Farm animal exposure, respiratory illnesses, and nasal cell gene expression.

BACKGROUND: Farm exposures in early life reduce the risks for childhood allergic diseases and asthma. There is less information about how farm exposures relate to respiratory illnesses and mucosal immune development. OBJECTIVE: We hypothesized that children raised in farm environments have a lower incidence of respiratory illnesses over the first 2 years of life than nonfarm children. We also analyzed whether farm exposures or respiratory illnesses were related to patterns of nasal cell gene expression. METHODS: The Wisconsin Infant Study Cohort included farm (n = 156) and nonfarm (n = 155) families with children followed to age 2 years. Parents reported prenatal farm and other environmental exposures. Illness frequency and severity were assessed using illness diaries and periodic surveys. Nasopharyngeal cell gene expression in a subset of 64 children at age 2 years was compared to farm exposure and respiratory illness history. RESULTS: Farm versus nonfarm children had nominally lower rates of respiratory illnesses (rate ratio 0.82 [95% CI, 0.69, 0.97]) with a stepwise reduction in illness rates in children exposed to 0, 1, or ≥2 animal species, but these trends were nonsignificant in a multivariable model. Farm exposures and preceding respiratory illnesses were positively related to nasal cell gene signatures for mononuclear cells and innate and antimicrobial responses. CONCLUSIONS: Maternal and infant exposure to farms and farm animals was associated with nonsignificant trends for reduced respiratory illnesses. Nasal cell gene expression in a subset of children suggests that farm exposures and respiratory illnesses in early life are associated with distinct patterns of mucosal immune expression.

Adaptation and evaluation of an ELISA for Trypanosoma evansi infection (surra) in elephants and its application to a serological survey in Thailand.

Trypanosoma evansi, the causative agent of surra, is widespread in domestic livestock and wildlife in South East Asia. Surra can affect cattle, buffaloes, horses and also Asian elephants (Elephas maximus). Despite the 'threatened to extinction' CITES status of elephant, surra's impact has not been thoroughly assessed yet in this species. This work offers to adapt an antibody enzyme-linked immunosorbent assay (ELISA) protocol, to detect Trypanosoma evansi antibodies in elephant serum. The test was validated with 365 negative-reference samples, which allowed the determination of a 16% positive threshold. The test was applied to a serological survey including 375 individuals. The estimated global seroprevalence was 2·1% (95% CI 1·1-4·2%). Therefore, surra does not appear to be endemic in Thai domestic elephants, but occasional outbreaks were reported to our laboratory during the survey period. These outbreaks seemed to be linked to close proximity to cattle or buffaloes, and led to severe clinical signs in elephants. Frequent relapses were observed after treatment with diminazene aceturate, the only trypanocide drug currently available in Thailand. Therefore, care should be taken to keep elephants away from bovine reservoirs, and to monitor the disease in this endangered species. ELISA proved to be reliable for screening purposes as well as for post-treatment monitoring.

Characterization of genome-wide segmental duplications reveals a common genomic feature of association with immunity among domestic animals.

BACKGROUND: Segmental duplications (SDs) commonly exist in plant and animal genomes, playing crucial roles in genomic rearrangement, gene innovation and the formation of copy number variants. However, they have received little attention in most livestock species. RESULTS: Aiming at characterizing SDs across the genomes of diverse livestock species, we mapped genome-wide SDs of horse, rabbit, goat, sheep and chicken, and also enhanced the existing SD maps of cattle and pig genomes based on the most updated genome assemblies. We adopted two different detection strategies, whole genome analysis comparison and whole genome shotgun sequence detection, to pursue more convincing findings. Accordingly we identified SDs for each species with the length of from 21.7 Mb to 164.1 Mb, and 807 to 4,560 genes were harboured within the SD regions across different species. More interestingly, many of these SD-related genes were involved in the process of immunity and response to external stimuli. We also found the existence of 59 common genes within SD regions in all studied species except goat. These common genes mainly consisted of both UDP glucuronosyltransferase and Interferon alpha families, implying the connection between SDs and the evolution of these gene families. CONCLUSIONS: Our findings provide insights into livestock genome evolution and offer rich genomic sources for livestock genomic research.

Pet-Related Infections.

Physicians and veterinarians have many opportunities to partner in promoting the well-being of people and their pets, especially by addressing zoonotic diseases that may be transmitted between a pet and a human family member. Common cutaneous pet-acquired zoonoses are dermatophytosis (ringworm) and sarcoptic mange (scabies), which are both readily treated. Toxoplasmosis can be acquired from exposure to cat feces, but appropriate hygienic measures can minimize the risk to pregnant women. Persons who work with animals are at increased risk of acquiring bartonellosis (e.g., cat-scratch disease); control of cat fleas is essential to minimize the risk of these infections. People and their pets share a range of tick-borne diseases, and exposure risk can be minimized with use of tick repellent, prompt tick removal, and appropriate tick control measures for pets. Pets such as reptiles, amphibians, and backyard poultry pose a risk of transmitting Salmonella species and are becoming more popular. Personal hygiene after interacting with these pets is crucial to prevent Salmonella infections. Leptospirosis is more often acquired from wildlife than infected dogs, but at-risk dogs can be protected with vaccination. The clinical history in the primary care office should routinely include questions about pets and occupational or other exposure to pet animals. Control and prevention of zoonoses are best achieved by enhancing communication between physicians and veterinarians to ensure patients know the risks of and how to prevent zoonoses in themselves, their pets, and other people.

Veterinary vaccines against toxoplasmosis.

Toxoplasma gondii is a cosmopolitan protozoan parasite that infects a wide range of mammal and bird species. Common infection leads to high economic (e.g., abortions in sheep) and human (e.g., congenital toxoplasmosis or neurotoxoplasmosis in humans) losses. With one exception (Toxovax for sheep), there are no vaccines to prevent human or animal toxoplasmosis. The paper presents the current state and challenges in the development of a vaccine against toxoplasmosis, designed for farm animals either bred for consumption or commonly kept on farms and involved in parasite transmission. So far, the trials have mostly revolved around conventional vaccines and, compared with the research using laboratory animals (mainly mice), they have not been very numerous. However, the results obtained are promising and could be a good starting point for developing an effective vaccine to prevent toxoplasmosis.

Prevalence of atopy and allergic diseases in Korean children: associations with a farming environment and rural lifestyle.

BACKGROUND: The results of recent studies suggest that factors in rural environments may protect against the development of allergic diseases, but the underlying mechanisms are not well understood. The aim of this study was to investigate the prevalence of allergic diseases, to establish if this prevalence is influenced by migration from rural to urban areas and to identify environmental risk factors associated with these diseases. METHODS: A cross-sectional study of children aged 9-12 years from a rural village, a rural town and an urban city in Korea was conducted. Demographic and disease-related information was obtained via a detailed questionnaire, and skin prick tests were performed. RESULTS: There were significant differences in lifestyle and environmental factors between children from the rural village, the rural town and the urban children. The prevalence of allergic diseases and atopy was higher in urban children. A lower prevalence of allergic diseases and atopy was associated with farming parents, contact with farm animals during pregnancy, owning pets or a stable, breast-feeding and having older siblings. A comparison of rural village and rural town children revealed no evidence of an association of allergic diseases and atopy with farming parents, contact with farm animals during pregnancy or owning a stable. On the other hand, having older siblings and antibiotic use during infancy were significantly associated with allergic diseases and atopy in these children. CONCLUSIONS: Protective factors associated with a farming environment and/or rural lifestyle may influence the prevalence of allergic diseases and atopy in Korean children.

Optimal reactive vaccination strategies for a foot-and-mouth outbreak in the UK.

Foot-and-mouth disease (FMD) in the UK provides an ideal opportunity to explore optimal control measures for an infectious disease. The presence of fine-scale spatio-temporal data for the 2001 epidemic has allowed the development of epidemiological models that are more accurate than those generally created for other epidemics and provide the opportunity to explore a variety of alternative control measures. Vaccination was not used during the 2001 epidemic; however, the recent DEFRA (Department for Environment Food and Rural Affairs) contingency plan details how reactive vaccination would be considered in future. Here, using the data from the 2001 epidemic, we consider the optimal deployment of limited vaccination capacity in a complex heterogeneous environment. We use a model of FMD spread to investigate the optimal deployment of reactive ring vaccination of cattle constrained by logistical resources. The predicted optimal ring size is highly dependent upon logistical constraints but is more robust to epidemiological parameters. Other ways of targeting reactive vaccination can significantly reduce the epidemic size; in particular, ignoring the order in which infections are reported and vaccinating those farms closest to any previously reported case can substantially reduce the epidemic. This strategy has the advantage that it rapidly targets new foci of infection and that determining an optimal ring size is unnecessary.

Prenatal animal contact and gene expression of innate immunity receptors at birth are associated with atopic dermatitis.

BACKGROUND: Cross-sectional studies have suggested that prenatal farm exposures might protect against allergic disease and increase the expression of receptors of the innate immune system. However, epidemiologic evidence supporting the association with atopic dermatitis remains inconsistent. OBJECTIVE: To study the association between prenatal farm-related exposures and atopic dermatitis in a prospective study. We further analyzed the association between the expression of innate immune genes at birth and atopic dermatitis. METHODS: A total of 1063 children who participated in a birth cohort study, Protection against Allergy-Study in Rural Environments, were included in this study. Doctor diagnosis of atopic dermatitis was reported by the parents from 1 to 2 years of age by questionnaire. Gene expression of Toll-like receptors (TLRs) and CD14 was assessed in cord blood leukocytes by quantitative PCR. RESULTS: Maternal contact with farm animals and cats during pregnancy had a significantly protective effect on atopic dermatitis in the first 2 years of life. The risk of atopic dermatitis was reduced by more than half among children with mothers having contact with 3 or more farm animal species during pregnancy compared with children with mothers without contact (adjusted odds ratio, 0.43; 95% CI, 0.19-0.97). Elevated expression of TLR5 and TLR9 in cord blood was associated with decreased doctor diagnosis of atopic dermatitis. A significant interaction between polymorphism in TLR2 and prenatal cat exposure was observed in atopic dermatitis. CONCLUSION: Maternal contact with farm animals and cats during pregnancy has a protective effect on the development of atopic dermatitis in early life, which is associated with a lower expression of innate immune receptors at birth.

Lifetime dog and cat exposure and dog- and cat-specific sensitization at age 18 years.

BACKGROUND: Prior research about whether keeping a dog or cat at home causes allergies to that pet has been limited to outcomes in early childhood. OBJECTIVE: Evaluate the association between lifetime dog and cat exposure and allergic sensitization to the specific animal at 18 years of age. METHODS: Participants enrolled in the Detroit Childhood Allergy Study birth cohort during 1987-1989 were contacted at the age 18 years. Sensitization to dog or cat was defined as animal-specific IgE ≥ 0.35 kU/L. Annual interview data from childhood and follow-up interviews at age 18 years were used to determine lifetime indoor dog and cat exposure (indoor was defined when the animal spent >50% of their time inside the house). Exposure was considered in various ways: first year, age groups and cumulative lifetime. Analyses were conducted separately for dogs and cats. RESULTS: Among males, those with an indoor dog during the first year of life had half the risk [relative risk (RR)=0.50, 95% confidence interval (CI) 0.27, 0.92] of being sensitized to dogs at age 18 compared with those who did not have an indoor dog in the first year. This was also true for males and females born via c-section (RR=0.33, 95% CI 0.07, 0.97). Overall, teens with an indoor cat in the first year of life had a decreased risk (RR=0.52, 95% CI 0.31, 0.90) of being sensitized to cats. Neither cumulative exposure nor exposure at any other particular age was associated with either outcome. CONCLUSIONS AND CLINICAL RELEVANCE: The first year of life is the critical period during childhood when indoor exposure to dogs or cats influences sensitization to these animals.

Farming environment and prevalence of atopy at age 31: prospective birth cohort study in Finland.

BACKGROUND: Cross-sectional studies have shown an association between the farming environment and a decreased risk of atopic sensitization, mainly related to contact with farm animals in the childhood. OBJECTIVE: Investigate the association of a farming environment, especially farm animal contact, during infancy, with atopic sensitization and allergic diseases at the age of 31. METHODS: In a prospective birth cohort study, 5509 subjects born in northern Finland in 1966 were followed up at the age of 31. Prenatal exposure to the farming environment was documented before or at birth. At age 31, information on health status and childhood exposure to pets was collected by a questionnaire and skin prick tests were performed. RESULTS: Being born to a family having farm animals decreased the risk of atopic sensitization [odds ratio (OR) 0.67; 95% confidence interval (CI) 0.56-0.80], atopic eczema ever (OR 0.77; 95% CI 0.66-0.91), doctor-diagnosed asthma ever (OR 0.74; 95% CI 0.55-1.00), allergic rhinitis at age 31 (OR 0.87; 95% CI 0.73-1.03) and allergic conjunctivitis (OR 0.86; 95% CI 0.72-1.02) at age 31. There was a suggestion that the reduced risk of allergic sensitization was particularly evident among the subjects whose mothers worked with farm animals during pregnancy, and that the reduced risk of the above diseases by farm animal exposure was largely explained by the reduced risk of atopy. Having cats and dogs in childhood revealed similar associations as farm animals with atopic sensitization. CONCLUSION AND CLINICAL RELEVANCE: Contact with farm animals in early childhood reduces the risk of atopic sensitization, doctor-diagnosed asthma and allergic diseases at age 31.

Therapeutic targeting of the innate immune system in domestic animals.

Since first being described in the fruit fly Drosophila melanogaster, the knowledge regarding Toll-like receptors (TLRs) has transformed our understanding of immunology. TLRs are a family of conserved pattern recognition receptors (PRR) that recognise specific microbial-associated molecular patterns and allow the cell to distinguish between self and non-self materials. The very property of the TLRs, to link innate and adaptive immunity, offers a novel opportunity to develop vaccines that engage TLR signalling. The presence of TLR ligands as adjuvants in conjunction with a vaccine is shown to increase the efficacy and response to the immunisation with a particular antigen. Here, we focus on the findings pertaining to TLR ligands as adjuvants and discuss the importance of these studies in the development of an optimal vaccine in farm and companion animals.

Toll-like receptors in domestic animals.

Toll-like receptors are pattern recognition receptors with which hosts recognize pathogen-associated molecular patterns (PAMP). This recognition process is translated rapidly into a meaningful defense reaction. This form of innate host defense is preserved in the animal kingdom: invertebrates heavily depend on it; higher vertebrates also have an adaptive immune system. Both adaptive and innate immune systems are intertwined in that the former also depends on an intact innate recognition and response system. Members of the TLR system cover recognition of parasitic, bacterial or viral germs. Due to the constraints imposed by the necessity to recognize PAMP and to interact with downstream signaling molecules, the TLR system is relatively conserved in evolution. Nevertheless, subtle species differences have been reported for several mammalian TLR members. Examples of this will be given. In all mammalian species investigated, part of the coding sequence is available for the most important TLR members, thus allowing study of expression of these TLR members in various tissues by reverse-transcription polymerase chain reaction in its classical (RT-PCR) and quantitative real time RT-PCR (qRT-PCR) form. In some species, the whole coding sequences of the most important or even all TLR members are known. This allows construction of cDNA and transfection of common host cells, thus permitting functional studies. Extensive investigations were devoted to the study of non-synonymous single nucleotide polymorphisms. In a few cases, expression of a given amino acid in the extracellular (ligand-binding) portion of TLR members could be associated with infectious diseases. This will be discussed below.

Opposing effects of cat and dog ownership and allergic sensitization on eczema in an atopic birth cohort.

OBJECTIVE: To examine risk factors for eczema at age 4 years. STUDY DESIGN: Beginning at 1 year of age, infants of atopic parents (n = 636) had annual clinical evaluations and skin prick tests (SPTs) to 15 aeroallergens and milk and egg. Parents completed validated surveys on eczema and environmental exposures. House dust samples were evaluated for allergens and endotoxin. Eczema was defined as a parental report of scratching, and redness, "raised bumps," or dry skin/scaling for 6 of the last 12 months. RESULTS: At age 4 years, a total of 90 children (14%) had eczema. Not having a dog before 1 year of age and being dog SPT+ at 1, 2, or 3 years of age conferred a 4-fold higher risk for eczema at age 4 years (adjusted odds ratio [aOR] = 3.9 [1.6-9.2]; P = .002). Among dog owners, however, dog SPT+ was not associated with significantly increased risk (aOR 1.3 [0.3-6.8]; P = .8). Among children with cats before 1 year of age, cat SPT+ conferred significantly increased risk for eczema (aOR = 13.3 [3.1-57.9]; P < .001). Among non-cat owners, cat SPT+ was not associated with increased risk (aOR = 1.1 [0.5-2.7]; P = .8). CONCLUSION: Dog ownership significantly reduced the risk for eczema at age 4 years among dog-sensitized children, cat ownership combined with cat sensitization significantly increased the risk.

The GABRIEL Advanced Surveys: study design, participation and evaluation of bias.

Exposure to farming environments has been shown to protect substantially against asthma and atopic disease across Europe and in other parts of the world. The GABRIEL Advanced Surveys (GABRIELA) were conducted to determine factors in farming environments which are fundamental to protecting against asthma and atopic disease. The GABRIEL Advanced Surveys have a multi-phase stratified design. In a first-screening phase, a comprehensive population-based survey was conducted to assess the prevalence of exposure to farming environments and of asthma and atopic diseases (n = 103,219). The second phase was designed to ascertain detailed exposure to farming environments and to collect biomaterial and environmental samples in a stratified random sample of phase 1 participants (n = 15,255). A third phase was carried out in a further stratified sample only in Bavaria, southern Germany, aiming at in-depth respiratory disease and exposure assessment including extensive environmental sampling (n = 895). Participation rates in phase 1 were around 60% but only about half of the participating study population consented to further study modules in phase 2. We found that consenting behaviour was related to familial allergies, high parental education, wheeze, doctor diagnosed asthma and rhinoconjunctivitis, and to a lesser extent to exposure to farming environments. The association of exposure to farm environments with asthma or rhinoconjunctivitis was not biased by participation or consenting behaviour. The GABRIEL Advanced Surveys are one of the largest studies to shed light on the protective 'farm effect' on asthma and atopic disease. Bias with regard to the main study question was able to be ruled out by representativeness and high participation rates in phases 2 and 3. The GABRIEL Advanced Surveys have created extensive collections of questionnaire data, biomaterial and environmental samples promising new insights into this area of research.

Physiological and proteomic evidences that domestication process differentially modulates the immune status of juvenile Eurasian perch (Perca fluviatilis) under chronic confinement stress.

The current study aimed to evaluate the influence of domestication process on the stress response and subsequent immune modulation in Eurasian perch juveniles (Perca fluviatilis) submitted to chronic confinement. Briefly, F1 and F4 generations were confined into small-size tanks and sampled 7 and 55 days after stocking. Cortisol and glucose levels as well as lysozyme activity and immunoglobulin level were evaluated in the serum. Spleen Somatic Index and spleen ROS production were also measured. A proteomic analysis was performed on serum sampled on day 7. Finally, both generations were genetically characterized using a microsatellite approach. Globally, results revealed that chronic confinement did not elicit a typical stress response but resulted in a prolonged immune stimulation. Proteomic results suggested that domestication process influenced the immune status of perch submitted to chronic confinement as the F1 confined fish displayed lower abundance of C3 complement component, transferrin and Apolipoprotein E. Microsatellite data showed a strong genetic drift as well as reduced genetic diversity, allelic number and heterozygosity along with domestication process. The present work is the first to report that fish under domestication can develop an immune response, assessed by a combined approach, following recurrent challenges imposed by captive environment despite a reduced genetic variation.

Adjuvants and delivery systems in veterinary vaccinology: current state and future developments.

Modern adjuvants should induce strong and balanced immune responses, and it is often desirable to induce specific types of immunity. As an example, efficient Th1-immunity-inducing adjuvants are highly in demand. Such adjuvants promote good cell-mediated immunity against subunit vaccines that have low immunogenicity themselves. The development of such adjuvants may take advantage of the increased knowledge of the molecular mechanisms and factors controlling these responses. However, knowledge of such molecular details of immune mechanisms is relatively scarce for species other than humans and laboratory rodents, and in addition, there are special considerations pertaining to the use of adjuvants in veterinary animals, such as production and companion animals. With a focus on veterinary animals, this review highlights a number of approaches being pursued, including cytokines, CpG oligonucleotides, microparticles and liposomes.

Immunoglobulin G antibody profiles against Anopheles salivary proteins in domestic animals in Senegal.

Although domestic animals may not be permissive for Plasmodium, they could nevertheless play a role in the epidemiology of malaria by attracting Anopheles away from humans. To investigate interactions between domestic animals and mosquitoes, we assayed immunoglobulin G (IgG) antibodies directed against the salivary proteins of Anopheles gambiae in domestic animals living in Senegalese villages where malaria is endemic. By Western blotting, sera from bovines (n=6), ovines (n=36), and caprines (n=36) did not react with Anopheles whole saliva. In contrast, equine sera recognized proteins in both saliva and salivary gland extracts. Two of the major immunogens (32 and 72 kDa) were also reactive in extracts from other major mosquito genera (Aedes and Culex), but reactions toAnopheles-specific antigens were detected in 12 of 17 horses. These data suggest that horses strongly react to Anopheles bites, and further experiments on horses are warranted to investigate the impact of this domestic animal species on the transmission of human malaria.

Interactions between commensal bacteria and viral infection: insights for viral disease control in farmed animals.

Viral diseases cause serious economic loss in farmed animals industry. However, the efficacy of remedies for viral infection in farmed animals is limited, and treatment strategies are generally lacking for aquatic animals. Interactions of commensal microbiota and viral infection have been studied in recent years, demonstrating a third player in the interaction between hosts and viruses. Here, we discuss recent developments in the research of interactions between commensal bacteria and viral infection, including both promotion and inhibition effect of commensal bacteria on viral pathogenesis, as well as the impact of viral infection on commensal microbiota. The antiviral effect of commensal bacteria is mostly achieved through priming or regulation of the host immune responses, involving differential microbial components and host signaling pathways, and gives rise to various antiviral probiotics. Moreover, we summarize studies related to the interaction between commensal bacteria and viral infection in farmed animals, including pigs, chickens, fish and invertebrate species. Further studies in this area will deepen our understanding of antiviral immunity of farmed animals in the context of commensal microbiota, and promote the development of novel strategies for treatment of viral diseases in farmed animals.

A novel fluorescence immunochromatographic assay strip for the diagnosis of schistosomiasis japonica.

BACKGROUND: Schistosomiasis japonica is a severe zoonosis. Domestic animals are the primary source of infection and play an important role in disease transmission. Surveillance and diagnosis play key roles in schistosomiasis control; however, current techniques for the surveillance and diagnosis of the disease have limitations. In this study, we developed a novel fluorescence immunochromatographic assay (FICA) strip to detect anti-Schistosoma japonicum antibodies in host serum. METHODS: A FICA strip was developed for the diagnosis of Schistosoma japonicum in domestic animals. Streptococcus protein G (SPG) and soluble egg antigen (SEA) were transferred onto a nitrocellulose (NC) membrane to form the control line (C) and the test line (T), respectively. With fluorescence activity as well as binding activity to multispecies IgG, the recombinant protein rSPG-RFP was expressed and employed as an antibody indicator in the FICA strips. RESULTS: The dual gene fusion plasmid was verified by PCR and restriction enzyme digestion. The expressed recombinant protein was 39.72 kDa in size, which was consistent with the predicted molecular weight. The western blot results showed binding activity between rSPG-RFP and IgGs from different hosts. Fluorescence microscopy also showed the fluorescence activity of the protein present. The affinity constant (Ka) values of rSPG-RFP with rabbit, donkey, mouse and goat IgG were 1.9 × 105, 4.1 × 105, 1.7 × 105 and 5.4 × 105, respectively. Moreover, based on the recombinant protein, the test strip for detecting S. japonicum in buffaloes could distinguish positive from negative serum. The lower limit of detection of the FICA strip was 1:10,000. Compared with ELISA, the FICA strips exhibited similar results in the diagnosis of infection in clinical bovine serum samples, with a kappa value of 0.9660 and P < 0.01. The cross-reactivities of the FICA strips with Haemonchus contortus and Schistosoma turkestanicum (30.15% and 91.66%, respectively) were higher than those of ELISA (26.98% and 87.5%, respectively). CONCLUSIONS: Based on the rSPG-RFP protein that we developed, strip detection can be completed within 15 min. Heightened sensitivity allows the strip to accurately identify schistosome antibodies in serum. In conclusion, this method is convenient, feasible, rapid and effective for detecting S. japonicum.