scholarly journals CHD and respiratory syncytial virus: global expert exchange recommendations

2017 ◽  
Vol 27 (8) ◽  
pp. 1504-1521 ◽  
Author(s):  
Robert M. R. Tulloh ◽  
Constancio Medrano-Lopez ◽  
Paul A. Checchia ◽  
Claudia Stapper ◽  
Naokata Sumitomo ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Heart Transplant ◽  
Severe Disease ◽  
Risk Groups ◽  
Steering Committee ◽  
Current Evidence ◽  
Evidence Based ◽  
Delphi Consensus ◽  
Tropical Regions ◽  
Syncytial Virus

AbstractBackgroundPalivizumab 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.MethodsAn international steering committee of clinicians with expertise in paediatric heart disease identified key questions concerning palivizumab administration; in collaboration with an additional international expert faculty, evidence-based recommendations were formulated using a quasi-Delphi consensus methodology.ResultsPalivizumab prophylaxis was recommended for children with the following conditions: <2 years with unoperated haemodynamically significant CHD, who are cyanotic, who have pulmonary hypertension, or symptomatic airway abnormalities; <1 year with cardiomyopathies requiring treatment; in the 1st year of life with surgically operated CHD with haemodynamically significant residual problems or aged 1–2 years up to 6 months postoperatively; and on heart transplant waiting lists or in their 1st year after heart transplant. Unanimous consensus was not reached for use of immunoprophylaxis in children with asymptomatic CHD and other co-morbid factors such as arrhythmias, Down syndrome, or immunodeficiency, or during a nosocomial outbreak. Challenges to effective immunoprophylaxis included the following: multidisciplinary variations in identifying candidates with CHD and prophylaxis compliance; limited awareness of severe disease risks/burden; and limited knowledge of respiratory syncytial virus seasonal patterns in subtropical/tropical regions.ConclusionEvidence-based immunoprophylaxis recommendations were formulated for subgroups of children with CHD, but more data are needed to guide use in tropical/subtropical countries and in children with certain co-morbidities.

scholarly journals Respiratory syncytial virus: diagnosis, prevention and management

2019 ◽  
Vol 6 ◽  
pp. 204993611986579 ◽  
Author(s):  
Rachael Barr ◽  
Christopher A. Green ◽  
Charles J. Sande ◽  
Simon B. Drysdale
Keyword(s):  
United Kingdom ◽  
Respiratory Syncytial Virus ◽  
Severe Disease ◽  
Severe Infection ◽  
Risk Groups ◽  
Control Measures ◽  
Respiratory Morbidity ◽  
The United Kingdom ◽  
Rsv Infection ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is responsible for a large burden of disease globally and can present as a variety of clinical syndromes in children of all ages. Bronchiolitis in infants under 1 year of age is the most common clinical presentation hospitalizing 24.2 per 1000 infants each year in the United Kingdom. RSV has been shown to account for 22% of all episodes of acute lower respiratory tract infection in children globally. RSV hospitalization, that is, RSV severe disease, has also been associated with subsequent chronic respiratory morbidity. Routine viral testing in all children is not currently recommended by the United Kingdom National Institute for Health and Care Excellence (NICE) or the American Academy of Pediatrics (AAP) guidance and management is largely supportive. There is some evidence for the use of ribavirin in severely immunocompromised children. Emphasis is placed on prevention of RSV infection through infection control measures both in hospital and in the community, and the use of the RSV-specific monoclonal antibody, palivizumab, for certain high-risk groups of infants. New RSV antivirals and vaccines are currently in development. Ongoing work is needed to improve the prevention of RSV infection, not only because of the acute morbidity and mortality, but also to reduce the associated chronic respiratory morbidity after severe infection.

scholarly journals Respiratory syncytial virus and airway microbiota -- A complex interplay and its reflection on morbidity

2020 ◽  
Author(s):  
Giovanni Rossi ◽  
Stefania Ballarini ◽  
Michela Silvestri ◽  
Oliviero Sacco ◽  
Andrew Colin
Keyword(s):  
Respiratory Syncytial Virus ◽  
Disease Severity ◽  
Respiratory Infections ◽  
Pediatric Population ◽  
Bacterial Species ◽  
Severe Disease ◽  
Microbial Community Composition ◽  
Positive Role ◽  
Syncytial Virus ◽  
Tract Infections

The immunopathology of respiratory syncytial virus (RSV) infection, the most common cause of lower respiratory tract infections (LRTI) in the pediatric population, with severe disease being the exception. The variability of the clinical presentation is incompletely explained by host, viral and environmental factors but, in infants and young children, disease severity is certainly linked to the physiological immune immaturity. There is evidence that the maturation of the host immune response is, at least in part, promoted by the composition of the nasopharyngeal microbiome that, modulating excessive inflammation, can counteract the predisposition to develop viral respiratory infections and lower the risk of disease severity. However, interaction between the nasopharyngeal microbiota and respiratory viruses can be bidirectional. Microbial dysbiosis can drive disease pathogenesis but may also represents a reflection of the disease-induced alterations of the local milieu. Moreover, viruses like RSV, can also increase the virulence of potential pathogens in nasopharynx, which is a main reservoir of bacteria, and therefore promote their spread to the lower airways causing superinfection. Negative changes in microbial community composition in early life may constitute a heightened risk towards severe RSV respiratory infection and bacterial superinfection, whilst specific groups of microorganisms can be associated with protection. A better understanding into the potential negative and positive role of the different nasopharyngeal bacterial species in disease prevention as well as into the possible benefits of microbiome therapeutic manipulation, may improve patient outcomes.

scholarly journals Fcγ Receptor IIa (FCGR2A) Polymorphism Is Associated With Severe Respiratory Syncytial Virus Disease in Argentinian Infants

2020 ◽  
Vol 10 ◽  
Author(s):  
María Pía Holgado ◽  
Silvina Raiden ◽  
Inés Sananez ◽  
Vanesa Seery ◽  
Leonardo De Lillo ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Virus Disease ◽  
Severe Disease ◽  
Critical Role ◽  
Fcγ Receptor ◽  
Factors Associated ◽  
Severe Group ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
The Relationship

BackgroundMost patients with respiratory syncytial virus (RSV) infection requiring hospitalization have no risk factors for severe disease. Genetic variation in the receptor for the Fc portion of IgG (FcγR) determines their affinity for IgG subclasses driving innate and adaptive antiviral immunity. We investigated the relationship between FcγRIIa-H131R polymorphism and RSV disease.MethodsBlood samples were collected from 182 infants ≤24-month-old (50 uninfected, 114 RSV-infected with moderate course and 18 suffering severe disease). FcγRIIa-H131R SNP genotypic frequencies (HH, HR, RR) and anti-RSV IgG1, IgG2 and IgG3 levels were studied.ResultsGenotypic frequencies for FcγRIIa-H131R SNP were comparable between uninfected and RSV-infected infants. In contrast, we found a significant higher frequency of HH genotype in severe RSV-infected children compared to moderate patients. Among severe group, HH infants presented more factors associated to severity than HR or RR patients did. Furthermore, compared to moderate RSV-infected infants, severe patients showed higher levels of anti-RSV IgG1 and IgG3.ConclusionsWe found an association between an FcγRIIa (H131) polymorphism and severe RSV disease, which points towards a critical role for interactions between FcγRs and immune complexes in RSV pathogenesis. This genetic factor could also predict the worse outcome and identify those infants at risk during hospitalization.

scholarly journals Interferon-Induced Protein 44 and Interferon-Induced Protein 44-Like Restrict Replication of Respiratory Syncytial Virus

2020 ◽  
Vol 94 (18) ◽  
Author(s):  
D. C. Busse ◽  
D. Habgood-Coote ◽  
S. Clare ◽  
C. Brandt ◽  
I. Bassano ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Mouse Model ◽  
Severe Disease ◽  
Early Time ◽  
Airway Epithelial Cells ◽  
Knockout Mouse Model ◽  
Antiviral Genes ◽  
Wide Range ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACT Cellular intrinsic immunity, mediated by the expression of an array of interferon-stimulated antiviral genes, is a vital part of host defense. We have previously used a bioinformatic screen to identify two interferon-stimulated genes (ISG) with poorly characterized function, interferon-induced protein 44 (IFI44) and interferon-induced protein 44-like (IFI44L), as potentially being important in respiratory syncytial virus (RSV) infection. Using overexpression systems, CRISPR-Cas9-mediated knockout, and a knockout mouse model, we investigated the antiviral capability of these genes in the control of RSV replication. Overexpression of IFI44 or IFI44L was sufficient to restrict RSV infection at an early time postinfection. Knocking out these genes in mammalian airway epithelial cells increased levels of infection. Both genes express antiproliferative factors that have no effect on RSV attachment but reduce RSV replication in a minigenome assay. The loss of Ifi44 was associated with a more severe infection phenotype in a mouse model of infection. These studies demonstrate a function for IFI44 and IFI44L in controlling RSV infection. IMPORTANCE RSV infects all children under 2 years of age, but only a subset of children get severe disease. We hypothesize that susceptibility to severe RSV necessitating hospitalization in children without predefined risk factors is, in part, mediated at the antiviral gene level. However, there is a large array of antiviral genes, particularly in the ISG family, the mechanism of which is poorly understood. Having previously identified IFI44 and IFI44L as possible genes of interest in a bioinformatic screen, we dissected the function of these two genes in the control of RSV. Through a range of overexpression and knockout studies, we show that the genes are antiviral and antiproliferative. This study is important because IFI44 and IFI44L are upregulated after a wide range of viral infections, and IFI44L can serve as a diagnostic biomarker of viral infection.

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.

scholarly journals Comparing Human Metapneumovirus and Respiratory Syncytial Virus: Viral Co-Detections, Genotypes and Risk Factors for Severe Disease

PLoS ONE ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. e0170200 ◽  
Author(s):  
Nina Moe ◽  
Sidsel Krokstad ◽  
Inger Heimdal Stenseng ◽  
Andreas Christensen ◽  
Lars Høsøien Skanke ◽  
...  
Keyword(s):  
Risk Factors ◽  
Respiratory Syncytial Virus ◽  
Severe Disease ◽  
Human Metapneumovirus ◽  
Syncytial Virus

scholarly journals Agreement between ELISA and plaque reduction neutralisation assay in Detection of respiratory syncytial virus specific antibodies in a birth Cohort from Kilifi, coastal Kenya.

2019 ◽  
Vol 4 ◽  
pp. 33
Author(s):  
Joyce U. Nyiro ◽  
Patience K. Kiyuka ◽  
Martin N. Mutunga ◽  
Charles J. Sande ◽  
Patrick K. Munywoki ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Birth Cohort ◽  
Prediction Interval ◽  
Pearson Correlation ◽  
Severe Disease ◽  
High Positive Correlation ◽  
Specific Antibodies ◽  
Positive Correlation ◽  
True Value ◽  
Syncytial Virus

Background:Severe disease associated with respiratory syncytial virus (RSV) infection occurs predominantly among infants under 6 months of age. Vaccines for prevention are in clinical development. Assessment of the vaccine effectiveness in large epidemiological studies requires serological assays which are rapid, economical and standardised between laboratories. The objective of this study was to assess the agreement between two enzyme linked immunosorbent assays (ELISA) and the plaque reduction neutralisation test (PRNT) in quantifying RSV specific antibodies.Methods:Archived sera from 99 participants of the Kilifi Birth Cohort (KBC) study (conducted 2002-2007) were screened for RSV antibodies using 3 methods: ELISA using crude RSV lysate as antigen, a commercial RSV immunoglobulin G (IgG) ELISA kit from IBL International GmbH, and PRNT. Pearson correlation, Bland-Altman plots and regression methods were used in analysis.Results:There was high positive correlation between the IBL RSV IgG ELISA and PRNT antibodies (Pearson r=0.75), and moderate positive correlation between the crude RSV lysate IgG ELISA and PRNT antibodies (r= 0.61). Crude RSV lysate IgG ELISA showed a wider 95% limit of agreement (-1.866, 6.157) with PRNT compared to the IBL RSV IgG ELISA (1.392, 7.595). Mean PRNT titres were estimated within a width of 4.8 log2PRNT and 5.6 log2PRNT at 95% prediction interval by IBL RSV IgG and crude RSV lysate IgG ELISA, respectively.Conclusion:Although, the IBL RSV IgG ELISA is observed to provide a reasonable correlate for PRNT assay in detecting RSV specific antibodies, it does not provide an accurate prediction for neutralizing antibody levels. An RSV neutralising antibody level is likely to fall within 2.4 fold higher and 2.4 fold lower than the true value if IBL RSV IgG ELISA is used to replace PRNT assay. The utility of an ELISA assay in vaccine studies should be assessed independent of the PRNT method.

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