Bovine Respiratory Disease Cases Research Articles

Randomized trial comparing the effects of tulathromycin, tildipirosin and gamithromycin used as first treatment for clinical bovine respiratory disease in commercial feedlot steers

Our objective was to compare effects of 3 macrolide antibiot­ics used as first-time bovine respiratory disease (BRD) treat­ment on primary health outcomes (retreatment, removal and mortality) in feedlot steers. Secondary outcomes included days-on-feed, rectal temperature and weight at the time of event occurrences. Crossbred beef steers (n = 978; average body weight [± SD] 655 ± 84.0 lb [297 ± 38.1 kg]) were enrolled across 2 commercial feedlots in the U.S. High Plains in a ran­domized complete block design. Steers were eligible for in­clusion if they were exhibiting clinical BRD symptoms from natural exposure and had not been previously treated with an antimicrobial drug for any reason including metaphylaxis. Treatment was administration of tulathromycin, tildipirosin or gamithromycin, at the time of first BRD diagnosis. Linear and generalized linear mixed models were used for statisti­cal analyses with significance threshold α = 0.05. At enroll­ment, animal weight (P = 0.98), rectal temperature (P = 0.58), and days-on-feed (P = 0.28) did not differ significantly between treatments. There was no evidence of differences for any health outcome (P ≥ 0.30), nor for any cattle characteristics at the time of retreatment, removal, or mortality (P ≥ 0.15). Treatment success (steers that were never retreated, removed, and/or were a BRD case fatality) ranged from 62.7 to 64.8% between treatments (P = 0.87). There was no evidence to reject the null hypothesis of similar effectiveness between these macrolides when administered to similar steer populations as first-time clinical BRD treatments.

Strategies for Bovine Respiratory Disease (BRD) Diagnosis and Prognosis: A Comprehensive Overview.

Despite significant advances in vaccination strategies and antibiotic therapy, bovine respiratory disease (BRD) continues to be the leading disease affecting the global cattle industry. The etiology of BRD is complex, often involving multiple microbial agents, which lead to intricate interactions between the host immune system and pathogens during various beef production stages. These interactions present environmental, social, and geographical challenges. Accurate diagnosis is essential for effective disease management. Nevertheless, correct identification of BRD cases remains a daunting challenge for animal health technicians in feedlots. In response to current regulations, there is a growing interest in refining clinical diagnoses of BRD to curb the overuse of antimicrobials. This shift marks a pivotal first step toward establishing a structured diagnostic framework for this disease. This review article provides an update on recent developments and future perspectives in clinical diagnostics and prognostic techniques for BRD, assessing their benefits and limitations. The methods discussed include the evaluation of clinical signs and animal behavior, biomarker analysis, molecular diagnostics, ultrasound imaging, and prognostic modeling. While some techniques show promise as standalone diagnostics, it is likely that a multifaceted approach-leveraging a combination of these methods-will yield the most accurate diagnosis of BRD.

First evaluation of the impact of a targeted subunit vaccine against bovine viral diarrhea virus in feedlot cattle.

Bovine respiratory disease (BRD) is a serious health and economic problem in the beef industry, which is often associated with transportation and caused by different pathogens. In this study, we evaluated the effect of a novel subunit targeted vaccine against bovine viral diarrhea virus (BVDV) in feedlot cattle, a major viral agent of BRD. The core of this novel vaccine is the fusion of the BVDV structural glycoprotein, E2, to a single-chain antibody, APCH, together termed, APCH-E2. The APCH antibody targets the E2 antigen to the major histocompatibility type II molecule (MHC-II) present in antigen-presenting cells. To evaluate the vaccine, 2,992 animals were randomly allocated into two groups, control group (N = 1,491) and treatment group (N = 1,501). Animals of both groups received the routine sanitary plan: two doses of clostridial, respiratory, and rabies vaccines. Animals within the treatment group also received two doses of a targeted subunit vaccine against BVDV. Serum samples were taken on the day of the first inoculation (T0) and 90 d later (T90). Viral circulation was monitored using an anti-P80 ELISA (virus-specific) and immune response was evaluated by anti-E2 ELISA (detects virus and vaccine immune responses). Only animals treated for respiratory disease were considered positive cases of BRD. Results demonstrate that the control group had significantly more animals treated for BRD cases compared to the treatment group (5.9% vs. 3.7%, P = 0.02). The control group had a greater number of animals positive for anti-P80 antibodies and significantly fewer animals positive for anti-E2 antibodies compared to the treatment group (69% vs. 61% and 71% vs. 99%, respectively, P = 0.003), consistent with natural viral circulation within this group. The treatment group, conversely, had fewer animals positive for anti-P80 antibodies and a greater number of animals positive for anti-E2 antibodies, consistent with a robust vaccine-induced antibody response and a reduction of the BVDV circulation within this group. The data indicate the new subunit targeted vaccine induced greater anti-E2 antibodies and reduced the amount of BVD virus circulation within the treatment group leading to a fewer number of animals needing to be treated for BRD.

Nasopharyngeal Bacterial Prevalence and Microbial Diversity at First Treatment for Bovine Respiratory Disease (BRD) and Its Associations with Health and Mortality Outcomes in Feedyard Cattle.

Bovine respiratory disease (BRD) is an economically important disease in feedyards influencing both animal welfare and antimicrobial utilization. Major pathogens associated with BRD have been identified in previous research, but little information is available on the relationship between nasopharyngeal microbiota and health outcomes. The objective of this study was to identify potential associations between nasopharyngeal microbiota and antimicrobial resistance patterns of clinical cases that lived or died compared to non-diseased controls. Enrolled animals were subdivided based on clinical disease status and case outcome (subsequent mortality). Deep nasopharyngeal swabs were collected on enrolled animals and submitted for bacterial isolation, antimicrobial susceptibility determination, and metagenomics analysis. Enrolled cattle were represented in three groups: animals at first treatment for BRD that subsequently died (BRDM, n = 9), animals at first treatment for BRD that subsequently lived (BRDL, n = 15), and animals that were never treated for BRD during the feeding phase (CONT, n = 11). Antimicrobial resistance patterns for Pasteurella multocida illustrated cattle in each outcome category had isolates that were pan-susceptible or only showed resistance to oxytetracycline. The relative abundance of species and genera illustrated few differences among the three outcomes. Higher alpha diversity was identified in BRDL compared to CONT at the species level, and both BRDL and BRDM showed increased alpha diversity compared to CONT at the general level. Overall, this work illustrated nasopharyngeal microbiota showed relatively few differences among BRD cases that lived or died compared to animals without BRD.

Molecular and genetic characterization of bovine parainfluenza type 3 European field and vaccine strains.

Bovine Parainfluenza Type 3 virus (BPIV-3) is an enveloped, non-segmented single-stranded, negative-sense RNA virus belonging to the Paramyxoviridae family (genus Respirovirus) with a well-known role in Bovine Respiratory Disease (BRD) onset. Being isolated for the first time in 1959, BPIV-3 currently circulates worldwide in cattle herds and is routinely tested in suspected BRD cases. Different commercial vaccines are available to prevent infection and/or to reduce the clinical signs associated with BPIV-3 infection, which are essential to prevent secondary infections. Despite years of molecular surveillance, a very limited number of complete genome sequences were made publicly available, preventing thus the understanding of the genetic diversity of the circulating strains in the field. In addition, no data about the genetic identity between field and vaccine strains is currently available. In this study, we sequenced the full-genome and genetically characterized BPIV-3 strains isolated from animals displaying respiratory illness in France and Sweden, as well as the vaccine strains contained in three different commercialized vaccines. Our results show that the sequences from France and Sweden belong to genotype C. However, a third sequence from Sweden from 2017 clustered within genotype A. The sequencing of vaccine strains revealed that two of the vaccine strains clustered within genotype C, whereas the third vaccine strain belonged to genotype A. Altogether, our findings suggest that both genotypes A and C circulate in Europe and that BPIV-3 field and vaccine strains are genetically divergent. Our sequencing results could be useful to better understand the genetic differences between the circulating field and vaccine BPIV-3 strains. This is crucial for a correct interpretation of diagnostic findings and for the assessment of BPIV-3 prevalence in cattle population.

Evaluation of predictive models to determine final outcome for feedlot cattle based on information available at first treatment for bovine respiratory disease.

To evaluate predictive model ability to determine whether an animal finished the feeding period using data known at first treatment for bovine respiratory disease (BRD). Additional comparisons evaluated the potential benefits of predictions by adding weather data, utilizing balancing techniques, and creating models for individual feedyards. This retrospective study included animal, pen, and feedyard data from 12 US feedyards from 2016 to 2021. The final dataset consisted of 96,382 BRD cases of which 14.2% did not finish the feeding phase. Five predictive models were trained and underwent threshold probability adjustment to maximize F1 score. Model performance was evaluated using accuracy, sensitivity specificity, positive and negative predictive values, and area under the receiver operating characteristics curve (AUC). Overall, model performance was low with a median AUC value of 0.675. The addition of weather data had little effect on AUC but resulted in more variation in sensitivity and specificity. Resampling the dataset had a limited effect on performance. Individual feedlot models had higher AUC values than others with the decision tree typically performing best in most feedyards. Results indicated some utility of predictive models evaluating BRD cases to predict cattle that did not finish the feeding phase. These models could be valuable in assisting health providers making decisions on individual cases.

Prevalence and characterization of seven-segmented influenza viruses in bovine respiratory disease complex

Bovine respiratory disease (BRD) complex is a multifactorial respiratory disease of cattle. Seven-segmented influenza C (ICV) and D (IDV) viruses have been identified in cattle with BRD, however, molecular epidemiology and prevalence of IDV and ICV in the diseased population remain poorly characterized. Here, we conducted a molecular screening of 208 lung samples of bovine pneumonia cases for the presence of IDV and ICV. Our results demonstrated that both viruses were prevalent in BRD cases and the overall positivity rates of IDV and ICV were 20.88% and 5.99% respectively. Further analysis of three IDV strains isolated from lungs of cattle with BRD showed that these lung-tropic strains belonged to D/Michigan/2019 clade and diverged antigenically from the circulating dominant IDV clades D/OK and D/660. Our results reveal that IDV and ICV are associated with BRD complex and support a role for IDV and ICV in the etiology of BRD.

Antimicrobial susceptibility and molecular characteristics of Mycoplasma bovis isolated from cases of bovine respiratory disease in Australian feedlot cattle

To date, antimicrobial susceptibility has not been reported for Australian Mycoplasma bovis isolates. This study determined minimal inhibitory concentrations (MICs) for 12 different antimicrobials against Australian M. bovis isolates and used whole genome sequencing to screen those showing high macrolide MICs for point mutations in target genes. Most lung tissue/swab samples from bovine respiratory disease cases (61/76, 80.3%) tested positive for M. bovis. A set of 50 representative isolates (50/61, 82.0%) that showed adequate growth, was used for MIC testing. Uniformly, low MIC values were confirmed for enrofloxacin (≤ 4 μg/mL), florfenicol (≤ 8 μg/mL), gamithromycin (≤ 2 μg/mL), spectinomycin (≤ 4 μg/mL), tetracycline (≤ 8 μg/mL), tiamulin (≤ 4 μg/mL), and tulathromycin (≤ 0.5 μg/mL). A small proportion (10%) of isolates exhibited high MICs (≥ 32 μg/mL) for tildipirosin, tilmicosin, tylosin, and lincomycin, which were above the epidemiological cut-off values for each antimicrobial (≥ 4 μg/mL). These isolates, originating from three Australian states, underwent whole genome sequencing/multilocus sequencing typing and were compared with the reference strain PG45 to investigate mutations that might be linked with the high macrolide/lincosamide MICs. All five belonged to ST52 and two macrolide associated mutations were identified within the 23 S rRNA gene (A2058G in two sequenced isolates and G748A in all sequenced isolates). Four additional 23 S rRNA gene mutations did not appear to be linked to macrolide resistance. Whilst the majority of Australian M. bovis isolates appear susceptible to the tested antimicrobials, emerging macrolide resistance was detected in three Australian states and requires continued monitoring.

Genomic profiling of Pasteurella multocida isolated from feedlot cases of bovine respiratory disease

Pasteurella multocida causes a range of diseases in many host species throughout the world, including bovine respiratory disease (BRD) which is predominantly seen in feedlot cattle. This study assessed genetic diversity among 139 P. multocida isolates obtained from post-mortem lung swabs of BRD-affected feedlot cattle in four Australian states: New South Wales, Queensland, South Australia, and Victoria during 2014–2019. Whole-genome sequencing (WGS) was used to determine capsular serogroup, lipopolysaccharide genotypes, multi-locus sequence types and phylogenetic relationships. Two capsular types (A and D), with most isolates (132/139; 95%) belonging to type A; and three lipopolysaccharide (LPS) genotypes were identified (L1 [6/139; 4.3%], L3 [124/139; 89.2%] and L6 [9/139; 6.4%)]). Multi-locus sequence types (STs) ST9, ST13, ST17, ST20, ST36, ST50, ST58, ST79, ST124, ST125, ST132, ST167, ST185, ST327, ST394, and three novel STs [ST396, ST397, and ST398] were identified, with ST394 (59/139; 42.4%) and ST79 (44/139; 32%) the most prevalent in all four states. Isolates displaying phenotypic resistance to single, dual or multiple antibiotics (macrolide, tetracycline and aminopenicillins) were predominantly ST394 (23/139; 17%). Laterally mobile elements identified in the resistant ST394 isolates included small plasmids, encoding macrolide and/or tetracycline resistance, distributed in all states; and chromosomally located integrative conjugative elements (ICEs) (4 ST394 and 1 ST125) from the same Queensland feedlot. This study highlights the genomic diversity, epidemiological relationships and AMR associations in bovine P. multocida isolates from Australia and provides insight into the unique ST prevalence compared to other major beef-producing countries.

Evaluation of practices used to reduce the incidence of bovine respiratory disease in Australian feedlots (to November 2021).

Bovine respiratory disease (BRD) has been identified as the most significant infectious disease of feedlot cattle in eastern Australia.1 Bovine respiratory disease causes economic loss due to medication costs, mortalities, excessive feed inputs associated with increased time on feed, reduced sale prices and associated labour costs. Bovine respiratory disease is a complex multifactorial condition with multiple animal, environmental and management risk factors predisposing cattle to illness. A range of microorganisms are implicated in BRD with at least four viral and five bacterial species commonly involved individually or in combination. The viruses most commonly associated with BRD in Australia are bovine herpesvirus 1 (BHV1), bovine viral diarrhoea virus (BVDV or bovine pestivirus), bovine parainfluenza 3 virus (PI3) and bovine respiratory syncytial virus (BRSV). More recently, bovine coronavirus has been identified as a potential viral contributor to BRD in Australia.2 A number of bacterial species have also been recognised as important to the BRD complex; these include Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Trueperella pyogenes and Mycoplasma bovis. Although one or more of the pathogens listed above can be isolated from clinical cases of BRD, there is no evidence that infection alone causes serious illness. This indicates that, in addition to specific infectious agents, other factors are crucial for the development of BRD under field conditions. These can be categorised as environmental, animal and management risk factors. These risk factors are likely to exert their effects through multiple pathways including reductions in systemic and possibly local immunity. For example, stressors such as weaning, handling at saleyards, transport, dehydration, weather conditions, dietary changes, comingling and pen competition might reduce the effectiveness of the immune system. Reduced immunocompetence can allow opportunistic infection of the lower airways with potential pathogens leading to the development of BRD. The objective of this paper is to critically review the evidence for management practices aimed at reducing the incidence of BRD in Australian feedlot cattle. Predisposing factors (Table 1) largely beyond the control of most feedlots, such as weather and exposure to respiratory viruses, are discussed separately, but these factors can generate indirect prevention responses that are discussed under the preventative practices categories. The current practices are classified as either animal preparation practices (Table 2) or feedlot management practices (Table 3).

Machine-Learning Approach for Risk Estimation and Risk Prediction of the Effect of Climate on Bovine Respiratory Disease

Bovine respiratory disease (BRD) is a major cause of illness and death in cattle; however, its global extent and distribution remain unclear. As climate change continues to impact the environment, it is important to understand the environmental factors contributing to BRD’s emergence and re-emergence. In this study, we used machine-learning models and remotely sensed climate data at 2.5 min (21 km2) resolution environmental layers to estimate the risk of BRD and predict its potential future distribution. We analysed 13,431 BRD cases from 1727 cities worldwide between 2005 and 2021 using two machine-learning models, maximum entropy (MaxEnt) and Boosted Regression Trees (BRT), to predict the risk and geographical distribution of the risk of BRD globally with varying model parameters. Different re-sampling regimes were used to visualise and measure various sources of uncertainty and prediction performance. The best-fitting model was assessed based on the area under the receiver operator curve (AUC-ROC), positive predictive power and Cohen’s Kappa. We found that BRT had better predictive power compared with MaxEnt. Our findings showed that favourable habitats for BRD occurrence were associated with the mean annual temperature, precipitation of the coldest quarter, mean diurnal range and minimum temperature of the coldest month. Similarly, we showed that the risk of BRD is not limited to the currently known suitable regions of Europe and west and central Africa but extends to other areas, such as Russia, China and Australia. This study highlights the need for global surveillance and early detection systems to prevent the spread of disease across borders. The findings also underscore the importance of bio-security surveillance and livestock sector interventions, such as policy-making and farmer education, to address the impact of climate change on animal diseases and prevent emergencies and the spread of BRD to new areas.

Calves severely affected by bovine respiratory disease have reduced protection against histone toxicity and exhibit lower complement activity.

Bovine respiratory disease (BRD) remains the greatest challenge facing the beef industry. Calves affected by BRD can manifest illness ranging from subclinical infection to acute death. In pathologies similar to BRD, extracellular histones have been implicated as major contributors to lung tissue damage. Histones are basic proteins responsible for DNA organization in cell nuclei, however when released extracellularly during cell injury or via neutrophil activation they become cytotoxic. Cattle suffering severe cases of BRD demonstrate reduced capacity to protect against the cytotoxic effects of histones, however, the protective mechanism(s) of serum remain(s) unknown. Therefore, the objective was to identify components within serum that contribute to protection against histone toxicity. Serum proteins from animals considered protective (P; N = 4) and nonprotective (NP; N = 4) against the toxic effects of histones were precipitated by the addition and incubation of exogenous histones. Proteins that interact with histones from both groups were isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and identified via label free "shotgun" proteomics. Sixteen candidate proteins increased by ≥2-fold change in P vs. NP animals were identified, with several associated with the complement system. A subsequent study was conducted to evaluate complement system activity and serum protective capacity against exogenous histones in feedlot heifers. Serum samples were collected from 118 heifer calves (BW at arrival = 229 ± 2.4 kg) at feedlot arrival. Animals were retrospectively assigned to groups consisting of: calves not requiring treatment with antibiotics for BRD (CONT; N = 80), calves treated once (1TRT; N = 21), calves treated twice (2TRT; N = 5), calves treated thrice (3TRT; N = 3), or calves that died from BRD within 1 wk of entering the feedlot (DA; N = 9). Serum from DA animals was less protective than CONT (P = 0.0005) animals against histone toxicity. Complement activity of DA animals was reduced compared to CONT (P = 0.0044) animals. Additionally, the use of both assays as a ratio resulted in increased ability to detect DA animals. Results suggest that cattle predisposed to severe cases of respiratory disease may have impaired complement activity presumably contributing to reduced protective capacity against histone toxicity.

PSV-A-4 Novel Method to Identify Cattle Predisposed to Severe Cases of Bovine Respiratory Disease

Abstract Respiratory disease in several species can range from subclinical infection to acute death. Bovine respiratory disease (BRD) remains the greatest economic challenge facing the beef industry. Histones are core proteins in chromosomal structure that, when released extracellularly, are cytotoxic and could contribute to exacerbated tissue necrosis during infection. Work in our laboratory demonstrated cattle suffering severe cases of BRD had limited capacity to protect against the cytotoxic effects of extracellular histones, however, the protective mechanism(s) remain unknown. Literature suggests components of the complement system interact with extracellular histones, but the effects on cytotoxic activity of histones is unclear. The objective of the current experiment was to evaluate protective capacity against extracellular histones and complement activity in feedlot heifers and subsequent disease outcomes. Serum samples were collected from 118 heifer calves (BW 229 ± 2.4 kg) at feedlot arrival and evaluated for protective capacity against histone toxicity employing an extracellular histone toxicity assay; and complement activity using a 50% hemolytic complement screening assay. Animals were retrospectively assigned to groups consisting of: calves not requiring treatment with antibiotics for BRD (NT; n = 80) or calves that died from BRD within 1 wk of entering the feedlot (DA; n = 9). Serum from DA animals was less (P < 0.001) protective than NT animals against histone toxicity. Complement activity of DA animals was reduced (P < 0.05) compared to NT animals. Using a ratio of both assays under stringent selection points, the positive predictive value was 75%, and negative predictive value was 94%. Results indicate that cattle predisposed to severe cases of respiratory have impaired complement activity presumably contributing to impaired protective capacity against histone toxicity. Analyzing these functional pathways may provide a novel selection tool against cattle predisposed to severe cases of BRD.

Efficiency-corrected PCR quantification for identification of prevalence and load of respiratory disease-causing agents in feedlot cattle.

Bovine respiratory disease (BRD) is the most prevalent disease in feedlot cattle worldwide with Bovine alphaherpesvirus 1 (BoAHV1), Histophilus somni, Mannheimia haemolytica, Mycoplasma bovis, Pasteurella multocida and Trueperella pyogenes accepted to be common etiological agents associated with BRD. Although these agents are common in the upper and lower airways in clinical BRD cases, some also exist as normal flora suggesting their presence in the upper airways alone is not necessarily informative with respect to disease status or risk. To determine the relationship between presence, load and disease status, we investigated the relationship between load in the upper airways at induction and active BRD cases in feedlot cattle using efficiency-corrected PCR quantification. By this approach, we were able to accurately determine the prevalence and load of the key BRD agents in the upper respiratory tract showing that cattle in the hospital pen had a higher prevalence, and load, of these agents both singly and in combination compared to cattle sampled at feedlot induction. A combination of agents was the most accurate indicator of BRD risk with cattle with four or more agents detected in the upper airway more likely to be undergoing treatment for BRD than non-BRD ailments. In addition, M. bovis was rarely detected at feedlot induction but was identified at high prevalence in cattle in the hospital pen. These findings present a potential new technological approach for the investigation, analysis and identification of BRD-associated viral and bacterial agents for Australian feedlot systems as well as for BRD disease management and treatment.

Mycoplasma bovis is associated with Mannheimia haemolytica during acute bovine respiratory disease in feedlot cattle.

Bovine Respiratory Disease (BRD) represents a significant burden to the health of feedlot cattle and the profitability of the beef industry in the US. Mannheimia haemolytica is widely regarded as the primary bacterial pathogen driving acute BRD. While Mycoplasma bovis is most commonly implicated in chronic cases of BRD, this agent's potential role in acute stages of BRD is unclear. Therefore, this study aimed to evaluate potential associations between M. bovis and M. haemolytica during acute BRD in feedlot cattle. Nasal swabs (n = 1,044) were collected over time from feedlot cattle (n = 270) enrolled in an experiment assessing the effect of vaccination for Bovine Respiratory Syncytial Virus (BRSV). Swabs were analyzed for detection of M. bovis, M. haemolytica, Pasteurella multocida, Histophilus somni, and BRSV via multiplex qPCR assays. Data were analyzed using inverse conditional probability weighted (ICPW) logistic regression models to investigate potential effects of M. bovis presence on arrival (d0), day seven (d7) and day 14 (d14) post-arrival on M. haemolytica prevalence on day 28 (d28) post-arrival, adjusting for the previous history of P. multocida, H. somni, BRSV, BRD morbidity, and body weight. The potential association between time-to-BRD detection and M. bovis presence on d0, d7, and d14 post-arrival, was inferred via an ICPW time-to-event model. The presence of M. bovis in nasal swabs collected on d7 post-arrival was significantly associated with an increase in the prevalence of M. haemolytica on d28 (prevalence difference: 45%; 95% Confidence Interval: 31%, 60%; P-value < 0.001). Significant time-varying coefficients for M. bovis presence were detected at d0, d7, and d14 post-arrival in the ICPW time-to-event model (P-value < 0.001). The shortest median time-to-BRD detection was 29 days in cattle that were M. bovis positive on d0, d7, and d14 post-arrival and in those that were positive on d0 and d14 post-arrival. Under the conditions of this study, our findings suggest that M. bovis may be influencing the respiratory environment during the acute phase of BRD, increasing the abundance of M. haemolytica, which could have important impacts on the occurrence of BRD.

In vitro antiviral activity of Thymbra spicata L. extract on bovine respiratory viruses (BCoV, BPIV-3, BRSV, BVDV and BoHV-1)

Viral pathogens are the primary agents in bovine respiratory disease cases, and there is no direct effective antiviral drug application. Thymbra is a genus of oregano commonly found in Turkey. The primary component (34.9%) of the extract obtained from Thymbra spicata L. is the carvacrol which is used in traditional medicine. This study evaluates the potential antiviral activity and inactivation efficiency of T. spicata L. extract against bovine respiratory viruses, including BCoV, BPIV-3, BRSV, BVDV and BoHV-1. To evaluate its effect on viral replication, viral titres were taken from infected cells treated with non-cytotoxic T. spicata L. extract concentrations (0.75% and 1.5%, 1.32 and 2.64µg/ml of carvacrol as active ingredient, respectively) and compared to non-treated infected cells. The viruses were treated directly with 1.5% T. spicata L. extract, and the viral titres were evaluated at certain time points to determine the efficiency of direct inactivation. The number of infectious virions for BCoV, BPIV-3, BRSV, BVDV and BoHV-1 treated with 1.5% T. spicata L. extract were decreased by 99.44%, 100.0%, 94.38%, 99.97% and 99.87%, respectively.T. spicata L. extract strongly inhibits the replication of mentioned viruses in a dose-dependent manner in vitro. In addition, T. spicata L. extract shared direct inactivation efficiency on the mentioned viruses in a time-dependent manner. This study shows the antiviral efficiency of T. spicata L. on BRD-related viral agents for the first time. The oregano species T. spicata and its main component, carvacrol, may have a potential for antiviral activity in the alternative treatment of respiratory viral diseases in cattle. Given the similarity of replication strategies, obtained data suggest the possible efficiency of T. spicata L. on human respiratory viruses.

Evaluating the environmental survivability of Mannheimia haemolytica on various potential fomites

Bovine respiratory disease (BRD) is an important cause of morbidity and mortality in beef and dairy cattle in North America. Of the significant bacteria implicated in BRD cases, Mannheimia haemolytica is the most common microbe isolated in clinical cases, yet little is known about its environmental survivability. The objective of this study was to examine relative survivability of M. haemolytica on metal, wood, and plastic under varying environmental conditions. Microenvironments were constructed at approximately 37℉ (3℃), 71℉ (22℃), and 97℉ (36℃) using plastic containers and monitored for temperature and humidity. Stainless steel, polypropylene, and wood spheres were inoculated with M. haemolytica, placed in each microenvironment, and cultured for viable bacteria at 0, 2, 6, 24, and 48 h after inoculation. Presence or absence of growth of M. haemolytica was confirmed by MALDI-TOF mass spectrometry. Both wood and plastic materials supported the recovery of viable bacteria for a much longer duration than stainless steel. Additionally, increased temperature and decreased humidity lowered bacterial viability. These results demonstrate that both material and environment are factors related to M. haemolytica survival, which has potential biosecurity implications when managing BRD in beef and dairy operations.

Factors associated with bovine respiratory disease case fatality in feedlot cattle.

Bovine respiratory disease (BRD) is the primary cause of morbidity and mortality in cattle feedlots. There is a need to understand what animal health and production factors are associated with increased mortality risk due to BRD. The aim of the present study was to explore factors associated with BRD case fatality in feedlot cattle. Four pens totaling 898 steers were monitored daily for visual signs of BRD such as difficult breathing and coughing, and animals exhibiting signs of BRD were taken to the hospital shed for further examination and clinical measures. Blood samples were obtained at feedlot entry and at time of first BRD pull from animals diagnosed with BRD (n = 121) and those that died due to BRD confirmed by postmortem examination (n = 16; 13.2% case fatality rate). Mixed-effects linear regression models were used to estimate differences in animal health and production factors and the relative concentrations of 34 identified blood metabolites between animals that survived versus those that died. Generalized linear mixed-effects models were used to obtain the odds of being seronegative (at both feedlot entry and first BRD pull) to 5 BRD viruses and having a positive nasal swab result at the time of first pull in died and survived animals. Animals that died from BRD had lower average daily gain (ADG), reduced weight at first BRD pull, higher visual BRD scores and received more treatments for BRD compared with animals that survived BRD (P < 0.05). The odds of being seronegative for bovine viral diarrhea virus 1 (BVDV-1) were 5.66 times higher for animals that died compared with those that survived (P = 0.013). The odds of having a positive bovine coronavirus nasal swab result were 13.73 times higher in animals that died versus those that survived (P = 0.007). Animals that died from BRD had higher blood concentrations of α glucose chain, β-hydroxybutyrate, leucine, phenylalanine, and pyruvate compared with those that survived (P < 0.05). Animals that died from BRD had lower concentrations of acetate, citrate, and glycine compared with animals that survived (P < 0.05). The results of the current study suggest that ADG to first BRD pull, weight at first BRD pull, visual BRD score, the number of BRD treatments, seronegativity to BVDV-1, virus positive to BCoV nasal swab, and that certain blood metabolites are associated with BRD case fatality risk. The ability of these measures to predict the risk of death due to BRD needs further research.

Evaluation of reticulorumen temperature boluses for the diagnosis of subclinical cases of bovine respiratory disease in feedlot cattle.

Bovine respiratory disease (BRD) is the most important and costly health issue of the feedlot industry worldwide. Remote monitoring of reticulorumen temperature has been suggested as a potential tool to improve the diagnostic accuracy of BRD. The present study aimed to evaluate 1) the difference and degree of reticulorumen hyperthermia episodes between healthy and subclinical BRD feedlot steers, and 2) determine the correlation between reticulorumen hyperthermia and lung pathology, performance, and carcass traits. Mixed-breed feedlot steers (n = 148) with a mean arrival weight of 321 ± 3.34 kg were administered a reticulorumen bolus at feedlot entry and monitored for visual and audible signs of BRD until slaughter when lungs were examined and scored for lesions indicative of BRD. Post-slaughter animals with no record of BRD treatment were assigned to one of three case definitions. Healthy steers had no visual or audible signs of BRD (i.e., CIS=1), and total lung consolidation score < 5% or pleurisy score < 3 at slaughter. Subclinical BRD cases had a CIS of 1, and a lung consolidation score ≥ 5% or a pleurisy score of 3 at slaughter. Mild CIS cases had at least one CIS of 2, and a lung consolidation score < 5% and a pleurisy score < 3 at slaughter. Subclinical BRD and mild CIS cases had longer total duration of reticulorumen hyperthermia, more episodes and longer average episode duration above 40.0 °C compared to healthy steers (P < 0.05). A moderate positive correlation was found between lung consolidation and total duration (r = 0.27, P < 0.001), episode duration (r = 0.29, P < 0.001), and number of episodes (r = 0.20, P < 0.05). Pleurisy score was also found to be moderately and positively correlated with total duration (r = 0.23, P < 0.01), episode duration (r = 0.37, P < 0.001), and number of episodes (r = 0.26, P < 0.01). Moderate negative correlations were found between reticulorumen hyperthermia and carcass traits including hot standard carcass weight (HSCW) (-0.22 ≤ r ≤ -0.23, P < 0.05) and P8-fat depth (-0.18 ≤ r ≤ -0.32, P < 0.05). Subclinical BRD reduced carcass weight by 22 kg and average daily gain (ADG) by 0.44 kg/day compared to healthy steers (P < 0.05), but mild CIS cases had no effect on performance (P > 0.05). The reticulorumen bolus technology appears promising for detection of subclinical BRD cases in feedlot cattle as defined by lung pathology at slaughter.

Identifying Loci Associated With Bovine Corona Virus Infection and Bovine Respiratory Disease in Dairy and Feedlot Cattle

Bovine coronavirus (BCoV) is associated with respiratory and enteric infections in both dairy and beef cattle worldwide. It is also one of a complex of pathogens associated with bovine respiratory disease (BRD), which affects millions of cattle annually. The objectives of this study were to identify loci and heritability estimates associated with BCoV infection and BRD in dairy calves and feedlot cattle. Dairy calves from California (n = 1,938) and New Mexico (n = 647) and feedlot cattle from Colorado (n = 915) and Washington (n = 934) were tested for the presence of BCoV when classified as BRD cases or controls following the McGuirk scoring system. Two comparisons associated with BCoV were investigated: (1) cattle positive for BCoV (BCoV+) were compared to cattle negative for BCoV (BCoV−) and (2) cattle positive for BCoV and affected with BRD (BCoV+BRD+) were compared to cattle negative for BCoV and BRD (BCoV−BRD−). The Illumina BovineHD BeadChip was used for genotyping, and genome-wide association analyses (GWAA) were performed using EMMAX (efficient mixed-model association eXpedited). The GWAA for BCoV+ identified 51 loci (p < 1 × 10−5; 24 feedlot, 16 dairy, 11 combined) associated with infection with BCoV. Three loci were associated with BCoV+ across populations. Heritability estimates for BCoV+ were 0.01 for dairy, 0.11 for feedlot cattle, and 0.03 for the combined population. For BCoV+BRD+, 80 loci (p < 1 × 10−5; 26 feedlot, 25 dairy, 29 combined) were associated including 14 loci across populations. Heritability estimates for BCoV+BRD+ were 0.003 for dairy, 0.44 for feedlot cattle, and 0.07 for the combined population. Several positional candidate genes associated with BCoV and BRD in this study have been associated with other coronaviruses and respiratory infections in humans and mice. These results suggest that selection may reduce susceptibility to BCoV infection and BRD in cattle.