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Influenza Infection (influenza + infection)

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Medical Sciences	100%

Selected Abstracts

An ex vivo swine tracheal organ culture for the study of influenza infection

INFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 1 2010
Sandro F. Nunes
Background The threat posed by swine influenza viruses with potential to transmit from pig populations to other hosts, including humans, requires the development of new experimental systems to study different aspects of influenza infection. Ex vivo organ culture (EVOC) systems have been successfully used in the study of both human and animal respiratory pathogens. Objectives We aimed to develop an air interface EVOC using pig tracheas in the study of influenza infection demonstrating that tracheal explants can be effectively maintained in organ culture and support productive influenza infection. Methods Tracheal explants were maintained in the air interface EVOC system for 7 days. Histological characteristics were analysed with different staining protocols and co-ordinated ciliary movement on the epithelial surface was evaluated through a bead clearance assay. Explants were infected with a swine H1N1 influenza virus. Influenza infection of epithelial cells was confirmed by immunohistochemistry and viral replication was quantified by plaque assays and real-time RT-PCR. Results Histological analysis and bead clearance assay showed that the tissue architecture of the explants was maintained for up to 7 days, while ciliary movement exhibited a gradual decrease after 4 days. Challenge with swine H1N1 influenza virus showed that the EVOC tracheal system shows histological changes consistent with in vivo influenza infection and supported productive viral replication over multiple cycles of infection. Conclusion The air interface EVOC system using pig trachea described here constitutes a useful biological tool with a wide range of applications in the study of influenza infection. [source]

Procoagulant and inflammatory response of virus-infected monocytes

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2002
J. J. M. Bouwman
Abstract Background Monocytes play a prominent role in inflammation, coagulation and atherosclerosis by their ability to produce tissue factor (TF) and cytokines. The aim of the present study was to establish whether virus-infected monocytes initiate coagulation. In addition, the production of cytokines by monocytes may accelerate the chronic process of atherosclerosis and may contribute to coronary syndromes by eliciting plaque instability. Materials and methods Monocytes were isolated by Vacutainer®, BD Biosciences, Alphen aan den Rijn, Netherlands and subsequent magnetic cell sorting (MACS®, Milteny Biotec, Bergish Gladbach, Germany). Coagulation times in normal pooled plasma and Factor VII-deficient plasma were measured after infection with cytomegalovirus (CMV), Chlamydia pneumoniae (Cp) and influenza A\H1N1. Anti-TF antibodies were added to neutralize TF expressed on monocytes. Interleukins (IL) 6, 8 and 10 were measured in the supernatants. Results Chlamydia pneumoniae- and CMV-infected monocytes decreased the clotting time by 60%, and influenza-infected monocytes by 19%, as compared to uninfected monocytes. Procoagulant activity was absent when Factor VII-deficient plasma or anti-TF antibodies were used. Monocytes produced both IL-6 and IL-8 after infection with CMV (317 pg mL,1 and 250 pg mL,1) or Cp (733 pg mL,1 and 268 pg mL,1). Similar results were obtained for influenza virus-infected monocytes, but the levels of both cytokines were 3,5-fold higher (1797 pg mL,1 and 725 pg mL,1). Interleukin-10 was not produced by infected monocytes. Conclusion The procoagulant activity of virus-infected monocytes is TF-dependent. Although influenza infection did not generate a significant reduction in clotting time, the pronounced expression of IL-6 and IL-8 may induce local and/or systemic inflammatory reactions, which may be associated with plaque rupture and atherosclerosis. The lack of production of the anti-inflammatory cytokine IL-10 may even accelerate these processes. [source]

Granzyme A expression reveals distinct cytolytic CTL subsets following influenza A virus infection

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2009
Jessica M. Moffat
Abstract CTL mediate anti-viral immunity via targeted exocytosis of cytolytic granules containing perforin and members of the granzyme (grz) serine protease family. Here, we provide the first analysis of grzA protein expression by murine anti-viral CTL. During the progression of influenza A virus infection, CTL expressed two divergent cytolytic phenotypes: grzA,B+ and grzA+B+. CTL lacked grzA expression during the initial rounds of antigen-driven division. High levels of grzA were expressed by influenza-specific CTL early post infection (day 6), particularly in tissues associated with the infected respiratory tract (bronchoalveolar lavage, lung). Following resolution of influenza infection, a small population of memory CTL expressed grzA. Interestingly, individual influenza A virus-derived epitope-specific CTL expressed different levels of grzA. The grzA expression hierarchy was determined to be KbPB1703=DbF262=KbNS2114>DbNP366=DbPA224 and inversely correlated with CTL magnitude. Therefore following influenza infection, a CTL cytolytic hierarchy was established relating to the different profiles of antigen expression and relative immunodominance. Analysis of CTL grzA expression during influenza virus immunity has enabled a more detailed insight into the cytolytic mechanisms of virus elimination. [source]

Determinants of influenza vaccination timing

HEALTH ECONOMICS, Issue 8 2005
Byung Kwang Yoo
Abstract New guidelines recommend different influenza vaccination timing for different subpopulations due to the limited availability of flu shots (FS). This study's objectives are to develop a theoretical model to demonstrate why some individuals choose to receive an early FS while others choose a late FS and to empirically explore the determinants of vaccination timing. Empirical results generally supported the theoretical results. Individuals vary their FS timing in response to variations in perceived risks, chronic condition levels reflecting their risk of influenza infection, and opportunity costs, measured by the presence of medical care other than an FS. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Immune regulation by 4-1BB and 4-1BBL: complexities and challenges

IMMUNOLOGICAL REVIEWS, Issue 1 2009
Chao Wang
Summary:, The tumor necrosis factor receptor family member 4-1BB plays a key role in the survival of activated and memory CD8+ T cells. Depending on the disease model, 4-1BB can participate at different stages and influence different aspects of the immune response, likely due to the differential expression of receptor and ligand relative to other costimulatory molecules. Studies comparing mild versus severe influenza infection of mice suggest that the immune system uses inducible receptors such as 4-1BB to prolong the immune response when pathogens take longer to clear. The expression of 4-1BB on diverse cell types, evidence for bidirectional as well as receptor-independent signaling by 4-1BBL, the unexpected hyperproliferation of 4-1BB-deficient T cells, and complex effects of agonistic anti-4-1BB therapy have revealed additional roles for the 4-1BB/4-1BBL receptor/ligand pair in the immune system. In this review, we discuss these diverse roles of 4-1BB and its ligand in the immune response, exploring possible mechanisms for the observed complexities and implications for therapeutic applications of 4-1BB/4-1BBL. [source]

CD4+ T-cell memory: generation and multi-faceted roles for CD4+ T cells in protective immunity to influenza

IMMUNOLOGICAL REVIEWS, Issue 1 2006
Susan L. Swain
Summary:, We have outlined the carefully orchestrated process of CD4+ T-cell differentiation from naïve to effector and from effector to memory cells with a focus on how these processes can be studied in vivo in responses to pathogen infection. We emphasize that the regulatory factors that determine the quality and quantity of the effector and memory cells generated include (i) the antigen dose during the initial T-cell interaction with antigen-presenting cells; (ii) the dose and duration of repeated interactions; and (iii) the milieu of inflammatory and growth cytokines that responding CD4+ T cells encounter. We suggest that heterogeneity in these regulatory factors leads to the generation of a spectrum of effectors with different functional attributes. Furthermore, we suggest that it is the presence of effectors at different stages along a pathway of progressive linear differentiation that leads to a related spectrum of memory cells. Our studies particularly highlight the multifaceted roles of CD4+ effector and memory T cells in protective responses to influenza infection and support the concept that efficient priming of CD4+ T cells that react to shared influenza proteins could contribute greatly to vaccine strategies for influenza. [source]

Antibody response to influenza infection of mice: different patterns for glycoprotein and nucleocapsid antigens

IMMUNOLOGY, Issue 4 2003
Robert Sealy
Summary Our previous studies of C57BL/6 mice intranasally infected with influenza virus (A/PR8) revealed a spike of virus-specific immunoglobulin A (IgA)-secreting antibody-forming cells (AFC) in the mediastinal lymph node (MLN) 7 days post-infection. Here we show that these AFC are directed only against viral glycoprotein, and not nucleocapsid antigens. The early IgA spike associates with a decline in glycoprotein-specific AFC during week 2 post-infection. In contrast to the glycoprotein-specific AFC, nucleocapsid-specific, IgA-secreting AFC develop gradually in the MLN and persist for more than 3 weeks post-infection. As peripheral lymph node reactions wane, the nucleocapsid-specific AFC appear as long-sustained populations in the bone marrow. Microanatomical examination of the respiratory tract in infected mice shows foci of infection established in the lung 2 days post-infection, from which virus spreads to infect the entire lining of the trachea by day 3. At this time, viral haemagglutinin can be seen within the MLN, probably on projections from infected dendritic cells. This feature disappears within a day, though viral antigen expression continues to spread throughout the respiratory tract. Total IgA- and IgG-secreting AFC appear histologically in large numbers during the first week post-infection, significantly preceding the appearance of germinal centres (revealed by peanut agglutinin staining in week 2). To explain these results, we suggest that the initial immunogenic encounter of B cells with viral antigens occurs about 3 days post-infection in the MLN, with antigens transported by dendritic cells from airway mucosa, the only site of viral replication. Viral glycoproteins expressed as integral membrane components on the surface of infected dendritic cells [probably in the absence of cognate T helper (Th) cells] promote members of expanding relevant B-cell clones to undergo an IgA switch and terminal local plasmacytoid differentiation. Anti-glycoprotein specificities are thus selectively depleted from progeny of activated B-cell clones which are channelled to participate in germinal centre formation (perhaps by cognate T helper cells when they become sufficiently frequent). One product of the germinal centre reaction is the long-sustained, bone marrow-resident population, which is accordingly rich in anti-nucleoprotein, but not anti-glycoprotein specificities. Of note, we find that AFC responses toward influenza virus and Sendai virus differ, even though viral replication is limited to the airway mucosa in each case. The response towards Sendai virus exhibits neither the early appearance of anti-glycoprotein AFC expressing IgA in draining lymph nodes, nor the subsequent relative deficit of this specificity from bone marrow AFC populations. [source]

Serologic survey of swine workers for exposure to H2N3 swine influenza A

INFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 3 2010
Amanda Beaudoin
Please cite this paper as: Beaudoin et al. (2010) Serologic survey of swine workers for exposure to H2N3 swine influenza A. Influenza and Other Respiratory Viruses 4(3), 163,170. Background, Of the 16 influenza A hemagglutinin (H) subtypes, only H1, H2 and H3 viruses have been shown to cause sustained human infection. Whereas H1 and H3 viruses currently circulate seasonally in humans, H2 viruses have not been identified in humans since 1968. In 2006, an H2N3 influenza virus was isolated from ill swine in the United States. Objective, To assess the potential for zoonotic influenza transmission, the current study looked for serologic evidence of H2 influenza infection among workers at two swine facilities, some exposed and some unexposed to H2N3-positive pigs. Methods, The sera were assessed for antibodies to swine H2 influenza and currently circulating seasonal human influenza A subtypes H1N1 and H3N2. Workers were interviewed to obtain details such as age, influenza vaccination history, experiences of influenza-like-illness, and use of personal protective equipment and hygiene when working with pigs. Exposure and risk factors for positive antibody titers were compared for exposed and unexposed individuals as well as for H2 antibody-positive and H2 antibody-negative individuals. Results, Blood was taken from 27 swine workers, of whom four had positive H2 antibody titers (,1:40). Three of the positive employees were born before 1968 and one had an unknown birth date. Only one of these workers had been exposed to H2N3-positive pigs, and he was born in 1949. Conclusions, These data do not support the hypothesis that swine workers were infected with the emergent swine H2N3 influenza A virus. [source]

An ex vivo swine tracheal organ culture for the study of influenza infection

The burden of influenza in East and South-East Asia: a review of the English language literature

INFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 3 2008
James M. Simmerman
Abstract, While human infections with avian influenza A (H5NI) viruses in Asia have prompted concerns about an influenza pandemic, the burden of human influenza in East and Southeast Asia has received far less attention. We conducted a review of English language articles on influenza in 18 countries in East and Southeast Asia published from 1980 to 2006 that were indexed on PubMed. Articles that described human influenza-associated illnesses among outpatients or hospitalized patients, influenza-associated deaths, or influenza-associated socioeconomic costs were reviewed. We found 35 articles from 9 countries that met criteria for inclusion in the review. The quality of articles varied substantially. Significant heterogeneity was noted in case definitions, sampling schemes and laboratory methods. Early studies relied on cell culture, had difficulties with specimen collection and handling, and reported a low burden of disease. The recent addition of PCR testing has greatly improved the proportion of respiratory illnesses diagnosed with influenza. These more recent studies reported that 11,26% of outpatient febrile illness and 6-14% of hospitalized pneumonia cases had laboratory-confirmed influenza infection. The influenza disease burden literature from East and Southeast Asia is limited but expanding. Recent studies using improved laboratory testing methods and indirect statistical approaches report a substantial burden of disease, similar to that of Europe and North America. Current increased international focus on influenza, coupled with unprecedented funding for surveillance and research, provide a unique opportunity to more comprehensively describe the burden of human influenza in the region. [source]

Influenza-associated hospitalization in urban Thai children

INFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 5-6 2007
Piyarat Suntarattiwong
Background, Studies in North America and Europe have shown that young children are at increased risk of serious complications and hospitalization from influenza infection. In Thailand, however, influenza is commonly considered a mild infection that rarely requires hospitalization. An improved understanding of the burden of serious complications from influenza infection in young children is needed to inform clinical treatment and vaccination guidelines. Methods, We conducted a prospective study of children 0,5 years of age with lower respiratory tract infection or influenza-like illness admitted to a pediatric tertiary-care hospital in Bangkok, Thailand during July 2004 to July 2005. All respiratory specimens were tested for influenza using a rapid antigen test and tissue cell culture. Results, Thirty-nine of 456 (8.6%) hospitalized children had culture-positive influenza. Eighty percent of hospitalized influenza patients had no underlying chronic illnesses. Nineteen (49%) influenza patients required hospital stays of 5 days or more and two patients required mechanical ventilation. Influenza activity demonstrated bimodal seasonal variation with peak activity from August to October and January to April. Cough was present in 38 (97%) cases and fever >38.5°C was significantly associated with influenza. Conclusion, Influenza is an important cause of hospitalization in children <5 years of age in Thailand. Children <5 years should be considered as a target group when establishing clinical guidelines for antiviral treatment and influenza vaccination. [source]

Review article: influenza A (H1N1) virus in patients with inflammatory bowel disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010
J.-F. RAHIER
Summary Background, Infection with influenza A (H1N1)v (swine flu) has caused widespread anxiety, among patients who are potentially immunocompromised, such as those being treated for inflammatory bowel disease. Aim, To provide guidance for physicians and their patients on the risk, prevention and management of influenza A (H1N1)v infection. Methods, Medline was searched using the following key words: ,swine flu', ,immunosuppression', inflammatory bowel disease', ,recommendations', ,immunization', ,vaccination'. Organizations such as European Centre for Disease Prevention and Control, the Centers for Disease Control and Prevention and the World Health Organization were consulted for recent papers and recommendations regarding immunocompromised patients and influenza A (H1N1)v infection. Results, Pandemic influenza A (H1N1) virus predominantly affects young patients. Those who are immunocompromised because of underlying disease or treatment are considered at higher risk of complications from influenza A (H1N1). They should be offered prevention (vaccination, postexposure prophylaxis) or treatment with antiviral drugs, if affected. Pneumococcal infection is a complication of influenza infection; therefore, pneumococcal vaccination appears advisable. Seasonal influenza vaccination is also recommended. Withdrawal of immunosuppressive treatment appears advisable during severe active infection if possible. Conclusions, Pragmatic advice is the best that can be offered in the current circumstances because of paucity of evidence. Investigation into the impact of influenza A (H1N1)v infection in young people with chronic conditions is needed. [source]

Should Health-Care Providers in the United States Have Access to Influenza Vaccines Formulated for the Southern Hemisphere?

JOURNAL OF TRAVEL MEDICINE, Issue 6 2008
Raymond A. Strikas MD
Background Influenza is the most common vaccine-preventable disease in travelers. It circulates year-round in the tropics, November to March in the northern hemisphere (NH), and April to October in the southern hemisphere (SH). In 2005, approximately 8.5 million US adults aged 18 years and older traveled to the Caribbean. A similar number traveled to the tropics and the SH. SH formulation of influenza vaccine is not available in the United States. We surveyed International Society of Travel Medicine (ISTM) members to ask if they would use SH influenza vaccine if available. Methods We electronically mailed a survey in December 2006 to 1,251 ISTM members in the United States. We asked if respondents would use SH vaccine for patients traveling to the SH or tropics, how many such patients per week they see, and their practice location. Results We received 157 responses for a response rate of 12.5%. Of these, 129 (82%) stated that they would be interested in having SH influenza vaccine available. Of those indicating interest, 73 (60%) reported seeing >10 patients traveling to the SH or tropics each week. Respondents reported practice settings in 34 states and the District of Columbia. Respondents requested more information about the likely cost of SH influenza vaccine, ordering conditions, vaccine use guidelines, comparability with NH vaccine, and approval of SH vaccine by the Food and Drug Administration. Conclusions Many travelers to the SH are at risk for influenza infection. Although only a limited number of ISTM members responded, respondents indicated considerable interest in availability of SH influenza vaccine for their patients. More data from travel medicine and other practitioners are needed on this topic. Inquiries are being made of influenza vaccine manufacturers about licensing SH influenza vaccines in the United States. Adding SH influenza vaccine to the vaccines available to NH clinicians could help mitigate the morbidity of influenza in travelers. [source]

Allergic airway inflammation is exacerbated during acute influenza infection and correlates with increased allergen presentation and recruitment of allergen-specific T-helper type 2 cells

CLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2004
B. J. Marsland
Summary Background Respiratory viral infections are a leading cause of the hospitalization of asthmatics, however, the cellular immunological interactions which underlie these two diseases remain elusive. Objective We sought to characterize the effect influenza viral infection has on allergic airway inflammation and to identify the cellular pathways involved. Methods We have used an ovalbumin (OVA) model of allergic airway inflammation, which involves sensitization of animals with OVA adsorbed in alum adjuvant followed by an intranasal challenge with OVA in phosphate-buffered saline. To study T cell recruitment into the lung, we adoptively transferred in vitro activated T cell receptor-transgenic T cells, which were subsequently identified by fluorescence-activated cell sorting (FACS) analysis. In addition, to study in vivo dendritic cell (DC) migration, we administered fluorescently labelled dextran and identified DCs that had phagocytosed it by FACS analysis. Results We found that different stages of influenza infection had contrasting effects upon the outcome of OVA-induced allergic airway inflammation. The allergic response against OVA was exacerbated during the acute stage of influenza infection; however, mice were protected against the development of airway eosinophilia at late time-points following infection. We investigated the mechanisms responsible for the virus-induced exacerbation and found that the response was partially independent of IL-4 and that there was increased delivery of inhaled allergens to the draining lymph node during the acute stage of the infection. In addition, virus-induced inflammation in the lung and draining lymph node resulted in the non-specific recruitment of circulating allergen-specific effector/memory cells. Conclusion In addition to virus-mediated damage to the lung and airways, influenza viral infection can also enhance unrelated local allergic responses. [source]