In 2017, the Journal of Dairy Science (JDS) celebrated 100 years of continuous publication. To mark that milestone, the journal’s editor commissioned 30 comprehensive reviews of progress in dairy research with emphasis on research that had been published in JDS (McNamara and Lucy, 2017). I was asked to write a review of progress in udder health (Ruegg, 2017) and while I realized a bit too late that my agreement meant that I needed to review 100 years of research, the process of reading and contemplating the past century of progress in udder health was thoroughly enjoyable. During the process of writing the paper, I learned an enormous amount about the history of udder health research and in this brief article I will highlight a few items of interest from the last century of research in our field.
Control of Streptococcus agalactiae dominated the first half-century
The significance of Streptococcus agalactiae as a cause of mastitis in the first half of this century cannot be overstated and while most developed regions have essentially eradicated this pathogen, understanding the role that it played in development of modern control programs is essential. During the first half of the 20th century, researchers estimated that approximately 50% of quarters of lactating cows were infected with Str. agalactiae and most control programs for mastitis have their origin in limiting transmission of this pathogen (Plastridge, 1958). Between 1917 and the 1960s almost all research was focused on control of mastitis caused by Str. agalactiae. While this research resulted in many important control strategies that are still in use, it is important to note that Str. agalactiae has many unique characteristics that are not shared with pathogens that are more prevalent on modern dairy farms. In contrast to most other mastitis pathogens, most strains of Str. agalactiae reside only in the udder of cows. The organism is highly infectious and has a low rate of spontaneous cure, but does not usually penetrate deeply into mammary gland tissue and is unusually responsive to antibiotic therapy. Thus, control of this organism is focused on identification and treatment of infected animals and during the Str. agalactiae era, the role of antibiotic therapy in controlling mastitis was strongly emphasized.
As Str. agalactiae was controlled Staphylococcus aureus emerged as an important cause of mastitis. While this organism shares a few characteristics with Str. agalactiae (low rate of spontaneous cure, primarily subclinical presentation, etc.), researchers rapidly recognized that antibiotic therapy was much less efficacious on Sta. aureus. As the decades have progressed, the diversity of etiologies of mastitis has evolved. It is important to understand that characteristics of emergent pathogens often vary from those of Str. agalactiae. Many mastitis pathogens on modern farms are opportunistic in nature, less infectious, have higher rates of spontaneous cure, and may not be responsive to antibiotics that were originally developed for treatment of Str. agalactiae and Sta. aureus. Understanding these differences can help us develop and use control programs that are appropriate and help us ensure that antibiotics are used appropriately and only for cases that will truly be responsive.
Most important contributions of important early researchers
In 1969, JDS published a series of symposium papers that described progress in mastitis control (Dodd et al., 1969, Neave et al., 1969, Norcross and Stark, 1969, Philpot, 1969, Read, 1969). This series should be required reading for all mastitis researchers as the summarized work lays the foundation for modern mastitis control programs and is the first research that emphasized research-based preventive strategies. Frank Dodd from the National Institute of Research in Dairying in the UK introduced the series. Dodd is recognized as an important pioneer in the field of mastitis control; his work has had enormous and lasting influence. In this symposium, Dodd et al. (1969) summarized data from a longitudinal study of 721 cows from 14 dairy herds and described the epidemiology of common pathogens of the era. In an accompanying paper, his co-worker (Neave et al., 1969) described results of field experiments that evaluated the impact of applying a “full hygiene system.” They described results of a series of experiments and field trials, that systematically evaluated use of pre-milking teat disinfection with individual towels, use of milking gloves, sanitation of teat cups and efficacy of post-milking teat dip. They reported that a program of “partial hygiene” (the preceding steps without using sanitizing teat cups) resulted in a dramatic reduction in new infections and advocated use of antibiotic therapy at dry off to further reduce infections. This seminal paper was titled “Control of Mastitis in the Dairy herd by Hygiene and Management” (Neave et al., 1969) and ultimately influenced the recently formed National Mastitis Council to develop a standardized mastitis control program that became known as the “5-Point Plan.” Eventually, this work became the basis of modern mastitis control and these researchers had an enormous and lasting impact on improving milk quality throughout the world.
The most intriguing experiment
By the mid-1950s, most rural areas of the U.S. had access to electricity and about 50% of cows in the U.S. were milked with milking machines. This was an important advance but created the need to define appropriate milking procedures. Early researchers had studied physiological mechanisms of milk secretion and ejection and had identified “pituitrin” (oxytocin) as a substance that was important in stimulating milk flow (McCandlish, 1918). As milking machines were adopted, researchers were concerned about identifying management practices that could reduce milk ejection. In one remarkable scientific paper, researchers described an experiment that had an objective of studying the effect of fright on milk ejection. To induce fear in milking cows, researchers described placing a cat on the back of a cow and then exploding paper bags every ten seconds for two minutes. Apparently the exploding bags were sufficient to induce fear without use of cats as the authors stated (in the materials and methods) that: “later the cat was dispensed with as unnecessary” (Ely and Petersen, 1941). This work clearly demonstrated that fear had a significant effect on reducing milk ejection but is unlikely to be replicated, as it would be very difficult to gain approval from modern Animal Care and Use Committees.
Top 4 quotes of the century of research
- As antimicrobials became available, researchers were keen to use them to cure mastitis but first they needed to determine appropriate doses and routes of administration. In one study, researchers described a series of experiments to determine the efficacy of sulfanilamide (Gildow et al., 1938). In this study, they administered massive oral doses (the doses were so high that they actually poisoned several cows) but noted that they failed to achieve effective concentrations in blood or milk. However, even though therapeutic concentrations were not achieved, the researcher noted that “treatment with sulfanilamide was successful in restoring normal flow and normal appearance of milk… but it did not eliminate the streptococci from the udder, nor prevent later acute attacks (Gildow et al., 1938).” This comment is the first indication that clinical impressions can be misleading in determining efficacy of antimicrobial compounds and illustrates the difficulty of separating the occurrence of inflammation from active intramammary infection (IMI). The over-reliance on resolution of inflammation as an indicator of treatment success has continued since that era.
2. Until indirect tests for subclinical mastitis were developed, control programs were focused on solving mastitis that was characterized by abnormal milk. A perceptive early researcher, recognized the ineffectiveness of controlling mastitis based on treatment of clinical cases and summarized his seminal paper (Murphy, 1956) with the memorable statement that “the utter futility of thinking that mastitis can be controlled by the treatment of clinical mastitis only should be obvious. This is merely cutting the tops off the weeds and leaving the roots.”
3. During the development of modern mastitis control programs, Neave and Dodd recognized the limitations of scientific advances and predicted the need for effective extension programs that were able to sufficiently motivate farmers (Neave et al., 1966). Summarizing how mastitis will be controlled they correctly noted that “It means that the control is going to depend on being able to persuade thousands of people of different abilities to conform to particular work patterns.” This prediction predates the current emphasis on understanding motivation of farmers by at least 40 years.
4. By the mid-1960s, limitations of antibiotic therapy in controlling mastitis were already well known. W. N. Philpot (Philpot, 1969) concluded a summary paper presented at the ADSA Mastitis Symposium with the following statement that is as relevant as it was when originally published: “Therapy can be a valuable adjunct to an effective program of mastitis control. It should be employed, however, with a full awareness that it is less than desirably effective in eliminating many existing infections and that it does not preclude the development of most new infections.”
Five papers every mastitis researcher should read
1. Murphy, 1956. In a seminal paper titled “Mastitis – the struggle for understanding,” Murphy (Murphy, 1956) describes years of struggling with ineffective control programs and concludes that “the problem is larger than any single effort put forth toward its understanding.” He presented eight points to help define the disease and noted that while >20 types of infections can cause mastitis, “at least 99% are caused by… Str. agalactiae, other streptococci, staphylococci and bacillary mastitis (including coliform, pseudomonas etc.).” He identified clinical, non-clinical and severe states and noted that while discrimination among pathogens could only be performed by laboratory testing the clinical and non-clinical states did not occur at the same frequency for all pathogens. Murphy (1956) further stated that shedding (and the chance of negative cultures) varied among pathogens over time and emphasized the need for pathogen-specific control programs so that appropriate treatment could be applied to cows affected with Str. agalactiae while calling for research to identify environmental sources of exposure for other pathogens. He presciently noted that treatment would not be the solution and called for research to define the value of various unproven management practices. The principles he laid out are as relevant today as they were when he described them more than a half-century ago.
2. Dodd et al., 1964. The significance of the work performed by UK researchers from the National Institute for Research in Dairying cannot be overstated and should be required reading for all mastitis workers. These early researchers applied systematic experiments to evaluate a management program that focused on understanding the dynamics of IMI (Dodd et al., 1964). Without the help of modern epidemiological techniques or knowledge of the correct terminology, they demonstrated that the percent of infected quarters within a herd (prevalence) was a simple function of the rate of new infections (incidence) and duration of those infections (Dodd et al., 1964). They noted that treatment was effective for reducing duration (and control of Str. agalactiae) but was of little value for eliminating staphylococcal infections, thus they emphasized that effective control should be directed at reducing the rate of new IMI. This principle remains the basis of mastitis control today.
3. “Coliform Mastitis – a Review” was authored by a committee of the National Mastitis Council and published in JDS (Coliform Comm. NMC et al., 1979). This comprehensive paper signaled the changing dynamics of IMI on modern dairy farms. The review included a description of growth requirements of various coliform bacteria, mechanisms of IMI (with emphasis on exposure and movement through the teat canal), an explanation of pathogenesis (including recognition that magnitude of inflammation is dependent on host factors), an excellent portrayal of epidemiology and risk factors and recommendations for a model control program. Since publication of this review, coliform organisms have become the most prevalent cause of mastitis for cows housed in confinement systems and this paper should be required reading for practitioners and others who work with these organisms.
4. Smith et al., 1985. In a comprehensive symposium paper titled “Environmental Mastitis: Cause, Prevalence, Prevention,” (Smith et al., 1985) described results of a longitudinal study of a university herd that characterized microbiological characteristics, epidemiology, control and treatment of both Gram-positive and Gram-negative pathogens that originate primarily from environmental exposure (Smith et al., 1985). They recognized the importance of reducing teat-end exposure, highlighted differences in susceptibility among cows, and contrasted differences among Gram-negative and Gram-positive (primarily Streptococcus spp.) opportunistic pathogens. Differences among pathogens, the importance of IMI during the dry period, the high rate of spontaneous clearance of Gram-negative IMI, and the increased rate of clinical cases (versus subclinical IMI) associated with environmental pathogens were all thoroughly described. They correctly predicted the challenges of reducing environmental mastitis in herds that have effectively controlled contagious organisms and summarized recommendations for mastitis control that remain relevant for modern, intensively-managed dairy farms.
5. Spencer, 1998. While several reviews of milking machine management have been published, Spencer wrote a review that succinctly defined the role of the milking machine in maintaining udder health. This review is noteworthy because by this time there had been tremendous progress in controlling the prevalence of Str. agalactiae and Sta. aureus and advances in milking machines had greatly improved vacuum stability. While Spencer (1998) noted that the milking machine can influence new IMI by serving as a fomite, allowing cross-infections within cows, damaging teat sphincters or creating teat impacts, he was one of the first to point out that the milking machine is rarely a direct cause of new IMI. This paper includes the widely cited conclusion that researchers can only attribute about 6.6% of new IMI to management of milking machines. He concluded that there was no convincing evidence linking the milking machine to the overall prevalence of herd infection (Spencer, 1998) and encouraged mastitis workers to focus on identification of other more significant risk factors.
Two things I learned about antibiotic therapy
Our recommendations for treatment and control of mastitis are based on programs that were developed to control Str. agalactiae and Sta. aureus, but the limitations of antibiotic therapy have been known almost since they were introduced. By 1969, a review article titled “Role of Therapy in Mastitis Control” was published as part of the ADSA mastitis symposium (Philpot, 1969). Philpot (1969) emphasized that the excellent prognosis for treatment of Str. agalactiae was partially because of the location of the infection in the milk duct system. In contrast, when referring to Sta. aureus, he reported that the “prognosis regarding therapy is disappointingly low” because the organisms “penetrate the duct walls of the udder and become established in numerous foci.” He further stated: “tissue barriers within the udder are of infinitely greater importance in therapeutic failures than the matter of drug resistance.” While he documented that a single treatment of penicillin would result in elimination of about 90% of IMI caused by Str. agalactiae, he cited five studies indicating an expected efficacy of 50% for treatment of staphylococci. Importantly, this is the first publication that includes recommendations of reviewing individual animal factors (age, stage of lactation, level of milk production, pedigree and the severity of infection) before deciding to use antibiotics to treat cows affected with Sta. aureus.
Use of blanket antibiotic therapy at dry off has always been controversial. Early mastitis workers recognized that about 50% of cows had IMI so use of antibiotic therapy to reduce duration of IMI was recommended as part of a comprehensive mastitis control program (Neave et al., 1969). The cost of discarded milk and the risk of milk residues (Albright et al., 1961) were recognized as limitations to using antibiotics to treat the large proportion of infected lactating cows so use of antibiotic dry cow therapy (DCT) was suggested. The risk of acquiring IMI during the dry period was known and additional benefits of reducing new IMI during this period had already been hypothesized (Neave et al., 1950). Similar to current concerns about giving antibiotics to animals that may not be infected, early researchers disagreed about which cows should be treated. Some researchers recommended treatment of all quarters of all cows while others believed that only infected cows should be treated (Philpot, 1969). Shortly after DCT was initiated, Natzke (Natzke, 1971) reviewed potential methods of selecting cows for dry treatment. After comparing bacterial culture, use of screening tests (such as California mastitis test or CMT) or review of clinical mastitis history, he stated that the limited sensitivity of each of those methods led to the conclusion “that the treatment of all quarters of all cows at the time of drying off is the preferred system.” Effectiveness of DCT (combined with teat dipping) was subsequently conclusively demonstrated by several field studies. Results of a later study comparing comprehensive DCT to selective DCT (cows selected based on history of clinical mastitis) demonstrated considerably reduced clearance of infections, increased new IMI and increased cases of clinical mastitis in cows that were in the selective treatment group, thus use of comprehensive DCT became established at an important component of mastitis control in dairy herds in North America and the UK (Ward and Schultz, 1974). While researchers continued to debate the use of antibiotics in apparently non-infected glands (Rindsig et al., 1978, Poutrel and Rainard, 1981, Schultze, 1983), the practice was an important aspect of programs that resulted in reduced prevalence of Str. agalactiae.
It is truly humbling to review the work that mastitis researchers have performed over the last 100 years. At the start of the period, little was known about the etiological agents, epidemiology of various pathogens, immunological responses to infection, routes of transmission, role of antimicrobial therapy, or appropriate management of milking machines and the milking process. The early researchers created tools to characterize subclinical infection, and identified the impact of mastitis on production, reproductive performance, product quality and animal well-being. The researchers proactively developed programs that were focused on prevention and even without modern molecular tools, they identified important risk factors that have allowed us to apply effective control programs and defeat the pathogens that most impacted milk quality and animal health. As new challenges arise, it behooves modern mastitis workers to familiarize ourselves with the historic research that laid the foundation for our work today and be sure that our work builds on (rather than replicates) historic knowledge.
Albright, J. L., S. L. Tuckey, and G. T. Woods. 1961. Antibiotics in Milk;A Review. J Dairy Sci 44(5):779-807.
Coliform Comm. NMC, R. J. Eberhart, R. P. Natzke, F. H. Newbould, B. J. Nonnecke, and P. D. Thompson. 1979. Coliform Mastitis – A Review. J Dairy Sci 62(1):1-22.
Dodd, F. H., D. R. Westgarth, F. K. Neave, and R. G. Kingwill. 1969. Mastitis–the strategy of control. J Dairy Sci 52(5):689-695.
Ely, F. and W. E. Petersen. 1941. Factors Involved in the Ejection of Milk. J Dairy Sci 24(3):211-223.
Gildow, E. M., D. L. Fourt, and A. O. Shaw. 1938. Sulfanilamide in the Treatment of Streptococcic Mastitis. J Dairy Sci 21(12):759-766.
McCandlish, A. C. 1918. The possibility of increasing milk and butterfat production by the administration of drugs. J Dairy Science 1:475-486.
McNamara, J. P. and M. C. Lucy. 2017. Journal of Dairy Science Volume 100 Special Issue: Introduction. J Dairy Sci 100(12):9892-9893.
Murphy, J. M. 1956. Mastitis – The Struggle for Understanding. J Dairy Sci 39(12):1768-1773.
Natzke, R. P. 1971. Therapy: One Component in a Mastitis Control System. J Dairy Sci 54(12):1895-1901.
Neave, F. K., A. H. Dodd, and E. Henriques. 1950. Udder infections in the dry period. J Dairy Res 17:37-49.
Neave, F. K., F. H. Dodd, and R. G. Kingwill. 1966. A method of controlling udder disease. Vet Rec 78:521-523.
Neave, F. K., F. H. Dodd, R. G. Kingwill, and D. R. Westgarth. 1969. Control of mastitis in the dairy herd by hygiene and management. J Dairy Sci 52(5):696-707.
Norcross, N. L. and D. M. Stark. 1969. Role of Immunization in Mastitis Control. J Dairy Sci 52(5):714-&.
Philpot, W. N. 1969. Role of Therapy in Mastitis Control. J Dairy Sci 52(5):708-713.
Plastridge, W. N. 1958. Bovine Mastitis: A Review. J Dairy Sci 41(9):1141-1181.
Poutrel, B. and P. Rainard. 1981. California Mastitis Test Guide of Selective Dry Cow Therapy. J Dairy Sci 64(2):241-248.
Read, R. B. 1969. Abnormal Milk Program of Interstate Milk Shippers Conference. J Dairy Sci 52(5):718-&.
Rindsig, R. B., R. G. Rodewald, A. R. Smith, and S. L. Spahr. 1978. Complete Versus Selective Dry Cow Therapy for Mastitis Control. J Dairy Sci 61(10):1483-1497.
Ruegg, P. L. 2017. A 100-Year Review: Mastitis detection, management, and prevention. J Dairy Sci 100(12):10381-10397.
Schultze, W. D. 1983. Effects of a selective regimen of dry cow therapy on intramammary infection and on antibiotic sensitivity of surviving pathogens. J Dairy Sci 66(4):892-903.
Smith, K. L., D. A. Todhunter, and P. S. Schoenberger. 1985. Environmental mastitis: cause, prevalence, prevention. J Dairy Sci 68(6):1531-1553.
Spencer, S. B. 1998. Recent research and developments in machine milking – a review. J Dairy Science 72:1907-1917.
Ward, G. E. and L. H. Schultz. 1974. Incidence and Control of Mastitis During the Dry Period<sup>1</sup>. J Dairy Sci 57(11):1341-1349.
Text: Pamela L. Ruegg, Michigan State University, USA Pictures: Twan Wiermans & UGent