortality' in confined cattle feeding operations.

The objective of the present study was to investigate health and survival in heifer calves, from 16 farms in southwestern Ontario. Research technicians visited the farms on a weekly schedule for 16 mo, starting in January 2008, and collected blood samples and various measurements to determine the overall health status of the calves. Data of 1,588 Holstein heifer calves from birth until 90 to 120 d of age were analyzed. Initially, a survival analysis was carried out to determine which factors surrounding birth increased a calf's risk of mortality. The factors examined were type of birth, calving ease, season of birth, serum total protein, weight during first week of life, treatment status during first week of life, total number of treatments, and bovine respiratory disease status. In general, calves born in fall (October-December), low serum total protein, low weight, and calves treated for illness during the first week of life, increasing number of treatments, and being treated for bovine respiratory disease all increased a calf's risk of mortality. Genetic parameters for requiring treatment for illness, survival, bovine respiratory disease, other diseases, height, and weight were estimated. Heritabilities for treatment, survival, and diseases were low, ranging from 0.04 to 0.07, and were not significant. Moderate and significant heritabilities were found for height (0.33 to 0.45) and weight (0.24 to 0.44). Treatment and survival to 90 to 120 d of age were favorably correlated, indicating that calves requiring less treatment have a higher survival rate and vice versa. Further, body weight was found to have a tendency of favorable genetic correlation (-0.22 to -0.53) with treatment for diseases, indicating that calves with higher body weight in their first month of life were genetically more resistant to diseases than those with average body weight. Overall, our results show the potential of using data on calfhood disease and survival in future dairy cattle breeding programs. Further investigation and improved data collection are required to determine the full impact of genetics on health and survival in dairy heifer calves., (Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Although bovine respiratory disease complex (BRDC) is common in post-weaning cattle, BRDC prediction models are seldom analyzed. The objectives of this study were to assess the ability to predict cumulative cohort-level BRDC morbidity using on-arrival risk factors and to evaluate whether or not adding BRDC risk classification and daily BRDC morbidity and mortality data to the models enhanced their predictive ability. Retrospective cohort-level and individual animal health data were used to create mixed negative binomial regression (MNBR) models for predicting cumulative risk of BRDC morbidity. Logistic regression models were used to illustrate that the percentage of correctly (within |5%| of actual) classified cohorts increased across days, but the effect of day was modified by arrival weight, arrival month, and feedlot. Cattle arriving in April had the highest (77%) number of lots correctly classified at arrival and cattle arriving in December had the lowest (28%). Classification accuracy at arrival varied according to initial weight, ranging from 17% (< 182 kg) to 91% (> 409 kg). Predictive accuracy of the models improved from 64% at arrival to 74% at 8 days on feed (DOF) when risk code was known compared to 56% accuracy at arrival and 69% at 8 DOF when risk classification was not known. The results of this study demonstrate how the predictive ability of models can be improved by utilizing more refined data on the prior history of cohorts, thus making these models more useful to operators of commercial feedlots.

Bovine respiratory disease (BRD) is one of the most common infectious causes of morbidity and mortality in young dairy cattle. The objective of this randomized clinical trial was to determine the effectiveness of 1 or 2 doses of a 5-way, modified-live viral vaccine, administered to heifer calves before weaning to aid in the prevention of BRD. The hypotheses were that vaccination would reduce the incidence of BRD and mortality, and that 2 doses would be more effective than 1. A total of 2,874 heifer calves from 19 commercial dairy farms in Minnesota and Ontario were enrolled at 1 to 7d of age and were followed until 3 mo of age. Calves were randomly assigned to receive a commercial, intramuscular, modified-live vaccine against bovine viral diarrhea virus types 1 and 2, bovine respiratory syncytial virus, bovine herpesvirus type 1, and parainfluenza virus type 3 at 15 to 21 d of age (2 wk only), 35 to 42 d (5 wk only), both 2 and 5 wk, or sterile saline at both times (unvaccinated controls). The incidence of failure of passive transfer was 11 or 32%, using cut-points of serum total protein of 5.2 and 5.7 g/dL, respectively. Overall, 22% of calves were treated at least once for BRD. The incidence risk of naturally occurring BRD was 7.7% before 2 wk of age, 8.0% between 2 and 5 wk, and 9.5% between 5 wk and 3 mo of age, and was not different between vaccination groups. Overall mortality throughout the 3-mo study period was 3.5%. Mortality was 1.6% before 2 wk of age, 0.5% between 2 and 5 wk, and 1.2% between 5 wk and 3 mo of age. The risk of mortality was not affected by vaccination. Mean average daily gain of 1.07 kg/d from 5 wk to 3 mo of age was not different between vaccine groups. In this population of commercial, home-raised calves, with an overall low incidence of failure of passive transfer, intramuscular vaccination with a multivalent, modified live viral vaccine at 2 or 5 wk of age or both was not associated with a decreased risk of BRD or mortality, or with growth until 3 mo of age. Reasons for these findings may include interference by maternal antibodies, unresponsiveness of the neonatal immune system, timing of immunity relative to pathogen exposure, disease caused by pathogens other than the viruses in the vaccine, or herd immunity. However, in populations with higher incidence of failure of passive transfer or risk of BRD, calves with low levels of specific antibodies may respond differently to vaccination., (Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Bovine respiratory disease complex (BRD) is a common disease in weaned dairy calves that incurs economic and welfare costs. This study was an extension of a randomized clinical trial in which a single injection of tulathromycin (TUL) or oxytetracycline (TET) was administered at first movement to group housing for the prevention of BRD in the 60 d following antimicrobial treatment (BRD60). Calves treated with TUL were 0.5 times [95% confidence interval (CI): 0.4 to 0.7] as likely to be treated for BRD60 as calves treated with TET. The objectives of the current study were to evaluate the long-term effects of BRD and antibiotic treatment on growth of heifers until breeding age, age at first calving, incidence of dystocia, milk production, and mortality before first calving and mortality before 120 d in milk. At entry to the breeding barn (382 d of age), calves that experienced BRD60 weighed 16.0±2.3 kg less than calves that did not. Survival to first calving was recorded for 98% (1,343/1,392) of the heifers on this trial. For TET and TUL heifers with BRD60, 63% (94/150) and 73% (64/88) survived to first lactation, respectively. For TET and TUL calves without BRD60, 84% (436/517) and 84% (494/588) survived to first lactation, respectively. The median age at first calving for heifers with and without BRD60 was 714 (95% CI: 705-723) and 702 (95% CI: 699-705) days, respectively. Heifers with BRD60 were 1.5 (95% CI: 1.1-2.2) times more likely to have a calving ease score ≥2 at their first calving compared with heifers without BRD60. The administration of TUL at movement to group housing may have a role in the prevention of BRD and in mitigating some of the long-term effects of this disease., (Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Most beef cattle are transported at least once during their lives, and this potentially stressful practice may affect subsequent health and performance. Limited research is available quantifying the effects of transport on feedlot performance and health, and particularly the risk of bovine respiratory disease complex (BRD), which is the most common disease of weaned calves after arrival to the feedlot. The objective of this retrospective study was to determine potential associations between distance traveled (DTV) during transportation with health (cumulative BRD morbidity and mortality of all causes) and performance (ADG and HCW) parameters in cattle cohorts (n = 14,601) that arrived to 21 U.S. commercial feedlots from 1997 to 2009. Multivariable mixed-effects negative binomial and linear regression models were employed to determine associations between health and performance outcomes with DTV and other cohort-level demographic variables. Cattle were transported a median of 552 km from origin to feedlot with a mean (± SEM) of 698 ± 4.4 km. The mean (±SEM) cumulative BRD morbidity was 4.9% ± 0.01% (median = 1.1%; range: 0 to 100%) whereas the mean (±SEM) cumulative mortality due to all causes was 1.3% ± 0.01% (median = 0.8%; range: 0 to 28.7%). Distance traveled was significantly associated (P < 0.05) with BRD morbidity, overall mortality, HCW and ADG, and its effects were modified by demographic characteristics (i.e., cohort region of origin, mean arrival BW, gender, and the season of the year) of the cohort. Knowledge of the distance traveled during transportation could allow a more precise prediction of cattle feedlot health and performance.

Objective: To evaluate serum haptoglobin concentration at feedlot arrival and subsequent performance and morbidity and mortality rates of calves that developed bovine respiratory disease., Animals: 360 heifer calves and 416 steer and bull calves., Procedures: Serum samples were obtained from cattle at the time of arrival to a feedlot (day -1) and analyzed for haptoglobin concentration. In experiment 1, calves were classified into groups with a low (< 1.0 μg/mL), medium (1.0 to 3.0 μg/mL), or high (> 3.0 μg/mL) serum haptoglobin concentration and allotted into pens on the basis of group. In experiment 2, calves were classified as having or not having detectable serum haptoglobin concentrations., Results: In experiment 1, average daily gain from days 1 to 7 decreased as haptoglobin concentration increased. Dry-matter intake (DMI) from days 1 to 21 decreased with increasing haptoglobin concentration, and DMI typically decreased from days 1 to 63. Total bovine respiratory disease morbidity rate typically increased with increasing haptoglobin concentration. At harvest, no differences in carcass characteristics were observed on the basis of haptoglobin concentration. In experiment 2, cattle with measureable serum haptoglobin concentrations at arrival weighed less throughout the experiment, gained less from days 1 to 7, and had lower DMI from days 1 to 42. Overall morbidity rate was not different between groups, but cattle with detectable serum haptoglobin concentrations had higher odds of being treated 3 times., Conclusions and Clinical Relevance: Serum haptoglobin concentration in cattle at the time of feedlot arrival was not associated with overall performance but may have limited merit for making decisions regarding targeted prophylactic treatment.

Bovine respiratory disease complex (BRDC), the most common cause of post-weaning disease in North American beef cattle, is a multifaceted process involving pathogen, host, environment, and management factors. Although the importance of describing and evaluating the timing of BRDC cases has been recognized, a formal analysis of the temporal patterns of BRDC has not been described in the literature. Our objectives were to classify within-cohort temporal patterns of BRDC cases during the first 100 days at risk, using operational data from commercial feedlots, and then to evaluate associations among temporal patterns and common cohort-level measures of feedlot performance and health, while controlling for common potential confounders. We used retrospective cohort-level and individual animal health data (2000-2008) from 10 U.S. feedlots. We defined cumulative distributions representing the timing of cases within cohorts using the daily percentage of cases relative to the total number of cases within a cohort. Ward's hierarchical clustering method was used to group cohorts exhibiting similar cumulative distributions of BRDC cases. Linear mixed models and generalized estimating equations then were used to determine associations between temporal patterns and economically important measures of cattle performance (mean daily weight gain, total days on feed, and carcass measures) and health (mortality risk and retreatment risk) outcomes, while accounting for possible confounding variables (gender, arrival month, arrival year, arrival weight, arrival risk classification, cumulative morbidity, and the feedlot itself). Cluster analysis identified seven different cohort-level temporal patterns of BRDC cases. Our independent variable of interest (temporal pattern) was associated with mean daily weight gain, total days on feed, and carcass weight, and the estimated effects were modified by arrival weight category and risk classification. Temporal patterns also were associated with USDA measures of carcass yield and quality that largely affect carcass price. We also found associations among temporal patterns and health outcomes (cumulative mortality and retreatment risk), and these effects were significantly modified by arrival weight and cumulative morbidity. Our results are the first to demonstrate that there are several temporal patterns of BRDC repeatedly observed among cohorts of feedlot cattle, and that these BRDC patterns may differentially affect cattle health and performance., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Incidence rates for bovine respiratory disease (BRD) in dairy cattle have remained essentially unchanged over the last 20 years. Dairy calves are more commonly affected than adult animals, with BRD being the principal cause of death in weaned dairy calves. The lack of progress in controlling respiratory disease demonstrates that there continues to be significant room for improvement in controlling this multifactorial syndrome, and that dairy producers need assistance in applying evolving husbandry practices to improve the health of dairy cattle. Therefore, it seems prudent to focus the management strategies on preventing disease through sound management of the transition period, along with sound vaccination and biosecurity programs., (Copyright 2010 Elsevier Inc. All rights reserved.)

This study charted 237 fatal cases of bovine respiratory disease (BRD) observed from May 2002 to May 2003 in a single Oklahoma feed yard. Postmortem lung samples were used for agent identification and histopathology. Late in the study, 94 skin samples (ear notches) were tested for Bovine viral diarrhea virus (BVDV) by immunohistochemistry (IHC). Bovine respiratory disease morbidity was 14.7%, and the mortality rate of all causes was 1.3%, with more than half (53.8%) attributed to BRD (0.7% total of all causes). The agents isolated were the following: Mannheimia haemolytica (25.0%), Pasteurella multocida (24.5%), Histophilus somni (10.0%), Arcanobacterium pyogenes (35.0%), Salmonella spp. (0.5%), and Mycoplasma spp. (71.4%). Viruses recovered by cell culture were BVDV-1a noncytopathic (NCP; 2.7%), BVDV-1a cytopathic (CP) vaccine strain (1.8%), BVDV-1b NCP (2.7%), BVDV-2a NCP (3.2%), BVDV-2b CP (0.5%), and Bovine herpesvirus 1 (2.3%). Gel-based polymerase chain reaction (PCR) assays were 4.6% positive for Bovine respiratory syncytial virus and 10.8% positive for Bovine coronavirus. Bovine viral diarrhea virus IHC testing was positive in 5.3% of the animals. The mean values were determined for the treatment data: fatal disease onset (32.65 days), treatment interval (29.15 days), number of antibiotic treatments (2.65), number of different antibiotics (1.89), and day of death (61.81 days). Lesions included the following: 1) duration: acute (21%), subacute (15%), chronic (40.2%), healing (2.8%), normal (18.1%), and autolyzed (2.8%); 2) type of pneumonia: lobar bronchopneumonia (LBP; 27.1%), LBP with pleuritis (49.1%), interstitial pneumonia (5.1%), bronchointerstitial pneumonia (1.4%), septic (0.9%), embolic foci (0.5%), other (2.8%), normal (10.3%), and autolyzed (2.8%); and 3) bronchiolar lesions: bronchiolitis obliterans (39.7%), bronchiolar necrosis (26.6%), bronchiolitis obliterans/bronchiolar necrosis (1.4%), other bronchiolar lesions (6.5%), and bronchiolar lesion negative (25.7%). Statistically significant relationships were present among the agents, lesions, and the animal treatment, disease onset, and mortality data. Clinical illnesses observed in this study were lengthier than those reported 16-20 years ago, based on fatal disease onset, treatment interval, and day of death.

The purpose of this study was to compare the efficacy and cost-effectiveness of florfenicol versus tulathromycin for initial treatment of undifferentiated fever in fall-placed steer calves that received metaphylactic tilmicosin on arrival at the feedlot. No significant differences (P > .10) were observed in undifferentiated fever relapses or the crude case fatality rate. Calves treated with florfenicol had a lower case fatality rate (P = .04) for bovine respiratory disease and Histophilus disease than did calves treated with tulathromycin. The net economic advantage of florfenicol over tulathromycin (Can$17.70/treated animal) was based on differences in costs for the trial drug and calf replacement owing to bovine respiratory disease and Histophilus disease case fatality.

The purpose of this study was to compare the efficacy and cost-effectiveness of tilmicosin (MIC) versus tulathromycin (DRAX) as a metaphylactic antimicrobial in feedlot calves at moderate risk for bovine respiratory disease (BRD). Calves that received DRAX had significantly (P < or = .05) lower initial BRD treatment rates compared with calves that received MIC. However, there were no significant differences in the BRD relapse rate, railer rate, total mortality rate, BRD mortality rate, average daily gain, and dry matter conversion between the two groups. The economic advantage of the MIC group was Can$8.29/animal. Based on these results, while DRAX was more efficacious in reducing initial treatments for BRD in feedlot calves at moderate risk for disease, MIC was more cost-effective. The lower initial BRD treatment costs in the DRAX group did not offset the higher metaphylactic cost of DRAX.

Two experiments were conducted at the Kansas State University Beef Cattle Research Center to determine the effects of feeding ground flaxseed (flax) during the receiving period on the growth, health, and subsequent finishing performance of heifers. Crossbred heifers (Exp. 1: n = 363, 214 +/- 1 kg of initial BW; Exp. 2: n = 377, 222 +/- 1 kg of initial BW) were purchased during January and April of 2006. Heifers were fed receiving rations based on steam-flaked corn with 0, 2, 4, or 6% ground flax (DM basis) for 56 d. Following the receiving period, cattle in Exp. 1 and 2 were fed steam-flaked corn-based diets for 150 and 147 d, respectively, and then slaughtered. Heifers were implanted 91 and 109 d before slaughter for Exp. 1 and 2, respectively. In Exp. 1, DMI during the receiving period tended to increase linearly (P = 0.09) with increasing flax in the diet. Average daily gain was 1.46, 1.56, 1.58, and 1.61 kg for heifers fed 0, 2, 4, and 6% flax, respectively (linear, P = 0.03). Final BW in Exp. 1 after the finishing period was increased (linear, P = 0.04) with increasing inclusion of flax in the receiving diets. In Exp. 2, growth performance and mortality during the receiving period were not different among treatments (P > 0.12). During the receiving period in Exp. 2, incidence of the first respiratory treatment tended to be greatest (P = 0.09) for heifers fed 4% flax. During the finishing period, DMI were 8.4, 8.4, 8.0, and 8.1 kg/d for 0, 2, 4, and 6% flax, respectively (linear, P = 0.05). In Exp. 2, LM areas were greatest (quadratic, P = 0.04) for cattle fed 2% flax at receiving. In general, feeding flax during the receiving period may have the potential to improve growth performance; however, performance between experiments was variable, and many factors excluding flax feeding may have contributed to this response.

The study objective was to determine health and performance of ranch calves from different preconditioning strategies during a 42-d receiving period when commingled with calves of unknown health histories from multiple sources. Steer calves from a single source ranch (RANCH) were weaned and immediately shipped to a feedlot (WEAN, initial BW = 247 +/- 29 kg); weaned on the ranch for 45 d before shipping, but did not receive any vaccinations (WEAN45, initial BW = 231 +/- 26 kg); or weaned, vaccinated with modified live viral vaccine, and held on the ranch for 45 d before shipping (WEANVAC45, initial BW = 274 +/- 21 kg). Multiple-source steers were purchased through auction markets (MARKET, initial BW = 238 +/- 13 kg), and upon receiving, a portion of ranch-origin steers from each weaning group was commingled with a portion of MARKET cattle (COMM). The experimental design was completely randomized with a 2 x 3 +1 factorial arrangement of treatments. Factors were RANCH vs. COMM and weaning management (WEAN vs. WEAN45 vs. WEANVAC45) as the factors; MARKET cattle served as the control. Calves of WEAN, WEAN45, and MARKET were vaccinated on arrival at the feedlot. Ranch-origin calves tended (P = 0.06) to have greater ADG than COMM or MARKET calves, although ADG was not affected (P = 0.46) by weaning management. Across the 42-d receiving period, DMI was not affected (P = 0.85) by cattle origin. However, MARKET, WEAN45, and WEANVAC45 calves consumed more (P < 0.001) DM than WEAN calves. Gain efficiency was not affected (P > or = 0.11) by treatment. Ranch-origin calves were less (P < 0.001) likely to be treated for bovine respiratory disease than MARKET calves; COMM calves were intermediate. Calves that were retained on the ranch after weaning (WEAN45 and WEANVAC45) were also less likely to be treated (P = 0.001) than MARKET or WEAN calves. As expected, differences in morbidity related to differences in health costs. Calves of WEAN45 and WEANVAC45 had less (P < 0.001) health costs than MARKET and WEAN calves. On arrival, serum haptoglobin concentrations were greater (P < 0.001) in MARKET and WEAN compared with WEAN45 and WEANVAC45 calves. Calves from a single source that are retained on the ranch for 45 d after weaning exhibit less morbidity and less health costs during the receiving period at the feedyard than when cattle are commingled or trucked to the feedyard immediately after weaning.

The purpose of this study was to compare the relative cost-effectiveness of florfenicol with that of tulathromycin for treatment of undifferentiated fever (UF) in feedlot calves at ultra-high risk of developing UF that receive metaphylactic tulathromycin on arrival at the feedlot. Calves that received therapeutic florfenicol had lower overall mortality (P=.045) and bovine respiratory disease mortality (P=.050) compared with calves that received therapeutic tulathromycin, but no significant differences were detected in feedlot performance, carcass characteristics, or other animal health variables. There was a net advantage of Can$41.19/treated animal in the florfenicol group versus the tulathromycin group. This study demonstrates that it is more cost-effective to use florfenicol than tulathromycin for the initial treatment of UF in feedlot calves at ultra-high risk of developing UF that receive on-arrival metaphylactic tulathromycin.

The aim of this study was to describe the microbiologic agents and pathologic processes in fatal bovine respiratory disease (BRD) of feedlot cattle and to investigate associations between agents and pathologic processes. Ninety feedlot calves diagnosed at necropsy with BRD and 9 control calves without BRD were examined, using immunohistochemical (IHC) staining and histopathologic studies. Mannheimia haemolytica (MH) (peracute, acute, and subacute cases) and Mycoplasma bovis (MB) (subacute, bronchiolar, and chronic cases) were the most common agents identified in fatal BRD cases. Significant associations (P < 0.10) were detected between microbiologic agents and between agents and pathologic processes. When IHC staining was used, 25/26 (96%) of animals that were positive for bovine viral diarrhea virus (BVDV) were also positive for MH; 12/15 (80 %) of animals that were positive for Histophilus somni (HS) were also positive for MB; and all of the animals that were positive for HS were negative for MH and BVDV. This quantitative pathological study demonstrates that several etiologic agents and pathologic processes are involved in fatal BRD of feedlot cattle.

Objective: To examine the effects of injectable vitamins A, D and E at feedlot entry on health and growth rate and the effects of injectable vitamin C at the time of treatment for bovine respiratory disease (BRD) on cattle health., Design: Systematic allocation of 2465 cattle at feedlot entry to: a commercial vitamin A, D and E preparation at the label dose rate; commercial vitamin A, D and E at twice the label dose rate; a formulation with no vitamin D, a lower concentration of vitamin A and a higher concentration of vitamin E; and the oil-based carrier alone at volumes corresponding to the above treatments. Comparisons of growth rate, disease and mortality were made between the groups at the conclusion of the feeding period. In a separate experiment, 176 cattle were alternately administered injectable vitamin C at the time of treatment for BRD, or were not injected with vitamin C, and mortality was compared between the groups., Results: There were no differences between cattle administered vitamin A, D and E at feedlot entry and the controls in growth rate (P=0.11), all diseases (P=0.99), BRD (P=0.60) or mortalities (P=0.95). Cattle treated with the higher vitamin E and lower vitamin A preparation had a higher (P=0.02) incidence of anorexia than the other groups. Fewer cattle treated with 5 g of vitamin C by intramuscular injection at the time of treatment with antibiotics for BRD subsequently died (P=0.04)., Conclusions: The routine injection of cattle with vitamins A, D and E at feedlot entry is unlikely to result in improvements in health and growth rate where cattle are provided with these vitamins in their diets at concentrations equal to the National Research Council recommendations. Mortality rate in cattle diagnosed with BRD may be reduced by intramuscular injection of vitamin C at the time of treatment with antibiotics.

A total of 894 calves at high risk for bovine respiratory disease were processed at two sites and randomly assigned to receive one of three antimicrobial metaphylactic regimens to determine if a two-drug regimen offered any advantage over the more conventional one-course regimens. On arrival, calves received either a two-course regimen of ceftiofur crystalline free acid (CCFA) followed by tulathromycin 8 days later (Group 1) or a one-course regiment of CCFA (Group 2) or tilmicosin (Group 3). At Site A, morbidity was significantly lower (52%) in Group 1 than in Group 2 (76.3%) and Group 3 (78.4%). At Site B, morbidity was significantly lower in Group 1 (2.6%) than in Group 2 (9.4%) and Group 3 (7.2%).

This study determined the prevalence of diseases and pathogens associated with mortality or severe morbidity in 72 Ontario beef feedlots in calves that died or were euthanized within 60 days after arrival. Routine pathologic and microbiologic investigations, as well as immunohistochemical staining for detection of bovine viral diarrhea virus (BVDV) antigen, were performed on 99 calves that died or were euthanized within 60 days after arrival. Major disease conditions identified included fibrinosuppurative bronchopneumonia (49%), caseonecrotic bronchopneumonia or arthritis (or both) caused by Mycoplasma bovis (36%), viral respiratory disease (19%), BVDV-related diseases (21%), Histophilus somni myocarditis (8%), ruminal bloat (2%), and miscellaneous diseases (8%). Viral infections identified were BVDV (35%), bovine respiratory syncytial virus (9%), bovine herpesvirus-1 (6%), parainfluenza-3 virus (3%), and bovine coronavirus (2%). Bacteria isolated from the lungs included M. bovis (82%), Mycoplasma arginini (72%), Ureaplasma diversum (25%), Mannheimia haemolytica (27%), Pasteurella multocida (19%), H. somni (14%), and Arcanobacterium pyogenes (19%). Pneumonia was the most frequent cause of mortality of beef calves during the first 2 months after arrival in feedlots, representing 69% of total deaths. The prevalence of caseonecrotic bronchopneumonia caused by M. bovis was similar to that of fibrinosuppurative bronchopneumonia, and together, these diseases were the most common causes of pneumonia and death. M. bovis pneumonia and polyarthritis has emerged as an important cause of mortality in Ontario beef feedlots.

The objective of this study was to characterize genetic and environmental factors influencing bovine respiratory disease (BRD) in beef cattle. Records from nine purebred and three composite breeds and a variety of F1 and three-way crosses, including the progeny of 12 additional different sire breeds produced over a 20-yr period (1983 to 2002), were evaluated for breed and heterozygosity effects on the observed incidence of BRD. Heterozygosity fractions for calves and dams were defined by generalized breed origins: British, Continental, and tropically adapted. Variance components were estimated for each pure and composite breed, and across all breeds and crossbreeds. The effect of incidence of observed BRD was determined by comparing groups of low and high years of incidence. Respiratory disease in this herd followed a standard epidemiological pattern of initial introduction, reaching an epidemic stage at 70 to 170 d of age, followed by a period of rapid decrease to weaning. Estimates of heritability of incidence of BRD were low, ranging from 0.00 to 0.26, with overall estimates of 0.07 and 0.19 depending on the data set analyzed. The highest incidence of BRD in preweaned calves occurred in the Braunvieh breed (18.8%). The genetic correlation between the direct and maternal genetic effects was generally large and negative, suggesting dams genetically superior for resisting BRD raise calves that are more susceptible. Perhaps maternally superior dams provide passive immunity to their calves, which delays the development of the calves' direct immune system, making them more prone to BRD during the preweaning period. Heterozygosity of calves decreased the incidence of BRD compared with purebred cattle. Calves that were Continental x British or tropically adapted x British breeds had a lower incidence of BRD than did calves of British x British breeds. As the annual incidence of BRD increased, there was an associated increase in the heritability estimate. The estimated heritability based on an underlying continuous scale was large (h2 = 0.48), inferring response to selection for BRD resistance could be large if the phenotype for BRD resistance was known.