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Diagnosis and Treatment of Metritis

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Dr. Stephen LeBlanc presented this for DAIReXNET as part of our educational video series. View the full presentation at https://www.youtube.com/watch?v=IH4vPuOTFyM

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Diagnosis and Treatment of Metritis

  1. 1. Diagnosis and treatment of metritis Stephen LeBlanc University of Guelph
  2. 2. Cows with post-partum metritis had lower DMI during the post- and pre- partum periods 0 4 8 12 16 20 -13 -10 -7 -4 -1 2 5 8 11 14 17 20 Healthy Mildly Metritic Severely Metritic DMI(kg) Day from Calving Clinical signs of infection Huzzey et al. 2007
  3. 3. Hour AverageDMIateachhour(kg)During the week before calving cows that develop post-partum severe metritis (n=12) consume less feed during the period immediately following fresh feed delivery (F.D.) F.D. F.D. Huzzey et al. 2007 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 0:00 4:00 8:00 12:00 16:00 20:00 Healthy Mildly Metritic Severely Metritic Courtesy of Dr. M. von Keyserlingk
  4. 4. Transition Health and CR at 1st AI 5719 cows in 7 US herds Santos et al RepDomRum 2010 Prevalence 56 27 17 15 16 20 21 12 10 7 3 2
  5. 5. Risk factors for uterine disease  Species of bacteria  Virulence factors  Strain  Level of contamination  Dry matter intake  Energy and lipid metabolic health  Stressors & hormonal changes  Hypocalcemia Bacteria Immune response Regulation of inflammation
  6. 6. Uterine E coli Are the E coli associated with metritis and endometritis specific uterine pathogens or do they have specific virulence factors? 1. Silva et al 2009 – 72 isolates from 12 healthy cows and 18 with metritis – no associations of phylogenetic group or specific virulence factors – Strain associations with herd 2. Sheldon et al 2010 – 114 isolates from 64 cows from 1 herd sampled at weeks 1 – 4 – Association of 1 group with metritis – Strains found in cows with metritis were more adherent and invasive to epithelium and LPS induced greater inflammatory response in culture 3. Bicalho et al 2010 – 611 E coli isolates from 374 cows in week 1 in 4 herds, screened for 32 virulence genes; subset of 117 cows screened for PVD in week 4 – 6 virulence genes associated with reproductive tract disease – Adherence factor (fimH) was the single strongest predictor of metritis (OR = 6)
  7. 7. Vaccination against reproductive tract disease • Total of 371 heifers from 1 herd vaccinated at ~ 50 and 20 d before calving with vaccine containing whole killed E. coli, F. necrophorum and T. Pyogenes ±FimH, leukotoxin, and pyolysin • SC vaccination with bacteria ± proteins – decreased metritis incidence • 12 to ~4% (Dx only at 6 DIM) • 28 to 16% (daily Dx by farm staff) – Decreased time to pregnancy • 120 to 94 median DIM – No effect on clinical endometritis (lavage visual at 35 DIM; 9%) or on prevalence of E. coli or F. necro at 2 or 6 DIM, or T. pyo ay 35 DIM Machado et al 2014
  8. 8. Neutrophil myeloperoxidase (iodination) activity – a measure of killing activity Cows with subclinical endometritis at 28 DIM n = 43 Cows with metritis < 14 DIM n = 18 Cows with normal uterine health n = 22
  9. 9. Neutrophil myeloperoxidase (iodination) activity – a measure of killing activity Cows in the highest quartile of DMI in the 3 weeks before calving Cows in the lowest quartile of DMI in the 3 weeks before calving
  10. 10. Associations of subclinical hypocalcemia with immune function and metritis • Martinez et al JDS 2012 • 110 cows in 1 herd in Florida • Pair-matched “high risk” (twins, stillbirth, dystocia, RP) with low risk cows • Subclinical hypo-Calcemia = ≤ 2.15 mmol/L at least once 1 – 3 DIM
  11. 11. Martinez et al JDS 2012
  12. 12. Martinez et al JDS 2012
  13. 13. Postpartum fever • 10-45% overall prevalence of fever (Kinsel, 2001; LeBlanc, 2002; Sheldon, 2004) • Not a good correlation between fever and bacterial infection 1 to 10 DIM (Sheldon et al 2004) – 56% of pyrexic cows had infection – Prevotella was associated with fever • Is fever alone a problem that requires antibiotics? • Are there cows that would benefit from antibiotics that do not have a fever? • Is there a useful threshold to distinguish these cows? – > 39.7 or 40 at any time? > 39.5 for 2 days? – Fetid discharge with or without fever? – Milk production? Attitude? Other clinical signs?
  14. 14. Physiology vs. pathology • Almost all cows have bacterial contamination of the uterus after calving • The same immune system mediators appear to be involved in healthy and affected cows – TLR4; IL1, 6, 8 , 10; (TNFα) • Difference lies in the magnitude, regulation, duration and effectiveness of the response Involution Pathological inflammation
  15. 15. Metritis diagnosis - repeatability • 6 samples of postpartum vaginal discharge (3 healthy, 2 metritis (1 repeated)) • 10 repetitions of each sample, randomized • 15 vets and final year vet students Kappa Colour 32 point chart Smell 1 – 5 scale Viscosity 1 – 5 scale Kappa statistic Inter-rater 0.15 0.27 0.44 Intra-rater 0.35 0.39 0.60 A central diagnostic criterion has only fair reliability Sannmann & Heuwieser JDS 2015
  16. 16. Metritis diagnosis - Temperature • Considered separately, rectal temperature associated with – Parity (0.2 C greater in lact=1) – Ketosis (higher in ketotic in lact=1) – Environmental THI (higher in June and July) • Must be interpreted in context Burfeind et al Therio 2014
  17. 17. RP and Metritis Impacts on Reproduction & Culling RP Metritis No Yes P-value No Yes P-value Pregnancy risk (%) First service 34.7 29.4 0.02 35.3 27.2 < 0.01 120 DIM 46.5 33.2 < 0.01 46.0 36.3 < 0.01 300 DIM 83.5 76.0 < 0.01 80.4 82.6 0.02 Culling risk (%) 30 DIM 3.2 6.3 0.34 3.6 4.5 0.70 63 DIM 6.4 9.0 0.71 6.8 7.2 0.92 300 DIM 16.9 18.5 0.69 17.0 18.0 0.83 No full-lactation effects when parity, production, DA, endometritis, pregnancy accounted for Dubuc et al, 2010
  18. 18. Metritis and Production Wittrock et al JDS 2011
  19. 19. Impact of Metritis on Milk Production Multiparous (metritis) Primiparous (metritis) 26 28 30 32 34 36 38 40 1 2 3 4 Milkproduction(kg/d). DHI test-days No metritis Metritis 250 kg less milk per lactation for multiparous cows with metritis 34 36 38 40 42 44 46 48 50 1 2 3 4 Milkproduction(kg/d) Dubuc et al, 2010
  20. 20. Impact of metritis • 1600 cow dry lot dairy in Argentina, TMR-fed • 303 cows examined at 5, 6, 7 DIM: T and gloved hand – “Clinical metritis” = fetid discharge (n=29; 10%) – “Puerperal metritis” = fetid discharge + T > 39.2 C (n=90; 30%) • Both randomly assigned to ceftiofur 2.2. mg/kg IM x 3 d or untreated • Cure = clear discharge at 21 DIM • No effect of ceftiofur on clinical cure (69%; n=100) or milk yield to 90 DIM; tended to increase CR at 1st TAI
  21. 21. Giuliodori et al JDS 2013 Impact of different forms of metritis
  22. 22. Prevalence of Uterine Disease Classification of risk for uterine disease Low risk High Risk (Dystocia, twins, RP) Metritis 12% 28% EXAM 35 DIM n=1116 n=956 Endometritis only 13% 13% PVD only 5% 15% Both 4% 10% Total 22% 38% Dubuc et al, 2010
  23. 23. Concepts of inflammatory response 1 42 3 5 UterineInflammation weeks Healthy Endometritis – excessive inflammation Endometritis – inadequate response
  24. 24. What impact does this have on this cow? Can we improve her outcomes?
  25. 25. Metritis treatment • Case definition = T > 39.5 + fetid discharge • 1) n = 406 cows (8 large herds) randomized to control, 1.1 or 2.2. mg/kg ceftiofur for 5 d Chenault et al , 2004 • 2) n = 982 cows (15 herds) randomized to 2 doses CCFA (3 d apart) or saline control McLaughlin et al JDS 2012 • Clinical cure (no fever; no fetid discharge) at day 14: –Ceftiofur:77% Saline: 62% –CCFA: 74% Saline: 55%
  26. 26. Wait and see? • 1 herd in Germany; daily metritis detection; Rx = 1 dose of CCFA (Sannmann et al Therio 2013) • 12 treated at Dx 1-4 DIM • 19 not treated at Dx 1-4 DIM – 12 never treated as no metritis at 5 – 10 DIM – 7 with delayed treatment at 5-10 DIM • 48 treated at Dx 5-10 DIM • No difference in fever at 4 d after Dx or clinical outcomes to 28 DIM • Ability to apply this likely depends on – Presence of complicating factors – Sensitivity of detection of worsening clinical condition – Heat stress • Larger scale study needed
  27. 27. Metritis treatment • n = 528 cases of fetid discharge (n=312) or metritis (fetid + T ≥ 39.5 C; n=216) from 1 large dairy in Florida; 268 matched healthy cows in comparison group • Blocked by metritis type, randomly assigned to 11 mg/kg ampicillin or 2.2 mg/kg ceftiofur q 24 h x 5 d • PreSynch 50 and 64 DIM, bred on estrus after 2nd PGF or 5-d Ovsynch with TAI at 84 DIM Lima et al JDS 2014
  28. 28. Metritis treatment • Among cows with fetid discharge only, 53% developed ≥ 1 day of fever while on antibiotics Lima et al JDS 2014
  29. 29. Metritis treatment Clinical cure Lima et al JDS 2014 • Ampicillin > ceftiofur days 5 and 7 • Cure at day 12 not different ~67% • No interactions of treatment with metritis type, parity, dystocia
  30. 30. Metritis treatment PVD and endometritis Lima et al JDS 2014 • Lower prevalence of PVD at 32 d with ampicillin than ceftiofur • No difference in endometritis at day 39
  31. 31. Metritis treatment – Reproductive performance Outcome Ampicillin Ceftiofur Healthy comparison P Cyclic 64 DIM 75% 76% 75% 0.96 Pregnant 1st AI 30 d 29% 29% 32% 0.87 60 d 28% 28% 31% 0.91 Loss 6% 6% 11% 0.52 Lima et al JDS 2014 These outcomes not different between fetid discharge and metritis
  32. 32. Metritis IU – Non-antibiotic • n = 220 cases of metritis (fetid discharge T > 39.5 C, systemic illness) from 1 large organic dairy in Texas, randomly assigned to 200 ml povidone iodine in 2 L water or 3.75 ml Optimum UterFlush in 117 ml water, each q 48 h x 3 d (Days 1,3,5) • All received hypertonic saline + dextrose IV and 5 Aspirin/d (duration = ?) • Tail chalk , estrus detection only Pinedo et al JDS 2015
  33. 33. Metritis IU – Non-antibiotic Outcome UterFlush Iodine Statistics (OR from models) Healthy comparison group Day 6 T > 39.5 C 31% 20% Fetid discharge 28% 11% OR = 0.2 {.09 - .45} Cure 70% 49% P = 0.003 Culled 4% 11% OR = 4.7 {1.4 - 16} Day 14 T > 39.5 C 12% 8% P = 0.38 Fetid discharge 1% 9% OR = .08 {.01 - .63} Cure 76% 66% P = 0.18 Culled 13% 22% OR = 2.8 {1.3 – 6.1} Day 30 Culled 16% 27% OR=3.1 {1.2 – 8.0} 2% AI by 150 DIM 62% 57% P=0.27 93% Pregnant 1st AI 38% 23% P =0.05 39% Pregnant 150 DIM 45% 30% OR=1.8{1.04-3.2} 75% Pregnant 300 DIM 59% 44% OR=1.9 {1.1-3.4} 90% Pinedo et al JDS 2015
  34. 34. Metritis Treatment Summary • Diagnostic criteria inconsistent and not well validated (Sannmann et al 2012) • Systematic review (Haimerl & Heuwieser 2014) – 23 studies; narrow set of research questions but overall high quality of evidence
  35. 35. Mastitis Treatment Summary • Cows with  2 of : T > 39.5; fetid discharge; dullness/off-feed can rationally be treated with systemic antibiotics • Ceftiofur, ampicillin, or penicillin likely to be similarly efficacious (Smith et al 1998; Drillich et al 2001; Chenault et al 2004; Lima et al 2014; review by Reppert VCNA 2015)
  36. 36. Metritis Treatment Summary • Expected outcomes: – Absence of fever in 80 – 100% of cows 2-6 days after treatment – Absence of fetid discharge 33 – 77% – No difference pregnancy rate between ceftiofur and ampicillin (Lima et al 2014) • More field research is needed to refine treatment selection criteria, and assess antimicrobial resistance, animal welfare, and economics

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