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helper t cell responses to respiratory viruses in the lung: development, virus suppression, and pathogenesis.the lung is an important line of defense that is exposed to respiratory infectious pathogens, including viruses. lung epithelial cells and/or alveolar macrophages are initially targeted by respiratory viruses. once respiratory viruses invade the cells of the lung, innate immunity is activated to inhibit viral replication. innate immune signaling also activates virus-specific adaptive immune responses. the helper t cells play pivotal roles in the humoral and cellular adaptive immune responses. he ...201728650258
respiratory syncytial virus bronchiolitis, weather conditions and air pollution in an italian urban area: an observational study.in this study we sought to evaluate the association between viral bronchiolitis, weather conditions, and air pollution in an urban area in italy.201728647513
development of respiratory syncytial virus (rsv) vaccines for infants.2017 will mark the 60(th) anniversary since the first isolation of rsv in children. in spite of concerted efforts over all these years, the goal of developing an effective vaccine against paediatric rsv disease has remained elusive. one of the main hurdles standing in the way of an effective vaccine is the fact that the age incidence of severe disease peaks within the first 3 months of life, providing limited opportunity for intervention. in addition to this complexity, the spectre of failed his ...201728646954
molecular epidemiology of human respiratory syncytial virus in iranian ≥60 years old hospitalized patients with acute respiratory symptoms.human respiratory syncytial virus (hrsv) is an important cause of acute respiratory infection (ari) and mortality in ≥60 years old population around the world. the aim of this study was to determine the frequency and circulating genotypes of hrsv in iranian patients ≥ 60 years old.201728646846
roles of non-coding rnas in respiratory syncytial virus (rsv) infection.analysis of host gene expression profiles following viral infections of target cells/tissues can reveal crucial insights into the host: virus interaction and enables the development of novel therapeutics and prophylactics. regions of the host genome that do not code for protein, encode structural, and functional non-coding rnas that are important not only in regulation of host gene expression but also may impact viral replication. this review summarizes the role of host non-coding rnas during re ...201728646339
national high-flow nasal cannula and bronchiolitis survey highlights need for further research and evidence-based guidelines.high-flow nasal cannula (hfnc) therapy provides noninvasive respiratory support for infant bronchiolitis and its use has increased following good clinical experiences. this national study describes hfnc use in finland during a severe respiratory syncytial virus (rsv) epidemic.201728643443
a new antiviral pregnane from a gorgonian-derived cladosporium sp. fungus.a new pregnane, 3α-hydroxy-7-ene-6,20-dione (1), and five known steroids (2-6), along with one known steroidal glycoside (7) were obtained from the fungus cladosporium sp. wz-2008-0042 cultured from a gorgonian dichotella gemmacea collected from the south china sea. the structure and absolute configuration of the new compound (1) were elucidated by comprehensive spectroscopic data and x-ray diffraction data. the compound has a rare configuration of 3α-oh that is different from most of pregnanes. ...201728641456
viral aetiology of wheezing in children under five.wheezing is a common problem in children under five with acute respiratory infections (aris). viruses are known to be responsible for a considerable proportion of aris in children. this study was undertaken to know the viral aetiology of wheezing among the children less than five years of age, admitted to a tertiary care hospital in eastern india.201728639594
does atopy affect the course of viral pneumonia?the presence of atopy is considered as a risk factor for severe respiratory symptoms in children. the objective of this study was to examine the effect of atopy on the course of disease in children hospitalised with viral pneumonia.201728634031
respiratory syncytial virus (rsv) in adult emergency department patients: do emergency providers consider rsv as an admission diagnosis?: a retrospective, observational study carried out at massachusetts general hospital, boston, ma.respiratory syncytial virus (rsv) has been recognized for over half a century as a cause of morbidity in infants and children. over the past 20years, data has emerged linking rsv as a cause of illness in adults resulting in 177,000 annual hospitalizations and up to 14,000 deaths among older adults.201728633906
severe viral pneumonia in adults: what is important for the icu physician? 201728633583
analysis of respiratory viral infections detected using multiplex real-time pcr in hwaseong, korea from 2013 to 2015.we investigated the incidences and age-related/seasonal variations of respiratory virus infections in a regional area in korea.201728627819
infections caused by hrsv a on1 are predominant among hospitalized infants with bronchiolitis in são paulo city.human respiratory syncytial virus is the main cause of respiratory infections in infants. several hrsv genotypes have been described. goals. to describe the main genotypes that caused infections in são paulo (2013-2015) and to analyze their clinical/epidemiological features. methods. 94 infants (0-6 months) with bronchiolitis were studied. clinical/epidemiological information was collected; a search for 16 viruses in nasopharyngeal secretion (pcr-real-time and conventional, sequencing, and phylo ...201728626754
preclinical assessment of safety of maternal vaccination against respiratory syncytial virus (rsv) in cotton rats.maternal immunization directed to control rsv infection in newborns and infants is an appealing vaccination strategy currently under development. in this work we have modeled maternal vaccination against rsv in cotton rats (cr) to answer two fundamental questions on maternal vaccine safety. we tested (i), whether a known, unsafe rsv vaccine (i.e., fi-rsv lot 100 vaccine) induces vaccine enhanced disease in the presence of passively transferred, rsv maternal immunity, and (ii) whether the same fi ...201728624306
broad-spectrum inhibition of respiratory virus infection by microrna mimics targeting p38 mapk signaling.the majority of antiviral therapeutics target conserved viral proteins, however, this approach confers selective pressure on the virus and increases the probability of antiviral drug resistance. an alternative therapeutic strategy is to target the host-encoded factors that are required for virus infection, thus minimizing the opportunity for viral mutations that escape drug activity. micrornas (mirnas) are small noncoding rnas that play diverse roles in normal and disease biology, and they gener ...201728624201
clinical course of community-acquired respiratory syncytial virus pneumonia in newborns hospitalized in neonatal intensive care unit. 201728621252
chd and respiratory syncytial virus: global expert exchange recommendations.palivizumab is the standard immunoprophylaxis against serious disease due to respiratory syncytial virus infection. current evidence-based prophylaxis guidelines may not address certain children with chd within specific high-risk groups or clinical/management settings.201728619123
epitope mapping and kinetics of cd4 t cell immunity to pneumonia virus of mice in the c57bl/6 strain.pneumonia virus of mice (pvm) infection has been widely used as a rodent model to study the closely related human respiratory syncytial virus (hrsv). while t cells are indispensable for viral clearance, they also contribute to immunopathology. to gain more insight into mechanistic details, novel tools are needed that allow to study virus-specific t cells in c57bl/6 mice as the majority of transgenic mice are only available on this background. while pvm-specific cd8 t cell epitopes were recently ...201728615708
recurrent rhinovirus infections in a child with inherited mda5 deficiency.mda5 is a cytosolic sensor of double-stranded rna (ds)rna including viral byproducts and intermediates. we studied a child with life-threatening, recurrent respiratory tract infections, caused by viruses including human rhinovirus (hrv), influenza virus, and respiratory syncytial virus (rsv). we identified in her a homozygous missense mutation in ifih1 that encodes mda5. mutant mda5 was expressed but did not recognize the synthetic mda5 agonist/(ds)rna mimic polyinosinic-polycytidylic acid. when ...201728606988
a human challenge model for respiratory syncytial virus kinetics, the pharmacological effect of a novel fusion inhibitor, and the modelling of symptoms scores.respiratory syncytial virus (rsv) causes acute lower respiratory tract infections, and is a major cause of hospital admissions and death in young children. limited treatments currently exist that can prevent or minimise exacerbation of the disease. the aims of this work were: 1) to develop a population pharmacodynamic model to describe rsv kinetics (rsvk) in nasal lavage, 2) evaluate the impact of an investigational fusion inhibitor, jnj-53718678, on rsvk, and 3) determine the relationship betwe ...201728606804
[expression of interferon-λ1 in respiratory epithelial cells of children with rsv infection and its relationship with rsv load].to investigate the expression of ifn-λ1 in respiratory epithelial cells of children with respiratory syncytial virus (rsv) infection and its relationship with rsv load.201728606236
microorganisms associated with pneumonia in children <5 years of age in developing and emerging countries: the gabriel pneumonia multicenter, prospective, case-control study.pneumonia, the leading infectious cause of child mortality globally, mainly afflicts developing countries. this prospective observational study aimed to assess the microorganisms associated with pneumonia in children aged <5 years in developing and emerging countries.201728605562
product review on the monoclonal antibody palivizumab for prevention of respiratory syncytial virus infection.respiratory syncytial virus (rsv) accounts for about 20% of all respiratory infections in children below the age of 5 y. it is associated with up to 63% of all acute respiratory infections and up to 81% of all viral lower respiratory tract infections causing hospitalization in infants and young children. rsv leads to seasonal epidemics between november and april in the northern hemisphere. most severe infections (rsv accounts for 50 to 80% of all cause bronchiolitis) affect infants younger than ...201728605249
the importance of rsv f protein conformation in vlps in stimulation of neutralizing antibody titers in mice previously infected with rsv.respiratory syncytial virus (rsv) is a significant respiratory pathogen but no vaccine is available. rsv infections present 2 major, unique problems. first, humans can experience repeated infections caused by the same virus sero-group indicating that protective memory responses to rsv infection are defective. second, most people have been infected with rsv by age 5. immune responses to these infections, while poorly protective, could impact the effectiveness of a vaccine. the goal of this study ...201728604155
usefulness of ct value in acute respiratory infections caused by respiratory syncytial virus a and b and influenza virus a (h1n1)pdm09, a (h3n2) and b.acute respiratory infections of viral cause are very frequent entities. the difficulty in evaluating the detection of a virus in these entities could be solved by determining the viral load.201728601216
respiratory syncytial virus infection compromises asthma tolerance by recruiting interleukin-17a-producing cells via ccr6-ccl20 signaling.asthma tolerance can be induced by breast-feeding or oral feeding with ovalbumin (ova). anergy or deletion of specific t cells and generation of t regulatory cells might contribute to this process. however, whether respiratory syncytial virus (rsv) infection would affect asthma tolerance is not very clear. here, we first established asthma and oral tolerance mouse models and then analyzed airway hypersensitivity and asthma-related genes in the lung, ccr6-expressing il-17a(+) cells in the lungs, ...201728599122
a safe and efficient bcg vectored vaccine to prevent the disease caused by the human respiratory syncytial virus.the human respiratory syncytial virus (hrsv) causes lower respiratory tract infections including pneumonia and bronchiolitis. such infections also cause a large number of hospitalizations and affects mainly newborns, young children and the elderly worldwide. symptoms associated with hrsv infection are due to an exacerbated immune response characterized by low levels of ifn-γ, recruitment of neutrophils and eosinophils to the site of infection and lung damage. although hrsv is a major health prob ...201728598702
intravenous palivizumab in respiratory syncytial virus infection after hematopoietic stem cell transplant in children.respiratory syncytial virus (rsv) infection can cause lower respiratory tract disease and mortality in pediatric hematopoietic stem cell transplant (hsct) recipients. we report two children who underwent hsct and developed rsv infection simultaneously at the bone marrow transplant unit. the treatment with intravenous palivizumab was provided and sequential viral loads were measured in nasopharyngeal (np) and whole blood samples. to our knowledge, this is the first report where rsv loads were mea ...201728598593
a four-biomarker blood signature discriminates systemic inflammation due to viral infection versus other etiologies.the innate immune system of humans and other mammals responds to pathogen-associated molecular patterns (pamps) that are conserved across broad classes of infectious agents such as bacteria and viruses. we hypothesized that a blood-based transcriptional signature could be discovered indicating a host systemic response to viral infection. previous work identified host transcriptional signatures to individual viruses including influenza, respiratory syncytial virus and dengue, but the generality o ...201728588308
outbreaks in the neonatal icu: a review of the literature.neonates in the neonatal icu (nicu) are uniquely vulnerable to colonization and infection with pathogens such as multidrug resistant gram-negative bacteria, which in turn are associated with increased infection-related morbidities and higher case-fatality rates. we reviewed the english, french, and german language literature published between 2015 and 2017, for reports of nicu outbreaks.201728582313
epigenetic silencing of irf1 dysregulates type iii interferon responses to respiratory virus infection in epithelial to mesenchymal transition.chronic oxidative injury produced by airway disease triggers a transforming growth factor-β (tgf-β)-mediated epigenetic reprogramming known as the epithelial-mesenchymal transition (emt). we observe that emt silences protective mucosal interferon (ifn)-i and iii production associated with enhanced rhinovirus (rv) and respiratory syncytial virus (rsv) replication. mesenchymal transitioned cells are defective in inducible interferon regulatory factor 1 (irf1) expression by occluding rela and irf3 ...201728581456
evaluation of the expression level of 12/15 lipoxygenase and the related inflammatory factors (ccl5, ccl3) in respiratory syncytial virus infection in mice model.human respiratory syncytial virus (rsv) is a leading cause of acute respiratory infection during early childhood and imposes a great burden on patients, parents, and society. disease is thought to be caused, at least partially, by an excessive immune response. pulmonary leukocyte infiltration is the result of a coordinated expression of diverse chemokines with distinct cellular specificities. lipoxygenases (loxs), as a key enzyme catalyzing deoxygenation of poly unsaturated fatty acids, regulate ...201728579398
modelled seasonal influenza mortality shows marked differences in risk by age, sex, ethnicity and socioeconomic position in new zealand.influenza is responsible for a large number of deaths which can only be estimated using modelling methods. such methods have rarely been applied to describe the major socio-demographic characteristics of this disease burden.201728579304
a phase 2 randomized, observer-blind, placebo-controlled, dose-ranging trial of aluminum-adjuvanted respiratory syncytial virus f particle vaccine formulations in healthy women of childbearing age.respiratory syncytial virus (rsv) causes significant morbidity and mortality in infants. we are developing an rsv fusion (f) protein nanoparticle vaccine for immunization of third trimester pregnant women to passively protect infants through transfer of rsv-specific maternal antibodies. the present trial was performed to assess the immunogenicity and safety of several formulations of rsv f vaccine in 1-dose or 2-dose schedules.201728579233
low retinol-binding protein and vitamin d levels are associated with severe outcomes in children hospitalized with lower respiratory tract infection and respiratory syncytial virus or human metapneumovirus detection.retinol binding protein and vitamin d were measured in children aged <5 years hospitalized with lower respiratory tract infection and respiratory syncytial virus and/or human metapneumovirus detections. low vitamin levels were observed in 50% of the children and were associated with significantly elevated risk of the need for intensive care unit admission and invasive mechanical ventilation.201728578159
unrelated umbilical cord blood transplantation for sickle cell disease following reduced-intensity conditioning: results of a phase i trial.hematopoietic stem cell transplantation from hla-matched sibling donors results in disease-free survival of >90% in patients with sickle cell disease (scd); however, only approximately 18% of these patients have suitable donors available. unrelated cord blood transplantation (ucbt) is one way to expand donor options for patients with severe scd, but historically has been associated with high graft rejection rates (50% to 62%). we hypothesized that the addition of thiotepa to a previously tested ...201728578010
stat1 represses cytokine-producing group 2 and group 3 innate lymphoid cells during viral infection.the appropriate orchestration of different arms of the immune response is critical during viral infection to promote efficient viral clearance while limiting immunopathology. however, the signals and mechanisms that guide this coordination are not fully understood. ifns are produced at high levels during viral infection and have convergent signaling through stat1. we hypothesized that stat1 signaling during viral infection regulates the balance of innate lymphoid cells (ilc), a diverse class of ...201728576981
mitochondrial protein p32/hapb1/gc1qr/c1qbp is required for efficient respiratory syncytial virus production.respiratory syncytial virus (rsv) is a major cause of respiratory infections in infants and the elderly, leading to more deaths than influenza each year, but there is no antiviral or efficacious vaccine currently available. here we examine the role in infection of the host mitochondrial protein p32 (habp/gc1qr/c1qbp) for the first time. rsv replication as well as infectious virus production was significantly reduced by p32 sirna knockdown, consistent with an important role for p32 in rsv infecti ...201728576489
association of c-reactive protein with bacterial and respiratory syncytial virus-associated pneumonia among children aged <5 years in the perch study.lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of c-reactive protein (crp) for identifying bacterial pneumonia. we evaluated the sensitivity and specificity of crp for identifying bacterial vs respiratory syncytial virus (rsv) pneumonia in the pneumonia etiology research for child health (perch) multicenter case-control study.201728575375
respiratory syncytial virus: prospects for new and emerging therapeutics.respiratory syncytial virus (rsv) is the major cause of lower respiratory tract infections (lrti) in infants, the elderly, and the immunocompromised. although the development of a rsv vaccine has been a priority for >50 years, there is still no vaccine available. treatment of rsv lrti has remained mostly supportive, i.e. hydration and oxygenation. palivizumab and ribavirin are the only options currently available for prevention and treatment of rsv infection, but evidence suggests that they are ...201728574729
efficacy and safety of ban huang oral liquid for treating bovine respiratory diseases.ban huang oral liquid was developed as a veterinary compound preparation by the lanzhou institute of husbandry and pharmaceutical sciences of the chinese academy of agricultural sciences (caas). the purpose of this study was to determine whether the oral liquid preparation of traditional chinese medicine, ban huang, is safe and effective for treating respiratory diseases in cattle.201728573221
natural killer t cell sensitization during neonatal respiratory syncytial virus infection induces eosinophilic lung disease in re-infected adult mice.respiratory syncytial virus (rsv) is a major viral pathogen that causes severe lower respiratory tract infections in infants and the elderly worldwide. infants with severe rsv bronchiolitis tend to experience more wheezing and asthma in later childhood. because invariant natural killer t (inkt) cells are associated with the asthma pathology, we investigated whether neonatal inkt cells are involved in the aggravation of pulmonary diseases following rsv infection in mice. intranasal exposure to th ...201728570692
effect of climate on incidence of respiratory syncytial virus infections in a refugee camp in kenya: a non-gaussian time-series analysis.respiratory syncytial virus (rsv) is one of the major causes of acute lower respiratory tract infections (alrti) in children. children younger than 1 year are the most susceptible to rsv infection. rsv infections occur seasonally in temperate climate regions. based on rsv surveillance and climatic data, we developed statistical models that were assessed and compared to predict the relationship between weather and rsv incidence among refugee children younger than 5 years in dadaab refugee camp in ...201728570627
respiratory syncytial virus associated myocarditis requiring venoarterial extracorporeal membrane oxygenation.severe fulminant myocarditis causing cardiogenic shock can be a rapidly progressing, life threatening condition. respiratory syncytial virus (rsv) is a very rare infectious culprit infrequently described in medical literature as a cause of myocarditis, particularly in adults. we present a case of acute fulminant myocarditis in a patient with pcr positive rsv infection requiring venoarterial extracorporeal membrane oxygenation (va-ecmo).201728567315
heme oxygenase-1 modulates human respiratory syncytial virus replication and lung pathogenesis during infection.human respiratory syncytial virus (hrsv) is the leading cause of severe lower respiratory tract infections in children. the development of novel prophylactic and therapeutic antiviral drugs against hrsv is imperative to control the burden of disease in the susceptible population. in this study, we examined the effects of inducing the activity of the host enzyme heme oxygenase-1 (ho-1) on hrsv replication and pathogenesis on lung inflammation induced by this virus. our results show that after hrs ...201728566367
a dynamic cell entry pathway of respiratory syncytial virus revealed by tracking the quantum dot-labeled single virus.studying the cell entry pathway at the single-particle level can provide detailed and quantitative information for the dynamic events involved in virus entry. indeed, the viral entry dynamics cannot be monitored by static staining methods used in cell biology, and thus virus dynamic tracking could be useful in the development of effective antiviral strategies. therefore, the aim of this work was to use a quantum dot-based single-particle tracking approach to monitor the cell entry behavior of th ...201728561831
respiratory-syncytial-virus- and rhinovirus-related bronchiolitis in children aged <2 years in an english district general hospital.bronchiolitis is the most common reason for hospitalization in young children. in addition to respiratory syncytial virus (rsv), other viruses have been increasingly implicated. guidance on testing has also changed.201728559125
age predicts cytokine kinetics and innate immune cell activation following intranasal delivery of ifnγ and gm-csf in a mouse model of rsv infection.respiratory syncytial virus (rsv) is the leading cause of lower respiratory tract infections in young children and is further associated with increased healthcare utilization and cost of care in the first years of life. severe rsv disease during infancy has also been linked to the later development of allergic asthma, yet there remains no licensed rsv vaccine or effective treatment. pre-clinical and clinical studies have shown that disease severity and development of allergic asthma are associat ...201728558308
national cohort study showed that infants with down's syndrome faced a high risk of hospitalisation for the respiratory syncytial virus.the respiratory syncytial virus (rsv) is a leading cause of hospitalisation in infants. we investigated this risk in children with down's syndrome under two years of age, adjusted for other known risk factors.201728556255
consecutive yearly outbreaks of respiratory syncytial virus in a haemato-oncology ward and efficacy of infection control measures.respiratory syncytial virus (rsv) causes significant respiratory tract infection in immunosuppressed patients.201728554834
coptidis rhizoma extract inhibits replication of respiratory syncytial virus in vitro and in vivo by inducing antiviral state.coptidis rhizoma is derived from the dried rhizome of ranunculaceous plants and is a commonly used traditional chinese medicine. although coptidis rhizoma is commonly used for its many therapeutic effects, antiviral activity against respiratory syncytial virus (rsv) has not been reported in detail. in this study, we evaluated the antiviral activities of coptidis rhizoma extract (cre) against rsv in human respiratory tract cell line (hep2) and balb/c mice. an effective dose of cre significantly r ...201728551874
virus detection by pcr following vaccination of naive calves with intranasal or injectable multivalent modified-live viral vaccines.we evaluated duration of pcr-positive results following administration of modified-live viral (mlv) vaccines to beef calves. twenty beef calves were randomly assigned to either group 1 and vaccinated intranasally with a mlv vaccine containing bovine alphaherpesvirus 1 (bohv-1), bovine respiratory syncytial virus (brsv), and bovine parainfluenza virus 3 (bpiv-3), or to group 2 and vaccinated subcutaneously with a mlv vaccine containing bovine viral diarrhea virus 1 and 2 (bvdv-1, -2), bohv-1, brs ...201728545321
pcpp-adjuvanted respiratory syncytial virus (rsv) sf subunit vaccine: self-assembled supramolecular complexes enable enhanced immunogenicity and protection.pcpp, a well-defined polyphosphazene macromolecule, has been studied as an immunoadjuvant for a soluble form of the postfusion glycoprotein of respiratory syncytial virus (rsv sf), which is an attractive vaccine candidate for inducing rsv-specific immunity in mice and humans. we demonstrate that rsv sf-pcpp formulations induce high neutralization titers to rsv comparable to alum formulations even at a low pcpp dose and protect animals against viral challenge both in the lung and in the upper res ...201728544850
humidified high-flow nasal cannula oxygen in bronchiolitis reduces need for invasive ventilation but not intensive care admission.to describe the changes to paediatric intensive care unit (picu) admission patterns and ventilation requirements for children with bronchiolitis following the introduction of humidified high-flow nasal cannula oxygen outside the picu.201728544665
a risk-adapted approach to treating respiratory syncytial virus and human parainfluenza virus in allogeneic stem cell transplantation recipients with oral ribavirin therapy: a pilot study.here we report the applicability of a protocol based on clinical conditions and risk factors (rfs) for managing 35 allogeneic hematopoietic stem cell transplantation (allo-hsct) recipients who developed a total of 52 episodes of respiratory viral infections (rvis) caused by respiratory syncytial virus (rsv; n=19), human parainfluenza virus (hpiv; n=29), or both (n=4) over a 2-year study period. risk categories were classified as high risk (cat-1) when the immunodeficiency scoring index was ≥3 an ...201728544152
serum ll-37 level is associated with severity of bronchiolitis and viral etiology.ll-37 is a host defense peptide with antimicrobial and immunomodulatory properties. we examined the relation of serum ll-37 levels to the severity of bronchiolitis and viral etiology.201728541502
significance of platelet count in children admitted with bronchiolitis.to determine the true prevalence of thrombocytosis in children less than 2 years of age with bronchiolitis, its association with risk factors, disease severity and thromboembolic complications.201728540196
the absence of interferon-β promotor stimulator-1 (ips-1) predisposes to bronchiolitis and asthma-like pathology in response to pneumoviral infection in mice.respiratory syncytial virus (rsv)-bronchiolitis is a major cause of infant morbidity and mortality and a risk factor for subsequent asthma. we showed previously that toll-like receptor (tlr)7 in plasmacytoid dendritic cells (pdcs) is critical for protection against bronchiolitis and asthma in mice infected with pneumonia virus of mice (pvm), the mouse homolog of rsv. this lack of redundancy was unexpected as interferon-β promotor stimulator-1 (ips-1) signalling, downstream of rig-i-like receptor ...201728539639
improved prefusion stability, optimized codon usage, and augmented virion packaging enhance the immunogenicity of respiratory syncytial virus fusion protein in a vectored-vaccine candidate.respiratory syncytial virus (rsv) is the most important viral agent of severe pediatric respiratory tract disease worldwide, but it lacks a licensed vaccine or suitable antiviral drug. a live attenuated chimeric bovine/human parainfluenza virus type 3 (rb/hpiv3) was developed previously as a vector expressing rsv fusion (f) protein to confer bivalent protection against rsv and hpiv3. in a previous clinical trial in virus-naive children, rb/hpiv3 was well tolerated but the immunogenicity of wild- ...201728539444
discovery of a prefusion respiratory syncytial virus f-specific monoclonal antibody that provides greater in vivo protection than the murine precursor of palivizumab.palivizumab, a humanized murine monoclonal antibody that recognizes antigenic site ii on both the prefusion (pre-f) and postfusion (post-f) conformations of the respiratory syncytial virus (rsv) f glycoprotein, is the only prophylactic agent approved for use for the treatment of rsv infection. however, its relatively low neutralizing potency and high cost have limited its use to a restricted population of infants at high risk of severe disease. previously, we isolated a high-potency neutralizing ...201728539438
airway t cells protect against rsv infection in the absence of antibody.tissue resident memory t (trm) cells act as sentinels and early responders to infection. respiratory syncytial virus (rsv)-specific trm cells have been detected in the lungs after human rsv infection, but whether they have a protective role is unknown. to dissect the protective function of trm cells, balb/c mice were infected with rsv; infected mice developed antigen-specific cd8(+) trm cells (cd103(+)/cd69(+)) in the lungs and airways. intranasally transferring cells from the airways of previou ...201728537249
risk of respiratory syncytial virus hospitalization in the first and second years of life in pediatric patients with congenital heart disease. 201728536747
macrophages produce il-33 by activating mapk signaling pathway during rsv infection.it has been reported that rsv infection can enhance il-33 production in lung macrophages. however, little is known about specific signaling pathways for activation of macrophages during rsv infection. in the present study, by using real-time rt-pcr as well as western blot assay, it became clear that rsv infection can enhance not only the expression of mrnas for mapk molecules (including p38, jnk1/2, and erk1/2), but also the levels of mapk proteins in lung macrophages as well as raw264.7 cells. ...201728531812
defining the vaccination window for respiratory syncytial virus (rsv) using age-seroprevalence data for children in kilifi, kenya.respiratory syncytial virus (rsv) is an important cause of lower respiratory tract disease in early life and a target for vaccine prevention. data on the age-prevalence of rsv specific antibodies will inform on optimizing vaccine delivery.201728531224
a single intranasal administration of virus-like particle vaccine induces an efficient protection for mice against human respiratory syncytial virus.human respiratory syncytial virus (rsv) is an important pediatric pathogen causing acute viral respiratory disease in infants and young children. however, no licensed vaccines are currently available. virus-like particles (vlps) may bring new hope to producing rsv vlp vaccine with high immunogenicity and safety. here, we constructed the recombinants of matrix protein (m) and fusion glycoprotein (f) of rsv, respectively into a replication-deficient first-generation adenoviral vector (fgad), which ...201728529001
frequency of respiratory viruses among patients admitted to 26 intensive care units in seven consecutive winter-spring seasons (2009-2016) in northern italy.the role of respiratory viruses in the etiology of community-acquired pneumonia (cap) is still debated. the advent of molecular assays has improved the identification of viruses in patients with cap and according to published studies, viruses account for 11-55% of adult cap cases.201728527970
unravelling respiratory syncytial virus outbreaks in buenos aires, argentina: molecular basis of the spatio-temporal transmission.respiratory syncytial virus (rsv) is the main viral cause of hospitalization due to acute lower respiratory tract infections in infants worldwide. several vaccines against rsv are under research and development, which are about to be approved. we evaluated transmission patterns in different settings to determine age-specific vaccination targets from a viral perspective. we sequenced the g glycoprotein's ectodomain of a constant clinical sampling between two epidemic outbreaks in a limited geogra ...201728527341
infection-mediated asthma: etiology, mechanisms and treatment options, with focus on chlamydia pneumoniae and macrolides.asthma is a chronic respiratory disease characterized by reversible airway obstruction and airway hyperresponsiveness to non-specific bronchoconstriction agonists as the primary underlying pathophysiology. the worldwide incidence of asthma has increased dramatically in the last 40 years. according to world health organization (who) estimates, over 300 million children and adults worldwide currently suffer from this incurable disease and 255,000 die from the disease each year. it is now well acce ...201728526018
passive and active immunization against respiratory syncytial virus for the young and old.respiratory syncytial virus (rsv) is the leading cause of lower respiratory tract infections in infants worldwide and also causes significant disease in the elderly. despite 60 years of rsv research and vaccine development, there is only one approved medicine to prevent rsv infections. palivizumab, a monoclonal antibody (mab) against the rsv fusion (f) protein, is indicated for preterm infants and children at high-risk for rsv infections. it is an active time in rsv vaccine and mab development w ...201728525961
vaccine development for respiratory syncytial virus.respiratory syncytial virus (rsv) is an important and ubiquitous respiratory pathogen for which no vaccine is available notwithstanding more than 50 years of effort. it causes the most severe disease at the extremes of age and in settings of immunodeficiency. although rsv is susceptible to neutralizing antibody, it has evolved multiple mechanisms of immune evasion allowing it to repeatedly infect people despite relatively little genetic diversity. recent breakthroughs in determining the structur ...201728525878
unexpected infection spikes in a model of respiratory syncytial virus vaccination.respiratory syncytial virus (rsv) is an acute respiratory infection that infects millions of children and infants worldwide. recent research has shown promise for the development of a vaccine, with a range of vaccine types now in clinical trials or preclinical development. we extend an existing mathematical model with seasonal transmission to include vaccination. we model vaccination both as a continuous process, applying the vaccine during pregnancy, and as a discrete one, using impulsive diffe ...201728524109
rapid tests for influenza, respiratory syncytial virus, and other respiratory viruses: a systematic review and meta-analysis.rapid diagnosis of respiratory virus infections contributes to patient care. this systematic review evaluates the diagnostic accuracy of rapid tests for the detection of respiratory viruses. we searched medline and embase for studies evaluating these tests against pcr as reference standard. 179 studies were included of which 134 evaluated rapid tests for influenza viruses, 32 for rsv, and 13 for other respiratory viruses. we used the bivariate random effects model for quantitative meta-analysis ...201728520858
changing diagnosis coding routines may confound the results of longitudinal childhood pneumonia studies.this swedish study compared the discharge diagnosis codes used for children up to the age of five hospitalised for acute lower respiratory tract infections before and after the introduction of the pneumococcal conjugate vaccine in 2007.201728510985
α-asarone suppresses the proliferation and migration of asmcs through targeting the lncrna-pvt1/mir-203a/e2f3 signal pathway in rsv-infected rats.asthma is a chronic inflammatory pulmonary disease and respiratory syncytial virus (rsv) infection is a common cause of lower respiratory tract illness in infants and young children. α-asarone presents many pharmacological effects and has been demonstrated to be useful in treating asthma. however, the functional mechanism of α-asarone in rsv-infected asthma has not been investigated. long non-coding rnas (lncrnas) have been reported to play critical roles in many biological processes. although m ...201728510638
real-life comparison of three general paediatric wards showed similar outcomes for children with bronchiolitis despite different treatment regimens.this study evaluated the effectiveness of three different treatments for bronchiolitis in a tertiary paediatric facility.201728510350
palivizumab prophylaxis in infants with cystic fibrosis does not delay first isolation of pseudomonas aeruginosa or staphylococcus aureus.respiratory syncytial virus (rsv) infections may worsen cystic fibrosis (cf) lung disease and favor pseudomonas aeruginosa (pa) or staphylococcus aureus (sa) acquisition, which is of particular importance in the youngest patients. we aimed to determine the effectiveness of pvz on microbiological outcomes in young children with cf. we conducted a retrospective case-control study to compare these outcomes in children who systematically received pvz (pvz+; n = 40) or not (pvz-; n = 140). one case w ...201728508992
bac-based recovery of recombinant respiratory syncytial virus (rsv).respiratory syncytial virus (rsv) is an enveloped, nonsegmented negative-strand rna virus, which causes lower respiratory tract infections and is a leading cause of mortality in young infants. there is no available rsv vaccine and currently administered prophylactic antibodies are limited to high-risk populations. current efforts to develop vaccines include development of live-attenuated rsv candidates. we describe here methods for preparation and recovery of recombinant rsv using an efficient b ...201728508217
heliox delivered by high flow nasal cannula improves oxygenation in infants with respiratory syncytial virus acute bronchiolitis.the objective of this study is to evaluate the hypothesis that use of heliox would result in improvement of gas exchange when used with high flow nasal cannula in infants with rsv acute bronchiolitis.201728506664
grape seed proanthocyanidin inhibits mucin synthesis and viral replication by suppression of ap-1 and nf-κb via p38 mapks/jnk signaling pathways in respiratory syncytial virus-infected a549 cells.airway epithelial cells are often infected by respiratory syncytial virus (rsv), one of the most common causes of asthma, bronchiolitis, chronic obstructive pulmonary disease, and pneumonia. during the infection process, excessive mucins instigate airway inflammation. however, the mechanism underlying rsv-induced airway hyper-responsiveness and inflammation is poorly understood. furthermore, no reliable vaccines or drugs for antiviral therapy are available. in this study, the effect of the natur ...201728502165
ongoing developments in rsv prophylaxis: a clinician's analysis.respiratory syncytial virus (rsv) is the most common respiratory pathogen in infants and young children worldwide. lower respiratory tract infection due to rsv is one of the most common causes of hospitalization for infants, especially those born premature or with chronic lung or heart disease. furthermore, rsv infection is an important cause of morbidity in adults, particularly in the elderly and immunocompromised individuals. the acute phase of this infection is often followed by episodes of w ...201728500974
respiratory syncytial virus infection accelerates lung fibrosis through the unfolded protein response in a bleomycin-induced pulmonary fibrosis animal model.emerging evidence has demonstrated that endoplasmic reticulum stress (er) is involved in the pathogenesis of idiopathic pulmonary fibrosis, however, the underlying mechanism remains unclear. viral infection often triggers a hyperinflammatory response by an expansion of the er. the present study was designed to observe the role of respiratory syncytial virus infection (rsv)‑induced er stress on lung fibrosis. in order to determine the role of er stress on the onset and progression of pulmonary fi ...201728498407
comparison of interferon and bovine herpesvirus-1-specific iga levels in nasal secretions of dairy cattle administered an intranasal modified live viral vaccine prior to calving or on the day of calving.thirty-two holstein cows were allocated to receive intranasal vaccination with modified live bovine herpesvirus-1 (bhv-1), bovine respiratory syncytial virus (brsv) and parainfluenza type 3 virus (pi3v) vaccine either two weeks prior to their projected calving date, or within 24h after calving. nasal secretions were collected twice at a 12-h interval on the day prior to vaccination (day 0) and at 2, 4, 7, 10 and 14days post vaccination to measure interferon (ifn) alpha, ifn-beta, ifn-gamma, and ...201728494927
complete heart block complicating the acute phase of respiratory syncytial virus bronchiolitis.respiratory syncytial virus is the most common pathogen causing lower respiratory tract infection in infants. in recent years, the importance of extrapulmonary complications and longterm sequelae including those involving the cardiovascular system has become apparent. we report on a 10 month old infant with respiratory syncytial virus bronchiolitis, the acute phase of which was complicated by irreversible complete heart block, which was managed conservatively.201728486756
comparison of first year of life acute otitis media admissions before and after the 13-valent pneumococcal conjugate vaccine.acute otitis media (aom) is a common childhood infection, which is usually managed in the outpatient setting. yet, the more severe cases are referred for inpatient treatment. we hypothesized that pneumococcal conjugate vaccines (pcvs), administered during the first year of life, would decrease aom admissions rate in this age group. we studied the characteristics of infants admitted with aom and acute mastoiditis (am) in the pcv13 era, routinely given from november 2010 to all infants.201728483246
ifnγ influences epithelial anti-viral responses via histone methylation of the rig-i promoter.the asthmatic lung is prone to respiratory viral infections that exacerbate the symptoms of the underlying disease. recent work has suggested that a deficient th1 response in early life may lead to these aberrant anti-viral responses. we investigated whether the inflammatory environment of the airway epithelium could modulate anti-viral gene expression via epigenetic mechanisms, in order to study the development of a long-term dysregulation of innate responses, which are a hallmark of asthma. we ...201728481620
acute viral bronchiolitis in infants (review).bronchiolitis is a common condition in children less than 2 years of age and is a leading cause of infant hospitalization. acute bronchiolitis is characterized by acute wheezing in infants or children and is associated with signs or symptoms of respiratory infection; the most common etiologic agent is respiratory syncytial virus. there is a lack of consensus regarding the clinical definition of acute viral bronchiolitis in children and hence the management varies across the globe. usually it doe ...201728480848
hospitalizations for respiratory syncytial virus among adults in the united states, 1997-2012.respiratory syncytial virus (rsv) is an established cause of serious lower respiratory disease in children, but the burden in adults is less well studied.201728480262
host dihydrofolate reductase (dhfr)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus.we have identified a series of 1-aryl-4,6-diamino-1,2-dihydrotriazines, structurally related to the antimalarial drug cycloguanil, as new inhibitors of influenza a and b virus and respiratory syncytial virus (rsv) via targeting of the host dihydrofolate reductase (dhfr) enzyme. most analogues proved active against influenza b virus in the low micromolar range, and the best compounds (11, 13, 14 and 16) even reached the sub-micromolar potency of zanamivir (ec50 = 0.060 μm), and markedly exceeded ...201728477572
a multi-laboratory study of diverse rsv neutralization assays indicates feasibility for harmonization with an international standard.a current barrier to the standardized evaluation of respiratory syncytial virus (rsv) vaccine candidates is the wide variety of virus neutralization assay formats currently in use for assessing immunogenicity. assay formats vary widely in labor intensiveness, duration, and sample throughput. furthermore, the cell lines and virus strains used are not consistent among formats. the purpose of this multi-laboratory study was to assess the variability across a diverse array of assay formats that quan ...201728476625
early life rhinovirus wheezing, allergic sensitization, and asthma risk at adolescence.early life rhinovirus (rv) wheezing illnesses and aeroallergen sensitization increase the risk of asthma at school age. whether these remain risk factors for the persistence of asthma out to adolescence is not established.201727312820
mortality due to respiratory syncytial virus. burden and risk factors.respiratory syncytial virus (rsv) is the most frequent cause of hospitalization and an important cause of death in infants in the developing world. the relative contribution of social, biologic, and clinical risk factors to rsv mortality in low-income regions is unclear.201727331632
nanobodies® as inhaled biotherapeutics for lung diseases.local pulmonary delivery of biotherapeutics may offer advantages for the treatment of lung diseases. delivery of the therapeutic entity directly to the lung has the potential for a rapid onset of action, reduced systemic exposure and the need for a lower dose, as well as needleless administration. however, formulation of a protein for inhaled delivery is challenging and requires proteins with favorable biophysical properties suitable to withstand the forces associated with formulation, delivery, ...201727373507
influenza-like illness-related emergency department visits: christmas and new year holiday peaks and relationships with laboratory-confirmed respiratory virus detections, edmonton, alberta, 2004-2014.emergency department (ed) visit volumes can be especially high during the christmas-new year holidays, a period occurring during the influenza season in canada.201727442911
differential lower airway dendritic cell patterns may reveal distinct endotypes of rsv bronchiolitis.the pathogenesis of respiratory syncytial virus (rsv) bronchiolitis in infants remains poorly understood. mouse models implicate pulmonary t cells in the development of rsv disease. t cell responses are initiated by dendritic cells (dcs), which accumulate in lungs of rsv-infected mice. in infants with rsv bronchiolitis, previous reports have shown that dcs are mobilised to the nasal mucosa, but data on lower airway dc responses are lacking.201727531529
cohort study of severe bronchiolitis during infancy and risk of asthma by age 5 years.severe bronchiolitis (ie, bronchiolitis requiring hospital admission) is thought to markedly increase asthma risk, with 30%-50% developing asthma by age 5 years. to date, studies of this association are small, and most are from outside the united states.201727523277
patterns in bacterial- and viral-induced immunosuppression and secondary infections in the icu.immunosuppression renders the host increased susceptible for secondary infections. it is becoming increasingly clear that not only bacterial sepsis, but also respiratory viruses with both severe and mild disease courses such as influenza, respiratory syncytial virus, and the human rhinovirus may induce immunosuppression. in this review, the current knowledge on (mechanisms of) bacterial- and virus-induced immunosuppression and the accompanying susceptibility toward various secondary infections i ...201727517143
development and validation of a score to predict mortality in children undergoing extracorporeal membrane oxygenation for respiratory failure: pediatric pulmonary rescue with extracorporeal membrane oxygenation prediction score.our objective was to develop and validate a prognostic score for predicting mortality at the time of extracorporeal membrane oxygenation initiation for children with respiratory failure. preextracorporeal membrane oxygenation mortality prediction is important for determining center-specific risk-adjusted outcomes and counseling families.201727548818
analytical characterization of an oil-in-water adjuvant emulsion.adjuvants are typically used in subunit vaccine formulations to enhance immune responses elicited by individual antigens. physical chemical characterization of novel adjuvants is an important step in ensuring their effective use in vaccine formulations. this paper reports application of a panel of quantitative assays developed to analyze and characterize an oil-in-water adjuvant emulsion, which contains glucopyranosyl lipid a (gla) and is a squalene-based emulsion. gla is a fully synthetic analo ...201727628187
rsv n-nanorings fused to palivizumab-targeted neutralizing epitope as a nanoparticle rsv vaccine.respiratory syncytial virus (rsv) is the leading cause of acute respiratory infections in children, yet no vaccine is available. the sole licensed preventive treatment against rsv is composed of a monoclonal neutralizing antibody (palivizumab), which targets a conformational epitope located on the fusion protein (f). palivizumab reduces the burden of bronchiolitis but does not prevent infection. thus, the development of rsv vaccines remains a priority. we previously evaluated nanorings formed by ...201727553073
in utero alcohol effects on foetal, neonatal and childhood lung disease.maternal alcohol use during pregnancy exposes both premature and term newborns to the toxicity of alcohol and its metabolites. foetal alcohol exposure adversely effects the lung. in contrast to the adult "alcoholic lung" phenotype, an inability to identify the newborn exposed to alcohol in utero has limited our understanding of its effect on adverse pulmonary outcomes. this paper will review advances in biomarker development of in utero alcohol exposure. we will highlight the current understandi ...201727613232
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