23rd Middle European Buiatrics Congress (XXIII MEBC), held near Brno, Czech Republic
This article provides a summary of the introductory keynote presentation – Bovine Mastitis, what’s new? – delivered by Dr. Sarne De Vliegher in section 2 on mastitis and udder health at the 23rd Middle European Buiatrics Congress, held near Brno, Czech Republic in late April of 2024. A general report on the entire conference was published in Veterinářství 6/2024.
Bovine mastitis, an old disease
Bovine mastitis is the inflammatory response to bacteria entering the bovine mammary gland via the teat canal trying to cause intramammary infection. Clinical mastitis is always characterized by abnormal milk and sometimes also by swelling or pain of the udder and may be accompanied by systemic signs such as elevated rectal temperature, lethargy and anorexia (Harmon, 1994). Subclinical mastitis is the form in which there are no abnormalities of the milk and the udder observable through the senses. Still, milk production decreases, bacteria are often present in the secretion and composition is altered (Harmon, 1994). In either form, mastitis in dairy cows is still a costly disease due to depression of milk yield, milk withdrawal, extra treatment and labour costs, and early culling. It should be prevented rather than cured (Halasa et al., 2007).
Mastitis is still an important disease not only for the dairy farmer but also for the dairy industry as a number of issues threaten the image of milk as a healthy product from healthy animals. In that respect, antibiotic usage should be reduced. On dairy farms antibiotic use is most often related to udder health (Lam et al., 2011; Stevens et al., 2016). Although antimicrobials remain vital for treatment of bacterial infections, also in dairy cattle, the industry has to act in a responsible and proactive way in the light of the ongoing debate instigated by the potential link between the use of antimicrobial products and the development of antimicrobial resistance in both animal and human pathogens. The EU regulation 2019/6, effective since January 28 2022, states that prophylactic use of antimicrobials is prohibited (other than in exceptional cases), meaning that we have to step up our efforts, for example at drying-off, when the routine administration of antibiotics is no longer permitted.
More focus on prevention
Improving udder health at the farm level is still based on the application of two basic principles: (1) reduction in duration of Existing intramammary infections (E) through the treatment of likely curable infections and culling of animals with likely incurable infections, and (2) reducing the incidence of New intramammary infections (N) by limiting exposure / infection pressure and enhancing the cows’ immunity. Improvement of udder health and application of the two principles will be obtained through working with mastitis prevention and control programs such as the one promoted by the National Mastitis Council (NMC, 2021 – currently under review). If we can improve mastitis management, better milk quality, better udder health and more judicious and lowered antimicrobial usage will be the results (Stevens et al., 2019).
Prevention of mastitis of course also relates to the epidemiology of the causative pathogens. In that respect, mastitis pathogens are stratified based on their ecology (host-adapted versus environmental) and their epidemiology [contagious, e.g. most S. agalactiae strains) versus opportunistic (e.g. most S. uberis strains)]. However, these classifications are (no longer) clear-cut, and with the increasing knowledge about ‘atypical’ strains, their overlap is becoming increasingly apparent.
New(er) tools and treatment options
Internal teat sealants. Teat sealants have been on the market for quite a few years. As the udder of cows at dry-off and cows before calving is at high risk of becoming infected (as a function of infection pressure) and because the natural keratin plug does not develop in all quarters (especially not in high-yielding cows) the use of such products has been proven to very effective (Dingwell et al., 2003). When applied correctly, they prevent the establishment of new intramammary infections during the dry period, leading to improved udder health in the first weeks of the new lactation (Green et al., 2002). Internal teat sealants can be used as part of a selective dry cow approach (see further) and can be combined with long-acting antibiotics in infected quarters/cows.
Vaccines. Mastitis vaccines are used to prevent mastitis caused by Escherichia coli and Klebsiella spp., Staphylococcus aureus and non-aureus staphylococci and in recent years also by S. uberis (Lam and De Vliegher, 2021). Vaccines aim to stimulate the specific humoral response through memory B lymphocytes that are activated to quickly produce specific antibodies after exposure to a specific mastitis pathogen. Another part of the working mechanism goes through stimulation of cellular immunity. Vaccines for environmental pathogens such as coliforms and S. uberis, primarily aim to limit severity of disease in order to decrease costs and culling (Wilson et al., 2009; Bradley et al., 2015). The most frequently described vaccine against E. coli is the J5 vaccine, which is frequently used in the United States (González et al., 1989). Vaccines for contagious mastitis (e.g. caused by most S. aureus strains) focus more on decreased shedding of bacteria, decreasing transmission and thus the number of new infections (Schukken et al., 2014; Piepers et al., 2016). Bovine practitioners are best placed to decide whether and what vaccine can be integrated as part of mastitis management improvements on a dairy farm using available data (clinical mastitis incidence, somatic cell counts, bacteriological culture results).
Selective treatment of clinical mastitis. When treating clinical mastitis, we aim at reaching pain relief and clinical and bacteriological cure. Before, it was advocated to treat any case of clinical mastitis as fast as possible with antimicrobials yet with the availability of rapid tests that can be performed either on farm or in the veterinary milk lab, we now have the option to selectively treat non-severe cases of clinical mastitis. This means that severe cases are treated as before yet mild or moderate cases are only treated with antimicrobials when the rapid test has shown (after 18-24 hours; it is recommended to administer non-steroidals in the meantime in all cases) a gram-positive bacterium is involved. In the case gram-negatives have grown or the test has yielded no growth as a result, the cow is not treated with antimicrobials. Negative consequences (e.g., clinical or bacteriological cure, somatic cell count, culling rate, milk yield, milk withdrawal) can be almost ruled out yet this relatively new treatment approach leads to a substantial drop in antimicrobial usage (de Jong et al., 2023).
Selective treatment of dry cows. Whereas we have advocated blanket treatment of cows at dry-off (both infected and noninfected cows and quarters receive long-acting antimicrobials) for years, we have now approached an era where enough evidence is available showing that only treating cows (or quarters) likely to be infected with major pathogens at dry-off with antimicrobials is the right option, at least on well-managed dairy farms.
Furthermore, since January 2022, routine administration of antimicrobials (e.g., at dry-off) and preventive administration (apart from exceptional cases as mentioned above) are no longer permitted in the EU. As early as the beginning of 2017, Dr. De Vliegher and six Western Europe experts reached the following consensus (Brdley et al., 2018):
- Administering an internal teat sealant (see before), at drying off, to all cows, on all farms is advised;
- Cows that are likely-infected need to receive antibiotic dry cow therapy in addition to teat sealants;
- Farms should be classified as “low risk” or “high risk” with regards to udder health and the approach on these farms should be different;
- Ultimately every herd is suitable for selective antibiotic dry cow therapy. “High risk herds” (e.g. with a bulk milk somatic cell count of more than 250,000 cells/ml in two of the past six months) have to go through a process of engagement and improve overall management and udder health. Veterinarians should aim to guide their clients through this first step. In subsequent correspondence, Dr. De Vliegher explained that in exceptional cases where it proves justified to temporarily implement blanket administration of antibiotics at dry-off for all cows as an exemption from the ban on preventive administration of antibiotics, he recommends that private veterinarians enter into a written agreement with farmers regarding a systematic approach to mastitis control aimed at improving udder health over a period of x months. This would make the farmers co-responsible and engaged in the process. The veterinarians must also be able to justify the prescription of an antimicrobial medicinal product according to legislation, particularly for prophylactic and metaphylactic purposes.
- Veterinarians should ensure training of the farm staff on selective dry cow treatment and the appropriate and primarily hygienic application of internal teat sealants.
- Identification of likely-infected cows at the end of lactation can be done using clinical mastitis history, somatic cell count data, conventional culture, rapid tests, … (Lipkens et al., 2019: McCubbin et al., 2022).
Mastitis control programmes. In his presentation, Prof. De Vliegher mentioned the historical 5-point British programme for contagious mastitis control, as well as the current (general) 10-point programme for environmental mastitis control (and targeted herd udder health management) developed in the USA (NMC, 2021). For European conditions, he recommended the following updated 7-point programme, as presented in M²-magazine (#18, 2017) by Tom Hemling (US):
- Disinfect all teats after milking (N)
- Treat all cases of clinical mastitis selectively based on rapid culture and record data once the bacteria are determined (N + E)
- Use dry cow teat sealant on all cows and selectively use dry cow therapy (N + E)
- Cull all cows with three or more cases of clinical mastitis (N + E)
- Maintain the milking machine properly (N)
- Milk a clean, dry, and disinfected teat (N)
- Use nutrition, stimulants, and vaccines to improve immunity (N + E)
Current and future innovations in treatment and prevention:
Acoustic Pulse Technology (APT, Armenta Ltd. – Israel) is a technology transferred from human medicine, where it has been used for 30 years. It is a technology for the treatment of clinical and subclinical mastitis through physical transcutaneous acoustic pulse therapy (i.e., without withdrawal periods) that improves cure and increases milk yield due to enhanced cell viability, improved healing, and anti-inflammatory factors.
Casein hydrolysate peptides (and specific protein fragments) especially designed for intramammary non-antibiotic preventive and therapeutic treatment of cows at drying-off (e.g. ImilacTM Mileutis Ltd.- Israel). This treatment accelerates udder involution and (self-) cure leading to improved health and performance in the subsequent lactation.
Bacteriophages and endolysins. Bacteriophages are viruses that infect bacteria by recognizing specific receptors on the cell wall of bacterial species or strains, which cause them to adsorb and inject their DNA (Vander Elst, 2023). They effectively target and lyse bacteria with extreme specificity (Nale and McEwan, 2023). For bovine mastitis, various sample sources have been explored for the purpose of isolating phages for the various mastitis causing pathogens including sewage, mastitic milk, cowshed wastewater, … Single-phage treatments can significantly reduce bacterial load. However, phage resistance was detected within as early as 2 h after treatment (Nale and McEwan, 2023). To curtail resistance and other issues including broadening host target coverage and specificity, and to improve lysis efficiency, a cocktail of diverse phages could form a solution (Nale and McEwan, 2023). Some other drawbacks include unwanted immune response instigated by the treatment (as seen in uninfected mammary gland quarters), milk blocking attachment of the phages, and the multi-bacterial cause of mastitis.
Endolysins are produced by phages and are peptidoglycan hydrolases that degrade the bacterial cell wall. They are investigated as promising, novel antimicrobials. Endolysins can ben stratified in so-called wild-type versus engineered endolysins (engineered using specific platforms). The latter are then hit-to-lead selected to finally select one top engineered candidate to be tested in preclinical models. Recently, such engineered endolysin NC5 was preclinically evaluated as add-on to cloxacillin treatment, decreasing bacterial load, neutrophil influx, and pro-inflammatory mediators in a murine model (Vander Elst et al., 2024). Both innovations have attracted attention, also in mastitis treatment, because of the need to find new non-antimicrobial approaches to deal with the disease.
Probiotics. The non-aureus staphylococci (NAS) have traditionally been seen as teat skin colonizers, being classified somewhere in between contagious and environmental in origin. Species-specific research performed over the last 10 years has revealed that some species are much more host-adapted (and likely contagious, such as S. chromogenes) than others (such as S. fleurettii, now Mammaliicoccus fleurettii). Still, an orofecal transmission route is also suspected for NAS as faecal shedding has been confirmed, with the same strains being present in faecal samples, on the teat end and in milk samples (Wuytack et al., 2019). More recent NAS work has focussed on the (species-specific) association with udder health and milk yield, substantiating that NAS intramammary infection results in moderately elevated SCC yet not in reduced milk yield (Valckenier, 2021). Combining the latter findings with the fact that many NAS harbour bacteriocin gene clusters, warrants further study because of potential protection exerted, e.g. when “treating” dry quarters with specific NAS strains (Beuckelaere et al., 2021).
Conclusions
Bovine mastitis is an old disease that still causes important economic losses. Prevention remains key and we (perfectly …) know how to do that. Treatment options using antibiotics have become limited because of new EU legislation yet this provides us with new opportunities such as selective treatments during lactation and at the drying-off, both of which should become standard practice. As well, innovations in non-antimicrobial treatment and prevention are under scrutiny and could hit the market in the next few years.
Acknowledgements
This article is based on both the contribution published in the proceedings and the presentation at the MEBC, which Dr. De Vliegher kindly provided to the author for the preparation of this article. The author appreciates Dr. De Vliegher for his generous provision of materials and granting permission to publish them. This paper was supported by the Ministry of Agriculture of the Czech Republic, projects NAZV QK22020292 and MZE–RO0523.
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