Source: KANSAS STATE UNIV submitted to NRP
AN INTEGRATED APPROACH TO CONTROL OF BOVINE RESPIRATORY DISEASES (NC-1027)
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
0226763
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
NC-_OLD1192
Project Start Date
Oct 1, 2011
Project End Date
Sep 30, 2016
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
KANSAS STATE UNIV
(N/A)
MANHATTAN,KS 66506
Performing Department
Diagnostic Medicine & Pathobiology
Non Technical Summary
BRD is a significant cause of economic loss and animal illness in cattle production systems. Better methods of control are needed that reduce the use of antibiotics and reduce animal suffering. In this project we utilize experimental models of infectious pneumonia in order to investigate behavioral, pathophysiological, clinical and morphological criteria that can lead to discoveries to lessen the impact of BRD. Changes in any of the parameters evaluated could lead to enhanced diagnostic and prognostic methods so that disease can be recognized sooner and treatments initiated earlier in the disease process. The experimental models also provide the opportunity to evaluate vaccine formulations directed against specific agents of BRD for efficacy and practical use. Determination of host ? response profiles to disease (inflammatory cytokines, substance P, and immunological status) create the opportunity to discover host responses that could be either enhanced or inhibited to improve the outcome of BRD. Outreach through newsletters, publications, symposia, and graduate and veterinary student training on topics related specifically to BRD or more general topics on bovine disease and well-being will be pursued.
Animal Health Component
(N/A)
Research Effort Categories
Basic
(N/A)
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3113310110150%
3113399110350%
Goals / Objectives
1. To aid the rapid identification and subsequent management of BRD by developing, validating and guiding the application of new state-of-the-art diagnostic tools. 2. To elucidate key steps in the dynamic interactions between pathogens, host immunity and the environment, and to determine how manipulation of these factors can reduce the risk of BRD. 3. To investigate the mechanisms by which infectious agents work singly or in combination to evade, suppress, or misdirect the host immune response, or to directly induce cellular or molecular pathology, in BRD. 4. To develop management practices, including rationally applied therapeutic and preventative interventions that minimize the impact of BRD on cattle health, welfare and productivity. 5. To promote open scientific exchange and dialogue among scientists, veterinarians, allied industry professionals and cattlemen to advance BRD research initiatives. 6. To facilitate the translation of research findings to practical field application by developing and integrating BRD educational programming for national veterinary and producer organizations focused on cattle health and management. The work at Kansas State will include components of all objectives. Outputs will include targeted research activities to determine biomarkers or behavioral characteristics that aid in disease diagnosis and prognosis, and a greater understanding of the pathogenesis of specific infectious pneumonias and the host responses to those agents. Events will be coordinated by the Beef Cattle Institute at KSU. Services will include the training of future food animal practitioners and animal health researchers. Products anticipated include improved vaccines and diagnostic tests or protocols, and educational tools.
Project Methods
Objectives 1-4 will be pursued using specific, hypothesis-driven research studies, studies for development of models for BRD, and experimental challenge studies to evaluate avenues to reduce the incidence and severity of BRD. These studies will also be used to gather behavioral and physiological data, and tissue/blood samples to ascertain immunological parameters, inflammatory cytokine profiles and serum chemistry values. Experimental endoscopic intrabronchial challenge models for pneumonic mannheimiosis (Mannheimia haemolytica) and mycoplasmosis (Mycoplasma bovis) will be used to induce pneumonia. Pre- and post-challenge behavior patterns will be assessed using accelerometers and pedometers to track posture (standing, lying down), and the number of steps taken. A commercial positioning system consisting of ear tags that emit a location signal to track calf position within the pen at any given time will be used to assess drinking, eating, distance traveled, and loafing habits of each calf. Data acquisition will be done continuously during study periods. Commercial software will be used for position and statistical analysis. Clinical data will consist of a clinical illness score (CIS) assigned by observation at selected time points. The CIS ranged from 1 (normal) to 4 (severe illness, moribund or have little response to human approach). Blood and serum will be obtained at selected time intervals for analyses to include (depending on the study), complete blood counts, serum chemistry profiles, inflammatory cytokine profiles (including IL-1, IL-6, TNF, and gamma interferon) using anti-cytokine antibody-coated polystyrene beads in a multiplex flow cytometric assay, and various other host-response markers (including substance P to be measured by a competitive immunoassay). Gross and histopathological exams of the lungs will be conducted at the termination of the studies. Lung lesions will be scored using a standardized system based on the percentage of each lung lobe with pneumonic change. Aerobic and mycoplasma cultures will be conducted on lung samples, as well as assays for viruses on selected studies. Objectives 5-6 will be pursued through the activities of the Beef Cattle Institute, which includes newsletters, regional training symposia and certificate programs. Additionally, the veterinary and graduate curricula at Kansas State offer advanced training in topics associated with BRD.

Progress 10/01/11 to 09/30/16

Outputs
Target Audience:Scientists, veterinary and animal science professionals, and producers Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Kansas State is the home of the Beef Cattle Institute (BCI). The purpose of the Beef Cattle Institute is to create a collaborative environment at Kansas State University to address issues facing the beef industry through education, research and outreach. The institute sponsors graduate and undergraduate certificate programs, workshops and seminars, and beef cattle performance and health training. The College of Veterinary Medicine and Pathobiology graduate group sponsor MS and PhD training independently or in conjunction with the DVM degree. How have the results been disseminated to communities of interest?Participants have presented extension presentations, seminars, abstracts, and have participated in national and international meetings to promote discussion and interactions. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? BRD was shown to have a negative impact on performance in dairy cattle even after the BRD was resolved. Viral metagenomic sequencing of nasal swabs from feedlot cattle identified 21 viruses, indicating the complexity of viral involvement in BRD. Meta-analysis of the effects of feeding antimicrobials and ionophores on performance parameters showed substantial heterogeneity. Mass-medication of feed did not alter gamithromycin susceptibility of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni isolated from cattle subsequently diagnosed with BRD. In an antimicrobial resistance study, nearly all enteric Salmonella isolates were susceptible to quinolones, despite the fact that a fluoroquinolone was used to treat BRD in these feedlot populations. Genotypes of M. haemolytica associated with diseased cattle lungs showed a relationship between disease and the presence of antibiotic resistance genes. Behavioral data obtained by accelerometers could not distinguish calves subclinically infected with Bovine Virus Diarrhea Virus from healthy calves. Studies on Mycobacterium bovis indicated that IL-17A could serve as a biomarker of infection and that IFN-γ/TNF-α/IL-2 response by T-cells are indicative of a protective response to bovine tuberculosis. PI-3 virus was found to interfere with the JAK/STAT pathway downstream of the type III IFN receptor as one possible mechanism by which PI-3 virus evades innate immune responses. A review of the role of γδ T cells in the immune response to BRSV in cattle was conducted.

Publications

  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Schaffer AP, Larson RL, Cernicchiaro N, Hanzlicek G, Bartle SJ, Thomson DU: The association between calfhood bovine respiratory disease complex and subsequent departure from the herd, mild production, and reproduction in dairy cattle. J Am Vet Med Assoc 248:1157-1164, 2016. DOI: 10.2460/javma.248.10.1157
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Namita M, Cernicchiaro N, Torres S, Li F, Hause BM: Metagenomic characterization of the virome associated with bovine respiratory disease in feedlot cattle identified novel viruses and suggests an etiologic role for influenza D virus. J Gen Virol 97(8), 2016. DOI: 10.1099/jgv.0.000492
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Cernicchiaro N, Corbin M, Quinn M, Prouty F, Branine ME, Renter D: Meta-analysis of the effects of laidlomycin propionate, fed alone or in combination with chlortetracycline, compared with monensin sodium, fed alone or in combination with tylosin, on growth performance, health, and carcass outcomes in finishing steers in North America. J Ani Sci 2016. DOI: 10.2527/jas2015-0086
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Smith AB, Renter D, Cernicchiaro N, Shi X, Nagaraja TG: Prevalence and Quinolone Susceptibilities of Salmonella Isolated from the Feces of Preharvest Cattle Within Feedlots that Used a Fluoroquinolone to Treat Bovine Respiratory Disease. Foodborne Pathogens and Disease 13(6): 303-308, 2016. DOI: 10.1089/fpd.2015.2081
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Clawson ML, Murray RW, Sweeney MT, Apley MD, DeDonder KD, Capik SK, Larson RL, Lubbers BV, White B, Kalbfleisch TS, Schuller G, Dickey Am, Harhay GP, Heaton MP, Chitko-McKown CG, Brichta-Harhay DM, Bono J, Smith T: Genomic signatures of Mannheimia haemolytica that associate with the lungs of cattle with respiratory disease, an integrative conjugative element, and antibiotic resistance genes. BMC Genomics 17(1), 2016. DOI: 10.1186/s12864-016-3316-8
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Dedonder KD, Harhay DM, Apley MD, Lubbers BV, Clawson ML, Schuller G, Harhay GP, White B, Larson RL, Capik SF, Riviere JE, Kalbfleisch T, Tessman RK: Observations on macrolide resistance and susceptibility testing performance in field isolates collected from clinical bovine respiratory disease cases. Vet Microbiol 192, 2016. DOI: 10.1016/j.vetmic.2016.07.021
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: DeDonder KD, Apley MD, Li M, Gehring R, Harhay DM, Lubbers BV, White BJ, Capik SF, KuKanich B, Riviere JE, Tessman RK: Pharmacokinetics and pharmacodynamics of gamithromycin in pulmonary epithelial lining fluid in naturally occurring bovine respiratory disease in multisource commingled feedlot cattle. J Vet Pharmacol Ther 39(2):157-66, 2016. doi: 10.1111/jvp.12267
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Bayne JE, Walz PH, Passler, White B, Theurer M, van Santen E: Use of three-dimensional accelerometers to evaluate behavioral changes in cattle experimentally infected with bovine viral diarrhea virus. Am J Vet Res 77(6):589-596, 2016. DOI: 10.2460/ajvr.77.6.589
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: White B, Goehl DR, Amrine D, Booker C, Wildman B, Perrett T: Bayesian evaluation of clinical diagnostic test characteristics of visual observations and remote monitoring to diagnose bovine respiratory disease in beef calves. Prevent Vet Med 126, 2016. DOI: 10.1016/j.prevetmed.2016.01.027
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Maggioli MF, Palmer MV, Thacker TT, Vordermeier M, McGill J, Larsen MH, Jacobs W, Waters WR: Polyfunctional cytokine production by central memory T cells from cattle in response to Mycobacterium bovis infection and BCG vaccination. J Immunol 196: 216.24, 2016
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Waters WR, Maggioli MF, Palmer MV, Thacker TC, McGill JL, Vordermeier HM, Berney-Meyer L, Jacobs WR, Jr, Larsen MH: Interleukin-17A as a biomarker for bovine tuberculosis. Clin Vaccine Immunol 23:168180, 2016. doi:10.1128/CVI.00637-15
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Maggioli MF, Palmer MV, Thacker TC, Vordermeier HM, McGill JL, Whelan AO, Larsen MH, Jacobs WR, Waters WR: Increased TNF-?/IFN-?/IL-2 and Decreased TNF-?/IFN-? Production by Central Memory T Cells Are Associated with Protective Responses against Bovine Tuberculosis Following BCG Vaccination. Frontiers Immunol 7:421, 2016. DOI=10.3389/fimmu.2016.00421
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: McGill JL, Rusk RA, Guerra-Maupome M, Briggs RE, Sacco RE: Bovine gamma delta T cells contribute to exacerbated IL-17 production in response to co-infection with bovine RSV and Mannheimia haemolytica. PLOS One, 2016. doi.org/10.1371/journal.pone.0151083
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Eberle KC, McGill JL, Reinhardt TA, Sacco RE: Parainfluenza virus 3 blocks antiviral mediators downstream of the interferon lambda receptor by modulating Stat1 phosphorylation. J Virol 90:29482958, 2016. doi:10.1128/JVI.02502-15.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: McGill JL, Sacco RE: Gamma delta T cells and the immune response to respiratory syncytial virus infection. Vet Immunol Immunopathol 181: 24-29, 2016. doi.org/10.1016/j.vetimm.2016.02.012


Progress 10/01/13 to 09/30/14

Outputs
Target Audience: Scientists and producers Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Kansas State is the home of the Beef Cattle Institute (BCI). The purpose of the Beef Cattle Institute is to create a collaborative environment at Kansas State University to adress issues facing the beef industry through education, research and outreach. The institute sponsors graduate and undergraduate certificate programs, workshops and seminars, and beef cattle performance and health training How have the results been disseminated to communities of interest? Participants have presented extension presentations, seminars, abstracts, and have participated in national and international meetings to promote discussion and interactions. What do you plan to do during the next reporting period to accomplish the goals? We will continue to conduct experimental challenge experiments to investigate the role of environmental conditions, treatments, and vaccines on BRD.

Impacts
What was accomplished under these goals? A Taqman multiplex real-time PCR assay consisting of three triplex reactions was developed and validated for simultaneous detection of 9 BRD pathogens [Bovine viral diarrhea virus (BVDV), Bovine respiratory syncytial virus (BRSV), Bovine coronavirus (BCoV) and Bovine herpesvirus type 1 (BHV-1/IBR), Mannheimia haemolytica (Mh), Pasteurella multocida (Pm), Histophilus somni (Hs), Bibersteinia trehalosi (Bt) and Mycoplasma bovis (Mb)]. The assay has PCR amplification efficiencies of 92.1-105.4% and correlation coefficients of 0.99-0.999. Transmisson of Mh was studied using nasopharyngeal cultures from forty calves. Calves with negative cultures were challenged with Mh and monitored for shedding. Calves with two positive initial cultures were classified naturally Mh positive. Culture status between study days for both the POS and NEG groups was inconsistent and POS calves were not consistently culture positive during daily monitoring. Pulse field gel electrophoresis performed on all positive cultures showed that the NEG calves did not shed the Mh challenge strain, but rather two distinct strains of Mh shared among all calves. These findings raise concerns about the use of a single nasal swab to establish the prevalence or strain of Mh within a pen. A neurokinin-1 antagonist (NK-1A) was evaluated in a Mh challenge model for its ability to reduce the severity and amount of pneumonia. Thirty-six heifers received high dose, low dose, or no treatment followed by challenge with Mh. No consistent differences between groups were present for behavioral parameters (clinical illness scores, time lying down, and distance walked), or lung lesions. These results did not indicate any clear benefit for the use of NK-1A to reduce the severity and amount of experimental pneumonia. Thirty-three heifers were metaphylactically treated with tildipirosin (ZUP), tulathromycin (DRX) or saline (SAL) followed by Mh challenge. ZUP-treated heifers had lower (P < 0.05) lung lesion scores compared with DRX- and SAL- treated heifers. The probability of receiving abnormal clinical illness scores was lower (P < 0.05) in ZUP-treated heifers compared to DRX- and SAL-treated animals. This study showed that heifers treated with tildipirosin 10 d before M. haemolytica challenge have less pulmonary damage and fewer clinical signs of illness compared to heifers treated with DRX or SAL.

Publications

  • Type: Journal Articles Status: Published Year Published: 2014 Citation: M.E. Theurer, R.L. Larson, B.J. White. A meta-analysis of vaccine effectiveness against bovine herpes virus, bovine viral diarrhea virus, bovine respiratory syncytial virus, and parainfluenza-type 3 virus in cattle for bovine respiratory disease complex. J Am Vet Med Assoc (In Print) D.E. Amrine, B.J. White, R.L. Larson, D.A. Mosier. Pulmonary lesions and clinical disease response to Mannheimia haemolytica challenge 10 days following administration of tildipirosin or tulathromycin. J Anim Sci 92:311-319, 2014. D. E. Amrine, B.J. White, R.L. Larson. Comparison of classification algorithms to predict outcomes of feedlot cattle identified and treated for Bovine Respiratory Disease. Comput Electron Agri. 2014 July 105:9-19. Doi: 10.1016/j.compag.2014.04.009. B. Fraser, D.E. Anderson, B.J. White, M.D. Miesner, D.E. Amrine. Associations of various physical and blood analysis variables with experimentally induced Mycoplasma bovis pneumonia in calves. Am J Vet Res. 2014. 75(2): 200-207. doi: 10.2460/ajvr.75.2.200. D.E. Amrine, B.J. White, R. L. Larson, D.A. Mosier. Determining differences in pulmonary lesions and clinical disease response to Mannheimia haemolytica challenge occurring 10 days after administration of tildipirosin, tulathromycin, or saline. 2014 J Anim Sci 92:311-319.


Progress 01/01/13 to 09/30/13

Outputs
Target Audience: Scientists and producers Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Diagnostic tools for the recognition of multiple viral and bacterial pathogens involved in BRD are under continued use and development. A real time polymerase chain reaction (PCR) panel assay (Bovine Respiratory Panel PCR) targeting 5 pathogens commonly associated with BRD: M. bovis, Bovine viral diarrhea virus (BVDV), Bovine respiratory syncytial virus (BRSV), Bovine coronavirus (BCoV), and Bovine herpesvirus type 1 (BHV-1/IBR) is currently in use and a real-time PCR procedure for four more BRD-associated pathogens, Pasteurella multocida, M. haemolytica, Histophilus somni and Bibersteinia trehalosi, is under development. Clinical illness scores and a variety of biological parameters, including bovine troponin I, were not found to be good predictors of pulmonary consolidation caused by experimentally induced pneumonia. The agreement among observers assigning CISs to calves was low; and that the accuracy of the CIS system in relation to that of pulmonary consolidation scoring varied with the severity of consolidation considered to represent bovine respiratory disease. There were changes in behavior and increased biomarkers in calves with experimental M. haemolytica pneumonia compared to normal calves during high ambient temperatures. Rectal temperatures in challenged cattle were higher than controls up to 24 h after challenge, but, nasal passage temperatures were less. Challenged calves spent less time at the grain bunk, less time at the hay feeder, and more time lying down compared with controls. Challenged calves had significantly greater concentrations of substance P, cortisol, haptoglobin, and metalloproteinase at various times after challenge compared with controls. We characterized 19 isolates from fatal cases of pneumonia obtained from a single outbreak of BRD by pulsed field gel electrophoresis, antimicrobial susceptibility profiles, and by evaluation of host immunologic responses between fatal and surviving cases. There were differences between the isolates, suggesting that most fatalities were caused by multiple unique strains rather than by one single strain of M. haemolytica. Between 2009 to 2011, there was a trend towards increasing multi-drug resistance in Mannheimia haemolytica isolates obtained from the Kansas Veterinary Diagnostic Laboratory. In 2009, just over 5% of isolates were resistant to 5 or more antimicrobials (pan-resistant). In 2011, more than 35% of the M. haemolytica isolates were characterized as pan-resistant. Net returns for cattle treated for BRD in a Midwestern feedlot decreased depending on the number of treatments received compared to animals that did not develop BRD. The magnitude of the decrease depended on the season during which cattle arrived at the feedlot, with significantly higher returns for cattle arriving during fall and summer than for cattle arriving during winter and spring. Evaluation of a predictive model for BRD upon feedlot arrival demonstrated the ability to improve models by utilizing more refined data on the prior history of cohorts, thus making these models more useful to operators of commercial feedlots. Cattle arriving in April had the highest number of lots correctly classified at arrival and cattle arriving in December had the lowest; classification accuracy at arrival varied according to initial weight. A study of management practices associated with preweaning BRD rates suggested that certain management practices may be indicators or predictors of preweaning BRD rates in cow-calf production systems. Bred heifer importation was associated with lower BRD rates, whereas weaned steer importation was associated with higher BRD rates. Feed supplementation with antimicrobials was positively associated with BRD rates.

Publications

  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Theurer M.E., Anderson D.E., White B.J., Miesner M.D., Mosier D.A., Coetzee J.F., Lakritz J., Amrine D.E. Effect of Mannheimia haemolytica pneumonia on behavior and physiologic responses of calves experiencing hyperthermal environmental conditions. J Anim Sci. 2013. 91:1-13. Hanzlicek G.A., Renter D.R., White B.J., Wagner B.A., Dargatz D.A., Sanderson M.W., Scott H.M., Larson R.E.. Management practices associated with the rate of pre-weaning calf respiratory disease: results from a national survey of U.S. cow-calf operations. 2013 J Am Vet Med Assoc. 242(9): 1271-1278. PMID: 23600786 Babcock A.H., White B. J., Renter D. G., Dubnicka S., Scott H.M. Predicting cumulative risk of bovine respiratory disease complex using feedlot arrival data and daily morbidity and mortality counts. Can J Vet Res. 2013. 77(1):33-44. Fraser BC, Anderson DE, White BJ, Miesner MD, Wheeler C, Amrine D, Lakritz J, Overbay T. Assessment of a commercially available point-of-care assay for the measurement of bovine cardiac troponin I concentration. Am J Vet Res. 2013 Jun; 74 (6):870-3 Amrine D.E., White B.J., Larson R.L, Anderson D.E, Mosier D.A, Cernicchiaro N. 2013. Precision and accuracy of clinical illness scores, compared with pulmonary consolidation scores, in Holstein calves with experimentally induced Mycoplasma bovis pneumonia. Am J Vet Res. 74:310-315. PMID: 23363359 Hanzlicek G.A., Lubbers B.V. Antimicrobial multidrug resistance and coresistance patterns of Mannheimia haemolytica isolated from bovine respiratory disease cases  a three-year (2009-2011) retrospective analysis. J Vet Diag Invest, 25:413-417, 2013. Cernicchiaro N., White B.J., Renter D.G., Babcock A.H. Evaluation of economic and performance outcomes associated with the number of treatments after an initial diagnosis of bovine respiratory disease in commercial feeder cattle. Am J Vet Res, 74:300-309, 2013. Rainbolt S., Moore M., Lubbers B., Davis R., Pillai D., Mosier D. Comparison of Mannheimia haemolytica isolates from an outbreak of Bovine Respiratory Disease. Merial-NIH Veterinary Scholars Symposium, East Lansing, MI, 2013. Woolums A., Berghaus R., Smith D., White B., Engelken T., Irsik M., Matlick D., Jones L., Ellis R., Smith I., Mason G., Waggoner E. A survey of herd-level risk factors for nursing beef calf bovine respiratory disease (BRD). J Am Vet Med Assoc, 243(4):538-547, 2013.


Progress 01/01/12 to 12/31/12

Outputs
OUTPUTS: The Kansas Diagnostic Laboratory is using a Bovine Respiratory Disease (BRD) PCR diagnostic panel that includes Mycoplasma bovis , bovine viral diarrhea virus (BVDV), infectious bovine rhinotracheitis (IBR), bovine coronavirus (BoCV), bovine respiratory syncytial virus (BRSV) and bovine parainfluenza virus (PI3). M. bovis and BVD are most frequently isolated, and often occur concurrently. Several trials were conducted in various sized feedlots to evaluate management practices and BRD. Wind speed, temperature and wind chill were associated with increased BRD. Distance traveled when first shipped to the feedlots was associated with increased BRD morbidity and overall mortality, and decreased carcass weight and average daily gain. Economic performance outcomes were compared with the number of times initial BRD cases were treated; net returns decreased with increasing numbers of BRD treatments. Importing bred heifers was associated with lower BRD, but operations that imported weaned steers had higher rates Operations that fed antibiotics to calves to prevent pre-weaning BRD had higher rates of BRD. The effects of transport-associated weight loss were associated with increased BRD morbidity and overall mortality, and decreased carcass weight and average daily gain. A study on BVDV was conducted to identify different genotypes in persistently infected (PI) cattle and to determine if PI cattle could produce transient infection in non-PI cattle after co-mingling. Approximately 96% of the non-PIs were transiently infected during the course of the co-mingling and approximately 50 percent of the cattle developed clinical BRD. We investigated clinical, behavioral, and pathophysiological data of potential value in detecting the onset and progression of BRD using experimental Mannheimia haemolytica and Mycoplasma bovis pneumonia models. Clinical illness scores (CIS) were assessed and remote triangulation devices recorded the amount of time calves spent in specific areas (near feed bunk, water, and shelter). Calves with more severe disease traveled less distance and spent less time at the hay bunk while spending more time in the shelter. The distance calves traveled was associated with the amount of lung lesion. PARTICIPANTS: Department of Diagnostic Medicine/Pathobiology: Natalia Cernicchiaro, Richard Hesse, Derek Mosier, Richard Oberst, Dave Renter Department of Clinical Sciences: David Anderson, Brad White, Mike Sanderson, Bob Larson, Dan Thomson, Mike Apley Department of Animal Sciences: Larry Hollis TARGET AUDIENCES: Scientists and producers PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
The parameters of potential value in detecting the onset and progression of BRD were evaluated with an experimental M. haemolytica pneumonia model. Studies are ongoing to determine those parameters of diagnostic and prognostic value. Studies on host factors involved in the onset and progression of BRD are ongoing. Investigations of the pathogens involved in BRD in feedlot settings are underway. Defining those conditions for specific cattle populations that enhance BRD may enable cattle health managers to develop models that predict and potentially manage these effects more effectively. Certain characteristics of management, such as the distance traveled during transportation, could allow a more precise prediction of cattle feedlot health and performance. The number of times BRD treatment occurs based on arrival season, gender, and weight class impact performance and net returns. Combining data on weight loss during transport with cohort demographics could allow a more precise prediction of health and performance of feedlot cattle. The association of certain clinical and behavioral parameters with illness and pulmonary lesions provide some predictors of the possible onset and severity of disease in addition to those traditionally used. Use of behavior monitoring systems may aid in recognition of respiratory tract disease in calves. Experimental models of infectious pneumonia were used to investigate behavioral, pathophysiological, clinical and morphological criteria that can lead to discoveries to lessen the impact of BRD. Changes in any of the parameters evaluated could lead to enhanced diagnostic and prognostic methods so that disease can be recognized sooner and treatments initiated earlier in the disease process. The experimental models also provide the opportunity to evaluate vaccine formulations directed against specific agents of BRD (notably M. haemolytica and M. bovis) for efficacy and practical use. Determination of host - response profiles to disease (inflammatory cytokines, substance P, and immunological status) create the opportunity to discover host responses that could be either enhanced or inhibited to improve the outcome of BRD. Manipulation of some of these responses could lead to decreased prophylactic and therapeutic use of antibiotics. Improved diagnostic capabilities also provide better information about the agents involved in BRD and how these can be specifically targeted.

Publications

  • Cernicchiaro, N., Renter, D.G., White, B.J., Babcock, A.H., Fox, J.T. 2011. The impact of weather variables on Bovine Respiratory disease (BRD) morbidity in finishing cattle. Canadian Association of Veterinary Epidemiology and Preventive Medicine (CAVEPM), May, St. Hyacinthe, Quebec, Canada.
  • Renter D.G., White B.J., Cernicchiaro N., Babcock A.H. 2011. Quantifying effects related to respiratory disease in commercial feedlot cattle. American Society of Animal Science (ASAS) and Argentine Association of Animal Production (AAPA) Conference October, Mar del Plata, Argentina.
  • Xiang, S., Renter, D.G., Cernicchiaro, N., White, B.J., Bello, N.M. 2011. Hierarchical Bayesian modeling of heteroskedasticity in average daily weight gain of feedlot cattle. Conference of Research Workers in Animal Diseases (CRWAD) December, Chicago, Illinois.
  • R. Hesse, J. Anderson, B. Breazeale, A. Fuller, J. Bai, E. Poulsen, G. Anderson, M. Hays and R. Oberst. 2011. Real-time PCR panel testing for bovine respiratory disease complex (BRDC) pathogens from clinical cases submitted to Kansas State Veterinary Diagnostic Laboratory (KSVDL). 5th Annual BVDV Symposium, San Diego, CA, November.
  • Theurer ME, White BJ, Anderson DE, Miesner MD, Mosier DA, Amrine DE, Spire MF. 2012. Effect of transportation during periods of extreme heat on physiological parameters and behavior in feedlot aged beef heifers. Proceedings, XXVII World Buiatrics Congress 2012, page 9. Lisbon, Portugal, June 3-8. Theurer ME, Anderson DE, White BJ, Miesner MD, Mosier DA, Amrine DE, Spire MF. 2012. Effect of Mannheimia haemolytica pneumonia on behavior and physiologic responses of calves experiencing hyperthermal environmental conditions. Proceedings, XXVII World Buiatrics Congress 2012, page 235. Lisbon, Portugal, June 3-8.
  • Cernicchiaro, N., Renter, D.G., White, B.J., Babcock, A.H., Fox, J.T. 2012. Associations between weather conditions during the first 45 days following feedlot arrival and daily respiratory disease risks in autumn-placed U.S. feeder cattle. J Anim Sci.; 90(4):1328-1337.
  • Cernicchiaro, N., White, B.J., Renter, D.G., Babcock, A.H., Kelly, L., Slattery, R. 2012. Associations between the distance traveled from sale barns to commercial feedlots in the United States and overall performance, risk of respiratory disease, and cumulative mortality in feeder cattle during 1997 to 2009. J Anim Sci.; 90(6):1929-1939.
  • Cernicchiaro, N., White, B.J., Renter, D.G., Babcock, A.H., Kelly, L., Slattery, R. 2012. Effects of weight loss during transit from sale barns to commercial feedlots on health and performance in feeder cattle cohorts arriving to feedlots from 2000 to 2008. J Anim Sci.; 90(6):1940-1947.
  • White BJ, Anderson D, Renter DG, Larson R, Mosier D, Kelly L, Theurer M, Robert B, Walz M. 2012. Clinical, behavioral, and pulmonary changes following Mycoplasma bovis challenge in calves. Am J Vet Res.; 73(4):490-497.
  • R.L. Larson and D.L. Step. 2012. Evidence-based effectiveness of vaccination against Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni in feedlot cattle for mitigating the incidence and effect of bovine respiratory disease complex. In: Buczinski S. and Vandeweerd J., ed. Veterinary Clinics of North America: Food Animal Practice Evidence-based veterinary medicine for the bovine veterinarian. Vol 28(1), Philadelphia, PA: W.B. Saunders Company; 97-106.
  • N. Cernicchiaro, D.G. Renter, B.J. White, J.T. Fox. 2012. Associations between weather conditions during the first 45 days following feedlot arrival and daily respiratory disease risks in autumn-placed U.S. feeder cattle. J Anim Sci. Apr 90(4): 1328-37. PMID:22147846
  • B.J. White, D.E. Anderson, D.G. Renter, R.L. Larson, D. Mosier, L. Kelly, M. Theurer, B. Robert, M. Walz. 2012. Clinical, behavioral, and pulmonary changes following Mycoplasma bovis challenge in calves. Am J Vet Res April, 73(4): 490-497. PMID: 22452495
  • Cernicchiaro, N., Bello, N.M., Xiang, S., White, B.J., Renter, D.G. 2012. Identifying sources of heteroskedasticity of average daily weight gain in commercial feedlot cattle using a hierarchical Bayesian approach. International Symposium of Veterinary Epidemiology and Economics (ISVEE) August, Maastricht, the Netherlands.
  • Cernicchiaro, N., Renter, D.G., White, B.J. 2012. Use of epidemiologic approaches and operational data to elucidate feedlot cattle health issues. International Symposium of Veterinary Epidemiology and Economics (ISVEE) August, Maastricht, the Netherlands.


Progress 01/01/11 to 12/31/11

Outputs
OUTPUTS: Clinical, behavioral, and pathophysiological data of potential value in detecting the onset and progression of BRD were evaluated with experimental Mannheimia haemolytica and Mycoplasma bovis pneumonia models. Clinical illness scores (CIS) were assessed in calves challenged with M. bovis and remote triangulation devices recorded the amount of time calves spent in specific areas (near feed bunk, water, and shelter). Pulmonary lesions ranged from 0 to 79.9 percent at 22 days post challenge. Calves with more severe disease traveled less distance and spent less time at the hay bunk while spending more time in the shelter. The distance calves traveled was associated with the mount of lung lesion. Similar results were obtained in a separate study where behavioral changes were detected between normal and endotoxin-exposed calves. Evaluation of other parameters (cytokines and substance P) for comparison are also being conducted. Several trials were conducted to develop a consistent experimental challenge model for M. bovis. Previous work with aerosol challenge models produced inconsistent results and minimal pulmonary lesions. Therefore a trial was conducted utilizing three delivery techniques: blind intratracheal challenge, endoscopic guided intrabronchial challenge or endoscopic challenge combined with aerosol challenge. The intratracheal and intrabronchial routes produced more consistent lesions, so these two routes were then compared using 2 different doses of M. bovis . The intratracheal route of administration utilizing a low dose challenge produced significantly different results between trials, whereas the endoscopic method with a high dose of M. bovis produced farily consistent median lung scores between trials. These data formed the basis for a challenge model that was used to evaluate the efficacy of vaccination against M. bovis. An ongoing diagnostic survey of agents involved in BRD using compiled results of a real-time PCR panel and bacteriologic isolations demonstrate the spectrum of viral and bacterial agents, and their combinations involved in BRD. M. bovis and bovine viral diarrhea virus (BVDV) were the most common pathogens detected either singly or in combination. A study on BVDV was conducted to identify different genotypes in persistently infected (PI) cattle and to determine if PI cattle could produce transient infection in non-PI cattle after co-mingling. PI cattle were co-mingled with non-PI cattle for 27 days and approximately 50 percent of the cattle developed clinical BRD. Approximately 96 percent of the non-PIs were transiently infected during the course of the co-mingling. Detection of PI status was 100 percent for all sample types by RRT-PCR. PARTICIPANTS: Investigators/Scientists: Derek Mosier, Dave Renter; Department of Diagnostic Medicine/Pathobiology, KSU David Anderson, Brad White, Mike Sanderson, Bob Larson, Dan Thomson, Mike Apley; Department of Clinical Sciences, KSU Richard Oberst, Richard Hesse; Kansas Veterinary Diagnostic Laboratory, KSU Collaborator: Hans Coetzee, College of Veterinary Medicine, Iowa State University Partner organization: Ceva Biomune, Lenexa, KS TARGET AUDIENCES: Veterinarians Beef cattle producers PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
In this project we utilized experimental models of infectious pneumonia in order to investigate behavioral, pathophysiological, clinical and morphological criteria that can lead to discoveries to lessen the impact of BRD. Changes in any of the parameters evaluated could lead to enhanced diagnostic and prognostic methods so that disease can be recognized sooner and treatments initiated earlier in the disease process. The experimental models also provide the opportunity to evaluate vaccine formulations directed against specific agents of BRD (notably M. haemolytica and M. bovis) for efficacy and practical use. Determination of host - response profiles to disease (inflammatory cytokines, substance P, and immunological status) create the opportunity to discover host responses that could be either enhanced or inhibited to improve the outcome of BRD. Manipulation of some of these responses could lead to decreased prophylactic and therapeutic use of antibiotics. Improved diagnostic capabilities also provide better information about the agents involved in BRD and how these can be specifically targeted.

Publications

  • B.J. White, G. Hanzlicek, M.W. Sanderson, D.E. Anderson, R.L. Larson. 2010. Mollicutes species and Mycoplasma bovis prevalence and association with health outcomes in beef feeder calves at arrival and initial treatment for bovine respiratory disease. Can Vet J. 2010, Sept. 51(9):1016-1018.
  • A.H. Babcock, D. G. Renter, B. J. White, S. Dubnicka, H.M. Scott. Temporal distributions of respiratory disease events within cohorts of feedlot cattle and associations with cattle health and performance indices. Prev Vet Med. 2010, 97:198-219.
  • G. Hanzlicek, B.J. White, D. Renter , D. Anderson, R. Larson. Association between the prevalence of Mollicutes and Mycoplasma bovis and health and performance in stocker calves. Vet. Rec. 2011, 168(1):21. Epub 2010 Dec. 17.
  • G.A. Hanzlicek, B.J. White, D.G. Renter, D. Blasi. A field study evaluating health, performance, and behavior differences in crossbred beef calves administered different vaccine-parasiticide product combinations. Vaccine. 2010, Aug. 28(37):5998-6005. Epub 2010 July 14.
  • B.J. White, D.E. Anderson, D.G. Renter, R.L. Larson, D. Mosier, L. Kelly, M. Theurer, B. Robert, M. Walz. 2011. Clinical, behavioral, and pulmonary changes following Mycoplasma bovis challenge in calves. Am J Vet Res , In press.
  • D. Amrine, B.J. White, D.E. Anderson, R.L. Larson, D. Mosier, D. Renter. 2011. Behavior and clinical changes in calves with induced Mycoplasma bovis pneumonia. American Association of Bovine Practitioners Annual Conference, St. Louis, MO. September 2011.
  • N. Cernicchiaro, D.G. Renter, B.J. White, A.H. Babcock, J.T. Fox. 2011. Association between weather conditions and bovine respiratory disease in feedlot calves. American Association of Bovine Practitioners Annual Conference, St. Louis, MO. September 2011.
  • N. Cernicchiaro, B.J. White, D.G. Renter, A.H. Babcock, L. Kelly, R. Slattery. 2011. Effects of transport distance and weight loss during transit on feedlot health and performance. American Association of Bovine Practitioners Annual Conference, St. Louis, MO. September 2011.
  • M.E. Theurer, D.E. Anderson, B.J. White, M.D. Miesner. 2011. Physiological and behavioral changes with variations in ambient temperature and exposure to lipopolysaccharides in cattle. American Association of Bovine Practitioners Annual Conference, St. Louis, MO. September 2011.
  • G. Hanzlicek, D. Renter, B.J. White, B.A. Wagner, D.A. Dargatz, M.W. Sanderson, H.M. Scott, R. Larson. 2011. Management practices associated with the rate of pre-weaning calf respiratory disease: results from a national survey of U.S. cow-calf operations. American Association of Bovine Practitioners Annual Conference, St. Louis, MO. September 2011.