Mild Clinical Disease Research Articles

Clinical Value of Deep Gray Matter 3T MRI Perfusion in Patients with Multiple Sclerosis

Abstract Background Multiple sclerosis is one of the most common non traumatic neurological disorders between adults. Magnetic resonance imaging is the most sensitive imaging modality for assessment of multiple patients. New MRI techniques have been improved which help in more accurate assessment of the disease extent, activity, severity and treatment prognosis. Recently, advanced quantitative MRI techniques have detected micro-structural alterations even in the normal appearing white and gray matter of multiple sclerosis patients. In dynamic susceptibility contrast MRI perfusion, the tissue perfusion is assessed by evaluation of a series of rapidly repeated T2*-weighted MR images resulting from the first pass of a contrast agent bolus through the tissue. Objective To highlight the role of MRI perfusion in detection of deep gray matter perfusion alteration in multiple sclerosis patients and its relation to the clinical disability and cognitive impairment Methods 40 patients who were proven as multiple sclerosis patients clinically were enrolled in this study, fulfilled the inclusion criteria. They were divided into two groups (group A with mild clinical disease and preserved cognitive functions, and group B with marked clinical disease and cognitive functions impairment) they were divided according to their clinical disability and cognitive functions status assessed by single experienced neurologist blind to the MRI findings, Additional 20 normal control cases in the same age group were included in the study. Perfusion parameters including cerebral blood volume, cerebral blood flow and mean transit time of the deep gray matter were compared for healthy controls and for the two study groups. Results The cerebral blood flow, cerebral blood volume and mean transit time values averaged over the thalamus, putamen, and caudate nuclei were significantly changed in group B (marked clinical disease with cognitive functions impairment) that shows marked decrease in perfusion parameters (cerebral blood volume and flow) and increased mean transit time compared with group A (mild clinical disease with no cognitive functions impairment) and the controls, With respect to group (A), there was no significant difference between the patients and controls Conclusion The decrease of tissue perfusion in the deep gray matter of patients with multiple sclerosis is associated with the severity of the clinical disease and cognitive impairment.

Crimean Congo hemorrhagic fever virus nucleoprotein and GP38 subunit vaccine combination prevents morbidity in mice

Immunizing mice with Crimean-Congo hemorrhagic fever virus (CCHFV) nucleoprotein (NP), glycoprotein precursor (GPC), or with the GP38 domain of GPC, can be protective when the proteins are delivered with viral vectors or as a DNA or RNA vaccine. Subunit vaccines are a safe and cost-effective alternative to some vaccine platforms, but Gc and Gn glycoprotein subunit vaccines for CCHFV fail to protect despite eliciting high levels of neutralizing antibodies. Here, we investigated humoral and cellular immune responses and the protective efficacy of recombinant NP, GP38, and GP38 forms (GP85 and GP160) associated with the highly glycosylated mucin-like (MLD) domain, as well as the NP + GP38 combination. Vaccination with GP160, GP85, or GP38 did not confer protection, and vaccination with the MLD-associated GP38 forms blunted the humoral immune responses to GP38, worsened clinical chemistry, and increased viral RNA in the blood compared to the GP38 vaccination. In contrast, NP vaccination conferred 100% protection from lethal outcome and was associated with mild clinical disease, while the NP + GP38 combination conferred even more robust protection by reducing morbidity compared to mice receiving NP alone. Thus, recombinant CCHFV NP alone is a promising vaccine candidate conferring 100% survival against heterologous challenge. Moreover, incorporation of GP38 should be considered as it further enhances subunit vaccine efficacy by reducing morbidity in surviving animals.

P308 CPa9-HNE: A NEUTROPHIL-DERIVED FRAGMENT OF CALPROTECTIN MEASURED IN SERUM CAN MONITOR ENDOSCOPIC AND CLINICAL DISEASE ACTIVITY IN ULCERATIVE COLITIS

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) presenting in remitting ulcerations of the colonic mucosa and submucosa. Mucosal healing is therefore an important treatment target. While fecal calprotectin is a common biomarker used to monitor mucosal healing in UC, patient compliance is low due to a preference for serological markers. This study aimed at investigating the association of serum calprotectin [CPa9-HNE], a non-invasive neo-epitope biomarker of neutrophil activity, with both clinical and endoscopic disease activity in UC. Methods The cohort included 49 patients with active UC and 50 and healthy controls (HC). Endoscopic and clinical disease activity was assessed using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and the full Mayo score. Serum calprotectin [CPa9-HNE] was measured, reflecting a human neutrophil elastase-derived fragment of calprotectin. Spearman’s rank correlation was applied. Group differences were evaluated using Kruskal-Wallis with Dunn‘s test, bonferroni corrected for MCP. Diagnostic and discriminative capabilities were assessed using receiver operating characteristic (ROC) statistics with are under the curve (AUC). Results CPa9-HNE was significantly elevated in patients with UC compared to HC (ng/ml [IQR]: 32.4 [29.0–52.3] vs. 26.0 [22.6–29.0], p<0.0001) and presented acceptable discriminative capabilities (AUC [95% CI]: 0.77 [0.67–0.87], p<0.0001). CPa9-HNE showed a moderate positive correlation to UCEIS and Mayo (ρ=0.42; ρ=0.48, both p<0.01). When patients were stratified according to endoscopic disease activity (UCEIS), CPa9-HNE was significantly elevated in patients with severe disease compared to those with mild disease (ng/ml [IQR]: 55.6 [40.9–66.4] vs. 28.9 [24.6–31.1], p<0.01) and could accurately discriminate between the two groups (fig 1A-B). Similarly, when patients were grouped according to the full Mayo score, CPa9-HNE was significantly elevated in patients with mild vs. severe disease (29.1 [24.3–32.4] vs. 62.9 [55.2–67.5], p<0.01) and moderate vs. severe disease (32.0 [29.2–39.2] vs. 62.9 [55.2–67.5], p<0.01), and could accurately discriminate between the groups (fig 1C-E). Conclusion CPa9-HNE was elevated in patients with UC compared with healthy subjects. Furthermore, CPa9-HNE accurately discriminated between patients with mild and severe endoscopic disease based on the UCEIS score, as well as between patients with mild, moderate, and severe clinical disease activity according to the full Mayo score. These findings highlight the potential use of CPa9-HNE as a non-invasive tool to monitor both endoscopic and clinical disease activity in UC, with the potential of guiding treatment decisions and better aligning with patient preferences.

Standalone middle meningeal artery embolization versus middle meningeal artery embolization with concurrent surgical evacuation for chronic subdural hematomas: a multicenter propensity score matched analysis of clinical and radiographic outcomes

BackgroundMiddle meningeal artery embolization (MMAE) has emerged as a promising therapy for chronic subdural hematomas (cSDHs). The efficacy of standalone MMAE compared with MMAE with concurrent surgery is largely unknown.MethodscSDH...

Type 1 Interferon-Stimulated Gene Expression and Disease Activity in Pediatric Rheumatic Diseases: No Composite Scores Needed?

Rheumatic diseases are characterized by different patterns of immune overactivation. This study investigated the correlation of whole blood type 1 interferon (IFN) stimulated gene (ISG), IL18, and CXCL9 expression with clinical disease activity in pediatric rheumatic diseases and assessed the required number of ISGs to be included in a composite type 1 IFN score. Whole blood-derived RNA and clinical data were collected from 171 mostly pediatric patients with connective tissue diseases (CTDs), systemic autoinflammatory diseases (SAIDs), monogenic interferonopathies (IFNPs) and other inflammatory diseases, and from 38 controls. The expression of six previously established ISGs, IL18, and CXCL9 was assessed by real-time polymerase chain reaction (471 samples). Individual and composite gene expression was assessed, and correlation and threshold analyses were performed. Correlation between ISG expression and clinical disease activity was strongest in CTD, especially in juvenile dermatomyositis (JDM) and IFNP, and modest in patients with SAID. Threshold ISG expression levels for the detection of at least mild clinical disease activity were substantially higher in patients with systemic lupus erythematosus compared with JDM. The correlation of expression levels of limited sets of ISGs and even individual ISGs with clinical disease activity were not inferior to a composite score of six ISGs. In a real-world cohort, individual ISG expression levels robustly reflected clinical disease activity in CTD and IFNP, especially in JDM, which would simplify such analyses in clinical routine and be more cost-effective. Threshold levels varied across diseases, potentially reflecting different mechanisms of type 1 IFN overactivation.

The clinical value of deep gray matter 3T MRI perfusion in patients with multiple sclerosis

Background. Multiple sclerosis (MS) is a common neurological disorder between adults. Magnetic resonance imaging (MRI) is the imaging modality of choice, new MRI techniques helped in more accurate assessment of the disease extent, activity and severity. In dynamic susceptibility contrast (DSC), the perfusion of the lesions as well as normally appearing white and gray matter of the brain have been assessed. Objective. To highlight the role of MRI perfusion of the deep gray matter in multiple sclerosis patients and its relation to their clinical disability and cognitive impairment Methods. 40 patients with MS were enrolled in this study, they were divided into two groups (group A with mild clinical disease and preserved cognitive functions, and group B with marked clinical disease and cognitive functions impairment) they were divided according to their clinical disability and cognitive impairment assessed by experienced neurologist, Additional 20 healthy controls were included. Perfusion parameters including cerebral blood volume(CBV), cerebral blood flow (CBF) and mean transit time (MTT) of the deep gray matter were compared for healthy controls and for the study groups. Results. The perfusion values of the thalamus, putamen and caudate were significantly changed in group B that shows marked decrease in CBV and CBF and increased MTT compared with group A and the controls, With respect to group (A), there was no significant difference between the patients and controls Conclusion. The decrease of perfusion of the deep gray matter in patients with MS is associated with the severity of the disease and cognitive impairment.

Immunization with Anaplasma centrale Msp2 HVRs Is Less Effective than the Live A. centrale Vaccine against Anaplasmosis.

Bovine anaplasmosis, caused by Anaplasma marginale, is the most prevalent tick-transmitted pathogen of livestock globally. In many parts of the world, Anaplasma centrale, a related organism, is used as a live blood-borne vaccine as it causes either no or only a mild clinical disease. Anaplasma centrale does not prevent infection with A. marginale but does prevent acute disease. Anaplasma centrale is prohibited from being used in the U.S. due to the risk of transmitting emerging pathogens. Both of these organisms encode proteins known as major surface protein 2 (Msp2), which is the most immunodominant protein for the organism. Both organisms persist in their host by evading clearance, i.e., the adaptive immune response, by recombining the hypervariable region (HVR) of msp2 with pseudogene alleles. The study goal was to test whether the Msp2 HVRs encoded by A. centrale are a sufficient source of immune stimulation to provide the clinical protection exhibited by the blood-borne vaccine. Calves were inoculated with recombinantly expressed A. centrale HVRs. Control groups were inoculated with saponin or infected with the A. centrale live vaccine and compared with the test group. A Western blot analysis demonstrated that the HVR immunizations and A. centrale live vaccine stimulated an immune response. All animals in the study became infected upon challenge with A. marginale-infected ticks. The saponin-immunized control group had a high PPE (5.4%) and larger drops in PCVs (14.6%). As expected, the A. centrale-immunized animals were protected from acute disease with lower (0.6%) parasitemia and lower drops in PCV (8.6%). The HVR-immunized group had intermediate results that were not statistically significantly different from either the negative or positive controls. This suggests that the HVR immunogen does not fully recapitulate the protective capacity of the live vaccine.

Comparison of two assays to diagnose herpes simplex virus in patients with central nervous system infections.

Multiplex PCR panels are frequently used for detecting the diagnosis of central nervous system infection, but have demonstrated lower sensitivity for herpes simplex virus (HSV) compared to targeted PCRs. Providers in our institution frequently order both multiplex (BioFire Meningitis/Encephalitis Panel (MEP)) and targeted HSV PCR (Diasorin Simplexa HSV-1/2 Direct), allowing comparison of assay performance in practice and a unique clinical characterization of patients with concordant positive or discordant results. We retrospectively analyzed all HSV testing performed using the two assays simultaneously in a large multi-center institution between 12/10/2018 and 6/6/2022. We described and compared laboratory, diagnostic and therapeutic data between patients with positive results on both assays with patients with discordant results. 1,387 patients were tested with both assays, of which 25 were positive on at least one assay. Eleven (44%) had discordant results; 9 were targeted-PCR-positive/MEP-negative and 2 were targeted-PCR-negative/MEP-positive. Compared with patients with concordant positive results, discordant targeted PCR-positive/MEP-negative patients had a higher PCR cycle threshold value (i.e., >35) and milder illness characterized by lower CSF WBC counts (4vs 152; p=0.032), fewer MRI abnormalities (37.5% vs. 87.5%; p=0.039), HSV meningoencephalitis as primary discharge diagnosis (33% vs. 100%; p<0.0001) and were more often treated with oral medication or none at all. Patients with discordant targeted PCR-positive/MEP-negative results represent a population with milder clinical disease. These findings will help clinicians and laboratorians determine when both targeted HSV and multiplex assays should be performed simultaneously and identify patients for whom a multiplex PCR may suffice, despite lower assay sensitivity.

FTP2.1 Management settings and follow-up of acute diverticulitis

Abstract Aims This audit evaluated our management of acute diverticulitis against the NICE and ACPGBI guidelines. We explored follow-up luminal investigations to ensure patients safety, and practicality of ambulatory management to potentially improve bed capacity and reduce costs. Method Retrospective data of patients presented acutely with CT-proven diverticulitis from 01/06/2021 to 31/10/2021 was collected. We focused on clinical, biochemical and radiological severity, management, and follow-up investigations. Results Records of 142 patients were evaluated, most of them had mild clinical disease with significant qSOFA score in only 8 patients. Most of patients had WCC of less than 15 and CRP of less than 100. Even in radiological severity, class 1a of modified Hinchey classification (uncomplicated disease) dominated with 96 patients. Interestingly, only 22 patients were treated via ambulatory care, while the remaining 120 received inpatient care. 10 of the inpatient treated patients required HDU/ ITU support and most of the hospital stays were 7 days or less. The treatment was predominantly non-operative, with only 4 patients required surgery and 6 others required radiological drainage. The 1-year follow-up showed only 16 readmissions. As for the follow-up investigations, 45 did not have any follow-up investigations or clinic reviews, 14 of them had complicated diverticulitis. Of the 97 patients who were followed up, 88 patients had endoscopic evaluation and 8 underwent CT colonography. Conclusion Since most patients of acute diverticulitis present with clinically, biochemically, and radiologically mild and uncomplicated disease, ambulatory management should be encouraged where possible. While 1-year readmissions remain low, it is crucial that patients, especially those with complicated disease, receive luminal investigations.

Abstract P1049: The Impact Of Endurance Exercise On Longer-term Myocardial Fibrosis Development And Ventricular Arrhythmogenicity In Murine Coxsackievirus B3 Myocarditis

Aims: Diagnostic work-up of athletes often reveals nonischaemic myocardial fibrosis, which is associated with cardiac dysfunction and malignant arrhythmias. Its isolated finding on magnetic resonance imaging is commonly attributed to preceding viral myocarditis. Previous murine studies have shown a negative effect of exercise early in the course of viral myocarditis. In this study, we investigate, for the first time, the impact of endurance exercise on myocardial fibrosis development and arrhythmogenicity in a murine viral myocarditis model. Methods &amp; Results: Eleven-week-old male C57BL/6J mice (n=72) were randomised to 8 weeks of treadmill running (EEX) or without exercise (SED). After 2 weeks, animals received a single injection with either coxsackievirus B3 to induce acute viral myocarditis (CVB) or vehicle as control (PBS). Exercise resulted in a milder clinical disease course, with less weight loss and better preserved running capacity. In addition, mortality was lower in exercising myocarditis mice (11 vs. 27%), however without statistical significance (P=0.23). Exercise during myocarditis increased the occurrence of interstitial fibrosis (limited or extensive distribution) at sacrifice ( i.e. 6 weeks after inoculation)(82.4% in CVB-EEX vs. 56.3% in CVB-SED; P=0.049). Additionally, exercise enhanced development of perivascular and/or interstitial fibrosis with extensive distribution (64.7% &amp; 64.7% in CVB-EEX vs. 50% &amp; 31.3% in CVB-SED; P=0.048). CVB-EEX animals demonstrated more myocardial scars on average, albeit not significantly (1.9 vs. 1.2; P=0.19), with similar scar distribution. Despite manifest fibrotic remodelling, collagen and fibrogenetic genes were not upregulated in the myocarditis groups at the time of sacrifice. In vivo right ventricular programmed electrical stimulation showed comparable ventricular arrhythmia inducibility in the myocarditis groups (P&gt;0.20). The longest arrhythmias and highest cumulative arrhythmia burden occurred in CVB-EEX, however, without reaching statistical significance when compared to CVB-SED (P=0.49). Conclusion: Endurance exercise during viral myocarditis enhances perivascular and interstitial fibrosis development, which may promote ventricular arrhythmogenicity.

Naturally-occurring serotype 3 Streptococcus pneumoniae strains that lack functional pneumolysin and autolysin have attenuated virulence but induce localized protective immune responses.

Streptococcus pneumoniae is an important cause of fatal pneumonia in humans. These bacteria express virulence factors, such as the toxins pneumolysin and autolysin, that drive host inflammatory responses. In this study we confirm loss of pneumolysin and autolysin function in a group of clonal pneumococci that have a chromosomal deletion resulting in a pneumolysin-autolysin fusion gene Δ(lytA'-ply')593. The Δ(lytA'-ply')593 pneumococci strains naturally occur in horses and infection is associated with mild clinical signs. Here we use immortalized and primary macrophage in vitro models, which include pattern recognition receptor knock-out cells, and a murine acute pneumonia model to show that a Δ(lytA'-ply')593 strain induces cytokine production by cultured macrophages, however, unlike the serotype-matched ply+lytA+ strain, it induces less tumour necrosis factor α (TNFα) and no interleukin-1β production. The TNFα induced by the Δ(lytA'-ply')593 strain requires MyD88 but, in contrast to the ply+lytA+ strain, is not reduced in cells lacking TLR2, 4 or 9. In comparison to the ply+lytA+ strain in a mouse model of acute pneumonia, infection with the Δ(lytA'-ply')593 strain resulted in less severe lung pathology, comparable levels of interleukin-1α, but minimal release of other pro-inflammatory cytokines, including interferon-γ, interleukin-6 and TNFα. These results suggest a mechanism by which a naturally occurring Δ(lytA'-ply')593 mutant strain of S. pneumoniae that resides in a non-human host has reduced inflammatory and invasive capacity compared to a human S. pneumoniae strain. These data probably explain the relatively mild clinical disease in response to S. pneumoniae infection seen in horses in comparison to humans.

Characterization of Chicken-Derived Genotype VII Newcastle Disease Virus Isolates from Northwest China

Newcastle disease virus (NDV) threatens global poultry production, with genotype VII the most prevalent strain in China. However, little information is available regarding viral multiplication and pathogenicity based inoculation route. The objectives of this study were to sequence NDV VII isolates and to analyze their biological characteristics in detail. A total of 86 oral and cloacal swabs were collected from Shaanxi and Gansu provinces in northwest China. Identification of genotype VII NDV based on the M gene was performed by qPCR. Viral multiplication and pathogenicity were assessed as a function of route of infection. We observed increased morbidity and mortality using intravenous injection, whereas intranasal, intraocular, and cloacal infections resulted in slower progression and milder clinical disease, with viral proliferation obvious in different tissues. These results provide an important basis for the clinical control and prevention of NDV epidemics in poultry.

Staphylococcal Scalded Skin Syndrome in Neonates: Case Series and Overview of Outbreaks.

Skin and soft tissue infections caused by Staphylococcus aureus (S. aureus) cover a wide spectrum of diseases in neonates, including staphylococcal scalded skin syndrome (SSSS). We describe a representative case of SSSS in neonatal twins, which despite recurrence showed a mild clinical disease course. This case was part of a small outbreak on a neonatal intensive care unit and therefore exemplifies the existence of neonatal outbreaks with skin and soft tissue infections by S. aureus. Diagnosis is generally based on the clinical picture and response to antibiotics, but can be aided by histology and cultures. Sequence-based molecular techniques are available to evaluate typing and virulence of S. aureus in outbreak or surveillance settings. The pillars of treatment are antibiotics and supportive care. Methicillin resistance remains a topic of concern, especially in outbreak settings. Our overview of numerous outbreaks of neonatal S. aureus skin infections underlines the importance of outbreak management strategies, including screening to identify the source of the outbreak, and limiting exposure through hygienic measures and establishment of physical boundaries.

Association Between Body Mass Index Variation and Early Mortality Among 834 Ethiopian Adults Living with HIV on ART: A Joint Modelling Approach.

Body mass index (BMI) is a simple and cost-effective tool for monitoring the clinical responses of patients living with human immunodeficiency virus (HIV) after antiretroviral therapy (ART) initiation, especially in resource-limited settings where access to laboratory tests are limited. Current evidence on the association between longitudinal BMI variation and clinical outcomes among adults living with HIV receiving ART is essential to inform clinical guidelines. Therefore, this study examines the association between BMI variation and premature mortality in adults living with HIV on ART. An institution-based retrospective cohort study was conducted among 834 adults living with HIV receiving ART from June 2014 to June 2020 at Debre Markos Comprehensive Specialized Hospital in Northwest Ethiopia. We first identified predictors of mortality and BMI variation using proportional hazards regression and linear mixed models, respectively. Then, the two models were combined to form an advanced joint model to examine the effect of longitudinal BMI variation on mortality. Of the 834 participants, 49 (5.9%) died, with a mortality rate of 4.1 (95% CI 3.1, 5.4) per 100 person-years. A unit increase in BMI after ART initiation corresponded to an 18% reduction in mortality risk. Patients taking tuberculosis preventive therapy (TPT), mild clinical disease stage, and changing ART regimens were at lower risk of death. However, patients with ambulatory/bedridden functional status were at higher risk of death. Regarding BMI variation over time, patients presenting with opportunistic infections (OIs), underweight patients, patients who started a Dolutegravir (DGT)-based ART regimen, and those with severe immunodeficiency had a higher BMI increase over time. However, patients from rural areas and overweight/obese patients experienced a lower BMI increase over time. BMI improvement after ART initiation was strongly associated with a lower mortality risk, regardless of BMI category. This finding implies that BMI may be used as a better predictor tool for death risk in adults living with HIV in Ethiopia. Additionally, patients who took a DGT-based ART regimen had a higher BMI increase rate over time, which aligns with possible positive effects, such as weight gain, of the DGT-based ART regimen in developing countries.

Comparative pathogenesis of two genotype VI.2 avian paramyxovirus type-1 viruses (APMV-1) in pheasants, partridges and chickens

ABSTRACT Newcastle disease (ND) is caused by virulent forms of avian paramyxovirus-1 (APMV-1) and is an economically important disease of poultry world-wide. Pigeon paramyxovirus 1 (PPMV-1), a sub-group of APMV-1 is endemic in Columbiformes and can cause infections of poultry. An outbreak of ND in partridges in Scotland, UK, in 2006 (APMV-1/partridge/UK(Scotland)/7575/06) was identified as a class II, genotype VI.2.1.1.2.1, more commonly associated with PPMV-1. It has been hypothesized that game birds may be a route of transmission into commercial poultry settings due to the semi-feral rearing system, which potentially brings them into contact with both wild-birds and poultry species. Therefore, the pathogenesis and transmission of APMV-1/partridge/UK(Scotland)/7575/06 in game birds and chickens was investigated, and compared to a contemporary PPMV-1 isolate, PPMV-1/pigeon/UK/015874/15. Viral shedding and seroconversion profiles demonstrated that pheasants were susceptible to infection with APMV-1/partridge/UK(Scotland)/7575/06 with limited clinical signs observed although they were able to excrete and transmit virus. In contrast, partridges and pheasants showed limited infection with PPMV-1/pigeon/UK/015874/15, causing mild clinical disease. Chickens, however, were productively infected and were able to transmit virus in the absence of clinical signs. From the data, it can be deduced that whilst game birds may play a role in the transmission and epidemiology of genotype VI.2 APMV-1 viruses, the asymptomatic nature of circulation within these species precludes evaluation of natural infection by clinical surveillance. It therefore remains a possibility that genotype VI.2 APMV-1 infection in game birds has the potential for asymptomatic circulation and remains a potential threat to avian production systems. RESEARCH HIGHLIGHTS Demonstration of infection of game birds with Pigeon paramyxovirus-1 (PPMV-1). There are differing dynamics of infection between different game bird species. Differing dynamics of infection between different PPMV-1 isolates and genotypes in game birds and chickens.

Assessing how biological sex effects tissue-resident memory T cell responses to influenza infection

Abstract The severity and outcome of influenza virus infection are dependent on various host factors including sex. During the 1918 influenza pandemic, males succumbed to viral infections more than females. Following seasonal influenza vaccination, haemagglutination inhibition titers are significantly higher in females than males. Additionally, the Tlr7 gene that recognizes influenza viruses is located on the X chromosome, resulting in higher expression in females. It is not known whether sex influences non-lymphoid tissue residency of lymphocytes during influenza infection. To explore this, we infected male and female mice intratracheally with 20 PFU influenza virus (A/PR8/H1N1). No significant change was noted in weight loss; however, females displayed a higher survival rate and milder clinical disease nine days post-infection. Lungs of female mice contained greater numbers of influenza-specific tissue-resident CD4+ T-cells compared to males. To assess the role of extra-lymphoid tissues in tissue residency in both sexes, we infected male and female lymphotoxin-a knockout (LTa KO) splenectomized mice that resulted in a total lack of all lymphoid tissues. Physiological differences trended the same for both males and females, with no significant weight difference; however, LTa KO females generated more tissue-resident CD4+ T-cells, while males displayed greater numbers of tissue-resident CD8+ T-cells. Overall, females generated a stronger immune response in the absence of lymphoid tissues in response to the virus. Taken together, our data reveal a novel sex-based effect of viral infection on tissue-resident lymphocytes and non-lymphoid tissue immunity. Supported by a grant from the W.M. Keck Foundation

Vaccination

Vaccination

Modeling SARS-CoV-2: Comparative Pathology in Rhesus Macaque and Golden Syrian Hamster Models.

Coronavirus disease 2019 (COVID-19) in humans has a wide range of presentations, ranging from asymptomatic or mild symptoms to severe illness. Suitable animal models mimicking varying degrees of clinical disease manifestations could expedite development of therapeutics and vaccines for COVID-19. Here we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulted in subclinical disease in rhesus macaques with mild pneumonia and clinical disease in Syrian hamsters with severe pneumonia. SARS-CoV-2 infection was confirmed by formalin-fixed, paraffin-embedded (FFPE) polymerase chain reaction (PCR), immunohistochemistry, or in situ hybridization. Replicating virus in the lungs was identified using in situ hybridization or virus plaque forming assays. Viral encephalitis, reported in some COVID-19 patients, was identified in one macaque and was confirmed with immunohistochemistry. There was no evidence of encephalitis in hamsters. Severity and distribution of lung inflammation were substantially more in hamsters compared with macaques and exhibited vascular changes and virus-induced cytopathic changes as seen in COVID-19 patients. Neither the hamster nor macaque models demonstrated evidence for multisystemic inflammatory syndrome (MIS). Data presented here demonstrate that macaques may be appropriate for mechanistic studies of mild asymptomatic COVID-19 pneumonia and COVID-19-associated encephalitis, whereas Syrian hamsters may be more suited to study severe COVID-19 pneumonia.

Absolute Eosinophil Count as a marker to differentiate COVID-19 from other short febrile illness

Purpose: Peripheral blood routine examination results are often abnormal in Covid-19. This study aimed to determine whether absolute eosinophil count can be used as a marker to differentiate covid-19 from other short febrile illness Materials and Methods: This was a single-center retrospective descriptive study which studied 1000 laboratory confirmed Covid-19 patients and 300 patients with non-Covid short febrile illness. The peripheral blood routine examination results and relevant demographic parameterson the first day of hospital visit for both groups; and the clinical disease severity category assigned to each patient in the Covid-19 group were obtained from the hospital electronic medical records and analysed at the end of the study using appropriate statistical tools. Results: The median AEC was 55 cells/mm3 (13.2-140.4) and 167.57cells/mm3 (83.6-247.4) in the Covid and non-Covid groups respectively (p &lt; 0.001). The median NLR was 2.6 (1.5-5.3) and 2.7 (1.9-4.2) in the Covid and non-Covid groups respectively (p=0.689). Upon comparing mild, moderate and severe clinical disease severity, median AEC was lowest and median NLR was highest in the severe category (p&lt; 0.001) Conclusion: A low AEC may help differentiate Covid-19 infection from other short febrile illness when used in conjunction with clinico-radiological features. An initial low AEC and high NLR can predict increased clinical disease severity.

A survey of sheep dicrocoeliosis in Sulaymaniyah slaughterhouse, northern Iraq in 2013-2014.

Dicrocoelium dendriticum is a helminth which lives in the bile ducts and gall bladder of mammalian definitive hosts. Dicrocoeliosis is thought to be endemic in some countries and it has an increasing prevalence in Northern Iraq, potentially due to increased importation of infected animals, particularly sheep, in high numbers from neighboring countries. The parasite's ability to infect rodents, wild animals, livestock and humans means this parasite is of significant interest in veterinary and human medicine. While D. dendriticum causes relatively mild clinical disease in animals, infection leads to liver condemnation at slaughter and subsequent economic losses to farmers. In this study, the livers of 91,486 sheep slaughtered at Sulaymaniyah New Slaughterhouse (Northern Iraq) were visually inspected for D. dendriticum infection between November 2013 and March 2014, with 1269 livers rejected due to D. dendriticum in this period, representing 29.4% of all condemned livers. The highest rate of rejection due to D. dendriticum infection was seen in December, possibly linked to increased numbers of intermediate host snails during the wet season. Routine inspection of condemned livers revealed adult flukes of D. dendriticum and eggs were seen in the faeces of imported sheep, indicating these animals may be a vector for introduction of D. dendriticum to this region. Due to the complex life cycle and wide range of animals which it infects, we cannot establish the exact route of introduction into Iraq; however, our study suggests that slaughterhouse workers, farmers and local health authorities should be aware of the presence of D. dendriticum, and the potential risks it represents to both human and animal health. Our data also suggest that some level of quarantine or border checks may be useful to prevent further introduction of D. dendriticum or other pathogens into Iraq, although this may prove difficult until accurate diagnostic assays are developed.