THIS ARTICLE IS SPONSORED BY THE MINNESOTA DAIRY HEALTH CONFERENCE.

THIS ARTICLE IS SPONSORED BY THE MINNESOTA DAIRY HEALTH CONFERENCE. ST. PAUL, MINNESOTA UNITED STATES OF MINNESOTA

Classificatin f Clinical Mastitis Severity: Fcus n E.Cli Jhn R. Wenz, DVM, MS In a clinical setting mild vs. severe mastitis is typically based n the extent and degree f systemic disease signs the cw is expressing. Upn evaluatin a cw with flakes and clts in the milk that is therwise nrmal is cnsidered t have mild clinical mastitis. This is in cntrast t the cw that simply "lks sick"; dehydrated, shwing signs f depressin and has little rumen activity, that is classified as having severe clinical mastitis. It is clear that the later cw requires mre supprtive care in an attempt t crrect physilgic abnrmalities. Hwever, apprpriate antimicrbial therapy is less clear. Shuld the 'severe' cw receive intramammary antibitics r parenteral antibitics, bth r nne? The imprtance f lcal inflammatry changes f the mammary gland in determining treatment and prgnsticating utcmes is als unclear. Fr sme, a firm quarter with a serum-like secretin (watery) is cnsidered a 'severe' sign carrying a grave prgnsis, even if the cw appears therwise nrmal. Hwever, there is little infrmatin in the scientific literature crrelating lcal clinical signs with imprtant utcmes f a clinical mastitis episde. Furthermre, it is imprtant t keep in mind what utcmes are being cnsidered. Outcmes imprtant t the dairy prducer are:. Will the cw survive the clinical mastitis episde? 2. Will the cw return t milk prductin r be culled? 3. Will the cw lse the affected quarter? 4. Will the cw need t be re-treated? In the absence f any 'scientific infrmatin' we generally use ur clinical experience t evaluate these utcmes and determine therapy. In the absence f 'better infrmatin' this is the best we can d, hwever, it is imprtant t realize that ur perceptin is ften bias by the last "catastrphic treatment failure" and/r "miraculus treatment success". T cmplicate matters further clinical mastitis research has ften failed t identify severity by any measure, r classified severity but gave n clear indicatin f hw it was assigned. Furthermre severity was ften defined based n physilgic parameters such as neutrphil chemiluminescence r xidative burst activity. While these parameters may be imprtant in the pathphysilgy f disease it is unclear hw they relate t the clinical signs easily evaluated in the field. This has especially been true with research f clifrm mastitis. This presentatin will present recent wrk we have dne at CSU t better classify clinical disease severity, with a fcus n clifrm mastitis. Severity and Clifrm Mastitis Acute clifrm mastitis (ACM) manifests as clinical disease ranging frm mild, shrt duratin cases t severe, peracute, life-threatening episdes. The severity f systemic signs in cws with a clifrm mastitis episde is strngly assciated with the degree f prductin lss and utcme f a clinical case. l Therefre, evaluatin f the severity f a clinical clifrm mastitis episde is imprtant in determining apprpriate therapy and making sund management decisins. Unfrtunately in the realm f mastitis research and amng 'the experts' there are many measures f the severity f clinical mastitis including; milk prductin changes, inflammatry changes in the gland, changes in milk cmpsitin and appearance, the extent and degree f systemic disease signs and hematlgical changes in the affected cw. Varius scring systems have been described t evaluate the severity f clinical mastitis.2-5 In mst f these studies severity classificatin was typically based n 97

nrmal versus abnrmal scring f physical characteristics f the mammary gland, the milk I and the presence r absence f systemic disease signs based n definitins recmmended by the Internatinal Dairy Federatin. 6 The highest severity scre was typically given t cws exhibiting any systemic disease signs. Hwever, such systems d little t evaluate the extent and degree f systemic disease invlvement, althugh systemic disease severity has a significant impact n milk prductin lsses and adverse utcmes. Furthermre, nne f these studies have shwn imprtant differences in the utcmes f a clinical mastitis event in cws based n such severity scring. Therefre we have been wrking t develp a clinical mastitis scring system that is simple yet effective in gruping cws accrding t their likely treatment needs and utcmes. Experimental clifrm mastitis Much f ur understanding f clifrm mastitis is based n the experimental disease mdel which invlves inculatin f a 'healthy' mammary gland with either purified endtxin r a pure culture f E. cli. Hwever, ur recent studies have identified imprtant areas in which experimentally induced disease fails t accurately mdel the naturally ccurring disease. A majr disparity, which may explain the imprtant differences we have bserved, is the diverse, multifactrial nature f innate hst defense mechanisms. Use f the experimental disease mdel selects fr cws that have shwn resistance t ACM. Cws chsen fr inclusin in studies incrprating the experimental disease mdel have a lw smatic cell cunt (SCC), typically have nt had clinical mastitis during the current lactatin and have n evidence f IMI (negative serial milk cultures). It can be argued these cws have superir, intact hst defenses cmpared with cws that succumb t the disease, presumably due t a failure f the same innate hst defenses. Based n the experimental disease mdel it was determined that bacteria are typically cleared frm the gland by the time clinical signs ccur and bacteremia des nt ccur. Recently we have reprted n a rapid, simple severity classificatin scheme fr ACM based n systemic disease signs (SSS) (Table ).7 Fr cws gruped accrding t this classificatin scheme, significant differences in hematlgical findings, number f bacteria in secretins frm the affected mammary gland, death and culling utcmes, and ccurrence f bacteremia were identified amng severity grups. Mre than half f the cws classified as severe died during the mastitis episde r were culled within 30 days, cmpared with nly 9% f thse classified as mild (Table 2). While the SSS appears t be cmplicated, in practice cws with three r mre abnrmal systemic signs (scring mderate r severe) clearly require mre attentin than thse that are systemically 'mild'. In herds that use a cre antigen vaccine (e.g. -5) we typically find -90% f cws with clinical mastitis are systemically mild. The distributin f cws by severity grup in Table 2 is nt representative f the expressin f clinical mastitis in a herd since mre cws with mderate and severe disease were enrlled t increase numbers in thse less frequent categries. 98

Table. Scheme fr classifying severity f acute clifrm mastitis in dairy cws based n systemic disease signs (SSS)* Variable Criteria Scre Rectal temperature (C [FD Hydratin status (degree f enphthalms) Rumen cntractin rate (cntractins/min) Attitude (signs f depressin) Ttal Scre- 0-2=Mild, 3-5=Mderate, 6-9=Scvere 37.8 (l00) - 39.27 (02.7) 39.33 (02.8) - 39.8 (03.7) > 39.8 (03.7) r < 37.8 (00) Nne Mild Mderate Marked ~2 Nne Mild Marked 2 2 3 2 2 Table 2. Outcme fllwing a clifrm mastitis episde f cws in mild, mderate and severe grups. Cws remaining in the herd 30 days after the mastitis episde were cnsidered retained. % Died r Severity (n) Survival Retentin Culled Status N. % Status N. % Mild (69) Died 0 Oa Culled 6 9" 9 3 Lived 69 00 Retained 63 9 Mderate Died 2" Culled 9 2 a,b 23 b (44) Lived 43 98 Retained 34 79 Severe (3) Died 6 9 b Culled 0 40 b 52 c Lived 25 8 Retained 5 60 Values within a clumn with different superscripts are significantly different (p<o.05). In cntrast t the experimental disease mdel we identified significant numbers f bacteria present in the milk f affected quarters at initial assessment and 48 hrs later. Furthermre, cws with mre severe systemic signs had significantly mre bacteria (Table 3). Almst a third f systemically mild and 75% f severe cws had> 00,000 cfu/rnl. These finding suggest intramammary treatment with an antibitic effective against gram negative bacteria may be indicated. 99

TaQle 3 Bacterial numbers by systemic severity scre at initial assessment (Ohr) and 48hrs Ohr 48hr 2 3 NG 2 3 Mild Mderate 27.9 Severe 9.3 = <0,000 cfulml, 2 = 0,000-00,000 cfulml, 3 = >00,000 cfulml, NG = n grwth. Values within a clumn with different superscripts are significantly different (p<0.05). We als fund significant differences in the percentage f cws with a psitive bld culture (bacteremia) when evaluated based n systemic disease severity (Table 4). 8 Grup islates are imprtant pathgenic bacteria such as E. cli, Klebsiella pneumniae, Pasteurella (Manheimia )hemlytica, and Pasteurella multcida. Nne f these rganisms were identified in cntrl cws cmpared t 42% f cws with severe systemic disease signs. It was interesting t find significantly mre cws with ACM f any severity with bld cultures psitive fr envirnmental streps, cagulase negative staphs and bacillus cmpared with cntrl cws. Table 4 Bacteremia in cws with clifrm mastitis Severity (n) All Grup Grup 2 Islates Bacillus Islates Islates spp. N. % N. % N. % N. % Cntrl (56) 7.a 0 Oa 9 5.8 a 3.9 a Mild (69) 2 30 b 3 4.3 b 0 5 b,c 6 b Mderate (44) 0 23 b 4 9. b 3 6.8a.c 5 b Severe (3) 5 48 c 3 42 c 3.2a. c 5 6 b Grup islates - E. cli, Pasteurella multcida, Pasteurella hemlytica, Klebsiella pneumniae, Enterbacter agglmerans, Salmnella typhimurium. Grup 2 islates - envirnmental streptccci, cagulase negative staphylccci and Acinetbacter spp.. Values within a clumn with different superscripts are significantly different (p<0.05). These results suggest parenteral antibitics may be indicated in cws with mre severe systemic disease signs. In fact a recent study fund treatment f cws with mre severe systemic disease signs assciated with clinical mastitis benefited frm systemic ceftifur treatment. 5 Fr cws with clifrm mastitis, death and culling was significantly lwer when treated M with ceftifur (4%) vs. thse nt treated (37%). Systemic disease severity scring has shwn pr utcmes are mre cmmn in cws with mre extensive (severe) systemic disease signs. Hwever, the majrity f cws in herds using a cre antigen vaccine have mild systemic disease and varying degrees f lcal 00

inflammatry changes in the udder. What is the imprtance f the presence and 'severity' f lcal disease signs? Lcal signs assciated with clinical mastitis Lcal clinical signs assciated with inflammatry changes f the mammary gland include: quarter firmness and swelling and secretin viscsity. Treatment and prgnsis f clinical mastitis is ften decided based n these signs, hwever, there have been n studies evaluating their assciatin with imprtant utcmes f clinical mastitis. In a recent study f 240 cws with systemically mild clinical mastitis we examined the assciatin between lcal clinical signs and imprtant clinical utcmes. 9 Cws were examined fr firmness and swelling f the affected mammary gland and character f the secretin (thin, thick r serum). Outcmes assessed were re-treatment, recurrent clinical mastitis episde in the same quarter 5-60 later, dried quarter, death r culling and sick pen days. Re-treatment was necessary in 27% and recurrence ccurred in 25% f clinical mastitis episdes. Dried quarter and culling ccurred in -5% f CM episdes and n deaths ccurred. When evaluated by culture result, re-treatment was necessary in abut 30% f all clinical episdes except thse with a N Grwth (NG) result in which nly 4% required retreatment. NG clinical mastitis was nt treated with intramammary antibitics in this study, hwever, if there was n imprvement after 3 days they were treated with cephapirin. Recurrence was abut 20% fr Gram neg and Gram psitive infectins vs. 3 % fr thse with a NG culture result. Many cnsider a clinical episde with a NG culture result t be a Gram neg (clifrm) infectin with lw numbers f bacteria present at the time a sample fr culture is taken. 0 While a clinical cure is mre easily achieved in these NG clinical episdes (even withut intramammary antibitics), the high recurrence rate (3 %) suggests a bacterilgic cure is ften nt achieved. In fact recurrence was abut 3 times mre likely in a cw with NG culture result vs. a cw with a Gram ps culture result. These data suggest treatment f NG clinical mastitis episdes with an intramammary antibitic effective against Gram neg bacteria may reduce the incidence f recurrence if a bacterilgic cure can be achieved. A serum-like secretin is ften cnsidered a grave lcal clinical sign. Many prducers and practitiners assciate a serum-like secretin with lss f the quarter. Accunting fr culture result we fund re-treatment was abut 3 times mre likely in cws with serum-like secretin which cntributed t thse cws having significantly lnger days in sick pen cmpared t cws withut a serum-like secretin. Hwever, there was n assciatin between a serum-like secretin and lss f quarter, death r culling. Re-treatment and recurrence was abut 4 times mre likely in cws with swelling f the quarter. This finding may be due t pr distributin f intramammary treatment in quarters with significant swelling. Swelling, hwever, was present in -70% f cws and therefre wuld have little discriminating ability. The dds f recurrence was -4 and 2.8 times greater in cws with a mixed Gram ps./gram neg. infectin and N grwth culture result respectively. Thse cws withut firmness were 4 times mre likely t recur than thse with firmness f the quarter. Presently, the significance f firmness f the gland vs. swelling f the gland is unclear, hwever, it likely relates t the underlying inflammatry prcess ccurring in the gland. It is pssible that the gland withut firmness had a less vigrus inflammatry respnse that did nt clear the bacteria as effectively. Thus that quarter has 0

greater dds f a recurrent clinical episde due t failure t achieve a bacterilgic cure. l This isjust wild speculatin at this pint. In this dataset there was n assciatin between mre catastrphic utcmes such as death, culling r lss f quarter and these utcmes did nt ccur very frequently in cws with systemically mild clinical mastitis. A serum-like secretin frm the quarter and swelling were assciated with a higher re-treatment rate cntrlling fr initial treatment and culture result. Lack f quarter firmness and swelling were assciated with a higher clinical mastitis recurrence rate in the same quarter. Presently it appears as thugh a tw-stage severity classificatin scheme may be in rder. First classify the cw based n systemic disease signs as described abve (Table ). Fr thse in the mderate and severe grups, the lcal inflammatry changes f the udder are less imprtant than addressing the systemic derangement f the cw. The quarter may be lst, but the primary fcus is nt t lse the cw. Secnd classify thse in the mild grup based n lcal signs (secretin, and the presence f firmness and swelling). At present, hwever, we have very little infrmatin n hw t apprach therapy f these cws t reduce the re-treatment and recurrence rate. Perhaps, if swelling f the mammary gland precludes adequate distributin f an effective antibitic, systemic therapy may be indicated. We recently reprted n a study evaluating the effect f intramuscular (i.m.) ceftifur (2.2 mg/kg) n imprtant utcmes f systemically mild clinical mastitis episdes including re-treatment and recurrence. The results f the study suggested that i.m. ceftifur treatment had n beneficial effects n the utcme f systemically mild clinical mastitis. Obviusly ceftifur des nt enter the milk t a significant degree; hwever, there were anecdtal reprts in ur area f significant reductin f recurrence assciated with clifrm mastitis in cws treated in this manner. Many f yu have prbably apprached clinical mastitis severity scring by the tw stage apprach described abve. It will be imprtant that mastitis researchers adpt a similar apprach t effectively classifies severity that will allw the results f treatment trials t be evaluated n the basis f systemic and lcal disease severity factrs which we have shwn are imprtant t cnsider. 02

References. Lhuis, J.A.C.M., Y.H. Schukken, J.H.M. Verheijeden, A. Brand and A.SJ.P.A.M. VanMiert. 990. Effect f severity f systemic signs during the acute phase f experimentally induced Escherichia cli mastitis n milk prductin lsses. J. Dairy Sci. 73(2): 333-34. 2. Hblet, K., G. Schnitkey, D. Arbaugh, et al. 99. Csts assciated with selected preventive practices and with episdes f clinical mastitis in nine herds with lw smatic cell cunts. J. Am. Vet. Med. Assc. 99(2):90-6. 3. Mrin, D.E., RD. Shanks, G.c. McCy. 998. Cmparisn f antibitic administratin in cnjunctin with supprtive measures versus supprtive measures alne fr treatment f dairy cws with clinical mastitis. J. Am. Vet. Med. Assc. 23(5):676-684. 4. Sisch, W., D. Mre, J. Fedn. 997. Use f physilgic variables t predict milk yield after clinical mastitis in dairy cattle. J. Am. Vet. Med. Assc. 2(4): 470-475. 5. Erskine, RJ., Bartlett, P.C., VanLente, J.L. and Phipps, C.R 2002. Efficacy f systemic ceftifur as a therapy fr severe clinical mastitis in dairy cattle. J. Dairy Sci. 85(0):257-2575. 6. Internatinal Dairy Federatin. 999. Suggested Interpretatin f Mastitis Terminlgy. Bulletin f the Internatinal Dairy Federatin N. 338:3-26. 7. Wenz, J.R, G.M. Barringtn, F.B. Garry, R.P. Dinsmre, RJ. Callan. 200a. Use f systemic disease signs t assess disease severity in dairy cws with acute clifrm mastitis. J. Am. Vet. Med. Assc. 28(4):567-572. 8. Wenz, J.R, G.M. Barringtn, F.B. Garry, K.D. McSweeney, RP. Dinsmre, RJ. Callan. 200 b. Bacteremia assciated with naturally ccurring acute clifrm mastitis in dairy cws.. Amer. Vet. Med. Assc. 29(7):976-98. 9. Wenz, J.R, K. Whitman, F.B. Garry. 2005. Assciatin between lcal (udder) clinical signs and imprtant utcmes f clinical mastitis episdes in dairy cattle. J. Dairy Sci. 88, Suppl.. 0. Mrin, D.E., P.D. Cnstable. 998. Characteristics f dairy cws during episdes f bacterilgically negative clinical mastitis r mastitis caused by Crynebacterium spp. J. Am. Vet. Med. Assc. 23(6):855-86.. Wenz J.R, F.B. Garry, J.E. Lmbard, R Elia, D. Prentice, RP. Dinsmre. 2005. Shrt Cmmunicatin: Efficacy f Parenteral Ceftifur fr Treatment f Systemically Mild Clinical Mastitis in Dairy Cattle.. J. Dairy Sci. 88:3496-3499. 03