1 Apr 2019
Emma Fishbourne discusses latest developments in a major cause of disease and economic loss to the UK dairy industry.
Emma Fishbourne
Job Title
Mastitis is still a significant cause of disease and economic loss to the UK dairy industry, with big welfare implications. With a growing world population, and concerns over sustainability and food security, we need to address the losses from the disease and reduce antimicrobial use. In the past few decades, we have seen a change in pathogens cultured from clinical cases, with increased isolation of opportunistic environmental pathogens or no growth. Improvements in diagnostics have challenged our understanding and classification of mastitis pathogens as contagious or environmental and research has highlighted the dry period origin of clinical mastitis cases seen in early lactation.
To control mastitis in the modern dairy herd, practitioners have had to adopt a farm-specific approach due to the vast environmental variation cows experience between farms across a 24-hour period. Work on milk microbiota has demonstrated the presence of bacterial DNA in milk from healthy cows with a low somatic cell count, leading to the possibility that manipulation of the microbiota of teats and mammary gland may provide new tools for mastitis control and genetic selection may also provide us with the opportunity to enhance host resistance to mastitis.
As dairy cattle practitioners, we want to improve the health and welfare of cattle under our care, while also improving productivity and efficiency for our clients’ businesses.
Mastitis remains one of the most significant diseases affecting dairy cows in the UK, despite widespread implementation of the five-point plan and an ever-growing body of research into risk factors and epidemiology. Mastitis results in economic losses to our clients’ businesses and it compromises animal welfare. It has also come into focus from growing concerns around sustainability of farming, global food security and antimicrobial use in food-producing animals.
In the past few decades, the incidence of mastitis in the UK has remained fairly consistent. A survey in 2007 of clinical and subclinical mastitis on 97 dairy farms in England and Wales found a mean incidence of clinical mastitis of 47 cases per 100 cows per year (estimated from historic farm records) and 71 cases per 100 cows per year (estimated from samples collected; Bradley et al, 2007).
The overall cost of mastitis is highly variable. In the US, clinical mastitis in the first 30 days of lactation has been estimated to cost US$444 (£338), broken down into US$128 (£97) in direct costs and US$316 (£241) in indirect costs (Rollin et al, 2015). Direct costs arise from the cost of drugs, discarded milk and increased labour, and indirect costs from production losses from damage to the mammary gland, somatic cell count (SCC) penalties, increased culling rate, increased risk of disease transmission to herd mates and reduced fertility performance.
Evidence is growing about the effect of mastitis on animal welfare. Dairy cows with clinical mastitis show changes in lying time, activity and feeding behaviour.
The reduction in lying time has been reasoned to be due to pain in the infected udder and shown to persist during the recovery period following a case of clinical mastitis (Fogsgaard et al, 2015). In Escherichia coli lipopolysaccharide-induced mastitis, meloxicam has been demonstrated to relieve pain, and decrease udder oedema and body temperature (Fitzpatrick et al, 2013), and the use of NSAIDs to treat severe acute toxic mastitis is widely used in practice.
The addition of meloxicam to standard antimicrobial therapy for mild or moderate clinical mastitis cases has also been shown to be beneficial. Using it in dairy cattle in the first 120 days of lactation has been shown to improve conception rates at first service (0.31 versus 0.21), increase the number of cows pregnant by 120 days after calving (0.40 versus 0.31) and reduce the number of services per conception (2.43 versus 2.92; McDougall et al, 2016).
The same study also concluded a higher probability of a bacteriological cure. The use of meloxicam and penethamate in cows with clinical mastitis has also been demonstrated to reduce SCC and culling compared with penethamate treatment alone (McDougall et al, 2009).
The use of meloxicam to treat mild or moderate cases of clinical mastitis in the first 120 days of lactation has been shown to be cost effective across many production systems, with a net economic benefit of €42 (£35) per clinical mastitis case (van Soest et al, 2018).
Historically, most mastitis was caused by Streptococcus species or Staphylococcus species. However, a shift has taken place in the past few decades towards opportunistic environmental organisms.
A UK study in 2007 isolated Streptococcus uberis and E coli from 23.5% and 19.8% of clinical samples, with 26.5% of samples producing no growth. A total of 39% of high cell count samples produced no growth, with coagulase-negative staphylococci isolated from 15% of samples, S uberis from 14% and Corynebacterium species from 10% (Bradley et al, 2007).
It is unclear if the increase in S uberis and E coli as the predominant pathogens associated with mastitis is apparent because contagious pathogens have been controlled, or whether a genuine increase in incidence has taken place. Molecular diagnostic techniques have highlighted different subspecies of the main mastitis pathogens can behave in different ways, showing it is an oversimplification to categorise them as “contagious” or “environmental”, as in reality many species can be transmitted in multiple ways (Green and Bradley, 2013).
A potential reason for the increase in culture-negative milk samples includes cows with chronic subclinical mastitis giving false-negatives because the large inflammatory response has successfully reduced the number of organisms to below the detection limit in most mastitis laboratories.
In mild or moderate clinical mastitis cases caused by opportunistic pathogens, these may have been successfully eliminated by the cow’s immune system before detection of inflammation.
The changes in mastitis pathogens have also occurred with changes in breeding and feeding for increased milk, and these could also have impacted on cow susceptibility. However, the knowledge we have gained on genetics also provides us with opportunities to enhance host resistance to mastitis through breeding.
Currently, the only way to determine if the clinical signs of a mild or moderate case of clinical mastitis are accompanied by active microbial infection is to perform milk culture.
To ensure accurate diagnosis, standardised culturing methods for milk samples have been developed and interest is growing in the UK for on-farm culture prior to the treatment of clinical mastitis.
Using on-farm culture, only non-severe cases that yield a Gram-positive or mixed culture are treated with antimicrobial drugs, compared to all cases of mastitis done conventionally. This, therefore, reduces antimicrobial use (Lago et al, 2011).
A UK study highlighted this approach may not be cost effective for many herds, and is primarily suitable for herds where Gram-negative pathogens are responsible for most clinical mastitis and the delay in treating does not reduce bacteriological cure (Down et al, 2017).
Mycoplasma species mastitis is a major problem in large US dairy herds, while in the UK we tend to see sporadic cases. However, we may see more here as the trend for large herds continues, as this is the most important risk factor for the disease.
Mycoplasma mastitis causes severe damage to the udder, results in significant losses in milk production and is often refractory to antibiotic treatment. Mycoplasma species are inherently resistant to penicillins and cephalosporins, while in-vitro resistance has been detected to all main antibiotic classes, including fluoroquinolones.
Mycoplasma species can also infect different sites in the body, invade host cells and form biofilms evading antimicrobial therapy. Affected animals can remain externally normal – even in severe cases – showing few overt clinical signs, and the disease is highly contagious.
Control involves regular monitoring and rapid segregation or culling of infected animals, and ensuring it is not bought in, so strict biosecurity of all cattle before entering the herd is vital. Only a few of the 25 or so mycoplasmas detected in cattle cause mastitis, and in Europe Mycoplasma bovis is the dominant species. Research does suggest the prevalence of Mycoplasma mastitis might be higher in other European countries compared to the UK, so this may be something to discuss with clients who are importing European cattle due to TB breakdowns.
Other risk factors for transmission to the rest of the herd include feeding waste milk or colostrum (so pasteurisation is recommended if this is practised), close contact of calves with adult dairy cattle and the lack of a well-separated sick or hospital pen.
Improved molecular diagnostic tests are assisting with rapid detection of Mycoplasma. An accurate diagnosis requires laboratory testing, although the presence of arthritis and/or pneumonia in a herd with mastitis increases the likelihood of a diagnosis of M bovis.
Routine monitoring of bulk milk tank cultures is often more effective and convenient than individual screening. It is feasible tests can detect a single positive cow in a herd of 1,000 cows due to the levels of bacteria shed in milk.
Following a positive result in the bulk tank, cows with elevated SCC in milk could then be screened (Nicholas et al, 2016, provides a good review of this).
The focus around management of the dry cow to control mastitis came in 2000, when DNA fingerprinting was used to show new infections of dry period origin were an important cause of clinical mastitis that developed later in the following lactation (Bradley and Green, 2000).
In 2002, the first internal teat sealant was introduced in the UK and these have been found to be useful in controlling environmental pathogens. The risk of new dry period infections is greatest just after drying off and just before parturition, and unlike antibiotic dry cow treatments the internal teat sealants provide protection for the entire dry period, sealing the teat ends and reducing susceptibility to new infections, because many cows don’t produce good keratin plugs to seal the teat ends (Biggs, 2017).
The use of internal teat sealants has also helped reduce antimicrobial use in dairy cattle over the past few years, with cows with low SCCs no longer routinely receiving antimicrobials at drying off and antimicrobial dry cow therapy reserved for cows with existing infections.
As practitioners, the importance of technique at drying off cannot be emphasised enough to our clients as a means to preventing loss of animals if sterility isn’t adhered to.
Vaccine development has proved difficult due to the heterogeneity of mastitis-causing bacteria and the unique environment of the mammary gland.
Field studies on a commercially available polyvalent mastitis vaccine directed against enterbacterial and staphylococcal species (Startva, Hipra UK) demonstrated a significant reduction in the severity of clinical mastitis cases in vaccinated cows compared to unvaccinated in the first 120 days of lactation, and an increase in milk and milk solids. However, no significant difference in the incidence or prevalence of clinical or subclinical mastitis is seen (Bradley et al, 2015).
An issue for milk culture is the delay in treating clinical cases, as it typically takes 24 to 48 hours and many samples do not culture anything. This has led to the development of culture-independent technologies that detect bacterial DNA, with the first milk microbiota of North American cows first described in 2012 following work on human milk samples. This demonstrated a much greater diversity of bacteria than had been previously reported from traditional culturing (Oikonomou et al, 2012).
Previously, researchers concluded culture-negative milk from quarters with low SCC was sterile, but initial studies using these new technologies are questioning the concept of milk sterility, with some researchers suggesting mastitis may be a multi-agent disease because of the wide variety of bacterial DNA collected from milk samples from healthy and inflamed quarters.
The issue with a lot of this work is that the origin of DNA in culture-negative milk samples is unknown. Sources of the bacterial DNA could include bacteria introduced during sample collection from the cow’s skin or environment, bacteria or bacterial DNA trapped within the keratin of the teat canal, or leukocytes.
Later studies have collected samples directly from the gland cistern, but this is invasive and not practical for clinical work. However, the work has demonstrated the presence of bacterial DNA in milk from healthy cows with a low SCC, leading to the possibility manipulation of the microbiota of teats and mammary gland may provide new tools for mastitis control.
Milk microbiota research is still in its early stages and poorly understood, with considerable variation in the methodology, meaning more research is required before this application can be used for either diagnostic or clinical applications. Practitioners should, therefore, take care when comparing results from different groups (Metzger et al, 2018).
