Bovine torovirus (BoTV) is a pleomorphic virus with a spike-bearing envelope and a linear, non-segmented, positive-sense single-stranded RNA genome. This kidney-shaped virus is associated with diarrhea in calves and apparently has a worldwide distribution. This review provides details of the history and taxonomy of BoTV since its discovery in 1979. Information about virion morphology and architecture, antigenic and biological properties, viral genome, protein composition, thermal and chemical stability, and pH and proteolytic enzymes resistance is also summarized. A major focus of this review is to postulate a possible epidemiological cycle for BoTV, based on epidemiological data obtained in our studies and other published data, and progressing from the newborn calf to the adult animal. The distribution, host range, pathogenesis, disease and clinical signs (under experimental and natural exposure), pathology, diagnosis, prevention, treatment and control of BoTV infections are also described. In addition, a discussion of the zoonotic implications of torovirus-like particles detected in patients with gastroenteritis that resemble and cross-react with BoTV is presented. Hopefully, the findings described here will alert others to the existence of BoTV in cattle and its contribution to the diarrheal disease complex. This review also highlights the need for continual vigilance for potential zoonotic viruses belonging to the order Nidovirales, such as the SARS coronavirus.

The tonsil of the soft palate in pigs is a secondary lymphoid tissue that provides a first line of defense against foreign antigens entering by the mouth or nares. It has been known for a long time to be the site of colonization of important swine and zoonotic bacterial pathogens. Initially our understanding of microbes present at this site came from culture-based studies. Very recently, sequence-based approaches have been used to identify the core microbiome of the swine tonsil. Although animal to animal and herd to herd variation was detected in these studies, >90 of the organisms detected belonged to the phyla Proteobacteria and Firmicutes. Members of the family Pasteurellaceae appeared to be predominate in the tonsil; however, the relative proportions of Actinobacillus, Haemophilus, and Pasteurella varied. Members of the families Moraxellaceae, Fusobacteriaceae, Veillonellaceae, and Neisseriaceae were also seen as frequent residents of the tonsil.

The objective of this article is to summarize the current state of knowledge of the complex interaction of porcine reproductive and respiratory syndrome virus (PRRSV) and porcine pulmonary intravascular macrophages (PIMs). PIMs play an important role in pulmonary surveillance, and in the past few years we have investigated their role in PRRSV infection. PRRSV antigens and nucleic acids have been demonstrated in PIMs both in vitro and in vivo. Examination of cultured PIMs infected with PRRSV revealed the accumulation of viral particles in the smooth-walled vesicles. PRRSV-infected PIMs in vitro yielded a virus titer similar to pulmonary alveolar macrophages. PRRSV infection induces either apoptosis or cell lysis of PIMs. The in vitro bactericidal activity of PRRSV-infected PIMs is significantly decreased. Phagocytic activity of PIMs, as measured by pulmonary copper clearance, is significantly decreased in PRRSV-infected pigs. This evidence supports the hypothesis that PRRSV-induced damage to PIMs results in increased susceptibility to bacteremic diseases. Recent studies with PRRSV and Streptococcus suis coinfection confirmed that PRRSV predisposes pigs to S. suis infection and bacteremia. These results could explain the increase in bacterial respiratory diseases and septicemias observed in PRRSV-infected pigs.

Listeria monocytogenes is amongst the most intriguing and well studied of the pathogenic bacteria. However, the understanding and perspective one has of L. monocytogenes depends to a large extent on the microbiological issues with which one is faced as a part of your professional duties. The focus of the veterinary clinician or investigator is likely to be foremost on the neurologic (circling disease) and reproductive diseases L. monocytogenes causes. To the food microbiologist, the principal concern is to prevent introduction of L. monocytogenes into food products, or to identify its presence and prevent its multiplication to numbers of organisms that are likely to pose a substantial risk to humans who ingest the product. To the cellular immunologist, listeriosis represents a robust murine model that helped to elucidate many important concepts in innate and adaptive immunity, and L. monocytogenes is a potential vector for delivery of novel vaccines. To the student of molecular pathogenesis, L. monocytogenes is a powerful and well-characterized model organism for studying the cellular microbiology of an intracellular pathogen. In this brief overview, I will attempt to highlight some of the classical observations, and contemporary insights, on L. monocytogenes and listeriosis, and integrate these perspectives into a common framework. By so doing, I hope to provide those with one perspective on listeriosis with an appreciation of the broad array of problems and issues faced by those who focus on some other aspect of L. monocytogenes and its pathogenesis.

Dendritic cells are central to the initiation of primary immune responses. They are the only antigen-presenting cell capable of stimulating naive T cells, and hence they are pivotal in the generation of adaptive immunity. Dendritic cells also interact with and influence the response of cells of the innate immune system. The manner in which dendritic cells influence the responses in cells of both the innate and adaptive immune systems has consequences for the bias of the adaptive response that mediates immunity to infection after vaccination or infection. It also provides an opportunity to intervene and to influence the response, allowing ways of developing appropriate vaccination strategies. Mouse and human studies have identified myeloid, lymphoid and plasmacytoid dendritic cells. Studies in domesticated animals with agents of specific infectious diseases have confirmed the applicability of certain of the generic models developed from mice or from in vitro studies on human cells. In vivo and ex vivo studies in cattle have demonstrated the existence of a number of subpopulations of myeloid dendritic cells. These cells differ in their ability to stimulate T cells and in the cytokines that they produce, observations clearly having important implications for the bias of the T-cell response. Dendritic cells also interact with the innate immune system, inducing responses that potentially bias the subsequent adaptive response.

HoBi-like viruses, also referred to as bovine viral diarrhea virus 3 (BVDV-3) and atypical pestivirus, have been proposed as a new putative bovine pestivirus species. These viruses were first identified in the last decade and are currently distributed in at least three continents. Published findings suggest that these viruses may be endemic at least in parts of South America and Asia. The clinical presentations in cattle, described in field outbreaks and controlled studies, are similar to those associated with BVDV and range from subclinical to mild clinical signs, sporadically associated with reproductive losses, respiratory illness and hemorrhagic syndrome. The complete host range of HoBi-like virus is unknown, but data suggest higher adaptation of HoBi-like viruses to ruminants than swine. Acute infections, characterized by mild clinical signs, such as low-grade pyrexia and leukopenia, have been observed in both cattle and sheep. Virus has been isolated from nasal swabs indicating that virus was being shed. While seroconversion has been observed in pigs, no clinical presentation or viral shedding was evident following inoculation. While some commercial BVDV diagnostic tests may detect HoBi-like viruses, these tests do not differentiate between BVDV and HoBi-like viruses. The differentiation of BVDV and HoBi-like viruses is critical to the design of surveillance programs for these viruses.

Routine procedures carried out on piglets (i.e. castration, tail docking, teeth clipping, and ear notching) are considered painful. Unfortunately the efficacy of current pain mitigation modalities is poorly understood. The aim of this systematic review was to synthesize the existing primary scientific literature regarding the effectiveness of pain management interventions used for routine procedures on piglets. The review question was, ‘In piglets under twenty-eight days old, undergoing castration, tail docking, teeth clipping, and/or methods of identification that involve cutting of the ear tissue, what is the effect of pain mitigation compared with no pain mitigation on behavioral and non-behavioral outcomes that indicate procedural pain and post-procedural pain?’ A review protocol was designed a priori. Data sources used were Agricola (EBSCO), CAB Abstracts (Thomson Reuters), PubMed, Web of Science (Thomson Reuters), BIOSIS Previews (Thomson Reuters), and ProQuest Dissertations & Theses Full Text. No restrictions on year of publication or language were placed on the search. Eligible studies assessed an intervention designed to mitigate the pain of the procedures of interest and included a comparison group that did not receive an intervention. Eligible non-English studies were translated using a translation service. Two reviewers independently screened titles and abstracts for relevance using pre-defined questions. Data were extracted from relevant articles onto pre-defined forms. From the 2203 retrieved citations forty publications, containing 52 studies met the eligibility criteria. In 40 studies, piglets underwent castration only. In seven studies, piglets underwent tail docking only. In one study, piglets underwent teeth clipping only, and in one study piglets underwent ear notching only. Three studies used multiple procedures. Thirty-two trial arms assessed general anesthesia protocols, 30 trial arms assessed local anesthetic protocols, and 28 trial arms assessed non-steroidal anti-inflammatory drugs (NSAIDs) protocols. Forty-one trial arms were controls where piglets received either placebo or no treatment. Forty-five outcomes were extracted from the studies, however only the results from studies that assessed cortisol (six studies), β-endorphins (one study), vocalisations (nine studies), and pain-related behaviors (nine studies) are reported. Other outcomes were reported in only one or two studies. Confident decision making will likely be difficult based on this body of work because lack of comprehensive reporting precludes calculation of the magnitude of pain mitigation for most outcomes.

There is a growing concern about the role of the environment in the dissemination of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG). In this systematic review, we summarize evidence for increases of ARG in the natural environment associated with potential sources of ARB and ARG such as agricultural facilities and wastewater treatment plants. A total of 5247 citations were identified, including studies that ascertained both ARG and ARB outcomes. All studies were screened for relevance to the question and methodology. This paper summarizes the evidence only for those studies with ARG outcomes (n = 24). Sixteen studies were at high (n = 3) or at unclear (n = 13) risk of bias in the estimation of source effects due to lack of information or failure to control for confounders. Statistical methods were used in nine studies; three studies assessed the effect of multiple sources using modeling approaches, and none reported effect measures. Most studies reported higher ARG concentration downstream/near the source, but heterogeneous findings hindered making any sound conclusions. To quantify increases of ARG in the environment due to specific point sources, there is a need for studies that emphasize analytic or design control of confounding, and that provide effect measure estimates.

The sensitivity of culturing Brachyspira hyodysenteriae was determined after sampling with swabs from porcine fecal specimens inoculated with tenfold dilutions of a field strain of these microbes. After storage of swabs, Brachyspira hyodysenteriaewas recovered throughout the first 3 weeks after inoculation from feces with more than 140 cells/g. Viable spirochetes could still be recovered after up to 83 days of storage from feces, with 1.4 × 106 cells or more per gram. Culture for Brachyspira spp. was performed on 285 rectal swabs, which were pooled in batches of five. The number of pooled samples positive for B. hyodysenteriae corresponded with the sum results of individual analysis of the corresponding collections of five samples. A PCR system based on the tlyA gene of B. hyodysenteriae was developed and tested on primary cultures of pooled samples. The results of the PCR assay showed a 97% correlation with the culture results. The prevalence of Brachyspira spp. was determined in five swine herds and found to be highest among breeding gilts and boars aged 13–16 weeks and among 6–12-week-old weaned pigs. In contrast, Brachyspiraspp. were only rarely found in sows, which may reflect the development of immunity by adult pigs to all species of the genus.

A cell culture system for the tick-borne rickettsia Anaplasma marginale offers new opportunities for research on this economically important pathogen of cattle. A. marginale multiplies in membrane-bound inclusions in host cells. Whereas erythrocytes appear to be the only site of infection in cattle, A. marginale undergoes a complex developmental cycle in ticks and transmission occurs via the salivary glands during feeding. We recently developed a cell culture system for A. marginale using a cell line derived from embryos of Ixodes scapularis. Here we review the use of this cell culture system for studying the interaction of A. marginale with tick cells. Several assays were developed using the A. marginale/tick cell system. An adhesion assay was developed for the identification of proteins required by A. marginale for adhesion to tick cells. The effect of antibodies against selected major surface proteins in inhibiting A. marginale infection was tested in an assay that allowed further confirmation of the role of surface proteins in the infection of tick cells. A drug screening assay for A. marginale was developed and provides a method of initial drug selection without the use of cattle. The culture system was used to test for enhancing effects of tick saliva and saliva components on A. marginale infection. The tick cell culture system has proved to be a good model for studying A. marginale–tick interactions. Information gained from these studies may be applicable to other closely related tick-borne pathogens that have been propagated in the same tick cell line.

Colistin, a peptide antibiotic belonging to the polymyxin family, is one of the last effective drugs for the treatment of multidrug resistant Gram-negative infections. Recent discovery of a novel mobile colistin resistance gene, mcr-1, from people and food animals has caused a significant public health concern and drawn worldwide attention. Extensive usage of colistin in food animals has been proposed as a major driving force for the emergence and transmission of mcr-1; thus, there is a worldwide trend to limit colistin usage in animal production. However, despite lack of colistin usage in food animals in the USA, mcr-1-positive Escherichia coli isolates were still isolated from swine. In this paper, we provided an overview of colistin usage and epidemiology of mcr-1 in food animals, and summarized the current status of mechanistic and evolutionary studies of the plasmid-mediated colistin resistance. Based on published information, we further discussed several non-colistin usage risk factors that may contribute to the persistence, transmission, and emergence of colistin resistance in an animal production system. Filling the knowledge gaps identified in this review is critical for risk assessment and risk management of colistin resistance, which will facilitate proactive and effective strategies to mitigate colistin resistance in future animal production systems.

The neurophysiological response of an animal to stress involves the production of a number of stress-related neurochemicals including the catecholamines norepinephrine and epinephrine. It is generally believed that such neurochemicals belong exclusively to the animal kingdom and that any role such neurochemicals play in the infective process is largely confined to host physiology and immunology-related parameters. This, however, is wholly incorrect as many of the bacterial species that are known to cause infections possess the capacity to not only recognize neuroendocrine hormones produced by the host in response to stress, but also synthesize the very same neurochemicals. Given this, infectious microorganisms are capable of directly responding to the neurochemical outflow resulting from a stress event and initiating pathogenic processes. Although the neuroendocrine environment of the lung following a stress event is not fully understood, it most likely possesses abundant levels of stress-related neurochemicals due to its rich blood supply and rich noradrenergic tissue innervation. The ability of microorganisms to recognize and produce neurochemicals that can influence the host, known as microbial endocrinology, provides for a mechanistic basis with which to examine the ability of stress to influence health and susceptibility to disease.

The primary source of data on bovine respiratory disease (BRD) prevalence in US adult dairy cattle is producer surveys, which estimate that 2.4–2.9% of cattle are affected. This estimate appears low when compared to calculations based on limited data regarding on-farm deaths due to BRD and the number of carcasses at slaughter with severe BRD. These calculations indicate that approximately 3% of dairy cows die on farm or go to slaughter with severe BRD. Not included in these data are cows that are treated for BRD and retained. The primary manifestation of BRD on dairy farms is in calves. Nationwide surveys have estimated that 12.4–16.4% of preweaned dairy heifer calves are affected with BRD, and 5.9–11% of calves are affected after weaning. More detailed prevalence studies have generally included a limited number of small farms, with limited calf age range studied. All studies relied on producer diagnosis. Prevalence in these studies ranged from 0 to 52%, with many cases occurring before weaning, and with BRD being associated with increased calf death rates. BRD affects heifer growth. It appears to have a small effect on age at first calving, and some studies have shown small effects on performance and herd life after calving. First lactation performance of heifers depends on many factors that can obscure the effects of calfhood BRD.

Listeria monocytogenes causes several clinical manifestations in humans and domestic animals. This bacterium is a saprophyte in soil and ensiled feeds, which are sources of infection for food producing animals (i.e. ruminants). The most common route of infection for people is via ingestion of contaminated ready-to-eat food products such as produce, soft cheeses and deli meats. In the United States, L. monocytogenes causes relatively few cases of clinical disease compared to other food-borne pathogens. However, clinical listeriosis is associated with high mortality, especially in immunocompromised patients, pregnant women, neonates, and the elderly. Listeria is an intracellular pathogen, which has been widely used in basic research to elucidate mechanisms of molecular pathogenesis and protective cell-mediated immunity. Despite the sizeable knowledge on L. monocytogenes pathogenesis, key points regarding listeriosis during pregnancy and the perinatal period remain unknown. This review summarizes listeriosis in humans and domestic animals during pregnancy, and animal models used to study the pathogenesis and immune response to L. monocytogenes infection during these periods.

Piglets reared in swine production in the USA undergo painful procedures that include castration, tail docking, teeth clipping, and identification with ear notching or tagging. These procedures are usually performed without pain mitigation. The objective of this project was to develop recommendations for pain mitigation in 1- to 28-day-old piglets undergoing these procedures. The National Pork Board funded project to develop recommendations for pain mitigation in piglets. Recommendation development followed a defined multi-step process that included an evidence summary and estimates of the efficacies of interventions. The results of a systematic review of the interventions were reported in a companion paper. This manuscript describes the recommendation development process and the final recommendations. Recommendations were developed for three interventions (CO2/O2 general anesthesia, non-steroidal anti-inflammatory drugs (NSAIDs), and lidocaine) for use during castration. The ability to make strong recommendations was limited by low-quality evidence and strong certainty about variation in stakeholder values and preferences. The panel strongly recommended against the use of a CO2/O2 general anesthesia mixture, weakly recommended for the use of NSAIDs and weakly recommended against the use of lidocaine for pain mitigation during castration of 1- to 28-day-old piglets.

Bovine viral diarrhea viruses (BVDV) are diverse genetically and antigenically. This diversity impacts both diagnostic testing and vaccination. In North America, there are two BVDV species, 1 and 2 with 3 subgentoypes, BVDV1a, BVDV1b and BVDV2a. Initially, US vaccines contained BVDV1a cytopathic strains. With the reporting of BVDV2 severe disease in Canada and the USA there was focus on protection by BVDV1a vaccines on BVDV2 disease. There was also emphasis of controlling persistently infected (PI) cattle resulted in studies for fetal protection afforded by BVDV1a vaccines. Initially, studies indicated that some BVDV1a vaccines gave less than 100% protection against BVDV2 challenge for fetal infection. Eventually vaccines in North America added BVDV2a to modified live virus (MLV) and killed BVDV1a vaccines. Ideally, vaccines should stimulate complete immunity providing 100% protection against disease, viremias, shedding, and 100% fetal protection in vaccinates when challenged with a range of diverse antigenic viruses (subgenotypes). There should be a long duration of immunity stimulated by vaccines, especially for fetal protection. MLV vaccines should be safe when given according to the label and free of other pathogens. While vaccines have now included BVDV1a and BVDV2a, with the discovery of the predominate subgenotype of BVDV in the USA to be BVDV1b, approximately 75% or greater in prevalence, protection in acute challenge and fetal protection studies became more apparent for BVDV1b. Thus many published studies examined protection by BVDV1a and BVDV2a vaccines against BVDV1b in acute challenge and fetal protection studies. There are no current BVDV1b vaccines in the USA. There are now more regulations on BVDV reproductive effects by the USDA Center for Veterinary Biologics (CVB) regarding label claims for protection against abortion, PI calves, and fetal infections, including expectations for studies regarding those claims. Also, the USDA CVB has a memorandum providing the guidance for exemption of the warning label statement against the use of the MLV BVDV in pregnant cows and calves nursing pregnant cows. In reviews of published studies in the USA, the results of acute challenge and fetal protection studies are described, including subgenotypes in vaccines and challenge strains and the results in vaccinates and the vaccinates' fetuses/newborns. In general, vaccines provide protection against heterologous strains, ranging from 100% to partial but statistically significant protection. In recent studies, the duration of immunity afforded by vaccines was investigated and reported. Issues of contamination remain, especially since fetal bovine serums may be contaminated with noncytopathic BVDV. In addition, the potential for immunosuppression by MLV vaccines exists, and new vaccines will be assessed in the future to prove those MLV components are not immunosuppressive by experimental studies. As new subgenotypes are found, the efficacy of the current vaccines should be evaluated for these new strains.

Bovine viral diarrhea virus (BVDV) has long been associated with a wide variety of clinical syndromes and immune dysregulation, many which result in secondary bacterial infections. Current understanding of immune cell interactions that result in activation and tolerance are explored in light of BVDV infection including: depletion of lymphocytes, effects on neutrophils, natural killer cells, and the role of receptors and cytokines. In addition, we review some new information on the effect of BVDV on immune development in the fetal liver, the role of resident macrophages, and greater implications for persistent infection.

Antibiotic resistance (AR) is ancient. Use of antibiotics is a selective driving force that enriches AR genes and promotes the emergence of resistant pathogens. It also has been widely accepted that horizontal gene transfer (HGT) occurs everywhere and plays a critical role in the transmission of AR genes among bacteria. However, our understanding of HGT processes primarily build on extensive in vitro studies; to date, there is still a significant knowledge gap regarding in situ HGT events as well as the factors that influence HGT in different ecological niches. This review is focused on the HGT process in the intestinal tract, a ‘melting pot’ for gene exchange. Several factors that potentially influence in vivo HGT efficiency in the intestine are identified and summarized, which include SOS-inducing agents, stress hormones, microbiota and microbiota-derived factors. We highlight recent discoveries demonstrating that certain antibiotics, which are widely used in animal industry, can enhance HGT in the intestine by serving as DNA-damaging, SOS-inducing agents. Despite recent progress, research on in vivo HGT events is still in its infancy. A better understanding of the factors influencing HGT in the intestine is highly warranted for developing effective strategies to mitigate AR in animal production as well as in future agricultural ecosystems.

Bovine respiratory disease (BRD) is the most expensive disease affecting United States cattle. Recently weaned calves are the focus of prevention and treatment research. Identifying affected cattle early in the course of BRD is difficult. Intervention during the early stages of BRD improves treatment outcomes; however, cattle as prey animals are excellent at hiding signs of disease, especially if the caregiver has not gained their trust. Depression, appetite loss, and changes in respiratory character are the principal signs used to identify BRD. Rectal temperatures from cattle pulled for treatment are a final measure of evaluation. Cattle suffering from subclinical BRD frequently escape identification and treatment. Observations of lungs at packing plants for anterior ventral (AV) lesions frequently document higher BRD incidence rates than observed pre-harvest, suggesting subclinical BRD is common. Data from numerous studies document lower average daily gains (ADG) from cattle with AV lung lesions at packing plants that were not treated for BRD compared with cattle with normal lungs. Scoring lung lesions at the packing plant can be a useful tool for gaining insight into BRD incidence. Data indicate that BRD lowers ADG by 0.2 lbs on average, and lowers the USDA Quality Grade by 50 marbling points.

We conducted a systematic review and network meta-analysis to determine the comparative efficacy of antibiotics used to control bovine respiratory disease (BRD) in beef cattle on feedlots. The information sources for the review were: MEDLINE®, MEDLINE In-Process and MEDLINE® Daily, AGRICOLA, Epub Ahead of Print, Cambridge Agricultural and Biological Index, Science Citation Index, Conference Proceedings Citation Index – Science, the Proceedings of the American Association of Bovine Practitioners, World Buiatrics Conference, and the United States Food and Drug Administration Freedom of Information New Animal Drug Applications summaries. The eligible population was weaned beef cattle raised in intensive systems. The interventions of interest were injectable antibiotics used at the time the cattle arrived at the feedlot. The outcome of interest was the diagnosis of BRD within 45 days of arrival at the feedlot. The network meta-analysis included data from 46 studies and 167 study arms identified in the review. The results suggest that macrolides are the most effective antibiotics for the reduction of BRD incidence. Injectable oxytetracycline effectively controlled BRD compared with no antibiotics; however, it was less effective than macrolide treatment. Because oxytetracycline is already commonly used to prevent, control, and treat BRD in groups of feedlot cattle, the use of injectable oxytetracycline for BRD control might have advantages from an antibiotic stewardship perspective.