Clinical Expression Of Disease Research Articles

Peripheral airways type 2 inflammation, neutrophilia and microbial dysbiosis in severe asthma.

BackgroundIL‐13 is considered an archetypal T2 cytokine central to the clinical disease expression of asthma. The IL‐13 response genes, which are upregulated in central airway bronchial epithelial of asthma patients, can be normalized by high‐dose inhaled steroid therapy in severe asthma. However, this is not the case within the peripheral airways. We have sought to further understand IL‐13 in the peripheral airways in severe asthma through bronchoalveolar analysis.MethodsBronchoalveolar lavage samples were collected from 203 asthmatic and healthy volunteers, including 78 with severe asthma. Inflammatory mediators were measured using a multiple cytokine immunoassay platform. This analysis was replicated in a further 59 volunteers, in whom 16S rRNA analysis of BAL samples was undertaken by terminal restriction fragment length polymorphism.ResultsSevere asthma patients with high BAL IL‐13, despite treatment with high‐dose inhaled corticosteroids, had more severe lung function and significantly higher BAL neutrophil percentages, but not BAL eosinophils than those with normal BAL‐13 concentrations. This finding was replicated in the second cohort, which further associated BAL IL‐13 and neutrophilia with a greater abundance of potentially pathogenic bacteria in the peripheral airways.ConclusionOur findings demonstrate a steroid unresponsive source of IL‐13 that is associated with BAL neutrophilia and bacterial dysbiosis in severe asthma. Our findings highlight the biological complexity of severe asthma and the importance of a greater understanding of the innate and adaptive immune responses in the peripheral airways in this disease.

A pasture-based experimental infection model for footrot in sheep

Footrot is a contagious disease of sheep and other small ruminants. The causative agent, Dichelobacter nodosus, is transmitted between hooves via contaminated pasture and soil. However, the bacterium cannot invade the epidermis unless it is compromised in some manner and water maceration, which follows prolonged exposure to a moist substrate, is the most common predisposing factor. Experimental infection models have been used extensively to study the aetiology, pathogenesis, treatment and prevention of footrot. In Australia, an indoor, pen-based, infection model involving standing sheep on wet mats and bandaging inoculum onto the foot has been used commonly but does not accurately represent the pasture environment and has an impact on animal welfare. Instead, we predisposed sheep on irrigated pasture and compared three methods for infecting them with D. nodosus: application of inoculum to the interdigital skin with a swab, dripping inoculum onto the interdigital skin with a pipette, and spraying inoculum onto the pasture on which the sheep grazed. We were able to establish D. nodosus infections using all three methods but selected the swab method for further use because the dose can be controlled. It was used in two field trials and infection was established in 70 %–100 % of sheep. The infection model developed in this study improves animal welfare by reducing the level of intervention. However, as the model is pasture-based, seasonal weather patterns need to be considered to ensure predisposition and disease expression. Further research will be required to understand the environmental conditions required for transmission of D. nodosus and the clinical expression of disease.

How ‘atypical’ is the neuroimaging signature of Alzheimer’s atypical variants? MRI and PET imaging of posterior cortical atrophy and logopenic variant of primary progressive aphasia

AbstractBackgroundAlzheimer’s disease clinical expression is highly heterogeneous: cognitive and anatomical variations exist on a multi‐axis spectrum with well‐described variants like posterior cortical atrophy (PCA) or logopenic variant of primary progressive aphasia (lvPPA) representing extreme phenotypes of so‐called “atypical” AD. Here, we provide an overview of our investigations of PCA and lvPPA using structural MRI and amyloid/tau‐PET imaging, emphasizing both the differences and the similarities between these phenotypes and more typical presentations of AD.MethodWe investigated 97 amyloid‐positive patients with a clinical diagnosis of AD (MCI or dementia stage), including 18 patients with PCA and 19 with lvPPA; the remaining patients are referred to as typical (tAD; Table 1). Patients received 3‐tesla MRI and PET with [11C]PIB and [18F]Flortaucipir. Standardized Uptake Value Ratio (SUVR) images were created using specific reference regions. Mean SUVR or cortical thickness values were extracted from 72 FreeSurfer regions, and cortical asymmetry indices were calculated.ResultAtypical variants tended to be younger and less likely to carry APOE4 than tAD (Table1). Global amyloid burden did not vary across phenotypes or with any clinical measure (Figure 1A). The cortical distribution of PIB was widespread and only showed minor differences between variants (Figure 2A). In contrast, global Flortaucipir‐SUVR was higher in atypical groups compared to tAD, and was lower in older patients across phenotypes (Figure 1A). Flortaucipir was consistently elevated in temporo‐parietal regions but also showed strong between‐variant regional differences (Figure 2B) that mirrored differences in cortical volume (Figure 3B). Flortaucipir and MRI asymmetries were strongly inter‐related and very common across all AD phenotypes rather than specific to atypical variants (Figure 3). However, asymmetry was systematic in lvPPA (84‐95% left‐predominant, 5% right‐predominant) and PCA (33% left‐predominant, 66% right‐predominant)ConclusionAtypical phenotypes share various features with tAD: i) widespread cortical amyloid deposition, ii) tau pathology in the temporo‐parietal areas, iii) higher tau burden associated with earlier disease onset, iv) a strong negative relationship between tau and local cortical volume. The main between‐phenotype differences were related to the distribution of tau and associated atrophy that were more left‐predominant and perisylvian in lvPPA, and more occipital and asymmetric in PCA.

Investigating the missing heritability of fetal haemoglobin level in Africa.

Investigating the missing heritability of fetal haemoglobin level in Africa.

Protective effect of club cell secretory protein (CC-16) on COPD risk and progression: a Mendelian randomisation study

BackgroundThe anti-inflammatory pneumoprotein club cell secretory protein-16 (CC-16) is associated with the clinical expression of chronic obstructive pulmonary disease (COPD). We aimed to determine if there is a causal effect...

Systemic Sclerosis

Systemic sclerosis (SSc) is a complex autoimmune rheumatic disease that is characterised by widespread skin and internal organ fibrosis, immune system dysregulation, and vasculopathy. The disease carries a significant burden of pain and disability that is potentially life-limiting because of major internal organ-based complications. Early diagnosis is vital and key investigations include the detection of SSc-associated autoantibodies and nailfold capillaroscopic abnormalities. Patients should be managed by a dedicated, specialist, multidisciplinary team. There is now a range of effective treatments available for many of the complications associated with the disease. Autologous haematopoietic stem cell transplantation may benefit a small subset of patients with very poor prognosis SSc. Important advances have been made in understanding the aetiopathogenesis of SSc, which is driving clinical trials of new therapeutic approaches. The purpose of this review is to provide a clinically focussed description of the relevant aetiopathogenesis, clinical expression of disease, approach to the assessment and treatment of SSc, and highlight the recent advances and future challenges associated with this complex disease.

Clinico-radiological dissociation of disease activity in MS patients: frequency and clinical relevance.

To investigate the prevalence and clinical relevance regarding disability progression in multiple sclerosis patients with a dissociation in clinical and radiological disease expression. We prospectively selected patients with early relapsing-remittingmultiple sclerosis (MS) or a clinically isolated syndrome (CIS) from the Amsterdam MS cohort. Patients underwent clinical examination at baseline, after 2years, 6years and a subset also after 11years, including the Expanded Disability Status Scale (EDSS), 25-foot walk test (25-FWT) and 9-hole peg test (9-HPT). Brain and spinal cord MRI scans were obtained at baseline and after 2years. Two years after baseline, patients with dissociation in their clinical and radiological disease progression were identified as: (1) patients with high clinical disease activity (defined by relapses) and low radiological disease activity (defined by white-matter lesions on T2-weighted imaging); or (2) patients with low clinical disease activity and high radiological disease activity. Binary logistic regression analyses were performed to predict disability progression after 6 and 11years of follow-up. Patients with low clinical and low radiological disease activity were used as the reference group. The prevalence of clinico-radiological dissociation was low (6.4% had high clinical and low radiological disease activity and 5.1% had a combination of low clinical and high radiological disease activity) compared to 88.5% of patients without a dissociation. Patients with a dissociation of clinical and radiological disease activity did not show a statistically significant difference in risk of disability progression after 6 and 11years. A clinico-radiological dissociation is rather a rare phenomenon in MS patients. The clinical relevance of such a dissociation regarding the prediction of disability progression is questionable.

Prognostic implications of pathogenic truncating variants in the TTN gene

Introduction and objectivesTTN gene truncating variants (TTNtv) are a frequent cause of dilated cardiomyopathy (DCM). However, there are discrepant data on the associated prognosis. Our objectives were to describe the prevalence of TTNtv in our cohort and to compare the clinical course with that described in the literature. MethodsWe included patients with DCM and genetic testing performed using next-generation sequencing. Through a systematic literature research, we collected information about carriers and affected relatives with TTNtv. We compared the cumulative percentage of affected carriers and the survival free of cardiovascular death. ResultsOne hundred and ten DCM patients were evaluated. A total of 13 TTNtv distributed in 14 probands were identified (12.7%). We found a 21.4% prevalence in familial cases. No significant differences in the relation between age and clinical disease expression were identified. Survival free of cardiovascular death curves constructed from data in the literature seems not to overestimate the risk in our population. ConclusionsThe identification of TTNtv in patients with DCM is frequent and provides relevant information about the disease prognosis. The risk of cardiovascular death should not be underestimated. Age related penetrance need to be considered in the familial evaluation.

Gender-related differences in systemic sclerosis.

Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease which is characterised by autoimmunity, widespread tissue fibrosis of the skin and internal organs, and vasculopathic alterations. SSc is more common in women but has a more severe expression of disease including internal organ-based complications and higher mortality in men. The extant literature shows that although important pathophysiological sex differences are present in SSc, behavioural differences (e.g. higher smoking rates in men) and occupational exposures may contribute to poorer outcomes in men with SSc. The higher death male death rate in the general population and greater prevalence of lung fibrosis are likely the key factors responsible for excess mortality found in men. Other important factors include (but are not limited to) a greater prevalence of the disease subset, delayed time to diagnosis, and higher disease activity in early disease in men. SSc carries a significant burden of disease-related morbidity; however, no qualitative studies to date have focussed on gender differences in SSc. The purpose of this review is to provide a comprehensive overview of gender differences in SSc including (but not limited to) epidemiology, pathophysiology, clinical expression of disease, mortality, SSc in transgender individuals, and psychosocial aspects of disease.

Locus coeruleus pathology in progressive supranuclear palsy, and its relation to disease severity

The locus coeruleus is the major source of noradrenaline to the brain and contributes to a wide range of physiological and cognitive functions including arousal, attention, autonomic control, and adaptive behaviour. Neurodegeneration and pathological aggregation of tau protein in the locus coeruleus are early features of progressive supranuclear palsy (PSP). This pathology is proposed to contribute to the clinical expression of disease, including the PSP Richardson’s syndrome. We test the hypothesis that tau pathology and neuronal loss are associated with clinical heterogeneity and severity in PSP.We used immunohistochemistry in post mortem tissues from 31 patients with a clinical diagnosis of PSP (22 with Richardson’s syndrome) and 6 control cases. We quantified the presence of hyperphosphorylated tau, the number of pigmented cells indicative of noradrenergic neurons, and the percentage of pigmented neurons with tau-positive inclusions. Ante mortem assessment of clinical severity using the PSP rating scale was available within 1.8 (±0.9) years for 23 patients.We found an average 49% reduction of pigmented neurons in PSP patients relative to controls. The loss of pigmented neurons correlated with disease severity, even after adjusting for disease duration and the interval between clinical assessment and death. The degree of neuronal loss was negatively associated with tau-positive inclusions, with an average of 44% of pigmented neurons displaying tau-inclusions.Degeneration and tau pathology in the locus coeruleus are related to clinical heterogeneity of PSP. The noradrenergic deficit in the locus coeruleus is a candidate target for pharmacological treatment. Recent developments in ultra-high field magnetic resonance imaging to quantify in vivo structural integrity of the locus coeruleus may provide biomarkers for noradrenergic experimental medicines studies in PSP.

Morphometric network differences in ageing versus Alzheimer's disease dementia.

Age being the main risk factor for Alzheimer's disease, it is particularly challenging to disentangle structural changes related to normal brain ageing from those specific to Alzheimer's disease. Most studies aiming to make this distinction focused on older adults only and on a priori anatomical regions. Drawing on a large, multi-cohort dataset ranging from young adults (n = 468; age range 18-35 years), to older adults with intact cognition (n = 431; age range 55-90 years) and with Alzheimer's disease (n = 50 with late mild cognitive impairment and 71 with Alzheimer's dementia, age range 56-88 years), we investigated grey matter organization and volume differences in ageing and Alzheimer's disease. Using independent component analysis on all participants' structural MRI, we first derived morphometric networks and extracted grey matter volume in each network. We also derived a measure of whole-brain grey matter pattern organization by correlating grey matter volume in all networks across all participants from the same cohort. We used logistic regressions and receiver operating characteristic analyses to evaluate how well grey matter volume in each network and whole-brain pattern could discriminate between ageing and Alzheimer's disease. Because increased heterogeneity is often reported as one of the main features characterizing brain ageing, we also evaluated interindividual heterogeneity within morphometric networks and across the whole-brain organization in ageing and Alzheimer's disease. Finally, to investigate the clinical validity of the different grey matter features, we evaluated whether grey matter volume or whole-brain pattern was related to clinical progression in cognitively normal older adults. Ageing and Alzheimer's disease contributed additive effects on grey matter volume in nearly all networks, except frontal lobe networks, where differences in grey matter were more specific to ageing. While no networks specifically discriminated Alzheimer's disease from ageing, heterogeneity in grey matter volumes across morphometric networks and in the whole-brain grey matter pattern characterized individuals with cognitive impairments. Preservation of the whole-brain grey matter pattern was also related to lower risk of developing cognitive impairment, more so than grey matter volume. These results suggest both ageing and Alzheimer's disease involve widespread atrophy, but that the clinical expression of Alzheimer's disease is uniquely associated with disruption of morphometric organization.

Risk factors in coronary women

We now know that about 1/3 of patients with ischemic heart disease are women. The clinical expression of coronary disease is different in women. The revelation is often acute in the form of an acute coronary syndrome. The objectives of this work are to describe the presentation of the disease and to identify the risk factors of the coronary woman in comparison with the man. A prospective study with dual aim, descriptive and analytical spread over the year about 160 cases of women admitted for SCA at the CHU Ibn Sina ANNABA; compared to 390 men also hospitalized for SCA during the same period. The overall hospital prevalence of SCA is 0.49%, its frequency in the cardiology department is 27%, of which 29% are women: the SCA in women is essentially in the form of NSTEMI (60% of cases). The risk profile is higher for women, characterized by: older age, frequent hypertension (64.4%), sedentary lifestyle (49.4%) and its consequences (Obesity: 32%, particularly abdominal obesity: 56.9%, metabolic syndrome: 62.5% and low HDLc: 71.6%). The prognosis of myocardial infarction remains worse in older women with many comorbidities, with a higher risk level and a more severe clinical form than in men.

Differential Effects of Influenza Virus NA, HA Head, and HA Stalk Antibodies on Peripheral Blood Leukocyte Gene Expression during Human Infection.

In this study, we examined the relationships between anti-influenza virus serum antibody titers, clinical disease, and peripheral blood leukocyte (PBL) global gene expression during presymptomatic, acute, and convalescent illness in 83 participants infected with 2009 pandemic H1N1 virus in a human influenza challenge model. Using traditional statistical and logistic regression modeling approaches, profiles of differentially expressed genes that correlated with active viral shedding, predicted length of viral shedding, and predicted illness severity were identified. These analyses further demonstrated that challenge participants fell into three peripheral blood leukocyte gene expression phenotypes that significantly correlated with different clinical outcomes and prechallenge serum titers of antibodies specific for the viral neuraminidase, hemagglutinin head, and hemagglutinin stalk. Higher prechallenge serum antibody titers were inversely correlated with leukocyte responsiveness in participants with active disease and could mask expression of peripheral blood markers of clinical disease in some participants, including viral shedding and symptom severity. Consequently, preexisting anti-influenza antibodies may modulate PBL gene expression, and this must be taken into consideration in the development and interpretation of peripheral blood diagnostic and prognostic assays of influenza infection.IMPORTANCE Influenza A viruses are significant human pathogens that caused 83,000 deaths in the United States during 2017 to 2018, and there is need to understand the molecular correlates of illness and to identify prognostic markers of viral infection, symptom severity, and disease course. Preexisting antibodies against viral neuraminidase (NA) and hemagglutinin (HA) proteins play a critical role in lessening disease severity. We performed global gene expression profiling of peripheral blood leukocytes collected during acute and convalescent phases from a large cohort of people infected with A/H1N1pdm virus. Using statistical and machine-learning approaches, populations of genes were identified early in infection that correlated with active viral shedding, predicted length of shedding, or disease severity. Finally, these gene expression responses were differentially affected by increased levels of preexisting influenza antibodies, which could mask detection of these markers of contagiousness and disease severity in people with active clinical disease.

Heritability in genetic heart disease: the role of genetic background

BackgroundMutations in genes encoding ion channels or sarcomeric proteins are an important cause of hereditary cardiac disease. However, the severity of the resultant disease varies considerably even among those with...

The evaluation of α-tocopherol concentration instead of α-tocopherol:cholesterol ratio in adult cystic fibrosis patients results in the overestimation of vitamin E deficiency

Introduction. It has been suggested that serum vitamin E concentrations in CF patients may not properly reflect the body resources of vitamin E. Therefore, we aimed to assess vitamin E status in CF adults relating it to reference values for healthy subjects, also taking into account the α‑tocopherol:cholesterol ratio. Material and Methods. The study group was composed of 33 CF patients − 18 (54.5%) females and 15 (45.5%) males − aged from 18 to 47 years. In all CF patients nutritional status and clinical expression of disease − lung function; Pseudomonas aeruginosa colonization; diabetes; cirrhosis; exocrine pancreatic function and vitamin E supplementation were analyzed. Vitamin E (α‑tocopherol) concentration was assessed by high‑performance liquid chromatography (HPLC).Resuls. CF adults have lower vitamin E concentrations (median: 830 µg/dl vs. 1132 µg/dl, p = 0.00174) and higher vitamin E: cholesterol ratio (median: 7.2 mg/g vs. 6.7 mg/g, p < 0.00001) than healthy subjects. The underlying factor that determines this phenomenon is related to low cholesterol levels observed in CF patients. The percentage of low vitamin E concentrations defined in comparison to healthy Polish peers is considerably higher than low vitamin E:cholesterol ratios (39.4% vs. 21.2%, p = 0.0011). Conclusions. The evaluation of α‑tocopherol concentration instead of α‑tocopherol:cholesterol ratio in CF adults results in the overestimation of vitamin E deficiency. Moreover, there is also potentially a large percentage of individuals with excessive vitamin E body resources. However, this aspect demands further studies.

Optimization of a Loop Mediated Isothermal Amplification (LAMP) Assay for In-Field Detection of Dichelobacter nodosus With aprV2 (VDN LAMP) in Victorian Sheep Flocks.

Dichelobacter nodosus is the primary etiological agent of footrot in sheep and has a variety of virulence factors. Of these, AprV2, an extracellular protease, has been shown to be capable of causing severe or “virulent” disease symptoms under the right conditions. Due to this, a loop-mediated isothermal amplification (LAMP) assay for the detection of aprV2-positive D. nodosus (VDN LAMP) was developed and evaluated for field use. A sample of 19 sheep flocks (309 sheep) in Victoria, Australia, were tested to determine the optimum conditions for in-field VDN LAMP assay use and sampling, for detecting aprV2-positive D. nodosus infected sheep. VDN LAMP performance was compared to a validated rtPCR that detects aprV2 and the benign strain counterpart, aprB2, using biologically duplicate samples to determine sensitivity and specificity. Flocks were sampled either in winter-spring (moist) or early summer (dry) conditions and had a range of clinical expressions of the disease ovine footrot. Variables considered for optimizing field performance were: sample collection method, sample preparation, clinical expression of disease, and nature of the feet when sampled (moist vs. dry, clean vs. soiled). The test was found to perform best when sheep were sampled with moist, clean feet, using a dry swab with the sample prepared in alkaline polyethylene glycol, pH 13.0, as the collection buffer. A sensitivity of 89% and specificity of 97% was seen when used in-field under these conditions, when compared to aprV2 detection by rtPCR, with “very good” agreement to rtPCR results. This study shows the VDN LAMP test is easy to use in-field to identify the presence of aprV2-positive D. nodosus in sheep flocks.

Clinical Parkinson disease subtyping does not predict pathology.

Parkinson disease is a clinicopathological construct at a crossroads. A new study reinforces the prognostic value of subtypes, but its findings challenge the relevance of pathology to the clinical expression of disease as data-driven Parkinson disease subtypes did not match up with severity or distribution of Lewy or Alzheimer pathologies.

The brain cognitive reserve hypothesis: A review with emphasis on the contribution of nuclear medicine neuroimaging techniques.

Neuropathological and clinical evidence indicates that the clinical expression of Alzheimer's disease (AD) occurs as neuropathology exceeds the brain reserve capacity. The brain or cognitive reserve (BCR) hypothesis states that high premorbid intelligence, education, and an active and stimulating lifestyle provide reserve capacity, which acts as a buffer against the cognitive deficits due to accumulating neuropathology. Neuroimaging studies that assessed the BCR hypothesis are critically reviewed with emphasis on study design and statistical analysis. Many studies were performed in the last two decades owing to the increasing availability of positron emission tomography (PET) and PET/computed tomography scanners and to the synthesis of new radiopharmaceuticals, including tracers for amyloid and tau proteins. Studies with different tracers provided complementary consistent results supporting the BCR hypothesis. Many studies were appropriately designed with a measure of reserve, a measure of brain anatomy/function/neuropathology, and a measure of cognitive functions that are necessary. Most of the early studies were performed with PET and [ 18 F]fluorodeoxyglucose, and occasionally with [ 15 O]water, reporting a significant association between higher occupation/education and lower glucose metabolism (blood flow) in associative temporo-parietal cortex in patients with AD and also in patients with MCI, after correcting for the degree in the cognitive impairment. On the contrary, performances on several neuropsychological tests increased with increasing education for participants with elevated [ 11 C]PiB uptake. Studies with the tracers specific for tau protein showed that patients with AD with elevated tau deposits had higher cognitive performances compared with patients with similar levels of tau deposits. BCR in AD is also associated with a preserved cholinergic function. The BCR hypothesis has been validated with methodologically sound study designs and sophisticated neuroimaging techniques using different radiotracers and providing an explanation for neuropathological and clinical observations on patients with AD.

Potential Causality and Emerging Medical Therapies for Lipoprotein(a) and Its Associated Oxidized Phospholipids in Calcific Aortic Valve Stenosis.

The prevalence of calcific aortic valve disease is increasing with aging of the population. Current treatment options for advanced or symptomatic aortic stenosis are limited to traditional surgical or percutaneous aortic valve replacement. Medical therapies that impact the progression of calcific aortic valve disease do not currently exist. New pathophysiological insights suggest that the processes leading to calcific aortic valve disease are metabolically active for many years before and during the clinical expression of disease. The identification of genetic and potentially causal mediators of calcific aortic valve disease allows opportunities for therapies that may slow progression to the point where aortic valve replacement can be avoided. Recent studies suggest that approximately one-third of aortic stenosis cases are associated with highly elevated lipoprotein(a) [Lp(a)] and pathways related to the metabolism of procalcifying oxidized phospholipids. Oxidized phospholipids can be carried by Lp(a) into valve leaflets but can also be formed in situ from cell membranes, lipoproteins, and apoptotic cells. This review will summarize the clinical data implicating the potential causality of Lp(a)/oxidized phospholipids, describe emerging therapeutic agents, and propose clinical trial designs to test the hypothesis that lowering Lp(a) will reduce progression aortic stenosis and the need for aortic valve replacement.

Dexamethasone treatment did not exacerbate Seneca Valley virus infection in nursery-age pigs

BackgroundSenecavirus A, commonly known as Seneca Valley virus (SVV), is a picornavirus that has been infrequently associated with porcine idiopathic vesicular disease (PIVD). In late 2014 there were multiple PIVD outbreaks in several states in Brazil and samples from those cases tested positive for SVV. Beginning in July of 2015, multiple cases of PIVD were reported in the United States in which a genetically similar SVV was also detected. These events suggested SVV could induce vesicular disease, which was recently demonstrated with contemporary US isolates that produced mild disease in pigs. It was hypothesized that stressful conditions may exacerbate the expression of clinical disease and the following experiment was performed. Two groups of 9-week-old pigs were given an intranasal SVV challenge with one group receiving an immunosuppressive dose of dexamethasone prior to challenge. After challenge animals were observed for the development of clinical signs and serum and swabs were collected to study viral shedding and antibody production. In addition, pigs were euthanized 2, 4, 6, 8, and 12 days post inoculation (dpi) to demonstrate tissue distribution of virus during acute infection.ResultsVesicular disease was experimentally induced in both groups with the duration and magnitude of clinical signs similar between groups. During acute infection [0–14 days post infection (dpi)], SVV was detected by PCR in serum, nasal swabs, rectal swabs, various tissues, and in swabs from ruptured vesicles. From 15 to 30 dpi, virus was less consistently detected in nasal and rectal swabs, and absent from most serum samples. Virus neutralizing antibody was detected by 5 dpi and lasted until the end of the study.ConclusionTreatment with an immunosuppressive dose of dexamethasone did not drastically alter the clinical disease course of SVV in experimentally infected nursery aged swine. A greater understanding of SVV pathogenesis and factors that could exacerbate disease can help the swine industry with control and prevention strategies directed against this virus.