Measurement of Progress and Results

Objective 1 Progress Measurements:

During year 1, NC-107 will hold a BRD diagnostic and pathogenesis symposium to be held in conjunction with Academy of Veterinary Consultants in December 2001.

At the end of the year 1, BRD summaries from 4 stations (MN, SD, IA IL) diagnostic laboratories will be compiled and summarized. By the end of year 3, BRD summaries from 8 stations (AL, IA, IL, KS, MN, OK, SD, TX) will be used and by the end of the project at year 5 all 13 diagnostic laboratory (AL, CA, CO, GA, IL, IA, KS, MN, MS, OK, SD, TX, WI) BRD data will be summarized. Each year these BRD epidemiological data will be examined at the NC-107 meeting for patterns and trends of emerging and/or re-emerging BRD pathogens. These summaries will be published in a peer reviewed article by year 5.

The large BRD field studies instituted by OK and TX for pathogen patterns and identification will be summarized yearly and these summaries will be published in a peer reviewed article by year 5.

The molecular diagnostic and typing methods developed for BVDV by SD and MI (in collaboration with AL and NE), M. bovis by IA (in collaboration with MN, SD and MI), M. hemolytica by MN (in collaboration with NADC and WI), coronavirus by LA (in collaboration with OK and TX), bovine herpesvirus by NE and OK and BRSV by CA and GA will be completed and validated by the end of year 2. These validated tests will be made available to the American Association of Veterinary Laboratory Diagnosticians, other diagnostic laboratories and peer reviewed papers will be published by year 5.

Objective 2 Progress Measurement:

It is expected that measuring progress made on studies of mechanisms will be less precise than measuring progress on intervention target development. At the end of Year 1 of the project, it is expected that the following studies will be completed: Work on MHC Class I down regulation by BHV-1 infection (NE); Comparisons between the p26 proteins of BIV and JDV (KS); Immunohistochemical evaluation on cases of AlP (GA); Cytotoxicity studies with BVDV (KS); A trial with a tobacco leaf recombinant BYDV vaccine (KS); Role of inflammatory cytokines in enhancing susceptibility of bovine leukocytes (WI); Major molecules delineated in signal transduction pathways of neutrophils and macrophages targeted by M. haemolytica leukotoxin (MN); Trials blocking expression of inflammatory cytokines in an in-vivo model ofM haemolytica pneumonia (MN); Determination of the relative contribution ofH. somnus LOS in endothelial cell apoptosis (WI).

After Year 3, the following studies will be completed: Latency mechanism studies with BHV-1 (NE); Role of the major BHV-1 glycoproteins in immunity will be determined (WI); An epitope vaccine producing cytotoxic T cell mediated protection against BHV-1 will be tested (NE); Interaction of allergens and BRSV (CA) and association of bacteria and BRSV in AIP (GA); Mechanisms of thrombocytopenia production by BVDV (KS and MI); Effects of BVDV infection on endocrine function (MI); Several virulence factors, including adherence factors of M. haemolytica will be characterized (OK, NADC); Cytotoxin ofM. bovis characterized (IA); Signaling receptors used by M. haemolytica leukotoxin characterized (MN); Role ofP2X7 endothelial cell receptor in apoptosis after H. somnus infection characterized; Lung antibacterial peptides characterized (IA).

Objective 3 Project Measurement

Pathogen reduction strategies with BVDV will be completed by year 2 by MI and AL. The application of new diagnostic methodologies developed under objective 1 will be integrated into cow-calf and feeder cattle management schemes and tested for effectiveness based on previous data. In addition, novel vaccine strategies will be applied by TX, OK, and AL to reduce pathogen load by developing herd immunity prior to weaning and shipment. Data and management information generated from long-term field vaccination studies by OK and TX will be analyzed during the later stages of the project. As compounds are developed and tested new antivirals will be evaluated by AL and MI. The non-specific host response to interferon will be examined by AL and SD in feeder cattle promoting generic protection during high risk periods.

Issues associated with metaphylaxis and antimicrobial susceptibility will be addressed during the first 3 years by TX, MI, and AL. The inappropriate use of antimicrobials and sub-therapeutic levels of antibiotics will continue to be examined throughout the project period. Management practices to reduce the potential for antimicrobial susceptibility will be generated from the data gathered during this period.