NC1192: An integrated approach to control of bovine respiratory diseases

(Multistate Research Project)

Status: Active

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SAES-422 Reports

Annual/Termination Reports:

[10/26/2021] [09/30/2022] [02/26/2023] [03/25/2024]

Date of Annual Report: 10/26/2021

Report Information

Annual Meeting Dates: 08/24/2021 - 08/24/2021
Period the Report Covers: 09/21/2020 - 08/24/2021

Participants

Brief Summary of Minutes

See attached report

Minutes Attachment:

2021-NC1192 General Report_102421.pdf

Accomplishments

Publications

Impact Statements

Date of Annual Report: 09/30/2022

Report Information

Annual Meeting Dates: 08/31/2022 - 08/31/2022
Period the Report Covers: 08/24/2021 - 08/31/2022

Participants

See meeting report

Participants Attachment:

2022-NC1192 Meeting Report.pdf

Brief Summary of Minutes

Please see attached file below for NC1192's 2022 annual report. Note that it was last updated from a previous version on 10/10/2022.

Minutes Attachment:

2022-NC1192 General Report_FINAL Rev1 10 10 22.pdf

Accomplishments

Publications

Impact Statements

Date of Annual Report: 02/26/2023

Report Information

Annual Meeting Dates: 01/24/2023 - 01/24/2023
Period the Report Covers: 08/31/2022 - 01/24/2023

Participants

See attached

Participants Attachment:

2023-NC1192 General Report_2-24-23.pdf

Brief Summary of Minutes

Accomplishments

Publications

Impact Statements

Date of Annual Report: 03/25/2024

Report Information

Annual Meeting Dates: 01/20/2024 - 01/20/2024
Period the Report Covers: 01/24/2023 - 01/24/2024

Participants

Manuel Chamorro, Auburn University
Roberto Palomares, University of Georgia
Natalia Cernicchiaro, Kansas State University
Florencia Meyer, Mississippi State University
Brandi Karisch, Mississippi State University
Amelia Woolums, Mississippi State University
Matthew Scott, Texas A&M University
Robert Valeris-Chacin, Texas A&M University
Lee Pinnell, Texas A&M University
Paul Morley, Texas A&M University
Andi Lear, University of Tennessee
Chris Chase, South Dakota State University
Alan Young, South Dakota State University

Brief Summary of Minutes

Summary of Annual Committee Meeting:

Date: Tue Jan 23, 2024

Location: Marriott Magnificent Mile, 4th Floor, Clark Ballroom

Time: 1-5pm Central Standard Time (NOTE: previously announced erroneously as Eastern time)

Agenda and items discussed:

1:00 PM: Introductions and welcome new members

1:30 PM: Update from Dr. Kathe Bjork, USDA NIFA, National Program Leader, Animal Health

2:00 - 3:15 PM: Presentation of station reports (10 - 15 min/report).

3:15 - 3:30 PM: Break

3:30 PM: Update from Administrative Advisor Dr. James Averill

4:00 PM: Business meeting

Items to discuss

BRD Symposium 2024: updates from Grant Dewell, Sharif Aly, Amelia Woolums

Update on webinars: Grant Dewell

Identify officers for 2024: next Secretary/President: Matthew Scott, TX

Future meeting plans: CRWAD 2025

New project proposal, 2025: writing committee: Matthew Scott, Robert Valeris-Chacin

5:00 PM: Adjourn

Accomplishments

Accomplishments:   Objective 1: To elucidate pathways by which host characteristics, pathogen virulence mechanisms, and environmental impacts interact to produce BRD, and to develop strategies to mitigate detrimental factors and enhance protective mechanisms. <ol> <li> Molecular epidemiological assessment of beef cattle management systems: how markets and vaccines influence health and disease (TX: Sarah Capik, Matthew Scott, Paul Morley, Lee Pinnell; MS:  Kelsey Harvey, Brandi Karisch, Amelia Woolums).  Two management decisions which have the potential to greatly impact BRD risk, but whose longitudinal effects are poorly understood, are preweaning vaccination and marketing strategy. In particular, we do not understand how they modulate host immunity and the host-pathogen relationship as cattle move through different production systems. We hypothesize that cattle management decisions related to reducing BRD risk influence host immunity and cellular activity and alter the composition of microbial communities. To test this hypothesis, we will analyze the 1) whole blood transcriptomes and 2) microbial DNA and RNA from the upper respiratory tract of cattle in a time-course, multi-omics approach.</li> </ol> <ul> <li>Controlling for shared gene expression over time, cattle, regardless of vaccination administration, demonstrated a continuous increase in gene expression related to specialized proresolving mediator (SPM) biosynthesis, which are profound regulators of both acute and chronic airway inflammation, CD28-dependent T-cell survival and co-stimulation, and carbohydrate/fatty acid metabolism.</li> </ul> <ul> <li>We further discovered that MLV-vaccinated cattle possessed DEGs which enriched for the downregulation of complement/coagulation cascades and the upregulation of Th17-cell-mediated immunity; critically, MLV-vaccinated calves did not demonstrate a change in type I interferon-associated gene expression prior to weaning.</li> <li>Leveraging the interaction between vaccination status and sale decision (Auction or Direct purchasing strategy prior to backgrounding), we discovered nearly 3,000 DEGs between cattle in the two market system groups, which contributed to antiviral defense (increased in Auction), cell growth regulation (decreased in Auction), immune activation and complement (increased in Auction), and inflammatory mediation (decreased in Auction).</li> <li>Auction cattle having previously been vaccinated during the cow-calf phase demonstrated lower gene expression and number of genes at backgrounding related to type I interferon production when compared to non-vaccinated Auction cattle at backgrounding.</li> <li>Work is ongoing to evaluate the transcriptomes of cattle during the cow-calf production period which would later develop BRD during backgrounding.</li> <li>The development of methodology to simultaneously extract and evaluate microbial DNA and RNA from nasopharyngeal swabs has been successful, with the anticipation of sequencing and analysis workflows to commence in spring 2024.</li> </ul> <ol start="2"> <li> Impact of the neonatal microbiome on morbidity and performance of beef and dairy cattle (TX-TAMU: Matthew Scott, Robert Valeris-Chacin, Sarah Capik; TX-WTAMU: John Richeson). One major knowledge gap in BRD pathogenesis is just how and when cattle are colonized with bacterial agents such as Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis. Although these bacteria are pathogens associated with BRD, they are also considered commensals that can be found in the respiratory tracts of clinically normal cattle. Little research has been performed regarding when these BRD commensals first colonize neonatal calves and the composition of the neonatal respiratory microbiome of beef and dairy calves has not been established. This study followed thirty calves starting at birth over the course of their lives to understand how the upper respiratory tract (URT) microbiome is established and how it changes over time. Bilateral nasal swabs were taken at birth (0h) and then 6, 12, and 24 hours later and the microbiome will be evaluated. Similarly, bilateral NPS were taken from the calves’ dams at birth as well as a vaginal swab and rectal swab taken at birth to explore the maternal respiratory, vaginal, and fecal microbiomes as sources for inoculation in neonates.</li> </ol> <ul> <li>Cow upper respiratory tract microbiome differed at 0h from that of their offspring.</li> <li>The URT microbiomes of dairy cows following birth were more dispersed than in calves. There was greater dispersion at 24h in calf URT microbiomes as they became increasingly dispersed compared to 0h or 6h.</li> <li>At 12h, calf fecal microbiome was more dispersed than at 6h. Calf age accounted for 10.6, 9.9, and 31% of the variance in the beta diversity of left URT, right URT, and fecal microbiomes, respectively.</li> <li>No differences were found between the left and right URT microbiomes after adjusting for calf age.</li> </ul> <ol start="3"> <li> Influence of tulathromycin metaphylaxis on the whole blood transcriptome of high-risk stocker cattle (TX: Matthew Scott, Robert Valeris-Chacin, Paul Morley; MS: Amelia Woolums, Brandi Karisch)  Metaphylaxis strategies are effective in reducing herd-level risk of BRD-associated morbidity and mortality, but the degree of efficacy across populations is highly variable and this management scheme may contribute to antimicrobial resistance (AMR) and refractory infectious respiratory disease. Limited molecular research exists to evaluate the effect of these antimicrobials on the microbial population and host response, and therefore there is little understanding of what triggers these therapeutic discrepancies. Therefore, we enrolled a population of high-risk commercial heifer calves in a randomized control trial (tulathromycin metaphylaxis (META) or negative control (NOMETA), evaluating the host blood transcriptome overtime with respect to naturally occurring BRD.</li> </ol> <ul> <li>When comparing META and NOMETA cattle who did not develop BRD, differential gene expression enriched for regulation of G protein-coupled receptor signaling (increased in META) and interferon alpha and beta signaling (decreased in META). Predicted protein interactions indicated G-couple protein activity with pro-inflammatory cytokine suppression in META at d21.</li> <li>When evaluating META and NOMETA cattle who would develop BRD, no differences in gene expression was observed; this demonstrates a consistent genomic pattern of cattle in response to clinical BRD manifestation.</li> <li>When evaluating cattle prior to and at time of BRD diagnosis, gene expression involved in increased neutrophil degranulation, decreased biosynthesis of specialized pro-resolving mediators (SPMs), and decreased regulation of the immune system was identified at time of treatment.</li> </ul> <ol start="4"> <li>Pathogenomics of the respiratory Mycoplasma bovisstrains circulating in cattle. (TX-TAMU:  Robert Valeris-Chacin, Paul Morley, Matthew Scott, Lee Pinnell, Alexis Thompson; MS: Amelia Woolums).   This collaborative project includes VERO - Texas A&M University, TVMDL, Kansas State VDL, and Mississippi State University.</li> </ol> <ul> <li>In this project,  boviscultures isolated from ante and post-mortem specimens were subcultured in the VERO lab. Subsequently, the DNA was extracted and due to the low biomass of M. bovis growth, a whole genome amplification was performed as a previous step before library preparation. Oxford nanopore native barcoding and flow cells compatible with the new Q20+ chemistry were used for library preparation and sequencing. The long reads were assembled and polished with Flye and Medaka, respectively. The complete genomes were annotated in Prokka with a reference M. bovis annotated genome downloaded from NCBI. Roary was employed to elucidate the pangenome and Snippy was utilized for the detection of single nucleotide polymorphisms (SNPs). Scoary was employed to estimate associations between the presence of genes in the M. bovis isolates and their metadata (with FDR=0.2 and empirical P values<0.05). Phylogenetic trees were constructed in Mega. Abricate was utilized to browse for virulence genes (VFDB full database) and antibiotic resistance genes (MEGARes).</li> <li>We received 54 isolates from the TVMDL recovered from lung lesions collected in 2021-2022. The isolates display Mycoplasma-like growth.</li> <li>Thirty-three isolates were determined to be bovis via a species-specific qPCR (using the uvrC gene).</li> <li>Mycoplasma bovis isolates clustered primarily by the type of operation (beef versus dairy). Group 3164 (an IS30 family transposase) and group 4289 (a hypothetical protein) were more prevalent in bovis isolates from animals older than 100 days.</li> <li>Related genes were detected as more prevalent in bovis isolates from animals in beef operations, group 3157 (IS30 family transpose) and group 4288 (hypothetical protein).</li> <li>Three virulence genes were detected in all isolates: elongation factor Tu (adherence), BMP family ABC transporter substrate-binding protein (p48, involved in immune modulation), and alpha-ketoacid dehydrogenase subunit beta (pdhB, adherence). Interestingly, one bovis isolate had a gene encoding tetracycline resistance (tet44).</li> </ul> <ol start="5"> <li> Identification of pathogen profiles and loci associated with resistance to BRD (WA: Holly Neibergs; TX-TAMU: C.D. Seabury).</li> </ol> <ul> <li>A USDA-NIFA funded proposal was continued to identify pathogen profiles and loci associated with enhanced resistance to BRD in 700 pre-weaned calves in Ohio. Bacteriology and virology are being used to identify pathogen profiles from mid-nasal and deep pharyngeal swabs and Illumina BovineHD BeadChips will be used for genotyping. Genome-wide association results will be compared with previous results in pre-weaned dairy calves in California and New Mexico. Sample collection is now complete, bacteriology and virology samples are submitted for diagnostic testing and DNA extraction of blood samples is ongoing.</li> </ul> <ol start="6"> <li>Initial levels and duration of specific BRSV-IgG-1 transferred from maternal colostrum or a colostrum replacer product to the respiratory tract [nasal secretions and bronchoalveolar fluid (BALF)] of dairy calves. (AL: Manuel Chamorro; MS: Amelia Woolums).   Colostrum derived antibodies against respiratory viruses are of major importance to reduce dairy calf morbidity and mortality associated with respiratory disease. Re-transfer of specific antibodies (i.e., IgG-1) to the upper respiratory tract has been previously described in dairy calves and play an important role on clinical protection; however, high levels of specific IgG-1 in the upper and lower respiratory tracts may negatively affect intranasal vaccination efficacy due to interference.</li> </ol> <ul> <li>AL and MS are evaluating the initial levels and decay of colostrum derived BRSV-IgG-1 in the respiratory tract (nasal secretions and BALF) of dairy calves fed maternal colostrum or a colostrum replacement at birth. Results from this study are preliminary and BRSV IgG-1 testing has not been performed. The mean serum IgG levels at 48 hours of are significantly greater in dairy calves receiving 6 L of maternal colostrum >22% Brix during the first 6 hours of life compared with dairy calves receiving 300 g of IgG from a colostrum replacement product during the same time frame (31 g/L vs. 15.5 g/L, respectively).</li> </ul>     Objective 2:  To develop and validate methodologies for accurate BRD diagnosis, objective risk assessment, and surveillance to detect new trends in BRD occurrence. <ol> <li> Assessment of BRD pathophysiology and development of diagnostics (TN: Lear; SD: Chase). SD provided the BVDV 1b BJ strain to TN for use in research relative to pathophysiology and diagnostics of BRD related pathogens. The study is currently ongoing with active collection of data. Expect study completion is fall 2024.</li> </ol>   Objective 3:  To develop and validate management practices and responsibly applied therapeutic and preventative interventions, such as vaccines, antimicrobials, and immunomodulators, to minimize the impact of BRD on cattle, producers, and society. <ol> <li> Comparison of the immune response and nasal microbiome following intranasal vaccination against respiratory viruses in newborn dairy calves on days 1 or 14 of age. (GA: Roberto Palomares, MS: Florencia Meyer):  Intranasal vaccination of neonatal calves is a strategy to circumvent vaccine antigen interference by maternal antibody and to prevent BRD. Little is known about the development and function of mucosa-associated lymphoid tissue in the URT of newborn calves and what factors, including the commensal microbiome, contribute to this early development.</li> </ol> <ul> <li>In this study 24 newborn dairy calves were randomly assigned to be intransally vaccinated on day 1 (n=12) or 14 (n=12) of life. Blood, nasal secretions and nasal swab samples were collected once a week for 8 weeks (starting between 6 and 24 h after birth) to compare the immune response and nasal microbiome.</li> </ul>   <ol start="2"> <li> Evaluation of effect of intranasal mineral (Cu, Zn & Mg) administration on bovine respiratory microbiome after stress, and the effect of intranasal administration on health status, nasal microbiome, and immune response of calves challenged with Bovine herpes virus 1. (AL: Manuel Chamorro, MS: Florencia Meyer,  GA:  Roberto Palomares).  </li> </ol> <ul> <li>This study was completed in two parts: one was done to determine if intranasal administration of a mineral formulation in dairy calves has the capacity to reduce haemolytica and P. multocida growth, and the effects on the composition and abundance of respiratory microbiome, before and after transportation stress.</li> <li>The second part of the study evaluated the effect of a mineral solution administered intranasally to calves before and after experimental BHV-1 infection on health status, bacterial growth, microbiome changes of the upper respiratory tract. The field portion of this study (IBR challenge, clinical evaluation, intranasal mineral treatment, and sample collection) was completed. Analysis of samples collected is in process.    </li> </ul>   <ol start="3"> <li> Evaluation of the stress-reducing effect of trace mineral injection in beef calves. (AL: João Bittar, GA: Roberto Palomares). </li> </ol> <ul> <li>Thirty beef calves were randomly assigned to 2 groups: ITM + modified-live virus vaccine (MLV) (n = 15) and ITM + saline SC (CONT) (n = 15). The calves were exposed to 3 types of stress: MLV vaccination (d0), nasal aerosol with bovine viral diarrhea virus-2 (BVDV-2) challenge (d5), and liver biopsy (d26). Serum cortisol concentration showed strong associations with the percentage of CD8+, BVDV2-SNA, and WC1CD25+ cells, and rectal temperature. The highest cortisol was reported 3 days after aerosol BVDV-2 challenge. Serum cortisol was decreased in ITM-treated calves 3 days post-BVDV-2 challenge, compared with CONT calves, with an average decrease of 18.5 ng/μL.  The ITM-treated calves were heavier and healthier (P < .01) than the CONT calves.</li> </ul>   <ol start="4"> <li> Transcriptomic profile of respiratory mucosa and lymphoid tissue in dairy calves challenged with BVDV and BHV1 after vaccination and trace minerals injection (GA: Roberto Palomares, TX: Matthew Scott).  The objective is to assess the transcriptomic profile of central and peripheral lymphoid tissue in dairy calves challenged with BVDV + BHV1 following vaccination and trace mineral injection (TMI).  This work is in progress. </li> <li> Evalution of the effects of Bacillus subtilis supplementation on health and weight gain in stockers on grass (MS: Brandi Karisch, Kelsey Harvey; TX: Reinaldo Cooke, Shay Mackey). In work with researchers at TX, MS evaluated the effects of a probiotic on health and growth in stockers on grass pastures fed dried distillers grains at 1% of body weight, with or without Bovacillus (Chr Hansen A/S) at 2 g/steer/d.  Cattle were weighted at days - 1 + 0, 14, 28, 56, and 90, and they were scored daily for signs of BRD.  12 pastures with 10 steers per pasture were randomly allocated to receive either treatment (n = 6 pastures per treatment).</li> </ol> <ul> <li>As of January 2024 the trial was completed. The results indicated a trend toward an effect of supplementation to increase weight gain (P= 0.09), but no difference in number of BRD treatments (P = 1.0).  However, there was a trend toward increased number of CON cattle dropping out due to disease (P = 0.08).  The decreased number of cattle dropping out due to severe disease may have indicated health benefits of treatment.</li> </ul>   <ol start="6"> <li>Evaluation of the effects of postweaning commingling and transport on bovine respiratory coronavirus shedding in dairy calves (MS: Florencia Meyer, Amelia Woolums; TX: Matthew Scott, Paul Morley, in collaboration with Noelle Noyes at the lead institution University of Minnesota). MS, TX and also the University of Minnesota will evaluate the impact of postweaning commingling and/or truck transport on bovine respiratory coronavirus shedding in dairy calves over 7 days post weaning.  Host immune gene expression, cortisol production, and proinflammatory cytokine production will be assessed before and after commingling and/or transport.</li> </ol> <ul> <li>As of January 2024, planning of the research is underway. Data collection will begin in summer 2024.</li> </ul>   <ol start="7"> <li> Metaphylaxis for respiratory disease in high-risk stocker cattle: impacts on Mannheimia haemolytica, the microbiome and the resistome (MS: Amelia Woolums, Brandi Karisch, Will Crosby; TX: Paul Morley, Lee Pinnell, Enrique Doster). In high risk stocker cattle receiving macrolide metaphylaxis or not, MS and TX 1) compared prevalence of nasopharyngeal (NP) MDR M. haemolytica isolates, AMR genes, and MGE, using culture, susceptibility testing, and whole genome sequencing; 2) compared NP metagenomes, using 16S amplicon sequencing; 3) compared the NP resistome, using target-enriched sequencing of AMR and MGE gene sequences; and 4) developed and used a novel target-enriched sequencing method to compare absolute abundance of M. haemolytica in metagenomes. This work provided a never- before reported description of the ecology of respiratory AMR in cattle receiving metaphylaxis, revealing targets for mitigating AMR.</li> </ol> <ul> <li>Results from completed field work were reported in 2023. As of January 2024 whole genome sequencing (WGS) of 244 haemolytica isolates (138 from META cattle and 106 from NO META cattle) collected at on day 0, 21, or 70 from cattle across all 4 trials is completed.  M. haemolytica isolates from cattle treated with META contained more AMR genes than cattle not receiving META, even though cattle that received META were less likely to require BRD treatment. </li> <li>Nasopharyngeal microbiome assessment indicated that Mycoplasma sp were significantly more abundant in cattle that had been treated with antimicrobials than cattle that had not.</li> <li>Quite surprisingly, assessment of the resistome indicated that the abundance of antimicrobial resistance genes for macrolide antimicrobials decreased after cattle received macrolide META. This was unexpected because bacteria isolated from these cattle displayed high rates of macrolide resistance. In contrast, abundance of aminoglycoside resistance genes increased, although no cattle were given aminoglycoside antimicrobials.</li> </ul> <ol start="8"> <li> Integrated transcriptome and multi-tissue mineral analyses of stocker cattle fed complexed or inorganic trace mineral supplement. (MS:  Kelsey Harvey, Brandi Karisch, Amelia Woolums; TX:  Matthew Scott.  Trace element supplementation is a common nutritional practice in post-weaned beef cattle production. Specific trace elements, such as copper and zinc, work together to promote T-cell-dependent immune function and humoral antibody production. However, trace element supplementation within a post-weaned beef production system often fails to recognize individual nutritional deficiencies and bioavailability of newly received cattle. Namely, this type of feeding practice may ultimately lead to over-supplementation. Additionally, the understanding of how beef cattle at high risk of developing BRD utilize trace minerals over time and their ability to combat inflammatory and infectious disease remain elusive. Therefore, our overall objective is to identify genomic mechanisms and spatial mineral trends related to trace mineral metabolism, central to inflammatory mediation and disease development, to better understand disease risk and mitigate prolonged inflammatory events.</li> </ol> <ul> <li>When comparing healthy cattle fed organically-sourced trace elements to inorganically-sourced trace elements, clear differences related to neutrophil function and degranulation (decreased in organic), MHC class I response and antigen presentation (increased in organic), T-cell proliferation and activity (increased in organic), and lipid/fatty acid metabolism (increased in organic).</li> <li>Further work is ongoing to evaluate the interactions between BRD acquisition and type of as-fed trace element supplement enrollment influence host gene expression, centered around inflammatory cytokine response and resolution.</li> </ul> Objective 4: To determine how attributes of cattle production systems including epidemiologic, societal, and economic forces contribute to BRD, and to develop ways to promote changes in those systems to reduce the occurrence of BRD and improve cattle health, welfare, productivity and antimicrobial stewardship. <ol> <li>Impact of management decisions during the cow-calf, backgrounding, and feedlot phases of beef production on BRD morbidity and mortality risks (TX: Matthew Scott, Sarah Capik; KS: Brad White, Bob Larson, David Amrine; MS: Kelsey Harvey, Brandi Karisch, Amelia Woolums). In this study TX, KS and MS will 1) examine the effect of vaccination twice during preweaning on preweaning performance and BRD morbidity and mortality during backgrounding; 2) quantify the impact of marketing decisions on BRD morbidity, mortality, and performance by comparing weaned beef calves sent directly to a backgrounding operation or sent via an auction market and order buyer; and 3) evaluate associations between pen and yard level management factors and health outcomes during the feedlot phase of production. We will also explore the impact of preweaning and marketing management decisions on inflammatory mediators and whether they are predictive of health outcomes or performance during backgrounding.</li> </ol> <ul> <li>Data collection for Specific Aims 1 and 2 are underway; year 2 of 3 is complete, with anticipated full statistical analyses to take place in spring 2025.</li> <li>Specific Aims 3 is complete and published. Relevant findings for Specific Aim 3 were that in certain instances (cattle weighing between 227–272 kg and group sizes of 100–175 head), having two water sources was associated with lower respiratory disease risk compared to only one water source, and that pen housing management factors were significantly associated with BRD incidence in the first 45 DOF, but effects were modified by demographic factors, such as arrival weight.</li> </ul>   Objective 5:  To promote dialogue and exchange among scientists, veterinarians, allied industry professionals and cattle producers to advance BRD research initiatives, to implement outreach, to disseminate research results, and to facilitate the translation of research findings to practical field applications.   <ol> <li> Organization of the Bovine Respiratory Disease Symposium (BRDS) 2024: Challenging Paradigms in August 7-8, 2024, in Denver, Colorado, in conjunction with the Academy of Veterinary Consultants (AVC) Summer 2024 meeting. Investigators that are part of the organizing committee include: Sharif Aly, Terry Lehenbauer, and Sarah Depenbrock (CA), Paul Morley (TX-TAMU), John Richeson (TX-WTAMU), Natalia Cernicchiaro (KS), Amelia Woolums (MS), Grant Dewell (IA), and Roger Saltman.  The symposium will feature a balance of presentations by scientists and veterinary consultants working with BRD, with ample time for discussion between the audience and the speakers' sessions.  A scientific poster session for researchers working on BRD will be held at the conference.  More information can be found at www.brdsymposium.org.</li> </ol> <ol start="2"> <li>Submission of letter of intent and full grant proposal to submit to USDA NIFA AFRI conference grant to support Bovine Respiratory Disease Symposium (BRDS) 2024.  Investigators: Sharif Aly, Terry Lehenbauer, and Sarah Depenbrock (CA), Paul Morley (TX-TAMU), John Richeson (TX-WTAMU), Natalia Cernicchiaro (KS), Amelia Woolums (MS), Grant Dewell (IA), and Roger Saltman.</li> </ol> <ol start="3"> <li>International collaboration with the University of São Paulo, Bovine Health Symposium (Simpósio Internacional de Sanidade Bovina) (SD: Chris Chase; MS: Amelia Woolums).  Project members and collaborators continue to engage with veterinarians and scientists at the University of São Paulo to present current information regarding pathogenesis, immunity, and resistance to bovine respiratory diseases, with symposia occurring in 2022 and 2024. </li> </ol>   Objective 6: To assess the economic impact of BRD across different sectors of cattle industry. <ol> <li>Assessment of the economic impact of late day pulmonary disease in feedlot cattle.  KS (Brad White, Bob Larson), TX (Matthew Scott), and MS (Amelia Woolums), with other collaborators, are working together on a new project to characterize late day pulmonary disease in feedlot cattle.  This work has just been funded and so is in the early stages of planning, but an assessment of the economic impact of late day pulmonary disease in feedlot cattle will be completed as part of this work. </li> </ol>   External funding obtained from Project activities: USDA-NIFA #2023-67015-39711 USDA-NIFA #2020-67016-31469 USDA-NIFA #2019-67015-29845 USDA-NIFA #2019-67017-29111

Publications

Website:  www.brdsymposium.org   Peer-reviewed publications Credille BC, Capik SF, Credille A, Crossley BM, Blanchard P, Woolums AR, Lehenbauer TW.  Agreement of antimicrobial susceptibility testing of Pasteurella multocida and Mannheimia haemolytica isolates from preweaned dairy calves with bovine respiratory disease.  Am J Vet Res. 2023.  Aug 14;84(11):ajvr.23.06.0140. doi: 10.2460/ajvr.23.06.0140. Print 2023 Nov 1. PMID: 37558231. Crosby WB, Karisch BB, Hiott LM, Pinnell LJ, Pittman A, Frye JG, Jackson CR, Loy JD, Epperson WB, Blanton J Jr, Capik SF, Morley PS.  Woolums AR. Tulathromycin metaphylaxis increases nasopharyngeal isolation of multidrug resistant Mannheinia haemolytica in stocker heifers.  Front Vet Sci.  2023.  Nov 20;10:1256997, doi:10.3389/fvets.2023.1256997.  PMID: 38053814.  Green MM, Woolums AR, Karisch BB, Harvey KM, Capik SF, Scott MA.  Influence of the at-arrival host transcriptome on bovine respiratory disease incidence during backgrounding.  Vet Sci. 2023. 2Mar 10; 10:211. https://doi.org/10.3390/vetsci10030211  Abdelfattah EM, Aly SS, Lehenbauer TW, Karle BM.  Effects of simplified group housing on behavior, growth performance and health of preweaned dairy calves on a California dairy. J Dairy Sci, IN PRESS  <a href="https://doi.org/10.3168/jds.2023-23820">https://doi.org/10.3168/jds.2023-23820</a>  Megahed AA, Bittar JHJ, Palomares RA, Mercadante VRG, Dias NW. Evaluation of the stress-reducing effect of trace mineral injection in beef calves. J Vet Intern Med. 2023 May-Jun;37(3):1278-1285. doi: 10.1111/jvim.16721. PMID: 37186325. Li Y, Liu M., Xu J, Koo C, Granberry F, Locke S, Palomares R, Habing G, Saif, LWang L, Wang Q.  Isolation and characterization of bovine coronavirus strains from dairy cows, dairy calves and beef cattle. 2024. Abstract.  Conference of Research Workers in Animals Diseases. Chicago IL.  Donlon JD, McAloon CG, Hyde R, Aly S, Pardon B, Mee JF.  A systematic review of the relationship between housing environmental factors and bovine respiratory disease in preweaned calves – Part 1: Ammonia, air microbial count, particulate matter and endotoxins. The Veterinary Journal 300-302 (2023) 106031. <a href="https://doi.org/10.1016/j.tvjl.2023.106031">https://doi.org/10.1016/j.tvjl.2023.106031</a> Perkins-Oines, S., Dias, N., Krafsur, G., Abdelsalam, K., Perry, G., Ensley, D., Jones, C., Chase, C.C.L., 2023. The effect of neonatal vaccination for bovine respiratory disease in the face of a dual challenge with bovine viral diarrhea virus and Mannheimia hemolytica. Vaccine 41, 3080–3091. <a href="https://doi.org/10.1016/j.vaccine.2023.04.005">https://doi.org/10.1016/j.vaccine.2023.04.005</a>  Reddout, C., Hernandez, L.P., Chase, C.C.L., Beck, P., White, F., Salak-Johnson, J.L., 2023. Immune phenotype is differentially affected by changing the type of bovine respiratory disease vaccine administered at revaccination in beef heifers. Frontiers Vet Sci 10, 1161902. <a href="https://doi.org/10.3389/fvets.2023.1161902">https://doi.org/10.3389/fvets.2023.1161902</a>  Donlon JD, McAloon CG, Hyde R, Aly S, Pardon B, Mee JF.  A systematic review of the relationship between housing environmental factors and bovine respiratory disease in preweaned calves – Part 2: Temperature, relative humidity and beddingThe Veterinary Journal 300-302 (2023) 106032 <a href="https://doi.org/10.1016/j.tvjl.2023.106032">https://doi.org/10.1016/j.tvjl.2023.106032</a> Rojas, H. A., White, B. J., Amrine, D. E., Larson, R. L., & Capik, S. F. (2022). Associations between pen management characteristics and bovine respiratory disease incidence in the first 45 days post-arrival in feedlot cattle. The Bovine Practitioner, 56(1), 40-52. https://doi.org/10.21423/BOVINE-VOL56NO1P40-52 Rojas, H. A., White, B. J., Amrine, D. E., Larson, R. L., Capik, S. F., & Depenbusch, B. E. (2022). Impact of Water Sources and Shared Fence Lines on Bovine Respiratory Disease Incidence in the First 45 Days on Feed. Veterinary Sciences, 9(11), 646. https://doi.org/10.3390/vetsci9110646   Research abstracts:  Ramirez B, McAllister H, Capik S, Valeris-Chacin R, Harvey K, Karisch B, Woolums A, Morley PS, Pinnell L, Scott M.  Update on the molecular epidemiological assessment of beef cattle management   systems.  Conference for Research Workers in Animal Disease (CRWAD).             Chicago IL.  January 20-23, 2024.  #P166. Ramirez B, McAllister H, Capik S, Valeris-Chacin R, Harvey K, Woolums A, Karisch B, Scott M. Longitudinal blood RNA-Seq analysis of cattle to determine the impact of vaccination and marketing on clinical BRD.  Conference for Research Workers in Animal Disease (CRWAD).  Chicago IL.  January 20-23, 2024.  #P131.                   Capik S, Larson R, White B, Amrine D, Karisch B, Harvey K, Parish J, Woolums A, McAllister H, Gouvea V, Scott M.  2023 update on the impact of management decisions on BRD morbidity, mortality, and performance in beef calves.  Conference for Research Workers in Animal Disease (CRWAD).  Chicago IL.  January 20-23, 2024.  #P106. Prosser H, Ramirez B, Valeris-Chacin R, Crosby W, Morley PS, Woolums A, Karisch B, Scott M.  Transcriptome analysis of high risk stocker cattle associates consistent inflammation-related pathways with BRD.  Conference for Research Workers in Animal Disease (CRWAD).  Chicago IL.  January 20-23, 2024.  #P063.              Crosby WB, Karisch BB, Hiott LM, Pinnell LJ, Doster E, Wolfe C, PIttman A, Frye JG, Jackson CR, Loy JD, Epperson WB, Blanton Jr. J, Capik S, Morley PS, Woolums AR.  Effect of metaphylaxis on the nasopharyngeal microbiome, resistome, and Mannheimia haemolytica in stocker heifers.  Conference for Research Workers in Animal Disease (CRWAD).  Chicago IL.  January 20-23, 2024.  #P002. Doster E, Wolfe C, Crosby WB, Clawson ML, Woolums AR, PInnell LJ.  Morley PS.  Enriching without culture: target-enriched metagenomics allows for strain-level characterization of M. haemolytica.  Conference for Research Workers in Animal Disease (CRWAD).             Chicago IL.  January 20-23, 2024.  #195. Tamm S, Crosby W, Pinnell L, Doster E, Newcomer B, Funk J, Capik S, Wolfe C, Richeson J, Gow S, Valeris-Chacin R, Woolums A, Morley PS.  Environmental, group and individual sampling for characterizing the ecology of Mannheimia haemolytica.  Conference for Research Workers in Animal Disease (CRWAD).  Chicago IL.  January 20-23, 2024.  #196.   Scott M. A., McAllister H. R., Green M. M., Woolums A.R., Karisch B.B., Harvey K. M., Capik S. F. Influence of modified-live viral vaccination and sale strategy on the developing immune system of beef cattle. 2023. Academy of Veterinary Consultants Summer Conference. Denver, CO. McAllister H. R., Capik S. F., Woolums A. R., Karisch B. B., Harvey K. M., Scott M. A. Effect of vaccination and marketing strategies on gene expression patterns in beef cattle via time course RNA-Seq. 2023. Conference of Research Workers in Animal Diseases (CRWAD). Chicago, IL. Scott M. A., Harvey K. M., Karisch B. B., Woolums A. R., Russell J. R. 2023. Integrated Transcriptome and Multi-Tissue Mineral Analyses of Healthy Stocker Cattle Fed Complexed or Inorganic Trace Mineral Supplement. Conference of the American Association of Bovine Practitioners. Milwaukee, WI Dudley E, Lamsal S, Morley PS, Scott M, Pinnell L, Kittana H, Thompson A, Valeris-Chacin R. (2024) Pathogenomics of the respiratory Mycoplasma bovis strains circulating in cattle. Conference of Research Workers in Animal Diseases (CRWAD). Chicago, IL   Magazine Articles Chase C.  Mycoplasma bovis: A challenging pathogen. American Dairymen, November 10, 2022. <a href="https://www.americandairymen.com/articles/mycoplasma-bovis-challenging-pathogen">https://www.americandairymen.com/articles/mycoplasma-bovis-challenging-pathogen</a> Chase C. Animal Health Matters: Water, the No.1 Nutrient. Farm Forum, February 7, 2023. <a href="https://www.farmforum.net/story/news/columnists/2023/02/07/animal-health-matters-water-the-no-1-nutrient/69880594007/">https://www.farmforum.net/story/news/columnists/2023/02/07/animal-health-matters-water-the-no-1-nutrient/69880594007/</a> Chase C.  Support material on mRNA vaccines.  National Institute of Animal Agriculture, May 2023. <a href="https://www.animalagriculture.org/resources/">https://www.animalagriculture.org/resources/</a> Chase C. Make a protection connection. Working Ranch June 2023; 18,4:44-46. <a href="https://www.qgdigitalpublishing.com/publication/?i=793186&p=1&view=issueViewer">https://www.qgdigitalpublishing.com/publication/?i=793186&p=1&view=issueViewer</a> Chase C. Is there a future for mRNA vaccines in commercial cattle production? Progressive Cattle, September 2023, 13,9:36-37. <a href="https://www.agproud.com/articles/57903-is-there-a-future-for-mrna-vaccines-in-commercial-cattle-production">https://www.agproud.com/articles/57903-is-there-a-future-for-mrna-vaccines-in-commercial-cattle-production</a>

Impact Statements

• The molecular epidemiological assessment of beef cattle health management provides new information and data regarding the impact of management on hundreds of host immune, inflammatory, and metabolic pathways. To our knowledge, this project is the first of its kind in beef cattle research. The information reveals potential targets for intervention (pharmacologic or otherwise) to improve cattle health. The data are publicly available and can be used by other researchers to test hypotheses related to the impact of management on host response.
• The neonatal microbiome study serves as the first of its kind to holistically evaluate the development of the microbial community in neonatal cattle, and compare neonatal microbiomes to that of their dams. These new insights provide foundational information regarding how microbial ecology relates to neonatal development, and may lead to the discovery of novel associations and predictors of respiratory disease during the cow-calf production phase.
• The project to assess the blood transcriptome in cattle receiving tulathromycin metaphylaxis project may provide experimental evidence for judicious antimicrobial usage to help minimize AMR development and maximize therapeutic success against BRD. The study highlights a potential secondary mechanism of action for tulathromycin in high-risk stocker cattle which may drive future investigations regarding secondary pharmacokinetics with respect to anti-inflammatory effect and genomic mechanisms in cattle which eventually develop BRD.
• The results of the assessment of blood transcriptome in cattle receiving tulathromycin metaphylaxis indicate a consistent inflammatory response at time of BRD treatment. This information may be leveraged for the development of predictive assays or novel treatment schemes against BRD.
• Evaluation of the pathogenomics of Mycoplasma bovis allowing for the elucidation of virulence mechanisms and the opportunity to improve the current molecular diagnostics of BRD. In fact, the M. bovis isolates will be used in a Hatch capacity project aiming to develop a targeted enrichment methodology to evaluate the M. bovis strain diversity.
• The project to identify pathogen profiles and loci associated with resistance to BRD will further the understanding of the etiology of BRD and the role that specific pathogens play in BRD in beef feedlot animals and in dairy calves; it will also provide additional genomic tools for selection of animals resistant/resilient to BRD.
• Understanding the duration of maternal immunity in the upper respiratory tract of calves could provide insight on clinical protection of colostral antibodies against BRD overtime. Additionally, data from duration of specific colostral antibodies in the respiratory tract of calves could improve intranasal vaccination efficacy by improving vaccination timing.
• Although the study in congoing, future impacts include the elucidation of immunological impacts of fetal exposure to BVDV, a BRD pathogen, and how this early life exposure will impact the health and risk of development of clinical BRD during calf hood.
• Determining whether day 1 versus day 14 priming IN vaccination gives better immunity to dairy heifers provides information to support more effective prevention of BRD and protection of their future health status.
• Elucidating the influence of nasal mineral administration on the microbiome ecosystem in stressed weaned dairy calves submitted to transportation (that were subsequently challenged with BHV1) could lead to new methods to prevent or decrease BRD in stressed populations.
• Intranasal minerals offer an opportunity to study alternatives to metaphylactic antibiotics for the prevention of BRD in beef calves after arrival to stocker or feedlot operations.
• Identifying gene expression affected by vaccination, trace mineral status, and virus infection provides new knowledge to help explain the differences in the observed enhanced immune response and improved health status of animals treated with ITM, providing a foundation for development and testing of new strategies to improve cattle health through improved immunity.
• The research evaluating bovine respiratory coronavirus shedding post co-mingling and transport will provide new knowledge regarding the relative impact of these two stressors, which will provide data to support the development of new models to predict disease, and new approaches to prevent disease, in calves and other hosts that are susceptible to disease after co-mingling and transport
• Research to evaluate the impact of tulathromycin metaphylaxis on antimicrobial resistance (AMR) demonstrated that information obtained by metagenomic sequencing can be different than that obtained by bacterial culture and in vitro susceptibility testing. This information will improve the application and interpretation of results of ongoing AMR research in cattle health management.
• The study evaluating the impacts of trace mineral supplementation on host whole blood transcriptomes represents the first reporting of combined host transcriptome and tissue mineral concentration in cattle treated with trace minerals. It provides new foundational knowledge regarding the inflammatory, immune, and metabolic system influences of trace mineral supplementation, which could eventually support more precise and effective use of trace mineral supplements.
• The project assessing preweaning vaccination and postweaning commingling will provide new information regarding the effects of common preweaning and marketing management decisions, which will support improved decision making by veterinarians and cattle producers trying to decide which practices have the greatest impact on calf health.
• The 2024 BRD Symposium will bring together scientists, educators, veterinarians, producers, and policy makers to explore and challenge our paradigms by sharing the latest BRD research, emerging management technologies, and systems that can be translated into industry practices that prevent and control BRD in beef and dairy cattle