Enterovirus D68 (EV-D68) virus has become more prevalent over the last 15 to 20 years. EV-D68 attacks the respiratory system and can cause severe disease in individuals who have underlying respiratory problems. There have also been reports of individuals with EV-D68 showing signs of neurological system problems and acute flaccid paralysis. Because of the increase in patients with EV-D68 and also the potential for neurological disease, an animal model is needed to study the disease and to evaluate experimental therapies for EV-D68 infection. To develop the animal model, 4-week old AG129 mice that lack alpha and beta interferon receptors, making them immunosuppressed, were used. The mice were infected with EV-D68 by the intranasal route to allow infection of the lungs. On day-3 post-infection the mice were euthanized and lungs were removed and homogenized for collection of virus. The newly collected virus was then used to infect another set of mice. This procedure was repeated 30 times. As passage number increased so did the amount of virus that was collected from the lungs of mice. The virus titer increased 320-fold between mouse passage 0 to 30. At the end of the thirtieth passage, multiple tissues (lungs, liver, kidney, spleen, blood, brain, spinal cord and leg muscle) were collected from infected mice over several days and titered to demonstrate how quickly the virus spread to various tissues within the mouse. The virus replicated most rapidly in the lungs and remained in the lungs longer than the other tissues evaluated. However, large quantities of virus were found in all tissues evaluated. Finally, several experimental antiviral compounds were evaluated: rupintrivir, pleconaril, ribavirin, enviroxime and guanidine, all of which showed therapeutic potential in cell culture. In the animal model rupintrivir, pleconaril, ribavirin and enviroxime did not show any therapeutic effect. Only guanidine reduced the amount of virus that was found in the lungs as well as in whole blood.

Lawsonia intracellularis and the disease it causes in horses, equine proliferative enteropathy (EPE), is an emerging pathogen of increasing importance to the horse industry from both an economic and welfare standpoint. Long recognized as an economically important disease of swine, the hallmark of EPE is a protein-losing enteropathy, where affected horses suffer weight loss and some ultimately succumb to the disease despite aggressive treatment. There are currently no known EPE preventative measures and the epidemiology of the disease remains poorly defined. While EPE is a sporadic disease affecting less than 25% of exposed horses, some farms experience clinical cases year after year. Further, weanlings are uniquely susceptible to this disease, although no conclusive reason for this predisposition has been identified. The overall hypothesis is that the host immune response plays a significant role in the susceptibility of weanlings to L. intracellularis infection and the occurrence of clinical equine proliferative enteropathy. To test this hypothesis, four individual hypotheses were proposed: (H1) previous farm history of EPE does not have an effect on weanling seroprevalence, (H2) passively-acquired antibodies do not have an effect on susceptibility to L. intracellularis and the occurrence of EPE, (H3) the serological status of mares can be used to determine the role they play in the epidemiology of EPE on endemic farms, and (H4) L. intracellularis-specific IFN-g expression is not associated with increased resistance to EPE.

<b>Background:</b> Comparative assessments of the vascular and upper gastrointestinal risks of different regimens of non-steroidal anti-inflammatory drugs (NSAIDs) are required. <b>Methods:</b> Meta-analyses were conducted, using individual participant data where possible, of placebo-controlled trials of a selective cyclo-oxygenase [COX]-2 inhibitor ('coxib') or traditional NSAID, or randomised trials of a coxib versus traditional NSAIDs. A prespecified subdivision of traditional NSAID regimens of those with antiplatelet activity (mainly naproxen) and those without (mainly diclofenac) was made. Primary outcomes were major vascular events (MVEs; nonfatal myocardial infarction, nonfatal stroke or vascular death) and upper gastrointestinal complications (UGICs; perforation, obstruction or bleed). <b>Findings:</b> Searches identified 788 trials: 200 comparisons of a coxib vs placebo (88,604 participants, mean follow-up 0.60 years), 206 comparisons of a traditional NSAID vs placebo (43,482 participants, 0.46 years) and 149 comparisons of a coxib vs traditional NSAID (137,466 participants, mean follow-up 0.95 years). Compared to placebo, allocation to a coxib increased the risk of MVEs (rate ratio 1.38, 95&percnt; CI 1.14-1.66), vascular mortality (1.58, 1.11-2.24) and UGICs (1.81, 1.17-2.81). Overall, in the population studied, coxibs were associated with three additional major vascular events (one fatal) and two (rarely fatal) upper gastrointestinal complications per 1000 person-years exposure. There was no evidence of heterogeneity by duration of follow-up, coxib type, dose (other than for celecoxib), or patient characteristics, for the primary outcomes. The risk of MVEs for traditional NSAIDs without antiplatelet activity (mostly diclofenac 75mg bd or ibuprofen 800mg tds) were comparable to coxibs (1.40, 1.15-1.72); but the risk of UGICs (1.98, 1.39-2.84) was significantly greater. For traditional NSAIDs with antiplatelet activity (mostly naproxen 500mg bd) there were no significant excess of MVEs (0.84, 0.66-1.08), but UGICs were substantially increased (4.06, 2.85-5.78). Both coxibs and traditional NSAIDs increased risk of hospitalisation for heart failure by about two-fold. <b>Interpretation:</b> The vascular and upper gastrointestinal risks of coxibs and high-dose tNSAID regimens can be predicted, allowing the choice of analgesia to be tailored for particular patients.

Despite advances in mosquito management, mosquito-borne disease in the United States is still of relevant public health concern and vector control is a top priority in preventing transmission of pathogens. Insecticide barrier sprays have become a common tool for suppression of mosquitoes in single-homeowner backyards. The application of the synthetic pyrethroid, lambda-cyhalothrin to perimeter vegetation with a backpack sprayer has been shown to significantly suppress mosquito levels for around 6 weeks. In an attempt to lengthen the effective duration of treatment, the IGR, pyriproxyfen, was added to a backpack mist blower with lambda-cyhalothrin, as adult mosquitoes exposed to pyriproxyfen have been shown to disseminate it to oviposition sites and to experience lowered fecundity. This treatment was compared to lambda-cyhalothrin alone and to a water control. Mosquito populations were sampled using CO2-baited CDC light traps, CDC gravid traps, human landing rates, and ovitraps. Leaf bioassays were performed. The following summer, the same treatments were applied with a truck-mounted mist blower to tree lines in Central Kentucky, to test the efficacy of an application method that could be used on large properties. Finally, bioassays were performed with water sampled from pyriproxyfen-treated containers, exposed to field conditions to test for residual efficacy.

Staphylococcus pseudintermedius affecting dogs is analogous to S. aureus on humans, acting as both normal flora and opportunistic pathogen. Methicillin resistance in S. pseudintermedius is recent, with the first documented occurrence of an isolate bearing the methicillin resistance gene, mecA, in 1999. This gene encodes penicillin binding protein 2a, which renders all beta-lactam drugs ineffective and functions as a “gateway” antibiotic resistance determinant. In the presence of ineffective antibiotics, opportunities for mutational events and acquisition of mobile genetic elements increase as microbial densities increase, often leading to multi-drug resistance. Methicillin-resistant S. pseudintermedius (MRSP) infections have become increasingly common. For example, approximately 30% of the S. pseudintermedius isolates tested by the University of Tennessee College of Veterinary Medicine Clinical Bacteriology Laboratory are resistant to methicillin. An increasing number of MRSP isolates are also resistant to most clinically useful antibiotics available to veterinarians except for chloramphenicol, and resistance to this antibiotic is common among European MRSP isolates. Chloramphenicol resistance has begun to appear in the US and if this trend continues there may soon be few viable antibiotic treatment options. Compared with the arrival of methicillin-resistant S. aureus in the 1960s, the opportunity currently exists to apply advanced molecular methods early in this recognized emergence of MRSP. To that end I have pursued projects utilizing multilocus sequence typing, pulsed-field electrophoresis, and SCCmec characterization of both susceptible and resistant S. pseudintermedius. The initial result was the detection of a clonal population of MRSP in the southeastern United States. Further characterization of this and other clonal lineages using genomic sequencing and real-time RT-PCR expression analysis of antibiotic resistance and quorum sensing genes revealed a marked difference in the regulation of antibiotic resistance between regional clones. These discoveries have interesting epidemiological implications and provide a foundation for the development of novel therapeutics to circumvent the expanding antibiotic resistance repertoire of MRSP. Potential targets identified by this work include membrane-bound beta-lactamase receptors responsible for the regulation of mecA, non-cognate auto-inducing peptides, and synthetic antisense oligonucleotides.

The objectives of this thesis were: (1) to evaluate the downregulation of the stallion hypothalamic-pituitary-gonadal (HPG) axis by a GnRH antagonist (acyline) based upon endocrine, seminal, testicular and behavioral effects, and (2) to assess recovery after treatment. Stallions were treated for 50 days (n=4; 330µg/kg acyline q 5d) and controls (n=4) received vehicle alone. Stallions were assessed pre-treatment and for 72 days after last treatment. Treatment induced declines (p<0.05) in FSH, LH, testosterone (to castrate levels) and estrone sulfate. Gonadotropins and testosterone returned to control values within nine days and estrone sulfate by 14 days after treatment discontinuation. Acyline-treated stallions failed to respond with FSH, LH and testosterone increase after exogenous GnRH stimulation (25µg gonadorelin, IV) compared to pre-treatment and control stimulation. Total sperm numbers and motility were reduced in acyline-treated stallions, as well as total seminal plasma protein and testicular volume (p<0.05). Time to ejaculation was increased in acyline group (p<0.5). Testicular, sexual behavior and most seminal parameters regained normal levels within 72 days after treatment ceased. Sperm output of acyline-treated stallions was regained within seven months after ending treatment. Acyline reversibly suppressed the stallion HPG axis, thus has potential for treating the androgen-dependent Equine-Arteritis-Virus carrier state and as behavior modulator.

Cattle health and production records (CHPR) are data collected by cattle producers and veterinarians in the form of measurements, observations, counts of events over time, and physiologic attributes that describe individual and group-level health and production. These data are useful to both veterinarians and cattle producers for making evidence-based decisions on cow-calf operations. Currently, there are no uniform, industry-wide methods of capturing and recording CHPR in the U.S. cow-calf industry. Although many cow-calf producers in the U.S. are thought to collect some form of CHPR, it is believed that relatively few are doing so in an electronic manner that facilitates optimal use and analysis of those records. Technology offers many opportunities to collect, record, and analyze CHPR for decision-making on cow-calf operations, with smartphones having great potential as a point-of-care CHPR collection device. Little is known regarding 1) barriers faced by producers to collecting and using CHPR, 2) interest of U.S. cow-calf producers in using technology such as smartphones for collecting and recording CHPR, and 3) the role of veterinarians in the collection and use of CHPR on U.S. cow-calf operations. The first study included in this dissertation was a survey of the cattle health and production record-keeping methods of cow-calf producers in Mississippi. The second study in this dissertation was a survey of cow-calf producers across the U.S. regarding their methods and opinions of cattle health and production record-keeping, their access to technology for record-keeping purposes, current types of data being collected on cow-calf operations, and the role of veterinarians in record-keeping on those cow-calf operations. The third study in this dissertation was a demonstration of common epidemiologic and biostatistical skills needed by veterinary practitioners to analyze CHPR and provide quality, evidence-based management recommendations to their cow-calf clients.

The humerus of a racing horse Thoroughbred is highly susceptible to stress fractures at a characteristic location as a result of cyclic loading. The propensity of a Thoroughbred to exhibit humeral fracture has made equines useful models in the epidemiology of stress fractures. In this study, a racing Thoroughbred humerus was simulated during training using a 3D finite element model in conjunction with a bone remodeling algorithm. Nine muscle forces and two contact forces were applied to the 3-dimensional finite element model, which contains four separate load cases representing fore-stance, mid-stance, aft-stance, and standing. Four different training programs were incorporated into the model, which represent Baseline Layup and Long Layup training programs along with two newly implemented programs for racing, which have an absence of a layup period, last a period of 24 weeks, and a race once every four weeks. Muscle and contact forces were rescaled for all load cases to simulate dirt, turf, and synthetic track surfaces. Bone porosity, damage, and BMU activation frequency were examined at the stress fracture site and compared with a control location called the caudal diaphysis. It was found that race programs exhibited similar remodeling patterns between each other. Damage at the stress fracture site and caudal diaphysis was reduced during all training programs for the turf and synthetic track surfaces with respect to the dirt track surface. Key findings also included changes in bone remodeling at the stress fracture site and caudal diaphysis as a result of turf and synthetic track surfaces. This model can serve as a framework for further studies in human or equine athletes who are susceptible to stress fractures.

As keeping backyard poultry rises, human contact with zoonotic pathogens will increase. One such pathogen that backyard enthusiasts have exposure risks to is Salmonella spp. which may cause a potential public health threat due to its increasing multidrug resistancy. Salmonella spp. were present in 33 of 50 samples collected from 29 sites with backyard poultry coops in San Luis Obispo County during March to May in 2014. Two different Hardy-CHROME™ Salmonella Selective Media plates were used to culture and isolate positive samples of Salmonella spp.. Each positive isolate was tested for antimicrobial sensitivity to 6 standard antibiotics: Ampicillin, Bacitracin, Erythromycin, Gentamicin, Penicillin, and Tetracycline, at the standard disk concentration levels. The Kirby-Bauer antimicrobial sensitivity test determined that 12 different profiles emerged from the Salmonella spp. isolates. All antimicrobial sensitivity profiles showed multidrug resistance in vitro with only high susceptibility to 2 major antibiotics, Gentamicin at 97% and Ampicillin at 51%. All profiles were resistant to 1 or more of the antimicrobials tested, plus the control. One Salmonella isolated was resistant to all 6 antimicrobials and another isolate to 5. The Salmonella spp. isolates proved multidrug resistance between 73%-100% to the other 4 antibiotics tested. The 24 Salmonella spp. positive sites displayed a lack of proper biosecurity and poultry husbandry practices. The criteria developed for accessing the poultry’s environment ranged from dedicated shoes for cleaning, egg handling, access to other animals and wildlife, number of birds and breeds or species in a coop, cleaning routine, over-all biosecurity and human interactions. Human exposure to Salmonella spp. pathogenic strains could increase due to environmental cross contamination and deficiencies in sanitation. The presence of Salmonella spp. with a diversity of antibiotic resistance serotypes is an important source of zoonotic pathogens for animal and human diseases that has public health risk implications.

Shelters often make euthanasia or adoption decisions based on the results of FeLV-FIV point-of-care tests but given the low estimated prevalence of these diseases and imperfect test performance, this might not be a good practice because of diagnostic error. The objectives of this study were to determine the true prevalence of FeLV and FIV in apparently healthy and sick shelter cats in Mississippi, estimate predictive value of the Zoetis Witness FeLV-FIV Rapid ImmunoMigration test results at the estimated true prevalences through Bayesian latent class modeling, and formulate testing recommendations for shelters. One chapter will review the literature on FeLV and FIV. The bulk of this thesis will focus on determining the true prevalence of retroviral infection in Mississippi shelter cat populations. The last chapter will use Bayesian modeling to estimate test performance and predictive value of test results in healthy and sick shelter cat populations.