Effects of injectable trace minerals administered concurrently with a modified live virus vaccine on long-term protection against bovine viral diarrhea virus acute infection in dairy calves.

The objective was to evaluate the effects of injectable trace minerals (ITM) concurrent with modified-live virus (MLV) vaccination on protection from bovine viral diarrhea virus (BVDV) infection in dairy calves. In a previous study (Palomares et al., 2016), thirty dairy calves received two doses of a MLV vaccine subcutaneously (SC), concurrently with ITM (n = 15) or saline (n = 15), SC. Five months later, 20 of these calves received ITM (G1, n = 10) or saline (G2, n = 10) according to their previous groups and were challenged intranasally with BVDV2. Five unvaccinated calves were also challenged with BVDV2 (G3). Blood samples were collected on days 0 (BVDV challenge), 3, 5, 6, 7, 8, 9, 11, 14, 18, 21, 32 and 61 for leukocyte count, virus isolation and BVDV serum neutralizing antibodies (SNA). Mild-moderate clinical signs were observed in G3 after BVDV challenge. Group 1 showed lower sum health score and nasal score on d5 and fecal score on d8 compared to G2. Rectal temperature and leukocyte counts were not different between G1 and G2. In contrast, G3 calves had significant leukopenia and lymphopenia from d3 to d7 (P < .05) and higher rectal temperatures on d6 to d8, compared to values on d0 (P < .05). All unvaccinated calves became viremic, while viremia was not detected in G1 or G2. Average daily gain was not different between vaccinated groups, however, only G1 calves had significantly greater (P = .04) ADG compared to non-vaccinated calves during the first 14 days post challenge. Vaccinated calves treated or not with ITM were protected from BVDV2 infection five months post-vaccination.

Effects of injectable trace minerals on humoral and cell-mediated immune responses to Bovine viral diarrhea virus, Bovine herpes virus 1 and Bovine respiratory syncytial virus following administration of a modified-live virus vaccine in dairy calves.

Our objective was to evaluate the effect of an injectable trace mineral (ITM) supplement containing zinc, manganese, selenium, and copper on the humoral and cell mediated immune (CMI) responses to vaccine antigens in dairy calves receiving a modified-live viral (MLV) vaccine containing BVDV, BHV1, PI3V and BRSV. A total of 30 dairy calves (3.5 months of age) were administered a priming dose of the MLV vaccine containing BHV1, BVDV1 & 2, BRSV, PI3V, and an attenuated-live Mannheimia-Pasteurella bacterin subcutaneously (SQ). Calves were randomly assigned to 1 of 2 groups: (1) administration of ITM SQ (ITM, n=15) or (2) injection of sterile saline SQ (Control; n=15). Three weeks later, calves received a booster of the same vaccine combination SQ, and a second administration of ITM, or sterile saline, according to the treatment group. Blood samples were collected on days 0, 7, 14, 21, 28, 42, 56, and 90 post-vaccination for determination of antibody titer, viral recall antigen-induced IFN-γ production, and viral antigen-induced proliferation by peripheral blood mononuclear cells (PBMC). Administration of ITM concurrently with MLV vaccination resulted in higher antibody titers to BVDV1 on day 28 after priming vaccination compared to the control group (P=0.03). Calves treated with ITM showed an earlier enhancement in PBMC proliferation to BVDV1 following vaccination compared to the control group. Proliferation of PBMC after BVDV stimulation tended to be higher on day 14 after priming vaccination in calves treated with ITM than in the control group (P=0.08). Calves that received ITM showed higher PBMC proliferation to BRSV stimulation on day 7 after priming vaccination compared to the control group (P=0.01). Moreover, calves in the ITM group also had an enhanced production IFN-γ by PBMC after stimulation with BRSV on day 21 after priming vaccination compared to day 0 (P<0.01). In conclusion, administration of ITM concurrently with MLV vaccination in dairy calves resulted in increased antibody titer to BVDV1, and greater PBMC proliferation to BVDV1 and BRSV recall stimulation compared to the control group, suggesting that ITM might represent a promising tool to enhance the humoral and CMI responses to MLV vaccines in cattle.

Prevalence of bacteremia in dairy cattle with acute puerperal metritis.

BACKGROUND: Acute puerperal metritis (APM) affects 30% of postpartum dairy cattle. Bacteremia negatively impacts survival in cattle with coliform mastitis. However, the prevalence of bacteremia in dairy cattle with APM is unknown. HYPOTHESIS: Bacteremia is detectable in a large proportion of cattle with APM. ANIMALS: Seventeen dairy cows with APM and 17 healthy dairy cattle. METHODS: Prospective case-control study. Cases were identified by daily monitoring of cattle in the first 10 days after calving. Controls were matched to cases by parity and days in milk. Cows were examined at the time of identification of APM. A complete blood count, serum biochemical analysis, and bacteriologic culture of blood and lochial fluid were performed on each animal at the time of diagnosis. The same samples were collected from healthy herdmates of a similar parity and days in milk. Blood culture results and clinicopathologic variables were compared between groups. Conditional logistic regression was used to evaluate factors associated with APM, whereas multivariate logistic regression was used to evaluate factors associated with bacteremia. RESULTS: Bacteremia occurred in 53% (9/17) of cattle with APM and 53% (8/15) controls. Bacillus spp. was the organism most commonly isolated from the bloodstream in cattle of both groups. Bacteremic cattle in both groups were significantly less likely to have basophils in the peripheral circulation (P = .02) and more likely to have higher serum globulin concentrations (P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Bacteremia is a common occurrence in postpartum dairy cattle. Further study is warranted to investigate the modes by which bacteria colonize the bloodstream in this population of animals and the importance of bacteremia on health and productivity of affected animals.

Comparative efficacy of enrofloxacin and tulathromycin for treatment of preweaning respiratory disease in dairy heifers.

Preweaning respiratory disease continues to have a substantial effect on the current and future productivity of dairy replacement animals. Establishing an effective treatment plan for the preweaned calf may have a significant effect on well-being and lifetime productivity by limiting any early development of chronic disease. The primary objective of this study was to examine the efficacy of treatment with tulathromycin (TUL) or enrofloxacin (ENR) on the risk of re-treatment, with a secondary objective of investigating the effect of disease and subsequent treatment choice on average daily gain (ADG). A total of 1,141 Holstein heifers from 4 farms were observed and systematically scored for evidence of respiratory disease from birth through weaning or the time of death. At the time of diagnosis, calves were randomly and blindly allocated into 2 treatment groups. The overall incidence of respiratory disease was 60.9%. In the univariable analysis, the incidence of re-treatment between 7 and 10d of initial therapy for calves treated with ENR was greater than that in calves treated with TUL (27.6 vs. 21.2%). After adjusting for farm ID, clinical score at first treatment, and weight at first treatment, the odds of re-treatment were 1.5 times higher for calves treated with ENR than with TUL. The percentage of calves that required more than one re-treatment was higher for calves that received ENR compared with those that received TUL (9.3 vs. 4.1%). We observed no difference in ADG between calves treated with ENR or TUL, and no difference in ADG between calves that were treated for respiratory disease and those that were not treated for respiratory disease. Appropriate drug therapy for preweaning respiratory disease may have an important role in reducing the odds of re-treatment during the preweaning period.

Mycoplasma bovis infections in cattle.

Mycoplasma bovis is a pathogen causing respiratory disease, otitis media, arthritis, mastitis, and a variety of other diseases in cattle worldwide. It is increasingly recognized by the veterinary and livestock communities as having an important impact on the health, welfare, and productivity of dairy and beef cattle. M. bovis diseases can be difficult to diagnose and control because of inconsistent disease expression and response to treatments and vaccines, and large gaps in our understanding of the epidemiology and pathophysiology of these diseases. There are limited data on which to base evidence-based decisions for treatment and control, and the literature contains differing clinical biases and opinions. This document is intended for veterinarians dealing with cattle and is focused on the cattle production systems of North America. The goal of the consensus statement panel was to encourage an evidence-based approach to M. bovis problems. The scientific literature was critically reviewed, including peer-reviewed journal articles and reviews obtained by database searches using the terms "Mycoplasma bovis" or "mycoplasma + cattle." Where other data were lacking, conference proceedings were reviewed as a source of expert opinion.

The effect of various Mycoplasma bovis isolates on bovine leukocyte responses.

Mycoplasma bovis (M. bovis) contributes to a number of clinical syndromes in cattle; in particular, chronic pneumonia that is poorly responsive to therapy has been increasingly recognized as an important cause of morbidity, mortality, and financial loss. M. bovis impairs host immune function, but little is known about whether field isolates vary significantly in their effect on immune function. This research tested the hypothesis that different field isolates vary in their ability to suppress cellular metabolism and cellular production of radical oxygen species (ROS) by bovine leukocytes. Total blood leukocytes from 6 cattle were exposed to six field isolates, two diagnostic lab isolates, and two high passage laboratory isolates of M. bovis, and ROS production was measured by oxidation of dihydrorhodamine 123 (DHR-123). Cellular metabolism was measured by reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Significant differences in the response to some field isolates were identified. Three field isolates and both diagnostic lab isolates significantly decreased ROS production by leukocytes from multiple cattle, while the high pass laboratory isolates did not. In contrast, MTT reduction was not significantly impaired by any of the M. bovis strains tested. M. bovis impairs ROS production by bovine leukocytes; the magnitude of the effect appears to be isolate-dependent, and is not related to a general impairment of cellular metabolism. Chronic M. bovis infection in some cattle may be related to impaired ability of leukocytes to produce ROS when exposed to M. bovis.

Evaluation of multiple immune parameters after vaccination with modified live or killed bovine viral diarrhea virus vaccines.

The development of immunity to vaccine antigen was examined using three prime/boost strategies and the progression of immune activities was evaluated over the course of 8 weeks. Calves were vaccinated and multiple immune parameters were evaluated using several methods to assess humoral or cellular immunity from the same samples in parallel. The three vaccination protocols used were a killed vaccine followed by a killed boost (killed/killed), MLV vaccine and boost (MLV/MLV), or a MLV vaccine and killed boost (MLV/killed). All the vaccines used included modified live IBR/PI3 viruses to make the bystander context as similar as possible. The Singer strain of BVDV was used as the source antigen in the killed vaccine, and the NADL strain of BVDV was used in the MLV vaccine. Controls received a vaccine containing only MLV IBR/PI3. The assessment panel measured SN titers, as well as lymphocyte proliferation, cytokine mRNA expression, intracellular cytokine production, and released IFN-gamma after in vitro stimulation with three strains of BVDV virus. MLV/MLV and MLV/killed groups developed significant SN titers to the type 1 BVDV virus strains, Singer and NADL, and low crossover titers were also seen to the type 2 strain, 890 over the evaluation period. These two groups showed significant proliferation in response to the NADL virus as compared to controls. Multiple immune assessments were conducted simultaneously to attempt to provide a broader, more in depth evaluation of immune response to these BVDV vaccination protocols. We observed that the correlation among most of the assays conducted were weak; the correlation between SN titers and cellular proliferation assays demonstrated a moderate correlation.

Bovine respiratory syncytial virus-specific IgE is associated with interleukin-2 and -4, and interferon-gamma expression in pulmonary lymph of experimentally infected calves.

OBJECTIVE: To study the local immune response of calves to bovine respiratory syncytial virus (BRSV) infection with emphasis on IgE production and cytokine gene expression in pulmonary lymph. ANIMALS: Twelve 6- to 8-week-old Holstein bull calves. Six similar control calves were mock infected to obtain control data. PROCEDURE: Lymphatic cannulation surgery was performed on 12 calves to create a long-term thoracic lymph fistula draining to the exterior. Cannulated calves were exposed to virulent BRSV by aerosol. Lymph fluid collected daily was assayed for BRSV and isotype-specific IgE antibody, total IgG, IgA, IgM, and protein concentrations. Interleukin-4 (IL-4), interleukin-2 (IL-2), and interferon-gamma were semi-quantitated by reverse transcription-polymerase chain reaction (RT-PCR). Cell counts and fluorescence-activated cell scanner (FACSCAN) analysis of T-cell subsets were performed on lymph cells. RESULTS: Calves had clinical signs of respiratory tract disease during days 5 to 10 after infection and shed virus. Bovine respiratory syncytial virus-specific IgE in infected calves was significantly increased over baseline on day 9 after infection. Mean virus-specific IgE concentrations strongly correlated with increases in severity of clinical disease (r = 0.903). Expression of IL-2, IL-4, and interferon-gamma was variably present in infected and control calves, with IL-4 expression most consistent during early infection. CONCLUSIONS AND CLINICAL RELEVANCE: Infection with BRSV was associated with production of BRSV-specific IgE, and IL-4 message was commonly found in lymph cells of infected calves. This finding supports the concept that BRSV-induced pathophysiology involves a T helper cell type-2 response. Effective therapeutic and prophylactic strategies could, therefore, be developed using immunomodulation to shift the immune response more toward a T helper cell type-1 response.

Evaluation of severe disease induced by aerosol inoculation of calves with bovine respiratory syncytial virus.

OBJECTIVE: To develop a model of bovine respiratory syncytial virus (BRSV) infection that induces severe disease similar to that seen in some cattle with naturally acquired BRSV infection. ANIMALS: 25 male Holstein calves, 8 to 16 weeks old. PROCEDURE: 17 calves were given a low-passage field isolate of BRSV by aerosolization; 8 control calves were given supernatant from noninfected cell culture. Disease was characterized by evaluating clinical signs, virus isolation and pulmonary function tests, and results of blood gas analysis, gross and histologic postmortem examination, and microbiologic testing. RESULTS: Cumulative incidence of cough, harsh lung sounds, adventitious sounds, and dyspnea and increases in rectal temperature and respiratory rate were significantly greater in infected calves. Three infected calves developed extreme respiratory distress and were euthanatized 7 days after inoculation. Virus was isolated from nasal swab specimens from all infected calves but not from mock infected calves. On day 7 after inoculation, mean PaO2 and PaCO2 were significantly lower, and pulmonary resistance was significantly higher, in infected calves. During necropsy, infected calves had varying degrees of necrotizing and proliferative bronchiolitis and alveolitis with syncytial formation. The 3 calves euthanatized on day 7 had emphysematous bullae in the caudal lung lobes; 1 had unilateral pneumothorax. CONCLUSION AND CLINICAL RELEVANCE: Severe disease similar to that seen in some cattle with naturally acquired BRSV infection can be induced in calves with a single aerosol exposure of a low-passage clinical isolate of BRSV. Our model will be useful for studying the pathogenesis of BRSV infection and for evaluating vaccines and therapeutics.

Interferon gamma production during bovine respiratory syncytial virus (BRSV) infection is diminished in calves vaccinated with formalin-inactivated BRSV.

Formalin-inactivated respiratory syncytial virus (FI-RSV) vaccination has been associated with severe disease in humans. Research in mice suggests that FI-RSV may prime for decreased interferon gamma (IFN-gamma) production at subsequent infection. Interferon-gamma production by peripheral blood mononuclear cells (PBMC) was measured following challenge of calves vaccinated with FI-BRSV to determine whether a similar mechanism is operative in a host naturally susceptible to RSV. Eight-week old male Holstein calves were administered FI-BRSV and mock challenge (V/M, n = 6); mock vaccination and BRSV challenge (M/C, n = 6) or FI-BRSV and BRSV challenge (V/C, n = 7). Vaccine was administered twice at a 2-week interval; challenge followed one month later. On days 0, 5 and 10 postchallenge (PC), PBMC were stimulated in vitro for 24 h with live BRSV, concanavalin A (positive control) or spent media (negative control). Supernatants were assayed for IFN-gamma using ELISA. Interferon-gamma production by BRSV-stimulated PBMC was increased in M/C and V/C calves as compared to V/M calves on day 5 PC (p < 0.015); and increased in M/C calves compared to V/C and V/M calves on day 10 PC (p < 0.015). Over time postchallenge, a significant increase in IFN-gamma production by BRSV-stimulated PBMC was seen in M/C calves (p < 0.025) but not in V/C calves. FI-BRSV vaccination of calves led to diminished IFN-gamma production postchallenge. Decreased IFN-gamma production may have contributed to impaired viral clearance and enhanced disease in FI-BRSV vaccinated calves.

A bovine model of vaccine enhanced respiratory syncytial virus pathophysiology.

A critical issue has been the observation that vaccination of children with a formalin-inactivated respiratory syncytial virus (RSV) vaccine is associated with disease enhancement. We have taken advantage of bovine RSV and our experience with this disease in calves to develop a natural model that parallels human disease. Using formalin-inactivated bovine RSV vaccine calves were either sham-vaccinated/infected, vaccinated/infected, or vaccinated/sham-infected and their clinical signs, pulmonary function, and histological lung lesions quantitatively scored. Interestingly there was significantly greater disease in vaccinated/infected calves and histological lesions in calves were similar to those of affected children. Finally, we note that vaccination did not induce neutralizing antibodies, but IgG antibodies were detected by ELISA. Our model of RSV enhanced disease is important because it provides quantifiable evidence of disease severity that can be applied to evaluate the mechanisms of immunopathology and the safety of candidate RSV vaccines.

Aortic and iliac artery thrombosis in calves: nine cases (1974-1993).

OBJECTIVE: To identify common clinical and diagnostic features of calves with aortic or iliac artery thrombosis that might aid in antemortem diagnosis of this condition. DESIGN: Retrospective case series. ANIMALS: 9 calves < or = 6 months old in which aortic or iliac artery thrombosis was confirmed at necropsy. RESULTS: All calves had an acute onset of paresis or flaccid paralysis of 1 or both hind limbs. Affected limbs were hypothermic and had diminished spinal reflexes and diminished pulse pressures. Diagnosis was definitively established in 2 calves by use of angiography. All 9 calves died or were euthanatized. CLINICAL IMPLICATIONS: This condition is rare and could be mistaken for more common diseases of young cattle, such as traumatic injury of the axial or appendicular skeleton, vertebral osteomyelitis, nutritional muscular dystrophy associated with vitamin E or selenium deficiency, injury to the sciatic or femoral nerves, or clostridial myositis.