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.

Bovine respiratory disease (BRD) is a frequent disease concern in dairy cattle and is most commonly diagnosed in young dairy heifers. The impact of BRD is highly variable, depending on the accuracy and completeness of detection, effectiveness of treatment, and on-farm culling practices. Consequences include decreased rate of weight gain, a higher culling risk either as heifers or as cows, delayed age at first service, delayed age at first calving, and in some cases, lower future milk production. In this data set of 104,100 dairy replacement heifers from across the USA, 36.6% had one or more cases diagnosed within the first 120 days of age with the highest risk of new cases occurring prior to weaning. Comparison of the raising cost for heifers with BRD and those without a recorded history of BRD resulted in an estimated cost per incident case occurring in the first 120 days of age of $252 or $282, depending upon whether anticipated future milk production differences were considered or not. Current market conditions contributed to a cost estimate that is significantly higher than previously published estimates, driven in part by the losses associated with selective culling of a subset of heifers that experienced BRD.

Increased antimicrobial resistance in bovine respiratory bacterial pathogens poses a threat to the effective control and prevention of bovine respiratory disease (BRD). As part of continued efforts to develop antimicrobial alternatives to mitigate BRD, the microbial community residing within the respiratory tract of feedlot cattle has been increasingly studied using next-generation sequencing technologies. The mucosal surfaces of upper and lower respiratory tracts of cattle are colonized by a diverse and dynamic microbiota encompassing commensal, symbiotic, and pathogenic bacteria. While a direct causal relationship between respiratory microbiota and the development of BRD in feedlot cattle has not been fully elucidated, increasing evidence suggests that the microbiota contributes to respiratory health by providing colonization resistance against pathogens and maintaining homeostasis. Certain management practices such as weaning, transportation, feed transition, and antibiotic application can disrupt the respiratory microbiota, potentially altering pathogen colonization. Microbiota-based approaches, including bacterial therapeutics that target restoring the normal respiratory microbiota, may provide new methods for mitigating BRD in feedlot cattle in place of antibiotics. In addition, the distinct bacterial respiratory microbial communities observed in BRD-affected and healthy feedlot cattle may allow for future application of microbiota-based techniques used in the diagnosis of BRD.

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 of considerable economic importance to the dairy industry, specifically among young animals. Several studies have demonstrated that BRD has a significant genetic component, with heritabilities ranging from 0.04 up to 0.22, which could be utilized to select more resistant animals. Taking advantage of available genomic data will allow more accurate genetic predictions to be made earlier in an animal's life. The availability of genomic data does not negate the necessity of quality phenotypes, in this case, records of BRD incidence. Evidence has shown that genetic selection is possible through the use of producer-recorded health information. The national dairy cooperator database currently has minimal records on respiratory problems. There is an existing pipeline for these data to flow from events recorded by producers on the farm to the national database used for genetic evaluation. Additional data could also be collected through the expansion of currently utilized termination codes and used in conjunction with the records of direct health events. Selection for animals with improved BRD resistance is possible at the national level; however, collection of additional phenotypes remains a significant hurdle.

Assessment of behavior is a longstanding strategy to assist the diagnosis of clinical bovine respiratory disease (BRD) in beef cattle. Cattle with systemic inflammation caused by infectious pathogen(s) display predictable behavioral adaptations compared to healthy cohorts. Behavioral alterations in BRD-affected cattle include lethargy, social isolation, and anorexia. However, behavior assessment to support BRD case definition in the production setting is challenging because: (1) other bovine diseases cause behavior alterations similar to BRD; (2) cattle have inherent prey instinct to disguise sickness behavior during human evaluation; (3) labor constraints dictate very brief observation of animal behavior; and (4) traditional behavior assessment is subjective and agreement is often poor. Some of these challenges may be overcome with the use of advanced technologies that allow continuous, remote, and objective behavior assessment of individual cattle. Automated methodologies for behavior assessment include three-axis accelerometers that quantify physical behaviors, systems that document feeding/watering behavior, and triangulation systems that document spatial behavior. Each of these behavior-monitoring approaches generates unique information and may facilitate early detection of BRD compared to traditional methods. Nevertheless, adoption of behavior assessment technologies for BRD diagnosis in beef operations hinges upon improved detection, positive return on investment, and successful integration within existing BRD management practices.

Veterinary diagnostic labs (VDLs) are important service agencies providing essential diagnostic testing for a wide variety of domestic animal species as well as wildlife. They serve key roles in disease monitoring and diagnosis as well as surveillance for diseases of consequence. Of the many roles VDLs serve, one is being a member of the larger team of professionals dealing with the management of the bovine respiratory disease (BRD) complex. VDLs provide a number of services related to the management of BRD. These include disease outbreak investigation, abnormal morbidity characterization, routine monitoring, and biosecurity screening for a variety of infectious agents via methods such as necropsy and histopathology, bacterial culture, antimicrobial sensitivity testing, virus isolation, and serological assays. VDLs continue to look for better methods and assays as instrumentation technology also grows and improves. This is reflected in the growing proliferation of molecular-based assays that provide a high degree of sensitivity and specificity. Professional staff in VDLs work in collaboration with those in academia and private industry to conduct basic research focusing on a different aspect of the BRD complex. VDLs remain a primary source of the varied field-origin infectious agents associated with BRD that are used for research purposes.

Bovine respiratory disease (BRD) is the most common cause of morbidity and mortality in North American beef cattle. In recent years, isolation of strains of Mannheimia haemolytica that are resistant to multiple different classes of antimicrobials has become commonplace. New research would suggest that the routine use of antimicrobials by some cattle operations might be driving emerging resistance patterns, with the majority of the spread observed due to propagation of strains of M. haemolytica that have acquired integrative conjugative elements. To date, there is little information evaluating the impact of antimicrobial resistance on clinical outcome in cattle with BRD.

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.

Weaning of beef calves is a stressful event that negatively impacts health and performance. A variety of interventions have been proposed to reduce stress and improve gains following weaning. This study used 288 7- to 8-month-old calves from two separate locations, to examine four different weaning strategies, as well as the impact of shipment. Calves were blocked by weight and sex, and then randomly assigned to one of four treatments: abrupt weaning (AW), where calves were separated from the dam on day 0 (D0) and allowed no further contact with the dam; fence line (FL), where calves were weaned on D0 but had fence line contact with dams for 7 days; nose flap (NF), where on day -6 calves received a nose flap that interferes with suckling, then had the flap removed and were weaned from the dam on D0; and intermittent separation (SEP), where calves were removed from dams for 24-h intervals on day -13 and day -6, then weaned on D0, but allowed fence line contact with the dam for 7 days. Each treatment group was further divided into two subgroups, one of which was shipped early (D0 for AW, day 7 for others) or shipped later (day 28). Body weight and sickness were recorded for all groups. Results showed a negative impact on gain for early shipping compared to later shipping, and poorer gain in AW calves than most other treatments. Results of the analyses of morbidity were inconclusive. This study found that delayed shipment following FL weaning improves performance under common management conditions for the US cow–calf industry.

The objective of this paper was to perform a critical review of the literature as it pertains to the current status of antimicrobial resistance in pathogens associated with bovine respiratory disease (BRD) in beef cattle and to provide a concise yet informative narrative on the most relevant publications available. As such, the scientific literature contained in PubMed, AGRICOLA, and CAB were searched in February of 2014 for articles related to susceptibility testing of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni from cases of BRD. Titles and abstracts were read and 105 articles that were relevant to the subject of BRD antibiotic resistance were attained for further review. After the application of exclusion criterion (publications must have originated from North America, be in English, adhere to standards set forth by the Clinical and Laboratory Standards Institute, and be concerning antimicrobial resistance in BRD in beef cattle), 16 articles remained and are the focus of this publication. Due to the disparate data from the few studies that investigate susceptibility testing of BRD pathogens, a quantitative assessment or meta-analysis was not performed on the studies presented in this review. However, considering diagnostic lab data, there appears to be a clear trend of a decrease in susceptibility of the three major BRD pathogens to the antimicrobials used commonly for treatment and control of BRD. Studies performing sensitivity testing on healthy cattle report much lower resistance, but it remains unclear if this is because of a true lack of resistance mechanisms, or if the isolates do contain quiescent genes for resistance that are only phenotypically expressed following the administration of an antimicrobial for either treatment or control of BRD. Future research to address this question of genotype and phenotypic expression before and after antimicrobial administration will further advance our knowledge in this area.

Fall-weaned calves entering the feedlot experience a variety of psychological and physical stressors, including maternal separation, transportation, social mixing, restraint, and dietary changes. Mixing calves from multiple sources also exposes them to respiratory pathogens at a time when maternal immunity has waned. Using an experimental bovine respiratory disease (BRD) challenge, we analyzed the effects of specific stressors on clinical disease and immune responses following bovine herpes virus (BHV-1/IBR) infection of naïve calves. Transportation stress was compared to either abrupt weaning plus transportation or transportation following a two-step weaning process. Transportation alone significantly (P < 0.05) increased BHV-1 shedding in nasal secretions despite elevated interferon-gamma production in the upper respiratory tract. In contrast, abrupt weaning and transportation, significantly (P < 0.05) increased serum haptoglobin on day 3 post-infection (PI) and blood leukocyte tumor necrosis factor α secretion on day 5 PI. These systemic responses were reduced by instituting a two-step weaning process 4 days prior to transportation and BHV-1 infection. In conclusion, these observations are consistent with earlier studies implicating weaning and transportation as stressors contributing to BRD severity and mortality. Current studies also revealed that different stressors or combination of stressors have distinct effects on host responses to viral infection in naïve calves.

Bovine respiratory disease (BRD) is the most expensive disease affecting United States cattle. Recently weaned calves are the focus of prevention and treatment research. Identifying affected cattle early in the course of BRD is difficult. Intervention during the early stages of BRD improves treatment outcomes; however, cattle as prey animals are excellent at hiding signs of disease, especially if the caregiver has not gained their trust. Depression, appetite loss, and changes in respiratory character are the principal signs used to identify BRD. Rectal temperatures from cattle pulled for treatment are a final measure of evaluation. Cattle suffering from subclinical BRD frequently escape identification and treatment. Observations of lungs at packing plants for anterior ventral (AV) lesions frequently document higher BRD incidence rates than observed pre-harvest, suggesting subclinical BRD is common. Data from numerous studies document lower average daily gains (ADG) from cattle with AV lung lesions at packing plants that were not treated for BRD compared with cattle with normal lungs. Scoring lung lesions at the packing plant can be a useful tool for gaining insight into BRD incidence. Data indicate that BRD lowers ADG by 0.2 lbs on average, and lowers the USDA Quality Grade by 50 marbling points.

Genetics is responsible for approximately half the observed change in performance internationally in well-structured cattle breeding programs. Almost all, if not all, individual characteristics, including animal health, have a genetic basis. Once genetic variation exists then breeding for improvement is possible. Although the heritability of most health traits is low to moderate, considerable exploitable genetic variation does exist. From the limited studies undertaken, and mostly from limited datasets, the direct heritability of susceptibility to BRD varied from 0.07 to 0.22 and the maternal heritability (where estimated) varied from 0.05 to 0.07. Nonetheless, considerable genetic variation clearly exists; the genetic standard deviation for the direct component (binary trait), although differing across populations, varied from 0.08 to 0.20 while the genetic standard deviation for the maternal component varied from 0.04 to 0.07. Little is known about the genetic correlation between genetic predisposition to BRD and animal performance; the estimation of these correlations should be prioritized. (Long-term) Breeding strategies to reduce the incidence of BRD in cattle should be incorporated into national BRD eradication or control strategies.

Clinical scoring systems have been proposed for respiratory disease diagnosis in calves, including the Wisconsin (WI) system (McGuirk in 2008) which uses five clinical signs, each partitioned into four levels of severity. Recently, we developed the California (CA) bovine respiratory disease (BRD) scoring system requiring less calf handling and consisting of six clinical signs, each classified as normal or abnormal. The objective of this study was to estimate the on-farm agreement between the WI and the CA scoring systems. A total of 100 calves were enrolled on a CA dairy and assessed for BRD case status using the two scoring systems simultaneously. The Kappa coefficient of agreement between these two systems was estimated to be 0.85, which indicated excellent agreement beyond chance. The simpler design and reduced calf handling required by the CA BRD scoring system may make it advantageous for on-farm use.

Pasteur described an organism causing fowl cholera in 1880. In 134 years we have progressed from crude vaccines for Pasteurella, to some refined vaccines, to a name change (Mannheimia), to autogenous vaccines (back to crude). In the last 25–30 years, we have attempted to mitigate the problem of bovine respiratory disease with antimicrobials and subsequently have a high incidence of multi-drug resistance. All of these attempts have resulted in little if any improvement in morbidity/mortality. Is it time to focus on the animal's response or lack of response to infectious pressure? Instead of focusing on the 10–50% morbid cattle should we focus on the 50–90% that are not compromised and determine why they stay healthy under the same environmental conditions?

Respiratory disease of young dairy calves is a significant cause of morbidity, mortality, economic loss, and animal welfare concern but there is no gold standard diagnostic test for antemortem diagnosis. Clinical signs typically used to make a diagnosis of respiratory disease of calves are fever, cough, ocular or nasal discharge, abnormal breathing, and auscultation of abnormal lung sounds. Unfortunately, routine screening of calves for respiratory disease on the farm is rarely performed and until more comprehensive, practical and affordable respiratory disease-screening tools such as accelerometers, pedometers, appetite monitors, feed consumption detection systems, remote temperature recording devices, radiant heat detectors, electronic stethoscopes, and thoracic ultrasound are validated, timely diagnosis of respiratory disease can be facilitated using a standardized scoring system. We have developed a scoring system that attributes severity scores to each of four clinical parameters; rectal temperature, cough, nasal discharge, ocular discharge or ear position. A total respiratory score of five points or higher (provided that at least two abnormal parameters are observed) can be used to distinguish affected from unaffected calves. This can be applied as a screening tool twice-weekly to identify pre-weaned calves with respiratory disease thereby facilitating early detection. Coupled with effective treatment protocols, this scoring system will reduce post-weaning pneumonia, chronic pneumonia, and otitis media.

One area where the feedlot industry has been historically weak is the area of BRD “case definition” or diagnosis. Numerous studies demonstrate a weak correlation between lung lesions at harvest and treatment history. This poor track record is due in part to lack of specific chute side diagnostic tools. To analyze the effectiveness of current diagnostic tools (temperature, manual lung scores, and Whisper® lung scores), two data sets were collected. The first evaluated the correlation between rectal temperature, manual lung scores, and case fatality rate in feedlot cattle pulled for BRD. The second evaluated the relative accuracy of Whisper® scores and rectal temperature. Fever was defined as a rectal temperature of 104.5° F or greater. Manual lung scores better correlated with case fatality rate than fever. When fever and Whisper® scores were compared, a Whisper® score of 1 or less better predicted survival than a temperature of less than 104.5° F. The combination of no fever and Whisper® score of 1 or less best predicted survival. The determination of Whisper® score along with rectal temperature in cattle identified with signs of acute BRD can improve case definition, improve risk assessment, and allow more targeted use of antibiotics.

Resistance is a qualitative interpretation of antimicrobial activity in vitro. Critical to management of bovine respiratory disease (BRD) is the clinical response in vivo. Attempts to connect activity in vitro to response in vivo have been complicated by the complexity of BRD, interpretation of antimicrobial activity in vitro, and inconsistent measures of clinical success or failure. During recent history, the discovery, development, and commercialization of antimicrobials have decreased. In response to resistance, voluntary and imposed restrictions on use of antimicrobials have been implemented. Resistance can be reversed using technology and knowledge of mechanisms of resistance. Perhaps approaches that reverse resistance will be used in clinical management of BRD in the future. The short answer to the question posed in the title is, ‘yes.’ Since antimicrobial drugs were discovered, resistance has been a consideration for selection of treatment of any infectious disease and BRD is not unique. In the opinion of the author, the more important question is, ‘How will antimicrobial resistance of BRD pathogens impact BRD management in the future?’

The USDA:APHIS National Animal Health Monitoring System collects data on health and health management in livestock and poultry populations throughout the USA in order to provide stakeholders with population estimates to use as benchmarks for comparison, to guide policy development, and to identify research needs and prioritize education efforts. Recent studies of both the beef cattle feedlot industry and dairy heifer rearing operations provided information about BRD occurrence as well as information about prevention and treatment practices used on these operations. While a great deal of effort is dedicated to BRD prevention, there are still opportunities to improve the strategies used. Despite efforts to prevent the disease, BRD continues to be widespread on both of these types of operations.