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Feature
Feature
Veterinary Record 125 years
Mastitis
The changing face of mastitis control Over the past 125 years, mastitis has been one of the most studied conditions of dairy cows. This is confirmed by a search of peer-reviewed literature covering this period, which revealed more than 12,000 papers. Yet mastitis is still one of the most relevant and problematic diseases to treat and control in practice, which is testament to the complexity and mutability of the condition. Although progress has been made, recent research suggests that substantial areas require better understanding. Here, Martin Green and Andrew Bradley reflect on the control of mastitis over past decades and look forward to an interesting future.
Mastitis – it’s still relevant!
Mastitis remains important and relevant in all modern dairy systems; it is one of the most significant drains on finances to the worldwide dairy industry, with losses from both clinical and subclinical disease. In developed dairy nations, the condition accounts for greater losses than any other endemic disease — typically, for example, several times more than losses from bovine viral diarrhoea (BVD) and Johne’s disease combined. However, the importance of mastitis extends far beyond the financial impact. In 2009, the Farm Animal Welfare Council (FAWC 2009) highlighted mastitis as a key condition in terms of cow welfare and declared ‘the incidence of endemic diseases in dairy cows, particularly mastitis and lameness, should be reduced urgently’. On a day-to-day basis, the welfare problems associated with mastitis tend to be overlooked. With growing concern over the sustainability of farming and global food security (Foresight 2011), the environmental impact, wastage and inefficiencies associated with mastitis have come sharply into focus (Hospido and Sonesson 2005) (Fig 1); for example, in the UK, the estimated number of cases of clinical mastitis is over one million per year. If we could prevent even half the number of cases currently seen, the milk retrieved would be sufficient to supply half the population of Wales (ie, approximately 1.5 million UK consumers). Mastitis is also Martin Green, BVSc, PhD, DCHP, DipECBHM, MRCVS Andrew Bradley, MA, VetMB, PhD, DCHP, DipECBHM, MRCVS School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Leicestershire LE12 5RD, UK e-mail: [email protected]
Veterinary Record is 125 years old this year. To celebrate, we are publishing an article each month focusing on a key clinical topic. Each article aims to look at what the challenges have been, how the topic has developed and what the future might hold. Articles published so far are listed in the box on p 521. The pictures on the right compare the first issue of Veterinary Record, published on July 14, 1888, with how it looks today
one of the most common reasons for using antimicrobials in dairy cows and, with the current political drive to reduce antimicrobial use in food-producing animals, the control of mastitis on national scales appears imperative. So mastitis in dairy cows remains important on many levels. Whether the push to control mastitis arises from an individual farm or from a national/international agenda, the local vet can play a key role in the farm team to deliver improved mastitis control. While this presents opportunities for veterinary involvement in herd health (mastitis is an obvious candidate for close veterinary involvement), curiously, recent research has highlighted that proactive veterinary involvement in high level mastitis management on English dairy farms is relatively uncommon; fewer than 20 per cent of dairy vets provide such a service to more than three clients (Higgins and others 2013).
Where have we come from? A brief look back
Dairy farming has been carried out for thousands of years, historically being one component of small, mixed farms. In the early 1900s, dairy-specific enterprises emerged and, at this time, the average herd
January 12, 2013 | Vol 172 No 2
Veterinary
ISSN 0042 - 4900
Record Journal of the British Veterinary Association
Radioactivity of faeces and urine from hyperthyroid cats treated with iodine-131 Picture: V. Lamb
Veterinary medicines VMD consults on changes to the regulations
Equine breeding
Identifying the causes behind reproductive failure veterinaryrecord.bvapublications.com
Cover Jan 12.indd 1
09/01/2013 18:01
size in the UK was probably around 10 to 15 cows. By the start of the last century, mastitis had clearly been identified as an important condition and the pathogens associated with mastitis were already being worked out (eg, Henderson 1904). By 1918, sources of infection and routes of transmission were being considered in the hope that infections could be reduced (Jones 1918). Once we reach the 1930s, mastitis was being categorised by pathogen (generally the same as those found today) and by clinical presentation (Minett 1930). Persistent bacterial ‘shedders’ were noted (Plastridge and Anderson 1936) and the importance of intramammary infections to public health had become clear (Brooks and Tiedeman 1937). Antibacterial treatments for mastitis were used in the 1930s (Stevenson 1939) and evaluations of treatments with penicillin (Schofield 1946) started soon after. The assessment of a variety of antimicrobial treatments for mastitis followed and even in 1963 it was noted that the most common reason for antibiotic use in cattle was mastitis (Uvarov 1963). By 1954, a variety of key observations relating to the control of mastitis had been made (Wilson 1952, 1954). Mastitis was clearly demarcated as either contagious November 30, 2013 | Veterinary Record | 517
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Feature
518 | Veterinary Record | November 30, 2013
Picture: Neave and others 1963, kindly supplied by James Booth
contagious manner, (‘readily spread from there are reports of more cow to cow by indirect environmental infection contact during milking’) patterns of S aureus or non-contagious (Sommerhäuser and (transmission by other others 2003). Similarly, routes). Streptococcus while E coli probably agalactiae was reported behaves primarily as to be the predominant an ‘environmental’ pathogen and infected pathogen, chronic cows were an accepted infections with reservoir of infection. contagious spread are Milkers’ hands and possible (Bradley and milking equipment were Green 2001). Maybe the already highlighted as most interesting example potentially important in is S uberis, which appears pathogen transmission to be associated with and prompt treatment FIG 1: With growing concern over the sustainability of farming and global food security, both environmental and culling were also the environmental impact, wastage and inefficiencies associated with mastitis are of and contagious patterns mentioned as potential increasing importance of infection (Zadoks control measures. and others 2003), Interestingly, by this New patterns, new approaches although the relative importance of these time it was recognised that S agalactiae Since the 1980s, new patterns of disease in farm mastitis outbreaks is currently hard could be eradicated from dairy herds, but have emerged and new approaches to to assess. In reality, however, although that eradication of the other pathogens mastitis control have been taken. Here, we there has been a great deal of strain-based would be difficult, if not impossible. highlight some of these. molecular research into mastitis pathogens By the early 1960s, information on (an excellent summary is given by Zadoks the spread of contagious mastitis was Rise of ‘environmental’ pathogens and others 2011), it arguably has yet to bear being pieced together more precisely The rising importance of Streptococcus uberis sufficient fruit in terms of being translated and important field studies were being and Escherichia coli as the predominant into major advances in clinical practice – conducted, notably at the National pathogens associated with mastitis in although disappointing, hopefully this will Institute for Research in Dairying most developed dairy nations is clear, change in the next five years (discussed later (NIRD). NIRD, which was established but whether there has been an absolute in this article). at the University of Reading in 1912 and increase in incidence or an apparent increase moved to Shinfield in 1923, was central because contagious pathogens have been Dry period infections to efforts to control dairy cow mastitis. In controlled is less certain. Either way, it Although, since the 1940s, it has been 1963, advice was being given regarding has become obvious that while the basic known that new intramammary infections foremilking to identify mastitis, washing measures of the five-point plan, when could occur during the dry period, the of hands with disinfectants during milking, applied accurately, help to reduce contagious importance of these infections was post-milking teat disinfection (Fig 2), mastitis, understanding and controlling the overlooked and their significance in terms of disinfection (or avoidance) of udder cloths, opportunistic intramammary pathogens herd mastitis control has only been clarified cluster disinfection and treatment of teat is proving a great deal more difficult and in the last decade. New infections are most sores (Neave and others 1963). Fifty years remains the focus of much research. That likely when the mammary gland is at its later, this advice is still not consistently said, it should also be recognised that, in most susceptible (just after drying off and in practised! the past 20 to 30 years or so, our cows have the few weeks up to and including calving) In the mid-1960s, important progress been bred and fed to produce a greater milk was made in the control of mastitis yield (average yields up from under 5000 to through the development of a simple and over 7000 litres per cow per year) and, as a effective mastitis control plan that could result of both genetics and environmental be easily communicated to, and taken up influences, this may well have impacted by, the dairy industry. This five-point plan on cow susceptibility. In fact, it can be devised at NIRD (Neave and others 1966, argued that, over this period, the incidence 1969, Smith and others 1967) essentially of mastitis per litre of milk produced has described the now well-known fivereduced dramatically. step approach to mastitis control: rapid identification and treatment of clinical Blurring of mastitis boundaries cases; routine whole-herd antibiotic Numerous research studies using a variety of dry cow therapy; post-milking teat molecular techniques have shown that it is disinfection; culling of chronically affected an oversimplification to categorise the main cows; and the routine maintenance of the mastitis pathogens as either ‘contagious’ milking machine. Uptake of the five-point or ‘environmental’ in terms of their mode plan resulted in a reduction in the incidence of transmission/infection. Rather, different of clinical mastitis (between 1967 and 1982 subspecies (‘strains’) of the major pathogens this fell from approximately 150 [Wilson appear to be able to behave in different ways, and Kingwill 1975] to approximately 40 although the mechanisms behind these [Wilesmith and others 1986] cases per differences are generally not understood. 100 cows per year) and a reduction in the For example, while most Staphylococcus prevalence of contagious pathogens and, aureus probably behave in a typically hence, bulk milk somatic cell counts. FIG 2: Teat dipping in 1963
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Feature schemes. These and are most likely include Countdown to cause clinical and Downunder subclinical disease (Australia), Smart in the early stages SAMM (New of lactation. While Zealand), the Dutch dry period infections Udder Health have been identified Programme, the in research studies Norwegian Mastitis (Fig 3), it has been Control Program, the appearance Cell Check (Animal of modern herd Health Ireland) health software and the DairyCo (Fig 4) that has Mastitis Control allowed widespread FIG 3: Molecular techniques have been used in mastitis research, such as this example using a Plan (Great Britain). application of this fingerprinting method to trace isolates from the dry period into lactation. But has research using Although the knowledge; the molecular biological techniques yet had sufficient influence on clinical practice? approaches within monitoring of early these schemes vary, lactation somatic this reflects to some extent the position and cell counts and rates of clinical mastitis has recommendations fits all’ to farm-specific requirements of the individual industries proved an excellent proxy for dry period approaches that include continuous disease within each country. However, all of the infections and, therefore, helped to inform monitoring. initiatives have sprung from the recognition farm control strategies. Another aspect of mastitis control, that improved mastitis control is vital to highlighted recently and championed by the enhance the competitiveness of a nation’s Heifer mastitis excellent Dutch Udder Health Programme, dairy industry. A variety of research studies over the past has been the importance of communication In general, on-farm mastitis control is five years has reaffirmed the importance of techniques and the need to facilitate change a good example of the need for iterative mastitis in heifers, including the importance on farm (Jansen and Lam 2012). Even when herd health management, the ‘manage – of intramammary infections before and we have sufficient technical knowledge, monitor – re-evaluate – manage’ cycle, and around the time of first calving. As with change does not always occur. This can be this now forms the basis of some mastitis many diseases, early-life infections can for a variety of reasons, including farmer control schemes. Indeed, mastitis lends itself be bad news, leading to reduced lifetime and vet motivations and attitudes, poor to close, precision monitoring with indices milk production, increased likelihood of communication and the need to act against for disease patterns having been worked out premature culling and a risk to herd mates social norms. Vets are, in fact, in a good and software readily available to automate from pathogen transmission (De Vliegher position to facilitate change by encouraging detailed monitoring. and others 2005, Archer and others 2013). and assisting farmers to take action, The prevalence of coagulase-negative although this may require learning a new set staphylococcal infections in heifers has A lot to look forward to? of skills (Higgins and others 2013). been a subject of particular interest in With extraordinary scientific advances being The importance of mastitis control several countries, although the exact role of made in many areas of veterinary medicine, at the national level has also become different species has yet to be clarified and including genetics/genomics and molecular more apparent in the last decade with the remains the subject of active research (they and computational biology, research in appearance of several national control have, in fact, in some cases, been associated with increased milk production). A current problem with the control of mastitis in heifers mirrors that of much of mastitis control; that there has been a lack of clinical trials to evaluate the best management strategies for disease control. Approaches to mastitis control on farm Although the five-point plan was, and is, successful up to a point, approaches to mastitis control in the modern dairy herd have had to move beyond this. The increased importance of environmental pathogens means that a greater focus is placed on identifying areas of risk for environmental infection, and this is not always straightforward. Unlike contagious mastitis, where attention is mostly focused on a specific area (milking routine and plant) at a specific time (milking), management of the environment, whether housed or at pasture, can be challenging. Betweenfarm variation in cow environments over a 24-hour period is vast and, thus, mastitis control has had to move away from the arguably simplistic ‘one set of
FIG 4: Excellent software is available to monitor clinical and subclinical mastitis for herd health purposes; mastitis is probably the dairy cow condition with the best methods of monitoring
November 30, 2013 | Veterinary Record | 519
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Feature the next five years could transform current knowledge and hopefully our on-farm approach to mastitis control. One criticism of mastitis (and other) research over the past 10 to 20 years is that, with notable exceptions, it has had insufficient impact at farm level. Fortunately, the importance of ‘research impact’ (research making a difference to real life) has recently gained impetus in the funding community and there is cautious optimism that, going forward, research outcomes will more commonly translate to clinical practice. Although not intended as an exhaustive collection, below we highlight some interesting areas that we believe could potentially make a difference. Ecological aspects of environmental pathogens A greater understanding of how to reduce the force of infection of mastitis pathogens in the environment would clearly be of value, but major questions exist. For example, what is the variation in faecal shedding of environmental pathogens and how can this be influenced? How can we more reliably influence bacterial survival in the environment under different climatic and managemental conditions? Can we improve the understanding of exactly when infections occur? Can we influence the infection process by altering ecological conditions? Can we ‘out-compete’ environmental pathogens with less pathogenic strains of bacteria? Bacterial communities We tend to consider the major mastitis pathogen species in isolation, but there is evidence in human and bovine research that this may not be the case. Therefore, the risk of infection and/or disease may be influenced by a dynamic microbial community in the mammary gland or environment. Understanding the role of this community and how it develops and changes over time could provide a new angle on the control of mastitis. Host genetics/genomics Although understanding genetic determinants of animal disease is at an early stage, great advances are occurring in this field and, with genomic information becoming more accessible, there will be opportunities to further the understanding of cow resistance to mastitis. Although a word of caution is needed (it is clear from existing research that for mastitis and many other infectious diseases, the genetic component may provide limited rewards in terms of disease control), any help is clearly worth having. It is already evident from studies in this field that it is unlikely that one or a few genes will be responsible for most of the variation in cow mastitis resistance, and thus a truly polygenic approach will be necessary. However, as data 520 | Veterinary Record | November 30, 2013
become available and computing methods improve, genomic predictions will become more sophisticated and accurate, and should translate through breeding policy to improved mastitis control on farm. Vaccination and non-specific immune support Arguably, vaccination remains the ‘holy grail’ of mastitis control. History is littered with attempts to develop a truly efficacious mastitis vaccine. J5 core antigen vaccines have proven to be a useful management tool, but they fail to prevent infection and only ameliorate the clinical signs of disease. Other vaccines have typically failed to provide protection at a meaningful level. Vaccination to control the contagious mastitis pathogens seems of lesser importance given our current knowledge and vaccination against environmental pathogens still seems to present an enormous challenge. Even if a truly efficacious vaccine against an environmental pathogen is developed and intramammary infection is prevented, it remains possible that any ecological niche left by such a vaccine could be filled by another environmental opportunist. This perhaps makes methods that result in ‘non-specific’ immune enhancement a potentially fruitful approach. Host-pathogen interactions The extent to which different pathogen strains behave differently in the mammary gland (of different hosts) and the mechanisms behind these differences remains another general area of research interest that could develop to fruition in the next five years. Such host-pathogen interactions may also be modified by environmental conditions, adding to the complexity. Although a vast area, advances in this field could lead to vaccine candidates or novel ways to influence the infection process. Informed decision making To make full use of molecular and genetic information as well as cow and farm information, ‘real-time decision support’ is a research area that should advance in terms of mastitis control. Essentially, this would mean identifying the best decision (eg, management change) in a given set of circumstances and its probability of success. Modern statistical and computing methods readily allow probabilistic predictions to be made and presented to the end user in a usable format. The key to success will be to make use of readily available information and to ensure results are relevant and accessible to the end user. Alternatives to antibiotics Approaches to reduce the use of antibiotics in mastitis control are going to be needed. The widespread prophylactic use of antibiotics, such as that seen with blanket application of dry cow therapy, is not
sustainable. Fortunately, alternatives for prevention of mastitis at this time of heightened risk already exist (internal teat sealants) and further developments in this area are likely in the future. Therapy in lactation perhaps presents more of a challenge; identification of efficacious alternatives appears a long way off. Diagnostics This is an area likely to advance in the near future. Already, technologies such as PCR, fingerprinting and MALDI-TOF-MS (matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry) are being adopted in clinical practice – further uptake and refinement of these methods is inevitable and one can envisage a time when the practitioner will be able to make a more informed decision about treatment and control measures to be adopted on-farm based on a better understanding of the pathogen strain involved. Somatic cell counting has been a cornerstone of mastitis monitoring for many years, providing a crude leucocyte count, but again the advent of new technologies means that differential counts of different leucocyte types will become a reality, enabling a more precise definition of the infection status of individual cows. New technologies A plethora of new technologies are becoming available in a vast number of areas and could lead to improved diagnosis, treatment and control of mastitis. Examples of areas in which exciting changes could be seen include new diagnostics (to enable early disease detection or identify the presence of pathogen strains known to behave in particular ways), parlour technologies (including robotics, improved in-line diagnostics to monitor mastitis and automated processes to reduce contagious transmission), behavioural technology systems (eg, to monitor movements, lying times, food intake, digestive/metabolic status) and improved software for mastitis monitoring and decision support. It is worth highlighting one common pitfall of new technologies: commercial pressure often means that new technologies reach the market before they are fully optimised and, in some cases, this can lead to disillusionment and technologies being inappropriately discredited.
Challenges and opportunities
In summary, mastitis in dairy cows has been recognised and studied for many decades. Important progress has been made over the years, but large challenges remain, especially around the control of environmental pathogens. Modern research and technologies are likely to lead to a multitude of possibilities for new improved approaches to mastitis control; hopefully some will reach clinical practice in the next five years.
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Feature Acknowledgement
The authors would like to thank James Booth for providing useful literature for this article.
References
ARCHER, S. C., MCCOY, F., WAPENAAR, W. & GREEN, M. J. (2013) Association between somatic cell count early in the first lactation and the lifetime milk yield of cows in Irish dairy herds. Journal of Dairy Science 96, 2951-2959 BRADLEY, A. J. & GREEN, M. J. (2001) Adaptation of Escherichia coli to the bovine mammary gland. Journal of Clinical Microbiology 39,1845-1849 BROOKS, P. B. & TIEDEMAN, W. V. D. (1937) Relation of bovine mastitis to human disease. American Journal of Public Health and the Nation’s Health 27, 334-338 DE VLIEGHER, S., BARKEMA, H. W., OPSOMER, G., DE KRUIF, A. & DUCHATEAU, L. (2005) Association between somatic cell count in early lactation and culling of dairy heifers using cox frailty models. Journal of Dairy Science 88, 560-568 FARM ANIMAL WELFARE COUNCIL (2009) Opinion on the welfare of the dairy cow. www.fawc.org.uk/pdf/ dcwelfar-091022.pdf. Accessed November 12, 2013 Foresight (2011) The Future of Food and Farming: Challenges and Choices for Global Sustainability. www. bis.gov.uk/assets/foresight/docs/food-and-farming/11547-future-of-food-and-farming-summary.pdf. Accessed November 18, 2013 HENDERSON, J. (1904) A contribution to the study of mastitis in cows. Journal of Comparative Pathology and Therapeutics 17, 24-27 Higgins, H. M., GREEN, M. J. & MADOUASSE, A. (2013) Facilitating change in herd health. In Dairy Herd Health. Ed M. Green. CABI HOSPIDO, A. & SONESSON, U. (2005) The environmental impact of mastitis: a case study of dairy herds. The Science of the Total Environment 1, 71-82 JANSEN, J. & LAM, T. J. (2012) The role of communication in improving udder health. Veterinary Clinics of North America: Food Animal Practice 28, 363-379 JONES, F. S. (1918) Studies in bovine mastitis: the sources of infection in streptococcic mastitis. Journal of Experimental Medicine 28, 735-748 MINETT, F . C. (1930) Clinical forms and bacteriology of bovine mastitis. Proceedings of the Royal Society of Medicine 23, 1344-1346
NEAVE, F. K., DODD, F. H. & KINGWILL, R. G. (1963) The control of udder disease by hygiene. A progress report of research at the National Institute for Dairying (Press release) NEAVE, F. K., DODD, F. H. & KINGWILL, R. G. (1966) A method of controlling udder disease. Veterinary Record 78, 521-523 NEAVE, F. K., DODD, F. H., KINGWILL, R. G. & WESTGARTH, D. R. (1969) Control of mastitis in the dairy herd by hygiene and management. Journal of Dairy Science 52, 696-707 PLASTRIDGE, W. N. & ANDERSON, E. O. (1936) Detection of shedders of streptococci responsible for infectious bovine mastitis. American Journal of Public Health and the Nation’s Health 26, 711-715 SCHOFIELD, F. W. (1946) Penicillin in the treatment of bovine mastitis. Canadian Journal of Comparative Medicine and Veterinary Science 10, 63-70 SMITH, A., WESTGARTH, D. R., JONES, M. R., NEAVE, F. K., DODD, F. H. & BRANDER, G. C. (1967) Methods of reducing the incidence of udder infection in dry cows. Veterinary Record 81, 504-510 SOMMERHÄUSER, J., KLOPPERT, B., WOLTER, W., ZSCHÖCK, M., SOBIRAJ, A. & FAILING, K. (2003) The epidemiology of Staphylococcus aureus infections from subclinical mastitis in dairy cows during a control programme. Veterinary Microbiology 96, 91-102 STEVENSON, W. G. (1939) Sulfanilamide in treatment of
bovine mastitis. Canadian Journal of Comparative Medicine 3, 147-160 UVAROV, O. (1963) Some antibiotic formulations for the treatment of bovine mastitis. Proceedings of the World Veterinary Congress. Hanover. pp 1337-1338 WILESMITH, J. W., FRANCIS, P. G. & WILSON, C. D. (1986) Incidence of clinical mastitis in a cohort of British dairy herds. Veterinary Record 118, 199-204 WILSON, C. D. (1952) The control of bovine mastitis. Veterinary Record 64, 525-530 WILSON, C. D. (1954) The present position with regard to bovine mastitis. Proceedings of the 72nd Annual Congress of the British Veterinary Association. Torquay WILSON, C. D. & KINGWILL, R. G. (1975) International Dairy Federation. Annual Bulletin 85, 422-438 ZADOKS, R. N., GILLESPIE, B. E., BARKEMA, H. W., SAMPIMON, O. C., OLIVER, S. P. & SCHUKKEN, Y. H. (2003) Clinical, epidemiological and molecular characteristics of Streptococcus uberis infections in dairy herds. Epidemiology and Infection 130, 335-349 ZADOKS, R. N., MIDDLETON, J. R., MCDOUGALL, S., KATHOLM, J. & SCHUKKEN, Y. H. (2011) Molecular epidemiology of mastitis pathogens of dairy cattle and comparative relevance to humans. Journal of Mammary Gland Biology and Neoplasia 16, 357-372
doi: 10.1136/vr.f7029
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The changing face of mastitis control Martin Green and Andrew Bradley Veterinary Record 2013 173: 517-521
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Feature
Feature
Veterinary Record 125 years
Mastitis
The changing face of mastitis control Over the past 125 years, mastitis has been one of the most studied conditions of dairy cows. This is confirmed by a search of peer-reviewed literature covering this period, which revealed more than 12,000 papers. Yet mastitis is still one of the most relevant and problematic diseases to treat and control in practice, which is testament to the complexity and mutability of the condition. Although progress has been made, recent research suggests that substantial areas require better understanding. Here, Martin Green and Andrew Bradley reflect on the control of mastitis over past decades and look forward to an interesting future.
Mastitis – it’s still relevant!
Mastitis remains important and relevant in all modern dairy systems; it is one of the most significant drains on finances to the worldwide dairy industry, with losses from both clinical and subclinical disease. In developed dairy nations, the condition accounts for greater losses than any other endemic disease — typically, for example, several times more than losses from bovine viral diarrhoea (BVD) and Johne’s disease combined. However, the importance of mastitis extends far beyond the financial impact. In 2009, the Farm Animal Welfare Council (FAWC 2009) highlighted mastitis as a key condition in terms of cow welfare and declared ‘the incidence of endemic diseases in dairy cows, particularly mastitis and lameness, should be reduced urgently’. On a day-to-day basis, the welfare problems associated with mastitis tend to be overlooked. With growing concern over the sustainability of farming and global food security (Foresight 2011), the environmental impact, wastage and inefficiencies associated with mastitis have come sharply into focus (Hospido and Sonesson 2005) (Fig 1); for example, in the UK, the estimated number of cases of clinical mastitis is over one million per year. If we could prevent even half the number of cases currently seen, the milk retrieved would be sufficient to supply half the population of Wales (ie, approximately 1.5 million UK consumers). Mastitis is also Martin Green, BVSc, PhD, DCHP, DipECBHM, MRCVS Andrew Bradley, MA, VetMB, PhD, DCHP, DipECBHM, MRCVS School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Leicestershire LE12 5RD, UK e-mail: [email protected]
Veterinary Record is 125 years old this year. To celebrate, we are publishing an article each month focusing on a key clinical topic. Each article aims to look at what the challenges have been, how the topic has developed and what the future might hold. Articles published so far are listed in the box on p 521. The pictures on the right compare the first issue of Veterinary Record, published on July 14, 1888, with how it looks today
one of the most common reasons for using antimicrobials in dairy cows and, with the current political drive to reduce antimicrobial use in food-producing animals, the control of mastitis on national scales appears imperative. So mastitis in dairy cows remains important on many levels. Whether the push to control mastitis arises from an individual farm or from a national/international agenda, the local vet can play a key role in the farm team to deliver improved mastitis control. While this presents opportunities for veterinary involvement in herd health (mastitis is an obvious candidate for close veterinary involvement), curiously, recent research has highlighted that proactive veterinary involvement in high level mastitis management on English dairy farms is relatively uncommon; fewer than 20 per cent of dairy vets provide such a service to more than three clients (Higgins and others 2013).
Where have we come from? A brief look back
Dairy farming has been carried out for thousands of years, historically being one component of small, mixed farms. In the early 1900s, dairy-specific enterprises emerged and, at this time, the average herd
January 12, 2013 | Vol 172 No 2
Veterinary
ISSN 0042 - 4900
Record Journal of the British Veterinary Association
Radioactivity of faeces and urine from hyperthyroid cats treated with iodine-131 Picture: V. Lamb
Veterinary medicines VMD consults on changes to the regulations
Equine breeding
Identifying the causes behind reproductive failure veterinaryrecord.bvapublications.com
Cover Jan 12.indd 1
09/01/2013 18:01
size in the UK was probably around 10 to 15 cows. By the start of the last century, mastitis had clearly been identified as an important condition and the pathogens associated with mastitis were already being worked out (eg, Henderson 1904). By 1918, sources of infection and routes of transmission were being considered in the hope that infections could be reduced (Jones 1918). Once we reach the 1930s, mastitis was being categorised by pathogen (generally the same as those found today) and by clinical presentation (Minett 1930). Persistent bacterial ‘shedders’ were noted (Plastridge and Anderson 1936) and the importance of intramammary infections to public health had become clear (Brooks and Tiedeman 1937). Antibacterial treatments for mastitis were used in the 1930s (Stevenson 1939) and evaluations of treatments with penicillin (Schofield 1946) started soon after. The assessment of a variety of antimicrobial treatments for mastitis followed and even in 1963 it was noted that the most common reason for antibiotic use in cattle was mastitis (Uvarov 1963). By 1954, a variety of key observations relating to the control of mastitis had been made (Wilson 1952, 1954). Mastitis was clearly demarcated as either contagious November 30, 2013 | Veterinary Record | 517
Downloaded from veterinaryrecord.bmj.com on September 5, 2014 - Published by group.bmj.com
Feature
518 | Veterinary Record | November 30, 2013
Picture: Neave and others 1963, kindly supplied by James Booth
contagious manner, (‘readily spread from there are reports of more cow to cow by indirect environmental infection contact during milking’) patterns of S aureus or non-contagious (Sommerhäuser and (transmission by other others 2003). Similarly, routes). Streptococcus while E coli probably agalactiae was reported behaves primarily as to be the predominant an ‘environmental’ pathogen and infected pathogen, chronic cows were an accepted infections with reservoir of infection. contagious spread are Milkers’ hands and possible (Bradley and milking equipment were Green 2001). Maybe the already highlighted as most interesting example potentially important in is S uberis, which appears pathogen transmission to be associated with and prompt treatment FIG 1: With growing concern over the sustainability of farming and global food security, both environmental and culling were also the environmental impact, wastage and inefficiencies associated with mastitis are of and contagious patterns mentioned as potential increasing importance of infection (Zadoks control measures. and others 2003), Interestingly, by this New patterns, new approaches although the relative importance of these time it was recognised that S agalactiae Since the 1980s, new patterns of disease in farm mastitis outbreaks is currently hard could be eradicated from dairy herds, but have emerged and new approaches to to assess. In reality, however, although that eradication of the other pathogens mastitis control have been taken. Here, we there has been a great deal of strain-based would be difficult, if not impossible. highlight some of these. molecular research into mastitis pathogens By the early 1960s, information on (an excellent summary is given by Zadoks the spread of contagious mastitis was Rise of ‘environmental’ pathogens and others 2011), it arguably has yet to bear being pieced together more precisely The rising importance of Streptococcus uberis sufficient fruit in terms of being translated and important field studies were being and Escherichia coli as the predominant into major advances in clinical practice – conducted, notably at the National pathogens associated with mastitis in although disappointing, hopefully this will Institute for Research in Dairying most developed dairy nations is clear, change in the next five years (discussed later (NIRD). NIRD, which was established but whether there has been an absolute in this article). at the University of Reading in 1912 and increase in incidence or an apparent increase moved to Shinfield in 1923, was central because contagious pathogens have been Dry period infections to efforts to control dairy cow mastitis. In controlled is less certain. Either way, it Although, since the 1940s, it has been 1963, advice was being given regarding has become obvious that while the basic known that new intramammary infections foremilking to identify mastitis, washing measures of the five-point plan, when could occur during the dry period, the of hands with disinfectants during milking, applied accurately, help to reduce contagious importance of these infections was post-milking teat disinfection (Fig 2), mastitis, understanding and controlling the overlooked and their significance in terms of disinfection (or avoidance) of udder cloths, opportunistic intramammary pathogens herd mastitis control has only been clarified cluster disinfection and treatment of teat is proving a great deal more difficult and in the last decade. New infections are most sores (Neave and others 1963). Fifty years remains the focus of much research. That likely when the mammary gland is at its later, this advice is still not consistently said, it should also be recognised that, in most susceptible (just after drying off and in practised! the past 20 to 30 years or so, our cows have the few weeks up to and including calving) In the mid-1960s, important progress been bred and fed to produce a greater milk was made in the control of mastitis yield (average yields up from under 5000 to through the development of a simple and over 7000 litres per cow per year) and, as a effective mastitis control plan that could result of both genetics and environmental be easily communicated to, and taken up influences, this may well have impacted by, the dairy industry. This five-point plan on cow susceptibility. In fact, it can be devised at NIRD (Neave and others 1966, argued that, over this period, the incidence 1969, Smith and others 1967) essentially of mastitis per litre of milk produced has described the now well-known fivereduced dramatically. step approach to mastitis control: rapid identification and treatment of clinical Blurring of mastitis boundaries cases; routine whole-herd antibiotic Numerous research studies using a variety of dry cow therapy; post-milking teat molecular techniques have shown that it is disinfection; culling of chronically affected an oversimplification to categorise the main cows; and the routine maintenance of the mastitis pathogens as either ‘contagious’ milking machine. Uptake of the five-point or ‘environmental’ in terms of their mode plan resulted in a reduction in the incidence of transmission/infection. Rather, different of clinical mastitis (between 1967 and 1982 subspecies (‘strains’) of the major pathogens this fell from approximately 150 [Wilson appear to be able to behave in different ways, and Kingwill 1975] to approximately 40 although the mechanisms behind these [Wilesmith and others 1986] cases per differences are generally not understood. 100 cows per year) and a reduction in the For example, while most Staphylococcus prevalence of contagious pathogens and, aureus probably behave in a typically hence, bulk milk somatic cell counts. FIG 2: Teat dipping in 1963
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Feature schemes. These and are most likely include Countdown to cause clinical and Downunder subclinical disease (Australia), Smart in the early stages SAMM (New of lactation. While Zealand), the Dutch dry period infections Udder Health have been identified Programme, the in research studies Norwegian Mastitis (Fig 3), it has been Control Program, the appearance Cell Check (Animal of modern herd Health Ireland) health software and the DairyCo (Fig 4) that has Mastitis Control allowed widespread FIG 3: Molecular techniques have been used in mastitis research, such as this example using a Plan (Great Britain). application of this fingerprinting method to trace isolates from the dry period into lactation. But has research using Although the knowledge; the molecular biological techniques yet had sufficient influence on clinical practice? approaches within monitoring of early these schemes vary, lactation somatic this reflects to some extent the position and cell counts and rates of clinical mastitis has recommendations fits all’ to farm-specific requirements of the individual industries proved an excellent proxy for dry period approaches that include continuous disease within each country. However, all of the infections and, therefore, helped to inform monitoring. initiatives have sprung from the recognition farm control strategies. Another aspect of mastitis control, that improved mastitis control is vital to highlighted recently and championed by the enhance the competitiveness of a nation’s Heifer mastitis excellent Dutch Udder Health Programme, dairy industry. A variety of research studies over the past has been the importance of communication In general, on-farm mastitis control is five years has reaffirmed the importance of techniques and the need to facilitate change a good example of the need for iterative mastitis in heifers, including the importance on farm (Jansen and Lam 2012). Even when herd health management, the ‘manage – of intramammary infections before and we have sufficient technical knowledge, monitor – re-evaluate – manage’ cycle, and around the time of first calving. As with change does not always occur. This can be this now forms the basis of some mastitis many diseases, early-life infections can for a variety of reasons, including farmer control schemes. Indeed, mastitis lends itself be bad news, leading to reduced lifetime and vet motivations and attitudes, poor to close, precision monitoring with indices milk production, increased likelihood of communication and the need to act against for disease patterns having been worked out premature culling and a risk to herd mates social norms. Vets are, in fact, in a good and software readily available to automate from pathogen transmission (De Vliegher position to facilitate change by encouraging detailed monitoring. and others 2005, Archer and others 2013). and assisting farmers to take action, The prevalence of coagulase-negative although this may require learning a new set staphylococcal infections in heifers has A lot to look forward to? of skills (Higgins and others 2013). been a subject of particular interest in With extraordinary scientific advances being The importance of mastitis control several countries, although the exact role of made in many areas of veterinary medicine, at the national level has also become different species has yet to be clarified and including genetics/genomics and molecular more apparent in the last decade with the remains the subject of active research (they and computational biology, research in appearance of several national control have, in fact, in some cases, been associated with increased milk production). A current problem with the control of mastitis in heifers mirrors that of much of mastitis control; that there has been a lack of clinical trials to evaluate the best management strategies for disease control. Approaches to mastitis control on farm Although the five-point plan was, and is, successful up to a point, approaches to mastitis control in the modern dairy herd have had to move beyond this. The increased importance of environmental pathogens means that a greater focus is placed on identifying areas of risk for environmental infection, and this is not always straightforward. Unlike contagious mastitis, where attention is mostly focused on a specific area (milking routine and plant) at a specific time (milking), management of the environment, whether housed or at pasture, can be challenging. Betweenfarm variation in cow environments over a 24-hour period is vast and, thus, mastitis control has had to move away from the arguably simplistic ‘one set of
FIG 4: Excellent software is available to monitor clinical and subclinical mastitis for herd health purposes; mastitis is probably the dairy cow condition with the best methods of monitoring
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Feature the next five years could transform current knowledge and hopefully our on-farm approach to mastitis control. One criticism of mastitis (and other) research over the past 10 to 20 years is that, with notable exceptions, it has had insufficient impact at farm level. Fortunately, the importance of ‘research impact’ (research making a difference to real life) has recently gained impetus in the funding community and there is cautious optimism that, going forward, research outcomes will more commonly translate to clinical practice. Although not intended as an exhaustive collection, below we highlight some interesting areas that we believe could potentially make a difference. Ecological aspects of environmental pathogens A greater understanding of how to reduce the force of infection of mastitis pathogens in the environment would clearly be of value, but major questions exist. For example, what is the variation in faecal shedding of environmental pathogens and how can this be influenced? How can we more reliably influence bacterial survival in the environment under different climatic and managemental conditions? Can we improve the understanding of exactly when infections occur? Can we influence the infection process by altering ecological conditions? Can we ‘out-compete’ environmental pathogens with less pathogenic strains of bacteria? Bacterial communities We tend to consider the major mastitis pathogen species in isolation, but there is evidence in human and bovine research that this may not be the case. Therefore, the risk of infection and/or disease may be influenced by a dynamic microbial community in the mammary gland or environment. Understanding the role of this community and how it develops and changes over time could provide a new angle on the control of mastitis. Host genetics/genomics Although understanding genetic determinants of animal disease is at an early stage, great advances are occurring in this field and, with genomic information becoming more accessible, there will be opportunities to further the understanding of cow resistance to mastitis. Although a word of caution is needed (it is clear from existing research that for mastitis and many other infectious diseases, the genetic component may provide limited rewards in terms of disease control), any help is clearly worth having. It is already evident from studies in this field that it is unlikely that one or a few genes will be responsible for most of the variation in cow mastitis resistance, and thus a truly polygenic approach will be necessary. However, as data 520 | Veterinary Record | November 30, 2013
become available and computing methods improve, genomic predictions will become more sophisticated and accurate, and should translate through breeding policy to improved mastitis control on farm. Vaccination and non-specific immune support Arguably, vaccination remains the ‘holy grail’ of mastitis control. History is littered with attempts to develop a truly efficacious mastitis vaccine. J5 core antigen vaccines have proven to be a useful management tool, but they fail to prevent infection and only ameliorate the clinical signs of disease. Other vaccines have typically failed to provide protection at a meaningful level. Vaccination to control the contagious mastitis pathogens seems of lesser importance given our current knowledge and vaccination against environmental pathogens still seems to present an enormous challenge. Even if a truly efficacious vaccine against an environmental pathogen is developed and intramammary infection is prevented, it remains possible that any ecological niche left by such a vaccine could be filled by another environmental opportunist. This perhaps makes methods that result in ‘non-specific’ immune enhancement a potentially fruitful approach. Host-pathogen interactions The extent to which different pathogen strains behave differently in the mammary gland (of different hosts) and the mechanisms behind these differences remains another general area of research interest that could develop to fruition in the next five years. Such host-pathogen interactions may also be modified by environmental conditions, adding to the complexity. Although a vast area, advances in this field could lead to vaccine candidates or novel ways to influence the infection process. Informed decision making To make full use of molecular and genetic information as well as cow and farm information, ‘real-time decision support’ is a research area that should advance in terms of mastitis control. Essentially, this would mean identifying the best decision (eg, management change) in a given set of circumstances and its probability of success. Modern statistical and computing methods readily allow probabilistic predictions to be made and presented to the end user in a usable format. The key to success will be to make use of readily available information and to ensure results are relevant and accessible to the end user. Alternatives to antibiotics Approaches to reduce the use of antibiotics in mastitis control are going to be needed. The widespread prophylactic use of antibiotics, such as that seen with blanket application of dry cow therapy, is not
sustainable. Fortunately, alternatives for prevention of mastitis at this time of heightened risk already exist (internal teat sealants) and further developments in this area are likely in the future. Therapy in lactation perhaps presents more of a challenge; identification of efficacious alternatives appears a long way off. Diagnostics This is an area likely to advance in the near future. Already, technologies such as PCR, fingerprinting and MALDI-TOF-MS (matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry) are being adopted in clinical practice – further uptake and refinement of these methods is inevitable and one can envisage a time when the practitioner will be able to make a more informed decision about treatment and control measures to be adopted on-farm based on a better understanding of the pathogen strain involved. Somatic cell counting has been a cornerstone of mastitis monitoring for many years, providing a crude leucocyte count, but again the advent of new technologies means that differential counts of different leucocyte types will become a reality, enabling a more precise definition of the infection status of individual cows. New technologies A plethora of new technologies are becoming available in a vast number of areas and could lead to improved diagnosis, treatment and control of mastitis. Examples of areas in which exciting changes could be seen include new diagnostics (to enable early disease detection or identify the presence of pathogen strains known to behave in particular ways), parlour technologies (including robotics, improved in-line diagnostics to monitor mastitis and automated processes to reduce contagious transmission), behavioural technology systems (eg, to monitor movements, lying times, food intake, digestive/metabolic status) and improved software for mastitis monitoring and decision support. It is worth highlighting one common pitfall of new technologies: commercial pressure often means that new technologies reach the market before they are fully optimised and, in some cases, this can lead to disillusionment and technologies being inappropriately discredited.
Challenges and opportunities
In summary, mastitis in dairy cows has been recognised and studied for many decades. Important progress has been made over the years, but large challenges remain, especially around the control of environmental pathogens. Modern research and technologies are likely to lead to a multitude of possibilities for new improved approaches to mastitis control; hopefully some will reach clinical practice in the next five years.
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Feature Acknowledgement
The authors would like to thank James Booth for providing useful literature for this article.
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doi: 10.1136/vr.f7029
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The changing face of mastitis control Martin Green and Andrew Bradley Veterinary Record 2013 173: 517-521
doi: 10.1136/vr.f7029
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