Randomized clinical trial of ketoprofen or ceftiofur for treatment of metritis in dairy cows.

Our objectives were to compare the efficacy of ketoprofen or ceftiofur for treatment of metritis in dairy cows considering subsequent health, production, and reproduction. Cows from 2 commercial dairy farms in Ontario, Canada were examined with a Metricheck device 3 times per week from 2 to 14 d in milk (DIM). Cows with metritis (fetid vaginal discharge; n = 193) were blocked by parity and fever (rectal temperature ≥39.5°C or <39.5°C) and within each block per farm, randomly assigned to receive 3 mg/kg BW of ketoprofen (KET) or 2.2 mg/kg of ceftiofur hydrochloride (CEF), once a day for 3 d. Day of enrollment was considered study d 0. Rectal temperature and attitude were evaluated in cows with metritis on study d 0, 3, 4, 7, 10, and 13, and vaginal discharge was evaluated on study d 4, 7, 10, and 13. Body condition was scored at enrollment and 35 DIM, and serum concentration of haptoglobin was measured at d 0, 2, 4, and 7. Cows with rectal temperature ≥39.5°C or a depressed attitude on d 3 were classified as clinical failure and received treatment with ceftiofur for 3 d (KET), or 2 additional days (CEF), to a maximum of 5 d of treatment with ceftiofur. At 35 ± 3 DIM cows were examined for uterine involution by transrectal palpation, purulent vaginal discharge (PVD) by Metricheck, and endometritis by endometrial cytology. Time to onset of cyclicity was assessed by serum progesterone (P4) measurements at 28, 42, and 56 DIM. Contemporary cows from the same farms without metritis (NOMET; n = 1,043) were used for comparison. Data were analyzed with mixed linear or logistic regression or Cox's proportional hazard models, including herd as a random effect. The proportion of clinical resolution of metritis on d 3 (96% vs. 92%), of cows with fever (from d 3 to d 13 after enrollment) or fetid discharge (from d 4 to d 13 after enrollment), and the number of medical treatments (3.1 vs. 3.3) were not different between CEF and KET, respectively. Cows in KET received fewer antibiotic treatments than cows in CEF (0.3 vs. 3.1). Uterine involution, the prevalence of PVD (50% vs. 47%) and subclinical endometritis (6.6% vs. 4.3%), and the proportion of cyclic cows (82% vs. 86%) did not differ between CEF and KET. Cows in KET had greater serum haptoglobin concentration from d 2 to 7 after enrollment. The incidence of mastitis, lameness, or displaced abomasum to 60 DIM and subclinical ketosis to 21 DIM did not differ among CEF, KET, and NOMET. There were no differences in median days to first AI (CEF = 68 d; 95% CI: 65-70; KET = 69 d; 95% CI: 68-72; NOMET = 69 d; 95% CI: 68-70), and median days to pregnancy (CEF = 118 d; 95% CI: 92-145; KET = 113 d; 95% CI: 90-135; NOMET = 105 d; 95% CI: 101-109), pregnancy at first AI at 33 d after insemination (CEF = 42%; KET = 41%; NOMET = 41%), pregnancy loss after first AI (CEF = 8%; KET = 11%; NOMET = 8%), hazard of pregnancy or hazard of culling up to 300 DIM. Milk yield was not different between CEF and KET during the first 10 weeks, but lesser in KET at wk 2 and 4 and CEF at wk 2, 4, and 6 than in NOMET. In this pilot-scale study, given early detection, we did not detect differences in subsequent health, milk yield, or reproductive performance in cows with metritis initially treated for 3 d with CEF or KET. Additional, larger studies are warranted.

Progesterone profiles in postpartum dairy cows with inflammatory disorders.

The objective of this prospective cohort study was to determine if progesterone (P4) profiles differed between dairy cows with or without inflammatory disorders early postpartum. A total of 708 cows from 2 commercial herds were enrolled 3 wk before parturition and examined for clinical health disorders (retained placenta, metritis, displaced abomasum, mastitis, or lameness) until 5 wk postpartum. Serum haptoglobin (Hp) was measured in blood at 2 and 6 (±2) DIM, metritis was assessed at 4, 8, 11, and 15 DIM, and purulent vaginal discharge and endometritis (≥6% polymorphonuclear cells in endometrial cytology sampled by cytobrush) were assessed at 35 ± 3 DIM. As Hp ≥0.8 g/L or endometritis were associated with ovarian dysfunction in previous studies, cows with serum Hp ≥0.8 g/L at either time point and endometritis, regardless of clinical disease, were classified as the cohort with inflammatory disorders (INFLAM; n = 139). Clinically healthy cows without difficult calving or twin birth, with Hp <0.8 g/L at both sampling times, without endometritis, and BCS ≥3.00 (1 to 5 scale) were classified as healthy (n = 133). Cows with only one of the 2 conditions (high Hp or endometritis) were excluded. Cohorts had serum P4 measured twice weekly from 35 to 70 (±3) DIM, and the first detected luteal phase (LP) during the sampling period was defined as the interval from onset of luteal activity (P4 increase to ≥1 ng/mL) until decline of P4 to <1 ng/mL. The odds of prolonged LP (≥21 d), average LP length, peak P4, and time to P4 decline (hazard rate) were analyzed using multivariable mixed logistic, linear, or Cox proportional hazard regression models including INFLAM status, parity, sampling day (when applicable), and herd as a random effect considering the covariates of season, milk yield at first DHIA test, and DIM at onset of cyclicity or LP length (when applicable). Cows with INFLAM had greater odds of prolonged LP (LSM ± SEM; 67% vs. 37% ± 7), greater average LP length (17 vs. 15 ± 2 d), lesser P4 at d 4 (4.6 vs. 5.5 ± 0.3 ng/mL) and d 7 (6.0 vs. 7.7 ± 0.3 ng/mL) of the LP, and lesser peak P4 (6.9 vs. 8.2 ± 0.3 ng/mL) during the LP than healthy cows. Status of INFLAM was associated with time to P4 decline in multiparous but not primiparous cows; the LP of INFLAM multiparous cows was less likely to have luteolysis (P4 decline) by d 14 [adjusted hazard ratio (AHR) and 95% CI: 0.54; 0.31 to 0.94] or by d 21 (AHR: 0.32; 0.12 to 0.84) than in healthy multiparous cows. In conclusion, postpartum cows with markers of systemic inflammation at wk 1 and uterine inflammation at wk 5 had altered luteal function (prolonged LP and lower P4 concentrations) before first breeding, which is a possible pathway linking postpartum health disorders and infertility.

Cross-sectional study of antimicrobial use and treatment decision for preweaning Canadian dairy calves.

Antimicrobials should be used prudently in farm animals to prevent the development of resistant bacteria in both humans and animals. The objective of this study was to investigate Canadian dairy producers' practices for antimicrobial use in the treatment of disease in preweaning dairy calves. In-person questionnaires were administered to 144 dairy producers across 5 provinces in Canada between July 2019 and August 2020. Almost all (96%) producers used antimicrobials to treat calves with respiratory disease, but only 27% indicated they had a written treatment protocol for respiratory disease. Most (95%) of these protocols for respiratory disease were developed with input from the herd veterinarian. Seventy-four percent of producers used antimicrobials to treat calf diarrhea, with 37% of producers having a written treatment protocol for calf diarrhea with input from the herd veterinarian. The combinations of signs adopted by the producers for antimicrobial treatment in calf respiratory disease and diarrhea were evaluated based on findings from other studies. More than half (56%) of producers who used antimicrobials for calf respiratory disease decided to use antimicrobials by evaluating multiple clinical signs. Eighty-two percent of producers who used antimicrobials for calf diarrhea made decisions based on systemic signs of disease, presence of bloody stool, no response to previous treatment, or on the recommendation from the herd veterinarian. Producers with a written treatment protocol had 3 to 7 times greater odds of using antimicrobials based on multiple signs or systemic signs of disease compared with those without a protocol. Further research may investigate other calf management practices related to decision-making by producers in using antimicrobials to improve antimicrobial stewardship on dairy farms.

Controlled trial of the effect of negative dietary cation-anion difference prepartum diets on milk production, reproductive performance, and culling of dairy cows.

Our objective was to assess the effects of feeding negative dietary cation-anion difference (DCAD) prepartum diets on milk production, reproductive performance, and culling. Cows from 4 commercial farms in Ontario, Canada were enrolled in a pen-level controlled trial from November 2017 to April 2019. Close-up pens (1 per farm) with cows 3 wk before calving were randomly assigned to a negative DCAD (TRT; -108 mEq/kg of dry matter; target urine pH 6.0-6.5) or a control diet (CON; +105 mEq/kg of dry matter with a placebo supplement). Each pen was fed TRT or CON for 3 mo (1 period), and then switched to the other treatment for the next period (4 periods per farm). Data from 15 experimental units (8 pen treatments in TRT and 7 in CON), with a total of 1,086 observational units (cows), were included. The effect of treatment on milk yield at the first 3 milk recording tests of lactation was assessed with linear regression models accounting for repeated measures. The risk of pregnancy at first artificial insemination and culling by 30, 60, and 305 d in milk (DIM) were analyzed with logistic regression models, and effects on time to first AI, pregnancy, and culling were assessed with Cox proportional hazards models. All models included treatment, parity, and their interactions, accounting for pen-level randomization and clustering of animals within farm with random effects, giving 10 degrees of freedom for treatment effects. Multiparous cows fed TRT produced more milk at the first (42.0 vs. 38.8 ± 1.2 kg/d) and second (44.2 vs. 41.7 ± 1.3 kg/d) milk tests. However, multiparous cows fed TRT tended to have 0.2 percentage units less milk fat content at these tests. Although multiparous cows fed TRT tended to have greater energy-corrected milk at the first test (least squares means ± standard error: TRT = 46.1 ± 0.9 vs. CON = 43.8 ± 1 kg/d), there were no differences observed in energy-corrected milk at the second or third tests. In primiparous cows, there was no effect of treatment on milk production. Multiparous cows fed TRT had greater pregnancy to first insemination (TRT = 42 ± 3 vs. CON = 32 ± 4%) and tended to have shorter time to pregnancy [hazard ratio (HR) = 1.20; 95% CI: 0.96-1.49]. In primiparous cows fed TRT, time to pregnancy was increased (HR = 0.76; 95% CI: 0.59-0.99). Culling by 30 DIM tended to be less in TRT (3.3 ± 1.1%) than CON (5.5 ± 1.8%). No effect of treatment on culling by 305 DIM was detected in primiparous cows, but in multiparous cows, the TRT diets decreased the odds of culling (21.3 ± 1.9 vs. 31.7 ± 2.8%) and daily risk of culling to 305 DIM (HR = 0.64; 95% CI: 0.46 to 0.89). Under commercial herd conditions, prepartum negative DCAD diets improved milk production and reproductive performance, and reduced culling risk in multiparous cows. In primiparous cows, TRT diets had no effect on milk yield or culling, but increased the time to pregnancy. Our results suggest that negative DCAD diets should be targeted to multiparous cows.

Controlled trial of the effect of negative dietary cation-anion difference on postpartum health of dairy cows.

The objective of this study was to assess the effects of feeding negative dietary cation-anion difference (DCAD) dry cow diets on postpartum health. Cows from 4 commercial dairy farms in Ontario, Canada, were enrolled in a pen-level controlled trial from November 2017 to April 2019. Close-up pens (1 per farm), with cows 3 wk before expected calving, were randomly assigned to a negative DCAD [TRT; -108 mEq/kg of dry matter (DM); target urine pH 6.0-6.5] or a control diet (CON; +105 mEq/kg of DM with a placebo supplement). Each pen was fed TRT or CON for 3 mo (1 period) then switched to the other treatment for the next period, with 4 periods per farm. Urine pH was measured weekly until calving, and body condition score (BCS) was measured at enrollment and at 5 wk postpartum. Data from 15 experimental units [8 TRT and 7 CON, with 1,086 (TRT: n = 681; CON: n = 405) observational units (cows)] that received the assigned diet for >1 wk were included. The incidence of milk fever (MF), retained placenta (RP), metritis, hyperketonemia (blood ß-hydroxybutyrate >1.2 mmol/L, measured weekly in wk 1 and 2), clinical mastitis within 30 DIM (MAST), displaced abomasum (DA) within 30 d in milk (DIM), purulent vaginal discharge (PVD, assessed once at wk 5), and number of disease events (≥1 or ≥2) were analyzed with logistic regression models with treatment, parity, BCS, and their interactions, accounting for pen-level randomization and clustering of animals within farm with random effects, giving 10 degrees of freedom to test treatment effects. Multiparous cows fed TRT had greater blood calcium between 1 and 4 DIM than multiparous cows fed CON, and the prevalence of subclinical hypocalcemia (total Ca ≤2.14 mmol/L) was lesser when fed TRT compared with CON (d 1: 73 ± 6% vs. 93 ± 4%; d 2: 65 ± 7% vs. 90 ± 5%), with no differences between treatments detected in primiparous cows. We detected interactions of treatment and BCS at enrollment for MF in multiparous cows and of treatment and parity for ≥2 disease events. Overconditioned (BCS ≥3.75) multiparous cows had reduced incidence of MF when fed TRT (TRT: 2 ± 1%, vs. CON: 13 ± 8%). We detected no treatment effects on RP, metritis, hyperketonemia, or PVD incidence. Cows fed TRT had lesser incidence of DA (1.7 ± 0.7% vs. 3.6 ± 1.6%) and tended to have lesser incidence of MAST compared with CON (1.8% ± 0.6% vs. 4.4 ± 1.4%). No treatment effect was detected on ≥1 disease events (TRT: 38 ± 7%, vs. CON: 42 ± 8%); however, multiparous cows on TRT were less likely to have ≥2 disease events than cows on CON (14 ± 4% vs. 23 ± 6%). Under commercial herd conditions, feeding prepartum diets with negative DCAD improved several measures of postpartum health.

Validation of a point-of-care handheld blood total calcium analyzer in postpartum dairy cows.

Our objective was to validate a point-of-care handheld blood total calcium analyzer (Ca meter, CM; TD-5220 Vet Ca2+, TaiDoc, New Taipei, Taiwan) to estimate circulating Ca concentrations in postpartum dairy cows. Whole blood was collected from 251 multiparous cows between 1 and 4 d in milk from 2 commercial dairy herds in Ontario, Canada. Blood total calcium concentration (tCa) was analyzed in whole blood, fresh plasma, and thawed plasma, and compared with tCa results from thawed serum analyzed in a diagnostic laboratory (using a Cobas Calcium Gen 2 kit, Roche Diagnostics, Indianapolis, IN) as the reference test (RT). Lin's concordance correlation coefficient (ßrho;) and Bland-Altman (B-A) plots were assessed to evaluate the agreement between the RT and CM results in each type of sample. Receiver operating characteristic curve analyses were used to describe the accuracy of each test against the categorized RT results (at a cut-point of ≤2.14 mmol/L). Samples where the meter gave a nonquantitative result ("high" or "low"; thawed plasma: 3/247; fresh plasma: 6/100; and whole blood: 20/98) were not included in the ßrho; and B-A analyses. Lin's correlation coefficients demonstrated poor agreement between tests (thawed plasma: ßrho; = 0.16; fresh plasma: ßrho; = 0.21; and whole blood: ßrho; = 0.23). Fresh plasma (using a cut-point of 2.55 mmol/L as measured on the CM) had the greatest diagnostic sensitivity (72%), specificity (86%), and accuracy (77%) for determining subclinical hypocalcemia, but that would still misclassify 23% of samples. In addition to substantial variability, the B-A plots revealed bias with changing concentrations of calcium. Because of low sensitivity on whole blood (58%) or thawed plasma (56%), measurement with the CM is not recommended on these types of samples. This rapid and low-cost meter was not sufficiently accurate to quantify blood Ca concentration, but when used with fresh plasma it might be useful as a screening tool for subclinical hypocalcemia.

The effect of prepartum negative dietary cation-anion difference and serum calcium concentration on blood neutrophil function in the transition period of healthy dairy cows.

Our objectives were to assess the effects of a diet with a negative dietary cation-anion difference (DCAD) before calving on phagocytosis (Pc) and oxidative burst (OB) function of circulating neutrophils, and to determine the associations of serum ionized (iCa) and total calcium (tCa) concentrations with Pc and OB in transition dairy cows. We hypothesized that multiparous cows fed a negative DCAD diet prepartum would have greater iCa and tCa, and thus improved Pc and OB. From 3 wk before expected parturition until calving, 38 healthy multiparous cows from 3 farms were assigned to negative DCAD treatment (TRT; -100 mEq/kg of diet dry matter; n = 21) or a control (CON; 95 mEq/kg of dry matter; n = 17) diet. Each farm was on one treatment or the other at a time, but all farms contributed cows to both groups. Urine pH was measured weekly and in TRT was 6.1 ± 0.8 with 80% of 50 samples <7 and 74% ≤ 6.5. Phagocytosis, OB, iCa, and tCa were measured at d -7, 1, and 4 relative to calving. Median fluorescence intensity for Pc (MFIP) and OB (MFIOB), and the shift of percentage of cells active for Pc (PPc) and OB (POB) were measured in isolated, stimulated neutrophils via flow cytometry. Outcomes were assessed with mixed linear regression models accounting for repeated measures. There were no differences between treatments in the 4 neutrophil function outcomes. Although MFIOB varied over time, there were no interactions of treatment with time for any outcome. Serum ionized and tCa did not differ between TRT and CON. The least squares means ± standard deviation for iCa were: d -7, 1.23 ± 0.12 vs. 1.21 ± 0.12; d 1, 1.07 ± 0.12 vs. 1.02 ± 0.12; d 4, 1.16 ± 0.12 vs. 1.17 ± 0.12 mmol/L for TRT and CON, respectively; and for tCa: d -7 2.39 ± 0.25 vs 2.44 ± 0.31; d 1, 2.01 ± 0.25 vs 1.97 ± 0.31; d 4, 2.33 ± 0.25 vs 2.32 ± 0.31 mmol/L, respectively. The proportion of blood samples with tCa <2.15mmol/L at d -7, 1 and 4 was 5, 76, and 13%, respectively, with no differences between TRT and CON. Correlations of iCa or tCa with each of the 4 polymorphonuclear leukocyte (PMN) function outcomes were weak (r < |0.3|). We did not observe the hypothesized differences in aspects of innate immunity in clinically healthy multiparous cows fed a negative DCAD. We underline that cows that experienced clinical disease were excluded from this study, which is important for interpretation of the results.