scholarly journals 2592. Lung Function as an Indicator of Vaccine Enhanced RSV Disease in Cotton Rats

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S901-S901
Author(s):  
Crystal Jones ◽  
Xiaolan Shen ◽  
Xiaoli Ping ◽  
Catherine Gallagher ◽  
Jeremy Beech ◽  
...  
Keyword(s):  
Lung Function ◽  
Vaccine Safety ◽  
Histopathological Analysis ◽  
Impaired Lung Function ◽  
Rsv Infection ◽  
Cotton Rats ◽  
Respiratory System Resistance ◽  
Syncytial Virus ◽  
Tract Infections ◽  
Infants And Young Children

Abstract Background Respiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract infections in infants and young children. Seronegative children previously vaccinated with formalin-inactivated live RSV formulated with aluminum (FIRSV) developed vaccine enhanced RSV disease (VERD), which is characterized by fever, wheezing, bronchopneumonia, and airway hyperresponsiveness (AHR). We investigated whether impaired lung function can serve as a marker for VERD in an animal model of RSV infection. Methods Uninfected and RSV-infected cotton rats intranasally challenged with 106 pfu of RSV A2 were anesthetized with pentobarbital and tracheostomized. A cannula was placed in the trachea and animals were connected to flexiVent™ (Scireq), which is a computer-controlled piston ventilator that analyzes pressure and volume signals in response to an oscillatory waveform applied at the animal’s airways. Vecuronium bromide was administered to ventilated animals to prevent independent breathing. To measure AHR, animals were exposed to increasing doses of inhaled methacholine, and methacholine-induced bronchoconstriction was measured. Results Two independent studies showed that RSV-infected cotton rats (n = 4) exhibited increased total respiratory system resistance (Rrs) and airway resistance (Rn) following methacholine challenge on days 4 and 6 post-infection compared with uninfected cotton rats (n = 4). Conclusion RSV-induced impairment in lung function can be exploited for the development of a more robust and objective method for assessing vaccine safety in a cotton rat model of respiratory disease compared with traditional histopathological analysis. Disclosures All authors: No reported disclosures.

scholarly journals Seasonality and geographical spread of respiratory syncytial virus epidemics in 15 European countries, 2010 to 2016

2018 ◽  
Vol 23 (5) ◽  
Author(s):  
Eeva K Broberg ◽  
Matti Waris ◽  
Kari Johansen ◽  
René Snacken ◽  
Pasi Penttinen ◽  
...  
Keyword(s):  
Primary Care ◽  
Respiratory Syncytial Virus ◽  
Surveillance Systems ◽  
European Economic Area ◽  
The European Union ◽  
Geographical Spread ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections ◽  
Infants And Young Children

Respiratory syncytial virus (RSV) is considered the most common pathogen causing severe lower respiratory tract infections among infants and young children. We describe the seasonality and geographical spread of RSV infection in 15 countries of the European Union and European Economic Area. We performed a retrospective descriptive study of weekly laboratory-confirmed RSV detections between weeks 40/2010 and 20/2016, in patients investigated for influenza-like illness, acute respiratory infection or following the clinician’s judgment. Six countries reported 4,230 sentinel RSV laboratory diagnoses from primary care and 14 countries reported 156,188 non-sentinel laboratory diagnoses from primary care or hospitals. The median length of the RSV season based on sentinel and non-sentinel surveillance was 16 (range: 9–24) and 18 (range: 8–24) weeks, respectively. The median peak weeks for sentinel and non-sentinel detections were week 4 (range: 48 to 11) and week 4.5 (range: 49 to 17), respectively. RSV detections peaked later (r = 0.56; p = 0.0360) and seasons lasted longer with increasing latitude (r = 0.57; p = 0.0329). Our data demonstrated regular seasonality with moderate correlation between timing of the epidemic and increasing latitude of the country. This study supports the use of RSV diagnostics within influenza or other surveillance systems to monitor RSV seasonality and geographical spread.

scholarly journals Therapeutic Antibodies for the Treatment of Respiratory Tract Infections—Current Overview and Perspectives

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 151
Author(s):  
Alexie Mayor ◽  
Adélaïde Chesnay ◽  
Guillaume Desoubeaux ◽  
David Ternant ◽  
Nathalie Heuzé-Vourc’h ◽  
...  
Keyword(s):  
Respiratory Tract Infections ◽  
Inflammatory Diseases ◽  
Treatment Strategies ◽  
Candida Spp ◽  
Medical Needs ◽  
Life Threatening ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections ◽  
Unmet Medical Needs

Respiratorytract infections (RTIs) are frequent and life-threatening diseases, accounting for several millions of deaths worldwide. RTIs implicate microorganisms, including viruses (influenza virus, coronavirus, respiratory syncytial virus (RSV)), bacteria (Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus aureus and Bacillus anthracis) and fungi (Pneumocystis spp., Aspergillus spp. and very occasionally Candida spp.). The emergence of new pathogens, like the coronavirus SARS-CoV-2, and the substantial increase in drug resistance have highlighted the critical necessity to develop novel anti-infective molecules. In this context, antibodies (Abs) are becoming increasingly important in respiratory medicine and may fulfill the unmet medical needs of RTIs. However, development of Abs for treating infectious diseases is less advanced than for cancer and inflammatory diseases. Currently, only three Abs have been marketed for RTIs, namely, against pulmonary anthrax and RSV infection, while several clinical and preclinical studies are in progress. This article gives an overview of the advances in the use of Abs for the treatment of RTIs, based on the analysis of clinical studies in this field. It describes the Ab structure, function and pharmacokinetics, and discusses the opportunities offered by the various Ab formats, Ab engineering and co-treatment strategies. Including the most recent literature, it finally highlights the strengths, weaknesses and likely future trends of a novel anti-RTI Ab armamentarium.

Reappraisal of respiratory syncytial virus as an aetiology of severe acute lower respiratory tract infections in children younger than 5 years in Nigeria

2019 ◽  
Vol 113 (8) ◽  
pp. 446-452
Author(s):  
Damilola M Oladele ◽  
Dimeji P Oladele ◽  
Rasheedat M Ibraheem ◽  
Mohammed B Abdulkadir ◽  
Rasaki Adewole Raheem ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Preventive Strategy ◽  
Lower Respiratory Tract Infections ◽  
Cross Sectional ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections

Abstract Background Acute lower respiratory tract infections (ALRIs) especially severe ALRIs, constitute a global high burden of morbidity and mortality in children <5 y of age and respiratory syncytial virus (RSV) has been documented to a play a major aetiological role. However, Nigerian reports on severe childhood RSV ALRIs are rare and most reports are old. With recent advances in RSV preventive strategy, arises the need for a recent appraisal of RSV infection in children with severe ALRI. The current study thus set out to determine the prevalence of RSV infection among hospitalized children <5 y of age and describe the related social determinants. Methods We performed a descriptive cross-sectional study conducted over 1 y of 120 children, ages 2–59 months, diagnosed with ALRI. Relevant data were obtained and an antigen detection assay was used for viral studies. Results The prevalence of RSV infection was 34.2% and its peak was in the rainy months. The proportion of infants in the RSV-positive group was significantly higher than that in the RSV-negative group (82.9% vs 54.4%; p=0.002). These findings were largely consistent with those of earlier reports. Conclusions RSV has remained a common cause of severe ALRI in infants, especially during the rainy months in Nigeria. It is thus suggested that more effort be focused towards implementing the current global recommendations for the prevention of RSV-associated LRI, particularly in infants.

scholarly journals Chemokine regulation of inflammation during respiratory syncytial virus infection

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1837 ◽  
Author(s):  
Rinat Nuriev ◽  
Cecilia Johansson
Keyword(s):  
Respiratory Syncytial Virus ◽  
The Elderly ◽  
Infection Process ◽  
Viral Control ◽  
Small Proteins ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections ◽  
Developed World ◽  
Immune Detection

Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infections especially in infants, immunocompromised individuals and the elderly and is the most common cause of infant hospitalisation in the developed world. The immune responses against RSV are crucial for viral control and clearance but, if dysregulated, can also result in immunopathology and impaired gas exchange. Lung immunity to RSV and other respiratory viruses begins with the recruitment of immune cells from the bloodstream into the lungs. This inflammatory process is controlled largely by chemokines, which are small proteins that are produced in response to innate immune detection of the virus or the infection process. These chemokines serve as chemoattractants for granulocytes, monocytes, lymphocytes and other leukocytes. In this review, we highlight recent advances in the field of RSV infection and disease, focusing on how chemokines regulate virus-induced inflammation.

scholarly journals Respiratory Syncytial Virus Prophylaxis in Special Populations: Is it Something Worth Considering in Cystic Fibrosis and Immunosuppression?

2011 ◽  
Vol 16 (2) ◽  
pp. 77-86
Author(s):  
William A. Prescott ◽  
David J. Hutchinson
Keyword(s):  
Respiratory Syncytial Virus ◽  
Cost Benefit ◽  
The United States ◽  
Randomized Controlled ◽  
Increased Risk ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
The Cost ◽  
Infant Hospitalization ◽  
Infants And Young Children

ABSTRACT Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of infant hospitalization in the United States. Prophylaxis with palivizumab is effective in reducing RSV hospitalizations in premature infants and in infants or children with chronic lung disease or congenital heart disease. Patients with CF or those who are immunocompromised may be at increased risk for RSV infection–related complications; hence, prophylaxis may prove beneficial to these populations. The extent of palivizumab use in the CF and immunocompromised populations is variable. Palivizumab appears to be safe and may be effective in infants and young children with CF and immunocompromise. However, well-designed, randomized, controlled trials published in peer-reviewed journals are lacking, and its routine use can therefore not be recommended at this time. If used in patients with CF or those who are immunocompromised, RSV prophylaxis should be restricted to peak outbreak months in order to optimize the cost benefit of palivizumab.

scholarly journals Loss of versican and production of hyaluronan in lung epithelial cells are associated with airway inflammation during RSV infection

2020 ◽  
pp. jbc.RA120.016196
Author(s):  
Gerald G. Kellar ◽  
Kaitlyn A. Barrow ◽  
Lucille M. Rich ◽  
Jason S. Debley ◽  
Thomas N. Wight ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Ex Vivo ◽  
Lung Epithelial Cells ◽  
In Vivo Studies ◽  
Critical Feature ◽  
Human Lung Fibroblast ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections

Airway inflammation is a critical feature of lower respiratory tract infections caused by viruses such as respiratory syncytial virus (RSV). A growing body of literature has demonstrated the importance of extracellular matrix (ECM) changes such as the accumulation of hyaluronan (HA) and versican in the subepithelial space in promoting airway inflammation; however, whether these factors contribute to airway inflammation during RSV infection remains unknown. To test the hypothesis that RSV infection promotes inflammation via altered HA and versican production, we studied an ex vivo human bronchial epithelial cell (BEC)/human lung fibroblast (HLF) co-culture model. RSV infection of BEC/HLF co-cultures led to decreased hyaluronidase expression by HLFs, increased accumulation of HA, and enhanced adhesion of U937 cells as would be expected with increased HA. HLF production of versican was not altered following RSV infection; however, BEC production of versican was significantly downregulated following RSV infection. In vivo studies with epithelial-specific versican-deficient mice [SPC-Cre(+) Vcan-/-] demonstrated that RSV infection led to increased HA accumulation compared to control mice which also coincided with decreased hyaluronidase expression in the lung. SPC-Cre(+) Vcan-/- mice demonstrated enhanced recruitment of monocytes and neutrophils in bronchoalveolar lavage fluid and increased neutrophils in the lung compared to SPC-Cre(-) RSV-infected littermates. Taken together, these data demonstrate that altered ECM accumulation of HA occurs following RSV infection and may contribute to airway inflammation. Additionally, loss of epithelial expression of versican promotes airway inflammation during RSV infection further demonstrating that versican’s role in inflammatory regulation is complex and dependent on the microenvironment.

scholarly journals Low Sensitivity of BinaxNOW RSV in Infants

2020 ◽  
Vol 222 (Supplement_7) ◽  
pp. S640-S647 ◽  
Author(s):  
Roy P Zuurbier ◽  
Louis J Bont ◽  
Annefleur C Langedijk ◽  
Mirjam Hamer ◽  
Koos Korsten ◽  
...  
Keyword(s):  
Molecular Diagnosis ◽  
Respiratory Tract Infections ◽  
Point Of Care ◽  
Test Results ◽  
Rapid Antigen Detection Test ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Low Sensitivity ◽  
Tract Infections ◽  
Point Of Care Detection

Abstract Background Respiratory syncytial virus (RSV) is a major cause of hospitalization in infants. Early detection of RSV can optimize clinical management and minimize use of antibiotics. BinaxNOW RSV (BN) is a rapid antigen detection test that is widely used. We aimed to validate the sensitivity of BN in hospitalized and nonhospitalized infants against the gold standard of molecular diagnosis. Methods We evaluated the performance of BN in infants with acute respiratory tract infections with different degrees of disease severity. Diagnostic accuracy of BN test results were compared with molecular diagnosis as reference standard. Results One hundred sixty-two respiratory samples from 148 children from October 2017 to February 2019 were studied. Sixty-six (40.7%) samples tested positive for RSV (30 hospitalizations, 31 medically attended episodes not requiring hospitalization, and 5 nonmedically attended episodes). Five of these samples tested positive with BN, leading to an overall sensitivity of BN of 7.6% (95% confidence interval [CI], 3.3%–16.5%) and a specificity of 100% (95% CI, 96.2%–100%). Sensitivity was low in all subgroups. Conclusions We found a low sensitivity of BN for point-of-care detection of RSV infection. BinaxNOW RSV should be used and interpreted with caution.

scholarly journals Epidemiology of Respiratory Syncytial Virus-Related Hospitalization Over a 5-Year Period in Italy: Evaluation of Seasonality and Age Distribution Before Vaccine Introduction

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 15
Author(s):  
Federica Barbati ◽  
Maria Moriondo ◽  
Laura Pisano ◽  
Elisa Calistri ◽  
Lorenzo Lodi ◽  
...  
Keyword(s):  
Intensive Care ◽  
Respiratory Syncytial Virus ◽  
Age Distribution ◽  
Vaccine Introduction ◽  
Herd Protection ◽  
Infection Risk Factors ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Italian Children ◽  
Tract Infections

Respiratory Syncytial Virus (RSV) is associated with most of the acute viral respiratory tract infections causing hospitalization with a peak during the first months of life. Many clinical trials of RSV vaccine candidates are being carried out. The aim of this study was to obtain epidemiologic information to give suggestions on target populations and prevention strategies before the introduction of new vaccines or monoclonal antibodies. We retrospectively evaluated, over a 5-year period (September 2014–August 2019), a population of hospitalized Italian children aged 0–6 years with a laboratory confirmed diagnosis of RSV infection. Risk factors, seasonality of RSV infection, distribution according to age, cases of coinfections and reinfections and cases needing Intensive Care Unit were evaluated. Hospitalizations due to RSV were 624 in the period under study. The peak was found between November and April, with 80.4% of cases recorded between December and February. 62.5% of cases were found in children under three months of age and 41% in children under 30 days old. The need for intensive care was associated with younger ages, with 70.9% of cases in children below three months of age. Unless the incoming vaccines demonstrate a strong herd protection effect, preventive strategies should be aimed at newborns or at maternal immunization.

scholarly journals A Cross-Study Biomarker Signature of Human Bronchial Epithelial Cells Infected with Respiratory Syncytial Virus

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Luiz Gustavo Gardinassi
Keyword(s):  
Functional Analysis ◽  
Respiratory Syncytial Virus ◽  
Bronchial Epithelial Cell ◽  
Epithelial Cell Line ◽  
Bronchial Epithelial ◽  
Rsv Infection ◽  
Novel Biomarkers ◽  
Syncytial Virus ◽  
Different Strains ◽  
Tract Infections

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 statistical methods and functional analysis together with the large amount of expression data provide opportunities to uncover novel biomarkers of inflammation and infections. In view of those facts publicly available microarray datasets from RSV-infected BEAS-2B cells were analyzed with linear model-based statistics and the platform for functional analysis InnateDB. The results from those analyses argue for the reevaluation of previously reported transcription patterns and biological pathways in BEAS-2B cell lines infected with RSV. Importantly, this study revealed a biosignature constituted by genes such asABCC4,ARMC8,BCLAF1,EZH1,FAM118A,FAM208B,FUS,HSPH1,KAZN,MAP3K2,N6AMT1,PRMT2,S100PBP,SERPINA1,TLK2,ZNF322, andZNF337which should be considered in the development of new molecular diagnosis tools.

scholarly journals Nasopharyngeal gene expression, a novel approach to study the course of respiratory syncytial virus infection

2014 ◽  
Vol 45 (3) ◽  
pp. 718-725 ◽  
Author(s):  
Corné H. van den Kieboom ◽  
Inge M.L. Ahout ◽  
Aldert Zomer ◽  
Kim H. Brand ◽  
Ronald de Groot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Pathogen Detection ◽  
Severe Disease ◽  
Host Gene ◽  
Host Gene Expression ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections

Respiratory syncytial virus (RSV) causes mild infections in the vast majority of children. However, in some cases, it causes severe disease, such as bronchiolitis and pneumonia. Development of severe RSV infection is determined by the host response. Therefore, the main aim of this study was to identify biomarkers associated with severe RSV infection.To identify biomarkers, nasopharyngeal gene expression was profiled by microarray studies, resulting in the selection of five genes: ubiquitin D, tetraspanin 8, mucin 13, β-microseminoprotein and chemokine ligand 7.These genes were validated by real-time quantitative PCR in an independent validation cohort, which confirmed significant differences in gene expression between mildly and severely infected and between recovery and acute patients.Nasopharyngeal aspirate samples are regularly taken when a viral respiratory tract infection is suspected. In this article, we describe a method to discriminate between mild and severe RSV infection based on differential host gene expression. The combination of pathogen detection and host gene expression analysis in nasopharyngeal aspirates will significantly improve the diagnosis and prognosis of respiratory tract infections.

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