Proven Respiratory Syncytial Virus Infection Research Articles

Antibiotics for bronchiolitis in children under two years of age.

Bronchiolitis is a serious, potentially life-threatening respiratory illness commonly affecting babies. It is often caused by respiratory syncytial virus (RSV). Antibiotics are not recommended for bronchiolitis unless there is concern about complications such as secondary bacterial pneumonia or respiratory failure. Nevertheless, they are often used. To evaluate the effectiveness of antibiotics for bronchiolitis in children under two years of age compared to placebo or other interventions. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 6), which includes the Cochrane Acute Respiratory Infection Group's Specialised Register, and the Database of Abstracts of Reviews of Effects, MEDLINE (1966 to June 2014), EMBASE (1990 to June 2014) and Current Contents (2001 to June 2014). Randomised controlled trials (RCTs) comparing antibiotics to placebo in children under two years diagnosed with bronchiolitis, using clinical criteria (including respiratory distress preceded by coryzal symptoms with or without fever). Primary clinical outcomes included time to resolution of signs or symptoms (pulmonary markers included respiratory distress, wheeze, crepitations, oxygen saturation and fever). Secondary outcomes included hospital admissions, length of hospital stay, readmissions, complications or adverse events and radiological findings. Two review authors independently analysed the search results. We included seven studies with a total of 824 participants. The results of these seven included studies were often heterogeneous, which generally precluded meta-analysis, except for deaths, length of supplemental oxygen use and length of hospital admission.In this update, we included two new studies (281 participants), both comparing azithromycin with placebo. They found no significant difference for length of hospital stay, duration of oxygen requirement and readmission. These results were similar to an older study (52 participants) that demonstrated no significant difference comparing ampicillin and placebo for length of illness.One small study (21 participants) with higher risk of bias randomised children with proven RSV infection to clarithromycin or placebo and found a trend towards a reduction in hospital readmission with clarithromycin.The three studies providing adequate data for days of supplementary oxygen showed no difference between antibiotics and placebo (pooled mean difference (MD) (days) -0.20; 95% confidence interval (CI) -0.72 to 0.33). The three studies providing adequate data for length of hospital stay, similarly showed no difference between antibiotics (azithromycin) and placebo (pooled MD (days) -0.58; 95% CI -1.18 to 0.02).Two studies randomised children to intravenous ampicillin, oral erythromycin and control and found no difference for most symptom measures.There were no deaths reported in any of the arms of the seven included studies. No other adverse effects were reported. This review did not find sufficient evidence to support the use of antibiotics for bronchiolitis, although research may be justified to identify a subgroup of patients who may benefit from antibiotics. Further research may be better focused on determining the reasons that clinicians use antibiotics so readily for bronchiolitis, how to reduce their use and how to reduce clinician anxiety about not using antibiotics.

Respiratory syncytial virus hospitalisation and subsequent risk of asthma

Journal of Paediatrics and Child HealthVolume 50, Issue 7 p. 571-571 Heads UpFree Access Respiratory syncytial virus hospitalisation and subsequent risk of asthma First published: 07 July 2014 https://doi.org/10.1111/jpc.12670_4AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat It has been known for a long time that almost all children will have had respiratory syncytial virus (RSV) infection by age 2 years, but only about 40% have a diagnosis of bronchiolitis and the 1% of infants who are hospitalised have an increased subsequent risk of recurrent wheezing or asthma. A meta-analysis of 15 studies of 82 008 babies including 1533 hospitalised for proven RSV infection found the increased risk of later asthma/wheezing was almost fourfold (odds ratio 3.84, 95% confidence interval 3.23–4.58).1 However, the association decreased with age and by 8 years of age, there was no added risk, suggesting the children had ‘grown out’ of their recurrent wheezing. Reference 1Regnier SA, Huels J. Pediatr. Infect. Dis. J. 2013; 32: 820– 826. PubMedWeb of Science®Google Scholar Reviewer: David Isaacs, david.isaacs@health.nsw.gov.au Nick Wood, Children's Hospital at Westmead Association between respiratory syncytial virus (RSV) hospitalisation and risk of asthma or wheezing by age. Volume50, Issue7July 2014Pages 571-571 ReferencesRelatedInformation

Prospective validation of a prognostic model for respiratory syncytial virus bronchiolitis in late preterm infants: a multicenter birth cohort study.

ObjectivesThis study aimed to update and validate a prediction rule for respiratory syncytial virus (RSV) hospitalization in preterm infants 33–35 weeks gestational age (WGA).Study DesignThe RISK study consisted of 2 multicenter prospective birth cohorts in 41 hospitals. Risk factors were assessed at birth among healthy preterm infants 33–35 WGA. All hospitalizations for respiratory tract infection were screened for proven RSV infection by immunofluorescence or polymerase chain reaction. Multivariate logistic regression analysis was used to update an existing prediction model in the derivation cohort (n = 1,227). In the validation cohort (n = 1,194), predicted versus actual RSV hospitalization rates were compared to determine validity of the model.ResultsRSV hospitalization risk in both cohorts was comparable (5.7% versus 4.9%). In the derivation cohort, a prediction rule to determine probability of RSV hospitalization was developed using 4 predictors: family atopy (OR 1.9; 95%CI, 1.1–3.2), birth period (OR 2.6; 1.6–4.2), breastfeeding (OR 1.7; 1.0–2.7) and siblings or daycare attendance (OR 4.7; 1.7–13.1). The model showed good discrimination (c-statistic 0.703; 0.64–0.76, 0.702 after bootstrapping). External validation showed good discrimination and calibration (c-statistic 0.678; 0.61–0.74).ConclusionsOur prospectively validated prediction rule identifies infants at increased RSV hospitalization risk, who may benefit from targeted preventive interventions. This prediction rule can facilitate country-specific, cost-effective use of RSV prophylaxis in late preterm infants.

Household Tobacco Smoke and Admission Weight Predict Severe Bronchiolitis in Infants Independent of Deprivation: Prospective Cohort Study

ObjectivesTo examine demographic, environmental and clinical factors associated with severe bronchiolitis in infants admitted to hospital and quantify the independent effects of these factors.DesignProspective cohort study.SettingAlder Hey Children's Hospital, Liverpool, United Kingdom.Participants378 infants admitted to hospital with a diagnosis of bronchiolitis, of whom 299 (79%) were antigen positive to respiratory syncytial virus (RSV).OutcomeSeverity of disease during admission, defined as “no need for supplemental oxygen” (reference group), “any need for supplemental oxygen” and “any need for mechanical ventilation”.ResultsUnivariate analysis found male sex (p = 0.035) and tobacco smoking by a household member (p<0.001) were associated with need for both supplemental oxygen and mechanical ventilation. Premature birth, low gestation, low birth weight, low admission weight and low corrected age on admission were also associated with need for mechanical ventilation (all p≤0.002). Deprivation scores (IMD 2004) were significantly higher in households where a member smoked compared to non-smoking households (p<0.001). The odds of smoking predicted by deprivation were 7 times higher (95%CI (3.59, 14.03)), when comparing the least and most deprived quintiles of the study population. Family history of atopic disease and deprivation score were not associated with severe disease. Multivariate multinomial logistic regression which initially included all covariates, found household tobacco smoking (adjusted OR = 2.45, 95%CI (1.60, 3.74) predicted need for oxygen supplementation. Household tobacco smoking (adjusted OR = 5.49, (2.78, 10.83)) and weight (kg) on admission (adjusted OR = 0.51, (0.40, 0.65)) were both significant predictors in the final model for mechanical ventilation. The same associations and similar size of effects were found when only children with proven RSV infection were included in analysis.ConclusionsLow admission weight and householder tobacco smoking increased the risk of severe bronchiolitis in infants admitted to hospital. These effects were independent of a standard deprivation measure. NIHR Study Ref. DHCS/G121/10.

921 Bacteraemia and Antibiotic Use in Severe Respiratory Syncytial Virus Infections

Aims: To determine the frequency of and the risk factors for bacteraemia in infants hospitalized in the pediatric intensive care unit (PICU) with respiratory syncytial virus (RSV) infection and to precise the current use of antibiotics in these patients. Methods: Retrospective study of infants, aged 0-24 months, admitted to a pediatric intensive care unit with proven RSV infection over a nine year period (2000-2008). Infants with concurrent bacteraemia and RSV infection were identified, and risk factors for bacteraemia were identified in univariate then in multivariate analysis (logistic regression model). The use of antibiotics in these infants was also precised. Results: During the study period, a total of 169 infants were admitted to the PICU with proven RSV infection. Blood cultures were realized in all infants. Fourteen (8.3%) of the 169 RSV positive infants had bacteraemia. RSV positive infants had a significantly higher incidence of bacteraemia if they had a C-reactive protein level superior to 88 mg/l (27%), a positive bacteriology of tracheal aspirates at admission (32%) or if they required high frequency ventilation (28.5%). Ninety three (55%) of the RSV infected infants received antibiotics. Conclusions: Bacteraemia is rare in RSV infected infants admitted to the PICU. However, the incidence of antibiotic prescription in these infants is high. Children with severe RSV infection are more likely to be bacteraemic if they had a C-reactive protein level superior to 88 mg/l, a positive bacteriology of tracheal aspirates at admission or if they required high frequency ventilation.

The influence over a period of 8 years of patterns of prescribing palizivumab for patients with and without congenitally malformed hearts, and in admissions to paediatric intensive care

To describe the pattern of prescribing for palivizumab in the Glasgow area over the period 1999 through 2007, and to compare recent prescribing to the current recommendations by the Joint Committee on Vaccination and Immunisation of the United Kingdom Department of Health. Our secondary objective was to describe admissions to paediatric intensive care in patients with respiratory syncytial virus receiving palivizumab. Tertiary children's hospital out-patient immunisation clinic and paediatric intensive care unit. Prospective analysis of prescribing and admissions data for the period 1999 through 2007. Number of prescriptions and admissions to the paediatric intensive care unit. The number of children receiving palivizumab annually initially rose more than 5-fold, from 17 in the season of 1999 and 2000 versus 115 in 2004 and 2005, although it has declined in the past 2 years, to 63 in 2006 and 2007, following publication of the recommendations of the Joint Committee on Vaccination and Immunisation established by the United Kingdom Department of Health. There has been no significant change in demographics of patients during this period. Prior to publication of these recommendations, 35 of 44 (80%) patients with congenitally malformed hearts who received palivizumab in the season of 2005 and 2006 deviated from the current recommendations, compared to 5 of 51 (10%) who received palivizumab for non-cardiac indications. No patients who received palivizumab required admission to the paediatric intensive care unit with proven respiratory syncytial virus infection over the 8 year period. The number of children receiving palivizumab initially increased significantly, although it has now fallen following implementation of national recommendations. Much prescribing, particularly for children with congenitally malformed hearts, did not fulfil current recommendations. The absence of admissions to paediatric intensive care reflects the success of targeted immunisation in our population.

Clinical evaluation of NucliSENS magnetic extraction and NucliSENS analytical specific reagents for the real-time detection of respiratory syncytial virus (RSV) in paediatric respiratory specimens

Aims: To evaluate the combination of NucliSENS magnetic extraction and NucliSENS analytical specific reagents (bioMérieux, Marcy L’Etoile, France) for the detection of respiratory syncytial virus (RSV) from a variety of...

Hospitalization for Respiratory Syncytial Virus Infection in Young Children

Because passive immunization against respiratory syncytial virus (RSV) is costly, its use should be restricted to well-defined groups of high risk children. We aimed to develop a clinical prediction rule that estimates the individual monthly risk of hospitalization for RSV infection in young children. A retrospective cohort study was conducted in the southwestern part of The Netherlands. We included children born between January 1, 1996 and December 31, 1998. Children hospitalized for proven RSV infection were compared with children not hospitalized for RSV infection. The monthly risk was estimated with a logistic regression model including 5 clinical predictors (gender, gestational age, birth weight, presence of bronchopulmonary dysplasia and age) and the mean seasonal monthly pattern of RSV infections. We compared the predictive performance of the prediction rule with the guidelines of the American Academy of Pediatrics (AAP). Information was collected on 2469 hospitalized children and 140,661 children who were 1,181,790 months at risk. All predictors were statistically significant, with age and the seasonal monthly RSV pattern having the strongest effects. The clinical prediction rule that included these predictors could better discriminate between high and low risk children than the AAP guidelines and would potentially reduce the number of immunizations by 20%. The prediction rule reliably estimates individual monthly risks of hospitalization for RSV infection in the population studied. It provides an improved index for passive immunization but further validation in other populations is required.

Bacteraemia and antibiotic use in respiratory syncytial virus infections

Aims: To examine the frequency of and risk factors for bacteraemia in children hospitalised with respiratory syncytial virus (RSV) infection; and to determine current use of antibiotics in hospitalised children...

Influenza A in Young Children with Suspected Respiratory Syncytial Virus Infection

Objectives: To determine the prevalence of influenza A in young children suspected of having respiratory syncytial virus (RSV) infection and to compare the clinical presentation of these patients with those who have proven RSV infection. Methods: Children younger than or at 36 months of age who presented to a pediatric emergency department (ED) with suspected RSV infection during the influenza A season of 2001–2002 were eligible. Eligible children had an RSV antigen test ordered as part of their initial clinical management. A consecutive sample of children was enrolled for prospective observational analysis. The main outcome measure was the prevalence of influenza A in young children with suspected RSV infection. The secondary outcome measure was a comparison of the clinical presentations, of the two groups. Results: During the study period, 420 patients presented for evaluation of respiratory illness. RSV tests were ordered on 251 patients. Of 197 eligible patients, 124 (63%) tested positive for RSV and 33 (17%) for influenza A. Influenza A patients were more likely to have temperatures at or above 39°C than RSV patients (36% vs. 15%; p = 0.01). RSV patients were more tachypneic (54 vs. 43 breaths/minute; p &lt; 0.0001) and more often had wheezing (90% vs. 8%; p &lt; 0.0001). Twenty influenza patients (61%) were hospitalized. Conclusions: This study found a high prevalence of influenza A in young children suspected of having RSV infection. Clinicians should consider influenza A in young febrile children presenting with respiratory illnesses.

Predicting deterioration in previously healthy infants hospitalized with respiratory syncytial virus infection.

To estimate the incidence of clinical deterioration leading to intensive care unit transfer in previously healthy infants with respiratory syncytial virus (RSV) infection hospitalized on a general pediatric unit and, to assess the hypothesis that history, physical examination, oximetry, and chest radiographic findings at time of presentation can accurately identify these infants. A virology database was used to identify and determine the disposition of all children </=1 year of age admitted to the Children's Hospital at Strong (CHaS) with RSV infection during the 1985 to 1994 respiratory seasons. Index patients were all previously healthy, full-term infants admitted initially to the general inpatient services at CHaS or Rochester General Hospital, a second University of Rochester teaching hospital, whose clinical deterioration led to transfer to the pediatric intensive care unit (PICU). These infants were matched retrospectively (for year and date of infection, sex, chronologic age, and race) with two hospitalized controls who did not require PICU transfer. Chest radiographic findings, respiratory rate (RR), O(2) saturation, and presence of wheezing at time of presentation to the emergency department (ED) were compared. During the study years, 542 previously healthy, full-term infants were admitted to the general pediatric unit at CHaS with proven RSV infection. Ten (1.8%; 95% confidence interval, 0.9%, 3.4%) were transferred subsequently to the PICU, primarily for close monitoring of progressive respiratory distress. Data for these patients and 7 patients transferred from Rochester General Hospital to the PICU at the CHaS were compared with those for control patients. The mean RR in the ED (63 vs 50), and O(2) saturation in the ED (88% vs 93%) were modestly abnormal in cases compared with controls. Wheezing on examination at time of presentation and chest radiographic findings did not differ between the two groups. A RR >80 and an O(2) saturation <85% at time of presentation each had a specificity >97% for predicting subsequent deterioration. Each parameter, however, had a sensitivity </=30%. Clinical deterioration requiring PICU admission is an uncommon occurrence in previously healthy infants admitted to a general pediatric inpatient unit with RSV infection. Extreme tachypnea and hypoxemia were both associated with subsequent deterioration; however, only a small proportion of patients who clinically deteriorated presented in this way. The clinical usefulness of these parameters, therefore, is limited. respiratory syncytial virus, deterioration, healthy infants, prediction.

Shedding of infectious virus and virus antigen during acute infection with respiratory syncytial virus.

Shedding of respiratory syncytial virus (RSV) in nasopharyngeal aspirates (NPA) of hospitalized children with acute respiratory infection was studied using direct antigen detection by time-resolved fluoroimmunoassay, rapid identification of infectious virus in centrifugally inoculated cell cultures by immunoperoxidase staining and conventional virus culture. Sequential NPAs, in which also local RSV-specific IgA response was measured, were collected from children with proven RSV infection. The shedding pattern was similar for both infectious virus and viral antigen. The overall agreement of the three methods was good (81%) in diagnostic specimens collected on admission, but markedly reduced (46%) in follow-up specimens. Secretory IgA was abundant in specimens giving discrepant or negative results only. The proportion of patients who shed RSV was high (> or = 87%) in the first week after onset of symptoms, and decreased sharply in the second week. An opposite temporal pattern was found in the proportion of patients with detectable RSV-IgA in their secretions. Sequentially isolated strains were antigenically stable as determined by their reactivity with a large panel of monoclonal antibodies. The findings suggest that RSV shedding should be monitored by using more than one method for virus detection.

Serodiagnosis of respiratory syncytial virus (RSV) infection in children as measured by detection of RSV-specific immunoglobulins G, M, and A with enzyme-linked immunosorbent assay

The diagnostic value of an enzyme-linked immunosorbent assay for detection of respiratory syncytial virus (RSV)-specific immunoglobulin G (IgG), IgM, and IgA in sera from infants and children with proven RSV infection, from a control group, and from patients with symptoms of viral respiratory disease was analyzed. Compared to virus isolation and RSV antigen detection methods, the sensitivity of this assay was 87% and the specificity was 79%. For IgG alone, these were 45 and 92%, for IgM alone they were 48 and 92%, and for IgA alone they were 74 and 95%, respectively.

Cellular and humoral immunity in recurrent respiratory syncytial virus infections.

Summary: A study of humoral and cellular immune responses to respiratory syncytial virus (RSV) was carried out in a research day care center over a period of 10 years. To analyze the cumulative effect of recurrent RSV infections, children were grouped by years of potential RSV exposure. RSV epidemics were documented each year from 1967 through 1979. Most epidemics occurred in January and February, but occasional RSV isolations were made in December or as late as May. Neutralizing antibodies to RSV were assayed in serum obtained in the fall and spring of each year. These data indicate that the majority of children became infected in each of the first 3 years of life. Cellular immunity, expressed as RSV-stimulated lymphocyte blastogenesis, was assayed in fall and spring blood samples during the latter 4 years of the study. The mean lymphocyte stimulation index (SI) was near unity before the first infection and rose gradually during year 1, 2, and 3 to a level of approximately 4.0 thereafter. To determine whether in vitro measures of immunity to RSV correlated with resistance to subsequent infection, the effect of antibody level on infection rates was examined. The infection rate for children with pre-existing titers of <16 was significantly higher than those with titers of 16 or greater, but infections also occurred in children with high titers. The effect of pre-existing cell-mediated immunity, as expressed by antigen-stimulated lymphocyte blastogenesis, also was analyzed. More children with low stimulation indices (<3.0) were infected but the difference between low and high reactors was not significant. When the combined effect of antibody titer and SI on infection rates was examined, protection correlated with serum antibody but no added effect could be related to CMI. The relationship of lymphocyte SI and clinical illness was examined by grouping subjects according to clinical illness syndromes associated with proven RSV infection. SI were statisticaly similar regardless of age or illness syndrome. Similar comparisons with pre-illness antibody titers revealed an inverse relation between height of titer and severity of clinical illness. Data derived from this prospective study of RSV infection do not support the hypothesis that cell-mediated immunity contributes significantly to resistance to infection or to disease pathogenesis. Because neither systemic humoral nor cell-mediated immunity appear to act directly in modifying RSV infection and disease expression, it is speculated that local immune mechanisms within the respiratory tract may be involved.

Alterations in Pulmonary Function Following Respiratory Viral Infection

Respiratory viral illness is a major cause of morbidity in both adults and children. This report focuses on both the acute and chronic effects on respiratory function of these ubiquitous infections. Infant airways are particularly vulnerable due to the relatively low conductance in immature peripheral airways. Bronchiolitis, caused predominantly by respiratory syncytial virus, is the most important of these viral illnesses and is emerging as a major risk factor for the subsequent development of obstructive airway disease in adults, possibly by interference with normal alveolar proliferation. The basic pathogenic mechanism involved in adult respiratory viral infection is bronchial hyperreactivity, presumably secondary to epithelial damage and resultant sensitization of rapidly adapting airway receptors. In addition, there may be virus-related alterations in the autonomic and humoral regulation of airway tone. Viral infections may alter the effects of common air pollutants on respiratory function.