Consecutive Respiratory Syncytial Virus Seasons Research Articles

Respiratory Syncytial Virus-related Community Chronic Obstructive Pulmonary Disease Exacerbations and Novel Diagnostics: A Binational Prospective Cohort Study.

Rationale: Respiratory syncytial virus (RSV) is a common global respiratory virus that is increasingly recognized as a major pathogen in frail older adults and as a cause of chronic obstructive pulmonary disease (COPD) exacerbations. There is no single test for RSV in adults that has acceptable diagnostic accuracy. Trials of RSV vaccines have recently shown excellent safety and efficacy against RSV in older adults; defining the frequency of RSV-related community infections and COPD exacerbations is important for vaccine deployment decisions. Objectives: This prospective study aimed to establish the frequency of outpatient-managed RSV-related exacerbations of COPD in two well-characterized patient cohorts using a combination of diagnostic methods. Methods: Participants were recruited at specialist clinics in London, United Kingdom, and Groningen, the Netherlands, beginning in 2017 and observed for three consecutive RSV seasons, during exacerbations, and at least twice yearly. RSV infections were detected by RT-PCR and serologic testing. Measurements and Main Results: A total of 377 patients with COPD attended 1,999 clinic visits and reported 310 exacerbations. There were 27 RSV-related exacerbations (8.7% of the total); of these, seven were detected only by PCR, 16 only by serology, and four by both methods. Increases in RSV-specific Nucleoprotein antibody were as sensitive as those in the antibody to Pre-Fusion or Post-Fusion for serodiagnosis of RSV-related exacerbations. Conclusions: RSV is associated with 8.7% of outpatient-managed COPD exacerbations in this study. Antibodies to RSV Nucleoprotein may have diagnostic value and are potentially important in a vaccinated population. The introduction of vaccines that prevent RSV is expected to benefit patients with COPD.

Risk factors associated with severe disease in respiratory syncytial virus infected children under 5 years of age.

ObjectiveTo evaluate risk factors for severe disease in children under 59 months of age hospitalized with respiratory syncytial virus (RSV) infection.Study designWe prospectively enrolled 1,096 cases of laboratory confirmed RSV infection during three consecutive RSV seasons in 2015–2018. Potential risk factors for severe disease were retrieved through patient questionnaires and linkage to national health registries. Need for respiratory support (invasive ventilation, bi-level positive airway pressure, or continuous positive airway pressure), and length of stay exceeding 72 h were used as measures of disease severity. Associations were investigated using multivariable logistic regression analyses. Multiple imputation was used to avoid bias and inference induced by missing data.ResultsRisk factors associated with a need for respiratory support included age younger than 3 months of age [aOR: 6.73 (95% CI 2.71–16.7)], having siblings [aOR: 1.65 (95% CI 1.05–2.59)] and comorbidity [aOR: 2.40 (95% CI 1.35–4.24)]. The length of hospital stay >72 h was significantly associated with being younger than 3 months of age [aOR: 3.52 (95% CI 1.65–7.54)], having siblings [aOR: 1.45 (95% CI 1.01–2.08)], and comorbidity [aOR: 2.18 (95% CI 1.31–3.61)]. Sub-group analysis of children younger than 6 months of age confirmed the association between both young age and having siblings and the need for respiratory support.ConclusionIn a large cohort of children <59 months hospitalized with RSV infection, young age, comorbidity, and having siblings were associated with more severe disease.

Clinical and Socioeconomic Burden of Respiratory Syncytial Virus in Iceland.

Respiratory syncytial virus (RSV), a very common pathogen, causes variable disease severity. In addition to considerable clinical burden on children, their families and healthcare facilities, RSV infections in children also carry significant direct and indirect socioeconomic burden. We analyzed data from 5 consecutive RSV seasons (2015-2020) and used virologically confirmed RSV infections and age <5 years as case definition. Clinical information was retrieved from electronic patient records. Costs were estimated by assuming an annual 30% attack rate and a combination of direct medical costs and calculations of societal costs of lost productivity. A total of 716 children younger than 5 years of age had confirmed RSV infection of which 254 needed hospitalizations, most of whom were previously healthy. The median length of admission was 3.6 days and 13 patients needed intensive care. The hospital admission incidence rate was 2.5/1000 children/year, but 9.1 for children younger than 1 years of age. The total annual cost of RSV was estimated at €4.3 million, of which 10% was direct healthcare costs. The clinical and socioeconomic disease burden of RSV in Iceland is substantial despite slightly lower hospital admission rates than other high-income countries. The prevention of RSV in young children, either through maternal or infant vaccination, has the potential to decrease both clinical and financial impact of the annual epidemics.

The azithromycin to prevent wheezing following severe RSV bronchiolitis-II clinical trial: Rationale, study design, methods, and characteristics of study population

Severe respiratory syncytial virus (RSV) bronchiolitis in early life is a significant risk factor for future recurrent wheeze (RW) and asthma. The goal of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis II (APW-RSV II) clinical trial is to evaluate if azithromycin treatment in infants hospitalized with RSV bronchiolitis reduces the occurrence of RW during the preschool years.The APW-RSV II clinical trial is a double-blind, placebo-controlled, parallel-group, randomized trial, including otherwise healthy participants, ages 30 days-18 months, who are hospitalized due to RSV bronchiolitis. The study includes an active randomized treatment phase with azithromycin or placebo for 2 weeks, and an observational phase of 18–48 months. Two hundred participants were enrolled during three consecutive RSV seasons beginning in the fall of 2016 and were randomized to receive oral azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for an additional 7 days, or matched placebo. The study hypothesis is that in infants hospitalized with RSV bronchiolitis, the addition of azithromycin therapy to routine bronchiolitis care would reduce the likelihood of developing post-RSV recurrent wheeze (≥3 episodes). The primary clinical outcome is the occurrence of a third episode of wheezing, which is evaluated every other month by phone questionnaires and during yearly in-person visits.A secondary objective of the APW-RSV II clinical trial is to examine how azithromycin therapy changes the upper airway microbiome composition, and to determine if these changes are related to the occurrence of post-RSV RW. Microbiome composition is characterized in nasal wash samples obtained before and after the study treatments.This clinical trial may identify the first effective intervention applied during severe RSV bronchiolitis to reduce the risk of post-RSV RW and ultimately asthma.

Risk factors for respiratory syncytial virus bronchiolitis hospitalizations in children with chronic diseases.

Respiratory syncytial virus (RSV) bronchiolitis is the most common lower respiratory tract disorder causing hospitalization in infants. Due to decreased hospitalization rates of premature infants following Palivizumab immune prophylaxis, the proportion of infants with chronic diseases not eligible for Palivizumab has increased. To characterize infants hospitalized during 2014-2018 with RSV bronchiolitis, to compare between those with and without chronic conditions, and to identify risk factors for severe disease. This retrospective study analyzed demographic and clinical data of patients younger than 2 years admitted with bronchiolitis during four consecutive RSV seasons. Of 1124 hospitalizations due to RSV bronchiolitis, 244 (22%) were in infants with chronic diseases. Although 20/1124 qualified for RSV prophylaxis, only eight received immune prophylaxis. Compared to otherwise healthy infants, children with chronic diseases had longer hospitalizations, median 4.8 days (interquartile range [IQR]: 3.4-8.3) versus 3.7 days (IQR: 2.7-5.1), p < .001; and higher pediatric intensive care unit (PICU) and readmission rates (9% vs. 4.5%, p = .007% and 3% vs. 1%, p = .055, respectively). Children with Down's syndrome comprised 2% of all hospitalizations, but 8% of PICU admissions; their median length of hospitalization was 10.7 days (IQR: 6.6-17.6). Respiratory tract malformations were present in 2% of hospitalizations, and comprised 4% of PICU admissions. Among infants admitted with RSV bronchiolitis, those with chronic diseases had longer hospitalizations and higher rates of transfer to the PICU. Children with multiple comorbidities, and especially those with Down's syndrome, are at particularly high risk for severe hospitalization and may benefit from RSV immune prophylaxis.

Palivizumab compliance in congenital heart disease patients: factors related to compliance and altered lower respiratory tract infection viruses after palivizumab prophylaxis.

Lower respiratory tract infections caused by respiratory syncytial virus can be severe during infancy, which requires admission to the hospital. These infections may be more severe especially in patients with congenital heart disease. Passive immunisation with palivizumab, a monoclonal antibody, is recommended in high-risk infants. We tried to determine the compliance rates, factors affecting compliance, and also other microorganisms responsible for lower respiratory tract infections after palivizumab prophylaxis in these patients. We evaluated patients' compliance to prophylaxis with palivizumab in two consecutive respiratory syncytial virus seasons from pharmacy records. We also investigated factors affecting compliance and the frequency of hospitalisations for lower respiratory tract infections. We investigated the causative microorganisms detected in hospitalised patients. In this study, 86.7% of the desired number of injections was achieved in 176 patients in two seasons. Out of these, 117 patients (66.4%) received all the doses they were prescribed. Although not statistically significant, compliance to prophylaxis was higher in male patients, cyanotic patients, those who started under 1 year old, and who lived in the city centre. Human metapneumovirus, parainfluenza type 3, and bocavirus were detected in the hospitalised patients. Patients with congenital heart disease can survive the period of infancy with less problem by making palivizumab prophylaxis more effective, and awareness about non- respiratory syncytial virus factors may be a guide for the development of new treatments.

Palivizumab Prophylaxis for infants 29 to 32 weeks gestation at birth: A 10-year audit from Vancouver Island using BC Guidelines.

After initially recommending palivizumab (PVZ), a monoclonal antibody against respiratory syncytial virus (RSV) for all infants 29 to 32 weeks at birth if <6 months age at season start, the American Academy of Pediatrics (AAP) and Canadian Paediatric Society (CPS) guidelines were revised. British Columbia was the only jurisdiction in North America to restrict eligibility for this group to those with additional risk factors, long before the change in national recommendations. To determine the risk for first season RSV admission for 29 to 32-week gestational age (GA) infants admitted to Victoria Neonatal Intensive Care Unit (NICU) that either received or were denied PVZ prophylaxis. Descriptive cohort study of infants eligible for prophylaxis according to earlier CPS guidelines. Instead, BC guidelines for prophylaxis were applied and data for Vancouver Island infants were collected over 10 consecutive RSV seasons. We followed 423 infants. Three hundred and thirty-six (79%) did not receive prophylaxis, of which 10 (3.0%; 95% confidence interval [CI] 1.4% to 5.4%) had an RSV hospitalization before the end of April during their first RSV season versus 3 admissions from 87 (3.5%; 95% CI 0.7% to 10%) infants who received prophylaxis. Our risk factor approach to RSV prophylaxis for infants born at 29 to 32 weeks GA resulted in a low (average incidence=3.1%) rate of RSV hospitalization. Our approach would offer considerable cost savings to RSV prophylaxis programs that continue to offer routine prophylaxis beyond 28/29 weeks GA at birth.

Prevalence of respiratory pathogens during two consecutive respiratory syncytial virus seasons at a tertiary medical care center.

To determine the etiological profiles of lower respiratory tract infection (LRI) in neonates during respiratory syncytial virus(RSV) season, and to define the clinical features of RSV-related infection and others. The retrospective study included newborn infants who were hospitalized for LRI during the two consecutive RSV seasons, and then tested for possible etiological agent by multiplex real-time polymerase chain reaction. All relevant data were reviewed, and the clinical characteristics of RSV-related infection were compared to those of others. Of 224 patients, 160 (71 %) were positive for at least one potentially causative agent. Of them, 65 % had RSV, and 15 % had more than on ecausative agent (co-infection). The RSV group had more the findings of respiratory distress (p< 0.01), abnormal chest radiography (p< 0.01), need for intensive care (p< 0.01), and duration of oxygen requirement (p< 0.01) but less fever on admission and duration of antibiotic use (for both, p< 0.01), and no longer hospital stay. Need of intensive care nursery was more common in patients with co-infection than others (25 % vs. 6.5 %, p< 0.01). This study highlighted that RSV was the most frequent agent in neonates hospitalized for LRI during the season, with a more severe clinical course than other detected pathogens. The disease severity of RSV infection may have seemed to be increased by the presence of coinfection and abnormal chest radiography.

Respiratory syncytial virus-neutralizing serum antibody titers in infants following palivizumab prophylaxis with an abbreviated dosing regimen.

BackgroundMonthly injections of palivizumab during the respiratory syncytial virus (RSV) season in at-risk infants reduces RSV-associated hospitalizations. However, the additive effect of naturally acquired immunity remains unclear. The objective of this study was to assess total neutralizing serum antibodies (NAb) against RSV in at-risk infants who had received an abbreviated course of palivizumab prophylaxis.MethodsSerum samples were collected from infants enrolled in the RSV Immunoprophylaxis Program in British Columbia, Canada over 2 consecutive RSV seasons (2013 to 2015). Infants in this program had received an abbreviated course of palivizumab in accordance with the provincial guidelines. Data were compared to adults and infants less than 12 months of age who did not receive palivizumab. Anti-RSV NAb titers were measured using an RSV microneutralization assay.FindingsInfants who received palivizumab had anti-RSV NAb titers at the end of the RSV season that persisted beyond what is expected from the pharmacokinetics of palivizumab alone. Moreover, 54% of the control infants who did not receive palivizumab and all tested adults had protective anti-RSV NAb titers.ConclusionsBased on our observations, we hypothesize that naturally acquired NAb provide additive protection, which may significantly reduce the need for additional doses of palivizumab in infants at risk of severe RSV infections.

Burden of Respiratory Syncytial Virus Hospitalizations in Canada.

Objective To examine the socioeconomic burden of respiratory syncytial virus (RSV) disease for Canadian infants hospitalized for the condition. Data and Methods The descriptive study used data collected in Alberta, Canada, during 2 consecutive RSV seasons. Infants (<1 year of age) were included if they had not received palivizumab and were hospitalized with a confirmed diagnosis of RSV. Hospitalization resource use and parental time burden, out-of-pocket costs, lost work productivity, and stress and anxiety were assessed. Results 13.4% of all infants (n = 67) had intensive care unit (ICU) admission, and average ICU stay for these infants was 6.5 days. Families had average out-of-pocket expenses of 736.69 Canadian dollars (CAD $), and the average time both parents spent in hospital was nearly 7 days (164.0 hours). For working parents (n = 43), average absenteeism was 49% and overall work impairment was 77.8%. Parents also exhibited significant parental stress (3.6 on the Parental Stressor Scale: 43.9 state anxiety and 36.9 trait anxiety scores). Conclusions Results indicate a high burden associated with the hospitalization of an infant due to RSV disease in terms of resource use, time, productivity, costs, and stress, even among a population of infants not considered to be at risk for the condition.

Insurance Status and the Risk of Severe Respiratory Syncytial Virus Disease in United States Preterm Infants Born at 32-35 Weeks Gestational Age.

Background. Database studies have identified that public health insurance status is associated with an increased risk of severe respiratory syncytial virus (RSV) disease in US infants. However, these studies did not adjust for the presence of other risk factors and did not evaluate the risk in preterm infants. Methods. In this study, we evaluate the independent association between public insurance and severe RSV disease outcomes adjusting for other risk factors. The prospective, observational RSV Respiratory Events among Preterm Infants Outcomes and Risk Tracking (REPORT) study was conducted over 2 consecutive RSV seasons at 188 US clinical sites that enrolled preterm infants born at 32-35 wGA who had not received RSV immunoprophylaxis with palivizumab. Adjusted incidence rates per 100 infant-seasons of the RSV-associated endpoints of outpatient lower respiratory tract infection (LRI), emergency department (ED) visits, RSV hospitalizations (RSVHs), and intensive care unit admissions during peak RSV season (November-March) were compared for infants with private and public insurance. Results. Of 1642 evaluable infants enrolled in the REPORT study, 50.1% had private insurance and 49.9% had public health insurance. Adjusted rates of RSV outpatient LRIs were similar; however, rates of ED visits (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.20-3.45) were higher for subjects with public insurance, with a similar but nonsignificant trend observed for hospitalization (HR, 1.61; 95% CI, .93-2.78). Conclusions. Socioeconomic status, as evaluated by public versus private healthcare insurance, is a significant independent risk factor for ED use in US preterm infants and may contribute to increased RSVHs in this population.

Respiratory syncytial virus-associated hospitalizations over three consecutive seasons in children with congenital heart disease

The purpose of this investigation was to analyze the burden of respiratory syncytial virus (RSV)-related hospitalizations in infants and children with congenital heart disease (CHD) over three consecutive RSV seasons. Retrospectively, all children with hemodynamically significant (HS-CHD) and not significant (HNS-CHD) CHD born between 2004 and 2008 at a tertiary care university hospital and identified by ICD-10 diagnoses were included. Data on RSV-related hospitalizations over the first three years of life covering at least three RSV seasons (November-April) were analyzed. The overall incidence of RSV-related hospitalization was 9.6% (58/602), without a statistically significant difference between HS-CHD and HNS-CHD (7.3% vs. 10.4%; p = 0.258). Recommendation of palivizumab prophylaxis did not influence the RSV hospitalization rates between groups. Patients with HS-CHD and early surgery were significantly less often hospitalized due to RSV compared to those with delayed surgery (1.3% vs. 14.3%; p = 0.003). The median duration of hospitalization was 8.5days (HS-CHD: 14 vs. 7days; p = 0.003). Thirteen patients (22.4%) were admitted to the intensive care unit (ICU), for a median of 10days. The median age at admission was 2months, with a significant difference between HS-CHD and HNS-CHD (6 vs. 2months; p = 0.001). The majority (97%) of RSV-related hospitalizations occurred before 12months of age. Patients with HS-CHD had a significantly more severe course of RSV disease and were older at the time of hospitalization. Early surgery seemed to significantly reduce the risk of RSV hospitalization during the first RSV season.

Respiratory syncytial virus infection in children with severe motor and intellectual disabilities

Children with severe motor intellectual disabilities (SMID) are at high risk of death from acute viral lower respiratory tract infections (LRTI). Although respiratory syncytial virus (RSV) is the most common cause of viral LRTI in children, there have been a few reports on the relationship between SMID and the severity of RSV-LRTI. The aim of the present study is to assess the influence of RSV-LRTI in children with SMID. A case-control study composed of children with SMID (n = 18) and previously healthy children (n = 43) less than 16years old hospitalized for RSV-LRTI was performed during five consecutive RSV seasons. The clinical presentation and the laboratory data in the SMID group were compared with those in the non-SMID group. In the bivariate analysis, the median age of the SMID group was higher than that of the non-SMID group (p = 0.002). Children with SMID had an increased risk for ventilation support (p = 0.057). The count of neutrophils in the SMID group was significantly increased (p = 0.012), whereas the proportion of bacterial co-infection was lower than that in the non-SMID group (p = 0.005). Multivariate logistic analysis showed that SMID was associated with longer oxygen usage [>7days: odds ratio (OR) 5.309, p = 0.033]. The present study revealed that children with SMID were prone to developing hypoxia by RSV-LRTI. The strategies for the treatment and prevention of RSV infection need to be improved in SMID children.

Life Years Gained From Palivizumab

Reply: In children younger than 5 years of age and particularly in those less than 1 year old, respiratory syncytial virus (RSV) is the most common viral cause of death, resulting in an estimated RSV-associated mortality rate of 3.2 per 100,000 person-years for the 1990/1991 through 1998/1999 seasons in the United States.1 Information about RSV-specific mortality was provided in 36 of 173 studies reviewed by Stensballe et al2 and was zero in 20 of them and 0.1%–12% in the remaining ones. Mortality caused by RSV infection was observed in 33% of the studies in developed countries and in 52% of the studies in developing countries. No difference could be detected when comparing mortality in field- and hospital-based studies or when studies conducted before 1980 were compared with those conducted after 1980.2 During a study period covering 8 consecutive RSV seasons, Thorburn3 reported on 406 RSV-positive patients admitted to the pediatric intensive care unit. Eighteen patients died due to RSV bronchiolitis resulting in an intensive care unit mortality rate of 4.4% and a total hospital RSV mortality rate of 1.7%. All of the RSV deaths were reported to have preexisting medical conditions including chronic lung disease in 12%. In infants and children with congenital heart disease, mortality rates of up to 37% have been reported in the early 1980s with rates ranging from 0% to 16.6% between 1992 and 2010.4 The study of Sampalis5 addressed the issue of health care utilization and morbidity subsequent to RSV hospitalization in non-bronchopulmonary dysplasia premature infants born between 32 and 35 weeks of gestation occurring during the first year of life in Canada. Between 1997 and 2000, a total of 2415 preterm infants hospitalized for proven or probable RSV were matched to 20,254 control infants. Data were impressive for the RSV cohort and control infants, respectively, regarding mean subsequent hospitalizations (2.96 versus 1.28), special care unit visits (0.67 versus 0.40), respiratory therapy visits (0.31 versus 0.13), physician consults (3.61 versus 0.89), in-hospital procedures (1.05 versus 0.81), outpatient visits (18.4 versus 7.54) and mean inpatient days (14.71 versus 5.04), with all differences being statistically significant (P < 0.001). Diagnoses for the RSV and control cohorts were respiratory conditions (64% versus 13%), fever (2.7% versus 0.7%), anorexia (2.2% versus 0.6%), lack of normal physiologic development (2.8% versus 1.1%; P < 0.05), overall deaths (8.1% versus 1.6%; P < 0.001) and sudden death (6.1% versus 0.3%; P < 0.001). In view of the above-mentioned remarkable RSV-related mortality rates reported in high-risk infants throughout the last decades, it seems to be highly justified to use the Sampalis5 data for calculating life years gained by palivizumab. We tried to use the Impact data6 to calculate life years gained for this patient group and obtained a similar result of 0.47 life years gained. The problem is that it is not possible to distinguish mortality rates between patients with need for hospitalization or not. But, nevertheless, results affirm our base case results. It is an interesting phenomenon that many authors criticize the so-called missing effect of palivizumab on the reduction of RSV-related mortality in the 2 placebo controlled trials that led to the license of the product6,7, but neither the Impact study6 in preterm infants with and without bronchopulmonary dysplasia nor the Feltes study7 in infants and children with hemodynamically significant congenital heart disease was powered to detect differences in rates of mortality. In addition, palivizumab still has to be seen in the light of the absence of specific treatment modalities and missing successful vaccine trials instead of research over half a century. Bernhard Resch, MD Research Unit for Neonatal Infectious Diseases and Epidemiology Division of Neonatology, Department of Pediatrics Medical University of Graz Graz, Austria Evelyn Walter, PhD Institute for Pharmaeconomic Research Vienna, Austria Mark J.C. Nuijten, MD, PhD Ars Accessus Medica Amsterdam, The Netherlands

Chest physiotherapy using passive expiratory techniques does not reduce bronchiolitis severity: a randomised controlled trial

Chest physiotherapy (CP) using passive expiratory manoeuvres is widely used in Western Europe for the treatment of bronchiolitis, despite lacking evidence for its efficacy. We undertook an open randomised trial to evaluate the effectiveness of CP in infants hospitalised for bronchiolitis by comparing the time to clinical stability, the daily improvement of a severity score and the occurrence of complications between patients with and without CP. Children <1 year admitted for bronchiolitis in a tertiary hospital during two consecutive respiratory syncytial virus seasons were randomised to group 1 with CP (prolonged slow expiratory technique, slow accelerated expiratory flow, rarely induced cough) or group 2 without CP. All children received standard care (rhinopharyngeal suctioning, minimal handling, oxygen for saturation ≥92%, fractionated meals). Ninety-nine eligible children (mean age, 3.9 months), 50 in group 1 and 49 in group 2, with similar baseline variables and clinical severity at admission. Time to clinical stability, assessed as primary outcome, was similar for both groups (2.9 ± 2.1 vs. 3.2 ± 2.8 days, P = 0.45). The rate of improvement of a clinical and respiratory score, defined as secondary outcome, only showed a slightly faster improvement of the respiratory score in the intervention group when including stethoacoustic properties (P = 0.044). Complications were rare but occurred more frequently, although not significantly (P = 0.21), in the control arm. In conclusion, this study shows the absence of effectiveness of CP using passive expiratory techniques in infants hospitalised for bronchiolitis. It seems justified to recommend against the routine use of CP in these patients.

Utilidad predictiva de ingreso por infección por virus respiratorio sincitial de diferentes asociaciones de factores de riesgo en prematuros de 32 a 35 semanas de gestación en España

Aim The aim of the study was to evaluate the risk factor associations for respiratory syncytial virus (RSV) hospitalization in preterm infants from 32 to 35 weeks gestation, treated during two consecutive RSV seasons in Spain. Patients and methods A database (FLIP-2) was used after excluding the infants who received prophylactic palivizumab. A total of 193 RSV+ admissions and 4568 non-hospitalized children were studied. The risk factors analyzed were: chronological age <=10 weeks at start of RSV season or to be born during the first 10 weeks of the season; school-age siblings or daycare attendance; mother smoking during pregnancy; male gender; breastfeeding <=2 months; >=4 adults at home; history of wheezing; small for gestational age; >=2 smokers at home. Results Logistic regression model included the first four previously mentioned risk factors as independently significant variables, with R 2 of 0.062 and area under curve of 0.687 ( P<0.001). Predictive values for a child with the four risk factors were: sensitivity 6.2%, specificity 98.6%, predictive positive value 16.2%, negative predictive value 96.1%, accuracy 94.9%, positive likelihood ratio 4.581, and negative likelihood ratio 0.951. Positive likelihood ratio for a child with the two major risk factors is 2.657. Conclusions Usefulness of different risk factor associations to predict hospitalization for respiratory syncytial virus infection in preterm infants 32 to 35 weeks gestation in Spain is low, although similar to other models.

Risk factors for severe RSV-induced lower respiratory tract infection over four consecutive epidemics

Variability in severity among different respiratory syncytial virus (RSV) seasons may influence hospital admission rates for RSV-induced lower respiratory tract infection (LRTI) in young children. The aim of the present study was to identify through logistic regression analysis, risk factors associated with higher likelihood to acquire RSV-induced LRTI, in children with symptoms severe enough to lead to hospital admission. Over four consecutive RSV seasons (2000–2004), records from children <4 years of age admitted for RSV-induced LRTI (“cases”) were compared with those from children with LRTI not due to RSV and not requiring hospitalization (“controls”). 145 “case-patients” and 295 “control-patients” were evaluated. Independent from the severity of the four epidemic seasons, seven predictors for hospitalization for RSV infection were found in the bivariate analysis: number of children in the family, chronological age at the onset of RSV season, birth weight and gestational age, birth order, daycare attendance, previous RSV infections. In the logistic regression analysis, only three predictors were detected: chronological age at the beginning of RSV season [aOR = 8.46; 95% CI:3.09–23.18]; birth weight category [aOR = 7.70; 95% CI:1.29–45.91]; birth order (aOR = 1.92; 95% CI:1.21–3.06). Conclusions: Independent from the RSV seasonality, specific host/environmental factors can be used to identify children at greatest risk for hospitalization for RSV infection.

Respiratory syncytial virus infection in 406 hospitalized premature infants: results from a prospective German multicentre database

Premature birth, chronic lung disease of prematurity (CLD), congenital heart disease and immunodeficiency predispose to a higher morbidity and mortality in respiratory syncytial virus (RSV) infection. This study describes the preterms hospitalised with RSV infection from the prospective German DSM RSV Paed database. The DMS RSV Paed database was designed for the prospective multicentre documentation and analysis of clinically relevant aspects of the management of inpatients with RSV infection. This study covers six consecutive RSV seasons (1999-2005); the surveillance took place in 14 paediatric hospitals in Germany. Of the 1,568 prospectively documented RSV infections, 26% (n=406) were observed in preterms [vs. 1,162 children born at term (74%)] and 3% (n=50) had CLD, of which 49 had received treatment in the last 6 months ('CLDplus'). A significantly higher proportion in the preterm group had congenital heart disease, nosocomial infection, and neuromuscular impairment. There were significantly more children older than 24 months in the preterm group. The attributable mortality was 0.2% (n=2) in children born at term vs. 1.2% (n=5) in the preterm group (p=0.015) [preterm plus CLD 8.0% (n=4 of 50); McIntosh grade 1, 8.6% (n=3 of 35) and McIntosh Grade 4, 15% (n=3 of 20)]. Eight patients were categorized as 'palivizumab failures'. In the multivariate analysis, premature birth, CLD(plus), and nosocomial infection were significantly and independently associated with the combined outcome 'complicated course of disease'. In conclusion, this is the first prospective multicentre study from Germany that confirms the increased risk for severe RSV disease in preterms, in particular in those with CLD treated in the last 6 months before the onset of the infection. From the perspective of our results, the statements of the German Society of Paediatric Infectious Diseases considering the use of passive immunisation (2003) seem reasonable.

Impact of Palivizumab on Admission to the ICU for Respiratory Syncytial Virus Bronchiolitis: A National Survey†

To assess the effect of palivizumab licensing for respiratory syncytial virus (RSV) prophylaxis on national pediatric ICU (PICU) admissions and on the need for mechanical ventilation due to RSV bronchiolitis in Israel. Prospective national surveillance survey. All PICUs in Israel. All patients admitted to a PICU because of acute bronchiolitis in two consecutive RSV seasons (November 2000 to April 2001 and November 2001 to April 2002). Data on demographic and epidemiologic factors and RSV prophylaxis status were collected for every infant with bronchiolitis who was admitted to a PICU in Israel in the year before and after issuance of the Israel Ministry of Health recommendation for palivizumab prophylaxis (January 2001). One hundred five patients were admitted to a PICU because of RSV bronchiolitis in the year before the recommendations were issued, and 123 patients were admitted in the year after they were issued. Mechanical ventilation was required by 33 and 42 children, respectively. Gestational age was > 32 weeks in 92.9% and 83.9% of the admitted patients, respectively, and 89% and 91% of the patients, respectively, were free of chronic lung disease (CLD). In both periods, 83% of the children who were admitted to a PICU did not meet the American Academy of Pediatrics criteria for RSV prophylaxis. Most of the children with severe RSV bronchiolitis needing PICU admission from 2000 to 2002 born at term did not have CLD and were not candidates for RSV prophylaxis according to the current recommendations.

Incidence of Respiratory Syncytial Virus Positivity in Young Italian Children Referred to the Emergency Departments for Lower Respiratory Tract Infection over Two Consecutive Epidemic Seasons

The rate and severity of respiratory syncytial virus (RSV) infections within the same nation may vary from one year to another. The "Osservatorio VRS" study collected epidemiological data on RSV infection among Italian children aged < or = 4 years referred to emergency departments of 14 centers, for suspected lower respiratory tract infections (LRTI) in two consecutive RSV seasons (October 2000-April 2001 and October 2001-April 2002). Medical history and physical examination were recorded and an immunoenzymatic RSV test was performed on nasal secretions. Study variables were collected and evaluated separately, then compared. In all, 272 and 756 children were included in the two seasons, respectively, of which 31.6% and 19.2% were RSV positive (+). Children of the first season had lower gestational and chronological age, higher rates of chronic lung disease (CLD), very low birth weight (< 1,500 g), larger use of corticosteroids or bronchodilators. Main risk factors for RSV infection were a young age (< 1 year) and a low birth weight (< 1,500 g). RSV infection reached its peak in February (first season) or March (second season), with an earlier appearance in the northern and central as compared to the southern regions. Rate of hospitalization and LRTI was higher in RSV+ children, especially if young. Although rhythms of the RSV seasons and patient characteristics may vary from one year to another, the severity of RSV disease in nonprophylaxed infants and young children remains high.