Innate immune defenses are crucial for survival in the first days and weeks of life. At birth, newborns are confronted with a vast array of potentially pathogenic microorganisms that were not encountered in utero. At this age, cellular components of the adaptive immune system are in a naïve state and are slow to respond. Antibodies received from the dam are essential for defense, but represent a finite and dwindling resource. Innate components of the immune system detect pathogen-associated molecular patterns (PAMPs) on microorganisms (and their products) by means of pattern-recognition receptors (PRRs). Soluble mediators of the innate system such as complement proteins, pentraxins, collectins, ficolins, defensins, lactoferrin, lysozyme etc. can bind to structures on pathogens, leading to agglutination, interference with receptor binding, opsonization, neutralization, direct membrane damage and recruitment of additional soluble and cellular elements through inflammation. Cell-associated receptors such as the Toll-like receptors (TLRs) can activate cells and coordinate responses (both innate and adaptive). In this paper, accumulated knowledge of the receptors, soluble and cellular elements that contribute to innate defenses of young animals is reviewed. Research interest in this area has been intermittent, and the literature varies in quantity and quality. It is hoped that documentation of the limitations of our knowledge base will lead to more extensive and enlightening studies.

Histophilus somni (Haemophilus somnus) is one of the key bacterial pathogens involved in the multifactorial etiology of the Bovine Respiratory Disease Complex. This Gram negative pleomorphic rod also causes bovine septicemia, thrombotic meningencephalitis, myocarditis, arthritis, abortion and infertility, as well as disease in sheep, bison and bighorn sheep. Virulence factors include lipooligosaccharide, immunoglobulin binding proteins (as a surface fibrillar network), a major outer membrane protein (MOMP), other outer membrane proteins (OMPs) and exopolysaccharide. Histamine production, biofilm formation and quorum sensing may also contribute to pathogenesis. Antibodies are very important in protection as shown in passive protection studies. The lack of long-term survival of the organism in macrophages, unlike facultative intracellular bacteria, also suggests that antibodies should be critical in protection. Of the immunoglobulin classes, IgG2 antibodies are most implicated in protection and IgE antibodies in immunopathogenesis. The immunodominant antigen recognized by IgE is the MOMP and by IgG2 is a 40 kDa OMP. Pathogenetic synergy of bovine respiratory syncytial virus (BRSV) and H. somni in calves can be attributed, in part at least, to the higher IgE anti-MOMP antibody responses in dually infected calves. Other antigens are probably involved in stimulating host defense or immunopathology as well.

This review aims to explain the influence and characterization of the microbiome in the ruminant digestive system by presenting the knowledge collected so far. The knowledge presented in this work is focused on the main factors affecting the microbiome and the main dependencies that have been found in it so far. The microbiome in the rumen is the first to come into contact with the biomass of the forage and its main purpose is to decompose into smaller particles or compounds. With the gradual increase in knowledge about the microbiome, there is a chance to manipulate it so that the animal continues to live in a symbiotic relationship with it, while reducing greenhouse gas emissions to the environment as well as increasing feed efficiency. Therefore, understanding the influence of the ruminant microbiome is the main step to achieve such results. However, learning the relationship between microorganisms is only at an early stage, because research focuses mainly on taxonomy. Future research should focus on interactions in the ecosystem which is the microbiome, on explaining individual functions and on influence of environmental factors.

Efforts to curb production losses caused by nematode parasitism in sheep have led to the development of a number of control methods to complement or replace anthelmintics. The need for alternative control measures stems from the emergence of anthelmintic-resistant parasitic nematodes with reports of multi-class resistance to these drugs now emerging. A number of these control methods such as predacious microfungi, protein supplementation, plant extracts in feed and vaccines have demonstrated potential to control infection but require development and examination under natural conditions. Breeding for natural resistance to nematode infection has already shown success in controlling the disease under natural conditions. Selection for resistance is currently based on fecal egg count measurements but identification of genetic indicators of resistance will provide a more efficient method of selection. Current quantitative trait loci for nematode resistance include the MHC genes, interferon gamma gene, IgE gene and microsatellites on chromosome 1, 5 and 6. This paper reviews the current alternatives to anthelmintics to control infection, with an emphasis on breeding for host resistance and identification of genetic indicators of resistance.

Influenza is a highly contagious respiratory pathogen that continues to evolve and threaten both veterinary and human public health. Influenza A viruses are continually undergoing molecular changes through mutations, reassortment, and, in rare instances, recombination. While they generally cause benign enteric infection in their natural reservoir of wild aquatic birds, they can cause catastrophic and potentially lethal disease outbreaks in humans, domestic poultry, and pigs when they cross the host species barrier. The continuing circulation of highly pathogenic (HP) H5N1 influenza viruses in domestic poultry in parts of Eurasia and the emergence and global spread of pandemic H1N1 2009 are current examples of influenza evolution. The spread of both HP H5N1 and pandemic H1N1 to multiple hosts emphasizes the potential for continued evolution. In this review, we discuss the current understanding of influenza A virus structure and strategies of variation, with a specific focus on the HP H5N1 and pandemic H1N1 influenza viruses. Additionally, we attempt to identify the gaps in our knowledge of H5N1 and pandemic H1N1 influenza viruses. These gaps include (i) an understanding of the molecular determinants of influenza virus and the host that permit efficient transmissibility and pandemic potential, (ii) the urgent need for prospective surveillance in apparently healthy swine, (iii) the molecular determinants of high pathogenicity in poultry, pigs, and people, (iv) the genetic basis of host susceptibility, (v) antigenic variability, (vi) the use of vaccine to control influenza, (vii) the role of wild birds as the reservoir of highly pathogenic avian influenza, (viii) the problems with vaccines, (ix) seasonality, (x) co-infections, and (xi) anti-influenza drug resistance. Our failure to eradicate HP H5N1 globally and to explain why H5N1 does not transmit efficiently in humans while an H1N1 pandemic virus of swine origin spread globally in months are key examples that emphasize the critical need to bridge these knowledge gaps. Future directions in influenza research that will help us resolve each of the above-mentioned knowledge gaps include complete genomic and proteomic analysis of both the virus and the host with the prospect of designing new control strategies and the development of genetically resistant hosts.

Shiga toxin-producing Escherichia coli (STEC) strains are food-borne pathogens that are an important public health concern. STEC infection is associated with severe clinical diseases in human beings, including hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS), which can lead to kidney failure and death. Cattle are the most important STEC reservoir. However, a number of STEC outbreaks and HUS cases have been attributed to pork products. In swine, STEC strains are known to be associated with edema disease. Nevertheless, the relationship between STEC of swine origin and human illness has yet to be determined. This review critically summarizes epidemiologic and biological studies of swine STEC. Several epidemiologic studies conducted in multiple regions of the world have demonstrated that domestic swine can carry and shed STEC. Moreover, animal studies have demonstrated that swine are susceptible to STEC O157:H7 infection and can shed the bacterium for 2 months. A limited number of molecular epidemiologic studies, however, have provided conflicting evidence regarding the relationship between swine STEC and human illness. The role that swine play in STEC transmission to people and the contribution to human disease frequency requires further evaluation.

Infection of sheep with the abomasal nematode Teladorsagia circumcincta can cause a relative protein deficiency and reduce growth rate in growing lambs. A key event appears to be the destruction of junctions between epithelial cells. If the infection is heavy or prolonged, this leads to increased mucus production, hyperplasia, decreased acid production, gastrinemia, inappetance and pepsinogenemia. The severity of the infection depends upon the extent of concurrent infection, the nutritional status of the host and genetically controlled variation in the ability to mount protective immune responses.

Food-borne intoxication, caused by heat-stable enterotoxins produced by Staphylococcus aureus, causes over 240,000 cases of food-borne illness in the United States annually. Other staphylococci commonly associated with animals may also produce these enterotoxins. Foods may be contaminated by infected food handlers during slaughter and processing of livestock or by cross-contamination during food preparation. S. aureus also causes a variety of mild to severe skin and soft tissue infections in humans and other animals. Antibiotic resistance is common in staphylococci. Hospital-associated (HA) S. aureus are resistant to numerous antibiotics, with methicillin-resistant S. aureus (MRSA) presenting significant challenges in health care facilities for over 40 years. During the mid-1990s new human MRSA strains developed outside of hospitals and were termed community-associated (CA). A few years later, MRSA was isolated from horses and methicillin resistance was detected in Staphylococcus intermedius/pseudintermedius from dogs and cats. In 2003, a livestock-associated (LA) MRSA strain was first detected in swine. These methicillin-resistant staphylococci pose additional food safety and occupational health concerns. MRSA has been detected in a small percentage of retail meat and raw milk samples indicating a potential risk for food-borne transmission of MRSA. Persons working with animals or handling meat products may be at increased risk for antibiotic-resistant infections. This review discusses the scope of the problem of methicillin-resistant staphylococci and some strategies for control of these bacteria and prevention of illness.

Many viruses, including bovine herpesvirus-1 (BHV-1), bovine respiratory syncytial virus (BRSV), parainfluenzavirus-3 (PI3), bovine coronavirus, bovine viral diarrhea virus and bovine reovirus, have been etiologically associated with respiratory disease in cattle. This review focuses on the pathogenesis of BHV-1 and BRSV, two very different agents that primarily cause disease in the upper and lower respiratory tract, respectively.

Antimicrobial resistance (AMR) is an emerging problem in companion animals, because of difficult-to-treat infections, possible pressure to use antimicrobials that are important in human medicine, and potential zoonotic transmission. The extent and importance of AMR in companion animals are poorly understood, in part because of limited surveillance; however, it is clear that resistance is problematic in many pathogens and commensals, including staphylococci, enterococci, Escherichia coli and Salmonella.

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.

Herd size is frequently studied as a risk factor for swine diseases, yet the biological rationale for a reported association with herd size (whether positive or negative) is rarely adequately discussed in published epidemiological studies. Biologically plausible reasons for a positive association between herd size and disease include a greater risk of introduction of pathogens from outside the herd, greater risk of transmission of pathogens within and among herds when the herd is large, and effects of management and environmental factors that are related to herd size. However, compared with owners of small herds, owners of large herds might more frequently adopt management and housing practices that mitigate this theoretically increased risk. We used studies of pleuritis, pneumonia and pseudorabies to describe the epidemiological issues involved in evaluations of the relationship between management factors, herd size and disease. In future studies, we recommend that (i) herd size be measured in a way that best characterizes the true population at risk; (ii) studies that evaluate management-related risk factors should account for herd size wherever possible; (iii) population-based studies of the interrelationships among management factors and between management factors, herd size, herd density and pig density be done; (iv) likely biological reasons for any herd-size effect be postulated; and (v) the distribution of herd sizes in the source population and the study sample be described.

The alphavirus replicon technology has been utilized for many years to develop vaccines for both veterinary and human applications. Many developments have been made to the replicon platform recently, resulting in improved safety and efficacy of replicon particle (RP) vaccines. This review provides a broad overview of the replicon technology and safety features of the system and discusses the current literature on RP and replicon-based vaccines.

The porcine tonsils are a group of lymphoepithelial tissues located at the common openings of the gastrointestinal and respiratory tracts. The tonsils participate in a variety of functions involving innate, cellular and humoral immunity at the local and systemic levels. Among these immunological functions is the continuous surveillance for the presence of foreign antigens at the openings of the gastrointestinal and respiratory tracts. Within the pig, the movement of lymphocytes, cytokines and chemotactic molecules from the tonsils to other lymphoid organs confers immunity to other portals of pathogen entry and facilitates an efficient and rapid systemic immune response. In spite of the immunological nature of the tonsils, some microorganisms have acquired adaptations that allow them to circumvent the tonsillar immune defenses and utilize the tonsils as a site of entry, replication and colonization. Several bacterial and viral pathogens persist asymptomatically within the tonsils, making identification of asymptomatic carrier animals difficult in disease control and/or pathogen elimination. This paper reviews the current information on the anatomy, immunology and pathobiology of porcine tonsils and discusses the tonsils as a site of pathogen entry, replication and colonization using Salmonella spp., classical swine fever virus and porcine reproductive and respiratory syndrome virus as examples.

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.

Transmissible spongiform encephalopathies (TSEs) are a family of neurodegenerative diseases characterized by their long incubation periods, progressive neurological changes, and spongiform appearance in the brain. There is much evidence to show that TSEs are caused by an isoform of the normal cellular surface prion protein PrPC. The normal function of PrPC is still unknown, but it exhibits properties of a cupro-protein, capable of binding up to six copper ions. There are two differing views on copper's role in prion diseases. While one view looks at the PrPC copper-binding as the trigger for conversion to PrPSc, the opposing viewpoint sees a lack of PrPC copper-binding resulting in the conformational change into the disease causing isoform. Manganese and zinc have been shown to interact with PrPC as well and have been found in abnormal levels in prion diseases. This review addresses the interaction between select trace elements and the PrPC.

Swine influenza is an important contagious disease in pigs caused by influenza A viruses. Although only three subtypes of influenza A viruses, H1N1, H1N2 and H3N2, predominantly infect pigs worldwide, it is still a big challenge for vaccine manufacturers to produce efficacious vaccines for the prevention and control of swine influenza. Swine influenza viruses not only cause significant economic losses for the swine industry, but are also important zoonotic pathogens. Vaccination is still one of the most important and effective strategies to prevent and control influenza for both the animal and human population. In this review, we will discuss the current status of swine influenza worldwide as well as current and future options to control this economically important swine disease.

Proliferative enteropathy (PE; ileitis) is a common intestinal disease affecting susceptible pigs raised under various management systems around the world. Major developments in the understanding of PE and its causative agent, Lawsonia intracellularis, have occurred that have led to advances in the detection of this disease and methods to control and prevent it. Diagnostic tools that have improved overall detection and early onset of PE in pigs include various serological and molecular-based assays. Histological tests such as immunohistochemistry continue to be the gold standard in confirming Lawsonia-specific lesions in pigs post mortem. Despite extreme difficulties in isolating L. intracellularis, innovations in the cultivation and the development of pure culture challenge models, have opened doors to better characterization of the pathogenesis of PE through in vivo and in vitro L. intracellularis–host interactions. Advancements in molecular research such as the genetic sequencing of the entire Lawsonia genome have provided ways to identify various immunogens, metabolic pathways and methods for understanding the epidemiology of this organism. The determinations of immunological responsiveness in pigs to virulent and attenuated isolates of L. intracellularis and identification of various immunogens have led to progress in vaccine development.

Avian pneumovirus (APV) primarily causes an upper respiratory disease recognized as turkey rhinotracheitis (TRT) or swollen head syndrome (SHS) in chickens. The virus was first isolated in South Africa during the early 1970s and has subsequently been reported in Europe, Asia and South America. In February 1997, a serologically distinct APV isolate was officially reported in the USA following an outbreak of TRT during the previous year. This was the first report of these virus types in the USA; they were previously considered exotic to the USA and Canada. The predicted matrix (M) proteins of European APV type A and B isolates share 89% identity in their amino acid sequence. However, the predicted M protein of APV/CO is only 78%similar to the APV type A and 77% similar to the APV type B protein sequence. The predicted amino acid sequence of the US APV isolate's fusion (F) protein has 72% sequence identity to the F protein of APV type A and 71%sequence identity to the F protein of type B. This compares with the 83%sequence identity between the predicted amino acid sequences of the F proteins of APV types A and B. The lack of sequence heterogeneity among the US APV isolates over 2 years suggests that these viruses have maintained a relatively stable population since the first outbreak of TRT. Phylogenetic analysis of the M and F proteins, together with the serological uniqueness of the US APV isolates, supports their classification as a new APV, designated type C.

Hepatitis E virus (HEV) is an emerging pathogen belonging to a newly recognized family of RNA viruses (Hepeviridae). HEV is an important enterically transmitted human pathogen with a worldwide distribution. It can cause sporadic cases as well as large epidemics of acute hepatitis. Epidemics are primarily waterborne in areas where water supplies are contaminated with HEV of human origin. There is increasing evidence, however, that many animal species are infected with an antigenically similar virus. A recently isolated swine virus is the best candidate for causing a zoonotic form of hepatitis E. The virus is serologically cross-reactive with human HEV and genetically very similar, and the human and swine strains seem to be cross-infective. Very recent evidence has also shown that swine HEV, and possibly a deer strain of HEV, can be transmitted to humans by consumption of contaminated meat. In this review, we discuss the prevalence, pathogenicity, diagnosis and control of human HEV, swine HEV, the related avian HEV and HEV in other hosts and potential reservoirs.