Prevention Of Bovine Respiratory Disease Research Articles

Bovine respiratory disease (BRD) in postweaning calves with different prevention strategies and the impact on performance and health status

Bovine respiratory disease (BRD) is one of the most common causes of morbidity and mortality in bovine calves, especially around the weaning period, when the calves are usually moved from individual to group housing. BRD has negative perfor­mance and economic consequences that extend well beyond the actual event. Therefore, we aimed to compare BRD morbid­ity, mortality and growth in dairy and dairy beef cross-bred calves during the first commingle groups using 2 different BRD prevention strategies. We hypothesized that one or both pre­vention strategies would reduce BRD morbidity and mortality, resulting in better health status and performance in calves.

Serological Profile for Major Respiratory Viruses in Unvaccinated Cows from High-Yielding Dairy Herds.

This study aims to determine the serological profile of high-yielding dairy cows for four main viruses (bovine alphaherpesvirus 1 (BoAHV1), bovine viral diarrhea virus (BVDV), bovine parainfluenza virus 3 (BPIV3), and bovine respiratory syncytial virus (BRSV)) related to bovine respiratory disease (BRD) in cattle herds worldwide. In this survey, 497 blood serum samples were collected from non-vaccinated dairy cows without clinical respiratory signs in 39 herds in the central-eastern mesoregion of Paraná State, South Brazil. The presence of neutralizing antibodies was determined by virus neutralization (VN) tests. VN antibodies against BoAHV1, BVDV, BPIV3, and BRSV were detected in 355 (71.4%), 280 (56.3%), 481 (96.8%), and 315 (63.4%) serum samples, respectively. The frequencies of seropositive herds for BoAHV1, BVDV, BPIV3, and BRSV were 79.5 (n = 31), 82.0 (n = 32), 100 (n = 39), and 84.6% (n = 33), respectively. The frequencies of seropositive cows varied according to the type of herd management and the number of cows in the herd. The detection of VN antibodies in unvaccinated dairy cattle herds demonstrated the endemic circulation of the four viruses in the herds evaluated. For BRD prevention, it is recommended to implement a vaccination program for cows that provides passive immunity in calves and active immunity in cows.

Antimicrobial Activities of α-Helix and β-Sheet Peptides against the Major Bovine Respiratory Disease Agent, Mannheimia haemolytica.

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in cattle raised in North America. At the feedlot, cattle are subject to metaphylactic treatment with macrolides to prevent BRD, a practice that may promote antimicrobial resistance and has resulted in an urgent need for novel strategies. Mannheimia haemolytica is one of the major bacterial agents of BRD. The inhibitory effects of two amphipathic, α-helical (PRW4, WRL3) and one β-sheet (WK2) antimicrobial peptides were evaluated against multidrug-resistant (MDR) M. haemolytica isolated from Alberta feedlots. WK2 was not cytotoxic against bovine turbinate (BT) cells by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. All three peptides inhibited M. haemolytica, with WK2 being the most efficacious against multiple isolates. At 8-16 µg/mL, WK2 was bactericidal against Mh 330 in broth, and at 32 µg/mL in the presence of BT cells, it reduced the population by 3 logs CFU/mL without causing cytotoxic effects. The membrane integrity of Mh 330 was examined using NPN (1-N-phenylnaphthylamine) and ONPG (o-Nitrophenyl β-D-galactopyranoside), with both the inner and outer membranes being compromised. Thus, WK2 may be a viable alternative to the use of macrolides as part of BRD prevention and treatment strategies.

Comparative effectiveness of intranasal and parenteral vaccines for prevention of bovine respiratory disease in feedlot heifers

Comparative effectiveness of intranasal and parenteral vaccines for prevention of bovine respiratory disease in feedlot heifers

Effect of on-arrival bovine respiratory disease vaccination on ultrasound-confirmed pneumonia and production parameters in male dairy calves: A randomized clinical trial

The high degree of commingling and accumulation of stressors during and after transport makes prevention of bovine respiratory disease (BRD) extremely challenging in the veal and dairy beef industry. Upon arrival, vaccination for agents involved in BRD is practically most achievable, but its efficacy under such conditions in dairy veal calves is unknown. Given the high prevalence of subclinical pneumonia in these settings, the primary objective of the present study was to determine the effect of 2 vaccination protocols administered upon arrival against bovine respiratory syncytial virus (BRSV), bovine parainfluenza type 3 virus (BPI-3), and Mannheimia haemolytica on clinical BRD and lung ultrasonographic findings in dairy veal calves. In addition, the effects of vaccination on average daily live weight gain and cold carcass weight were determined. In this randomized clinical trial, 443 male dairy calves were assigned to one of 3 groups: a negative, placebo-controlled group (n = 151), a vaccination group with 2 subcutaneous injections 4 wk apart with an inactivated vaccine containing BRSV, BPI-3, and M. haemolytica (parenteral [PE] group; n = 149) and a second vaccination group receiving an intranasal live-attenuated vaccine containing BRSV and BPI-3 and 2 subcutaneous vaccinations with the same inactivated vaccine as the PE vaccination group (intranasal-parenteral [IN-PE] group; n = 143). Clinical scoring and quick thoracic ultrasonography (qTUS) were performed on all calves on arrival (wk 0), at the peak of respiratory disease (outbreak; wk 1), at the end of the first antimicrobial group treatment (wk 3), and at a long-term evaluation point (wk 10). Culture and nanopore sequencing on nonendoscopic bronchoalveolar lavage (nBAL) samples were used to identify pathogens involved in the outbreak. Upon arrival, 15.1% of the calves had lung consolidation ≥1cm and incidence quickly rose to 42.8% during the outbreak. In both the PE and IN-PE group, the odds of pneumonia in wk 10 were reduced by 62% (odds ratio [OR] = 0.38; 95% confidence interval [CI] = 0.23-0.64) and 41% (OR = 0.59; 95% CI = 0.37-0.96), respectively. Short-term cure rate (50.3%), as determined immediately after the first group antimicrobial treatment, was not influenced by vaccination. In contrast, long-term cure rate, determined at wk 10, was affected by vaccination with higher cure in the PE group compared with the control group (69.4% vs. 51.2%; OR = 2.2; 95% CI = 1.1-5.0). Average daily gain in the first 10 wk of production was not affected by vaccination. Vaccination resulted in an increase in cold carcass weight of 3.5 and 4.3 kg in the PE (95% CI = -0.9-7.9) and IN-PE group (95% CI = -0.17-8.7), respectively. In conclusion, under the conditions of the present study, vaccination upon arrival resulted in a reduced prevalence of pneumonia at wk 10 of production, likely caused both by an improved cure rate of secondary infections and a reduced incidence of new cases between outbreak and long-term evaluation. The present protocol, using qTUS for pneumonia detection and nBAL diagnostics for pathogen identification adds a new dimension to randomized clinical trials on respiratory disease in calves.

Development of a spore-based mucosal vaccine against the bovine respiratory pathogen Mannheimia haemolytica

Bovine respiratory disease (BRD) is a significant health issue in the North American feedlot industry, causing substantial financial losses due to morbidity and mortality. A lack of effective vaccines against BRD pathogens has resulted in antibiotics primarily being used for BRD prevention. The aim of this study was to develop a mucosal vaccine against the BRD pathogen, Mannheimia haemolytica, using Bacillus subtilis spores as an adjuvant. A chimeric protein (MhCP) containing a tandem repeat of neutralizing epitopes from M. haemolytica leukotoxin A (NLKT) and outer membrane protein PlpE was expressed to produce antigen for adsorption to B. subtilis spores. Adsorption was optimized by comparing varying amounts of antigen and spores, as well as different buffer pH and reaction temperatures. Using the optimal adsorption parameters, spore-bound antigen (Spore-MhCP) was prepared and administered to mice via two mucosal routes (intranasal and intragastric), while intramuscular administration of free MhCP and unvaccinated mice were used as positive and negative control treatments, respectively. Intramuscular administration of MhCP elicited the strongest serum IgG response. However, intranasal immunization of Spore-MhCP generated the best secretory IgA-specific response against both PlpE and NLKT in all samples evaluated (bronchoalveolar lavage, saliva, and feces). Since proliferation of M. haemolytica in the respiratory tract is a prerequisite to lung infection, this spore-based vaccine may offer protection in cattle by limiting colonization and subsequent infection, and Spore-MhCP warrants further evaluation in cattle as a mucosal vaccine against M. haemolytica.

Dynamics of subclinical pneumonia in male dairy calves in relation to antimicrobial therapy and production outcomes.

Quick thoracic ultrasonography (qTUS) is increasingly used as an on-farm method to diagnose clinical and subclinical pneumonia in dairy calves. The primary objective of this prospective cohort study was to describe dynamics of lung consolidation in a purchase-dependent production system for male dairy calves in relation to antimicrobial therapy and respiratory diagnostics. In addition, we studied the association of cured and uncured pneumonia with average daily gain (ADG) and cold carcass weight (CCW). The third objective was to determine the effects of arriving with lung consolidation on the probability of developing chronic unresponsive pneumonia and reduced performance. A total of 295 male dairy calves were intensively followed by qTUS and clinical scoring on 7 strategic occasions (wk 1, 2, 3, 4, 6, 8, and 12) during the production cycle. Of the calves, 17.6% (52/295) arrived with a lung consolidation ≥1 cm. At the first outbreak of respiratory disease (wk 1 after arrival), this incidence had risen to 30.8%. Initial therapy with tulathromycin and subsequently doxycycline appeared ineffective, resulting in a increase to 43.8% of calves having pneumonia in wk 4. At the start of the first outbreak (wk 1), the majority (86.8%) of the pneumonia cases were subclinical. At wk 4, the outbreak became more clinical, and treatment with amoxicillin resulted in a cure risk of 52.7%. Culture and nanopore sequencing diagnostics on nonendoscopic broncho-alveolar lavage (nBAL) samples identified bovine respiratory syncytial virus and Mycoplasma bovis as the dominant agents in the first outbreak. The isolated M. bovis strain showed mutations associated with macrolide resistance. The second outbreak was characterized by a Pasteurella multocida superinfection and isolation of multiple M. bovis strains from nBAL diagnostic testing. Evaluated over the complete observation period, 83.4% of the calves developed consolidations ≥1 cm on qTUS. Of these calves, 53.9% (135/246) were cured by antimicrobial therapy. Chronic pneumonia (≥30 subsequent days of pneumonia) was seen in 13.9% of the animals (n = 41). Calves with uncured or chronic pneumonia had a lower ADG (992 ± 174 g/d and 930 ± 146 g/d, respectively) compared with calves that never developed pneumonia (ADG = 1,103 ± 156 g/d). In contrast, calves that did fully cure trended toward a lower ADG than calves that never developed pneumonia, but differences were no longer significant. Also, the effect of uncured pneumonia was no longer significant for CCW. Calves with lung consolidation upon arrival had a lower ADG (981 ± 159 g/d vs. 1,045 ± 159 g/d) and were more likely to develop chronic pneumonia [odds ratio = 4.2; 95% confidence interval = 2.1-8.6] compared with calves without consolidation upon arrival. Animals with chronic pneumonia, in turn, had a lower CCW than animals without chronic pneumonia (10.3 ± 4.4 kg; 95% confidence interval: 1.6-19.1 kg). This study documents the consequences of subclinical pneumonia upon arrival and pneumonia developed later in the production cycle on production outcomes in a veal calf setting. Both qTUS and nBAL diagnostics provide important information, offering potential for better control and prevention of bovine respiratory disease in dairy calves.

Scoping Review on Risk Factors and Methods for the Prevention of Bovine Respiratory Disease Applicable to Cow-Calf Operations.

Simple SummaryBovine respiratory disease (BRD) is common in cattle populations and has been named as one of three diseases where antibiotics are most frequently used in cow–calf operations in California. Antibiotics are typically used to treat or prevent the disease, but recent concerns about antibiotic resistance of pathogens in animals or spreading from animals to people have led to the call for more judicious use of these drugs. The present review summarizes the English scientific literature on articles about risk factors for the disease as well as ways to prevent BRD that are applicable to cow–calf operations. Numerous management and animal factors have been identified as increasing the risk for BRD. Vaccinations, metaphylactic use of antibiotics, and feed supplements are areas of research into the prevention of BRD. Genetics have also been explored to determine the heritability of BRD resistance. While vaccinations and metaphylactic use of antibiotics have been evaluated in multiple systematic reviews and meta-analyses, these types of summaries are missing for commonly studied feed supplements, such as yeast and trace minerals, and the use of nitric oxide releasing substance to prevent BRD. Further, it would be beneficial to summarize the knowledge on management related risk factors in literature reviews.The presented scoping review summarizes the available research evidence and identifies gaps in knowledge for bovine respiratory disease (BRD) prevention. Published literature on BRD from 1990 to April 2021 was searched in online databases, including Medline, CAB s, Scopus, Biosis, and Searchable Proceedings of Animal Conferences. Citations were systematically evaluated in a three-stage approach using commercial software and summarized in a scoping review format. A total of 265 publications were included in this review with herd/farm management (27.9%) as the most prevalent factors studied, followed by metaphylaxis (24.5%), vaccinations (24.1%), diet formulations, and nutritional supplementations (17.7%), animal characteristics (10.2%), and less common interventions and risk factors (6.4%). A high proportion of studies under herd/farm management (73%), metaphylaxis (86%), vaccinations (70%), animal characteristics (78%), and less common interventions and risk factors (59%) showed either significant effects on reducing BRD morbidity or significant differences of BRD between treatments. However, diet and nutritional supplementations reduced BRD only in 30% of research publications. Most studies on BRD were performed in feedlot populations, and more studies in cow–calf populations are needed. We further suggest meta-analyses on the use of yeast and trace mineral supplementation, and nitric oxide-releasing solution for BRD prevention.

Prevalence of BRD-Related Viral Pathogens in the Upper Respiratory Tract of Swiss Veal Calves.

Simple SummaryIn bovines, infection of the respiratory tract is frequent. It may lead to severe disease and death, and often requires antimicrobial treatment. Antimicrobial treatment is known to be related to antimicrobial resistance, which poses a threat to public health; therefore, efforts to better understand the causes of airway infection must be undertaken. Many different pathogens may be responsible for disease onset, including viruses. The aim of this study was to describe the prevalence of respiratory viruses in Swiss veal calves and to identify risk factors for infection. In a convenience sample of 764 swabs, prevalence rates were determined for bovine respiratory syncytial virus (BRSV, 2.1%), bovine parainfluenza-3 virus (BPI3V, 3.3%), bovine coronavirus (BCoV, 53.5%), influenza D virus (IDV, 4.1%), and influenza C virus (ICV, 0%). Due to the high prevalence rate, risk factors were investigated for BCoV. Younger calves tested positive more frequently than older calves. Increasing group size was associated with increasing probability for occurrence of BCoV. To summarize, different viral pathogens circulate in veal calves.The prevention of bovine respiratory disease is important, as it may lead to impaired welfare, economic losses, and considerable antimicrobial use, which can be associated with antimicrobial resistance. The aim of this study was to describe the prevalence of respiratory viruses and to identify risk factors for their occurrence. A convenience sample of 764 deep nasopharyngeal swab samples from veal calves was screened by PCR for bovine respiratory syncytial virus (BRSV), bovine parainfluenza-3 virus (BPI3V), bovine coronavirus (BCoV), influenza D virus (IDV), and influenza C virus (ICV). The following prevalence rates were observed: BRSV, 2.1%; BPI3V, 3.3%; BCoV, 53.5%; IDV, 4.1%; ICV, 0%. Logistic mixed regression models were built for BCoV to explore associations with calf management and housing. Positive swab samples were more frequent in younger calves than older calves (>100 days; p < 0.001). The probability of detecting BCoV increased with increasing group size in young calves. Findings from this study suggested that young calves should be fattened in small groups to limit the risk of occurrence of BCoV, although an extended spectrum of risk factors for viral associated respiratory disorders such as nutritional aspects should be considered in future studies.

The role of the bovine respiratory bacterial microbiota in health and disease.

Increased antimicrobial resistance in bovine respiratory bacterial pathogens poses a threat to the effective control and prevention of bovine respiratory disease (BRD). As part of continued efforts to develop antimicrobial alternatives to mitigate BRD, the microbial community residing within the respiratory tract of feedlot cattle has been increasingly studied using next-generation sequencing technologies. The mucosal surfaces of upper and lower respiratory tracts of cattle are colonized by a diverse and dynamic microbiota encompassing commensal, symbiotic, and pathogenic bacteria. While a direct causal relationship between respiratory microbiota and the development of BRD in feedlot cattle has not been fully elucidated, increasing evidence suggests that the microbiota contributes to respiratory health by providing colonization resistance against pathogens and maintaining homeostasis. Certain management practices such as weaning, transportation, feed transition, and antibiotic application can disrupt the respiratory microbiota, potentially altering pathogen colonization. Microbiota-based approaches, including bacterial therapeutics that target restoring the normal respiratory microbiota, may provide new methods for mitigating BRD in feedlot cattle in place of antibiotics. In addition, the distinct bacterial respiratory microbial communities observed in BRD-affected and healthy feedlot cattle may allow for future application of microbiota-based techniques used in the diagnosis of BRD.

Effectiveness of two intranasal vaccines for the control of bovine respiratory disease in newborn beef calves: A randomized non-inferiority multicentre field trial

Bovine respiratory syncytial virus (BRSV) and bovine parainfluenza-3 virus (bPI3V) are major causes of bovine respiratory disease (BRD) in newborn calves worldwide. Vaccination is widely used to prevent BRD, and intranasal vaccines for BRSV and bPI3V were developed to overcome interference from BRSV and bPI3V-specific maternally derived antibodies. Many experimental challenge trials have demonstrated that intranasal vaccines for BRSV and bPI3V are efficacious, but effectiveness under field conditions has been demonstrated less often, especially for newborn beef calves. The objective of this field trial was to compare the effectiveness of a newly available commercial BRSV-bPI3V intranasal vaccine with that of a benchmarked one in newborn beef calves reared in a cow-calf system. A total of 935 calves from 39 farms were randomized into two vaccine groups (Bovalto Respi Intranasal [Vaccine A], n=468; Rispoval RS+PI3 Intranasal [Vaccine B], n=467), and monitored during the in-house risk period up to three months after vaccination. Non-inferiority analysis was performed by calculating the difference in BRD prevalence between the two vaccine groups.No significant differences were observed between vaccines regarding clinical outcomes of morbidity, mortality, duration between vaccination and BRD occurrence, or treatments required. Because the upper limit of the 2-sided 95% confidence interval of the difference in BRD prevalence between the two treatment groups (0.8%) was less than the margin of non-inferiority (δ=5%), a non-inferiority of Vaccine A was concluded. In conclusion, Vaccine A is at least as effective as Vaccine B for the prevention of BRD in newborn beef cattle in a cow-calf system under field conditions.

Efficacy of sodium iodide for prevention of respiratory disease in preweaned dairy calves.

To determine the pharmacokinetics of sodium iodide (NaI) following oral administration to preweaned dairy calves, and to assess the efficacy of NaI for prevention of bovine respiratory disease (BRD) in preweaned calves at a commercial calf-raising facility. 434 healthy preweaned dairy calves. In the first of 2 experimental trials, each of 7 calves received NaI (20 mg/kg, PO) once. Blood and nasal fluid samples were collected at predetermined times before (baseline) and for 72 hours after NaI administration for determination of iodine concentrations. Pharmacokinetic parameters were determined by noncompartmental analysis. In the second trial, 427 calves at a calf-raising facility were randomly assigned to receive NaI (20 mg/kg, PO, 2 doses 72 hours apart; n = 211) or serve as untreated controls (216). Health outcomes were compared between the 2 groups. For all 7 calves in the pharmacokinetic trial, the iodine concentration in both serum and nasal fluid samples was significantly increased from the baseline concentration and exceeded the presumed therapeutic iodine concentration (6.35 μg/mL) throughout the sampling period. In the on-farm trial, the odds of being treated for BRD before weaning for NaI-treated calves were twice those for control calves (OR, 2.04; 95% CI, 1.38 to 3.00). Results suggested that, although oral administration of NaI (20 mg/kg) to preweaned dairy calves achieved iodine concentrations presumed to be effective in both serum and nasal fluid, it was not effective for prevention of BRD in preweaned calves at a commercial calf-raising facility.

Polymicrobial Biofilm Interaction Between Histophilus somni and Pasteurella multocida.

Histophilus somni and Pasteurella multocida are two of multiple agents responsible for bovine respiratory disease (BRD) in cattle. Following respiratory infection of calves with H. somni, P. multocida may also be isolated from the lower respiratory tract. Because H. somni may form a biofilm during BRD, we sought to determine if P. multocida can co-exist with H. somni in a polymicrobial biofilm in vitro and in vivo. Interactions between the two species in the biofilm were characterized and quantified by fluorescence in situ hybridization (FISH). The biofilm matrix of each species was examined using fluorescently tagged lectins (FTL) specific for the exopolysaccharide (EPS) using confocal laser scanning microscopy. Bacterial interactions were determined by auto-aggregation and biofilm morphology. Pasteurella multocida and H. somni were evenly distributed in the in vitro biofilm, and both species contributed to the polymicrobial biofilm matrix. The average biomass and biofilm thickness, and the total carbohydrate and protein content of the biofilm, were greatest when both species were present. Polymicrobial bacterial suspensions auto-aggregated faster than single species suspensions, suggesting physical interactions between the two species. Almost 300 P. multocida genes were significantly differentially regulated when the bacteria were in a polymicrobial biofilm compared to a mono-species biofilm, as determined by RNA-sequencing. As expected, host genes associated with inflammation and immune response were significantly upregulated at the infection site following H. somni challenge. Encapsulated P. multocida isolates not capable of forming a substantial biofilm enhanced an in vitro polymicrobial biofilm with H. somni, indicating they contributed to the polymicrobial biofilm matrix. Indirect evidence indicated that encapsulated P. multocida also contributed to a polymicrobial biofilm in vivo. Only the EPS of H. somni could be detected by FTL staining of bovine tissues following challenge with H. somni. However, both species were isolated and an immune response to the biofilm matrix of both species was greater than the response to planktonic cells, suggesting encapsulated P. multocida may take advantage of the H. somni biofilm to persist in the host during chronic BRD. These results may have important implications for the management and prevention of BRD.

Preweaning cost of bovine respiratory disease (BRD) and cost-benefit of implementation of preventative measures in calves on California dairies: The BRD 10K study

Bovine respiratory disease (BRD) is a multifactorial disease that is estimated to affect 22% of preweaned dairy calves in the United States and is a leading cause of preweaning mortality in dairy calves. Overall cost of calfhood BRD is reflected in both the immediate cost of treating the disease as well as lifetime decrease in production and increased likelihood of affected cattle leaving the herd before their second calving. The goal of this paper was to develop an estimate of the cost of BRD based on longitudinal treatment data from a study of BRD with a cohort of 11,470 preweaned dairy calves in California. Additionally, a cost-benefit analysis was performed for 2 different preventative measures for BRD, an increase of 0.47 L of milk per day for all calves or vaccination of all dams with a modified live BRD vaccine, using differing assumptions about birth rate and number of calves raised per year. Average short-term cost of BRD per affected calf was $42.15, including the use of anti-inflammatory medications in the treatment protocols across all management conditions. The cost of treating BRD in calves appears to have increased in recent years and is greater than costs presented in previous studies. A cost-benefit analysis examined different herd scenarios for a range of cumulative incidences of BRD from 3 to 25%. Increasing milk fed was financially beneficial in all scenarios above a 3% cumulative incidence of BRD. Use of a modified live vaccine in dams during pregnancy, examining only its value as a form of BRD prevention in the calves raised on the farm, was financially beneficial only if the cumulative incidence of BRD exceeded 10 to 15% depending on the herd size and whether the dairy farm was raising any bull calves. The cost-benefit analysis, under the conditions studied, suggests that producers with high rates of BRD may benefit financially from implementing preventative measures, whereas these preventative measures may not be cost effective to implement on dairy farms with very low cumulative incidences of BRD. The long-term costs of calfhood BRD on lifetime productivity were not factored into these calculations, and the reduction in disease may be associated with additional cost savings and an improvement in calf welfare and herd life.

Development of Bacterial Therapeutics against the Bovine Respiratory Pathogen Mannheimia haemolytica.

Bovine respiratory disease (BRD) is a major cause of morbidity and mortality in beef cattle. Recent evidence suggests that commensal bacteria of the bovine nasopharynx have an important role in maintaining respiratory health by providing colonization resistance against pathogens. The objective of this study was to screen and select bacterial therapeutic candidates from the nasopharynxes of feedlot cattle to mitigate the BRD pathogen Mannheimia haemolytica In a stepwise approach, bacteria (n = 300) isolated from the nasopharynxes of 100 healthy feedlot cattle were identified and initially screened (n = 178 isolates from 12 different genera) for growth inhibition of M. haemolytica Subsequently, selected isolates were evaluated for the ability to adhere to bovine turbinate (BT) cells (n = 47), compete against M. haemolytica for BT cell adherence (n = 15), and modulate gene expression in BT cells (n = 10). Lactobacillus strains had the strongest inhibition of M. haemolytica, with 88% of the isolates (n =33) having inhibition zones ranging from 17 to 23 mm. Adherence to BT cells ranged from 3.4 to 8.0 log10 CFU per 105 BT cells. All the isolates tested in competition assays reduced M. haemolytica adherence to BT cells (32% to 78%). Among 84 bovine genes evaluated, selected isolates upregulated expression of interleukin 8 (IL-8) and IL-6 (P < 0.05). After ranking isolates for greatest inhibition, adhesion, competition, and immunomodulation properties, 6 Lactobacillus strains from 4 different species were selected as the best candidates for further development as intranasal bacterial therapeutics to mitigate M. haemolytica infection in feedlot cattle.IMPORTANCE Bovine respiratory disease (BRD) is a significant animal health issue impacting the beef industry. Current BRD prevention strategies rely mainly on metaphylactic use of antimicrobials when cattle enter feedlots. However, a recent increase in BRD-associated bacterial pathogens that are resistant to metaphylactic antimicrobials highlights a pressing need for the development of novel mitigation strategies. Based upon previous research showing the importance of respiratory commensal bacteria in protecting against bronchopneumonia, this study aimed to develop bacterial therapeutics that could be used to mitigate the BRD pathogen Mannheimia haemolytica Bacteria isolated from the respiratory tracts of healthy cattle were characterized for their inhibitory, adhesive, and immunomodulatory properties. In total, 6 strains were identified as having the best properties for use as intranasal therapeutics to inhibit M. haemolytica If successful in vivo, these strains offer an alternative to metaphylactic antimicrobial use in feedlot cattle for mitigating BRD.

Pharmacokinetics and Pharmacodynamics of Gamithromycin Treatment of Pasteurella multocida in a Murine Lung Infection Model.

Gamithromycin is approved for the treatment and prevention of bovine respiratory disease (BRD), which is caused mainly by Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma species. In this study, multiple dosage regimens were administered to the neutropenic mouse lung infection model in order to investigate the pharmacokinetic/pharmacodynamic (PK/PD) parameters of gamithromycin treatment of P. multocida and to further define the PK/PD parameter that best correlates with the efficacy of gamithromycin against P. multocida. The PK characteristics of gamithromycin were analyzed after a single subcutaneous (s.c.) injection (1, 3, 6, and 9 mg/kg). The concentration–time profiles of unbound (f) gamithromycin in plasma samples were analyzed by non-compartmental analysis. The main PK parameters of gamithromycin for the area under the concentration–time curve from 0 to 24 h (f AUC0–24) and the peak drug concentration (f C max) values ranged from 0.86 to 8.42 µg·h/ml and from 0.55 to 5.69 µg/ml, respectively. The PD values were calculated based on multiple s.c. injections over 24 h (1, 3, 6, and 9 mg/kg at 6, 8, 12, and 24 h, respectively; total dosage 1–36 mg/ kg). The minimum inhibitory concentration (MIC) of gamithromycin against P. multocida in mice serum was 0.15 μg/ml. Analysis of PK/PD indices using the inhibitory effect E max model indicated a strong correlation (R 2 = 0.9624) between the f AUC0–24/MIC ratio and various antibacterial effects. The area under the unbound concentration–time curve over 24 h to MIC (f AUC0–24/MIC) predicted for bacteriostatic action, 1-log10 reduction, 2-log10 reduction, and 3-log10 reduction were 56.77, 90.18, 143.06, and 239.44 h, respectively. These in vivo data may facilitate gamithromycin dosage optimization against P. multocida in veterinary medicine.

Respiratory viruses identified in western Canadian beef cattle by metagenomic sequencing and their association with bovine respiratory disease.

Bovine respiratory disease (BRD) causes considerable economic losses in North America. The pathogenesis involves interactions between bacteria, viruses, environment and management factors. Primary viral infection can increase the risk of secondary fatal bacterial infection. The objective of this study was to use metagenomic sequencing to characterize the respiratory viromes of paired nasal swabs and tracheal washes from western Canadian feedlot cattle, with or without BRD. A total of 116 cattle (116 nasal swabs and 116 tracheal washes) were analysed. The presence of influenza D virus (IDV), bovine rhinitis A virus (BRAV), bovine rhinitis B virus (BRBV), bovine coronavirus (BCV) and bovine respiratory syncytial virus (BRSV) was associated with BRD. Agreement between identification of viruses in nasal swabs and tracheal washes was generally weak, indicating that sampling location may affect detection of infection. This study reported several viruses for the first time in Canada and provides a basis for further studies investigating candidate viruses important to the prevention of BRD.

Beef producer survey of the cost to prevent and treat bovine respiratory disease in preweaned calves.

OBJECTIVE To estimate costs associated with prevention and treatment of bovine respiratory disease (BRD) in preweaned calves on US beef cow-calf operations. DESIGN Cross-sectional survey. SAMPLE 43 beef cow-calf producers whose operations had a history of BRD in preweaned calves. PROCEDURES Mail and electronic surveys were developed and administered to producers in Nebraska, North Dakota, and South Dakota to obtain information regarding costs of BRD prevention and treatment. Descriptive statistics were generated. Mixed linear regression models were used to assess factors associated with the costs of vaccines, medicine, and labor and percentage time spent on prevention and treatment of BRD in cows, replacement heifers, and preweaned calves. RESULTS 7 mail and 36 electronic surveys were completed. Median annual costs for BRD vaccines were $2.25, $4.00, and $6.25/animal, and median annual labor costs for vaccination were $4.58, $3.00, and $5.00/animal for cows, heifers, and preweaned calves, respectively. Median annual costs for medicine and labor to treat preweaned calves for BRD were $11.00 and $15.00/ affected calf, respectively. Adjusted mean annual BRD vaccine cost for preweaned calves ($7.67/animal) was significantly greater than that for cows ($3.18/animal) and heifers ($4.48/animal). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that labor costs associated with BRD vaccination and treatment were similar to or exceeded the cost of vaccines and medicine, and most of those labor costs were associated with gathering and sorting cattle. Therefore, costs associated with labor as well as medicine and vaccines should be considered during the development of BRD prevention and treatment plans.

Efficacy of a DNA immunostimulant for on-arrival control of bovine respiratory disease in fall-placed feedlot calves

A randomized complete block design trial was conducted in a commercial finishing feedlot in southern Alberta, Canada using auction-market origin fall-placed steer calves (n = 5430; initial body weight 618 ± 22 lb; 280.9 ± 10.0 kg) to evaluate the comparative efficacy of on-arrival treatment with a DNA immunostimulant and tulathromycin versus tulathromycin alone for prevention of bovine respiratory disease (BRD). The addition of the DNA immunostimulant reduced first-pull treatment rates for BRD (P=0.02), case fatality rate for BRD (P=0.08), mortality rate for BRD (P=0.03), mortality rate for BRD and histophilosis (P=0.09), average daily gain (P&lt;0.01) with dead weights included, and increased dry matter conversion (P&lt;0.01) with dead weights included.

Identification of novel drug targets in bovine respiratory disease: an essential step in applying biotechnologic techniques to develop more effective therapeutic treatments.

BackgroundBovine Respiratory Disease (BRD) is a major problem in cattle production which causes substantial economic loss. BRD has multifactorial aetiologies, is multi-microbial, and several of the causative pathogens are unknown. Consequently, primary management practices such as metaphylactic antimicrobial injections for BRD prevention are used to reduce the incidence of BRD in feedlot cattle. However, this poses a serious threat in the form of development of antimicrobial resistance and demands an urgent need to find novel interventions that could reduce the effects of BRD drastically and also delay/prevent bacterial resistance.Materials and methodsWe have employed a subtractive genomics approach that helps delineate essential, host-specific, and druggable targets in pathogens responsible for BRD. We also proposed antimicrobials from FDA green and orange book that could be repositioned for BRD.ResultsWe have identified 107 putative targets that are essential, selective and druggable. We have also confirmed the susceptibility of two BRD pathogens to one of the proposed antimicrobials – oxytetracycline.ConclusionThis approach allows for repositioning drugs known for other infections to BRD, predicting novel druggable targets for BRD infection, and providing a new direction in developing more effective therapeutic treatments for BRD.