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influenza mortality in the united states, 2009 pandemic: burden, timing and age distribution.in april 2009, the most recent pandemic of influenza a began. we present the first estimates of pandemic mortality based on the newly-released final data on deaths in 2009 and 2010 in the united states.201323717567
a plant extract of ribes nigrum folium possesses anti-influenza virus activity in vitro and in vivo by preventing virus entry to host cells.infections with influenza a viruses (iav) are still amongst the major causes of highly contagious severe respiratory diseases not only bearing a devastating effect to human health, but also significantly impact the economy. besides vaccination that represents the best option to protect from iav infections, only two classes of anti-influenza drugs, inhibitors of the m2 ion channel and the neuraminidase, often causing resistant iav variants have been approved. that is why the need for effective an ...201323717460
impact of the availability of an influenza virus rapid antigen test on diagnostic decision making in a pediatric emergency department.fever is one of the most commonly seen symptoms in the pediatric emergency department. the objective of this study was to observe how the rapid testing for influenza virus impacts on the management of children with fever.201323714754
evaluation of a proximity extension assay for the detection of h1 2009 pandemic influenza viruses.the rapid influenza diagnostic tests (ridts) are widely distributed, simple to use, but often lack sensitivity as compared to gold standard methods (viral culture and nucleic acid detection technologies). applying ridts outside of epidemic or pandemic infections results in large numbers of false negatives. hence, a sensitive ridt that would reduce the number of false negatives would result in an increased clinical value. we evaluated the potential of a proximity extension assay (pea) for the det ...201323707923
design of inhibitors of influenza virus membrane fusion: synthesis, structure-activity relationship and in vitro antiviral activity of a novel indole series.the fusion of virus and endosome membranes is an essential early stage in influenza virus infection. the low ph-induced conformational change which promotes the fusogenic activity of the haemagglutinin (ha) is thus an attractive target as an antiviral strategy. the anti-influenza drug arbidol is representative of a class of antivirals which inhibits ha-mediated membrane fusion by increasing the acid stability of the ha. in this study two series of indole derivatives structurally related to arbid ...201323707194
influenza-associated global amnesia and hippocampal imaging abnormality.the acute phase of influenza infection is rarely associated with significant cognitive dysfunction. we describe a case of a 24 year-old man who developed global amnesia in the acute phase of influenza a infection. his deficits resolved over the course of several weeks. transient abnormalities of diffusion and t2-weighted imaging were seen in the bilateral hippocampi. we review cerebral complications of influenza and discuss the possible role of previously proposed mechanisms in our patient's cas ...201423697757
influenza: propagation, quantification, and storage.influenza viruses are negative-sense, single-stranded, enveloped rna viruses belonging to the family orthomyxoviridae. three types exist, influenza a, b, and c. all infect humans, but only a and b are major human pathogens. influenza type a viruses are divided into subtypes based on genetic and antigenic differences in the two surface spike proteins, hemagglutinin (ha) and neuraminidase (na). the appropriate cell lines to be used for isolation of influenza a or b viruses depend on the clinical i ...201323686827
the prospects and challenges of universal vaccines for influenza.vaccination is the most effective way to reduce the impact of epidemic as well as pandemic influenza. however, the licensed inactivated influenza vaccine induces strain-specific immunity and must be updated annually. when novel viruses appear, matched vaccines are not likely to be available in time for the first wave of a pandemic. yet, the enormous diversity of influenza a viruses in nature makes it impossible to predict which subtype or strain will cause the next pandemic. several recent scien ...201323685068
equine influenza--a global perspective.to date, equine influenza outbreaks have been reported all over the world with the exception of a small number of island nations including new zealand and iceland. influenza is endemic in europe and north america and is considered to be of potentially major economic significance to the equine industry worldwide. the importation of subclinically infected vaccinated horses, and inadequate quarantine procedures have resulted in several major outbreaks in susceptible populations for example, in aust ...201323680107
pharmacokinetic-pharmacodynamic determinants of oseltamivir efficacy using data from phase 2 inoculation studies.given the limited understanding about pharmacokinetic-pharmacodynamic (pk-pd) determinants of oseltamivir efficacy, data from two phase 2 influenza virus inoculation studies were evaluated. healthy volunteers in studies 1 and 2 were experimentally infected with influenza a/texas (the concentration of neuraminidase inhibitor which reduced neuraminidase activity by 50% [ic(50)] = 0.18 nm) or b/yamagata (ic(50) = 16.76 nm), respectively. in study 1, 80 subjects received 20, 100, or 200 mg of oral o ...201323669386
inferring patterns of influenza transmission in swine from multiple streams of surveillance data.swine populations are known to be an important source of new human strains of influenza a, including those responsible for global pandemics. yet our knowledge of the epidemiology of influenza in swine is dismayingly poor, as highlighted by the emergence of the 2009 pandemic strain and the paucity of data describing its origins. here, we analyse a unique dataset arising from surveillance of swine influenza at a hong kong abattoir from 1998 to 2010. we introduce a state-space model that estimates ...201323658205
sequence, cloning, and analysis of the fluvirucin b1 polyketide synthase from actinomadura vulgaris.fluvirucin b1 , produced by actinomadura vulgaris, is a 14-membered macrolactam active against a variety of infectious fungi as well as influenza a. despite considerable interest from the synthetic community, very little information is available regarding the biosynthetic origins of the fluvirucins. herein, we report the identification and initial characterization of the fluvirucin b1 polyketide synthase and related enzymes. the cluster consists of five extender modules flanked by an n-terminal ...201323654262
acceptance of vaccination against the 2009 pandemic influenza a among health-care workers in pune, maharashtra. 201323649146
adamantane and neuraminidase inhibitor resistance among circulating human influenza a viruses in cuba during 2006-2010. 201323648224
the universal epitope of influenza a viral neuraminidase fundamentally contributes to enzyme activity and viral replication.the only universally conserved sequence among all influenza a viral neuraminidases is located between amino acids 222 and 230. however, the potential roles of these amino acids remain largely unknown. through an array of experimental approaches including mutagenesis, reverse genetics, and growth kinetics, we found that this sequence could markedly affect viral replication. additional experiments revealed that enzymes with mutations in this region demonstrated substantially decreased catalytic ac ...201323645684
a statistical strategy to identify recombinant viral ribonucleoprotein of avian, human, and swine influenza a viruses with elevated polymerase activity.reassortment of influenza a viruses can give rise to viral ribonucleoproteins (vrnps) with elevated polymerase activity and the previous three pandemic influenza viruses contained reassorted vrnps of different origins. these suggest that reassorted vrnp may be one of the factors leading to a pandemic virus. in this study, we reconstituted chimeric vrnps with three different viral strains isolated from avian, human and swine hosts. we applied a statistical strategy to identify the effect that the ...201323634764
influenza a matrix protein m2 downregulates cftr: inhibition of chloride transport by a proton channel of the viral envelope. 201323605001
structural comparison of the wild-type and drug-resistant mutants of the influenza a m2 proton channel by molecular dynamics simulations.the influenza a m2 channel in the viral envelope is a ph-regulated proton channel that is crucial for viral infection and replication. amantadine and rimantadine are two m2 inhibitors that have been widely used as anti-influenza drugs. however, due to naturally occurring drug-resistant mutations, their inhibition ability has gradually decreased. these drug-resistant mutations are found at various positions on the transmembrane domain of the m2 protein and could be categorized to three types: mut ...201323594107
formation of raft-like assemblies within clusters of influenza hemagglutinin observed by md simulations.the association of hemagglutinin (ha) with lipid rafts in the plasma membrane is an important feature of the assembly process of influenza virus a. lipid rafts are thought to be small, fluctuating patches of membrane enriched in saturated phospholipids, sphingolipids, cholesterol and certain types of protein. however, raft-associating transmembrane (tm) proteins generally partition into ld domains in model membranes, which are enriched in unsaturated lipids and depleted in saturated lipids and c ...201323592976
anti-leukemia t cells in aml: tnf-α⁺ cd8⁺ t cells may escape detection and possibly reflect a stage of functional impairment.leukemia-associated antigens such as proteinase-3 (pr3) and wilms' tumor protein-1 (wt-1) are potential targets of t-cell responses, which can be monitored by t-cell assays within vaccination trials and after allogeneic stem cell transplantation (sct). in chronic myeloid leukemia (cml) an aberrant cytokine profile of antigen-specific t-cells with predominant tnf-α secretion has previously been described. the aim of this study was to investigate whether these tnf-α(+)/ifn-γ(-) cd8(+) t-cells can ...201323571180
the value of neuraminidase inhibitors for the prevention and treatment of seasonal influenza: a systematic review of systematic reviews.controversy has arisen regarding the effectiveness of neuraminidase inhibitors (nis), especially against influenza-related complications. a literature search was performed to critically assess the evidence collected by the available systematic reviews (srs) regarding the benefits and disadvantages of nis (oseltamivir, zanamivir) compared to placebos in healthy and at-risk individuals of all ages for prophylaxis and treatment of seasonal influenza. a sr was done using the cochrane database of sys ...201323565231
high yield production of influenza virus in madin darby canine kidney (mdck) cells with stable knockdown of irf7.influenza is a serious public health problem that causes a contagious respiratory disease. vaccination is the most effective strategy to reduce transmission and prevent influenza. in recent years, cell-based vaccines have been developed with continuous cell lines such as madin-darby canine kidney (mdck) and vero. however, wild-type influenza and egg-based vaccine seed viruses will not grow efficiently in these cell lines. therefore, improvement of virus growth is strongly required for developmen ...201323555825
the influence of 150-cavity binders on the dynamics of influenza a neuraminidases as revealed by molecular dynamics simulations and combined clustering.neuraminidase inhibitors are the main pharmaceutical agents employed for treatments of influenza infections. the neuraminidase structures typically exhibit a 150-cavity, an exposed pocket that is adjacent to the catalytic site. this site offers promising additional contact points for improving potency of existing pharmaceuticals, as well as generating entirely new candidate inhibitors. several inhibitors based on known compounds and designed to interact with 150-cavity residues have been reporte ...201323544106
differences between asthmatics and nonasthmatics hospitalised with influenza a infection. 201323543643
differential transport of influenza a neuraminidase signal anchor peptides to the plasma membrane.influenza a neuraminidase is essential for virus release from the cell surface of host cells. given differential structures of the n-terminal sequences including the transmembrane domains of neuraminidase subtypes, we investigated their contribution to transport and localization of subtypes n1, n2 and n8 to the plasma membrane. we generated consensus sequences from all protein entries available for these subtypes. we found that 40n-terminal the forty n-terminal amino acids are sufficient to conf ...201323523923
development of novel bioanalytical methods to determine the effective concentrations of phosphorodiamidate morpholino oligomers in tissues and cells.phosphorodiamidate morpholino oligomers (pmo) are neutrally charged, sequence-specific antisense agents that interfere with targeted gene expression. pmo have been shown to be highly specific and potent therapies after cellular uptake, yet methods to detect pmo in tissue and inside the cell are limited. we offer in this report novel methods for the detection of cellular resident pmo using flow cytometry-fluorescence in situ hybridization (flow fish) and a sandwich hybridization technique to quic ...201323515175
hospital-based influenza surveillance in korea: hospital-based influenza morbidity and mortality study group.influenza epidemics occur annually with variations in size and severity. hospital-based influenza morbidity & mortality was established to monitor influenza epidemics and their severity, which is composed of two surveillance systems: emergency room-based and inpatient-based surveillance. regarding emergency room-based surveillance, influenza-like illness index (influenza-like illness cases per 1,000 emergency room-visiting subjects), number of laboratory-confirmed cases and the distribution of i ...201323508916
antibody and cd8+ t cell memory response to influenza a/pr/8/34 infection is reduced in treadmill-exercised mice, yet still protective.moderate exercise may decrease the severity of influenza infection and reduce lung viral load. the possibility that an exercise-associated reduction in lung viral load early in infection could contribute to decreased serum antibody and reduced memory response were investigated. balb/c mice exercised for 8 wk and were then infected with influenza a/pr/8/34 (intranasal route). influenza-specific serum antibody was assessed for 6 mo post primary infection, at which time mice were infected again wit ...201323493360
use of nonpharmaceutical interventions to reduce transmission of 2009 pandemic influenza a (ph1n1) in pennsylvania public schools.school-based recommendations for nonpharmaceutical interventions (npis) were issued in response to the threat of 2009 pandemic influenza a (ph1n1). the implementation and effectiveness of these recommendations has not been assessed.201323488889
dynamic nuclear polarization study of inhibitor binding to the m2(18-60) proton transporter from influenza a.we demonstrate the use of dynamic nuclear polarization (dnp) to elucidate ligand binding to a membrane protein using dipolar recoupling magic angle spinning (mas) nmr. in particular, we detect drug binding in the proton transporter m2(18-60) from influenza a using recoupling experiments at room temperature and with cryogenic dnp. the results indicate that the pore binding site of rimantadine is correlated with previously reported widespread chemical shift changes, suggesting functional binding i ...201323480101
the cardiovascular manifestations of influenza: a systematic review.influenza accounts for 3 to 5 million cases of severe illness and up to 300,000 deaths annually, presenting a considerable burden to healthcare services. a spectrum of cardiovascular complications has been reported in association with influenza infection. this can occur through direct effects of the virus on the myocardium or through exacerbation of existing cardiovascular disease. direct myocardial involvement presenting as myocarditis is not uncommon during influenza infection. clinical presen ...201323474244
clinical profiles associated with influenza disease in the ferret model.influenza a viruses continue to pose a threat to human health; thus, various vaccines and prophylaxis continue to be developed. testing of these products requires various animal models including mice, guinea pigs, and ferrets. however, because ferrets are naturally susceptible to infection with human influenza viruses and because the disease state resembles that of human influenza, these animals have been widely used as a model to study influenza virus pathogenesis. in this report, a statistical ...201323472182
surveillance and vaccine effectiveness of an influenza epidemic predominated by vaccine-mismatched influenza b/yamagata-lineage viruses in taiwan, 2011-12 season.the 2011-12 trivalent influenza vaccine contains a strain of influenza b/victoria-lineage viruses. despite free provision of influenza vaccine among target populations, an epidemic predominated by influenza b/yamagata-lineage viruses occurred during the 2011-12 season in taiwan. we characterized this vaccine-mismatched epidemic and estimated influenza vaccine effectiveness (ve).201323472161
pandemic influenza in the 2009/2010 season in central poland: the surveillance study of laboratory confirmed cases.we retrospectively studied confirmed cases of influenza obligatorily reported to health authorities in central poland during the 2009/2010 season. each case was traced and examined with a questionnaire. the samples were tested for influenza a and b by rt-pcr. a total of 561 cases of influenza, including 185 in children under 14 years old, were detected. four hundred and eighty four people were hospitalized, including 142 children under 14. thirty two patients died, all with pre-existing risk fac ...201323462501
development of a neutralization assay for influenza virus using an endpoint assessment based on quantitative reverse-transcription pcr.a microneutralization assay using an elisa-based endpoint assessment (elisa-mn) is widely used to measure the serological response to influenza virus infection and vaccination. we have developed an alternative microneutralization assay for influenza virus using a quantitative reverse transcription pcr-based endpoint assessment (qpcr-mn) in order to improve upon technical limitations associated with elisa-mn. for qpcr-mn, infected mdck-london cells in 96-well cell-culture plates are processed wit ...201323437084
influenza neuraminidase operates via a nucleophilic mechanism and can be targeted by covalent inhibitors.development of novel influenza neuraminidase inhibitors is critical for preparedness against influenza outbreaks. knowledge of the neuraminidase enzymatic mechanism and transition-state analogue, 2-deoxy-2,3-didehydro-n-acetylneuraminic acid, contributed to the development of the first generation anti-neuraminidase drugs, zanamivir and oseltamivir. however, lack of evidence regarding influenza neuraminidase key catalytic residues has limited strategies for novel neuraminidase inhibitor design. h ...201323422659
a microfluidic immunomagnetic bead-based system for the rapid detection of influenza infections: from purified virus particles to clinical specimens.seasonal and novel influenza infections have the potential to cause worldwide pandemics. in order to properly treat infected patients and to limit its spread, a rapid, accurate and automatic influenza diagnostic tool needs to be developed. this study therefore presents a new integrated microfluidic system for the rapid detection of influenza infections. it integrated a suction-type, pneumatic-driven microfluidic control module, a magnetic bead-based fluorescent immunoassay (fia) and an end-point ...201323420191
maternal and fetal recovery after severe respiratory failure due to influenza: a case report.during pregnancy women are at increased risk of severe complications to influenza infection, including death of mother or fetus, especially if chronic comorbid medical conditions such as diabetes mellitus are present.201323414816
hepatitis b core-based virus-like particles to present heterologous epitopes.since the first effort to recombinantly express the hepatitis b core protein (hbc) in bacteria, the remarkable virion-like structure has fuelled interest in unraveling the structural and antigenic properties of this protein. initial studies proved hbc virus-like particles to possess strong immunogenic properties, which can be conveyed to linked antigens. more than 35 years later, numerous studies have been performed using hbc as a carrier protein for antigens derived from over a dozen different ...201323414409
chd6, a cellular repressor of influenza virus replication, is degraded in human alveolar epithelial cells and mice lungs during infection.the influenza virus polymerase associates to an important number of transcription-related proteins, including the largest subunit of the rna polymerase ii complex (rnap ii). despite this association, degradation of the rnap ii takes place in the infected cells once viral transcription is completed. we have previously shown that the chromatin remodeler chd6 protein interacts with the influenza virus polymerase complex, represses viral replication, and relocalizes to inactive chromatin during infl ...201323408615
low and decreasing vaccine effectiveness against influenza a(h3) in 2011/12 among vaccination target groups in europe: results from the i-move multicentre case-control study.within the influenza monitoring vaccine effectiveness in europe (i-move) project we conducted a multicentre case–control study in eight european union (eu) member states to estimate the 2011/12 influenza vaccine effectiveness against medically attended influenza-like illness (ili) laboratory-confirmed as influenza a(h3) among the vaccination target groups. practitioners systematically selected ili / acute respiratory infection patients to swab within seven days of symptom onset. we restricted th ...201323399425
decline in influenza vaccine effectiveness with time after vaccination, navarre, spain, season 2011/12.this study evaluates the influenza vaccine effectiveness (ve) in preventing laboratory-confirmed cases in navarre, spain, in the 2011/12 season in which the peak was delayed until week 7 of 2012. we conducted a test-negative case–control study. patients with influenza-like illness in hospitals and primary healthcare were swabbed for testing by reverse transcription-polymerase chain reaction. influenza vaccination status and other covariates were obtained from healthcare databases. the vaccinatio ...201323399423
effectiveness of seasonal 2012/13 vaccine in preventing laboratory-confirmed influenza infection in primary care in the united kingdom: mid-season analysis 2012/13.the early experience of the united kingdom (uk) is that influenza b has dominated the influenza 2012/13 season. overall trivalent influenza vaccine (tiv) adjusted vaccine effectiveness (ve) against all laboratory-confirmed influenza in primary care was 51% (95% confidence interval (ci): 27% to 68%); tiv adjusted ve against influenza a alone or influenza b alone was 49% (95% ci: -2% to 75%) and 52% (95% ci: 23% to 70%) respectively. vaccination remains the best protection against influenza.201323399421
neuraminidase inhibitors for influenza: a review and public health perspective in the aftermath of the 2009 pandemic.the objectives of this study were to: (1) reflect on key stages in the discovery, development and pre-pandemic use of neuraminidase inhibitors (nais), (2) summarise the evidence of nai effectiveness for treatment and prophylaxis of seasonal influenza prior to the 2009 pandemic, and (3) summarise the evidence base generated during the 2009 pandemic period.201323279893
pharmacokinetics of single and multiple oral doses of arbidol in healthy chinese volunteers.arbidol is licensed in russia and china for prophylaxis and treatment of influenza a and b. this study was to assess the pharmacokinetics of single and multiple doses of arbidol in healthy chinese volunteers.201323391367
modeling the membrane environment has implications for membrane protein structure and function: influenza a m2 protein.the m2 protein, a proton channel, from influenza a has been structurally characterized by x-ray diffraction and by solution and solid-state nmr spectroscopy in a variety of membrane mimetic environments. these structures show substantial backbone differences even though they all present a left-handed tetrameric helical bundle for the transmembrane domain. variations in the helix tilt influence drug binding and the chemistry of the histidine tetrad responsible for acid activation, proton selectiv ...201323389890
participation of icus in critical care pandemic research: a province wide, cross-sectional survey.little information exists to identify barriers to participation in pandemic research involving critically ill patients. we sought to characterize clinical research activity during the recent influenza a pandemic and to understand the experiences, beliefs, and practices of key stakeholders involved in pandemic research implementation.201323385105
sample size considerations for one-to-one animal transmission studies of the influenza a viruses.animal transmission studies can provide important insights into host, viral and environmental factors affecting transmission of viruses including influenza a. the basic unit of analysis in typical animal transmission experiments is the presence or absence of transmission from an infectious animal to a susceptible animal. in studies comparing two groups (e.g. two host genetic variants, two virus strains, or two arrangements of animal cages), differences between groups are evaluated by comparing t ...201323383167
the evolutionary dynamics of receptor binding avidity in influenza a: a mathematical model for a new antigenic drift hypothesis.the most salient feature of influenza evolution in humans is its antigenic drift. this process is characterized by structural changes in the virus's b-cell epitopes and ultimately results in the ability of the virus to evade immune recognition and thereby reinfect previously infected hosts. until recently, amino acid substitutions in epitope regions of the viral haemagglutinin were thought to be positively selected for their ability to reduce antibody binding and therefore were thought to be res ...201323382426
contrasting the epidemiological and evolutionary dynamics of influenza spatial transmission.in the past decade, rapid increases in the availability of high-resolution molecular and epidemiological data, combined with developments in statistical and computational methods to simulate and infer migration patterns, have provided key insights into the spatial dynamics of influenza a viruses in humans. in this review, we contrast findings from epidemiological and molecular studies of influenza virus transmission at different spatial scales. we show that findings are broadly consistent in lar ...201323382422
[influenza a ph1n1 meningoencephalitis: a case report].the influenza virus causes epidemics and pandemics with high morbidity and mortality. according to the world health organization, this virus causes 3-5 million cases of severe illness and 250,000 to 500,000 deaths each year. the disease is mainly respiratory and the most common complications are pneumonia, exacerbation of underlying diseases and less frequently respiratory complications. we report a 6-year-old patient with meningoencephalitis due to a new influenza a (ia), strain ph1n1, with vir ...201723381709
incidence and risk factors for acute respiratory illnesses and influenza virus infections in australian travellers to asia.respiratory infections including influenza are a common cause of acute short-term morbidity in travellers and yet the risk of these infections is poorly defined.201323380660
recent progress and challenges in the discovery of new neuraminidase inhibitors.at present, the key public health concern is to define the way in which the next influenza pandemic should be controlled. while influenza vaccines are available, their effectiveness could be significantly reduced if new strains differ significantly from those of the vaccines. therefore, antiviral drugs play an important role in the prevention and management of influenza. the influenza neuraminidase (na), a surface-glycoprotein enzyme involved in releasing the virus from the host cell, has been c ...201323369206
[review: influenza a and its vaccine]. 201223363857
lessons from the history of quarantine, from plague to influenza a.in the new millennium, the centuries-old strategy of quarantine is becoming a powerful component of the public health response to emerging and reemerging infectious diseases. during the 2003 pandemic of severe acute respiratory syndrome, the use of quarantine, border controls, contact tracing, and surveillance proved effective in containing the global threat in just over 3 months. for centuries, these practices have been the cornerstone of organized responses to infectious disease outbreaks. how ...201323343512
an approximation of herd effect due to vaccinating children against seasonal influenza - a potential solution to the incorporation of indirect effects into static models.indirect herd effect from vaccination of children offers potential for improving the effectiveness of influenza prevention in the remaining unvaccinated population. static models used in cost-effectiveness analyses cannot dynamically capture herd effects. the objective of this study was to develop a methodology to allow herd effect associated with vaccinating children against seasonal influenza to be incorporated into static models evaluating the cost-effectiveness of influenza vaccination.201323339290
the burden of influenza b: a structured literature review.we reviewed the epidemiology, clinical characteristics, disease severity, and economic burden of influenza b as reported in the peer-reviewed published literature. we used medline to perform a systematic literature review of peer-reviewed, english-language literature published between 1995 and 2010. widely variable frequency data were reported. clinical presentation of influenza b was similar to that of influenza a, although we observed conflicting reports. influenza b-specific data on hospitali ...201323327249
comparison of the detection of influenza a and b viruses by different methods.to investigate the detection of influenza viruses by three different methods.201223321198
antiviral activity of the plant extracts from thuja orientalis, aster spathulifolius, and pinus thunbergii against influenza virus a/pr/8/34.influenza viruses cause significant morbidity and mortality in humans through epidemics or pandemics. currently, two classes of anti-influenza virus drugs, m2 ion-channel inhibitors (amantadin and rimantadine) and neuraminidase inhibitors (oseltamivir and zanamivir), have been used for the treatment of the influenza virus infection. since the resistance to these drugs has been reported, the development of a new antiviral agent is necessary. in this study, we examined the antiviral efficacy of th ...201323314378
myocarditis associated with influenza a h1n1pdm2009.acute myocarditis is a well-known complication of influenza infection. the frequency of myocardial involvement in influenza infection varies widely, with the clinical severity ranging from asymptomatic to fulminant varieties. the worst cases can result in death due to impaired cardiac function, although such fulminant myocarditis associated with influenza infection is rare, as shown by previous papers. following the 2009 influenza pandemic, we reported on the clinical features of a cohort of 15 ...201223304476
the functional cd8 t cell memory recall repertoire responding to the influenza a m1(58-66) epitope is polyclonal and shows a complex clonotype distribution.the cd8 memory t cell repertoire to the influenza a derived m1(58-66) epitope shows a restricted v genes and cdr3 sequences usage. the repertoire is highly polyclonal and the clonotype distribution has been described as consisting of two components, one showing a power law-like distribution and the other composed of a few clonotypes with a very high relative frequency. the question is whether the complex repertoire defined by its ability to flourish in a short term recall culture corresponded to ...201323295548
cross-protection against drifted influenza viruses: options offered by adjuvanted and intradermal vaccines.antigenic drift, the evolutionary mechanism of influenza viruses, results in an increased susceptibility of vaccinated subjects against circulating viruses. new vaccines able to grant a broader and cross-reactive immune response against drifted influenza variants are needed. several strategies were explored to enhance the immunogenicity of plain vaccines: adjuvants, carriers and intradermal administration of influenza vaccine emerge as a promising options. to evaluate the ability of a mf59-adjuv ...201323295230
comparative analysis of hemagglutination inhibition titers generated using temporally matched serum and plasma samples.influenza-specific hemaggluitination inhibition (hai) antibody titer, an indicator of immunity to influenza, is often used to measure exposure to influenza in surveillance and immunogenicity studies. traditionally, serum has been the specimen of choice for hai assays, but a desire to reduce the amount of blood collected during studies and the availability of plasma in archived sample collections warrant the evaluation of plasma for hai titer. therefore, the relationship between serum and plasma ...201223284613
influenza epidemiology, vaccine coverage and vaccine effectiveness in sentinel australian hospitals in 2012: the influenza complications alert network (flucan).influenza is mostly a mild, self-limiting infection and severe infection requiring hospitalisation is uncommon. immunisation aims to reduce serious morbidity and mortality. the influenza complications alert network (flucan) is a sentinel hospital-based surveillance program that operates at 15 sites across all states and territories in australia. this study reports on the epidemiology of hospitalisation with confirmed influenza, estimate vaccine coverage and influenza vaccine protection against h ...201324890961
[an elderly case of post-gastrectomy aspiration pneumonia following an influenza virus a infection].a 85-year-old female was admitted to our hospital because of a fever and unconsciousness. three days prior to admission, she had been diagnosed to have influenza a, and oseltamivir was therefore prescribed. the symptoms due to the influenza infection, including the fever, thereafter rapidly resolved. she regularly took 10 mg zopiclone for insomnia before sleeping. on the day of admission, she was drowsy with fever. chest radiography showed bilateral massive infiltration of the lungs. chest ct im ...201324622140
implementation of filmarray respiratory viral panel in a core laboratory improves testing turnaround time and patient care.the filmarray respiratory virus panel detects 15 viral agents in respiratory specimens using polymerase chain reaction. we performed filmarray respiratory viral testing in a core laboratory at a regional children's hospital that provides service 24 hours a day 7 days a week. the average and median turnaround time were 1.6 and 1.4 hours, respectively, in contrast to 7 and 6.5 hours documented 1 year previously at an on-site reference laboratory using a direct fluorescence assay (dfa) that detecte ...201323270907
[safety update on vaccination during pregnancy].during influenza a pandemia, the vaccination on pregnant women has raised many questions. pandemia, easiness of travelling, and insufficient vaccinal coverage, expose these patients to infection which may have serious consequences on their pregnancy and on the child to born. on pregnant women, the precautionary principle is a priority and the evaluation of epidemiological risk is essential, in order to prevent adverses events. prophylactic vaccinal administration against infections should be ass ...201223241255
[neuraminidase inhibitors resistance in influenza viruses and the related mechanisms].influenza viruses are highly contagious for human population and result in acute respiratory infectious diseases ranging from mild to severe. neuraminidase (na) inhibitors (nais) (oseltamivir, zanamivir, peramivir and laninamivir), which target the na glycoproteins of influenza a and b viruses are widely used in the prophylaxis and treatment of influenza virus infection. however, the substitutions of amino acids in na or ha gene may lead to resistances to nais. nai-resistance-related substitutio ...201223233936
synthesis and antiviral activity of conformational analogues of leucamide a.in order to study the effect of heterocyclic core conformational state of leucamide a on its anti-influenza virus a activity, five conformational analogues were prepared by replacing the pro-leu dipeptide in the molecule with various amino acids. the amino acids used were of 2 to 6 carbons. the results showed that these replacements not only changed the conformational relationship between the 4,2-bisheterocycle tandem pair and the third heterocycle, but also had dramatic effect on its activity a ...201223222900
evaluation of the limit of detection of the bd veritor™ system flu a+b test and two rapid influenza detection tests for influenza virus.we evaluated the limits of detection of 3 rapid influenza diagnostic tests-bd veritor™ system for flu a+b, binax now® influenza a+b, and quickvue® influenza-for influenza strains circulating in 2010-2012. limits of detection varied by influenza strain, with veritor™ flu a+b test showing the lowest limit of detection for all strains.201323219228
modeling rapidly disseminating infectious disease during mass gatherings.we discuss models for rapidly disseminating infectious diseases during mass gatherings (mgs), using influenza as a case study. recent innovations in modeling and forecasting influenza transmission dynamics at local, regional, and global scales have made influenza a particularly attractive model scenario for mg. we discuss the behavioral, medical, and population factors for modeling mg disease transmission, review existing model formulations, and highlight key data and modeling gaps related to mo ...201223217051
perinatal exposure to environmental tobacco smoke (ets) enhances susceptibility to viral and secondary bacterial infections.studies suggest childhood exposure to environmental tobacco smoke (ets) leads to increased incidence of infections of the lower respiratory tract. the objective of this study was to determine whether perinatal exposure to ets increases the incidence, morbidity and severity of respiratory influenza infection and whether a secondary bacterial challenge at the peak of a pre-existing viral infection creates an enhanced host-pathogen susceptibility to an opportunistic infection. timed-pregnant female ...201223202826
clinic- and hospital-based sentinel influenza surveillance, uganda 2007-2010.to assess the epidemiology and seasonality of influenza in uganda, we established a sentinel surveillance system for influenza in 5 hospitals and 5 outpatient clinics in 4 geographically distinct regions, using standard case definitions for influenzalike illness (ili) and severe acute respiratory illness (sari).201223169978
influenza surveillance in 15 countries in africa, 2006-2010.in response to the potential threat of an influenza pandemic, several international institutions and governments, in partnership with african countries, invested in the development of epidemiologic and laboratory influenza surveillance capacity in africa and the african network of influenza surveillance and epidemiology (anise) was formed.201223169960
subclinical influenza virus a infections in pigs exhibited at agricultural fairs, ohio, usa, 2009-2011.agricultural fairs are associated with bidirectional, interspecies transmission of influenza virus a between humans and pigs. we examined pigs exhibited at agricultural fairs in ohio during 2009-2011 for signs of influenza-like illness and collected nasal swab specimens from a representative subset of these animals. influenza virus a was recovered from pigs at 12/53 (22.6%) fairs during the 3-year sampling period. pigs at 10/12 (83.3%) fairs from which influenza virus a was recovered did not sho ...201223171654
fluorescence polarization-based assay using n-glycan-conjugated quantum dots for screening in hemagglutinin blockers for influenza a viruses.attachment of influenza virus to susceptible cells is mediated by viral protein hemagglutinin (ha), which recognizes cell surface glycoconjugates that terminate in α-sialosides. to develop anti-influenza drugs based on inhibition of ha-mediated infection, novel fluorescent nanoparticles displaying multiple biantennary n-glycan chains with α-sialosides (a2-pc-qds) that have high affinity for the ha were designed and constructed. the a2-pc-qds enabled an easy and efficient fluorescence polarizatio ...201323164994
modeling the impact of air, sea, and land travel restrictions supplemented by other interventions on the emergence of a new influenza pandemic virus.during the early stages of a new influenza pandemic, travel restriction is an immediate and non-pharmaceutical means of retarding incidence growth. it extends the time frame of effective mitigation, especially when the characteristics of the emerging virus are unknown. in the present study, we used the 2009 influenza a pandemic as a case study to evaluate the impact of regulating air, sea, and land transport. other government strategies, namely, antivirals and hospitalizations, were also evaluat ...201223157818
[monitoring of influenza virus b and clinical features of pediatric pneumonia caused by influenza virus b only].to investigate the epidemiological features of influenza virus b (ivb) in the winter and the clinical features of pediatric pneumonia caused by ivb only.201223146729
mhc class i-presented t cell epitopes identified by immunoproteomics analysis are targets for a cross reactive influenza-specific t cell response.influenza virus infection and the resulting complications are a significant global public health problem. improving humoral immunity to influenza is the target of current conventional influenza vaccines, however, these are generally not cross-protective. on the contrary, cell-mediated immunity generated by primary influenza infection provides substantial protection against serologically distinct viruses due to recognition of cross-reactive t cell epitopes, often from internal viral proteins cons ...201223144892
pancytopenia associated with influenza a infection. 201323142324
seasonal influenza vaccine efficacy and its determinants in children and non-elderly adults: a systematic review with meta-analyses of controlled trials.the true level of influenza vaccine efficacy is controversial and many factors may influence its estimation.201223142300
detection of drug-induced conformational change of a transmembrane protein in lipid bilayers using site-directed spin labeling.as a target of antiviral drugs, the influenza a m2 protein has been the focus of numerous structural studies and has been extensively explored as a model ion channel. in this study, we capitalize on the expanding body of high-resolution structural data available for the m2 protein to design and interpret site-directed spin-labeling electron paramagnetic resonance spectroscopy experiments on drug-induced conformational changes of the m2 protein embedded in lipid bilayers. we obtained data in the ...201323139077
influenza-associated neurological complications.while mostly diagnosed in the pediatric population, neurological complications of pandemic influenza a infection may affect young and previously healthy adults, and may follow a fulminant, severe, and occasionally fatal course. we reviewed severe neurological complications secondary to influenza infection reported in the literature, in attempt to outline recurrent syndromes that may assist the clinician in making a timely diagnosis. vigilance and awareness of these clinical entities are key in t ...201323138546
troop education and avian influenza surveillance in military barracks in ghana, 2011.influenza a viruses that cause highly pathogenic avian influenza (hpai) also infect humans. in many developing countries such as ghana, poultry and humans live in close proximity in both the general and military populations, increasing risk for the spread of hpai from birds to humans. respiratory infections such as influenza are especially prone to rapid spread among military populations living in close quarters such as barracks making this a key population for targeted avian influenza surveilla ...201223137234
overview of influenza viruses.the influenza virus (iv) is still of great importance as it poses an immanent threat to humans and animals. among the three iv-types (a, b, and c) influenza a viruses are clinically the most important being responsible for severe epidemics in humans and domestic animals. aerosol droplets transmit the virus that causes a respiratory disease in humans that can lead to severe pneumonia and ultimately death. the high mutation rate combined with the high replication rate allows the virus to rapidly a ...201323124938
broad-range neutralizing anti-influenza a human monoclonal antibodies: new perspectives in therapy and prophylaxis.broadly neutralizing monoclonal antibodies (mabs) directed against different subtypes of influenza a viruses are novel tools for the potential development of effective anti-influenza prophylactic and therapeutic strategies. in both cases, the main candidates for passive transfer and new vaccine development are represented by protective mabs directed against influenza hemagglutinin (ha). a large number of mabs directed against influenza ha has been developed to date. however, even if they can be ...201223109007
effect of two injections of non-adjuvanted influenza a h1n1pdm2009 vaccine in renal transplant recipients: inserm c09-32 transfluvac trial.enhancing vaccine immunogenicity in kidney transplant recipients, particularly against influenza, is required since the immunosuppression used to prevent graft rejection limits vaccine immunogenicity. we therefore investigated the immunogenicity and safety of a double dose non-adjuvanted vaccination regimen against influenza h1n1pdm2009 in kidney transplant adult recipients.201223103195
vgkc complex antibodies in pediatric severe acute encephalitis: a study and literature review.antibodies to surface proteins like voltage-gated potassium channel (vgkc) complexes are increasingly found in different neurologic diseases and encephalitis in adults and recently, in children. detecting such antibodies can help identify forms of encephalitis that may respond to immuno-therapies. however, there are few reports on vgkc complex antibodies in pediatric severe acute encephalitis.201323088843
evaluation of the specificity and sensitivity of a potential rapid influenza screening system.influenza remains a serious worldwide health threat with numerous deaths attributed to influenza-related complications. it is likely that transmission of influenza and both the morbidity and mortality of influenza could be reduced if inexpensive but reliable influenza screening assays were more available to the general public or local medical treatment facilities. this report provides the initial evaluation of a pilot system designed by lucigen corp. (middleton, wi, usa) as a potential rapid nea ...201323083638
surveillance of 16 respiratory viruses in patients with influenza-like illness in nanjing, china.much less is known about the etiology of influenza-like illness in china. a continuous surveillance of 16 respiratory viruses was conducted from november 2010 to october 2011 of outpatients with influenza-like illness in nanjing, china. the two largest general hospitals and a provincial virus laboratory in nanjing participated in this study. throat swabs were collected from outpatients during medical visits for influenza-like illness and were tested for 16 respiratory viruses using pcr. three hu ...201223080506
the compensatory g88r change is essential in restoring the normal functions of influenza a/wsn/33 virus matrix protein 1 with a disrupted nuclear localization signal.g88r emerged as a compensatory mutation in matrix protein 1 (m1) of influenza virus a/wsn/33 when its nuclear localization signal (nls) was disrupted by r101s and r105s substitutions. the resultant m1 triple mutant m(nls-88r) regained replication efficiency in vitro while remaining attenuated in vivo with the potential of being a live vaccine candidate. to understand why g88r was favored by the virus as a compensatory change for the nls loss and resultant replication deficiency, three more m1 tr ...201323077315
the influenza a segment 7 mrna 3' splice site pseudoknot/hairpin family.the 3' splice site of the influenza a segment 7 transcript is utilized to produce mrna for the critical m2 ion-channel protein. in solution a 63 nt fragment that includes this region can adopt two conformations: a pseudoknot and a hairpin. in each conformation, the splice site, a binding site for the sf2/asf exonic splicing enhancer and a polypyrimidine tract, each exists in a different structural context. the most dramatic difference occurs for the splice site. in the hairpin the splice site is ...201223064116
meeting of the who working group on polymerase chain reaction protocols for detecting subtype influenza a viruses – geneva, june 2012. 201223061104
possible association between alice in wonderland syndrome and influenza a infection. 201223037657
[the first cases of influenza a/hini diagnosed in spain]. 201323010065
clinical, scientific and ethnographic studies of influenza in quarantine.from the time of the spanish influenza pandemic in 1918 to the present seclusion of volunteers in quarantine units, either modified hotels, phase i units or specially constructed clinics, have been key in investigating new vaccines and antivirals. carefully selected healthy, young volunteers undergo a 10-12-day sojourn under intense medical supervision. clinical sampling includes nasal and throat washes for virus recovery, blood for clinical chemistry, analysis of b- and t-cell response and, mor ...201223002974
multiplex-microsphere-quantitative polymerase chain reaction: nucleic acid amplification and detection on microspheres.we report the development of a new system to monitor the amplification of nucleic acids on microspheres. this was realized by the design of (i) a "universal" oligonucleotide "tagged" polymerase chain reaction (pcr) forward primer, (ii) a sensor sequence complementary to the universal sequence on the forward pcr primer modified with a fluorescent dye, and (iii) a universal oligonucleotide coupled to luminex microspheres. the pcr takes place with the microspheres present in the reaction tube. with ...201323000310
acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function.exposure to diesel exhaust particles (dep) is thought to exacerbate many pre-existing respiratory diseases, including asthma, bronchitis and chronic obstructive pulmonary disease, however, there is a paucity of data on whether dep exacerbates illness due to respiratory viral infection.201322994877
miller fisher syndrome associated with influenza a infection.a 36-year-old, previously healthy man presented with miller fisher syndrome (mfs) five days after he was diagnosed with an influenza a infection by a rapid antigen test. he had not received any recent vaccinations. he had no loss of consciousness. bilateral ophthalmoplegia, blepharoptosis, areflexia, and ataxic gait were noted. one week after treatment with intravenous immunoglobulin, his ophthalmoplegia, blepharoptosis, and ataxic gait had gradually improved, and his deep tendon reflexes return ...201222989838
evaluation of five rapid diagnostic kits for influenza a/b virus.influenza viruses cause seasonal epidemics associated with high morbidity and mortality. however, even during periods of epidemic prevalence, clinical diagnoses are problematic. rapid diagnostic tests for the detection of pandemic influenza a/b virus are valuable for their ease of use. many rapid influenza diagnostic kits were introduced recently in the republic of korea (rok), including directizen ez flu a and b (becton dickinson, sparks, usa), binax now influenza a/b antigen kit (binax, portla ...201322989409
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