Source: MICHIGAN STATE UNIV submitted to
REDUCING ECONOMIC LOSSES AND FOOD SAFETY RISKS RELATED TO MASTITIS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
0162886
Grant No.
(N/A)
Project No.
MICL01708
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Apr 1, 2009
Project End Date
Mar 31, 2014
Grant Year
(N/A)
Project Director
Erskine, RO, J..
Recipient Organization
MICHIGAN STATE UNIV
(N/A)
EAST LANSING,MI 48824
Performing Department
Large Animal Clinical Sciences
Non Technical Summary
Mastitis is a an important disease of dairy cattle, and therapy of mastitis is often unsuccessful Vaccination and immune enhancement strategies for mastitis are not successful This purpose of this project is to reduce losses form amstitis from better therapeutic intervention and enhancing the immune resistance of the cow to infection. Severe coliform mastitis continues to cause significant losses to dairy producers. Current vaccines offer limited protection for dairy catle. We have furthered our understanding of the immunological changes that occur from immunization with of currently available vaccines. Our research is attempting to improve methods to vaccinate dairy cattle to protect them from this disease. Severe coliform mastitis continues to cause significant losses to dairy producers. Current vaccines offer limited protection for dairy catle. We have furthered our understanding of the immunological changes that occur from immunization with of currently available vaccines. Our research is attempting to improve methods to vaccinate dairy cattle to protect them from this disease. Mastitis continues to cause significant losses to dairy producers. Current vaccines offer limited protection for dairy cattle. We have furthered our understanding of the immunological changes that occur from immunization with currently available vaccines. Our research is improving methods to vaccinate dairy cattle to protect them from this and other diseases
Animal Health Component
100%
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
3113410109075%
3113410118025%
Knowledge Area
311 - Animal Diseases;

Subject Of Investigation
3410 - Dairy cattle, live animal;

Field Of Science
1090 - Immunology; 1180 - Pharmacology;
Goals / Objectives
There are two main objectives of our research plan over the next five years: 1) Continue to determine efficacy of antibacterial drugs as a therapy for clinical mastitis. Special emphasis will be given to severe clinical mastitis. Additionally, we will establish protocols that encourage prudent drug use in relation to pre-harvest food safety, reduce the risk of developing resistance of pathogens to antibacterial drugs, and practice sound pharmacokinetic and pharmacodynamic principles. 2) We will develop and enhance the efficacy and technology of Gram-negative bacterins. Under this objective, there will be three foci: Apply novel management practices to try to maximize the efficacy of currently available vaccines. Develop new generation of core-antigen bacterins that will enhance cell mediated and humoral responses to immunization in dairy cattle. Determine factors (nutritional and infectious) that may alter the response of cattle to core-antigen immunization.
Project Methods
Objective 1 - Continue to determine efficacy of antibacterial drugs as a therapy for clinical mastitis. In conjunction with commercial dairies and private practitioners, we will continue to evaluate potential application of MIC antibiograms for designing mastitis therapy protocols. We will collect representative bacterial isolates from participating herds and establish an MIC data base through the services of the Diagnostic Center for Population and Animal Health, Microbiology laboratory. This information will be used to identify the best therapy protocols. Outcomes to be measured will include cull rates and mortality related to mastitis, days in the sick pen and amount of milk discarded following the clinical mastitis case, and incidence of recurring cases. Objective 2- Apply novel management practices to try to maximize the efficacy of currently available vaccines and develop new generation of core-antigen bacterins that will enhance cell mediated and humoral responses to immunization in dairy cattle. It is anticipated that different bacterin formulations will be tested in dairy cattle to determine 1) serum and milk IgG1 and IgG2 responses, and 2) the to promote T-cell maturation as indicated by proliferation and cytokine response to the bacterin antigen. Following this initial phase, potential candidates will be tested in cattle for safety and efficacy in reducing the severity of clinical coliform mastitis. Collaboration is also expected with Dr. Lorraine Sordillo, Meadowbrook Professor of Animal Health, Department of Large Animal Clinical Sciences. Determine factors (nutritional and infectious) that may alter the response of cattle to core-antigen immunization. Preliminary studies in conjunction with Dr, Sordillo have suggested that cows infected with Bovine Leukosis Virus (BLV) may have impaired responses to immunization, including core-antigen bacterins. One area of investigation that has received little attention is the potential impact of BLV status and altered immune function on vaccine efficacy. The overall goal of this project is to determine the impact of BLV status on J5 bacterin vaccine protocols. If we determine that BLV infection alters the ability of the bovine immune system to respond to vaccination, the implications for maintaining the health and well being of dairy cattle in the face of infectious challenge from mastitis pathogens, and potentially organisms that cause disease in other tissue systems, will be far-reaching. RJ Erskine has a part-appointment in cooperative extension, and thus regularly participates in outreach activities and learning progrmas. This opportunity, coupled with publications in peer-reviewed and industry-related journals, will be used to disseminate information gained from this research to the target audience.

Progress 04/01/09 to 03/31/14

Outputs
Target Audience: Dairy producers Veterinary practitioners Regulatory and Milk Co-operative field representatives Extension Educators Veterinary and undergraduate students Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Graduate training was provided for R Moore and W Escalante (doctorate candidates), and E. Kabara (post-doctoral). Several veterinary and undergraduate students were employed for the project. How have the results been disseminated to communities of interest? A major outreach effort has engaged various audiences through online and social media. Our goal is to provide information and advice to veterinarians, dairy producers, dairy farm managers, dairy farm employees and consumers.Toward that goal, we launched the website (http://www.qualitymilkalliance.com) in April 2013. Since then, we have published 24 articles in English and Spanish that have attracted 4,000 visitors. The most popular posts so far have been: (1) Herd Somatic Cell Counts: The Complete Story, (2) Farm visit (photos) and (3) Quality Milk Is All About Teamwork. Our strategy to promote the websiteincludes using social media (YouTube, Facebook and Twitter). We have established a Facebook page athttps://www.facebook.com/pages/Quality-Milk-Alliance/147462438740648. We use this page primarily to announce new material on the website. We tweet as Quality Milk Now -https://twitter.com/qualitymilknow. In addition to using Twitter to promote new material on the website, we also retweet relevant comments by others and comment on dairy and farm news. As of June 1, 2014, there have been 75 “likes” on Facebook and 170 followers on Twitter. The plan is to post new material on the website at least every two weeks, using Facebook and Twitter to expand our audience. Additionally, we are assembling a media library of images and video that we can use for various purposes. Additional outreach efforts such as webinars, presentations, and shortcourses will increase awareness, on the part of dairy producers and veterinarians, of drug residue avoidance and has demonstrated (through hands-on laboratory experiences) how to implement on-farm bacteriology to reduce antibiotic use in the therapy for mastitis. Therapeutic strategies that implement sound pharmacological principles as the foundation for prudent antibiotic use were promoted. A manual (in English and Spanish) for use by veterinarians to train employees and herd managers how to avoid drug residues (in milk and meat) was developed and will be made available on the QMA website. To date, presentations or posters have been presented at the annual meetings of the National Mastitis Council, American Association of Bovine Practitioners, and Society of Rural Sociologists, and The Great Lakes Regional Dairy Conference. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? We have continued outreach efforts to promote better stewardship of antibiotic use on dairy farms. Mastitis is the single most common cause of antibiotic use in adult dairy cattle. Thus, we have focused on reducing unwarranted use of antibiotic therapy for the treatment of this disease. Key contributions included workshops on mastitis bacteriology for dairy producers and veterinary practices to help these stakeholders make better therapeutic decisions. Additionally, several presentations were given to veterinary practitioner and dairy producer groups to highlight the interaction between poor therapeutic decisions and residues in meat and milk. To help dairy producers make better therapeutic decisions for cows with mastiutis, we tested the reliability and practicality of a novel bacteriology media (NeoFilm; Neogen Corporation, Lansing, MI) for detecting and differentiating causative pathogens in milk collected from cows with clinical mastitis . A successful pilot study was completed that demonstrated that thuis system was able to predict classes of causative microbes on a comparable basis to standard bacteriology. Also, the system was proven to be applicable and practical for dairy producers to use on farm. We are currently working on an extension-based USDA-NIFA funded project to reduce mastitis and antibiotic use to improve dairy farm profitability, cow welfare and milk quality. A major thrust of this project has been to develop an on-farm evaluation system for use by producers and veterinarians to assess challenges in milk quality (Quality Milk Alliance [QMA]; qualitymilkalliance.com). Although the QMA system will evaluate traditional areas of farm management related to mastitis control (milking techniques, milking equipment function, cow environment, treatment and monitoring of infected cows), this evaluation system will be unique in that it will also include the management culture of the farm; thus helping to identify communication and employee management barriers to mastitis control. Information collected from a pilot study in the winter of 2014 from dairy producers in Michigan, as well as focus group discussions among producers, veterinarians and employees, have identified key concerns of dairy stakeholders with respect to herd mastitis control programs: 1) the desire for producers to attain assistance in employee training and education, 2) the potential role that veterinarians can play in providing this need, and 3) the desire of employees to be further educated and receive more consistent training. We are in a position to help address these stakeholder concerns by applying the QMA evaluation onto farms as part of a three year intervention study in three states. Finally, our team investigated methods to improve host immune responses during the peri-parturient period, a critical time in the lactation cycle of a cow for resistance to mastitis. Intense lipid mobilization during the transition period in dairy cows is associated with increased disease susceptibility. The potential impact of altered plasma nonesterified fatty acids (NEFA) concentrations and composition on host inflammatory responses that may contribute to disease incidence and severity are not known. The objective of this research is to evaluate if increased NEFA concentrations modify vascular inflammatory responses in vitro by changing the expression of important inflammatory mediators that are important in the pathogenesis of infectious diseases of transition cows such as mastitis and metritis. Uncontrolled inflammation contributes to the increased incidence and severity of infectious diseases in periparturient dairy cattle. In particular, the role of n-3 fatty acid content in altering the profile of vasoactive eicosanoids and attenuating endothelial cell inflammatory responses is a central aim of our work.

Publications

  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Raphael, W., L. Halbert L, G. A. Contreras, and L.M. Sordillo. 2014. Association between polyunsaturated fatty acid- derived oxylipid biosynthesis and leukocyte inflammatory marker expression in periparturient dairy cows. J Dairy Sci. 97:3615-3625
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Kabara E, Sordillo LM, Holcombe S, Contreras GA. 2014. Adiponectin links adipose tissue function and monocyte inflammatory responses during bovine metabolic stress. Comp Immunol Microbiol Infect Dis. 37:49-58.
  • Type: Book Chapters Status: Published Year Published: 2014 Citation: Ruegg PL, RJ Erskine and DE Morin. 2014. Mammary Gland Health. In Large Animal Internal Medicine, 5th edition, BP Smith, editor, pp. 1015-1043.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2014 Citation: RJ Erskine and JR Middleton. Failure of Mastitis Therapy: Is it the Bugs, Drugs, or Us? Shortcourse presented at the 53rd Annual Mtng National Mastitis Council, Ft Worth, TX, Jan, 2014.
  • Type: Conference Papers and Presentations Status: Other Year Published: 2014 Citation: RJ Erskine. Dont Forget Antibiotic Residues&.and Other Related Topics. Great Lakes Regional Dairy Conference, Mt Pleasant, MI, February, 2014
  • Type: Conference Papers and Presentations Status: Other Year Published: 2014 Citation: RJ Erskine Who is Making the Treatment Decisions on the Dairy Farm? Michigan Dairy Industry Conference, Frankenmuth, MI May, 2014.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2014 Citation: RJ Erskine and JR Middleton. Failure of Mastitis Therapy: Is it the Bugs, Drugs, or Us? Shortcourse presented at the Regional Mtng National Mastitis Council, Ghent, Belgium, August, 2014.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Mattmiller, S.A., B.A. Carlson, J.C. Gandy, and L.M. Sordillo. 2014. Reduced macrophage selenoprotein expression alters oxidized lipid metabolite biosynthesis from arachidonic and linoleic acid. J Nutr Biochem. 2014 25:647-654.
  • Type: Websites Status: Published Year Published: 2014 Citation: http://qualitymilkalliance


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

Outputs
Target Audience: Dairy producers Veterinary practitioners Regulatory and Milk Co-operative field representatives Extension Educators Veterinary and undergraduate students Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Graduate training was provided for SA Mattmiller and W. Raphael (doctorate candidates). Several veterinary and undergraduate students were employed for the project. How have the results been disseminated to communities of interest? Dedicated website, seminars and presentations for dairy producers and veterinary practitioners, poster and papaers presented at scientific meetings What do you plan to do during the next reporting period to accomplish the goals? Outreach efforts have resulted in increased awareness on the part of dairy producers and veterinarians of drug residue avoidance and has demonstrated (through hands-on laboratory experiences) how to implement on-farm bacteriology to reduce antibiotic use in the therapy for mastitis. We will continue these efforts by developing an on-farm evaluation system that will help identify and decrease barriers to mastitis control and prudent antibiotic use. Research efforts have demonstrated that bovine endothelial cells cultured with enriched concentrations of n-3 fatty acids decreased the expression of proinflammatory cytokines, adhesion molecules, and reactive oxygen species with a concomitant increase in the biosynthesis of proresolving eicosanoids, including resolvins, protectins, and lipoxins. This showed for the first time that increasing the n-3 FA content of endothelial cell phospholipids could alter the expression of eicosanoids and control the magnitude of inflammatory responses. Additionally, in vitro exposure of endothelial cells to NEFA mixtures, that mimicked the composition and concentration found in cows during the transition period, were found to alter inflammatory responses. Future studies of specific mechanisms by which high NEFA concentrations induce vascular proinflammatory changes, or the mechanisms by which resolvins, protectins, and lipoxins may modify endothelial inflammatory pathways, may elucidate means to reduce the severity and duration of diseases that are typically observed during intense lipid mobilization stages such as in the transition period of dairy cows.

Impacts
What was accomplished under these goals? We have continued outreach efforts to promote better stewardship of antibiotic use on dairy farms. Mastitis is the single most common cause of antibiotic use in adult dairy cattle. Thus, we have focused on reducing unwarranted use of antibiotic therapy for the treatment of this disease. Key contributions included workshops on mastitis bacteriology for dairy producers and veterinary practices to help these stakeholders make better therapeutic decisions. Additionally, several presentations were given to veterinary practitioner and dairy producer groups to highlight the interaction between poor therapeutic decisions and residues in meat and milk. A series of extension-based meetings on drug residue avoidance was offered throughout the winter of 2012-2013. A second approach from our team investigated methods to improve host immune responses during the peri-parturient period, a critical time in the lactation cycle of a cow for resistance to mastitis. Intense lipid mobilization during the transition period in dairy cows is associated with increased disease susceptibility. The potential impact of altered plasma nonesterified fatty acids (NEFA) concentrations and composition on host inflammatory responses that may contribute to disease incidence and severity are not known. The objective of this research is to evaluate if increased NEFA concentrations modify vascular inflammatory responses in vitro by changing the expression of important inflammatory mediators that are important in the pathogenesis of infectious diseases of transition cows such as mastitis and metritis. Uncontrolled inflammation contributes to the increased incidence and severity of infectious diseases in periparturient dairy cattle. In particular, the role of n-3 fatty acid content in altering the profile of vasoactive eicosanoids and attenuating endothelial cell inflammatory responses is a central aim of our work.

Publications

  • Type: Conference Papers and Presentations Status: Published Year Published: 2013 Citation: Schewe, R.L., J. Kayitsinga, G.A. Contreras, R.J. Erskine, R.O. Martinez. Barriers to Reducing Antibiotic Use in the Dairy Industry. Rural Sociological Society, New York, NY; August, 2013.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2013 Citation: R.L. Schewe, J. Kayitsinga, C. Odom, G.A. Contreras, P Durst, R.J. Erskine, E.P. Hovingh, R.O. Martinez, R. Mobley, S. Moore,L. Sordillo. Mastitis and Antimicrobial Usage on Dairy Herds in Michigan, Pennsylvania, and Florida. Yale Food Systems Symposium: Urbanization and Transformation. New Haven,CT; October, 2013.
  • Type: Other Status: Published Year Published: 2013 Citation: R.L. Schewe, J. Kayitsinga, G.A. Contreras, R.O. Martinez, P. Durst, S. Moore, E.P. Hovingh, R. Mobley , L.M. Sordillo , R.J. Erskine. Development of a Dairy Farm Evaluation System to Reduce Mastitis and Antimicrobial Use. American Association of Bovine Practitioners (poster and abstract), Milwaukee, WI September, 2013.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Raphael W. and L.M. Sordillo. Dietary Polyunsaturated Fatty Acids and Inflammation: The Role of Phospholipid Biosynthesis. Review. Int. J. Mol. Sci. 2013, 14(10), 21167-21188.


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

Outputs
OUTPUTS: We have continued outreach efforts to promote better stewardship of antibiotic use on dairy farms. Mastitis is the single most common cause of antibiotic use in adult dairy cattle. Thus, we have focused on reducing unwarranted use of antibiotic therapy for the treatment of this disease. Key contributions included workshops on mastitis bacteriology for dairy producers and veterinary practices to help these stakeholders make better therapeutic decisions. Additionally, several presentations were given to veterinary practitioner and dairy producer groups to highlight the interaction between poor therapeutic decisions and residues in meat and milk. A series of extension-based meetings on drug residue avoidance was commenced at the end of the year and will continue through early 2013. A second approach from our team investigated methods to improve host immune responses during the peri-parturient period, a critical time in the lactation cycle of a cow for resistance to mastitis. Intense lipid mobilization during the transition period in dairy cows is associated with increased disease susceptibility. The potential impact of altered plasma nonesterified fatty acids (NEFA) concentrations and composition on host inflammatory responses that may contribute to disease incidence and severity are not known. The objective of this research is to evaluate if increased NEFA concentrations modify vascular inflammatory responses in vitro by changing the expression of important inflammatory mediators that are important in the pathogenesis of infectious diseases of transition cows such as mastitis and metritis. Uncontrolled inflammation contributes to the increased incidence and severity of infectious diseases in periparturient dairy cattle. In particular, the role of n-3 fatty acid content in altering the profile of vasoactive eicosanoids and attenuating endothelial cell inflammatory responses is a central aim of our work. PARTICIPANTS: LM Sordillo, GA Contreras, and RJ Erskine are faculty in the Department of Large Animal Clinical Sciences. Graduate training was provided for SA Mattmiller and W. Raphael (doctorate candidates). Several veterinary and undergraduate students were employed for he project. Collaborators and partnering organizations included: Michigan State University Extension, Michigan Milk Producers Association, and the Michigan Department of Agriculture and Rural Development. TARGET AUDIENCES: Dairy producers Veterinary practitioners Regulatory and Milk Co-operative field representatives Extension Educators Veterinary and undergraduate students PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Outreach efforts have resulted in increased awareness on the part of dairy producers and veterinarians of drug residue avoidance and has demonstrated (through hands-on laboratory experiences) how to implement on-farm bacteriology to reduce antibiotic use in the therapy for mastitis. Additionally, therapeutic strategies that implement sound pharmacological principles as the foundation for prudent antibiotic use were promoted. Research efforts have demonstrated that bovine endothelial cells cultured with enriched concentrations of n-3 fatty acids decreased the expression of proinflammatory cytokines, adhesion molecules, and reactive oxygen species with a concomitant increase in the biosynthesis of proresolving eicosanoids, including resolvins, protectins, and lipoxins. This showed for the first time that increasing the n-3 FA content of endothelial cell phospholipids could alter the expression of eicosanoids and control the magnitude of inflammatory responses. Additionally, in vitro exposure of endothelial cells to NEFA mixtures, that mimicked the composition and concentration found in cows during the transition period, were found to alter inflammatory responses. Future studies of specific mechanisms by which high NEFA concentrations induce vascular proinflammatory changes, or the mechanisms by which resolvins, protectins, and lipoxins may modify endothelial inflammatory pathways, may elucidate means to reduce the severity and duration of diseases that are typically observed during intense lipid mobilization stages such as in the transition period of dairy cows.

Publications

  • Contreras, G.A., S.A. Mattmiller, W. Raphael, J.C. Gandy, L.M. Sordillo. 2012. Enhanced n-3 phospholipid content reduces inflammatory responses in bovine endothelial cells. J Dairy Sci 95:5729-5736.
  • Contreras, G.A., W. Raphael, S.A. Mattmiller, J. Gandy, L.M. Sordillo. 2012. Nonesterified fatty acids modify inflammatory response and eicosanoid biosynthesis in bovine endothelial cells. J Dairy Sci 95:5011-5023.
  • Erskine RJ. Vaccination strategies for mastitis. Vet Clin North Am Food Anim Pract. 2012 Jul;28(2):257-270.


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

Outputs
OUTPUTS: 1 ) We have continued to investigate the immunology of core-antigen bacterins directed towards the protection against coliform mastitis, and better stewardship of antibiotic use on dairy farms. Continuing education seminars regarding the immunology of J5 Escherichia coli bacterins and prudent antibiotic use in the therapy of mastitis were presented at Quality Milk Short Course for Dairy Practitioners, - St Peters, MN (Univ of Minnesota) July, 2011 Quality Milk Short Course of the Dairy Production Medicine Program for Dairy Practitioners, State College, PA (Pennylvania State University) October, 2011 NOSAI Japan- Veterinary Shortcourse, East Lansing, MI, Oct, 2011 Antimicrobial Stewardship in Canadian Agriculture and Veterinary Medicine Conference, Toronto, ONT, Nov, 2011 2 ) The role of oxidative stress on mammary gland inflammatory responses to mastitis-causing pathogens was investigated. Studies have identified key enzymatic pathways that could be targeted for therapeutic intervention. In addition lipid mobilization during the transition period was identified as an important underlying cause of increased inflammatory responses to mastitis-causing pathogens. Ongoing research is elucidating that changing the composition of plasma fatty acids and leukocyte phospholipid content may alter the severity and duration of inflammation associated with coliform mastitis Seminars regarding oxidative stress and mastitis were presented at Annual Conference of the Japan Veterinary Medical Association, Gifu, Japan. February 2011. Pacific Northwest Animal Nutrition and Management Conference, Portland, Oregon. October 2011. PARTICIPANTS: R Erskine provided leadership of this project and was the PI for the J-5 bacterin studies. A Contreras was the primary contributor for the lipid mobilization studies, in addition to LM Sordillo. PC Bartlett provided statistical analysis. LM Sordillo provided laboratory collaboration TARGET AUDIENCES: Dairy producers, veterinarians. and other dairy industry professionals PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
Coliform mastitis continues to be a disease with important economic consequences for dairy producers in Michigan, the U.S. and globally. The core-antigen bacterins are an important technology in helping to reduce the impact of this disease. However, limitations have been determined with the use of these bacterins, and we continue to explore new methods to enhance the benefits of this technology. Cows are subjected to dynamic changes in fat mobilization during periods of negative energy balance, particularly near parturition and early lactation. These changes can alter the ability of dairy cattle to respond to inflammation caused by colifrom mastitis, and ultimately the outcome of infection. Manipulation of the fatty acids in plasma, and thus leukocyte membranes, through nutrition may affect the cow's ability to reduce the severity of infection.

Publications

  • Contreras, G.A. and L.M. Sordillo. 2011. Lipid mobilization and inflammatory responses during the transition period. Comp. Immunol. Microbiol. Infectious Dis. 34:281-289.
  • Aitken, S.L., C.M. Corl, and L.M. Sordillo. 2011. Pro-inflammatory and pro-apoptotic gene expression of TNF-alpha stimulated bovine mammary endothelial cells. Vet. Immunol. Immunopathol. 140:282-290.
  • Hill, T.M., M.J. VandeHaar, L.M. Sordillo, D.R. Catherman, H.G. Bateman, and R.L. Schlotterbeck. 2011. Fatty acid intake alters growth and immunity in milk-fed calves. J. Dairy Sci. 94:3936-3948.
  • Aitken, S.L., C.M. Corl, and L.M. Sordillo. 2011. Immunopathology of Mastitis: Insights into disease recognition and resolution. J. Mammary Gland Neoplasia. Epub ahead of print: DOI: 10.1007/s10911-011-9230-4.
  • Sordillo, L.M. 2011. New concepts in the causes and control of mastitis. J. Mammary Gland Neoplasia. Epub ahead of print: DOI: 10.1007/s10911-011-9239-8
  • Sordillo, L.M. and S. L. Aitken 2011. Mammary Resistance Mechanisms - Endogenous. In: Fuquay, J.W., Fox, P.F. and McSweeney, P.L.H. (eds), Encyclopedia of Dairy Sciences, Second Edition, vol. 3, pp. 386-391. San Diego: Academic Press.
  • Contreras, G.A. and L.M. Sordillo. 2011. Lipid mobilization and inflammatory responses during the transition period. Comp. Immunol. Microbiol. Infectious Dis. 34:281-289.
  • Contreras, G.A. and J.M. Rodriguez. 2011. Mastitis: Comparative Etiology and Epidemiology. J. Mammary Gland Neoplasia. DOI: 10.1007/s10911-011-9234-0
  • Contreras, G.A. 2011. Mycoplasma bovis in dairy cattle. Mycoplasma bovis en el ganado lechero. Albeitar 26:28-30.
  • Erskine R.J., C. M. Corl, J. C. Gandy, and L. M. Sordillo. 2011. Effect of infection with bovine leukosis virus on lymphocyte proliferation and apoptosis in dairy cattle. Am J Vet Res. Aug;72(8):1059-64.
  • Erskine RJ, P.C. Bartlett, K.M. Sabo, and L.M. Sordillo. Bovine Leukemia Virus Infection in Dairy Cattle: Effect on Serological Response to Immunization against J5 Escherichia coli Bacterin. Vet Med Intl. Volume 2011 (2011), Article ID 915747, 5 pages doi:10.4061/2011/915747
  • Mattmiller, S.A., C.M. Corl, J.C. Gandy, J.J. Loor, and L.M. Sordillo. 2011. Glucose transporter and hypoxia-associated gene expression in the mammary gland of transition dairy cattle. J. Dairy Sci. 94:2912-2922.


Progress 01/01/10 to 12/31/10

Outputs
OUTPUTS: We have continued to determine the immunology of core-antigen bacterins directed towards the protection against coliform mastitis. 1) Recently completed trials determined that infection with Bovine Leukosis Virus (BLV) may impair the ability of dairy cattle to serologically respond to a series of multiple immunizations with J5 Escherichia coli bacterin. Additional research has determined that lymphocytes from BLV infected cattle may have altered cell proliferation in and apoptotic mechanisms than non-BLV infected cattle. 2) Continuing education seminars regarding the immunology of J5 Escherichia coli bacterins and prudent antibiotic use in the therapy of mastitis were presented at The National Mastitis Council, Regional Meeting, Grand Rapids, MI, Sept, 2010, Minnesota Quality Milk Program for Veterinarians, St Peters, MN, May, 2010, and Immunology Short course for Bovine Veterinarians, Guelph, Ontario, June, 2010 The role of oxidative stress on mammary gland inflammatory responses to mastitis-causing pathogens was investigated. These studies identified for the first time key enzymatic pathways that could be targeted for therapeutic intervention. 1) Lipid mobilization during the transition period was identified as an important underlying cause of increased inflammatory responses to mastitis-causing pathogens. Preliminary studies showed that changing the composition of plasma fatty acids and leukocyte phospholipid content and alter the severity and duration of inflammation associated with coliform mastitis 2) Seminars regarding oxidative stress and mastitis were presented at The International Meeting of Production Diseases in Farm Animals. Gent, Belgium June, 2010. World Buiatrics Congress, Santiago, Chili. November, 2010 Tthe American Association of Bovine Practitioners. Albuquerque, New Mexico, August, 2010. The National Mastitis Council, Regional Meeting, Grand Rapids, MI, Sept, 2010, PARTICIPANTS: R Erskine provided leadership of this project and was the PI for the J-5 bacterin studies. A Contreras was the primary contributor for the lipid mobilization studies as part of a PhD thesis, LM Sordillo served as thesis advisor. PC Bartlett provided statistical analysis. LM Sordillo provided laboratory collaboration TARGET AUDIENCES: Dairy producers, veterinarians. and other dairy industry professionals PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Coliform mastitis continues to be a disease with important economic consequences for dairy producers in Michigan, the U.S. and globally. The core-antigen bacterins are an important technology in helping to reduce the impact of this disease. However, limitations have been determined with the use of these bacterins. IOur research has demonstrated that the presence of BLV in a dairy cow may affect her response to immunization, and possibly natural infection, with coliform bacteria. BLV is a disease that is prevalent in nearly all U.S. dairies, and may infect, on average, 45 to 50% of the adult cattle in a herd. Cows are subjected to dynamic changes in fat mobilization during periods of negative energy balance, particularly near parturition and early lactation. These changes can alter the ability of dairy cattle to respond to inflammation caused by colifrom mastitis, and ultimately the outcome of infection. Manipulation of the fatty acids in plasma, and thus leukocyte membranes, through nutrition may affect the cow's ability to reduce the severity of infection.

Publications

  • Erskine RJ, Brockett AR, Beeching ND, Hull RW, Bartlett PC. 2010. Effect of changes in number of doses and anatomic location for administration of an Escherichia coli bacterin on serum IgG1 and IgG2 concentrations in dairy cows. Am J Vet Res. 71:120-124.
  • Contreras, G.A., N.J. OBoyle, T.H. Herdt, and L.M. Sordillo. 2010. Lipid mobilization in periparturient dairy cows influences the composition of plasma nonesterified fatty acids and leukocyte phospholipid fatty acids. J. Dairy Sci. 93:2508-2516
  • Corl, C.M., G.A. Contreras, and L.M. Sordillo. 2010. Lipoxygenase metabolites modulate vascular-derived platelet activating factor production following endotoxin challenge. Vet. Immunol. Immunopathol. 136:98-107.
  • Corl, C.M., H.R. Robinson, G.A. Contreras, S.J. Holcombe, V.L. Cook, and L.M. Sordillo. 2010. Ethyl puruvate diminishes the endotoxin-induced inflammatory response of bovine mammary endothelial cells. J. Dairy Sci. 93:5188-5199.
  • Sordillo, L.M. and I.K. Mullarky. 2010. Cutting edge technologies in animalomics. Vet. Immunol. Immunopathol. In press. DOI 10.1016/j.vetimm.2010.10.010


Progress 01/01/09 to 12/31/09

Outputs
OUTPUTS: We have continued to determine the immunology of core-antigen bacterins directed towards the protection against coliform mastitis. 1) Recently completed trials determined that a series of multiple immunizations with J5 Escherichia coli bacterin is more effective in stimulating antibody response when injection sites are sequentially rotated about the body, as opposed to injection in the same body location. This data was analyzed and published 2) We are continuing to investigate the effect of Bovine Leukosis Virus disease status on the immune response in dairy cattle following immunization with J5 Escherichia coli bacterin, and IBR and BVD antigens. When completed, the results will help determine if cows that have advanced to a leukosis stage of the disease have an impaired ability to produce antibody responses, and/or lymphocytes cytokine response following immunization. 3) Continuing education seminars regarding the immunology of J5 Escherichia coli bacterins and prudent antibiotic use in the therapy of mastitis were presented at The National Mastitis Council, Regional Meeting, Wilkes-Barre, PA, May, 2009 Maumee Bay Dairy Health Symposium, Oregon, OH, August, 2009 Minnesota Quality Milk Program for Veterinarians, St Peters, MN, Sept and Oct, 2009 PARTICIPANTS: R Erskine provided leadership of this project and was the PI for the J-5 bacterin studies. PC Bartlett provided statistical analysis. LM Sordillo provided laboratory collaboration TARGET AUDIENCES: Dairy producers, veterinarians. and other veterinary health professionals PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Coliform mastitis continues to be a disease with important economic consequences for dairy producers in Michigan, the U.S. and globally. The core-antigen bacterins are an important technology in helping to reduce the impact of this disease. However, limitations have been determined with the use of these bacterins. Our research has demonstrated a more effective method in administering multiple doses of the J5 bacterin. Additionally, we are investigating if the prevalence of BLV in a dairy herd may help explain some of the variability in vaccination response. BLV is a disease that is prevalent in nearly all U.S. dairies, and may infect, on average, 45 to 50% of the adult cattle in a herd.

Publications

  • Kaneene JB, Warnick LD, Bolin CA, Erskine RJ, May K, Miller R. Changes in Multi-drug Resistance of Enteric Bacteria Following an Intervention to Reduce Antimicrobial Resistance in Dairy Calves.J Clin Microbiol. 47:4109-4112, 2009


Progress 01/01/08 to 12/31/08

Outputs
OUTPUTS: We have continued to determine the immunology of core-antigen bacterins directed towards the protection against coliform mastitis. 1) Recently completed trials determined that a series of multiple immunizations with J5 Escherichia coli bacterin is more effective in stimulating antibody response when injection sites are sequentially rotated about the body, as opposed to injection in the same body location. 2) We are continuing to investigate the effect of Bovine Leukosis Virus disease status on the immune response in dairy cattle following immunization with J5 Escherichia coli bacterin, and IBR and BVD antigens. When completed, the results will help determine if cows that have advanced to a leukosis stage of the disease have an impaired ability to produce antibody responses, and/or lymphocytes cytokine response following immunization. 3) Continuing education seminars regarding the immunology of J5 Escherichia coli bacterins and prudent antibiotic use in the therapy of mastitis were presented at The Michigan Veterinary Conference, Lansing, MI, January, 2008 The National Mastitis Council, Regional Meeting, Green Bay, WI, August, 2008 The Czech Republic Buiatric Society, Brno, Czech Republic, October, 2008 The Central Canadian Veterinary Association, Ottawa, Canada, November, 2008 PARTICIPANTS: RJ Erskine; Professor; Large Animal Clinical Sciences PC Bartlett; Professor; Large Animal Clinical Sciences LM Sordillo; Professor; Large Animal Clinical Sciences TARGET AUDIENCES: Dairy producers and veterinarians PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Coliform mastitis continues to be a disease with important economic consequences for dairy producers in Michigan, the U.S. and globally. The core-antigen bacterins are an important technology in helping to reduce the impact of this disease. However, limitations have been determined with the use of these bacterins. Our research has demonstrated a more effective method in administering multiple doses of the J5 bacterin. Additionally, we are investigating if the prevalence of BLV in a dairy herd may help explain some of the variability in vaccination response. BLV is a disease that is prevalent in nearly all U.S. dairies, and may infect, on average. 45 to 50% of the adult cattle in a herd.

Publications

  • SA Wagner and RJ Erskine, Decision Making in Mastitis Therapy , in Current Veterinary Therapy, 5th edition, Food Animal Practice; D.E. Anderson and M. Rings, ed., 2008


Progress 01/01/07 to 12/31/07

Outputs
Hyperimmunization of lactating dairy cows with J5 E coli bacterin (6 doses) reduced the risk of severe mastitis caused by gram-negative pathogens as compared to cows administered three doses. This was especially evident during mid-lactation (45 to 150 days in milk). The reduction of severe mastitis was associated with increased levels of anti-J5 IgG2 antibody in the serum of hyperimmunized cows. Intramammary staphylococcal infections are common in cows and heifers at calving. Intramammary antibiotic are useful in eliminating existing infections in cows at dry-off and have been shown to be useful in preventing new infections in heifers. However, pre-partum intramammary infusion of antibiotics is not practical on many farms. Tylosin is a macrolide that has a high milk:blood ratio, so that tylosin is concentrated and trapped in milk. These studies assessed the systemic use of tylosin to treat staphylococcal infections before calving in primipartum and multipartum cows.

Impacts
We have furthered our understanding of reducing the economic losses in dairy cows from mastitis. The use of J5 bacterins enhances the immune resisitance of dairy cattle, and thus reduces the effects of infection. Our work has demonstrated that current commercial bacterins, though beneficial, are limited in protection, and that development of new applications of this technology may further improve immiune resistance. Additionally, pre-partum therapy of heifers, with systemic, rather than intramammary administration, may be beneficial in reducing the rate of new infections at calving. This would be a more efficient method of administration as compared to intramammary infusion.

Publications

  • Erskine R.J., E.J. VanDyk, P.C. Bartlett, J.L. Burton, M.C. Boyle. Effect of hyperimmunization with an Escherichia coli J5 bacterin in adult lactating dairy cows. J Am Vet Med Assoc 231:1092-1097, 2007.
  • Contreras, GA, Guterbock WM and Sears PM. 2007 Comparison of Systemic and Intra mammary Dry Cow Treatment. Proc. 46th Annual Meeting of the Natl Mast Council. Pg 290.
  • Contreras, GA, Guterbock WM and Sears PM. 2007. Comparison of Systemic and Intra mammary Dry Cow Treatment. Meeting of the 39th Annual Convention of the Am Assoc of Bovine Practitioners. Pg 131
  • Contreras, GA, Guterbock WM and Sears PM. Comparison of Systemic and Intra mammary Dry Cow Treatment. Meeting of the 39th Annual Convention of the Am Assoc of Bovine Practitioners. 2007
  • Contreras, GA, Guterbock WM and Sears PM. Comparison of Systemic and Intra mammary Dry Cow Treatment. Proc. 46th Annual Meeting of the Natl Mast Council. 2007


Progress 01/01/06 to 12/31/06

Outputs
In order to continue to seek methods to improve disease resistance of the cow to coliform organisms that can cause severe clinical mastitis, we continued to investigate the impact of immunization of lactating dairy cattle with J5 Escherichia coli bacterins. In a recently completed project, we determined that cows immunized with six doses of a commercially available J5 core-antigen bacterin had higher serum immunoglobulin G2 responses than did cows administered three doses. Additionally, hyperimmunized (six dose) cows had a reduced incidence of severe mastitis from 40 to 120 days in milk of lactation. This period of lactation corroborated with previous studies that determined that this period of lactation is a time of higher risk for severe mastitis in dairy cattle. Furthermore, hyperimmunization improved survival in the herd up to 305 days in milk. A manuscript will be submitted to the Journal of the American Veterinary Medical Association in February of 2007. We are continuing these investigations to determine the effect of injection site and number of doses on serum immunoglobulin G1 and G2 responses and on lymphocyte cytokine responses when stimulated with J5 E. coli antigen. Additionally, we recently completed a cooperative project with researchers at the Atlantic Veterinary College (Prince Edward Island) and at North Dakota State University to determine the effect of culture-based antibacterial drug therapy on mild clinical mastitis as compared to empirical therapy. We administered antibacterial drugs to lactating dairy cows affected with mild clinical mastitis either immediately following clinical detection or after waiting 24 hours until bacterial culture of milk samples from the affected quarter were examined to determine the causative agent. Results have not been analyzed at this time, but preliminary data will be presented at the annual meeting of the National Mastitis Council in January of 2007.

Impacts
Mastitis is the most costly disease of the U.S. dairy industry, and is the leading cause of antibiotic use in adult dairy cattle. Preventive methods, such as vaccinations, could decrease the use of antibiotics, which in turn would reduce the risk of antibiotic contaminated milk and the development of antibiotic-resistant microbes. By improving the vaccination protocol to prevent severe cases of coliform mastitis, we enhanced cow productivity, survival, and welfare. This is a cost-effective economic asset for dairy producers. We intend to continue these investigations to further improve vaccination protocol strategies, and ultimately improve the efficacy of the vaccines.

Publications

  • Erskine RJ Overview of literature of antimicrobial resistance in mastitis pathogens. In Proceedings of the 45th Annual Meeting of the National Mastitis Council, Tampa, FL, 2006.


Progress 01/01/05 to 12/31/05

Outputs
There are two main objectives of our research plan over the next five years: 1) Continue to determine efficacy of antibacterial drugs as a therapy for clinical mastitis. Special emphasis will be given to severe clinical mastitis. Additionally, we will establish protocols that encourage prudent drug use in relation to pre-harvest food safety, reduce the risk of developing resistance of pathogens to antibacterial drugs, and practice sound pharmacokinetic and pharmacodynamic principles. We have continued to participate in a collaborative project with SA Wagner at North Dakota State University determining the effect of culture-derived therapy as compared to empirical therapy for the treatment of mild clinical mastitis. We have entered over one hundred cows on the trial 2) We will develop and enhance the efficacy and technology of Gram-negative bacterins. In particular, we will study those bacterins that use core-antigen technology as a basis of antigen targeting. Under this objective, there will be four foci: Apply novel management practices to try to maximize the efficacy of currently available vaccines. Identify and purify the proteins derived from whole-cell E.coli lysates that are only recognized by IgG2 from hyperimmune serum, as opposed to non-hyperimmune serum. Clone the identified proteins to increase yield. Our field study determining the effect of hyperimmunization (six doses) of J5 bacterin as compared to the standard three dose regimen on the incidence and severity of clinical coliform mastitis continues. We have entered over 1,200 cows on the trial, and nearly 1,000 cows have completed their lactations. Initial results indicate that hyperimmunization increases serum IgG2 anti-coliform antibody response, as well as protects cows in the first half of lactation.

Impacts
Severe coliform mastitis continues to cause significant losses to dairy producers. Current vaccines offer limited protection for dairy catle. We have furthered our understanding of the immunological changes that occur from immunization with of currently available vaccines. Our research is attempting to improve methods to vaccinate dairy cattle to protect them from this disease. Severe coliform mastitis continues to cause significant losses to dairy producers. Current vaccines offer limited protection for dairy catle. We have furthered our understanding of the immunological changes that occur from immunization with of currently available vaccines. Our research is attempting to improve methods to vaccinate dairy cattle to protect them from this disease. Mastitis continues to cause significant losses to dairy producers. Current vaccines offer limited protection for dairy cattle. We have furthered our understanding of the immunological changes that occur from immunization with currently available vaccines. Our research is improving methods to vaccinate dairy cattle to protect them from this and other diseases

Publications

  • No publications reported this period


Progress 01/01/04 to 12/31/04

Outputs
We have continued a field study in two dairy herds to determine the effect of hyper-immunization with J5 bacterin on the incidence and severity of clinical coliform mastitis in lactating dairy cattle. To date, three hundred animals have completed the trial. Cows are administered either three or six doses of the bacterin, and differences between the vaccination groups will be recorded for incidence, mortality, and survival in herd. Serum ELISAs will be used to determine if hyper-immunized (6x) cows attained higher serum IgG2 concentrations that normally (3x) vaccinated animals. Additionally, we are participating in a cooperative study with investigators at North Dakota State University to compare the efficacy of empirical antibacterial drug therapy versus the use of bacteriology as a selection criteria of therapy for mild clinical mastitis. Cows with mild clinical mastitis will be administered 5 x 200 mg doses of cephapirin by intramammary infusion every 12 hours immediately after detection of the clinical mastitis case, or after a milk sample is collected for bacteriology and results are obtained 24 hours later. Cows with Gram-positive organisms isolated on culture will be administered 5 x doses of cephapirin. Cows that yielded no organisms, or Gram-negative bacteria following culture will not be treated. Outcomes will include days of milk lost form production on account of mastitis and withholding of milk, survival in herd, and relapse rate of clinical mastitis cases.

Impacts
Severe coliform mastitis continues to cause significant losses to dairy producers. Current vaccines offer limited protection for dairy catle. We have furthered our understanding of the immunological changes that occur from immunization with of currently available vaccines. Our research is attempting to improve methods to vaccinate dairy cattle to protect them from this disease.

Publications

  • R.J. Erskine, J.S. Cullor, M. Shaellibaum, R. Yancey, aand A. Zecconi. 2004. Bovine mastitis pathogens and trends in resistance to antibacterial drugs. in Proceedings of the 43rd Annual Mtng of the National Mastitis Council, Charlotte, N.C. 400-414.
  • Chaiyotwittayakun, A., J.L. Burton, P.S.D. Weber, K. Kizilkaya, F.F. Cordoso, and R. J. Erskine. 2004. Hyperimmunization of steers with J5 Escherichia coli bacterin:Effects on isotype specific serum antibody responses and cross reactivity with heterogenous gram-negative bacteria. J. Dairy Sci. 87:3375-3385.


Progress 01/01/03 to 12/31/03

Outputs
Recent studies performed by our research group determined that repeated exposure of dairy cattle to J5 bacterin (hyperimmunized monthly for a total of twelve doses) resulted in a higher serum responses (as determined by ELISA) for all antibody isotypes as compared to cattle administered the typical three dose protocol. It was noted that at least five doses were needed in order to increase the response for IgG1 and IgG2, indicating isotype switching. Sera from hyperimmunized cattle were found to be more cross-reactive for a wide variety of Gram-negative bacteria than sera from cattle administered three doses. Additionally, serum from hyperimmunized animals promoted better in vitro phagocytosis of PMN than serum from cows that were administered a standard three-dose protocol, probably because of higher levels of IgG2, an important opsonin of bovine neutrophils. We were also able to isolate and purify IgG1 and IgG2 anti-J5 E. coli antibodies from serum of hyperimmunized cattle by using affinity chromatography. Of particular interest, was the use of hyperimmune serum for Western blot binding of proteins derived from whole-cell lysates of Gram-negative pathogens separated by SDS-PAGE. Although numerous proteins were bound by both immunoglobulin isotypes, two protein bands, one at about 37 kDa, and the other in the 8.5-10 kDa range, were recognized by IgG2 in serum only after six immunizations. (Chaiyotwittayakun, 2003). This suggests that not only does hyperimmunization induce isotype switching, but a shift in antigen recognition as well. This offers the possibility that repeated exposure of the immune system to the core-antigen bacterin induces T-cell-derived mutations in the Fab (antigen binding) portion of antibodies, although the phenomenon could also be explained by expansion of other clones that respond to more lowly expressed protein antigens. The identified proteins may provide target antigens to develop and enhance Gram-negative bacterin technology.

Impacts
Severe coliform mastitis continues to cause significant losses to dairy producers. Current vaccines offer limited protection for dairy catle. We have furthered our understanding of the immunological changes that occur from immunization with of currently available vaccines. Our research is attempting to improve methods to vaccinate dairy cattle to protect them from this disease.

Publications

  • Chaiyotwittayakun, A., J.L. Burton, P.S.D. Weber, K. Kizilkaya, F.F. Cardoso, and R.J. Erskine. 2003. Hyperimmunization of Steers With J5 Escherichia coli Bacterin: Effects on Isotype-Specific Serum Antibody Responses and Cross Reactivity With Heterogeneous Gram-Negative Bacteria. Journal of Dairy Science (in review).
  • Burton, J.L, P.M. Coussens, M. VandeHaar, M. Allen, G.W. Smith, and J.J. Ireland. 2004. Functional Genomics and the Dairy Cow: From Genes to the Farm. Michigan Dairy Review (in press) (see also http://www.msu.edu/user/mdr/)
  • Weber, P.S.D., T. Toelboell, L-C. Chang, J. Durrett-Tirrell, P.M. Saama, G.W. Smith, and J.L. Burton. 2004. Mechanisms of glucocorticoid-induced down regulation of neutrophil L-selectin in cattle: Evidence for effects at the genome level and primarily on blood neutrophils. Journal of Leukocyte Biology (accepted for publication).
  • Madsen, S.A., L-C. Chang, M-C. Hickey, G.J.M. Rosa, P.M. Coussens, and J.L. Burton. 2003. Microarray analysis of gene expression in blood neutrophils of parturient cows. Physiological Genomics (in press) (also see 10.1152/physiolgenomics.00121.2003, at: http://physiolgenomics.physiology.org/papbyrecent.shtml)
  • Suchyta, S.P., S. Sipkovsky, R. Kruska, A. Jeffers, A. McNulty, M.J. Coussens, R.J. Tempelman, R.G. Halgren, P.M. Saama, D.E. Bauman, Y.R. Boisclair, J.L. Burton, R.J. Collier, E.J. DePeters, T.A. Ferris, M.C. Lucy, M.A. McGuire, J.F. Medrano, T.R. Overton, T.P. Smith, G.W. Smith, T.S. Sonstegard, J.N. Spain, D.E. Spiers, J. Yao, and P.M. Coussens. 2003. Development and testing of a high-density cDNA microarray resource for cattle. Physiological Genomics 15:158-164.
  • Erskine RJ, SA Wagner, FJ DeGraves. Mastitis therapy and pharmacology. Vet Clinics N Am: Food Animal Practice, 19:109-138, 2003.
  • JL Burton, RJ Erskine. Immunity and mastitis: Some new ideas for an old disease. Vet Clinics N Am: Food Animal Practice, 19:1-45, 2003.


Progress 01/01/02 to 12/31/02

Outputs
Continued investigation of the response of the bovine immune system to hyperimmunization with Gram-negative bacterins derived from core-antigen technology has determined that: 1)serum antibody responses and end-point titers (as measured by ELISA)for dairy cattle increase for IgM, IgG1 and IgG2. This response is most notable for the IgG isotypes only after 6 immunizations. 2) the specific isotype antibodies that are elicited are cross-reactive for numerous Gram-negative pathogens (ELISA), and that this response increased with increasing number of immunizations. Additionally, affinity chromotography of hyperimmune serum resulted in the separation of IgG1 and IgG2, which was then used for specific bacterial antigen recognition by use of western-blot analysis. Preliminary results indicate that isotype switching and antigen maturation occur as a result of hyperimmunization. IgG2 was also determined to promote neutrophil phagocytosis of Green-Fluorescent-Protein-transformed J5 mutant Escherichia coli. Work in progress will include: 1) the effects of hyperimmunization of core-antigen vaccines on milk production and health of dairy cattle 2) elucidation of specific antigens that are recognized by the mature antibodies elicited from hyperimmunization, 3) determination of antibody responses for specific isotypes in whey, and 4) the duration of the serum antibody response in hyperimmunized cattle.

Impacts
Concerns over the variable efficacy of antibiotic therapy for mastitis in dairy cattle, the potential for drug residues in dairy foods that may result from therapy of dairy cattle, and developing resistance of bacteria in response to on-farm antibiotic use, provides a need to develop new dairy farm management strategies and technologies that will prevent mastitis. As mastitis is the primary cause of antibiotic use on dairy farms, preventive methods would help to reduce drug use. J5 E coli bacterins that are commercially avalable for dairies as an aid to prevent severe coliform mastitis have variable success. We have determined that repeated immunization beyond labeled instrutions creates a positive change in the antibody response of dairy cattle. Additionally, we may find novel antigens of the bacteria, such as proteins, that can be used to improve the efficacy of existing vaccines. If this is successful, we will reduce the incidence of severe forms of coliform mastitis in dairy herds. This will result in fewer losses of cows and milk production for dairy producers from this disease. Additionally, this should reduce the use of antibiotics on dairy farms, thus reducing the risk of drug residues in milk, and the development of antibiotic resistance among bacteria.

Publications

  • Chaiyotwittayakun, A.C., Erskine, R.J., Bartlett, P.C.. Herdt, T., Harmon, R.J. 2002. The effect of ascorbic acid and L-Histidine therapy on acute mammary inflammation in dairy cattle. J. Dairy Sci. 85:60-67.
  • Erskine RJ, Walker, R.D., Bolin, C.A., Bartlett, P.C., White, D.G. 2002. Trends in antibacterial susceptibility of mastitis pathogens during a seven-year period. J. Dairy Sci. 85:1111-1118.
  • Erskine R.J., Bartlett, P.C, VanLente, J.L., Phipps, C.R. 2002. Efficacy of systemic ceftiofur as a therapy for severe clinical mastitis in dairy cattle. J. Dairy Sci. 85:2571-2575.
  • Perkins K.H., M.J. VandeHaar, M.J., Burton, J.L, Liesman, J.S., Erskine, R.J., Elsasser, T.H. 2002 Clinical responses to intramammary endotoxin infusion in dairy cows subjected to feed restriction. J Dairy Sci 85:1724-1731.
  • Madsen, S.A., Weber, P.S.D., Burton, J.L. 2002. Altered blood neutrophil gene expression in periparturient dairy cows. Vet. Immunol. Immunopathol. 86:159-175.


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

Outputs
Our objectives are to develop and evaluate methods for enhancing the immune system response of dairy cattle to mastitis pathogens. Special emphasis is placed on those technologies that offer alternatives to antibacterial therapy, and developing protocols for antibacterial use on dairy farms that will result in efficacious therapy, as well as contribute to better public health. We continue to determine the impact of J-5 anti-coliform vaccines on host response and are exploring novel methods to use this technology to prevent severe clinical mastitis. Additionally, we have started a surveillance of antibacterial susceptibility data collected from the Animal Health Diagnostic Laboratory to determine trends in antibacterial resistance of mastitis pathogens.

Impacts
Antibacterial resistance has not been increasing among mastitis pathogens collected from dairies in Michigan. Preliminary studies have demonstrated that increased frequency of vaccination with J5 bacterin, in addition to that prescribed by the manufacturer, may enhance immune response in dairy cattle against coliform mastitis.

Publications

  • Gibbons-Burgener, S.N., Kaneene, J.B., Lloyd, J.W., Leykam, J.F., Erskine, R.J. 2001. Reliability of three bulk-tank antimicrobial residue detection assays used to test individual milk samples from cows with mild clinical mastitis. American Journal of Veterinary Research 62:1716-1720.
  • Smith, K. Phipps, C.R., Burton, J.L., Erskine, R.J. 2001. Serum antibody responses in Holstein cows immunized five times with J5 bacterin. Journal of Dairy Science 79:Supl 1, 151.


Progress 01/01/00 to 12/31/00

Outputs
The goal of this project is to determine the potential clinical use of passive immunization of dairy cattle with purified anti-coliform antibodies for the treatment and prevention of coliform mastitis and other endotoxin-induced shock diseases. We have successfully achieved our goals of this project. We hyperimmunized steers with a core antigen anti-J5 E. coli bacterin, and determined by ELISA the presence of high concentrations of anti-J5 antibodies in serum. By salt fractionation, and a two-step affinity chromatography purification, we were able to isolate and purify in mg quantities anti-J5 IgG2 antibodoes. This isotype has been determined in vitro to enhance neutrophil phagocytosis because of strong opsonization characteristics. We plan to continue this research by testing the efficacy of these purified anti-J5 antibodies to prevent an experimental E. coli mastitis by passively immunizing dairy cattle directly into the mammary gland.

Impacts
(N/A)

Publications

  • No publications reported this period


Progress 01/01/99 to 12/31/99

Outputs
The goal of this project is to develop and evaluate methods for modulating host responses of dairy cattle to mastitis pathogens. With respect to public concern regarding food safety in products derived from agriculture, special emphasis is being given to evaluating the suitability of antimicrobial therapy for mastitis, alternative methods of treatment, and methods for enhancing prevention. Research continued in 1999 determined that parenteral vitamin C therapy may enhance the clinical outcome of cows undergoing endotoxin induced shock and calving induced increases in plasma cortisol is associated with decreased expression of glucocorticoid receptors in leukocytes of dairy cattle. Decreased glucocorticoid receptor expression is associated with decreased immune function of leukocytes. Additionally, the association of quality assurance programs with the occurrence of antibiotic residues in milk of Michigan dairies was determined. Current research involves the isolation, purification, and characterization of immunoglobulins attained from serum of cattle that are immunized repeatedly with a commercial core-antigen anti coliform vaccine.

Impacts
(N/A)

Publications

  • No publications reported this period


Progress 01/01/98 to 12/31/98

Outputs
The goal of this project is to develop and evaluate methods for modulating host responses to mastitis pathogens. With respect to public concern regarding food safety in products derived from agriculture, special emphasis is being given to evaluating the suitability of antimicrobial therapy for mastitis, alternative methods of treatment, and methods for enhancing prevention. Research completed in 1998 determined thatparenteral vitamin C therapy may alter the anti oxidant capacity of plasma in cows undergoing endotoxic shock, and immunization with hemolysin-based bacterin may enhance therapeutic efficacy in cows with chronic S. aureus mastitis. Current research includes purification and characterization of immunoglobulin collected from cattle that are hyperimmunized with core antigen J 5 E. coli bacterin.

Impacts
(N/A)

Publications

  • Erskine R., Sears,P.,Bartlett, P. 1998. Efficacy of postmilking disinfection with benzyl alcohol versus iodophor in the prevention of new intramammary infections in lactating cows. J Dairy Sci, 81:116.
  • Erskine R., Bartlett,P. 1992. Recombinant bovine interleukin-2 and dry cow therapy. J Dairy Sci, 81:107.


Progress 01/01/97 to 12/31/97

Outputs
The goal of this project is to 1) develop livestock management systems that will produce residue-free animal products, and 2) evaluate therapeutic modalities that are commonly used in the context of infectious and metabolic disease with respect to efficacy and residue status. Considering public concern regarding food safety in products derived from animal agriculture, special emphasis is being given to evaluating the suitability of antimicrobial therapy for mastitis, alternative methods of treatment, and methods enhancing prevention. Research completed in 1996 determined that 1)benzyl alcohol based germicidal teat dip was not as effective as 1% iodophor in preventing new intramammary infections caused by Staphylococcus aureus, and 2) recombinant bovine somatotropin (bST) does not affect the incidence of clinical mastitis or the frequency and duration of antimicrobial therapy of clinical mastitis. Current research includes studies on the effect of bST on production and economic losses resulting from clinical mastitis.

Impacts
(N/A)

Publications

  • No publications reported this period


Progress 01/01/96 to 12/30/96

Outputs
The goal of this project is to 1) develop livestock management systems that willproduce residue-free animal products, and 2) evaluate therapeutic modalities that are commonly used in the context of infectious and metabolic disease with respect to efficacy and residue status. Considering public concern regarding food safety in products derived from animal agriculture, special emphasis is being given to evaluating the suitability of antimicrobial therapy for mastitis, alternative methods of treatment, and methods enhancing prevention. Research completed in 1996 determined that 1)benzyl alcohol based germicidal teat dip was not as effective as 1% iodophor in preventing new intramammary infections caused by Staphylococcus aureus, and 2) recombinant bovine somatotropin (bST) does not affect the incidence of clinical mastitis or the frequency and duration of antimicrobial therapy of clinical mastitis. Current research includes studies on the effect of bST on production and economic losses resulting from clinical mastitis.

Impacts
(N/A)

Publications

  • ERSKINE, RJ, BARTLETT, PC. 1996. Comparative efficacies of intramuscular ceftiofur &intramammary penicillin-novobiocin for treatment of Streptococcus agalactiae mastitis in dairy cows. JAmVetMed Asc. 208:258-260. Halbert LW, ERSKINE RJ, BARTLETT PC, JOHNSON GL. 1996. Incidence of false positive results for assays used to detect antibiotics in milk. J. Food Protection 59:886-888.


Progress 01/01/95 to 12/30/95

Outputs
The long range goal of Michigan States's effort in this project is to develop and evaluate techniques for modulating host responses to mastitis pathogens. With respect to public concern regarding food safety in products derived from animal agriculture, special emphasis is being given to evaluating the suitability of antimicrobial therapy for mastitis, alternative methods of treatment, and methods of enhancing prevention. Mastitis continues to be the most costly disease for the U.S. dairy industry, and the primary cause of antimicrobial residues in marketed milk. Research completed in 1995 determined that 1) systemic ceftiofur does not attain therapeutic concentrations in the mammary gland during acute inflammation associated with coliform mastitis, 20 parenteral vitamin E administered before parturition does not reduce the incidence or severity of clinical mastitis in lactating cattle, 3) systemic ceftiofur is not effective for the treatment of Streptococcus agalactiae mastitis, and 4) lipopolysaccharide core-antigen vaccine is not effective in reducing the incidence of clinical mastitis caused by coliform bacteria in herds with a low incidence of this disease. Current research includes studies on 1) the effect of bovine somatotropin (BST) on the incidence and severity of clinical mastitis during lactation, and 2) the comparative efficacy of two germicides used for post-milking teat sanitation.

Impacts
(N/A)

Publications

  • NO PUBLICATIONS REPORTED THIS PERIOD.


Progress 01/01/94 to 12/30/94

Outputs
The long range goal of Michigan State's effort in this project is to 1) develop livestock management systems that will uniformly produce residue-free animal products, and 2) evaluate therapeutic modalities that are commonly used in the context of infectious and metabolic disease with respect to efficacy and residue status. With respect to public concern regarding food safety in products derived from animal agriculture, special emphasis is being given to evaluating the suitability of antimicrobial therapy for mastitis, alternative methods of treatment, and methods of enhancing prevention. Mastitis continues to be the most costly disease for the U.S. dairy industry, and the primary cause of antimicrobial residues in marketed milk. Research completed in 1994 determined that 1) oxytetracycline and 2) the immune modulator interleukin-2 are not effective as supplemental treatments for Staphylococcus aureus mastitis when administered to cows at the end of lactation. Current research includes studies on 1) the efficacy of lipopolysaccharide core-antigen vaccines in preventing Gram-negative mastitis, 2) the effect of parenteral vitamin-E on the incidence and severity of clinical mastitis in the peri-parturient period, and 3) the effect of bovine somatotropin (BST) on the incidence and severity of clinical mastitis throughout an entire lactation.

Impacts
(N/A)

Publications

  • TYLER, J.W., DEGRAVES, F.W., ERSKINE, R.J., KIRK, J.H. 1994. Milk production in cows with endotoxin-induced mastitis treated with isotonic or hypertonic sodium chloride solution. J Am Vet Med Assoc 204:1949-1952.
  • ERSKINE, R.J., BARTLETT, P.C., CRAWSHAW, P.C., GOMBAS, D.M. 1994. Efficacy of intramuscular oxytetracycline as a dry cow treatment for Staphylococcus aureus mastitis. J Dairy Sci 77:3347-3353.
  • ERSKINE, R.J., BARTLETT, P.C. 1994. Dry cow treatment of Staphylococcus aureus mastitis: Revisited. Proceedings of the National Mastitis Council, 20-27.