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structural and nonstructural viral proteins are targets of t-helper immune response against human respiratory syncytial virus.proper antiviral humoral and cellular immune responses require previous recognition of viral antigenic peptides that are bound to hla class ii molecules, which are exposed on the surface of antigen-presenting cells. the helper immune response is critical for the control and the clearance of human respiratory syncytial virus (hrsv) infection, a virus with severe health risk in infected pediatric, immunocompromised, and elderly populations. in this study, using a mass spectrometry analysis of comp ...201627090790
respiratory syncytial virus hospitalizations in healthy preterm infants: systematic review.studies have explored the risk for and impact of respiratory syncytial virus (rsv) infection requiring hospitalization among healthy preterm infants born at 29-35 weeks of gestational age not given rsv immunoprophylaxis. we performed a systematic review and qualitative synthesis of these studies.201627093166
comparison of cepheid xpert flu/rsv xc and biofire filmarray for detection of influenza a, influenza b, and respiratory syncytial virus.the xpert flu/rsv xc was compared to the filmarray respiratory panel for detection of influenza (flu) a, flu b, and respiratory syncytial virus (rsv), using 128 nasopharyngeal swabs. positive agreements were 100% for flu a and rsv and 92.3% for flu b. the xpert may be useful in clinical situations when extensive testing is not required and may serve an important role in laboratories already performing broader respiratory panel testing.201627098956
characterization of epitope-specific anti-respiratory syncytial virus (anti-rsv) antibody responses after natural infection and after vaccination with formalin-inactivated rsv.antibodies against the fusion (f) protein of respiratory syncytial virus (rsv) play an important role in the protective immune response to this important respiratory virus. little is known, however, about antibody levels against multiple f-specific epitopes induced by infection or after vaccination against rsv, while this is important to guide the evaluation of (novel) vaccines. in this study, we analyzed antibody levels against rsv proteins and f-specific epitopes in human sera and in sera of v ...201627099320
antigenic fingerprinting following primary rsv infection in young children identifies novel antigenic sites and reveals unlinked evolution of human antibody repertoires to fusion and attachment glycoproteins.respiratory syncytial virus (rsv) is the major cause of pneumonia among infants. here we elucidated the antibody repertoire following primary rsv infection and traced its evolution through adolescence and adulthood. whole genome-fragment phage display libraries (gfpdl) expressing linear and conformational epitopes in the rsv fusion protein (f) and attachment protein (g) were used for unbiased epitope profiling of infant sera prior to and following rsv infection. f-gfpdl analyses demonstrated mod ...201627100289
a phase 1a, first-in-human, randomized study of a respiratory syncytial virus f protein vaccine with and without a toll-like receptor-4 agonist and stable emulsion adjuvant.respiratory syncytial virus (rsv) causes significant illness in older adults resulting in substantial health and economic impact. a successful vaccine would reduce morbidity in this growing segment of the population.201627102821
acute myopericarditis caused by human metapneumovirus.human metapneumovirus is known to be similar to respiratory syncytial virus. because of an incomplete protective immune response to new genotypes, re-infection occurs frequently, especially in the elderly. however, the clinical manifestations of human metapneumovirus need to be further characterized in adults. a 73-year-old woman presented to the emergency room with acute dyspnea, chest discomfort and influenza-like illness. the patient was diagnosed with human metapneumovirus infection, complic ...201627104014
advances in rsv vaccine research and development - a global agenda.respiratory syncytial virus (rsv) is an important cause of viral lower respiratory tract illness in infants and children globally, but no vaccine is currently available to protect these vulnerable populations. live-attenuated vaccine approaches have been in development for decades, but achieving the appropriate balance between immunogenicity and safety has proven difficult. immunoprophylaxis with the neutralizing monoclonal antibody palivizumab is limited to high-risk infants, but cost requireme ...201627105562
detection and characterization of viruses as field and vaccine strains in feedlot cattle with bovine respiratory disease.this study investigated viruses in bovine respiratory disease (brd) cases in feedlots, including bovine herpesvirus-1 (bohv-1), bovine viral diarrhea virus (bvdv), bovine respiratory syncytial virus (brsv), bovine coronaviruses (bocv) and parainfluenza-3 virus (pi3v). nasal swabs were collected from 114 cattle on initial brd treatment. processing included modified live virus (mlv) vaccination. seven brd necropsy cases were included for 121 total cases. mean number of days on feed before first sa ...201627108192
respiratory syncytial virus-associated hospitalization in premature infants who did not receive palivizumab prophylaxis in italy: a retrospective analysis from the osservatorio study.due to different social and epidemiological factors, the eligibility criteria to receive palivizumab prophylaxis may be different between countries, especially in "otherwise healthy" late preterm infants.201627112952
aetiology of childhood pneumonia in a well vaccinated south african birth cohort: a nested case-control study of the drakenstein child health study.pneumonia is a leading cause of mortality and morbidity in children globally. the cause of pneumonia after introduction of the 13-valent pneumococcal conjugate vaccine (pcv13) has not been well studied in low-income and middle-income countries, and most data are from cross-sectional studies of children admitted to hospital. we aimed to longitudinally investigate the incidence and causes of childhood pneumonia in a south african birth cohort.201627117547
use of palivizumab with other infection control measures to control respiratory syncytial virus outbreaks in neonatal care units.no guidelines exist on the use of palivizumab during outbreaks of respiratory syncytial virus (rsv) in neonatal intensive care units (nicus). we aimed to describe an outbreak of rsv in nicu settings and the role of palivizumab in controlling the outbreak.201627118823
respiratory syncytial virus seasonality in brazil: implications for the immunisation policy for at-risk populations.respiratory syncytial virus (rsv) infection is the leading cause of hospitalisation for respiratory diseases among children under 5 years old. the aim of this study was to analyse rsv seasonality in the five distinct regions of brazil using time series analysis (wavelet and fourier series) of the following indicators: monthly positivity of the immunofluorescence reaction for rsv identified by virologic surveillance system, and rate of hospitalisations per bronchiolitis and pneumonia due to rsv i ...201627120006
combined virus-like particle and fusion protein-encoding dna vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease.a safe and effective vaccine against respiratory syncytial virus (rsv) should confer protection without causing vaccine-enhanced disease. here, using a cotton rat model, we investigated the protective efficacy and safety of an rsv combination vaccine composed of f-encoding plasmid dna and virus-like particles containing rsv fusion (f) and attachment (g) glycoproteins (ffg-vlp). cotton rats with ffg-vlp vaccination controlled lung viral replication below the detection limit, and effectively induc ...201627123586
infections and coinfections by respiratory human bocavirus during eight seasons in hospitalized children.the human bocavirus (hbov) has been identified in respiratory infections in children in a large number of studies. despite this, the pathogenic role of the hbov is under discussion. the main objectives of the study were: to determine the incidence of hbov in hospitalized children; to describe the main clinical features of the positive children; and to compare the data with those from other viral infections in the same population. a prospective study was performed between 2005 and 2013 including ...201627124519
estimating respiratory syncytial virus-associated hospitalization in the first year of life among infants born at 32-35 weeks of gestation.prophylaxis against respiratory syncytial virus-associated hospitalization (rsv-h) with anti-rsv monoclonal antibody is not considered cost-effective for routine use in most jurisdictions. the aim of this study was to develop a scoring tool to estimate local risk of rsv-h in the first year of life among moderately premature infants to assist in prophylaxis decision making.201627124687
respiratory syncytial virus-associated hospitalizations over three consecutive seasons in children with congenital heart disease.the purpose of this investigation was to analyze the burden of respiratory syncytial virus (rsv)-related hospitalizations in infants and children with congenital heart disease (chd) over three consecutive rsv seasons. retrospectively, all children with hemodynamically significant (hs-chd) and not significant (hns-chd) chd born between 2004 and 2008 at a tertiary care university hospital and identified by icd-10 diagnoses were included. data on rsv-related hospitalizations over the first three ye ...201627126331
nasopharyngeal microbiota, host transcriptome, and disease severity in children with respiratory syncytial virus infection.respiratory syncytial virus (rsv) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. known risk factors, however, incompletely explain the variability of rsv disease severity, especially among healthy children. we postulate that the severity of rsv infection is influenced by modulation of the host immune response by the local bacterial ecosystem.201627135599
epidemiological and clinical characteristics of respiratory viral infections in children in shanghai, china.acute respiratory tract infections (artis) due to various viruses are not only the most common causes of upper and lower respiratory infection but are also major causes of morbidity and mortality in children. in this study, we investigated the prevalence and clinical characteristics of children with virus-related artis and determined the spectrum of respiratory viruses and their correlation with meteorological variables in jiading district, shanghai, china. nasopharyngeal swabs from 2819 childre ...201627138548
enhanced detection of respiratory pathogens with nanotrap particles.the influenza virus is a leading cause of respiratory disease in the united states each year. while the virus normally causes mild to moderate disease, hospitalization and death can occur in many cases. there are several methodologies that are used for detection; however problems such as decreased sensitivity and high rates of false-negative results may arise. there is a crucial need for an effective sample preparation technology that concentrates viruses at low abundance while excluding residen ...201627145085
identification of respiratory syncytial virus nonstructural protein 2 residues essential for exploitation of the host ubiquitin system and inhibition of innate immune responses.respiratory syncytial virus (rsv) is a leading cause of lower respiratory tract infection in young children worldwide. the rsv nonstructural protein 2 (ns2) is a multifunctional protein that primarily acts to antagonize the innate immune system by targeting stat2 for proteasomal degradation. we investigated the structural determinants of ns2 important for interaction with the host ubiquitin system to degrade stat2 during infection. we found that ns2 expression enhances ubiquitination of host pro ...201627147743
egfr interacts with the fusion protein of respiratory syncytial virus strain 2-20 and mediates infection and mucin expression.respiratory syncytial virus (rsv) is the major cause of viral lower respiratory tract illness in children. in contrast to the rsv prototypic strain a2, clinical isolate rsv 2-20 induces airway mucin expression in mice, a clinically relevant phenotype dependent on the fusion (f) protein of the rsv strain. epidermal growth factor receptor (egfr) plays a role in airway mucin expression in other systems; therefore, we hypothesized that the rsv 2-20 f protein stimulates egfr signaling. infection of c ...201627152417
predictors of asthma following severe respiratory syncytial virus (rsv) bronchiolitis in early childhood.we sought to identify predictors of asthma development following severe early childhood rsv bronchiolitis. different definitions of asthma were also compared.201627152482
sixteen years of evolution of human respiratory syncytial virus subgroup a in buenos aires, argentina: ga2 the prevalent genotype through the years.human respiratory syncytial virus (hrsv) is the main viral cause of acute lower respiratory tract infections (lrti) in children worldwide. in recent years, several preclinical trials with vaccine candidates have been reported. it is in this sense that molecular epidemiological studies become important. understanding viral dispersion patterns before and after the implementation of a vaccine can provide insight into the effectiveness of the control strategies. in this work we analyzed the molecula ...201627154330
chimeric virus-like particles containing a conserved region of the g protein in combination with a single peptide of the m2 protein confer protection against respiratory syncytial virus infection.to investigate the feasibility and efficacy of a virus-like particle (vlp) vaccine composed of the conserved antigenic epitopes of respiratory syncytial virus (rsv), the chimeric rsv vlps hbcδ-tg and hbcδ-tg/m282-90 were generated based on the truncated hepatitis b virus core protein (hbcδ). hbcδ-tg consisted of hbcδ, the conserved region (aa 144-204) of the rsv g protein. hbcδ-tg was combined with a single peptide (aa 82-90) of the m2 protein to generate hbcδ-tg/m282-90. immunization of mice wi ...201627154395
metagenomic characterization of the virome associated with bovine respiratory disease in feedlot cattle identified novel viruses and suggests an etiologic role for influenza d virus.bovine respiratory disease (brd) is the most costly disease affecting the cattle industry. the pathogenesis of brd is complex and includes contributions from microbial pathogens as well as host, environmental and animal management factors. in this study, we utilized viral metagenomic sequencing to explore the virome of nasal swab samples obtained from feedlot cattle with acute brd and asymptomatic pen-mates at six and four feedlots in mexico and the usa, respectively, in april-october 2015. twen ...201627154756
exploring the dynamics of respiratory syncytial virus (rsv) transmission in children.respiratory syncytial virus (rsv) is the main cause of lower respiratory tract infections in children. whilst highly seasonal, rsv dynamics can have either one-year (annual) or two-year (biennial) cycles. furthermore, some countries show a 'delayed biennial' pattern, where the epidemic peak in low incidence years is delayed. we develop a compartmental model for rsv infection, driven by a seasonal forcing function, and conduct parameter space and bifurcation analyses to document parameter ranges ...201627155294
respiratory syncytial virus infection activates il-13-producing group 2 innate lymphoid cells through thymic stromal lymphopoietin.respiratory syncytial virus (rsv) is a major health care burden with a particularly high worldwide morbidity and mortality rate among infants. data suggest that severe rsv-associated illness is in part caused by immunopathology associated with a robust type 2 response.201627156176
respiratory syncytial virus hospitalisation trends in children with haemodynamically significant heart disease, 1997-2012.the aim of the study was to evaluate the trends in respiratory syncytial virus-related hospitalisations and associated outcomes in children with haemodynamically significant heart disease in the united states of america. study design the kids' inpatient databases (1997-2012) were used to estimate the incidence of respiratory syncytial virus hospitalisation among children ⩽24 months with or without haemodynamically significant heart disease. weighted multivariable logistic regression and chi-squa ...201727161255
prevalence of neutralizing antibodies to common respiratory viruses in intravenous immunoglobulin and in healthy donors in southern china.acute respiratory infections (aris) are a leading cause of death among children under the age of 5. however, there are no effective drugs for most of these severe viral infections. passive immunotherapy with convalescent plasma or hyperimmune intravenous immunoglobulin (h-ivig) is a potential therapeutic option for serious viral infections. it is important to find a suitable source of convalescent plasma and of h-ivig containing high titer neutralizing antibodies (nabs).201627162653
biochemical effect of resistance mutations against synergistic inhibitors of rsv rna polymerase.als-8112 is the parent molecule of als-8176, a first-in-class nucleoside analog prodrug effective in the clinic against respiratory syncytial virus (rsv) infection. the antiviral activity of als-8112 is mediated by its 5'-triphosphate metabolite (als-8112-tp, or 2'f-4'clch2-cytidine triphosphate) inhibiting the rna polymerase activity of the rsv l-p protein complex through rna chain termination. four amino acid mutations in the rna-dependent rna polymerase (rdrp) domain of l (quad: m628l, a789v, ...201627163448
recurrent rhabdomyolysis in a child. case presentation.viral myositis associated with infections rarely may cause rhabdomyolysis. there is no any pediatric case with severe recurrent rhabdomyolysis triggered by infections in the literature. we reported a two-year-old boy who was hospitalized three times due to severe rhabdomyolysis associated with viral myositis in the winter months. this is the first child case presentation with severe rhabdomyolysis triggered by infections. prednisolone and intravenous immunoglobulin treatments were ineffective in ...201627164356
administration of palivizumab in the nicu.the american academy of pediatrics recommends palivizumab prophylaxis against respiratory syncytial virus (rsv) for infants at high risk for severe disease within 72 hours of hospital discharge to prevent community-associated rsv. the american academy of pediatrics does not recommend palivizumab to prevent health care-associated rsv (ha-rsv).201627164941
[airway inflammation induced by poly(i:c) stimulation in the late stage of respiratory syncytial virus infection in mice and its mechanism].to investigate the pathogenic mechanisms of airway inflammation and recurrent wheezing induced by recurrent respiratory virus infection after respiratory syncytial virus (rsv) infection.201627165597
temporal association between the influenza virus and respiratory syncytial virus (rsv): rsv as a predictor of seasonal influenza.epidemiologists agree that there is a prevailing seasonality in the presentation of epidemic waves of respiratory syncytial virus (rsv) infections and influenza. the aim of this study is to quantify the potential relationship between the activity of rsv, with respect to the influenza virus, in order to use the rsv seasonal curve as a predictor of the evolution of an influenza virus epidemic wave. two statistical tools, logistic regression and time series, are used for predicting the evolution of ...201627165946
molecular identification and epidemiological features of human adenoviruses associated with acute respiratory infections in hospitalized children in southern china, 2012-2013.acute respiratory infections (ari) are the major worldwide health problem associated with high morbidity and mortality rates. human adenovirus (hadv) is one of the most common pathogens associated with viral ari, and thus calls for specific diagnosis and better understanding of the epidemiology and clinical characteristics.201627171486
efficacy of intranasal vaccination with a multivalent vaccine containing temperature-sensitive modified-live bovine herpesvirus type 1 for protection of seronegative and seropositive calves against respiratory disease.objective to evaluate efficacy and duration of immunity of the bovine herpesvirus type 1 (bhv-1) fraction of a trivalent vaccine also containing parainfluenza virus-3 and bovine respiratory syncytial virus fractions administered intranasally (in) for protection of calves against infectious bovine rhinotracheitis (ibr). design controlled challenge study. animals 120 dairy calves (3 to 8 days old) seronegative for antibody against bhv-1 (experiments 1 and 2) or seropositive for maternally derived ...201627172345
the burden of severe respiratory syncytial virus disease among children younger than 1 year in central and eastern europe.globally, respiratory syncytial virus (rsv) is the most common cause of serious lower respiratory tract infections (lrtis) in young children, and is a major cause of hospital admission in children <1 year of age. the study evaluated the severity of rsv-associated lrti disease among premature (<36 weeks gestational age (ga)) and term children <1 year of age and assessed the influence of ga on outcomes of rsv lrti hospitalization in central and eastern europe (cee).201627174177
nasopharyngeal microbiome in respiratory syncytial virus resembles profile associated with increased childhood asthma risk. 201627174483
a regional cohort study of the treatment of critically ill children with bronchiolitis.to describe the treatment practices in critically ill children with rsv bronchiolitis across four regional picus in the northeastern united states, and to determine the factors associated with increased icu length of stay in this population.201627177013
respiratory viruses and children.respiratory viruses place a great disease burden especially on the youngest children in terms of high rates of infection, bacterial complications and hospitalizations. in developing countries, some viral infections are even associated with substantial mortality in children. the interaction between viruses and bacteria is probably much more common and clinically significant than previously understood. respiratory viruses frequently initiate the cascade of events that ultimately leads to bacterial ...201627177731
invasive pneumococcal disease rates linked to meteorological factors and respiratory virus circulation (catalonia, 2006-2012).to study the impact of meteorological data and respiratory viral infections on invasive pneumococcal disease (ipd) rates.201627178436
enhanced allergic responsiveness after early childhood infection with respiratory viruses: are long-lived alternatively activated macrophages the missing link?early childhood infection with respiratory viruses, including human rhinovirus, respiratory syncytial virus (rsv) and influenza, is associated with an increased risk of allergic asthma and severe exacerbation of ongoing disease. despite the long recognition of this relationship, the mechanism linking viral infection and later susceptibility to allergic lung inflammation is still poorly understood. we discuss the literature and provide new evidence demonstrating that these viruses induce the alte ...201627178560
morbidity and mortality among patients with respiratory syncytial virus infection: a 2-year retrospective review.previous studies have demonstrated high morbidity and mortality for adult patients with respiratory syncytial virus (rsv) infection. we performed a retrospective, multicenter, two-year chart review of all patients (n = 334) testing positive for rsv by the proflu + (®) influenza a/b and rsv assay (hologic, bedford, ma). we analyzed indicators of morbidity and mortality in children <6 years old, immunocompetent and immunosuppressed adults, and transplant patients. significant morbidity and mortali ...201627179369
a new real-time rt-qpcr assay for the detection, subtyping and quantification of human respiratory syncytial viruses positive- and negative-sense rnas.human respiratory syncytial virus (rsv) is a major health problem and the main cause of hospitalization due to bronchiolitis. rsv is divided into two antigenic subgroups, rsv-a and -b that co-circulate worldwide. rapid and sensitive detection is desirable for proper patient handling while assessment of viral load may help to evaluate disease severity and progression. finally rsv subtyping is needed to determine the prevalence and pathogenicity of each rsv subgroup, as well as their sensitivity t ...201627180039
vaccines against respiratory syncytial virus: the time has finally come.respiratory syncytial virus causes a significant public health burden, particularly in very young infants and the frail elderly. the legacy of enhanced rsv disease (erd) from a whole formalin-inactivated rsv vaccine, and the complex biology of the virus and the neonate have delayed the development of effective vaccines. however, new insights into factors associated with erd and breakthroughs in understanding the antigenic structure of the fusion (f) glycoprotein have increased optimism that vacc ...201627182820
viral infections in neonates with suspected late-onset bacterial sepsis-a prospective cohort study.objective the aim of our study was to evaluate the occurrence of viral infections in infants with suspected late-onset bacterial sepsis in a neonatal intensive care unit. methods in a prospective study, infants with suspected late-onset bacterial sepsis underwent viral testing alongside routine blood culture sampling. using a multiplex reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay, nasopharyngeal aspirates were analyzed for adenovirus, respiratory syncytial vi ...201727182999
rsv neutralization by palivizumab, but not by monoclonal antibodies targeting other epitopes, is augmented by fc gamma receptors.palivizumab efficiently blocks respiratory syncytial virus (rsv) infection in vitro. however, virus neutralization assays generally omit fc region-mediated effects. we investigated the neutralization activity of rsv-specific monoclonal antibodies on cells with fc receptors. subneutralizing concentrations of antibodies resulted in antibody-dependent enhancement of rsv infection in monocytic cells. contrary to antibodies targeting other epitopes, the neutralization by palivizumab was augmented in ...201627185625
antiviral activity of favipiravir (t-705) against a broad range of paramyxoviruses in vitro and against human metapneumovirus in hamsters.the clinical impact of infections with respiratory viruses belonging to the family paramyxoviridae argues for the development of antiviral therapies with broad-spectrum activity. favipiravir (t-705) has demonstrated potent antiviral activity against multiple rna virus families and is presently in clinical evaluation for the treatment of influenza. here we demonstrate in vitro activity of t-705 against the paramyxoviruses human metapneumovirus (hmpv), respiratory syncytial virus, human parainflue ...201627185803
predictive factor for first wheezing episode.the aim of study was to evaluate various risk in patients who were hospitalized with moderate to severe virus-induced wheezing. infants hospitalized with virus-induced wheezing were enrolled in the study. respiratory viruses were detected in nasopharyngeal swab and total ige levels and skin prick tests were performed in all patients. the mean age of the patients was 11.2±9 months. the most common detected viral agents were respiratory syncytial virus, (33.6%), influenza virus (16.3.%). children ...201727186699
respiratory syncytial virus and cellular stress responses: impact on replication and physiopathology.human respiratory syncytial virus (rsv), a member of the paramyxoviridae family, is a major cause of severe acute lower respiratory tract infection in infants, elderly and immunocompromised adults. despite decades of research, a complete integrated picture of rsv-host interaction is still missing. several cellular responses to stress are involved in the host-response to many virus infections. the endoplasmic reticulum stress induced by altered endoplasmic reticulum (er) function leads to activat ...201627187445
in hot pursuit of the first vaccine against respiratory syncytial virus.human respiratory syncytial virus (rsv) is the leading cause of severe lower respiratory tract infection, such as bronchiolitis, bronchitis, or pneumonia, in both infants and the elderly. despite the global burden of diseases attributable to rsv infection, no clinically approved vaccine is available, and a humanized monoclonal antibody for prophylaxis is not readily affordable in developing countries. there are several hurdles to the successful development of rsv vaccines: immune-vulnerable targ ...201627189271
caffeine for the treatment of apnea in bronchiolitis: a randomized trial.to evaluate the efficacy and safety of caffeine citrate in the treatment of apnea in bronchiolitis.201627189681
robust cytokine and chemokine response in nasopharyngeal secretions: association with decreased severity in children with physician diagnosed bronchiolitis.bronchiolitis causes substantial disease in young children. previous findings had indicated that a robust innate immune response was not associated with a poor clinical outcome in bronchiolitis. this study tested the hypothesis that increased concentrations of cytokines and chemokines in nasal wash specimens were associated with decreased severity in bronchiolitis.201627190183
targeting human respiratory syncytial virus transcription anti-termination factor m2-1 to inhibit in vivo viral replication.human respiratory syncytial virus (hrsv) is a leading cause of acute lower respiratory tract infection in infants, elderly and immunocompromised individuals. to date, no specific antiviral drug is available to treat or prevent this disease. here, we report that the smoothened receptor (smo) antagonist cyclopamine acts as a potent and selective inhibitor of in vitro and in vivo hrsv replication. cyclopamine inhibits hrsv through a novel, smo-independent mechanism. it specifically impairs the func ...201627194388
coinfections of the respiratory tract: viral competition for resources.studies have shown that simultaneous infection of the respiratory tract with at least two viruses is common in hospitalized patients, although it is not clear whether these infections are more or less severe than single virus infections. we use a mathematical model to study the dynamics of viral coinfection of the respiratory tract in an effort to understand the kinetics of these infections. specifically, we use our model to investigate coinfections of influenza, respiratory syncytial virus, rhi ...201627196110
population-attributable risk of risk factors for recurrent wheezing in moderate preterm infants during the first year of life.recurrent wheezing in young infants has a high prevalence, influences quality of life, and generates substantial health care costs. we previously showed that respiratory syncytial virus infection is an important mechanism of recurrent wheezing in moderate preterm infants. we aimed to provide population-attributable risks (par) of risk factors for recurrent wheezing during the first year of life in otherwise healthy moderate preterm infants.201627199198
comparison of intravenous palivizumab and standard of care for treatment of respiratory syncytial virus infection in mechanically ventilated pediatric patients.evidence suggests palivizumab may be beneficial for respiratory syncytial virus (rsv) infection in pediatric patients, although it is only approved by the us food and drug administration for rsv prophylaxis. the objective of this study is to compare outcomes among pediatric patients with rsv infection who received intravenous palivizumab and standard of care versus standard of care alone.201727199622
double epigenetic modulation of high-dose chemotherapy with azacitidine and vorinostat for patients with refractory or poor-risk relapsed lymphoma.more active high-dose chemotherapy (hdc) regimens are needed for refractory lymphomas. the authors previously combined infusional gemcitabine with busulfan and melphalan (gem/bu/mel) pursuing dna damage repair inhibition. subsequently, they combined gem/bu/mel with vorinostat, which facilitates chemotherapy access to dna. the resulting regimen was safe and synergistic. however, vorinostat induced dna methyltransferase up-regulation, which could be preclinically abrogated by azacitidine, increasi ...201627203405
a population study of respiratory rehospitalisation in very preterm infants in the first 3 years of life.very premature infants consume healthcare resources following discharge from neonatal intensive care units (nicu). this study aimed to evaluate the burden of respiratory related rehospitalisation within the first 3 years post discharge in very premature infants in an australian population.201627203818
evaluation of case definitions to detect respiratory syncytial virus infection in hospitalized children below 5 years in rural western kenya, 2009-2013.in order to better understand respiratory syncytial virus (rsv) epidemiology and burden in tropical africa, optimal case definitions for detection of rsv cases need to be identified.201627207342
cyclopiazonic acid, an inhibitor of calcium-dependent atpases with antiviral activity against human respiratory syncytial virus.human respiratory syncytial virus (rsv) is a common cause of lower respiratory tract infections in infants and young children worldwide, yet no vaccine or effective antiviral treatment is available. to search for new anti-rsv agents, we developed a cell-based assay that measures inhibition of rsv-induced cytopathic effect (cpe) and identified cyclopiazonic acid (cpa), an intracellular calcium atpase inhibitor as a rsv inhibitor (ec50 values 4.13 μm) by screening of natural product library. cpa i ...201627210812
respiratory syncytial virus immunoprophylaxis in high-risk infants and development of childhood asthma.respiratory syncytial virus (rsv) lower respiratory tract infection is implicated in asthma development. rsv immunoprophylaxis during infancy is efficacious in preventing rsv-related hospitalizations and has been associated with decreased wheezing in the first years of life.201727212083
respiratory syncytial virus whole-genome sequencing identifies convergent evolution of sequence duplication in the c-terminus of the g gene.respiratory syncytial virus (rsv) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. extensive sequence variability within and between rsv group a and b viruses and the ability of multiple clades and sub-clades of rsv to co-circulate are likely mechanisms contributing to the evasion of herd immunity. surveillance and large-scale whole-genome sequencing of rsv is currently limited but would help identify its evolution ...201627212633
aerosolized ribavirin: the most expensive drug for pneumonia.dramatic, overnight cost increases of important orphan and generic medications have recently come under public and government scrutiny. we highlight the case of aerosolized ribavirin, an important antiviral agent in hematopoietic stem cell transplantation which, because of substantial price increases, may now cost more than the transplant procedure itself.201627214684
delta inulin-derived adjuvants that elicit th1 phenotype following vaccination reduces respiratory syncytial virus lung titers without a reduction in lung immunopathology.respiratory syncytial virus (rsv) is a significant cause of lower respiratory tract infections resulting in bronchiolitis and even mortality in the elderly and young children/infants. despite the impact of this virus on human health, no licensed vaccine exists. unlike many other viral infections, rsv infection or vaccination does not induce durable protective antibodies in humans. in order to elicit high titer, neutralizing antibodies against rsv, we investigated the use of the adjuvant advax™, ...201627215855
intranasal administration of rsv antigen-expressing mcmv elicits robust tissue-resident effector and effector memory cd8+ t cells in the lung.cytomegalovirus vectors are promising delivery vehicles for vaccine strategies that aim to elicit effector cd8+ t cells. to determine how the route of immunization affects cd8+ t-cell responses in the lungs of mice vaccinated with a murine cytomegalovirus vector expressing the respiratory syncytial virus matrix (m) protein, we infected cb6f1 mice via the intranasal or intraperitoneal route and evaluated the m-specific cd8+ t-cell response at early and late time points. we found that intranasal v ...201727220815
a chimeric pneumovirus fusion protein carrying neutralizing epitopes of both mpv and rsv.respiratory syncytial virus (rsv) and human metapneumovirus (hmpv) are paramyxoviruses that are responsible for substantial human health burden, particularly in children and the elderly. the fusion (f) glycoproteins are major targets of the neutralizing antibody response and studies have mapped dominant antigenic sites in f. here we grafted a major neutralizing site of rsv f, recognized by the prophylactic monoclonal antibody palivizumab, onto hmpv f, generating a chimeric protein displaying epi ...201627224013
development of acquired immunity following repeated respiratory syncytial virus infections in cotton rats.respiratory syncytial virus (rsv) infections occur every year worldwide. most infants are infected with rsv by one year of age and are reinfected because immune responses after the first infection are too weak to protect against subsequent infections. in the present study, immune responses against rsv were investigated in order to obtain a better understanding of repetitive rsv infections in cotton rats. no detectable neutralizing antibody (nt) was developed after the first infection, and the se ...201627224021
detection of human metapneumovirus and respiratory syncytial virus by real-time polymerase chain reaction among hospitalized young children in iran.acute respiratory infection plays an important role in hospitalization of children in developing countries; detection of viral causes in such infections is very important. the respiratory syncytial virus (rsv) is the most common etiological agent of viral lower respiratory tract infection in children, and human metapneumovirus (hmpv) is associated with both upper and lower respiratory tract infections among infants and children.201627226877
sentinel1: an observational study of respiratory syncytial virus hospitalizations among u.s. infants born at 29 to 35 weeks' gestational age not receiving immunoprophylaxis.objective sentinel1 characterized u.s. preterm infants 29 to 35 weeks' gestational age (wga) < 12 months old hospitalized for laboratory-confirmed respiratory syncytial virus (rsv) disease and not receiving rsv immunoprophylaxis during the 2014 to 2015 rsv season. study design this is a noninterventional, observational, cohort study. results a total of 702 infants were hospitalized with community-acquired rsv disease, of whom an estimated 42% were admitted to the intensive care unit (icu) and 20 ...201727233106
maternal immunization: optimizing protection for the mother and infant.immunizing the pregnant woman to protect both the mother and her infant from infection has been utilized increasingly over the last decade. new outbreaks of pandemic influenza and the resurgence of pertussis have resulted in policy changes and shifts in health authority recommendations for a number of vaccines aimed to protect both pregnant women and their infants in the first months of life. the ability of maternal immunoglobulin igg antibodies to be transported readily across the healthy intac ...201627233120
aeroallergen-induced il-33 predisposes to respiratory virus-induced asthma by dampening antiviral immunity.frequent viral lower respiratory infections in early life are an independent risk factor for asthma onset. this risk and the development of persistent asthma are significantly greater in children who later become sensitized.201627236500
core bead chromatography for preparation of highly pure, infectious respiratory syncytial virus in the negative purification mode.respiratory syncytial virus (rsv) is an important human pathogen, and is the most frequent viral cause of severe respiratory disease in infants. in addition, it is increasingly being recognized as an important cause of respiratory disease in the elderly and immunocompromised. although a passive prophylactic treatment does exist for high-risk neonates and children, the overall disease burden warrants the development of a safe and effective prophylactic vaccine for use in otherwise healthy newborn ...201627238375
[th17/treg imbalance mediated by il-8 in rsv-infected bronchial epithelial cells].to explore the mechanisms for an increase in susceptibility of asthma induced by respiratory syncytial virus (rsv), to observe the expression of interleukin-8 (il-8) in human bronchial epithelial cells (hbecs) after rsv infection and to invesigate the regulatory effect of il-8 on th17/treg differentiation.201627241142
respiratory syncytial virus infection in infants in rural nepal.respiratory syncytial virus (rsv) pneumonia is a leading cause of infant mortality worldwide. the risk of rsv infection associated with preterm birth is not well-characterized in resource-limited settings. we aimed to obtain precise estimates of risk factors and disease burden of rsv in infants in rural southern nepal.201627241525
human metapneumovirus circulation in the united states, 2008 to 2014.human metapneumovirus (hmpv) infection causes respiratory illness, including bronchiolitis and pneumonia. however, national hmpv seasonality, as it compares with respiratory syncytial virus (rsv) and influenza seasonality patterns, has not been well described.201627244790
clinical characterisation and phylogeny of respiratory syncytial virus infection in hospitalised children at red cross war memorial children's hospital, cape town.respiratory syncytial virus (rsv) is a major cause of lower respiratory tract infection in young children in both the community and hospital setting.201627246848
the mechanisms of delayed onset type adverse reactions to oseltamivir.oseltamivir is recommended for the treatment and prophylaxis of influenza in persons at higher risk for influenza complications such as individuals with diabetes, neuropsychiatric illnesses, and respiratory, cardiac, renal, hepatic or haematological diseases. however, a recent cochrane review reported that reduction of antibody production, renal disorders, hyperglycaemia, psychiatric disorders, and qt prolongation may be related to oseltamivir use. the underlying mechanisms are reviewed. there i ...201627251370
suppression of irg-1 reduces inflammatory cell infiltration and lung injury in respiratory syncytial virus infection by reducing production of reactive oxygen species.respiratory syncytial virus (rsv) infection is a common cause of lower respiratory tract illness in infants and children. rsv is a negative-sense, single-strand rna (ssrna) virus that mainly infects airway epithelial cells. accumulating evidence indicates that reactive oxygen species (ros) production is a major factor for pulmonary inflammation and tissue damage of rsv disease. we investigated immune-responsive gene-1 (irg1) expression during rsv infection, since irg1 has been shown to mediate i ...201627252532
identification and characterization of influenza virus entry inhibitors through dual myxovirus high-throughput screening.influenza a virus (iav) infections cause major morbidity and mortality, generating an urgent need for novel antiviral therapeutics. we recently established a dual myxovirus high-throughput screening protocol that combines a fully replication-competent iav-wsn strain and a respiratory syncytial virus reporter strain for the simultaneous identification of iav-specific, paramyxovirus-specific, and broad-spectrum inhibitors. in the present study, this protocol was applied to a screening campaign to ...201627252534
phosphorylation of human metapneumovirus m2-1 protein upregulates viral replication and pathogenesis.human metapneumovirus (hmpv) is a major causative agent of upper- and lower-respiratory-tract infections in infants, the elderly, and immunocompromised individuals worldwide. like all pneumoviruses, hmpv encodes the zinc binding protein m2-1, which plays important regulatory roles in rna synthesis. the m2-1 protein is phosphorylated, but the specific role(s) of the phosphorylation in viral replication and pathogenesis remains unknown. in this study, we found that hmpv m2-1 is phosphorylated at a ...201627252537
modelling estimates of the burden of respiratory syncytial virus infection in children in the uk.the burden of respiratory syncytial virus (rsv) illness is not well characterised in primary care. we estimated the burden of disease attributable to rsv in children in the uk between 1995 and 2009.201627256085
discovery and characterization of phage display-derived human monoclonal antibodies against rsv f glycoprotein.respiratory syncytial virus (rsv) is a leading cause of lower respiratory tract infection in infants, the elderly and in immunosuppressed populations. the vast majority of neutralizing antibodies isolated from human subjects target the rsv fusion (f) glycoprotein, making it an attractive target for the development of vaccines and therapeutic antibodies. currently, synagis® (palivizumab) is the only fda approved antibody drug for the prevention of rsv infection, and there is a great need for more ...201627258388
exposure to common respiratory bacteria alters the airway epithelial response to subsequent viral infection.colonization of the airways with potential pathogenic bacteria is observed in a number of chronic respiratory diseases, such as copd or cystic fibrosis. infections with respiratory viruses are known triggers of exacerbations of these diseases. we here investigated if pre-exposure to bacteria alters the response of lung epithelial cells to subsequent viral infection.201627259950
human metapneumovirus infections in hematopoietic cell transplant recipients and hematologic malignancy patients: a systematic review.over the past decade, reported incidence of human metapneumovirus (hmpv) has increased owing to the use of molecular assays for diagnosis of respiratory viral infections in cancer patients. the seasonality of these infections, differences in sampling strategies across institutions, and small sample size of published studies make it difficult to appreciate the true incidence and impact of hmpv infections. in this systematic review, we summarized the published data on hmpv infections in hematopoie ...201627260872
epidemiology of community-acquired pneumonia and implications for vaccination of children living in developing and newly industrialized countries: a systematic literature review.this systematic review evaluated the epidemiology of community-acquired pneumonia in children <6 y of age within 90 developing and newly industrialized countries. literature searches (1990-2011), based on medline, embase, cochrane, cab global health, who, unicef, country-specific websites, conferences, health-technology-assessment agencies, and the reference lists of included studies, yielded 8,734 records; 62 of 340 studies were included in this review. the highest incidence rate among included ...201627269963
limited evidence on the management of respiratory tract infections in down's syndrome: a systematic review.to systematically review the effectiveness of preventative and therapeutic interventions for respiratory tract infections (rtis) in people with down's syndrome.201627273687
ten-year study of the stringently defined otitis-prone child in rochester, ny.this review summarizes a prospective, longitudinal 10-year study in rochester, ny, with virtually every clinically diagnosed acute otitis media (aom) confirmed by bacterial culture of middle ear fluid. children experiencing 3 episodes within 6 months or 4 episodes in 12 months were considered stringently defined otitis prone (sop). we found stringent diagnosis compared with clinical diagnosis reduced the frequency of children meeting the op definition from 27% to 6% resulting in 14.8% and 2.4% r ...201627273691
a cross-study biomarker signature of human bronchial epithelial cells infected with respiratory syncytial virus.respiratory syncytial virus (rsv) is a major cause of lower respiratory tract infections in children, elderly, and immunocompromised individuals. despite of advances in diagnosis and treatment, biomarkers of rsv infection are still unclear. to understand the host response and propose signatures of rsv infection, previous studies evaluated the transcriptional profile of the human bronchial epithelial cell line-beas-2b-infected with different strains of this virus. however, the evolution of statis ...201627274726
intensive care unit admission and death rates of infants admitted with respiratory syncytial virus lower respiratory tract infection in mexico.respiratory syncytial virus (rsv) is the most common etiology for acute respiratory infection hospital admissions in young children. case fatality rates for hospitalized patients range between 0% and 3.4%. recent reports indicate that deaths associated with rsv are uncommon in developed countries. however, the role of this virus as a current cause of mortality in other countries requires further examination.201627276178
modelling estimates of age-specific influenza-related hospitalisation and mortality in the united kingdom.influenza is rarely confirmed with laboratory testing and accurate assessment of the overall burden of influenza is difficult. we used statistical modelling methods to generate updated, granular estimates of the number/rate of influenza-attributable hospitalisations and deaths in the united kingdom. such data are needed on a continuing basis to inform on cost-benefit analyses of treatment interventions, including vaccination.201627278794
a recombinant respiratory syncytial virus vaccine candidate attenuated by a low-fusion f protein is immunogenic and protective against challenge in cotton rats.although respiratory syncytial virus (rsv) is the leading cause of lower respiratory tract infections in infants, a safe and effective vaccine is not yet available. live-attenuated vaccines (lavs) are the most advanced vaccine candidates in rsv-naive infants. however, designing an lav with appropriate attenuation yet sufficient immunogenicity has proven challenging. in this study, we implemented reverse genetics to address these obstacles with a multifaceted lav design that combined the codon de ...201627279612
approved antiviral drugs over the past 50 years.since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) hiv infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis b virus (hbv) infections (lamivudine, interferon ...201627281742
risk and protective factors for childhood asthma: what is the evidence?to summarize the principal findings on risk and protective factors for childhood asthma, we retrieved systematic reviews on these topics in children (aged 1 to 18 years), up to january 2016, through medline, embase, cinahl, scopus, and cdsr. a total of 227 studies were searched from databases. among those, 41 systematic reviews (srs) were included: 9 focused on prenatal factors, 5 on perinatal factors, and 27 on postnatal factors. of these 41 srs, 83% had good methodological quality, as determin ...201727286779
molecular evolution of the fusion protein gene in human respiratory syncytial virus subgroup a.we studied the molecular evolution of the fusion protein (f) gene in the human respiratory syncytial virus subgroup a (hrsv-a). we performed time-scaled phylogenetic analyses using the bayesian markov chain monte carlo (mcmc) method. we also conducted genetic distance (p-distance), positive/negative selection, and bayesian skyline plot analyses. furthermore, we mapped the amino acid substitutions of the protein. the mcmc-constructed tree indicated that the hrsv f gene diverged from the bovine rs ...201627291709
time series analysis of rsv and bronchiolitis seasonality in temperate and tropical western australia.respiratory syncytial virus (rsv) causes respiratory illness in young children and is most commonly associated with bronchiolitis. rsv typically occurs as annual or biennial winter epidemics in temperate regions, with less pronounced seasonality in the tropics. we sought to characterise and compare the seasonality of rsv and bronchiolitis in temperate and tropical western australia. we examined over 13 years of rsv laboratory identifications and bronchiolitis hospitalisations in children, using ...201627294794
a preliminary assessment of the role of ambient nitric oxide exposure in hospitalization with respiratory syncytial virus bronchiolitis.some in vitro studies have indicated a possible link between respiratory syncytial virus (rsv) infection and exposure to nitric oxide (no). however, these studies used much higher no concentrations than normally found in the ambient environment. this preliminary study explored whether an association was present with short-term exposure to no in the environment. rsv-related admission data between november 2011 and february 2012 were obtained from sheffield children's hospital. the dates of admiss ...201627294948
potential sirna molecules for nucleoprotein and m2/l overlapping region of respiratory syncytial virus: in silico design.human respiratory syncytial virus (rsv) is a leading cause of severe lower respiratory tract disease in the pediatric population, elderly and in immunosuppressed individuals. respiratory syncytial virus is also responsible for bronchiolitis, pneumonia, and chronic obstructive pulmonary infections in all age groups. with this high disease burden and the lack of an effective rsv treatment and vaccine, there is a clear need for discovery and development of novel, effective and safe drugs to prevent ...201627303618
simultaneous antibiofilm and antiviral activities of an engineered antimicrobial peptide during virus-bacterium coinfection.antimicrobial-resistant infections are an urgent public health threat, and development of novel antimicrobial therapies has been painstakingly slow. polymicrobial infections are increasingly recognized as a significant source of severe disease and also contribute to reduced susceptibility to antimicrobials. chronic infections also are characterized by their ability to resist clearance, which is commonly linked to the development of biofilms that are notorious for antimicrobial resistance. the us ...201727303744
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