Latest approaches for the management of mastitis

Milk is one of the most important foods of human beings and is recognized globally as a complete diet due to presence of essential components required for human health. India has a good number of dairy animal populations which plays an important role in economy of the country. India continues to be the largest producer of milk in the world (19% of the world’s total milk production) with annual milk production of 176 million tons in 2017-18(BAHS, DAHD&F, GOI). The per capita availability of milk in India is above the ICMR recommended level of 280 gram per day. By the year 2030 milk demand would be around 200 MT.

With this existing rate of growth in milk production (6.37%) supply is likely to fall short of demand in the next two decades. There are several barriers in achieving the production targets among which mastitis is one of the biggest challenging impediments since the affected quarter may have 30% less productivity and a cow may loss 15% production (Shrivastva et al., 2015)

 

Causating agents:

It can be of an infectious, traumatic or toxic nature. Of the several causes of mastitis, the microbes are the vital players in causing bovine mastitis. More than135microbial species, subspecies and serovars have been isolated from the bovine mammary glands(Watts, 1988). Subclinical mastitis is believed to be more prevalent than clinical mastitis in most countries. Recent studies reported high incidence of subclinical mastitis ranging from 20 to 83 per cent in cows and 45 per cent in buffaloes. According to Kumari et al., 2018  the prevalence of subclinical mastitis in five states of Punjab, Haryana, Uttar Pradesh, Madhya Pradesh, and Maharashtra was 53.52%, 51.18%, 39.58 %, 62.49 % and 35.11 % respectively.

 

Breed, species, age, parity, stage of lactation, dry period, transition period, milking interval, udder defence, etc. Important pathogenic risk factors include presence of number of organisms on teat skin and their virulence factors. Various environmental factors like housing system, climate, heat stress, milking hygiene, udder hygiene, milking machine, milking techniques etc.can play a crucial role in the occurrence of mastitis. Global estimated economic losses per year due to mastitis amounts to USD 35 billion. The annual economic loss due to mastitis in India has been calculated to be approximately Rs.7165.51 crores; (Project Directorate on Animal Disease Monitoring and Surveillance, 2011) Decreased milk quality, milk rejection, cost of treatment, loss of udder Tissue; culling of animal. The economic losses due to bovine subclinical mastitis is in range of Rs.21, 677/- to 88,340/- per animal per lactation (Rathod et al., 2017). Other causes are the elimination of milk containing antibiotics used in treating sick animals, loss of genetic value by culling cows early and more expensive replacement, veterinary fees, drug expenditures, payments of extra labor hours and the commercial value reduction of cows removed. The economic losses associated with mastitis have been estimated to be due to reduced milk yield (up to 70%), milk discard after treatment (9%), cost of veterinary services  (7%) and premature culling (14%).

 

Premilking preparation includes cleaning teats before unit attachment and examination for clinical mastitis and abnormal milk. The combination of effective teat cleaning and fore stripping will provide sufficient stimulation for milk letdown. Proper teat-end disinfection can reduce teat surface bacteria. Pre-dipping is most effective in the control of environmental pathogens (E. coli and environmental streptococci)(Ruegg et al., 1987, Fox et al., 1997). A minimum contact time of 20-30 seconds is needed for effective disinfection.

 

After a cow has finished milking, a signal to the individual control system is given, the milk line is closed and disinfection fluid is sprayed into mouthpiece chamber of teat liner. The unit is detached within 1 s. after which the system allows about 10-15 seconds for the disinfection fluid to disinfect the liner then rinsed 6-10 times with alternating cold water, followed by compressed air to remove any chemical residue and clean each liner (Riekerink et al., 2012)

 

Solutions :

Various dipping solution-Iodophor solution (0.1% - 1%), Sodium hypochlorite (4%), Chlorhexidine(0.35–0.55%), DodecylBenzene Sulfonic Acid (DDBSA), Quaternary Ammonium compounds(0.05- 1.0%)

Alternative to these chemicals are herbal products– Mastidip, Mastilep, Phytomast, etc.

Minimize the slipping or falloffs to less than 5% of cow’s milking. Heavy clusters, uneven weight distribution within the cluster, blocked air admission holes or poor liner design are other common causes of slips and falloffs.

 

Dry Cow Therapy:

Treating or infusing teat of lactating dairy animals with long acting antibiotics or teat sealants or both at drying-off following last milking for management of subclinical mastitis is called dry cow therapy (Biggs, 1998). It not only helps in preventing the risk of udder infection during dry period but also the milk yield in subsequent lactations is increased. This therapy cures existing infections and prevents new infections in the early dry period.     

 

California mastitis test (CMT), Somatic cell count (SCC), Electrical conductivity test (EC), White side test (WST), Sodium lauryl sulphate test (SLST) Surf field mastitis test (SFMT), Chloride test, Catalase test, Bromothymol blue test (BTB), NAGase test,  Infrared Thermography(IRT),  Proteomic techniques. PCR, Rennet coagulation test, Lactose determination test, Modified Hulendorfer Mastitis probe (MHMP), Radial immunodiffusion test Arginase enzyme, Lactate dehydrogenase (LDH), Alkaline Phosphatase (ALP), Alanine aminotransferase (ALT) Generally post mastitis management is done through antibiotics.

However,their regular use poses many problems like widespread bacterial resistance against antibiotics, no new drug in pipeline, chemical residues in milk indirectly affecting human health, violation of guidelines for organic farming. These challenges demand the need for therapeutic advancements for managing mastitis.

 

Advances in therapeutic management:

Nanotechnology: Nanotechnology has enabled to synthesize nanosized particles using them in a wide range of applications, particularly in drug delivery. Nanoparticles possess increased surface areas and therefore have increased interactions with biological targets (such as bacteria) compared with micronparticles. Moreover, they are much more likely to enter cells than micron particles. The nanoparticles may be considered potential delivery systems in the treatment of bovine mastitis since they may be taken up by the phagocytes. As example, silver nanoparticles showed to inhibit S. Aureus isolated from subclinical mastitis (Dehkordi etal., 2011).

Bacteriophages: Bacteriophage therapy can be a possible alternative to antibiotics in the fight against mastitis infections. Phages presented several features critical to their use as phage therapy, like wide range of host, high lytic activity, and thermostability, do not affect normal microbiota, eco-friendly, etc.

Phage K is an anti-staphylococcus phage, with lytic and antimicrobial action and has been used as a prophylactic measure in infections caused by S. aureus.

Kwiatek et al. isolated a new virulent phage (MSA6) from a cow with mastitis, which presented a wide lytic spectrum against staphylococcal strains of bovine origin. Fenton et al. 2013 tested bacteriophage-derived peptidase; CHAPK against S. aureus isolated from mastitis infected cows. CHAPK was effective against bio?lms either by preventing bio?lm formation or by disrupting established bio?lms of staphylococci strains associated with bovine mastitis.

Vaccination: Nowadays, vaccination became an important area in mastitis control strategies.Effect of vaccination depends on several factors: type of vaccine, age of cow, environmental conditions. Streptococcus uberis vaccine: Bacterin vaccine, Live vaccine, Subunit vaccine, Recombinant cytokine vaccine (IL-2, TNF-a), Staphylococcus aureus: Bactrin, E.Coli vaccine: J-5“bactrin”and “mastiguard” J-Vac.           

 

Plant-Derived Antimicrobial: Plants are promising sources of new biologically active agents with antimicrobial action. Moreover, plant-derived drugs have the advantage of not inducing resistance after prolonged exposure (Domadia et al., 2007, Ohno et al., 2003) Eg. diterpenes.

Fonseca et al. tested three diterpenes: manool, ent-kaurenoic acid, and entcopalic acid against several bovine mastitis pathogens. Entcopalic acid (CA) was the most active against most of the microorganisms tested. Besides its antibacterial potential, CA did not to cause a cytotoxic effect on human fibroblast cell line, so this fact encourages its possible use on bovine mastitis control and treatment.

Some of the plants and their parts with promising results against mastitis pathogens have been used. These include Tinospora cordifolia, Curcuma longa, Allium stivum, Azadirachtaindica, Ocimumsanctum, Terminaliachebula, Morindacitrifolia, Taraxacummongolicum, Eucalyptusglobulus.

 

Animal-Derived Antimicrobial: The immunomodulators, naturally produced by mammals, such as lactoferrin, acts as potential non-antibiotic antimicrobial agents for treatment and prevention of bovine mastitis. Lactoferrin is a glycoprotein found in several body secretions such as saliva, tears, bronchial mucus, and milk. This molecule exhibited an antibacterial effect against E. coli, S. aureus, coagulase-negative staphylococci, Pseudomonas aeruginosa and K. pneumonia (Kutila et al., 2003). Other example include β-lacto globulin (whey), marine sponges (Cinachyrella sp., Haliclona sp., and Petromica citrine)

 

Bacteria and Bacteria-Derived Antimicrobials:

 Natural compounds produced by bacteria presenting antimicrobial action can be alternative antibiotics for the control and treatment of bovine mastitis. Weisella confusa (lactic acid bacteria) and its metabolites active against S. aureus and S. Agalactiae (Serna-Cock et al., 2012).  Bouchard et al. tested live lactobacillus casei as mammary probiotics. These bacteria were able to prevent the internalization of S. aureus into mammary epithelial cells and therefore reduce chronicity and recurrence of S. aureus mastitis infections.

 

Stem cell therapy:

 Stem cells are commonly defined as “cells capable of self-renewal through replication and differentiating into specific lineages”. Besides this, stem cells have important property that they also serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the person or animal is alive. Secreted factors of these stem cells have multiple positive effects like their role in the formation of new blood vessels and promotion in migration of cells, both of which are integral in healing tissue damaged by mastitis. Some factors protect epithelial cells from damage caused by bacterial toxins, and others proved to be antimicrobial peptides that play a role in killing bacteria. It could also help the antibiotics work better, since they produce some of those antibiotic properties (Van de Walle, 2018).

 

 With the advancement of molecular/ quantitative genetics, marker-assisted selection (MAS) are one of the novel ways for selecting disease resistant breeds for mastitis. Candidate genes can be chosen on the basis of known relationship between physiological/biochemical processes as well as production traits so called Quantitative Trait Loci (QTL) (Deb et al., 2012). Various novel genes has been identified and their association analysis with SCC revealed mastitis resistant biomarkers viz. TLR2 (Zhang et al., 2009), TLR4 (Deb et al., 2013), IL8 (Chen et al., 2011), BRCA1, (Xu et al., 2011), CACNA2D1 (Yuan et al., 2011).

 

Conclusion:

Advances in mastitis research have brought new technologies that can be used to solve complex problems confronting dairy production. A better understanding of the multiplicity of pathogens causing mastitis their virulence, knowledge of mammary gland immunology, will facilitate development of effective mastitis vaccines. Novel developments, strategies, and advances in mastitis diagnosis, treatment and prevention (phages, stem cell therapy, nanoparticles etc.)can improve udder health and result in reduced severity of mastitis, increased production and profitability.