Respiratory Syncytial Virus Illness Research Articles

EFFECTIVENESS OF PALIVIZUMAB IN PREVENTING RSV HOSPITALIZATION IN HIGH-RISK CHILDREN: A PROSPECTIVE OBSERVATIONAL MULTICENTER STUDY

Background: Palivizumab is indicated for the prevention of serious respiratory syncytial virus (RSV) disease in high-risk infants.Aims: The purpose of the study was to assess the real-world effectiveness and safety of palivizumab in children at high risk for serious RSV disease during the 2014−2015 RSV season in the Russian Federation.Methods: A prospective, observational, multicentre, cohort study was conducted in a population of infants at high-risk for serious RSV illness: infants born ≤35 weeks of gestation and infants ≤24 months with bronchopulmonary dysplasia (BDP) or congenital heart disease (CHD), who were administered palivizumab immunoprophylaxis in routine clinical settings. The study was conducted at 16 investigational sites of European Russia and Western Siberia.Results: A total of 359 infants were enrolled (180 boys and 179 girls). Of them, 148 (41.2%) infants had BDP, 45 (12.5%) infants had hemodynamically significant CHD, and 166 (46.2%) children of prematurity were at the risk of RSV. The majority of infants (86.9%) received three or more injections during the course of study. Of the 359 participants enrolled, 11 (3.1%; 95% CI 1.5−5.4) patients were hospitalized for lower respiratory tract infection. A RSV diagnostic test was performed in 9 infants, and RSV was detected in one patient giving an overall incidence of RSV hospitalization as 0.3% (95% CI 0.0−1.5).Conclusions: This study showed that immunoprophylaxis with palivizumab was associated with a low rate of RSV hospitalization. Overall, therapy with palivizumab was well-tolerated and showed a favourable benefit-risk profile.

Association of Dynamic Changes in the CD4 T-Cell Transcriptome With Disease Severity During Primary Respiratory Syncytial Virus Infection in Young Infants.

Nearly all children are infected with respiratory syncytial virus (RSV) within the first 2 years of life, with a minority developing severe disease (1%-3% hospitalized). We hypothesized that an assessment of the adaptive immune system, using CD4+ T-lymphocyte transcriptomics, would identify gene expression correlates of disease severity. Infants infected with RSV representing extremes of clinical severity were studied. Mild illness (n = 23) was defined as a respiratory rate (RR) < 55 and room air oxygen saturation (SaO2) ≥ 97%, and severe illness (n = 23) was defined as RR ≥ 65 and SaO2 ≤ 92%. RNA from fresh, sort-purified CD4+ T cells was assessed by RNA sequencing. Gestational age, age at illness onset, exposure to environmental tobacco smoke, bacterial colonization, and breastfeeding were associated (adjusted P < .05) with disease severity. RNA sequencing analysis reliably measured approximately 60% of the genome. Severity of RSV illness had the greatest effect size upon CD4 T-cell gene expression. Pathway analysis identified correlates of severity, including JAK/STAT, prolactin, and interleukin 9 signaling. We also identified genes and pathways associated with timing of symptoms and RSV group (A/B). These data suggest fundamental changes in adaptive immune cell phenotypes may be associated with RSV clinical severity.

Therapeutic efficacy of a respiratory syncytial virus fusion inhibitor

Respiratory syncytial virus is a major cause of acute lower respiratory tract infection in young children, immunocompromised adults, and the elderly. Intervention with small-molecule antivirals specific for respiratory syncytial virus presents an important therapeutic opportunity, but no such compounds are approved today. Here we report the structure of JNJ-53718678 bound to respiratory syncytial virus fusion (F) protein in its prefusion conformation, and we show that the potent nanomolar activity of JNJ-53718678, as well as the preliminary structure–activity relationship and the pharmaceutical optimization strategy of the series, are consistent with the binding mode of JNJ-53718678 and other respiratory syncytial virus fusion inhibitors. Oral treatment of neonatal lambs with JNJ-53718678, or with an equally active close analog, efficiently inhibits established acute lower respiratory tract infection in the animals, even when treatment is delayed until external signs of respiratory syncytial virus illness have become visible. Together, these data suggest that JNJ-53718678 is a promising candidate for further development as a potential therapeutic in patients at risk to develop respiratory syncytial virus acute lower respiratory tract infection.

Costs of hospitalization with respiratory syncytial virus illness among children aged

BackgroundRespiratory syncytial virus (RSV) is the leading cause of acute respiratory illness in young children and results in significant economic burden. There is no vaccine to prevent RSV illness but a number of vaccines are in development. We conducted this study to estimate the costs of severe RSV illness requiring hospitalization among children <5 years and associated financial impact on households in Bangladesh. Data of this study could be useful for RSV vaccine development and also the value of various preventive strategies, including use of an RSV vaccine in children if one becomes available.MethodsFrom May through October 2010, children aged <5 years with laboratory–confirmed RSV were identified from a sentinel influenza program database at four tertiary hospitals. Research assistants visited case–patients’ homes after hospital discharge and administered a structured questionnaire to record direct medical costs (physician consultation fee, costs for hospital bed, medicines and diagnostic tests); non–medical costs (costs for food, lodging and transportation); indirect costs (caregivers’ productivity loss), and coping strategies used by families to pay for treatment. We used WHO–Choice estimates for routine health care service costs. We added direct, indirect and health care service costs to calculate cost–per–episode of severe RSV illness. We used Monte Carlo simulation to estimate annual economic burden for severe RSV illness.FindingsWe interviewed caregivers of 39 persons hospitalized for RSV illness. The median direct cost for hospitalization was US$ 62 (interquartile range [IQR] = 43–101), indirect cost was US$ 19 (IQR = 11–29) and total cost was US$ 94 (IQR = 67–127). The median out–of–pocket cost was 24% of monthly household income of affected families (US$ 143), and >50% families borrowed money to meet treatment cost. We estimated that the median direct cost of RSV–associated hospitalization in children aged <5 years in Bangladesh was US$ 10 million (IQR: US$ 7–16 million), the median indirect cost was US$ 3.0 million (IQR: 2–5 million) in 2010.ConclusionRSV–associated hospitalization among children aged <5 years represents a substantial economic burden in Bangladesh. Affected families frequently incurred considerable out of pocket and indirect costs for treatment that resulted in financial hardship.

Clinical and Socioeconomic Burden of Respiratory Syncytial Virus Infection in Children.

Vaccines and antivirals against respiratory syncytial virus (RSV) are being developed, but there are scarce data on the full impact of RSV infection on outpatient children. We analyzed the burden of RSV illness in a prospective cohort study of children aged ≤13 years during 2 consecutive respiratory seasons in Turku, Finland (2231 child-seasons of follow-up). We examined the children and obtained nasal swabs for the detection of RSV during each respiratory illness. The parents filled out daily symptom diaries throughout the study. Of 6001 medically attended respiratory infections, 302 (5%) were caused by RSV. Per 1000 children, the average annual RSV infection incidence rates among children aged <3, 3-6, and 7-13 years were 275, 117, and 46 cases, respectively. In children aged <3 years, acute otitis media developed in 58%, and 66% of children in this age group received antibiotics. The mean duration of RSV illness was longest (13.0 days) and the rate of parental work absenteeism was highest (136 days per 100 children with RSV illness) in children aged <3 years. The burden of RSV is particularly great among outpatient children aged <3 years. Young children are an important target group for the development of RSV vaccines and antivirals.

Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus.

The lack of a licensed vaccine for respiratory syncytial virus (RSV) can be partly attributed to regulatory hurdles resulting from vaccine enhanced respiratory disease (ERD) subsequent to natural RSV infection that was observed in clinical trials of formalin-inactivated RSV (FI-RSV) in antigen-naïve infants. To develop an effective vaccine that does not enhance RSV illness, it is important to understand how formalin and heat inactivation affected the antigenicity and immunogenicity of FI-RSV compared to native virus. Informed by atomic structures of RSV fusion (F) glycoprotein in prefusion (pre-F) and postfusion (post-F) conformations, we demonstrate that FI-RSV predominately presents post-F on the virion surface, whereas infectious RSV presents both pre-F and post-F conformations. This significant antigenic distinction has not been previously appreciated. Thus, a stabilized pre-F antigen is more representative of live RSV than F in its post-F conformation, as displayed on the surface of FI-RSV. This finding has major implications for discriminating current pre-F-based immunogens from FI-RSV used in historical vaccine trials.

Respiratory Tract Infection and Risk of Hospitalization in Children with Congenital Heart Defects During Season and Off-Season: A Swedish National Study.

Respiratory tract infections (RTI) are common among young children, and congenital heart defect (CHD) is a risk factor for severe illness and hospitalization. This study aims to assess the relative risk of hospitalization due to RTI in winter and summer seasons for different types of CHD. All children born in Sweden and under the age of two, in 2006–2011, were included. Heart defects were grouped according to type. Hospitalization rates for respiratory syncytial virus (RSV) infection and RTI in general were retrieved from the national inpatient registry. The relative risk of hospitalization was calculated by comparing each subgroup to other types of CHD and otherwise healthy children. The relative risk of hospitalization was increased for all CHD subgroups, and there was a greater increase in risk in summer for the most severe CHD. This included RSV infection, as well as RTI in general. The risk of hospitalization due to RTI is greater for CHD children. Prophylactic treatment with palivizumab, given to prevent severe RSV illness, is only recommended during winter. We argue that information to healthcare staff and parents should include how the risk of severe infectious respiratory tract illnesses, RSV and others, is present all year round for children with CHD.

Clinical Presentation and Birth Outcomes Associated with Respiratory Syncytial Virus Infection in Pregnancy.

BackgroundRespiratory syncytial virus (RSV) is the most important cause of viral pneumonia in children worldwide. A maternal vaccine may protect both the mother and infant from RSV illness. The epidemiology and clinical presentation of RSV in pregnant and postpartum women is not well-described.MethodsData were collected from a prospective, randomized trial of influenza immunization in pregnant women in rural southern Nepal. Women were enrolled in their second trimester of pregnancy and followed until six months postpartum. Active weekly home-based surveillance for febrile respiratory illness was performed. Mid-nasal swabs collected with episodes of respiratory illness were tested for RSV by real-time polymerase chain reaction.ResultsRSV was detected in 14 (0.4%) illness episodes in 3693 women over 3554 person-years of surveillance from 2011–2014. RSV incidence was 3.9/1000 person-years overall, and 11.8/1000 person-years between September and December. Seven (50%) women sought care for RSV illness; none died. Of the 7 (50%) illness episodes during pregnancy, all had live births with 2 (29%) preterm births and a median birthweight of 3060 grams. This compares to 469 (13%) preterm births and a median birthweight of 2790 grams in women without RSV during pregnancy. Of the 7 mothers with postpartum RSV infection, RSV was detected in 4 (57%) of their infants.ConclusionsRSV was an uncommon cause of febrile respiratory illness in mothers during pregnancy in Nepal. These data will inform prevention and therapeutic strategies against RSV in resource-limited settings.

Clinical Endpoints for Respiratory Syncytial Virus Prophylaxis Trials in Infants and Children in High-income and Middle-income Countries.

Respiratory syncytial virus (RSV) continues to cause significant clinical and economic burden around the world. Historically, RSV-associated hospitalization was used as a primary endpoint for RSV prophylaxis trials in infants. However, because of the changing epidemiology and healthcare system landscape, this endpoint has become a critical bottleneck on the pathway to licensure for new therapeutics. A panel of 7 RSV experts was convened (Chicago, IL, May 22, 2014) to evaluate the challenges of defining RSV prevention endpoints for clinical trials and to develop endpoints that are clinically meaningful while minimizing subjectivity and bias to achieve sufficient consistency of response for regulatory approval. Particular consideration was given to the ability to collect data systematically and consistently in countries with different healthcare practices and systems, while capturing the greatest proportion of disease impact. The group consensus was that a clinically meaningful primary endpoint could include medically attended RSV illness in settings beyond RSV-associated hospitalizations alone, in particular, a composite reduction in hospitalization, emergency room or urgent care center visits because of an RSV respiratory infection. Relevant secondary endpoints included reductions in RSV lower respiratory tract infection, RSV-related intensive care unit rates, subsequent recurrent wheezing or asthma and direct and indirect costs.

Caesarean section and hospitalization for respiratory syncytial virus infection: a population-based study.

Hospitalization for respiratory syncytial virus (RSV) infection and asthma share common determinants, and meta-analyses indicate that children delivered by caesarean section (CS) are at increased risk of asthma. We aimed to investigate whether birth by CS is associated with an increased risk of hospitalization for RSV illness. This was a population-based national register-based cohort study, conducted between January, 1997 and June, 2003, which included all children born in Denmark and all hospitalizations for RSV disease in them from 0 to 23 months of age. We used Cox regression with adjustment for prematurity, asphyxia, birthweight, multiple births, single parenthood, maternal smoking during pregnancy, older siblings and asthma diagnoses up to 2 weeks before hospitalization for RSV infection, to compare the effects of acute or elective CS versus vaginal delivery, on subsequent hospitalization for RSV disease. A test for homogeneity was used to assess for effect over time. 399,175 children with 10,758 hospitalizations for RSV illness were included; 31,715 were born by acute CS and 30,965 by elective CS. Adjusted hazard ratios for hospitalization for RSV infection in children born by acute CS and by elective CS were 1.09 (1.01-1.17) and 1.27 (1.19-1.36), respectively. The effect of elective CS remained unchanged throughout the first 2 years of life (P = 0.53), whereas the effect of acute CS was only present in the second year of life (P = 0.001). Delivery by caesarian section is associated with an increased risk of hospitalization for RSV infection. This effect continues at least throughout the first 2 years of life.

Children with Down Syndrome Are High-Risk for Severe Respiratory Syncytial Virus Disease

To assess Down syndrome as an independent risk factor for respiratory syncytial virus (RSV) hospitalization in children younger than 3 years of age and to evaluate illness severity. A retrospective cohort study of children enrolled in the military health system database was conducted. The effect of Down syndrome on RSV hospitalization was assessed by Cox proportional hazards model, while we controlled for risk factors. Disease severity was assessed by length of hospital stay, need for respiratory support, and age at hospitalization. The study included 633 200 children and 3 209 378 person-years. Children with Down syndrome had a hospitalization rate of 9.6% vs 2.8% in children without Down syndrome. Down syndrome had a greater adjusted hazard ratio (HR) for RSV hospitalization than most risk factors, 3.46 (95% CI 2.75-4.37). A sensitivity analysis demonstrated HR 3.21 (95% CI 2.51-4.10) for patients with Down syndrome ages 0-23 months and HR 5.07 (95% CI 2.21-11.59) ages 24-36 months. The median (IQR) length of stay of children with and without Down syndrome was 4 days (2-7) and 2 days (1-4) (P < .001). Patients with Down syndrome had a greater risk of requiring respiratory support (relative risk 5.5; 95% CI, 2.5-12.3). The median (IQR) ages at admission for children with and without Down syndrome were 9.8 months (5.5-17.7) and 3.5 months (1.7-8.7) (P < .001). Down syndrome is independently associated with an increased risk for RSV hospitalization. Children with Down syndrome are older at time of RSV hospitalization and have more severe RSV illness than children without Down syndrome. This increased risk for hospitalization continues beyond 24 months.

Transmission of respiratory syncytial virus infection within families.

Background. Because the production of an effective respiratory syncytial virus (RSV) vaccine for infants is challenging, vaccination of other family members is one viable alternative to prevent severe RSV illnesses in infants. Methods. In a prospective study, we enrolled all family members of children who were hospitalized with RSV infection. Nasal swabs for RSV detection were obtained from all participating family members. Data on respiratory symptoms in the family members prior to and after the child's admission were collected using standardized questionnaires. Results. At the time of or within 1 week after the index child's hospitalization, RSV was detected in 40 (77%) of the 52 families and in 60 (47%) of 129 family members. Forty-nine (82%) of RSV detections in the family members were associated with respiratory symptoms. A sibling or a parent was the probable primary case of RSV in 30 (58%) families. Respiratory syncytial virus loads in the nasal swabs were significantly higher (10(7.7)) in index children than in their parents (10(5.1), P < .0001). Conclusions. In most cases, the likely source of an infant's RSV infection is an older sibling or a parent. These findings support the strategy of reducing the burden of RSV in infants by vaccination of their family members.

The prevention of respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is the most significant cause of acute respiratory tract infections in infants and young children worldwide. RSV accounts for approximately 70% of hospitalizations for bronchiolitis and 40% of pneumonia among infants <1 year of life. RSV infection seems to be associated with recurrent wheezing during the first decade of life and impaired respiratory health-related quality of life in adults [1]. Universal prevention of RSV infection is based on environmental prophylaxis aimed at minimizing the spread of the virus good hand hygiene in the home, and limiting direct contact of high-risk children with other children and adults with respiratory tract infections. Exposure to tobacco smoke should be avoid in family with infants, breastfeeding should be encouraged. Pharmacological prophylaxis is based on the administration of palivizumab (Synagis ®, MedImmune) during the epidemic period to the children at risk [2]. Palivizumab is a humanized monoclonal antibody directed to an epitope in the A antigenic site of F protein of RSV. It is designed to provide passive immunity against RSV and thereby prevent or reduce the severity of RSV infection [2]. The aim of this work is to provide Italian neonatologists shared recommendations regarding palivizumab use in premature and other at-risk infants in the light of new emerging evidence. The peak incidence of severe RSV disease occurs between 2 and 3 months of age. The risk of serious RSV illness is highest among preterm neonates, children with chronic lung disease, congenital heart disease [3,4]. The children with the above mentioned clinical conditions, particularly in cases of hospitalization, are more likely to require admission to an intensive care unit and need mechanical ventilation. In addition they have high rates of re-hospitalization for lower respiratory tract infections [5,6]. Therefore, all these categories of infants are likely to benefit from prophylaxis, and have been included in the recommendations. Specific recommendations are provided according to gestational age at birth RSV infections occur most frequently during the period between October-March. According to this observation, prophylaxis with Palivizumab is indicated in this 5-6 months long seasonal window of RSV infection. The duration of prophylaxis (up to one year or up to two years of life during the seasonal period) depends on the underlying condition. Palivizumab is clinically effective; however, the cost is very high. In our opinion strict criteria for patient selection and reduced drug costs would improve the cost-effectiveness of the prophylaxis [7].

Risk of current asthma among adult smokers with respiratory syncytial virus illnesses in early life.

Risk of subsequent asthma-like symptoms after early-life lower respiratory illness (LRI) caused by respiratory syncytial virus (RSV) is increased during the first decade of childhood and diminished thereafter by adolescence. To determine the relation of early-life RSV-LRI on adult asthma-like symptoms and its interactive role with adult smoking. A total of 1,246 nonselected infants were enrolled at birth and prospectively followed. Virologically confirmed RSV-LRIs were assessed during the first 3 years of life. At age 22, 24, 26, and 29 years, current asthma and smoking behavior were evaluated by questionnaire. Peak flow variability was assessed at age 26 and expressed as amplitude % mean. A longitudinal analysis was used to investigate the relation of RSV-LRI and active smoking to adult outcomes. Neither RSV-LRI nor active smoking were directly associated with increased current adult asthma or peak flow variability. However, there was a significant interaction between RSV-LRI and active smoking in relation to current asthma (P for interaction = 0.004) and peak flow variability (P for interaction = 0.04). Among subjects with early RSV-LRI, those who actively smoked were 1.7 times more likely to have current asthma (95% confidence interval, 1.2-2.3; P = 0.003) and had greater amplitude % mean (10.0% vs. 6.4%; P = 0.02) than nonsmokers. Among subjects without early RSV-LRI, there was no difference in asthma risk or peak flow variability between active smokers and nonsmokers. Smoking is associated with increased risk of having asthma in young adults who had RSV-LRI in early life but not among subjects without these illnesses.

Hospitalization for Respiratory Syncytial Virus Illness in Down Syndrome Following Prophylaxis With Palivizumab

Down syndrome (DS) is a risk factor for respiratory syncytial virus (RSV) hospitalization, but little is known about prophylaxis in these children. CARESS is a prospective registry of children who received ≥1 dose of palivizumab during the 2006-2012 RSV seasons across 32 sites in Canada. The objective was to compare respiratory illness hospitalization and RSV hospitalization (RSVH) hazard ratios in DS children aged <2 years who received palivizumab versus children who received prophylaxis for standard indications (SI) and for other medical illnesses (MI). 13,310 children were enrolled; DS (600; 4.5%), SI (11,081; 83.3%) and MI (1629, 12.2%), with DS children increasing over the duration from 0.1% (2006) to 4.5% (2012). Participants were significantly different in mean birth weight, gestational and enrollment age and risk factors. Children in each group received an average of 4.3 ± 1.4 (DS), 4.1 ± 1.6 (SI) and 4.5 ± 1.4 (MI) palivizumab injections per RSV season, with DS, differing significantly from SI [F(2, 13,307) = 43.6, P = 0.01] but not MI [F(2, 13 307) = 43.6, P = 0.07]. Compliance rates were similar across the groups. While a significantly greater proportion of SI children had RIHs compared with DS, [hazard ratio: 0.64 (0.48-0.84); P = 0.001] hazard ratios were similar for DS and MI. RSVH incidence rates were: 1.53%, 1.45% and 2.27% for DS, SI and MI, respectively. Neither group nor compliance affected time to RSVH. The proportion of DS children who received palivizumab in CARESS has increased almost 45-fold. RSVH rates were low in DS following prophylaxis and hazards were similar to those found in SI and MI.

Risk Factors for Respiratory Syncytial Virus Illness Among Patients with Chronic Obstructive Pulmonary Disease

Respiratory syncytial virus (RSV), although not typically considered an important pathogen in adults, may cause acute exacerbation of chronic obstructive pulmonary disease (COPD). It is unclear which COPD patients are at highest risk for developing serious RSV illness. Our objective was to identify risk factors for RSV illness among adult patients with COPD. We conducted a pooled analysis of data from COPD patients in 2 previously published longitudinal studies that examined RSV infection in high risk adults for ≤ 2 RSV seasons. Risk factors for RSV illness studied included age, sex, race, smoking status, exposure to children, home oxygen use, inhaled or oral steroid use, instrumental activities of daily living scores, and co-morbid conditions. Outcomes studied included symptomatic and medically attended RSV illness. Logistic regression was used to identify significant risk factors for RSV illness among older adults with COPD. Among 379 patients with COPD, the rate of symptomatic RSV illness was 11.1% (42/379); almost half (20/42) of whom required medical attention. In multivariable analyses, congestive heart failure (odds ratio [OR] = 4.18; 95% CI: 1.38, 12.69) and exposure to children (OR = 2.38; 95% CI: 1.03, 5.51) were risk factors for symptomatic RSV illness. Congestive heart failure (OR = 4.16; 95% CI: 1.02, 17.01) was the only significant risk factor for developing medically attended RSV illness. Exposure to children and congestive heart failure are risk factors for RSV illness among adult patients with COPD. Future prospective, well-designed studies are needed to corroborate these findings and examine other risk factors, including history of exacerbations.

Overview of respiratory syncytial virus disease in young children

Correspondence: J Michael Hoopes MedImmune, LLC, 1 MedImmune Way, Gaithersburg, MD 20878, USA Tel +1 301 398 5520 Fax +1 301 398 8520 Email hoopesm@medimmune.com Abstract: Respiratory tract illnesses associated with respiratory syncytial virus (RSV) were first reported more than 160 years ago and gained acceptance as a major respiratory pathogen in the late 1950s. Annual epidemics show a seasonal pattern typically beginning in the late fall and ending in early spring, averaging 5 months in length, and varying in time of onset, offset, and duration depending on geographic location. Manifestations of RSV illness primarily involve the upper respiratory tract but can spread to the lower airways and lead to bronchiolitis and/or pneumonia. Initial infection occurs in approximately two-thirds of children during the first year of life; nearly all children are infected at least once by 2 years of age. Reinfection is common throughout life, but initial illness during infancy generally presents with the most severe symptoms. Medical risk conditions that consistently predispose young children to serious lower respiratory tract infection (LRTI) include congenital heart disease, chronic lung disease, and premature birth. Serious LRTI due to RSV is the leading cause of hospitalization in infants and young children worldwide and annual mean hospital expenses have been estimated to exceed 1 billion dollars in the United States. Young children incur more inpatient and outpatient visits for RSV LRTI than for influenza. RSV has a greater impact than influenza on hospitalization in infants with respect to length of stay, severity/course of disease, and resultant needs for ancillary treatments. Unlike many other childhood illnesses, a vaccine is not currently available for preventing RSV disease.

Systematic literature review assessing tobacco smoke exposure as a risk factor for serious respiratory syncytial virus disease among infants and young children.

BackgroundThe role of environmental tobacco smoke (ETS) exposure as a risk factor for serious respiratory syncytial virus (RSV) disease among infants and young children has not been clearly established. This systematic review was conducted to explore the association between ETS exposure and serious RSV disease in children younger than 5 years, including infants and young children with elevated risk for serious RSV disease.MethodsA systematic review of English-language studies using the PubMed and EMBASE databases (1990–2009) was performed to retrieve studies that evaluated ETS as a potential risk factor for serious RSV illness. Studies assessing risk factors associated with hospitalization, emergency department visit, or physician visit due to RSV (based on laboratory confirmation of RSV or clinical diagnosis of RSV) in children under the age of 5 years were included.ResultsThe literature search identified 30 relevant articles, categorized by laboratory confirmation of RSV infection (n = 14), clinical diagnosis of RSV disease (n = 8), and assessment of RSV disease severity (n = 8). Across these three categories of studies, at least 1 type of ETS exposure was associated with statistically significant increases in risk in multivariate or bivariate analysis, as follows: 12 of 14 studies on risk of hospitalization or ED visit for laboratory-confirmed RSV infection; 6 of 8 studies of RSV disease based on clinical diagnosis; and 5 of the 8 studies assessing severity of RSV as shown by hospitalization rates or degree of hypoxia. Also, 7 of the 30 studies focused on populations of premature infants, and the majority (5 studies) found a significant association between ETS exposure and RSV risk in the multivariate or bivariate analyses.ConclusionWe found ample evidence that ETS exposure places infants and young children at increased risk of hospitalization for RSV-attributable lower respiratory tract infection and increases the severity of illness among hospitalized children. Additional evidence is needed regarding the association of ETS exposure and outpatient RSV lower respiratory tract illness. Challenges and potential pitfalls of assessing ETS exposure in children are discussed.

Residential crowding and severe respiratory syncytial virus disease among infants and young children: A systematic literature review

BackgroundThe objective of this literature review was to determine whether crowding in the home is associated with an increased risk of severe respiratory syncytial virus (RSV) disease in children younger than 5 years.MethodsA computerized literature search of PubMed and EMBASE was conducted on residential crowding as a risk factor for laboratory-confirmed RSV illness in children younger than 5 years. Study populations were stratified by high-risk populations, defined by prematurity, chronic lung disease of prematurity, hemodynamically significant congenital heart disease, or specific at-risk ethnicity (i.e. Alaska Native, Inuit), and mixed-risk populations, including general populations of mostly healthy children. The search was conducted for articles published from January 1, 1985, to October 8, 2009, and was limited to studies reported in English. To avoid indexing bias in the computerized databases, the search included terms for multivariate analysis and risk factors to identify studies in which residential crowding was evaluated but was not significant. Methodological quality of included studies was assessed using a Cochrane risk of bias tool.ResultsThe search identified 20 relevant studies that were conducted in geographically diverse locations. Among studies of patients in high-risk populations, 7 of 9 found a statistically significant association with a crowding variable; in studies in mixed-risk populations, 9 of 11 found a significant association with a crowding variable. In studies of high-risk children, residential crowding significantly increased the odds of laboratory-confirmed RSV hospitalization (i.e. odds ratio ranged from 1.45 to 2.85). In studies of mixed-risk populations, the adjusted odds ratios ranged from 1.23 to 9.1. The findings on the effect of residential crowding on outpatient RSV lower respiratory tract infection were inconsistent.ConclusionsResidential crowding was associated with an increased risk of laboratory-confirmed RSV hospitalization among high-risk infants and young children. This association was consistent despite differences in definitions of residential crowding, populations, or geographic locations.

Epidemiology of Respiratory Syncytial Virus Infection in Preterm Infants

This review focuses on the burden of respiratory syncytial virus (RSV) infection in preterm infants with and without chronic lung disease (bronchopulmonary dysplasia, BPD). The year-to-year and seasonal variations in RSV activity are key aspects of RSV epidemiology, and knowledge/monitoring of local RSV activity is mandatory for guidance of prophylaxis with the monoclonal antibodies palivizumab and in the near future motavizumab. Morbidity expressed in rates of hospitalizations attributable to RSV illness revealed a mean of 10 percent in preterm infants without and 19 percent (p=0.016) with BPD. Mortality rates diverged widely, and case fatality rates have been reported to range from 0 to 12 percent. The typical clinical picture of lower respiratory tract infection is not different in term and preterm infants, but rates of apnoeas are significantly increased in preterms, ranging from 4.9 to 37.5 percent with decreasing rates observed in more recent studies. Until a RSV vaccine is developed and will be available, prophylaxis with palivizumab is the only preventative strategy other than hand hygiene and contact measures that significantly reduces RSV hospitalization rates in preterm infants both with and without BPD.