Introduction
Mastitis is an important welfare and economic disease of ruminants in countries where livestock are kept due to associated economic losses and significant public health implications, particularly due to the emergence and transmission of resistant bacteria to humans via the food chain [1,2]. The disease is associated with changes in the quantity and quality of milk, and pathological changes in mammary tissues of the udder [3]. A number of pathogens have been reported as agents of mastitis but Staphylococcus species are the most frequently identified pathogen in cases of mastitis in ruminants [4,5]. Additional reported pathogens of mastitis include members of the Enterobacteriaceae, Streptococcus species, Pseudomonas aeruginosa, Corynebacteria, Mannheimia haemolytica, and fungi [6,62]. In addition to these pathogens, a number of factors including, stage of lactation, age of cows in the herd, milk routine, poor milking hygiene, improper management, teat injuries, and faulty milking machines are reported to hasten the onset of mastitis in ruminants [1,7,8].
Table 1.
Distribution of ruminant mastitis, etiologic agents, and risk factors.
| Country | Host animal | Sample size (Milk samples) | Category of mastitis (SCM and CM) | Bacteria isolated | Diagnostic test | Identifiable risk factors | Reference | |
|---|---|---|---|---|---|---|---|---|
| United States | Dairy cow | Six herd | - | - | NAS (S. chromogenes, S. haemolyticus, S. simulans, and S. epidermidis) | Bacteriologic culture and identification and PCR | Stage of lactation | Jenkins et al. [36] |
| United States | Dairy cow | 189 dairy herd (365) | - | - | S. aureus | Bacteriologic culture and identification, PCR, spa typing, and MLST | - | Patel et al. [3] |
| Canada | Dairy cow | 115,294 | SCM | - | NAS | CMT, bacteriologic culture and identification, and PCR | - | Nobrega et al. [33] |
| Belgium | Dairy cow | 386 | SCM | - | NASM species | Bacteriologic culture and identification and RAPD-PCR | - | Reydams et al. [12] |
| Turkey | Dairy cow | 500 | SCM | - | Staphylococcus spp., Corynebacterium spp., Bacillus spp., Acinetobacter spp., E. coli, and Mycoplasma spp. | CMT and bacteriologic culture and identification | - | Sağlam et al. [73] |
| Greece | Dairy sheep | 2,198 ewes from 111 farms | SCM | - | NAS and S. aureus | CMT and bacteriologic culture and identification | Breed, management system, and application of post-milking teat dipping | Vasileiou et al. [74] |
| Italy | Dairy sheep | 2,198 | - | CM | S. uberis, S. epidermidis, and S. aureus | Bacteriologic culture and identification | Manual milking | Marogna et al. [54] |
| Italy | Dairy sheep | 120 | - | - | NAS (S. epidermidis) | Bacteriologic culture and identification and PCR-RFLP | - | Turchi et al. [55] |
| Italy | Dairy sheep and goat | 84 | SCM | CM | S. aureus | Bacteriologic culture and identification and PCR | - | Parco et al. [75] |
| Italy | Dairy goat and sheep | 204 | SCM | CM | NAS (S. epidermidis, S. chromogenes, S. haemolyticus, S. caprae, and S. simulant) | Bacteriologic culture and identification, MALDI-TOF MS, and gap PCR–RFLP | - | Rosa et al. [40] |
| Italy | Dairy goat and sheep | 57 | SCM | CM | S. uberis, S. dysgalactiae, Streptococcus parauberis, and S. gallolyticus | Bacteriologic culture and identification, MALDI-TOF MS, and gap PCR–RFLP | - | Rosa et al. [40] |
| Columbia | Dairy cows | 40 dairy cows (960 milk samples | SCM | - | NAS (S. epidermidis, S. chromogenes, S. sciuri, S. simulans, S. haemolyticus, and S. capitis) | CMT and bacteriologic culture and identification | - | Andrade-Becerra et al. [76] |
| Brazil | Dairy goat | 9 | SCM | CM | S. aureus | Bacteriologic culture and identification and PCR | - | Lima et al. [2] |
| Brazil | Dairy cow | 57 | SCM | - | S. aureus Enterobacter spp. | CMT Bacteriologic culture and identification |
- | Garcia-Sanchez et al. [77] |
| Brazil | Dairy cow | 530 dairy cows 67 non-milk |
SCM | - | S. aureus | Bacteriologic culture and identification and MALDI-TOF MS | Parity and herd size | Silva et al. [8] |
| Brazil | Dairy goats | 268 | SCM | - | S. aureus, S. epidermidis, E. coli, S. saprophyticus, and S. caprae | Strip cut test, CMT, and bacteriologic culture and identification | Lack of access to veterinary service | Lima et al. [78] |
| Ethiopia | Dairy cow | 167 dairy farms | SCM | CM | S. aureus | CMT, bacteriologic culture and identification, and PCR | - | Mekonnen et al. [7] |
| Ethiopia | Dairy cow | 404 lactating cows | - | - | S. intermedius, S. hyicus, S. aureus, and NAS (S. lentus and S. sciuri) | Bacteriologic culture and identification | Age, stage of lactation, type of housing, interval of bedding and cleaning, and previous history of mastitis | Dabele et al. [79] |
| Northern Ethiopia | Sheep and Goat | 135 sheep, 255 goats | SCM | - | NAS, E. coli, S. aureus, and streptococci | CMT and bacteriologic culture | Age, parity, and stage of lactation | Gebrewahid et al. [23] |
| Southern Ethiopia | Dairy cow | 529 | SCM | - | S. aureus | CMT and bacteriologic culture and identification | Herd size, bedding material, and milking procedure | Abebe et al. [16] |
| Algeria | Dairy cow | 418 dairy cows | SCM | CM | S. aureus and NAS | SCC, bacteriologic culture and identification, and spa typing | - | Zaatout et al. [80] |
| Algeria | Dairy goat | 854 | SCM | CM | S. aureus, streptococci, and NAS | CMT and Bacteriologic culture and identification | Gabli et al. [51] | |
| Egypt | Dairy Goat | 336 half milk samples from 177 dairy goats | SCM | CM | Corynebacterium pseudotuberculosis and S. aureus | SCC and bacteriologic culture and identification | - | Nabih et al. [62] |
| Egypt | Dairy Goat | 249 lactating goat (477 milk sample) | SCM | CM | NAS, S. aureus, and streptococci | SCC and bacteriologic culture and identification | Stage of lactation | Hussein et al. [58] |
| Egypt | Dairy goat and Sheep | 289 | SCM | - | S. aureus, NAS (S. epidermidis, S. hominis, S. cohnii, and S. saprophyticus), E. coli, Streptococcus spp., Klebsiella spp., and Pseudomonas spp. | CMT, bacteriologic culture and identification, and API staph kit | - | Abdalhamed et al. [81] |
| Rwanda | Dairy cows | 256 | SCM | - | NAS and S. aureus | CMT | Parity and breed | Ndahetuye et al. [67] |
| Tanzania | Dairy cow | 416 | SCM | - | S. aureus, E. coli, P. aeruginosa, Micrococcus, Klebsiella, and S. epidermidis | CMT and bacteriologic culture and identification | - | Suleiman et al. [82] |
| Uganda | Dairy cow | 239 (milk and sour milk samples) | NA | NA | S. aureus | Bacteriologic culture and identification and PCR | - | Asiimwe et al. [4] |
| Nigeria | Dairy goat and sheep | 348 mammary gland secretions | SCM | CM | S. aureus, Streptococcus spp., E. coli, Klebsiella spp., Proteus, Bacillus cereus, Citrobacter, and Morganella morganii | CMT and bacteriologic culture and identification | - | Danmallam et al. [83] |
| Nigeria | Dairy goats | 250 lactating goats | SCM | CM | S. aureus, NAS (S. chromogenes, S. epidermidi, and Mammaliicoccus lentus), E. coli, and S. agalactiae | CMT and bacteriologic culture and identification | - | Danmallam and Pimenov [84] |
| Nigeria | Dairy goat and sheep | 200 milk samples | NA | NA | Methicillin-resistant S. aureus (MRSA) | Bacteriologic culture and identification and PCR | - | Omoshaba et al. [85] |
| Nigeria | Dairy cow | 180 milk samples | NA | NA | S. aureus | Bacteriologic culture and identification | Water source | Yakubu et al. [86] |
| Nigeria | Dairy cow | 180 milk samples | NA | NA | MRSA | Bacteriologic culture and identification and PCR | - | Aliyu et al. [87] |
| Nigeria | Dairy cows, sheep and goat | 1,052 milk samples | SCM | CM | E. coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter aerogenes, and Serratia marcescens | Bacteriologic culture and identification, PCR, and sequencing | - | Anueyiagu et al. [88] |
| Nigeria | Dairy cows | 200 milk samples | NA | NA | MRSA | Bacteriologic culture and identification and PCR | - | Gaddafi et al. [89] |
| Malaysia | Dairy cow | 100 | SCM | - | S. hyicus and S. aureus | Bacteriologic culture and identification | Position of quarters and stage of lactation | Chin et al. [90] |
| Malaysia | Dairy goat | 51 | SCM | Bacillus, NAS, Listeria, and Neisseria | Bacteriologic culture and identification | Omar and Mat-Kamir [58] | ||
| India | Dairy cow | 159 cows and 636 quarters | SCM | CM | - | Modified CMT | Parity and stage of lactation | Subramanian et al. [17] |
| Bangladesh | Dairy cow | 200 milk samples | SCM | - | - | White side test, CMT, and surf field mastitis test | Breed management type and stage of lactation | Islam et al. [91] |
| Pakistan | Dairy goat | 100 goats (200 milk samples) | SCM | - | S. aureus, B. subtilis, B. cereus, Proteus vulgaris, Citrobacter species, E. coli, Micrococcus luteus, S. epidermidis, and S. agalactiae | CMT and bacteriologic culture and identification | - | Pirzada et al. [52] |
| Iran | Dairy sheep | 900 milk samples from 400 ewes | SCM | - | NAS (S. epidermidis, S. xylosus, and S. chromogene) | CMT, PCR, and RFLP | - | Rahman et al. [92] |
| Iran | Dairy sheep | 1,192 | SCM | - | S. aureus and NAS | CMT and bacteriologic culture | - | Narenji et al. [93] |
| Iran | Dairy cow, sheep, and goat | 67 | NA | NA | MRSA | Bacteriologic culture and PCR | - | Dastmalchi Saei and Panahi [94] |
MALDI-TOF MS: Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry; MRSA: Methicillin-Resistant Staphylococcus aureus; NA: Not applicable; SCM: Subclinical mastitis; CM: Clinical mastitis; SCC: Somatic Cell Count; CMT: California Mastitis Test; PCR: Polymerase Chain Reaction; MLST: Multilocus Sequence Typing; spa: Staphylococci protein A; RAPD-PCR: Random amplified polymorphic DNA; RFLP-PCR: Restriction Fragment Length Polymorphism.
The common species of bacteria that causes clinical and subclinical mastitis in cattle include Staphylococcus aureus, Streptococcus agalactiae, coliform bacteria such as Escherichia coli, environmental streptococci (Streptococcus uberis), and nonaureus staphylococci (NAS) such as Staphylococcus chromogenes, Staphylococcus hyicus, and Staphylococcus simulans [9,10] (Table 1). In buffaloes, the bacteria commonly associated with mastitis are S. agalactiae, Streptococcus dysgalactiae, Streptococcus faecalis, and S. uberis [11]. NAS and mammaliicocci (NASM) are the most prevalent bacteria in ruminants [12]. These NAS are found in a wide range of ecological habitats including the bovine teat canal, the farm environment ( bedding), teat apices, bulk milk tanks, and feces [9,12–15]. Thus, the persistent nature of these pathogens in dairy herds.
The rate of intramammary infection (IMI) as a result of S. aureus deserves utmost attention due to the increased prevalence and different presentation of the disease. Staphylococcus aureus is incriminated in cases of acute clinical mastitis and subclinical mastitis [2]. Generally, mastitis can be divided into clinical and subclinical mastitis. In animals affected with clinical mastitis, milk production drops, and the affected animal may show local or systemic clinical signs of bacteremia. Animals suffering from subclinical mastitis show a normal appearance of the udder, but the milk contains an abnormally high number of inflammatory cells, which is usually detectable by the California mastitis test (CMT) [16]. The severity of mastitis depends on pathogen factors (the severity and duration of the infection and characteristics of the causative microbes), host factors (the nutritional or immune status and milk production of the cow), and environmental factors (ambient temperature, humidity, or cleanliness) [17].
The diagnostic tools available for the diagnosis of subclinical mastitis include CMT, somatic cell counting, and milk component analysis [18,19]. Meanwhile, clinical mastitis can be detected via observation of clinical signs such as abnormal appearance of milk, inflammation of the udder, and other systemic signs of anorexia, fever, or agalactia [10]. Methods for the identification of etiological agents include bacterial culture and polymerase chain reaction (PCR) [19]. The common therapeutic regime for cases of clinical mastitis in ruminants includes intramammary infusions (intramammary β-lactam antibiotic infusions and dry cow therapy), systemic antibiotics (intramuscular oxytetracycline), and other supportive therapy and anti-inflammatory drugs (dexamethasone) [20]. Table 1 shows the distribution, etiologic agents, and risk factors for ruminant mastitis. The table shows that both clinical and subclinical mastitis are prevalent in most parts of the world and that S. aureus appears to be the common bacteria in most cases of mastitis in animals. This article reviews clinical and subclinical mastitis in ruminants as it relates to etiology, risk factors, diagnosis, and clinical management.
Methodology
Search strategy, inclusion criteria, and selection of key terms
In this narrative review, a comprehensive literature search of all relevant articles was performed to identify the articles published in Science Direct, Web of Science, PubMed, Scopus, MEDLINE, Google Scholar, LISTA, and AJOL. All observational studies (cross-sectional, cohort, case-control), experimental studies (randomized controlled trials), and intervention studies were included. Studies that reported mastitis in livestock, bacteria isolated from milk, and milk products, and risk factors were also included. Also, works of literature that reported the clinical management of mastitis and English articles published from 2017 to 2023 were used in this study. Studies that lack sufficient data or relevant information required for data extraction or quality assessment. Key terms used were ruminant mastitis, mastitis in ruminants, mastitis in sheep, goat, and cow, mastitis in dairy herd, risk factors of mastitis in livestock, diagnosis of mastitis in livestock, prevalence of mastitis in livestock, clinical management of mastitis in ruminants, treatment of mastitis in livestock. Other keywords or phrases were descriptive such as dairy sheep, dairy cattle, dairy goats, United States, Europe, Asia, and Africa.
Etiology of clinical and subclinical mastitis in ruminants
Staphylococcal aureus
Staphylococcus aureus are Gram-positive cocci bacteria that have developed complex resistance and virulence determinants [21]. The initial differentiation of this genus is based on its ability to coagulate plasma. Members of this genus associated with bovine mastitis are S. aureus and S. hyicus with the latter considered a minor mastitis pathogen and is usually grouped with NAS [22]. However, they are associated with a minute increase in milk somatic cell count (SCC), with no impact on the quantity of milk produced. Staphylococcus aureus is considered a contagious mastitis pathogen because of its ability to ability to enter the mammary gland via the teat canals and its widespread prevalence. Most clinical cases of mastitis caused by S. aureus are chronic and subclinical in nature with periodic bouts of mild clinical mastitis. However, clinical mastitis caused by S. aureus can result in systemic signs, or the affected mammary gland can become gangrenous [23–25]. In most instances, transmission of S. aureus is linked with chronically infected mammary glands, colonization of the mucous membrane and the skin, nares, and via injury to the hock. These IMIs caused by S. aureus usually lead to subclinical mastitis with inefficient treatment results based on current therapies [25–27].
Herds with a large proportion of cows with mastitis due to S. aureus tend to have higher bulk-tank SCC (BTSCC) and cows that are affected chronically will have an increase in SCC [10]. Staphylococcus aureus mastitis infections are difficult to treat and normally once the infection has become established it is extremely hard to eliminate [28]. As this infection becomes more chronic in nature, it tends to cause a greater inflammatory response which will result in permanent changes to the secretory tissue and this leads to scar tissue formation within the udder, which inevitably results in poorer responses to treatment. The detection of a hard, lumpy, indurated udder is a good indicator that the cow has suffered repeated bouts of infection and inflammation and may well be a carrier cow with a chronic long-term infection and an elevated SCC. However, if new infections in the initial stages after the invasion of the mammary gland are detected, the progress of the case is good and the cow can be treated successfully [29].
It is uncommon for S. aureus to cause an acute gangrenous mastitis infection in ruminants. Gangrenous mastitis is a condition that is commonly not caused by a specific strain of Staphylococcus, but mainly due to changes in the immune status of the udder. In gangrenous mastitis, the skin of the teat and lower parts of the udder will develop a blue/black discoloration and will be cold upon touch. In some cases of gangrenous mastitis, the surface of the skin of the udder may have blisters [29,30].
NASM species
The bacterial genus Staphylococcus is a class of Gram-positive bacteria that comprises of about 85 species and 30 subspecies [31]. This genus is mainly divided into two large groups according to their ability to coagulate rabbit plasma, with S. aureus a coagulase-positive staphylococci species and the most pathogenic and NASM that lacks ability to coagulate rabbit plasma [32].
NASM have been traditionally considered as a microbiome of the skin and have been reported to cause Intramammary infections (IMIs) in immunocompromised cows [33,34]. However, these groups of bacteria have become notorious for their ability to be the main cause of subclinical mastitis in ruminants [35]. It has now been observed that NASM infections do cause more severe damage to the mammary gland tissues than previously reported. To bring out a better and more robust perspective into the impact of NASM on the tissues of the mammary gland, more than 50 species have been detected as major causes of ruminant mastitis, and this has also led to identification of species-specific virulence and pathogenesis determinants associated with NASM, as each of these species are distinct in the effects on milk yield, mode of transmission, SCC, susceptibility to antimicrobials, and potential reservoirs, thus suggesting that some species may be more pathogenic than others [9,36].
And because the pathogenicity of these bacteria has not yet been fully elucidated, animal models present a viable alternative for the study of these bacteria; however, it is expensive and an alternative for deciphering experimental mammary infection through the use of small ruminants, and this knowledge offers a better insight into improving preventive and treatment options [37]. NAS are prevalent in the teat apices of lactating cows that are isolated from fecal samples, and their uniqueness in epidemiology, ecology, udder health, protective traits, or virulence characteristics have been observed among other species within NAS [15,38,39].
Even though Staphylococcus epidermidis, S. chromogenes, Staphylococcus vitulinus, Staphylococcus xylosus, S. simulans, and Mammaliicoccus sciuri are the predominant NASM species recovered from the skin and tips of dairy cows teats, these increase the probability of the cow to develop IMI during milking. However, S. xylosus, S. chromogenes, and Staphylococcus haemolyticus are the most dominant species found in milk samples [9,40,41]. In addition, more NASM are recovered in used beddings than in unused beddings, suggesting the possibility of contamination [42]. Some species are biofilm-produced, which allows NASM to persist on the milker’s hands, utensils, and milking equipment giving room for the dissemination of these pathogens to other cows, and possibly to other farms [43,44]. The sustainability and spread of these pathogens are influenced by geographic region, climate, environmental factors, access to pasture and sources of water, production type, and host factors including the number of calves and antimicrobial use [31]. Hence it is important to identify the natural niche of the several NASM species, which will help define their inclusion as host-adapted pathogens and environmental-adapted pathogens. It also reflects their nature and level of adaptation to the teat canal, skin, and host udder [45]. Surprisingly, these pathogens (NASM) potentially help to protect the udder against infection by dominant pathogens of mastitis as a result of the production of bacteriocin. Species including S. chromogenes, S. epidermidis, S. capitis capitis, S. capitis pasteuri, S. epidermidis, S. capitis saprophyticus, S. simulans, S. sciuri, S. xylosus, and S. capitis warneri from the mammary gland of cows are potential sources of bacteriocin, presenting a unique opportunity for future characterization and prospective clinical applications [46].
Streptococcal species
Streptococcus agalactiae (S. agalactiae) is a Gram-positive beta-hemolytic, small colony that has a bluish appearance on Edwards’s medium [47]. Streptococcus agalactiae is an obligate udder pathogen. It has difficulty surviving outside the udder and is currently regarded as the most contagious mastitis pathogen. The control measures focused on reducing the prevalence of infected cows, and this strategy is highly effective [10]. Streptococcus agalactiae was also known to cause major chronic mastitis outbreaks before the antibiotic era [48]. Many dairy herds in the developed world have an S. agalactiae-free status. However, there are still same herds where these pathogens have not been eliminated to date [47]. With no proper attention to biosecurity practices and milking procedures, S. agalactiae can be introduced and spread rapidly in a herd resulting in substantial economic loss [48,49]. However, in endemically infected herds, the bacteria survives within the milking cow population by spreading readily between milking cows. When individual cows are cleared of infection by antibiotic dry cow therapy, the herd soon becomes re-infected from these infected milking cows once they calve and rejoin the milking herd [48,49].
Streptococcus agalactiae is easily isolated from milk samples and is diagnosed when aesculin-negative, CAMP (Christie, Atkinson, Munch, and Peterson)-positive streptococci are identified in milk samples obtained from bulk tanks or individual cows. Streptococcus agalactiae is an obligate udder pathogen, and Real Time Polymerase Chain Reaction (RT-PCR) is a useful diagnostic tool for infected cows [10].
Coliform bacteria
Coliform bacteria are defined as Gram-negative rod-shaped organisms that can ferment lactose. These organisms grow on MacConkey agar which results in a characteristic pink colony. Escherichia coli and several other genera, such as Klebsiella, Neterobacter, and Serratia (some are nonlactose fermenting) are commonly associated with bovine mastitis, while other coliforms such as Citrobacter spp. only rarely cause mastitis. Coliform organisms include both pathogenic and nonpathogenic strains that are ubiquitous in the dairy farm environment and are frequently shed in faces [10].
Once coliform bacteria infect the mammary gland, they multiply rapidly, but most do not adhere to or invade the epithelial cells [10]. If the cow’s immune responses are rapid (within 4 hours) and efficient, infection is quickly eliminated (within 12–36 hours) and there will be little long-term impact on cow health or productivity [17]. Although the majority of clinical cases of mastitis caused by coliform bacteria are mild, up to 30% of cases may result in systemic signs such as anorexia, fever, or a marked drop in milk production. The cow may die or may recover within a few days returning to full milk production or with a partial loss, or rarely the infection may persist producing chronic mastitis [48]. In contrast to environmental streptococcal mastitis, intramammary antibiotic treatment at dry-off is considered less effective in preventing coliform mastitis during the dry period. The use of internal teat sealant combined with appropriate intramammary antibiotics has been shown to result in a reduced frequency of new infections caused by coliform bacteria [10]. Control of mastitis caused by coliform bacteria is based on reducing teat-end exposure to these organisms. Improving hygiene conditions of the cows’ surroundings and during the milking routine, reducing cow density, and ensuring that cows have access to an adequate diet are fundamental steps used for reducing the incidence of coliform infections [10].
Escherichia coli
Most cases of clinical mastitis caused by E. coli are preceded by low SCC values, and the transient nature of most E. coli infections is evidenced by the rapid return of SCC to relatively normal levels within weeks of the occurrence of a clinical case [10]. The clinical signs of mastitis caused by E. coli include a hot, hard, and swollen quarter with a watery, sometimes serous discharge (a clear yellow fluid-like serum). The emerging therapeutic plan for treating cases of mastitis due to E. coli is the administration of anti-endotoxic drugs using any nonsteroidal anti-inflammatory agents [17].
Mastitis in Small Ruminants
Mastitis in dairy sheep
Mastitis is recognized as a major disease problem in all intensive sheep production systems worldwide [50–53]. Initially, the diagnosis of mastitis in the ewe is so self-evident that it does not require any amplification. However, losses through deaths and premature culling can be significant in some flocks, with estimates of about 5% annual culling rate because of mastitis [10,54]. Clinical mastitis in sheep occurs sporadically and most of them are predisposed by teat lesions. Individual SCCs are not commonly used in sheep to detect subclinical mastitis [55].
In almost all instances, mastitis is caused by a bacterial infection. Although most bacteria can cause both clinical and subclinical mastitis, S. aureus, Pasteurella haemolytica, and various yeasts and molds are organisms frequently reported to be recovered from milk samples of ewes manifesting clinical signs of mastitis [10]. Bluebag (clinical mastitis with a hard, cold, and swollen udder) is typically caused by P. haemolytica or S. aureus [50–53,56]. NAS are minor pathogens in dairy cows but as major pathogens in dairy sheep and have been frequently reported to be the most common isolated pathogens recovered from cases of subclinical mastitis in dairy ewes [56]. Other pathogens typically recovered from subclinical mastitis infections in ewes include Corynebacterium spp., yeast, Streptococcus spp., Enterobacteriaceae, and S. aureus [10,57,62]. Yeast and mold infection in ewes is often associated with unhygienic administration of intramammary treatments [10].
Ewes that develop clinical mastitis are often seriously ill and should be treated immediately per protocols that have been developed in consultation with the flock veterinarian. Most treatments for severe clinical mastitis are administered systemically, and the ewe may require supportive therapy [56]. No antibiotic compounds are U. S. Food and Drug Administration (USFDA)-approved for the treatment or prevention of mastitis to date in milking sheep and off-label use of drugs as these purposes must be prescribed and supervised by a licensed veterinarian [10,54]. Intramammary dry-off therapy has been shown to positively influence milk yield, and SCC in subsequent lactation is recommended [10,50,51].
Mastitis in dairy goats
Mastitis is an important disease in small ruminants raised for dairy production, and its prevalence varies with management (5%–55%) [50,51]. Most cases of mastitis occur in subclinical form, and producers who do not routinely measure individual animal’s SCCs are unable to determine the impact of subclinical mastitis on production and milk quality [52,58]. The prevalence of subclinical mastitis has been shown to be decreased in goat herds that practice good teat dipping and premilking teat sanitation [10].
In goats, subclinical mastitis due to Intramammary infection (IMI) is particularly problematic, and thus reliable monitoring and detection tools are required to ensure good and quality milk yield. Even though the SCC is considered a good biomarker for the detection of IMI in dairy ruminants, it, however, is subjected to physiological changes related to age, parity, estrus, stage of lactation, and other determinants. These variations undermine the specificity of the diagnostic value of this practical and cost-effective test. Generally, late lactation causes a significant increase in SCCs in dairy cows, goats, and sheep. However, in goats, the degree of increase is so high that SCC may not be able to distinguish infected from and uninfected udders [53,59,60].
Clinical mastitis in goats is often associated with infection by Staphylococcus spp., Streptococcus spp., P. aeruginosa, Clostridium perfringens, Enterobacteriaceae, Mycoplasma spp., E. coli, Bacillus spp., Listeria, and miscellaneous pathogens like yeast [51,61,62]. In many regions of the world, mastitis in goats is associated with infection by a variety of Mycoplasma spp., and milk samples with chronically increased SCC are tested for the presence of Mycoplasma [57]. Most mastitis treatments in goats involve off-label drug usage and therefore the treatment of clinical mastitis should be performed using protocols developed by a veterinary practitioner who has a valid veterinary-client-patient relationship [10]. Experimental studies have shown that clearance times of antibiotic preparations from the mammary glands of goats may differ markedly from those from bovine mammary glands. In cases where the rapid elimination of oxytetracyclines and erythromycin occurs, to the extent that therapeutic efficiency may be compromised, long-acting preparations such as cefoperazone are preferred [57].
Economic impact of mastitis
The occurrence of subclinical and clinical mastitis during milking differs between herds, even though subclinical mastitis is more dominant than clinical mastitis. Because of the variation in the magnitude of their detection at the herd level, the economic influence of subclinical mastitis is more difficult to quantify and predict between herds [31,58,63]. There is comparatively more empirical evidence on the influence of clinical mastitis on productivity and health than subclinical mastitis [64]. Economic losses due to mastitis include direct costs because of diagnostic tests, veterinary services, drugs, and labor and indirect costs linked with future loss of milk yield, premature culling, and replacement of cows with mastitis. At the level of the farm, dairy owners underestimate the cost of mastitis. Interestingly though long-term milk production losses due to mastitis contribute to a significant portion of the economic losses in the dairy sector [63,64], the economic impact of preventive measures should also be considered in the overall cost of mastitis. The duration of economic losses varies markedly between countries, based on determinants such as the price of milk, cost of treatment, and replacement animals [64]. Infections due to NASM can result in milk inflammation of the mammary gland tissues that causes a 4-fold increase in the SCC, decreasing both the quality and cost of milk. Nonetheless, an SCC low in bulk milk translates to economic gains for the milk producers to improve the quality of the milk [64,65].
Diagnosis of clinical mastitis
Detection of clinical mastitis is based on observation of foremilk and observation of the clinical signs of mastitis. Common clinical signs of mastitis are the presence of abnormal appearance of milk (presence of clots or serum), swelling, redness, or edema observed in one or more quarters and severely affected animals will exhibit systemic signs such as anorexia, fever, or agalactia [66,67].
Recording the standardized severity scores can help veterinarians to better define the pattern of clinical mastitis on individual farms, hence this practice should be encouraged. One of the severities scoring systems uses a three-point scale that combines the appearance of milk with the progression to additional clinical signs [1 (mild mastitis)=abnormal milk only; 2 (moderate mastitis)=abnormal milk and abnormal udder; 3 (severe mastitis)=systemic symptoms]. This system is practical, intuitive, simply recorded, and can be an important way to access detection intensity [10]. Veterinarians are rarely asked to treat mild and moderate cases of clinical mastitis and, therefore, may not understand the true incidence of clinical mastitis on many dairy farms [10].
The bulk-tank milk (BTM) offers an essential tool for assessing and routine monitoring of milk quality, in addition to diagnosing subclinical mastitis in dairy herds [38]. NAS are increasingly being reported in BTM especially pathogens such as Staphylococcus equorum, and S. chromogenes found predominantly in the United States [38,42]. These pathogens may likely have arisen from the mammary gland through shedding or the result of contamination from the teat skin, improperly cleaned milking systems, and the farm environment [38]. The prevalence of NAS in BTM can be estimated through a combination of species identification, straining typing, and the origin of the different NAS species.
In diagnostic microbiology, the etiologic agents of ruminant mastitis, staphylococci, and streptococci isolated from milk samples are identified based on biochemical characterization or commercial biochemical galleries. These methods, even though useful, however, have some limitations in identifying bacterial species of veterinary importance, and also because these tests were for decades optimized to target human infections. Interestingly techniques such as matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) have changed the landscape of bacterial identification as it provides a fast and accurate identification approach and is being utilized with great success in the identification of mastitis pathogens [40,68].
Clinical management of mastitis
Traditionally, mastitis is treated with the use of antimicrobials, interestingly though, the success of treatment is low in many instances. For example, the use of enrofloxacin in small ruminant mastitis has been widely accepted by the routes of administration and this has proven to be effective in the resolution of mastitis. However, the concept of tolerance, persistence, and resistance generates greater complexity to the flaws of antimicrobial therapies [56,69]. The efficacy of antibiotic therapy depends on the pathogen causing clinical mastitis. Cows with cases of mild (severity score 1) and moderate (severity score 2) clinical mastitis and no bacterial growth in the milk are unlikely to benefit from antibiotic therapy. Cows with mycoplasma mastitis or mastitis caused by opportunistic pathogens such as P. aeruginosa, Serratia marcesens, Prototheca zopfii, or Candida spp. are unlikely to respond to antibiotic therapy. Antimicrobial therapy for mastitis cases caused by these pathogens should be avoided as may lead to unnecessary risk for drug residues and the development of antimicrobial resistance [70].
On the other hand, antimicrobial drugs can enhance the resolution of many cases of streptococcal or staphylococcal mastitis episodes. The prototype for therapeutic success is the treatment of mastitis caused by S. agalactiae. This organism tends to be highly susceptible to intramammary therapy with β-lactam drugs. This organism is an obligate udder pathogen in dairy cattle, remains superficial in mammary tissue, and has a high level of susceptibility to therapy [71]. Thus, S. agalactiae can essentially be eradicated from a herd by simultaneously treating all infected cows, including subclinical infections. For other Gram-positive pathogens, systemic administration of antimicrobial drugs is not likely to attain any better cure rates than intramammary infusions [71]. This reflects the relatively poor distribution of most drugs used in clinical cases of mastitis in ruminants into the mammary gland, particularly β-lactam, sulphonamide, and aminoglycosides.
Clinical mastitis in ruminants due to S. aureus is difficult to treat due to the resistance to antibacterials (particularly β-lactams). Staphylococcus aureus can survive intracellularly following phagocytosis, where antibacterial concentrations are reduced. In addition, S. aureus also has numerous extracellular substances that impart an ability to survive in the presence of a hostile host immune system. Consequently, the elimination of mastitis caused by this pathogen is often not as successful as with other Gram-positive pathogens [72].
Therefore, the combination of parenteral and intramammary treatment regimens may be helpful to eliminate a higher proportion of S. aureus infections. In experimental infections in lactating cows, the combined use of intra-muscular procaine penicillin G and intramammary amoxicillin (18/35 infected quarters) achieved a better cure rate than intramammary amoxicillin (10/40 infected quarters) did alone. Dry cows with S. aureus mastitis had an improved cure rate when administered with 11 mg/kg of oxytetracycline IM in addition to intramammary antibacterial as compared to cows administered intramammary infusions only [70]. Lipophilic antibacterial drugs distribute very well into mammary tissue and are the best candidates for systemic administration [70]. Affected quarters should be monitored by culture or SCC for at least 60 days to make sure the treatment protocol has successfully eliminated the clinical mastitis condition.
Acknowledgments
The authors wish to acknowledge with thanks the critical inputs provided by some colleagues in the Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, during the preparation of this manuscript.
Conflict of interest
No conflict of interest to declare.
Authors contribution
FFAJ, AAB, and ELTC conceived the idea and developed the mainframe of this manuscript. AAB and ELTC prepared the first draft which was modified by FFAJ. AAB, ELTC, IDP, and NT prepared the second draft which was read by FFAJ who made technical inputs. All the authors read and approved the final version.
