Mastitis in non-bovine dairy species, companion animals and breastfeeding mothers. Chris Knight

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Mastitis in non-bovine dairy species, companion animals and breastfeeding mothers Chris Knight

Objectives To stimulate thought/discussion regarding the relevance and importance of mastitis and mastitis research in non-bovine farmed species To highlight issues related to diagnosis of mastitis in non-dairy farmed species To highlight the knowledge gap when comparing bovine and human mastitis To do this in a Nordic context

Follow-up on the NordForsk CoLact Human Mastitis Action Point Stage 1: Chris Knight and Linda Kvist to review the human mastitis literature with a view to proposing a unifying definition suitable for general use Stage 2: Input from veterinary mastitis specialist(s) Stage 3: Draft proposal for primary prevention research project.

World milk production

Goat milk production

World Milk Production

Perspectives Differ!

Meat production

Sheep mortality Cause of death diagnosed at autopsy Incidence (%) Mastitis 11 Acute fluke 7 Johnes disease 6 Ovine pulmonary adenocarcinoma 6 Bacterial bronchopneumonia 6 Chronic suppurative pneumonia 6 Pulmonary neoplasia 6 Other cause of death (individually minor events) 26 Autolysis 9 No diagnosis 17 No cause of death diagnosis 6 Strugnell and Lovatt (2013) Proc. BSAS 4(1) 14

Ovine mastitis Recent reviews: Conington et al 2008 (objective: increased genetic resistance) Mavrogianni et al 2011 (therapy) Estimates of prevalence in both dairy and meat sheep vary, but values in excess of 33% are reported In addition to S. aureus, Mannheimia haemolytica is a common isolate Modelling suggests that a 10% reduction in incidence would save 2.7M pa in the UK Texel industry

Caprine mastitis Recent review focused on diagnostic tools: Koop et al 2012 Typically lower incidence of clinical mastitis than in cattle, but higher subclinical Why? Interpretation of SCC data is different to that in cattle

SCC Changes in SCC during lactation 700 600 500 400 300 200 100 0 0 10 20 30 40 50 60 Lactation week

Buffalo mastitis Joshi and Gokhale 2006, Ann. N.Y. Acad. Sci. Compared improved and periurban production Actually focused on bovine mastitis Cited evidence of lower subclinical mastitis incidence in buffalo compared to cattle (5-20% vs 10-50%) Clinical mastitis claimed to be between 1 and 10% Significant effect of season claimed but not supported by data (15.05 vs 13.97% and 8.89 vs 7.04%, rainy vs summer, cows vs buffalo) Very few truly comparative data, most rather old

At Dubai dairy, camels are the new cows International Herald Tribune, Wed 25 th August 2010 Benefit: 3X more Vit C, low lactose Problem: salty taste Solution: feed carrots and dates to the 700 camels

Camel mastitis Several recent reports Typically 30-40% subclinical mastitis Typically 5-10% clinical mastitis SCC appears to be useful High incidence of blind quarters Traditional management probably predisposes to mastitis Pathogen profiles probably similar to cattle

430 /kg powder

Equine mastitis Very few reports since a number of short reviews in the 1980s A recent review of milking horse herds in Netherlands/Flanders identified 13 such farms

Canine mastitis Few scientific reports, mainly case studies Issues: Dairy farm reservoir (eg Streptococcus canis) Pseudopregnancy Perinatal mortality Chronic subclinical mastitis and carcinomas One experimental challenge study used Staphylococcus intermedius (Ververidis et al 2007) Therapy has been reviewed (Wiebe and Howard 2009) Feline mastitis is less well documented

Porcine mastitis Gerjets et al 2009, 2011 Mastitis-metritis-agalactia syndrome, postpartum dysgalactia syndrome, puerperal mastitis, coliform mastitis Typically around 13% of sows affected, range up to 60% in some herds Associated with E coli but cause and effect not established, and recent research shows no difference in infection rate or virulence factors between healthy and diseased sows Risk factors include increased fecundity, being a gilt, bith intervention. Birth induction and season are not risk factors

Risk analysis overview Category of animal Incidence Diagnosis Treatment Family herds Known, amenable Well developed Dairy cows AMS herds to management Developed Well developed Large herds improvement In development Some Other milked ruminants information, management intervention possible Less well developed Less well developed Non-milked ruminants Companion animals Very scarce information. Often wrongly(?) assumed to be low incidence Scarce information. Most do not lactate, so incidence probably low Poorly developed Reliance on lay knowledge Little opportunity Little opportunity Breastfeeding mothers Some information, quite variable. Probably similar incidence to well managed dairy cow herd Variable, self diagnosis and healthcare worker rates differ Variable, major debate regarding effectiveness of antibiotics but little data

Potential for use of high-dose oxytocin to improve diagnosis of mastitis in dairy cows and beef suckler cows Lina Jonsson, Christopher Knight and Kerstin Svennersten-Sjaunja Swedish University of Agricultural Sciences and University of Copenhagen lina.jonsson@miris.se chkn@sund.ku.dk

Aim Our objective was to investigate a possible physiological basis for the development of a single-visit milk-based mastitis diagnostic test suitable for use in beef suckler cows. We hypothesised that high-dose oxytocin would create leaky mammary tight junctions, increased SCC and shedding of pathogen into milk, and thereby provide a milk sample with enhanced diagnostic potential

Introduction The problem Subclinical Mastitis -Diagnosed as SCC > 200K cells/ml in milk from several milk samples Beef suckler cows -Assumed to have a low frequency of subclinical mastitis - Recent studies shows that this is not the case. Persson Waller K, Persson Y and Stengärde L (2012). Mastitis in beef cows: a threat against calf growth? CRU Report 27 p16. ISBN 978-91- 576-9013-5

Material and methods 14 Dairy cows. 10 cows with a previous history of high SCC (HIGH). 4 cows SCC < 50 000 cells/ ml milk (LOW). Milked twice a day over an 11 day study period. Milk samples were collected as shown in the next slide. At the AM milking on day 3, 100iu of oxytocin was given. The sample taken that afternoon, approx. 8 h after the oxytocin was given, was designated the test sample. Samples were analysed for mastitis pathogens, SCC and gross composition using standard methodologies.

Experimental Milking Experimental design Experimental Day Fore SCC, Bacteriology Bulk SCC, Composition Hind Bacteriology Day number 1 2 3 4 10 11 1 2 3 4 5 6 7 8 9 10 11 12 Sample number Oxytocin Test sample

Results No evidence of increased pathogens in sample 5 or 6. SCC increased markedly in sample 6 and recovered to pre-oxytocin levels thereafter.

SCC *10 3 / ml Results SCC (Individual HIGH cow) 3500 3000 2500 2000 1500 1000 500 RF RB LB LF 0 1 2 3 4 5 6 7 8 9 10111213141516171819202122 Milkings

SCC *10 3 / ml Results SCC (Individual LOW cow) 500 400 300 200 100 RF RB LB LF 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Milkings

SCC *10 3 / ml Results ( Hard to categorize cow) 7000 6000 5000 4000 RF 3000 RB LB LF 2000 1000 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Milkings

Results Diagnosed subclinical mastitis (quarters) Samples 1-5 (Milk) Test sample (Modified milk) 15 18 Missclassified at least once (quarters) 6 (40%) 2 (11%) Clinical signs (samples) 72 14 Missed by scc (samples) 25 (35%) 1 (7%)

Conclusions Measurement of SCC in the single sample collected approximately 8h after oxytocin administration was shown to have much better diagnostic potential than other single samples. High-dose oxytocin could be a useful mastitis diagnostic tool in beef suckler cows, and in dairy cows where frequent sampling is not possible.

Evolving dairy farms

Think out of the box? No, think things into the box! DairyCare Frequent, regular, reproducible, manipulatable, controllable, time on its hands

Stress related biomarkers Cortisol Inflammatory cytokines Systemic Blood Saliva Milk (and modified milk) Sweat Hair Minutes Weeks Local?

DairyCare Proposed COST Action in dairy animal health and welfare Involving 20 EU countries, 5 non-eu Economic dimension of 22M euro WG1: Biomarker-based welfare technologies WG2: Activity-based welfare technologies WG3: System-level welfare technologies

Risk analysis overview Category of animal Incidence Diagnosis Treatment Family herds Known, amenable Well developed Dairy cows AMS herds to management Developed Well developed Large herds improvement In development Some information, Other milked ruminants management intervention possible Less well developed Less well developed Non-milked ruminants Companion animals Very scarce information. Often wrongly(?) assumed to be low incidence Scarce information. Most do not lactate, so incidence probably low Poorly developed Reliance on lay knowledge Little opportunity Little opportunity Breastfeeding mothers Some information, quite variable. Probably similar incidence to well managed dairy cow herd Variable, self diagnosis and healthcare worker rates differ Variable, major debate regarding effectiveness of antibiotics but little data

Human Mastitis Mastitis Mammitis Mastadenitis Milk fever

Self-diagnosis Health worker Definition required Pathogens Blocked ducts Cracked nipples Physiological mastitis Causes 3 rd NBC Meeting Copenhagen 2009 Suckling Breast pump Researcher Clinical vs Subclinical Diagnosis Mastitis Incidence Management Antibiotic: (Systemic) (Local) (Prophylactic) Acute phase response Analysis of milk Order of magnitude variation 3% to 30% Consequences Mother: Pain Anxiety Breast cancer? Baby: Nutrition Protection Disease vector Oxytocin Liniment Analgesia

Suggested definition for multidisciplinary research use Mastitis is inflammation of the breast Mastitis can be assumed to be present if the subject reports or has a red, tender, hot or swollen area of the breast, together with one or more of the following: a high temperature symptoms of fever (body aches, headaches, chills) a diagnosis of mastitis from a medical practitioner Kinlay et al (1998) Med. J. Aust. 169, 310

Terminology to avoid or restrict to specific use Lactational mastitis avoid, use non-lactational when needed Puerperal mastitis strict definition needed if it is to be useful (<5d?) Contagious mastitis, environmental mastitis not useful outside bovine mastitis Supparative mastitis should be rendered redundant Infective mastitis, infectious mastitis avoid (infective is generalized risk, infectious is specific risk) Pathogenic mastitis suggested use for when a known mastitis pathogen has been identified alternative would be to adopt the diagnostic term intramammary infection Physiological inflammation (of the mammary gland) use to describe the local inflammatory response to prolonged milk accumulation

Suggested definitions for mothers Mastitis is inflammation of the breast You have mastitis if you have a red, tender, hot or swollen area of the breast, together with either a high temperature or symptoms of fever (body aches, headaches, chills) If you have mastitis your milk is still safe for your baby. You should continue to breastfeed from both breasts and seek immediate medical advice and treatment?

Self-diagnosis Health worker Definition required Pathogens Blocked ducts Cracked nipples Physiological mastitis Causes Treatment: Antibiotic or not? Suckling Breast pump Researcher Clinical vs Subclinical Diagnosis Mastitis Incidence Management Antibiotic: (Systemic) (Local) (Prophylactic) Acute phase response Analysis of milk Consequences Mother: Pain Anxiety Breast cancer? Baby: Nutrition Protection Disease vector Prevention: How? Oxytocin Liniment Analgesia

Antibiotic treatment A/B use for human mastitis: Finland: 38% Australia: 75% USA: 86% Sweden: 15% (mostly following bacteriology) Cochrane review: 2009, updated in 2013

Antibiotic use: Cochrane review

Kvist, 2013

Cusack and Brennan 2011

Management of mastitis: Cochrane review Crepinsek et al 2012 Five trials in total, 960 women A/B vs none: no significant difference (NSD) Specialist advice vs usual care: NSD Specialist diet vs normal diet: NSD Other therapies vs none: NSD

Scott et al 2008 Prospective longitudinal study of 420 breastfeeding mothers in Glasgow Cases self-diagnosed or detected at subsequent telephone interview 74 women (18%) experienced at least one episode of mastitis, repeated incidence occurring in almost one-third More than half of new cases occurred in first four weeks of lactation Lactation duration was not decreased Of 57 mothers who received advice, 6 were inappropriately advised Of 30 mothers who received antibiotic, 10 were inappropriately prescribed Retrospective bacteriological analysis did not yield useful research conclusions

Pathogens Blocked ducts Cracked nipples Self-diagnosis Health worker Physiological mastitis Causes Suckling Breast pump Researcher Clinical vs Subclinical Diagnosis Mastitis Incidence Management Antibiotic: (Systemic) (Local) (Prophylactic) Acute phase response Analysis of milk Consequences Mother: Pain Anxiety Breast cancer? Oxytocin Liniment Analgesia Baby: Nutrition Protection Disease vector

Chicken and egg? Why treat with antibiotic? Do blocked ducts cause mastitis? Or does mastitis cause blocked ducts? Why NOT treat with antibiotic?

Potential animal models Similar mammary anatomy Allows for intra-lobular pathogen challenge Allows for sealing individual ducts Discrete suckling episodes of very different frequencies Supplementary questions: Is infection transmitted from lobule to lobule? In this regard, is nipple hygiene particularly important when blocked ducts need to be cleared? When does physiological inflammation start (cross-species)?

Follow-up on the CoLact Human Mastitis Action Point Stage 1: Chris Knight and Linda Kvist to review the human mastitis literature with a view to proposing a unifying definition suitable for general use Stage 2: Input from veterinary mastitis specialist(s) Stage 3: Draft proposal for primary prevention research project.

Where to start? Post-feed routine Weaning strategy Early lactation strategy Hit recurrent mastitis hard