The genesis for this special issue on pestiviruses was a joint meeting on pestiviruses organized by the US BVDV Symposia Committee and the European Society for Veterinary Virology that was held October 14 and 15, 2014 in Kansas City, MO. The theme of the meeting was “Pestiviruses: Old enemies and new challenges”. The impetus for this joint effort was the recognition that regional approaches to disease control are at odds with the worldwide traffic in animal products and biologics. Further, the control of newly recognized pestiviruses, such as HoBi-like viruses, is more effective when approached as a global challenge rather than any one nation's problem. The joint meeting featured talks by researchers from North America, South America, Australia and Europe. The papers in this issue arose from keynote talks presented at the joint meeting and are organized around the following themes; pestiviruses and the immune system, genetic variability, the emergence of new pestiviruses and pestivirus control programs.

Loop-mediated isothermal amplification (LAMP) is a simple, powerful state-of-the-art gene amplification technique used for the rapid diagnosis and early detection of microbial diseases. Many LAMP assays have been developed and validated for important epizootic diseases of livestock. We review the LAMP assays that have been developed for the detection of 18 viruses deemed notifiable of ruminants, swine and poultry by the World Organization for Animal Health (OIE). LAMP provides a fast (the assay often takes less than an hour), low cost, highly sensitive, highly specific and less laborious alternative to detect infectious disease agents. The LAMP procedure can be completed under isothermal conditions so thermocyclers are not needed. The ease of use of the LAMP assay allows adaptability to field conditions and works well in developing countries with resource-limited laboratories. However, this technology is still underutilized in the field of veterinary diagnostics despite its huge capabilities.

This review identifies priorities for beef cattle welfare research in the USA. Based on our professional expertise and synthesis of existing literature, we identify two themes in intensive aspects of beef production: areas where policy-based actions are needed and those where additional research is required. For some topics, considerable research informs best practice, yet gaps remain between scientific knowledge and implementation. For example, many of the risk factors and management strategies to prevent respiratory disease are understood, but only used by a relatively small portion of the industry. This is an animal health issue that will require leadership and discussion to gain widespread adoption of practices that benefit cattle welfare. There is evidence of success when such actions are taken, as illustrated by the recent improvements in handling at US slaughter facilities. Our highest priorities for additional empirical evidence are: the effect of technologies used to either promote growth or manage cattle in feedlots, identification of management risk factors for disease in feedlots, and management decisions about transport (rest stops, feed/water deprivation, climatic conditions, stocking density). Additional research is needed to inform science-based recommendations about environmental features such as dry lying areas (mounds), shade, water and feed, as well as trailer design.

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.

The objective of this paper was to perform a critical review of the literature as it pertains to the current status of antimicrobial resistance in pathogens associated with bovine respiratory disease (BRD) in beef cattle and to provide a concise yet informative narrative on the most relevant publications available. As such, the scientific literature contained in PubMed, AGRICOLA, and CAB were searched in February of 2014 for articles related to susceptibility testing of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni from cases of BRD. Titles and abstracts were read and 105 articles that were relevant to the subject of BRD antibiotic resistance were attained for further review. After the application of exclusion criterion (publications must have originated from North America, be in English, adhere to standards set forth by the Clinical and Laboratory Standards Institute, and be concerning antimicrobial resistance in BRD in beef cattle), 16 articles remained and are the focus of this publication. Due to the disparate data from the few studies that investigate susceptibility testing of BRD pathogens, a quantitative assessment or meta-analysis was not performed on the studies presented in this review. However, considering diagnostic lab data, there appears to be a clear trend of a decrease in susceptibility of the three major BRD pathogens to the antimicrobials used commonly for treatment and control of BRD. Studies performing sensitivity testing on healthy cattle report much lower resistance, but it remains unclear if this is because of a true lack of resistance mechanisms, or if the isolates do contain quiescent genes for resistance that are only phenotypically expressed following the administration of an antimicrobial for either treatment or control of BRD. Future research to address this question of genotype and phenotypic expression before and after antimicrobial administration will further advance our knowledge in this area.

Infection of pregnant cows with noncytopathic (ncp) bovine viral diarrhea virus (BVDV) induces rapid innate and adaptive immune responses, resulting in clearance of the virus in less than 3 weeks. Seven to 14 days after inoculation of the cow, ncpBVDV crosses the placenta and induces a fetal viremia. Establishment of persistent infection with ncpBVDV in the fetus has been attributed to the inability to mount an immune response before 90–150 days of gestational age. The result is ‘immune tolerance’, persistent viral replication and shedding of ncpBVDV. In contrast, we describe the chronic upregulation of fetal Type I interferon (IFN) pathway genes and the induction of IFN-γ pathways in fetuses of cows infected on day 75 of gestation. Persistently infected (PI) fetal IFN-γ concentrations also increased at day 97 at the peak of fetal viremia and IFN-γ mRNA was significantly elevated in fetal thymus, liver and spleen 14–22 days post maternal inoculation. PI fetuses respond to ncpBVDV infection through induction of Type I IFN and IFN-γ activated genes leading to a reduction in ncpBVDV titer. We hypothesize that fetal infection with BVDV persists because of impaired induction of IFN-γ in the face of activated Type I IFN responses. Clarification of the mechanisms involved in the IFN-associated pathways during BVDV fetal infection may lead to better detection methods, antiviral compounds and selection of genetically resistant breeding animals.

The bovine mammary gland is a dynamic and complex organ composed of various cell types that work together for the purpose of milk synthesis and secretion. A layer of endothelial cells establishes the blood–milk barrier, which exists to facilitate the exchange of solutes and macromolecules necessary for optimal milk production. During bacterial challenge, however, endothelial cells divert some of their lactation function to protect the underlying tissue from damage by initiating inflammation. At the onset of inflammation, endothelial cells tightly regulate the movement of plasma components and leukocytes into affected tissue. Unfortunately, endothelial dysfunction as a result of exacerbated or sustained inflammation can negatively affect both barrier integrity and the health of surrounding extravascular tissue. The objective of this review is to highlight the role of endothelial cells in supporting milk production and regulating optimal inflammatory responses. The consequences of endothelial dysfunction and sustained inflammation on milk synthesis and secretion are discussed. Given the important role of endothelial cells in orchestrating the inflammatory response, a better understanding of endothelial function during mastitis may support development of targeted therapies to protect bovine mammary tissue and mammary endothelium.

The control and prevention of bovine viral diarrhea virus (BVDV) infections has provided substantial challenges. Viral genetic variation, persistent infections, and viral tropism for immune cells have complicated disease control strategies. Vaccination has, however, provided an effective tool to prevent acute systemic infections and increase reproductive efficiency through fetal protection. There has been substantial controversy about the safety and efficacy of BVDV vaccines, especially when comparing killed versus modified-live viral (MLV) vaccines. Furthermore, numerous vaccination protocols have been proposed to protect the fetus and ensure maternal antibody transfer to the calf. These issues have been further complicated by reports of immune suppression during natural infections and following vaccination. While killed BVDV vaccines provide the greatest safety, their limited immunogenicity makes multiple vaccinations necessary. In contrast, MLV BVDV vaccines induce a broader range of immune responses with a longer duration of immunity, but require strategic vaccination to minimize potential risks. Vaccination strategies for breeding females and young calves, in the face of maternal antibody, are discussed. With intranasal vaccination of young calves it is possible to avoid maternal antibody interference and induce immune memory that persists for 6–8 months. Thus, with an integrated vaccination protocol for both breeding cows and calves it is possible to maximize disease protection while minimizing vaccine risks.

Toxoplasma gondii is a protozoa that causes toxoplasmosis in people and other animals. It is considered one of the most common parasitic infections in the world due to its impressive range of hosts, widespread environmental contamination and the diverse means by which animals can be infected. Despite its ubiquity and numerous ongoing research efforts into both its basic biology and clinical management, many aspects of diagnosis and management of this disease are poorly understood. The range of diagnostic options that is available for veterinary diagnostic investigators are notably more limited than those available to medical diagnosticians, making accurate interpretation of each test result critical. The current review joins other reviews on the parasite with a particular emphasis on the history and continued development of diagnostic tests that are useful for veterinary diagnostic investigations. An understanding of the strengths and shortcomings of current diagnostic techniques will assist veterinary and public health officials in formulating effective treatment and control strategies in diverse animal populations.

Classical swine fever is a highly contagious disease that affects domestic and wild pigs worldwide. The causative agent of the disease is Classical swine fever virus (CSFV), which belongs to the genus Pestivirus within the family Flaviviridae. On the genome level, CSFV can be divided into three genotypes with three to four sub-genotypes. Those genotypes can be assigned to distinct geographical regions. Knowledge about CSFV diversity and distribution is important for the understanding of disease dynamics and evolution, and can thus help to design optimized control strategies. For this reason, the geographical pattern of CSFV diversity and distribution are outlined in the presented review. Moreover, current knowledge with regard to genetic virulence markers or determinants and the role of the quasispecies composition is discussed.

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.

Passive immunization with pathogen-specific egg yolk antibodies (IgY) is emerging as a potential alternative to antibiotics for the treatment and prevention of various human and animal diseases. Laying hens are an excellent source of high-quality polyclonal antibodies, which can be collected noninvasively from egg yolks. The use of IgY offers several advantages in that it is environmentally friendly, nontoxic, and reduces the numbers of animals required for antibody production. This paper reviews the use of IgY antibodies in the treatment and prevention of enteric pathogen infections in poultry. Brief descriptions of the production, structure, and properties of IgY are also presented. Some limitations of the technology and future perspectives are discussed.

Until the early 1990s there were just three recognized species in the pestivirus genus, bovine viral diarrhea virus (BVDV), border disease virus (BDV) and classical swine fever virus (CSFV). Subsequently BVDV were divided into two different species, BVDV1 and BVDV2 and four additional putative pestivirus species have been identified, based on phylogenetic analysis. The four putative pestivirus specices, listed in chronological order of published reports, are Giraffe (isolated from one of several giraffes in the Nanyuki District of Kenya suffering from mucosal disease-like symptoms), HoBi (first isolated from fetal bovine serum originating in Brazil and later from samples originating in Southeast Asia), Pronghorn (isolated from an emaciated blind pronghorn antelope in the USA), and Bungowannah (isolated following an outbreak in pigs, resulting in still birth and neonatal death, in Australia). In addition to the emergence of putative new species of pestivirus, changes in host and virulence of recognized or ‘classic’ pestiviruses have led to reevaluation of disease control programs and management of domestic and wildlife populations.

The following history has been compiled and written by the authors. The historical facts are available from the Conference of Research Workers in Animal Diseases (CRWAD) archives, dating back to letters and summaries written by the founders, and by a few of the Secretary-Treasurers from the early decades through 2014. The Organization and Purpose: The CRWAD is a non-profit organization and has been since its origin. The sole purpose of CRWAD is to discuss and disseminate the most current research advances in animal diseases. Graduate students and industry and academic professionals present and discuss the most recent advances on subjects of interest to the CRWAD and of importance to the global livestock and companion animal industries. The oral and poster abstracts of new and unpublished data presented at the meeting sessions are published each year in the CRWAD Proceedings (formerly the CRWAD Abstracts). CRWAD publishes, copyrights, and distributes the Proceedings. The presentations are arranged into the following 10 sections, according to the primary topic of the presentation: Bacterial Pathogenesis, Biosafety and Biosecurity, Companion Animal Epidemiology, Ecology and Management of Foodborne Agents, Epidemiology and Animal Health Economics, Immunology, Pathobiology of Enteric and Foodborne Pathogens, Respiratory Diseases, Vector-Borne and Parasitic Diseases, and Viral Pathogenesis. Prospective members should be actively engaged in animal disease research or research administration. Meeting information and membership applications may be obtained by contacting the Executive Director or by visiting the CRWAD website. Annual abstracts are currently available on-line at the On-line Meeting Planner and Itinerary Builder, with access through the CRWAD website.

Bungowannah virus was discovered following an outbreak of stillbirths and sudden death in young pigs. Affected animals consistently showed a myocardopathy with signs of cardiac failure. After virus isolation and PCR investigations were unsuccessful, direct fetal inoculation was undertaken. Nucleic acid purified from serum from infected fetuses was subjected to sequence-independent single-primer amplification and nucleic acid sequencing. Sequences consistent with a pestivirus were obtained. The entire genome was identified but was genetically remote from the recognized pestivirus species. This virus was not recognized by pan-pestivirus reactive monoclonal antibodies but was subsequently detected in cell cultures by immunoperoxidase staining using convalescent sow serum. Experimental infections of sows at different stages of gestation reproduced the myocarditis syndrome. Pre-weaning losses of 70 and 29% were observed following infection at days 35 and 90, respectively. Piglets infected at day 35 were shown to be persistently infected, while chronic infections were observed after fetal infection at day 55. Chronically infected piglets showed growth retardation and were viremic for up to 7 months. Myocarditis was associated with infection in late gestation (day 90). Non-pregnant sheep and cattle have been experimentally infected but with no evidence of disease. Infection of pregnant cattle in early gestation resulted in both maternal and fetal infection, but all infected fetuses mounted an antibody response to the virus. Analysis of the nucleic acid sequence confirmed that Bungowannah has a number of changes not observed in other pestiviruses. Genes encoding some of the structural proteins remain fully functional when inserted into a bovine viral diarrhea virus (BVDV) backbone. Cell culture-based studies have shown that Bungowannah virus will grow in cells extending from humans to bats as well as farm animals.

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.

In 2001, border disease virus (BDV) was identified as the cause of a previously unreported disease in Pyrenean chamois (Rupicapra pyrenaica) in Spain. Since then, the disease has caused a dramatic decrease, and in some cases collapse, of chamois populations and has expanded to nearly the entire distribution area in the Pyrenees. Chamois BDV was characterized as BDV-4 genotype and experimental studies confirmed that it was the primary agent of the disease. The infection has become endemic in the Central and Eastern Pyrenees. However, while most Pyrenean chamois populations have been severely affected by the disease, others have not, despite the circulation of BDV in apparently healthy individuals, suggesting the existence of different viral strategies for persisting in the host population. Changes in the interplay of pathogen, host and environmental factors may lead to the formation of different disease patterns. A key factor influencing disease emergence may be pathogen invasiveness through viral mutation. Host factors, such as behavior, immunity at the population level and genetic variability, may also have driven different epidemiological scenarios. Climatic and other ecological factors may have favored secondary infections, such as pneumonia, that under particular circumstances have been major contributing factors in the high mortality observed in some areas.

Programs for control and eradication of bovine viral diarrhea virus (BVDV) are often considered prudent when the expense of a control program within a specified time frame effectively prevents loss due to disease and the expense of control does not exceed the costs associated with infection. In some geographic areas, concerns about animal welfare or desires to reduce antibiotic usage may motivate BVDV control even when control programs are associated with a lack of financial return on investment. In other geographic areas, concerns about financial return on investment may be the key motivating factor in considering implementation of BVDV control programs. Past experiences indicate that systematic, well-coordinated control programs have a clear potential for success, while voluntary control programs in cultures of distributed decision-making often result in notable initial progress that ultimately ends in dissolution of efforts. Segmentation of the cattle industry into cow–calf producers, stocker/backgrounders, and feedlot operators amplifies the distribution of decision-making regarding control programs and may result in control measures for one industry segment that are associated with significant costs and limited rewards. Though the host range of BVDV extends well beyond cattle, multiple eradication programs that focus only on testing and removal of persistently infected (PI) cattle have proven to be effective in various countries. While some individuals consider education of producers to be sufficient to stimulate eradication of BVDV, research surrounding the adoption of innovative health care procedures suggests that the process of adopting BVDV control programs has a social element. Collegial interactions and discussions may be crucial in facilitating the systematic implementation necessary to optimize the long-term success of control programs. Compulsory control programs may be considered efficient and effective in some regions; however, in a nation where individual identification of cattle remains voluntary, the likelihood of effective compulsion to control BVDV within a farm or ranch appears to be very unlikely. While currently available diagnostic tests are sufficient to support BVDV eradication via systematic, well-coordinated programs, the development of a diagnostic procedure to safely and consistently detect the gestation of a PI fetus after 5 months of gestation would be a valuable research breakthrough. This desired testing modality would allow diagnosis of PI calves, while the dam continues to provide biocontainment of the infected fetus. This development could speed the progress of control programs in achieving the goal of BVDV control and eventual eradication.

Classical swine fever (CSF) is endemic in large parts of the world and it is a major threat to the pig industry in general. Vaccination and stamping out have been the most successful tools for the control and elimination of the disease. The systematic use of modified live vaccines (MLV), which are very efficacious and safe, has often preceded the elimination of CSF from regions or countries. Oral vaccination using MLV is a powerful tool for the elimination of CSF from wild boar populations. Bovine virus diarrhea (BVD) is endemic in bovine populations worldwide and programs for its control are only slowly gaining ground. With two genotypes BVD virus (BVDV) is genetically more diverse than CSF virus (CSFV). BVDV crosses the placenta of pregnant cattle resulting in the birth of persistently infected (PI) calves. PI animals shed enormous amounts of virus for the rest of their lives and they are the reservoir for the spread of BVDV in cattle populations. They are the main reason for the failure of conventional control strategies based on vaccination only. In Europe two different approaches for the successful control of BVD are being used: Elimination of PI animals without or with the optional use of vaccines, respectively.