The United States dairy industry continues to experience significant monetary drain through the losses associated with common diseases.  Bovine mastitis is the most costly infectious disease currently affecting dairy cattle. While significant advances have been made in controlling some types of mastitis, the complex etiology of the disease and ongoing changes in dairy practices dictate that new and more effective methods for control and treatment be developed over time. Single site studies are often limited in terms of expertise and cattle numbers. A multi-state project provides advantages in terms of increased numbers of herds and cattle as well as multiple levels of expertise. 

Mastitis is defined as an inflammation of the mammary gland that is almost always associated with bacterial infection. Mastitis affects every dairy farm and approximately 38% of dairy cows in the United States experience clinical signs. The National Mastitis Council estimates that this devastating disease complex costs the dairy industry more than 2 billion dollars per year or approximately $180.00 per cow. These losses are primarily due to lost milk production, increased veterinary costs, increased cow mortality, and discarded milk. 

Currently, intramammary antibiotic therapy is the most widely used and most effective management strategy to eliminate intramammary infections (IMI) and alleviate pain and suffering.  Bovine mastitis is a unique disease wherein multiple infectious agents can trigger an inflammatory response.  When considering treatment of an individual cow for mastitis, the causative infectious agent is usually unknown.  Therefore, producers commonly treat with different combinations of antibiotics and routes of treatments.  This common management strategy can lead to overuse of antibiotics, thus increasing the risk of residues in milk and the selection for antibiotic resistant pathogens.  Growing consumer concerns regarding antibiotic use, the risk of antibiotic residues in milk and meat and the potential for antimicrobial resistance have led to the examination of alternative strategies for controlling mastitis while reducing the use of antibiotics on-farm, which is one of the primary goals of this multi-state group. 

The identification of alternative therapeutics are advocated in an April, 2015 White House mandate titled “National Action Plan for Combating Antibiotic-Resistant Bacteria”, which only underscores our approaches.  According to priorities within the 2014 farm bill, examining new management strategies to treat bovine mastitis will expand our knowledge regarding the use of non-antibiotic alternative therapies to treat disease thereby reduce production costs and enhance nutritional quality of products for human consumption while improving animal health.  In addition, international agencies, including the Food and Agriculture Organization (FAO) of the United Nations, the World Health Organization (WHO) and the World Organization for Animal Health (OIE), have also emphasized the need to find alternative approaches to treatment of animal disease and to identify the role of antibiotics used in animal agriculture in the emergence of antimicrobial resistance of human pathogens. 

The purpose of NE-1048 is to coordinate multidisciplinary research efforts on mastitis that are being conducted at various laboratories throughout the United States and internationally, e.g. Canada and Europe. The magnitude and scope of attempting to solve these problems extend far beyond the ability of any one institution. The ability to cooperate on a regional, national, and international basis allows the integration of resources and knowledge to address this problem. Recognition of the need for a coordinated effort to study resistance of the pathogen and the need for non-antibiotic alternative therapeutics for the dairy cow for the control of mastitis resulted in the design and initiation of multi-State Project NE-1048. The NE-1048 project has provided a forum for new and established researchers to develop collaborative relationships, and to share resources and expertise.  NE-1048 meetings are well attended and 30-40 presentations are typically made by participants each year. International visitors and collaborators are often included in these presentations. 

In the United States (US), cash receipts from marketing of milk during 2016 totaled $33.7 billion (NASS, 2017). In the US, the dairy industry contributes >$140 billion per year to the national economy and provides > 900,000 jobs making it a vital part of our nation’s economy and food system (Adcock et al., 2015; ERS, 2015).   However, the dairy industry continues to experience significant monetary drain through the losses associated with common diseases. Bovine mastitis is the most costly infectious disease currently affecting dairy cattle. Recent estimates suggest that economic losses due to clinical and subclinical mastitis are in the range of $200 per cow per year (Liang et al., 2013). These losses are primarily due to lost milk production, increased veterinary costs, increased cow mortality, and discarded milk. While significant advances have been made in controlling some types of mastitis, the complex etiology of the disease, ongoing changes in dairy practices, and the pressure to reduce antibiotic usage dictate that new and more effective methods for control and treatment be developed over time. Single site studies are often limited in terms of expertise and cattle numbers. A multistate project provides advantages in terms of increased numbers of herds and cattle as well as multiple levels of expertise. 

The purpose of NE-1048 is to coordinate multidisciplinary research efforts on mastitis that are being conducted at various laboratories throughout the United States. The magnitude and scope of attempting to solve these problems extend far beyond the ability of any one institution. The ability to cooperate on a regional and national basis allows the integration of resources and knowledge to address this problem. Recognition of the need for a coordinated effort to study resistance of the dairy cow to mastitis resulted in the design and initiation of original multi-State Project NE-1048. The NE-1048 project has provided a forum for new and established researchers to develop collaborative relationships, and to share resources and expertise. The NE-1048 project is comprised of three objectives 1) characterization of host mechanisms associated with mastitis susceptibility and resistance, 2) characterization and manipulation of virulence factors of mastitis pathogens for enhancing host defenses, and 3) assessment and application of new technologies that advance mastitis control, milk quality, and dairy food safety. Accomplishments in the last 5 years are listed below by objective. 

Objective 1: Characterization of host mechanisms associated with mastitis susceptibility and resistance.

Achievements include the dietary supplementation of OmniGen ® (GA), 2,4-thiazolidinedione (OR), retinol-binding protein (RBP; ID) and vitamin E (MD) to improve the host immune response during mastitis. Other major achievements include the negative relationship between severity of negative energy balance and fat mobilization on important inflammatory mediators (MI), the ability of white blood cells to kill invading microorganisms (WA), the negative impact of antimicrobial resistance on the host immune response (NY), the response of peripheral tissues during mastitis (MD, OR), characterizing the nutrient utilization by leukocytes during mastitis (MD), identification of dermal fibroblasts as a model cell to investigate genetic and epigenetic differences between cows in their innate responses to mastitis causing pathogens (VT), and that CXCR1 may be a promising new candidate gene for mastitis susceptibility (TN). Whole genome SNP association studies also have led to a series of new candidate genes that will be evaluated (TN).

Objective 2: Characterization and manipulation of virulence factors of mastitis pathogens for enhancing host defenses.

Major achievements for this objective are 1) the identification of iron-sulfur cluster metabolism as a virulence factor associated with S. aureus (NJ); 2) S. uberis adhesion molecule (SUAM) is a relevant virulence factor (TN) and 3) certain genes are involved with enhancing antimicrobial resistance of mastitis causing pathogens such as Klebsiella spp. (Quebec), Escherichia coli (E. coli; NY) and Staphylococcus aureus (S. aureus; NY).

Objective 3: Assessment and application of new technologies that advance mastitis control, milk quality, and dairy food safety.

Achievements include controlling mastitis via the use of ultrasound scanning to monitor mastitis (CT), the use of an Automated Milk Leukocyte Differential (MLD) Test for detecting IMI (MN), teat dip efficiency trials to reduce the incidence of mastitis (WA),  the development of multiple decision support tools aimed at improving milk quality, reducing mastitis and economics (KY), examining alternative therapeutics for the prevention or treatment of mastitis to reduce antibiotic usage (MO, MD, Quebec), continuing outreach efforts to promote better stewardship of antibiotic use on dairy farms (MI, MO, MN, WI) and improving animal welfare via the development of behavioral monitors (KY, VA, MA).

The mastitis research workers group has met in conjunction with the NE-1048 annual meeting for many years, and in recent years, the mastitis research workers topics have been included in NE-1048 minutes, showing current active areas of research by NE-1048 members. International visitors and collaborators are often included in these presentations. In addition to the mastitis research workers conference, the NE-1048 members provide new management strategies to reduce antibiotic usage and technology transfer to the scientific community and industry stakeholders. In the last 4 years, members of the project have collectively published multiple book chapters, in excess of 192 peer-reviewed journal articles, over 300 abstracts and proceedings, and presented numerous oral and poster presentations related to mastitis, milk quality, and food safety. Venues for oral and poster presentations have included the National Mastitis Council regional and annual meetings (attendees include researchers, veterinarians, dairy producers, and representatives from industry), Conference for Research Workers in Animal Diseases, American Association of Bovine Practitioners annual meetings, International Dairy Federation meetings, American Dairy Science Association meetings, World Buiatrics Congress meetings, American Society of Microbiology meetings, Conference on Production Diseases in Farm Animals, Plant and Animal Genome Conference, Agriculture and Agri-Food Canada - Food Safety meetings, American College of Veterinary Internal Medicine annual forum meetings, and several regional extension and veterinary continuing education meetings.

The continuation of the NE-1048 multistate project is of utmost importance to foster research in mastitis leading to the provision of science based information to dairy producers and the dairy industry. The impact of the European Union's strict enforcement of import regulations on milk quality highlights the need to continue efforts to reduce the incidence of mastitis and antibiotic use. These new regulations require milk export companies to certify that any farm contributing milk must show a bulk milk cell count below 400,000 cells/mL. This regulation has been supported by the National Mastitis Council as a goal for all US dairies. Mechanisms leading to improvement in milk quality, dairy animal welfare, and appropriate use of antimicrobial therapeutics form the basis of research conducted in the NE-1048 multistate project. It is clear that continued mastitis research and education are required to maintain the global competitiveness of the US dairy industry (USDA APHIS, 2016). Furthermore, the animal agriculture industry in general is under closer scrutiny than ever before by various interest groups. The work of NE-1048 is clearly focused on reducing mastitis, reducing antibiotic use and improving economic outcome and animal welfare. Mastitis is the most significant animal health issue in the dairy industry. In summary, continuation of the NE-1048 project is a productive group of collaborators that has provided new and meaningful information to all levels of the dairy industry from the bench scientist to the dairy producer with regard to bovine mastitis control, treatment and prevention. In the next 5 years we will continue to pursue collaborative projects under our 3 stated objectives which will lead to new information of value to the management of dairy cattle mastitis. Mastitis is an evolving disease syndrome, as is the science that studies mastitis; therefore, continued research efforts are needed.