The mammary gland fulfils a diversity of physiological, immunological and biochemical functions (Oliver & Sordillo, Reference Oliver and Sordillo1989). As part of the reproductive system of mammals, it undergoes repeated cycles of structural development, functional differentiation and regression (Hurley Reference Hurley1989; Hurley & Loor, Reference Hurley, Loor and Fuquay2011). During these cycles, the mammary gland of adult animals undergoes three distinct functional transitions: (i) from involution to lactogenesis (including the colostrogenesis), (ii) from lactogenesis to lactation and (iii) from lactation to involution. In each of these phases, marked changes occur in the size, structure and function of the organ; moreover, distinct changes also occur in the mammary secretion during each of the above physiological transitions (Oliver & Sordillo, Reference Oliver and Sordillo1989). In ruminants, mammary involution occurs at the end of each lactation period and is characterised by the reduction of numbers of mammary epithelial cells coupled with the extensive proteolytic degradation of the extracellular matrix (Quarrie et al. Reference Quarrie, Addey and Wilde1996; Flint et al. Reference Flint, Boutinaud, Tonner, Wilde, Hurley, Accorsi, Kolb, Whitelaw, Beattie and Allan2005).
In sheep, in dairy-type production systems, mammary involution can be effected either progressively (i.e. milking frequency is gradually decreased over a period of several days or weeks) or abruptly (i.e. milking is stopped at once) (Gelasakis et al. Reference Gelasakis, Valergakis, Fortomaris and Arsenos2010). In mutton-production systems, cessation of lactation, and consequent mammary involution, is always abrupt, taking place when lambs are removed from their dam (Sargison, Reference Sargison2008). From the viewpoint of udder health management, recent work has shown that the procedure for udder drying-off (i.e. progressive or abrupt cessation of lactation) does not affect the risk of subsequent intramammary infection and development of mastitis (Petridis et al. Reference Petridis, Mavrogianni, Fragkou, Gougoulis, Tzora, Fotou, Skoufos, Amiridis, Brozos and Fthenakis2013).
The period from complete cessation of milk removal until the beginning of the subsequent lactation period (i.e. parturition) is termed the ‘dry-period’. The dry-period is distinguished in three distinct stages: (i) stage of active involution, (ii) stage of the ‘steady-state’ involution and (iii) stage of redevelopment and lactogenesis (including colostrogenesis). The dry-period is of importance in the health management of sheep for optimum milk production in the subsequent lactation period (Contreras et al. Reference Contreras, Sierra, Sanchez, Corrales, Marco, Paape and Gonzalo2007; Fthenakis et al. Reference Fthenakis, Arsenos, Brozos, Fragkou, Giadinis, Giannenas, Mavrogianni, Papadopoulos and Valasi2012).
During the stage of active involution, there is (i) easier invasion of pathogens, owing to dilatation of the teat orifice and duct as a result of milk accumulation into the mammary gland and consequent increased pressure to the teat, whilst the protective keratin plug which seals the teat canal is not yet formed (Dingwell et al. Reference Dingwell, Leslie, Schukken, Sargeant, Timms, Duffield, Keefe, Kelton, Lissemore and Conklin2004), and (ii) impaired defensive ability of the mammary gland as a result of decreased concentration of lactoferrin and lactoferrin:citrate ratio (Smith & Oliver, Reference Smith and Oliver1981; Nickerson, Reference Nickerson1989; Oliver & Sordillo, Reference Oliver and Sordillo1989), decreased phagocytic ability of leucocytes (Sordillo & Nickerson, Reference Sordillo and Nickerson1988; Tatarczuch et al. Reference Tatarczuch, Philip, Bischof and Lee2000, Reference Tatarczuch, Bischof, Philip and Lee2002) and reduced amount of immunoglobulins in lacteal secretions (Sordillo et al. Reference Sordillo, Nickerson, Akers and Oliver1987). The above predispose the mammary gland to new mastitis cases during involution and support recrudescence of subclinical infections that had occurred during the previous lactation period (Orphanou, Reference Orphanou1987; Barkema et al. Reference Barkema, Schukken, Lam, Beiboer, Wilmink, Benedictus and Brand1998; Saratsis et al. Reference Saratsis, Leontides, Tzora, Alexopoulos and Fthenakis1998).
Remodelling of the mammary gland during involution, characterised by the renewal of damaged or senescent mammary epithelial cells, is essential for optimum milk production during the subsequent lactation period (Capuco et al. Reference Capuco, Akers and Smith1997). Intramammary infections during that period would adversely affect normal development of mammary epithelial cells and, thus, quality and quantity of milk to be produced (Sordillo & Nickerson, Reference Sordillo and Nickerson1988).
Udder health management at the end of a lactation period aims (i) to cure infections which have occurred during the previous lactation period and (ii) to prevent development of new intramammary infections during the dry-period (Fthenakis et al. Reference Fthenakis, Arsenos, Brozos, Fragkou, Giadinis, Giannenas, Mavrogianni, Papadopoulos and Valasi2012). Initially, clinical examination of the mammary glands of ewes in the flock should be carried out; that way, ewes with mammary abnormalities can be identified. The udder of all ewes in the flock is examined by palpation, whilst the animals are run through a race (Orphanou, Reference Orphanou1987; Saratsis et al. Reference Saratsis, Leontides, Tzora, Alexopoulos and Fthenakis1998). If mammary abnormalities are suspected, animals should be individually examined. Diffuse hardness, abscesses and nodules in the mammary glands are the most common clinical findings during the examination (Saratsis et al. Reference Saratsis, Leontides, Tzora, Alexopoulos and Fthenakis1998). Samples (e.g. mammary secretion, abscess material) should also be collected for bacteriological examination (Fthenakis, Reference Fthenakis1994; Saratsis et al. Reference Saratsis, Leontides, Tzora, Alexopoulos and Fthenakis1998; Mavrogianni et al. Reference Mavrogianni, Fthenakis, Brooks, Papaioannou, Cripps, Taitzoglou, Brellou and Saratsis2005).
Based on the results of the clinical examination of the udder and the ancillary tests performed (e.g. bacteriological examination) the following categories of ewes should be considered for culling: (i) animals with at least one mammary gland permanently damaged, (ii) animals chronically affected and (iii) animals that had shown incidents of relapsing mastitis or had not fully responded to mastitis treatment during the preceding lactation period. The benefits of culling such animals include: (i) decrease of veterinary expenses for mastitis control in the flock, (ii) elimination of sources of potential infection for other animals in the flock and (iii) decrease of flock bulk somatic cell counts in the subsequent lactation period (Mavrogianni et al. Reference Mavrogianni, Menzies, Fragkou and Fthenakis2011). Moreover, lambs (especially in large litters) from ewes with extensive mammary lesions do not thrive well and may require additional feeding (Fthenakis & Jones, Reference Fthenakis and Jones1990a), which increases expenses and labour in the flock.
The above procedures should be complemented by administration (preferably by the intramammary route) of antibiotics, which is an integral part of udder health management (Fthenakis et al. Reference Fthenakis, Arsenos, Brozos, Fragkou, Giadinis, Giannenas, Mavrogianni, Papadopoulos and Valasi2012). The objective of the present paper is to review the significance of administration of antibiotics at the end of a lactation period/beginning of the dry-period in ewes.
Pathogens involved in ‘dry-period mastitis’
The main pathogens involved in the so-called ‘dry-period mastitis’ are primarily coagulase-negative staphylococci (Saratsis et al. Reference Saratsis, Leontides, Tzora, Alexopoulos and Fthenakis1998; Croft et al. Reference Croft, Duffield, Menzies, Leslie, Bagg and Dick2000; Chaffer et al. Reference Chaffer, Leitner, Zamir, Winkler, Glickman, Ziv and Saran2003; Gonzalo et al. Reference Gonzalo, Tardaguila, De La Fuente and San Primitivo2004; Shwimmer et al. Reference Shwimmer, Kenigswald, Van Straten, Lavi, Merin, Weisblit and Leitner2008; Spanu et al. Reference Spanu, Berger, Thomas and Ruegg2011). Reservoirs of these microorganisms are the subclinically infected mammary glands, although these bacteria are also part of the normal flora of the udder skin, which renders their control difficult. In sheep, these organisms are frequent aetiological agents of clinical or subclinical mastitis and elicit a strong host response (Fthenakis & Jones, Reference Fthenakis and Jones1990b; Pengov, Reference Pengov2001). Various coagulase-negative staphylococcal species are involved in the aetiology of the disease. Phenotypic tests (e.g. API Staph ID 32) are used often for speciation of these organisms. Genotypic methods can provide information (Sampimon et al. Reference Sampimon, Zadoks, De Vliegher, Supre, Haesebrouck, Barkema, Sol and Lam2009) for use in epidemiological studies, e.g. regarding increased prevalence and persistence of infection by some staphylococcal species in flocks.
Other organisms involved in dry-period mastitis are streptococci (Chaffer et al. Reference Chaffer, Leitner, Zamir, Winkler, Glickman, Ziv and Saran2003; Linage & Gonzalo, Reference Linage and Gonzalo2008) and Trueperella pyogenes (Saratsis et al. Reference Saratsis, Leontides, Tzora, Alexopoulos and Fthenakis1998). As these bacteria are not frequent aetiological agents of mastitis in lactating mammary glands, the findings raise a question regarding a possible increased susceptibility of involuting ovine mammary glands to those organisms.
Benefits of administration of antibiotics at the end of a lactation period
Intramammary administration of antibiotics
The principle of antibiotic administration at the end of a lactation period involves the intramammary infusion of a pharmaceutical preparation to both mammary glands of ewes in the flock. In all published work carried out in dairy flocks, a significantly greater cure rate of mammary abnormalities recorded at the end of lactation has been achieved after administration of the antibiotics. Pharmaceutical preparations used in the studies include combinations of antibiotics, which afford a broader spectrum of antibacterial activity. Although a variety of products is licensed for administration in ewes, preferably the product for administration should be selected on the results of susceptibility testing of bacteria (Constable & Morin, Reference Constable and Morin2003; Mavrogianni et al. Reference Mavrogianni, Menzies, Fragkou and Fthenakis2011) to be isolated from samples (e.g. mammary secretion, abscess material) from ewes individually examined, as detailed above. Moreover, antibiotic administration has led to a smaller incidence of new infections during the dry-period, which indicates the preventive role of the procedure during a period of high risk for intramammary infections and underlines the usefulness of strategic administration. The beneficial effects of the administration are clearly shown in the subsequent lactation, when increased milk yields of treated ewes have been recorded.
Chaffer et al. (Reference Chaffer, Leitner, Zamir, Winkler, Glickman, Ziv and Saran2003) found that prevalence of intramammary infections in ewes at drying-off was 45%; cure rate after intramammary administration of a combination of benzylpenicillin, nafcilin and dihydrostreptomycin at the end of lactation period was found to be 65% 15–20 d after the subsequent lambing, compared with 6·5% cure rate in control animals. In a similar study, Shwimmer et al. (Reference Shwimmer, Kenigswald, Van Straten, Lavi, Merin, Weisblit and Leitner2008) reported that prevalence of intramammary infections in ewes at drying-off was 47·5%; cure rate after intramammary administration of the above combination at the end of lactation period was found to be 71% 2–4 weeks after the subsequent lambing, compared with 8% cure rate in control animals. These authors also documented that mean milk yield throughout the lactation period subsequent to antibiotic administration increased by 19% and flock bulk milk mean somatic cell counts during the same period decreased to 1·0×106 from 2·5×106 in the previous lactation period (Shwimmer et al. Reference Shwimmer, Kenigswald, Van Straten, Lavi, Merin, Weisblit and Leitner2008). De Santis et al. (Reference De Santis, Mencarelli, Nieddu, Farina, Mazzette, Sanna and Virdis2001) reported that cure rate of intramammary infections in ewes after intramammary administration of cloxacillin at the end of the lactation period was >60% 4–59 d after the subsequent lambing, compared with <50% cure rate in control animals. De Santis et al. (Reference De Santis, Mencarelli, Nieddu, Farina, Mazzette, Sanna and Virdis2001) and Spanu et al. (Reference Spanu, Berger, Thomas and Ruegg2011) also documented that treated ewes had significantly smaller somatic cell counts in the subsequent lactation compared with controls. However, Gonzalo et al. (Reference Gonzalo, Linage, Carriedo, Juarez, Beneitez, Martinez and De La Fuente2009) found beneficial results in decreasing flock bulk milk somatic cell counts only in machine-milked ewes and not in hand-milked animals.
Linage & Gonzalo (Reference Linage and Gonzalo2008) reported that prevalence of intramammary infections in ewes at drying-off was 49%; cure rate after intramammary administration of a combination of penethemate and framycetin at the end of the lactation period was 82% 5 d after the subsequent lambing, compared with 13% cure rate in control animals. Moreover, these authors found that incidence risk of new intramammary infections, during the dry-period was 8% in treated and 23% in control ewes. Gonzalo et al. (Reference Gonzalo, Tardaguila, De La Fuente and San Primitivo2004) found that prevalence of intramammary infections in ewes at drying-off was 54·5%; cure rate after intramammary administration of a combination of penicillin and novobiocin at the end of a lactation period was 61·5% at the subsequent lambing. Moreover, these authors indicated that milk yield of ewes increased by 7% in the lactation period subsequent to antibiotic administration, as a result of decreased incidence of new intramammary infections during the dry-period (Gonzalo et al. Reference Gonzalo, Tardaguila, De La Fuente and San Primitivo2004).
Finally, Petridis et al. (Reference Petridis, Mavrogianni, Gougoulis, Amiridis, Brozos and Fthenakis2012) reported that cure rate of intramammary infections in ewes, after administration of a combination of procaine penicillin and neomycin at drying-off was ⩾50% 10 d after the subsequent lambing, significantly higher than that in untreated glands. The authors observed these beneficial effects independently of the procedure used for drying-off (i.e. progressive or abrupt).
Thus, it becomes evident that in dairy ewes intramammary administration of antimicrobial agents at the end of a lactation period is effective in curing intramammary infections present at cessation of a lactation period, as well as in minimising the risk for intramammary infections during the dry-period. Moreover, there are further benefits from a potential increase in milk yield and a decrease in flock bulk milk somatic cell counts during the subsequent lactation period.
The procedure has been found to be just as beneficial in ewes in mutton-production systems (Hendy et al. Reference Hendy, Pugh and Harris1981; Watson & Buswell Reference Watson and Buswell1984; Hueston et al. Reference Hueston, Boner and Baertsche1989). In mutton-production systems, healthy mammary glands of the dam and increased milk yield during the first month of a lactation period are important for optimum growth rate of lambs (Fthenakis & Jones, Reference Fthenakis and Jones1990a).
One might suggest that differences in the length of the dry-period, which reflect differences in production systems, may potentially affect the efficacy of intramammary administration of antibiotics at the end of a lactation period. However, Linage & Gonzalo (Reference Linage and Gonzalo2008), who studied this particular factor in their work, did not find any significant differences in the efficacy of administration between groups of ewes with varying length of the dry-period.
Injectable administration of antibiotics
McCarthy et al. (Reference McCarthy, Lindsey, Gore and Notter1988) proposed the intramuscular administration of procaine penicillin to ewes at the end of a lactation period, after administration of which prevalence of subclinical mastitis at lambing was found to be 27% in treated animals and 31% in controls. Croft et al. (Reference Croft, Duffield, Menzies, Leslie, Bagg and Dick2000) indicated that the subcutaneous injection of tilmicosin one month prior to the expected start of the lambing period, concurrently with the anti-clostridial vaccination, led to a 43% decrease in mammary abnormalities at the subsequent lambing. Moreover, the latter authors documented that mean bodyweight of 50-d-old lambs of treated ewes was greater by 520 g than that of lambs of control ewes and attributed the benefit to cure of pre-existing intramammary infections in treated ewes, which led to increased milk yield by the animals (Croft et al. Reference Croft, Duffield, Menzies, Leslie, Bagg and Dick2000).
In comparison with intramammary administration, it is noteworthy that an advantage of injectable administration is the minimal risk of potential iatrogenic contamination of the mammary glands, as handling of the udder is avoided.
The publications regarding administration of antibiotics to ewes at the beginning of the dry-period are summarised in Table 1.
Table 1. Summary presentations of publications regarding administration of antibiotics to ewes at the beginning of the dry-period
‘Complete’ or ‘selective’ antibiotic administration?
Administration of antibiotics to ewes at drying-off may be performed on all animals in a flock (‘complete’) or only on those considered to be infected (‘selective’). The need for selective administration was developed owing to public concerns regarding (i) potential antibiotic residues in the food chain and (ii) increased incidence of antibiotic-resistant bacterial strains in animals. Moreover, selective administration has a smaller cost to the farmer and a decreased risk of potential iatrogenic contamination of the mammary glands (Mavrogianni et al. Reference Mavrogianni, Menzies, Fragkou and Fthenakis2011).
In the selective administration approach, there may be a query regarding criteria to be used in the selection of animals that will receive the antibiotic preparation. Clinical examination of all animals in the flock, as discussed above, has a small cost and can be used to identify animals in need of antibiotic administration. The procedure can be complemented with bacteriological examination of samples collected from clinically affected udders, which will support the decision for selection of the most appropriate antibiotic (Orphanou, Reference Orphanou1987; Saratsis et al. Reference Saratsis, Leontides, Tzora, Alexopoulos and Fthenakis1998). Milk somatic cell counting alone, as a means of identifying ewes in need of antibiotic administration, may not be a useful method, because somatic cell counts have been found to increase physiologically at the end of a lactation period, i.e. even in healthy ewes (Fthenakis, Reference Fthenakis1995), and hence are not indicative of intramammary infection. Gonzalo et al. (Reference Gonzalo, Tardaguila, De La Fuente and San Primitivo2004) did not find any significant differences between the two methods (i.e. complete or selective) in the cure of pre-existing intramammary infections. Bogolin & Vasiu (Reference Bogolin and Vasiu2008) used selective treatment in ewes with subclinical mastitis and reported a cure rate of 78·5% in the treated animals.
A disadvantage of selective administration is the incomplete protection of the untreated ewes in the flock against new intramammary infections during the dry-period (Berry & Hillerton, Reference Berry and Hillerton2002; Bergonier & Berthelot, Reference Bergonier and Berthelot2003), especially during the stage of active involution when there is an increased risk of mastitis (Orphanou, Reference Orphanou1987; Barkema et al. Reference Barkema, Schukken, Lam, Beiboer, Wilmink, Benedictus and Brand1998; Saratsis et al. Reference Saratsis, Leontides, Tzora, Alexopoulos and Fthenakis1998).
Potential concerns regarding intramammary administration of antibiotics at the end of a lactation period
Administration of the antibiotic preparation should be performed under good hygienic conditions and thorough disinfection of the respective teat, in order to prevent insertion of pathogens, which may subsequently cause mastitis. Organisms that may be introduced into the teat at that point include Pseudomonas aeruginosa and Aspergillus fumigatus (Las Heras et al. Reference Las Heras, Dominguez, Lopez, Paya, Pena, Mazzucchelli, Garcia and Fernandez-Garayzabal2000; Bergonier & Berthelot, Reference Bergonier and Berthelot2003; Spanu et al. Reference Spanu, Berger, Thomas and Ruegg2011) for which organisms the antibiotics usually administered are not effective.
It has been proposed, during intramammary antibiotic administration, to use partial insertion of the tip of the tube or to use short-tipped tubes, with the aim of avoiding excessive dilatation of the teat canal and destruction of its protective lining (Bergonier & Berthelot, Reference Bergonier and Berthelot2003; Bergonier et al. Reference Bergonier, De Cremoux, Rupp, Lagriffoul and Berthelot2003). The results of Gonzalo et al. (Reference Gonzalo, Tardaguila, De La Fuente and San Primitivo2004) indicated that the procedure was as effective as complete insertion of the tip of the tube into the teat. In view of previous findings, which pointed out the significance of damaged teats as a risk factor for development of mastitis (Mavrogianni et al. Reference Mavrogianni, Cripps, Papaioannou, Taitzoglou and Fthenakis2006; Fragkou et al. Reference Fragkou, Papaioannou, Cripps, Boscos and Fthenakis2007), this may be a useful suggestion. Moreover, this method allows some antibiotic to be left inside the teat canal, in that way preventing bacterial invasions into the mammary parenchyma.
After administration of the antibiotic, definite and complete cessation of the lactation period is essential for success of the procedure (Fthenakis et al. Reference Fthenakis, Arsenos, Brozos, Fragkou, Giadinis, Giannenas, Mavrogianni, Papadopoulos and Valasi2012). This implies that ewes should not be milked again after administration of the antibiotic, whilst in mutton-production systems, lambs should have been removed from their dams before that.
Finally, some concerns have been voiced regarding potential problems with residues of the antibiotics in milk of the subsequent lactation (Chaffer et al. Reference Chaffer, Leitner, Zamir, Winkler, Glickman, Ziv and Saran2003; Linage & Gonzalo, Reference Linage and Gonzalo2008; Shwimmer et al. Reference Shwimmer, Kenigswald, Van Straten, Lavi, Merin, Weisblit and Leitner2008). Nevertheless, it should be noted that, at least in the European Union, veterinary pharmaceutical products are only licensed if adequate scientific evidence can be presented about residues in the animal products (e.g. meat, milk) and if appropriate withdrawal periods have been calculated (Athanasiou et al. Reference Athanasiou, Orfanou, Fragkou, Gougoulis and Nerou2009). Calculation of withdrawal periods for intramammary veterinary pharmaceutical products at the beginning of the dry-period takes into account minimum length of the dry-period, as well as minimum time after parturition that milk cannot be given for human consumption. For example, in the study by Linage & Gonzalo (Reference Linage and Gonzalo2008), no antibiotic residues in milk were detected as early as 54 h after the lambing subsequent to antibiotic administration. Therefore, maintenance of the prescribed withdrawal periods is essential to safeguard public health.
Concluding remarks
Implementation of intramammary administration of antibiotics at the end of a lactation period improves the welfare of animals and affords significant financial benefits to the farmer. These benefits are pretty obvious in dairy production systems, but they can also be significant in mutton-production systems. The procedure will provide maximum benefit in flocks with increased incidence of intramammary infections, where it can bring dramatic improvement in the financial performance of the flock. Although no premium payment schemes based on milk somatic cell counts are enforced in the European Union, if such schemes were to be applied, financial benefits would increase greatly; flock bulk somatic cells counts decrease in the subsequent lactation period, which would lead to higher payment for milk produced.
The procedure should always be applied as part of a strategic udder health management plan in a flock. A mastitis prevention scheme during lactation will minimise the incidence of the disease; effective treatment of cases of the disease during lactation will decrease the bacterial populations in the flock and limit risk of infection of other animals. Administration of antibiotics at the end of a lactation period will complement the above procedures and will contribute to improved mammary health for the forthcoming lactation period.
