Assessment of pain associated with bovine respiratory disease and its mitigation with flunixin meglumine in cattle with induced bacterial pneumonia.

Pleuritic chest pain from bacterial pneumonia is often reported in human medicine. However, studies investigating pain associated with bovine respiratory disease (BRD) are lacking. The objectives of this study were to assess if bacterial pneumonia elicits a pain response in calves with experimentally induced BRD and to determine the analgesic effects of transdermally administered flunixin. A total of 26 calves, 6-7 mo of age, with no history of BRD were enrolled into one of three treatment groups: 1) experimentally induced BRD + transdermal flunixin at 3.3 mg/kg twice, 24 h apart (BRD + FTD); 2) experimentally induced BRD + placebo (BRD + PLBO); and 3) sham induction + placebo (CNTL + PLBO). Calves induced with BRD were inoculated with Mannheimia haemolytica via bronchoalveolar lavage. Outcomes were collected from -48 to 192 h post-treatment and included serum cortisol, infrared thermography, mechanical nociceptive threshold, substance P, kinematic gait analysis, visual analog scale (VAS), clinical illness score, computerized lung score, average activity and rumination level, prostaglandin E2 metabolite, plasma serum amyloid A, and rectal temperature. Outcomes were evaluated using either a generalized logistic mixed model for categorical variables or a generalized linear mixed model for continuous variables. Right front force differed by treatment (P = 0.01). The BRD + PLBO had lower mean force applied to the right front limb (85.5 kg) compared with BRD + FTD (96.5 kg; P < 0.01). Average VAS differed by a treatment by time interaction (P = 0.01). The VAS scores differed for BRD + PLBO at -48 (3.49 mm) compared with 168 and 192 h (13.49 and 13.64 mm, respectively) (P < 0.01). Activity for BRD + PLBO was higher at -48 h (27 min/h) compared with 48, 72, 120, and 168 h (≤ 22.24 min/h; P < 0.01). Activity differed by a treatment by time interaction (P = 0.01). Activity for BRD + FTD was higher at -48 and 0 h (28.2 and 28.2 min/h, respectively) compared to 48, 72, 96, and 168 h (≤23.7 min/h; P < 0.01). Results show a combination of reduced activity levels, decreased force on the right front limb, and increased VAS pain scores all support that bacterial pneumonia in cattle is painful. Differences in right front force indicate that flunixin transdermal may attenuate certain pain biomarkers in cattle with BRD. These findings suggest that BRD is painful and analgesic drugs may improve the humane aspects of care for cattle with BRD.

Assessment of bovine respiratory disease progression in calves challenged with bovine herpesvirus 1 and Mannheimia haemolytica using point-of-care and laboratory-based blood leukocyte differential assays.

Blood leukocyte differentials can be useful for understanding changes associated with bovine respiratory disease (BRD) progression. By improving turnaround time, point-of-care leukocyte differential assays (PCLD) may provide logistical advantages to laboratory-based assays. Our objective was to assess BRD progression in steers challenged with bovine herpesvirus 1 and Mannheimia haemolytica using point-of-care and laboratory-based blood leukocyte differentials. Thirty Holstein steers (average body weight of 211 kg + 2.4 kg) were inoculated intranasally on day 0 with bovine herpesvirus 1 and intrabronchially on day 6 with Mannheimia haemolytica. Blood leukocytes differentials were measured using both assays from study days 0 to 13. Linear mixed models were fitted to evaluate the associations between: (1) the type of assay (laboratory-based or PCLD) with respect to leukocyte, lymphocyte, and neutrophil concentrations; (2) study day with cell concentrations; and (3) cell concentrations with lung consolidation measured at necropsy. Point-of-care leukocyte, lymphocyte, and neutrophil concentrations were significantly associated (P < 0.05) with the respective cell concentrations obtained from the laboratory-based leukocyte differential. Cell concentrations reported by both assays differed significantly (P < 0.05) over time, indicating shifts from healthy to viral and bacterial disease states. Lymphocyte concentrations, lymphocyte/neutrophil ratios obtained from both assays, and band neutrophil concentrations from the laboratory-based assay were significantly associated (P < 0.05) with lung consolidation, enhancing assessments of disease severity. The PCLD may be a useful alternative to assess BRD progression when laboratory-based leukocyte differentials are impractical.

Comparison of a traditional bovine respiratory disease control regimen with a targeted program based upon individualized risk predictions generated by the Whisper On Arrival technology.

The study objective was to determine if cattle health and performance comparing a targeted bovine respiratory disease (BRD) control program based on individualized risk prediction generated by a novel technology (Whisper On Arrival) was superior to a negative control (no metaphylaxis) yet no different than a positive control (conventional BRD control; 100% application). Across four study sites, auction market-derived beef calves were randomly allocated to one of four BRD control treatment groups: 1) Negative control (Saline), 2) Positive control (Tildipirosin [TIL] to 100% of the group), 3) Whisper-high (±TIL based on conservative algorithm threshold), and 4) Whisper-low (±TIL based on aggressive algorithm threshold). Within either Whisper On Arrival group, only calves predicted to be above the algorithm threshold by the technology (determined a priori) were administered TIL leaving the remainder untreated. Cattle were followed to either a short-term timepoint (50 or 60 d; health outcomes, all sites; feed performance outcomes, two sites) or to closeout (two sites). Data were analyzed as a completely randomized block design separately at each site. Across all sites, BRD control antibiotic use was reduced by 11% to 43% between the two Whisper On Arrival treatment groups compared to the positive control. The positive control and both Whisper On Arrival groups reduced (P ≤ 0.05) BRD morbidity compared to negative controls at both the short-term timepoint at three of the four sites and at closeout at one of two sites. The positive control and both Whisper-managed groups had improved (P ≤ 0.05) average daily gain (ADG), dry-matter intake (DMI), and feed efficiency compared to negative controls at the short-term timepoint at one of two sites. At closeout, the positive control and both Whisper-managed groups improved (P ≤ 0.05) ADG (deads-in) compared to the negative control at one of the two sites. At one of two sites, the positive control and the Whisper-high group displayed an improvement (P ≤ 0.05) in hot carcass weight compared to the negative control. The Whisper On Arrival technology maintained the benefits of a conventional BRD control program yet reduced BRD control antibiotic use by 11% to 43%. This technology maintained the benefits of a conventional BRD control program while reducing antibiotic costs to the producer and supporting judicious antimicrobial use.

Performance of multiple diagnostic methods in assessing the progression of bovine respiratory disease in calves challenged with infectious bovine rhinotracheitis virus and Mannheimia haemolytica1.

The objective of this study was to evaluate the diagnostic performance of chute-side diagnostic methods for detecting physiological and pathological changes as indicators of early bovine respiratory disease (BRD) in calves experimentally inoculated with infectious bovine rhinotracheitis virus (IBR) and Mannheimia haemolytica (Mh). A challenge study was performed over 14 d in 30 Holstein steers [average weight (±SEM) = 211 kilograms (kg) ± 2.4 kg] inoculated on day 0 with IBR and on day 6 with Mh. Diagnostic methods included clinical illness scores (CIS), lung auscultation using a computer-aided stethoscope (CAS), rectal temperature, facial thermography, pulse oximetry, and bilateral thoracic ultrasonography. Animals were randomized into 1 of 5 necropsy days (days 6, 7, 9, 11, and 13) when the percentage of lung consolidation was estimated. The effect of study day on the results of the diagnostic methods and associations between each diagnostic method's values with lung consolidation measured at necropsy were determined with mixed models. Values for all diagnostic methods differed significantly (P < 0.01) by day. During the IBR phase (days 0 to 6) calves had "normal" to "moderate" CIS, whereas during the Mh phase (days 6.5 to 13) scores were predominantly "severe" to "moribund." Similarly, CAS scores were "normal" and "mild acute" during the IBR phase and "mild acute" to "moderate acute" after the Mh challenge. Oxygen saturation did not differ significantly between days 0, 1, 2, 4, and 6; however, significantly decreased 12 h after inoculation with Mh (P < 0.05). Mean lung consolidation between animal's right and left side recorded by ultrasound was 0.13% (±0.07) before the inoculation with Mh. However, during the Mh phase, mean consolidation increased significantly over time (P < 0.05). The percentage of lung consolidation at necropsy ranged from 1.7% (±0.82) on day 6 to 55.4% (±7.49) on day 10. Clinical illness scores, rectal temperature, facial thermography, oxygen saturation, and ultrasonography were significantly associated (P < 0.05) with lung consolidation at necropsy. In addition, there was a significant trend (P = 0.07) between CAS and lung consolidation scores at necropsy. These chute-side diagnostic methods are useful for detecting disease progression on animals with early stages of BRD.

A Randomized Trial to Assess the Effect of Fluoroquinolone Metaphylaxis on the Fecal Prevalence and Quinolone Susceptibilities of Salmonella and Campylobacter in Feedlot Cattle.

The study objective was to determine effects of fluoroquinolone metaphylaxis on fecal prevalence of Salmonella and Campylobacter and fecal prevalence of quinolone-resistant Salmonella and Campylobacter in feedlot cattle. On Day 0, cattle (n = 288) at risk for bovine respiratory disease (BRD) were randomly assigned to either a nontreated control pen (12 pens) or a fluoroquinolone-treated (enrofloxacin; Baytril® 100) pen (12 pens). Rectal fecal samples were collected from cattle on days 0, 7, 14, 21, and 28. Feces were cultured for Salmonella enterica and Campylobacter spp. using enrichment and selective isolation methods, and confirmed by serology and PCR. Susceptibilities to nalidixic acid and ciprofloxacin were determined using microbroth dilution methods. Data analyses were performed using linear mixed models. Overall, Salmonella sp. and Campylobacter spp. were recovered from 10.2% (139/1,364) and 12.4% (170/1,364) of the fecal samples, respectively. Campylobacter species included hyointestinalis, jejuni, and coli. Neither Salmonella sp. nor Campylobacter spp. prevalence was significantly impacted by fluoroquinolone treatment (p = 0.80, p = 0.61, respectively). However, Salmonella prevalence differed between study weeks (p < 0.01) with prevalence decreasing over time. Before treatment, 98.9% (91/92) of Salmonella isolates were susceptible to nalidixic acid and ciprofloxacin. All Salmonella recovered posttreatment (n = 43) were susceptible to both antimicrobials. The majority of Campylobacter spp. recovered before treatment were resistant to nalidixic acid (23/35; 65.7%) and ciprofloxacin (21/35; 60.0%). There was no significant treatment by week interaction (p = 0.85) or treatment effects (p = 0.61) on the posttreatment prevalence of Campylobacter resistance. There was, however, a significant week effect (p = 0.05), with Campylobacter resistance prevalence decreasing over time. In this 28-day study, we found no evidence that a fluoroquinolone used for metaphylaxis significantly impacts fecal prevalence of Salmonella sp. or Campylobacter spp. or the fecal prevalence of nalidixic acid or ciprofloxacin resistance.

A simulation model to quantify the value of implementing whole-herd Bovine viral diarrhea virus testing strategies in beef cow-calf herds.

Although numerous diagnostic tests are available to identify cattle persistently infected (PI) with Bovine viral diarrhea virus (BVDV) in cow-calf herds, data are sparse when evaluating the economic viability of individual tests or diagnostic strategies. Multiple factors influence BVDV testing in determining if testing should be performed and which strategy to use. A stochastic model was constructed to estimate the value of implementing various whole-herd BVDV cow-calf testing protocols. Three common BVDV tests (immunohistochemistry, antigen-capture enzyme-linked immunosorbent assay, and polymerase chain reaction) performed on skin tissue were evaluated as single- or two-test strategies. The estimated testing value was calculated for each strategy at 3 herd sizes that reflect typical farm sizes in the United States (50, 100, and 500 cows) and 3 probabilities of BVDV-positive herd status (0.077, 0.19, 0.47) based upon the literature. The economic value of testing was the difference in estimated gross revenue between simulated cow-calf herds that either did or did not apply the specific testing strategy. Beneficial economic outcomes were more frequently observed when the probability of a herd being BVDV positive was 0.47. Although the relative value ranking of many testing strategies varied by each scenario, the two-test strategy composed of immunohistochemistry had the highest estimated value in all but one herd size-herd prevalence permutation. These data indicate that the estimated value of applying BVDV whole-herd testing strategies is influenced by the selected strategy, herd size, and the probability of herd BVDV-positive status; therefore, these factors should be considered when designing optimum testing strategies for cow-calf herds.

Comparison of iatrogenic transmission of Anaplasma marginale in Holstein steers via needle and needle-free injection techniques.

OBJECTIVE: To compare iatrogenic transmission of Anaplasma marginale during sham vaccination between needle and needle-free injection techniques. ANIMALS: 26 Holstein steers confirmed negative for anaplasmosis by use of a competitive ELISA (cELISA) and an A marginale-specific reverse transcription (RT)-PCR assay. PROCEDURES: An isolate of A marginale was propagated to a circulating parasitemia of 2.0% in a splenectomized steer. Sham vaccination was performed in the left cervical muscles of the splenectomized parasitemic steer with a hypodermic needle fitted to a multiple-dose syringe. The same needle and syringe were used to sham vaccinate a naïve steer. This 2-step procedure was repeated until 10 naïve steers (group ND) were injected. Similarly, sham vaccination of the left cervical muscles of the splenectomized parasitemic steer and another group of 10 naïve steers (group NF) was performed by use of a needle-free injection system. Five control steers were not injected. Disease status was evaluated twice weekly for 61 days by use of light microscopy, a cELISA, and an A marginale-specific RT-PCR assay. RESULTS: Iatrogenic transmission was detected in 6 of 10 steers in group ND. Disease status did not change in the NF or control steers. Sensitivity of light microscopy, cELISA, and RT-PCR assay was 100% on days 41, 41, and 20 after sham vaccination, respectively; however, only cELISA and RT-PCR assay sustained a sensitivity of 100% thereafter. CONCLUSIONS AND CLINICAL RELEVANCE: Needle-free injection was superior to needle injection for the control of iatrogenic transmission of A marginale.

Metaphylactic antimicrobial therapy for bovine respiratory disease in stocker and feedlot cattle.

This article provides an overview of implementing metaphylactic antimicrobial protocols to certain classes of cattle on arrival to stocker and feedlot production systems. The goal of this management practice is to reduce the negative health and performance effects induced by bovine respiratory disease (BRD). This article emphasizes the multiple factors that influence the decision for mass medication, including weight (age) of the cattle, distance traveled, environmental conditions, previous health history, visual inspection of the cattle at arrival, and prediction of the risk of disease. Current data suggest that metaphylactic programs significantly reduce negative health effects and improve feed performance that can be observed in cattle stricken with BRD.

The efficacy of three chlortetracycline regimens in the treatment of persistent Anaplasma marginale infection.

Chemosterilization is reported in cattle fed chlortetracycline hydrochloride (CTC) at dosages ranging from 1.1mg/kg for 120 days to 11 mg/kg for 30-60 days. The relationship between plasma CTC drug concentration and carrier clearance has not been described. Chronic carrier status was established in 21 steers with a Virginia isolate of Anaplasma marginale and confirmed by cELISA and an A. marginale-specific RT-PCR. Four negative, splenectomized steers served as active disease transmission sentinels. Steers were randomized to receive 4.4 mg/kg/day (LD); 11 mg/kg/day (MD); or 22 mg/kg/day (HD) of oral chlortetracycline; or placebo (CONTROL) for 80 days. The LD, MD and HD treatment groups consisted of 5 infected steers and 1 splenectomized steer; CONTROL group had six infected steers and 1 splenectomized steer. The daily treatments and ration were divided equally and fed twice daily. Blood samples were collected semi-weekly for determining plasma drug concentration by ultrahigh performance liquid chromatography-mass spectrometry/mass spectrometry method and assessment of disease status by both cELISA and RT-PCR. Mean (CV%) chlortetracycline plasma drug concentrations in the LD, MD, and HD groups were 85.3 (28%), 214.5 (32%) and 518.9 (40%)ng/mL during days 4 through 53 of treatment. A negative RT-PCR assay result was confirmed in all CTC-treated groups within 49 days of treatment; however, cELISA required an additional 49 to 88 days before similar results. Subinoculation of splenectomized steers confirmed chemosterilization. These results are important for influencing future chemosterilization strategies and impacting free trade policy among countries and regions of contrasting endemicity.