Burden Of Respiratory Syncytial Virus Research Articles

Infectious Burden of Respiratory Syncytial Virus in Relation to Time of Birth Modifies the Risk of Lower Respiratory Tract Infection in Infancy

The risk of respiratory syncytial virus (RSV) infection according to calendar month of birth has previously been demonstrated. We hypothesize that the real-time infectious burden (IB) of RSV, in relation to time and county of birth, modifies the risk of lower respiratory tract infection (LRTI) in infants, an association that has not been investigated previously, and may be used as an alternative measure of RSV risk when drafting RSV immunoprophylaxis guidelines. Thirty thousand eighty-seven pregnancies were included from July 1, 2003, to July 31, 2006. IB was defined by month and county as the number of RSV detections per inhabitant. IB for 5 periods ante- and postnatally was calculated for each child. Outcome variables were maternally reported hospitalization for LRTI before age 6 months and LRTI before age 12 months. Logistic regression was used to estimate associations between IB and LRTI. The odds of hospitalization for LRTI rise with increased IB the first 3 months after birth. Low IB: odds ratio (OR) 1.17 (95% confidence interval [CI]: 0.98-1.39); medium IB: OR 1.42 (95% CI: 1.21-1.68); high IB: OR 2.51 (95% CI: 2.15-2.94). High IB 3-0 months before birth confers a lower odds of hospitalization for LRTI the first 6 months of life, OR 0.51 (95% CI: 0.43-0.61). Similar results were seen for maternally reported LRTI the first 12 months of life. We find an association between real-time RSV infectious burden and LRTI in infancy: high burden before birth is protective and high burden after birth increases the risk.

A Model of the Costs of Community and Nosocomial Pediatric Respiratory Syncytial Virus Infections in Canadian Hospitals

Approximately one in 10 hospitalized patients will acquire a nosocomial infection (NI) after admission to hospital, of which 71% are due to respiratory viruses, including the respiratory syncytial virus (RSV). NIs are concerning and lead to prolonged hospitalizations. The economics of NIs are typically described in generalized terms and specific cost data are lacking. To develop an evidence-based model for predicting the risk and cost of nosocomial RSV infection in pediatric settings. A model was developed, from a Canadian perspective, to capture all costs related to an RSV infection hospitalization, including the risk and cost of an NI, diagnostic testing and infection control. All data inputs were derived from published literature. Deterministic sensitivity analyses were performed to evaluate the uncertainty associated with the estimates and to explore the impact of changes to key variables. A probabilistic sensitivity analysis was performed to estimate a confidence interval for the overall cost estimate. The estimated cost of nosocomial RSV infection adds approximately 30.5% to the hospitalization costs for the treatment of community-acquired severe RSV infection. The net benefits of the prevention activities were estimated to be equivalent to 9% of the total RSV-related costs. Changes in the estimated hospital infection transmission rates did not have a significant impact on the base-case estimate. The risk and cost of nosocomial RSV infection contributes to the overall burden of RSV. The present model, which was developed to estimate this burden, can be adapted to other countries with different disease epidemiology, costs and hospital infection transmission rates.

The Incidence and Clinical Burden of Respiratory Syncytial Virus Disease Identified through Hospital Outpatient Presentations in Kenyan Children

BackgroundThere is little information that describe the burden of respiratory syncytial virus (RSV) associated disease in the tropical African outpatient setting.MethodsWe studied a systematic sample of children aged <5 years presenting to a rural district hospital in Kenya with acute respiratory infection (ARI) between May 2002 and April 2004. We collected clinical data and screened nasal wash samples for RSV antigen by immunofluorescence. We used a linked demographic surveillance system to estimate disease incidence.ResultsAmong 2143 children tested, 166 (8%) were RSV positive (6% among children with upper respiratory tract infection and 12% among children with lower respiratory tract infection (LRTI). RSV was more likely in LRTI than URTI (p<0.001). 51% of RSV cases were aged 1 year or over. RSV cases represented 3.4% of hospital outpatient presentations. Relative to RSV negative cases, RSV positive cases were more likely to have crackles (RR = 1.63; 95% CI 1.34–1.97), nasal flaring (RR = 2.66; 95% CI 1.40–5.04), in-drawing (RR = 2.24; 95% CI 1.47–3.40), fast breathing for age (RR = 1.34; 95% CI 1.03–1.75) and fever (RR = 1.54; 95% CI 1.33–1.80). The estimated incidence of RSV-ARI and RSV-LRTI, per 100,000 child years, among those aged <5 years was 767 and 283, respectively.ConclusionThe burden of childhood RSV-associated URTI and LRTI presenting to outpatients in this setting is considerable. The clinical features of cases associated with an RSV infection were more severe than cases without an RSV diagnosis.

Respiratory viruses in neonates hospitalized with acute lower respiratory tract infections

BackgroundThe burden of respiratory syncytial virus (RSV) in neonates has not been clearly studied. The aims of this study were to determine the overall distribution of respiratory viruses in neonates hospitalized with acute lower respiratory tract infectiosns (ALRI) and to describe the clinical characteristics of RSV infections in these neonates.MethodsFrom January 2009 through May 2010, neonates aged <1 month who were hospitalized with ALRI and did not have underlying disease were included in the study. Viruses were identified on multiplex reverse transcription polymerase chain reaction using nasal swab samples. Clinical variables were evaluated between the RSV and non‐RSV infection groups.ResultsOf the 108 infants included in the study, 46 (42.6%) had RSV; human rhinovirus (18.5%), human parainfluenza virus 3 (7.5%), and human metapneumovirus (3.7%) were the next most common infections. Codetections accounted for 8.3% of the cases. Crowding increased the risk of RSV infection compared to the non‐RSV group (OR, 16.5; P = 0.001). The RSV group had a greater incidence of dyspnea ( P = 0.027), pneumonia (P < 0.001), requirement for oxygen ( P < 0.001), and prolonged hospitalization ( P = 0.011) than the non‐RSV group.Conclusions RSV was the most common viral etiology in neonates without underlying diseases who were hospitalized with ALRI. The disease severity of RSV infection was worse than that of other detected viral infections. Strict prevention strategies should be considered in overcrowded situations.

A High Burden of Respiratory Syncytial Virus Associated Pneumonia in Children Less than Two Years of Age in a South East Asian Refugee Population

BackgroundPneumonia is a major cause of childhood mortality and morbidity approximately 1.6 million deaths and 150 million episodes occur annually in children <5 years. Respiratory syncytial virus (RSV) may be responsible for up to 25% of cases and 12% of deaths making it an important potential vaccine target, although data from South East Asia is scarce.MethodsWe followed a birth cohort of Burmese refugee children, born over a one year period, for two years. Pneumonia episodes were diagnosed using WHO criteria. A chest radiograph, nasopharyngeal aspirate and non-specific markers of infection were taken during each episode.ResultsThe incidence of RSV-associated pneumonia was 0.24 (95% CI 0.22–0.26) episodes per child year. All children with pneumonia received antibiotic treatment, following WHO guidelines. The highest incidence was in the 2–12 month age group. The commonest diagnosis in a child with RSV-associated pneumonia was non-severe pneumonia (239/362∶66.0%), however the incidence of RSV-associated severe or very severe pneumonia was 0.08 (95% CI 0.01–0.10) episodes per child year. Birth in the wet season increased the risk of severe disease in children who had their first episode of RSV-associated pneumonia aged 2–11 months (OR 28.7, 95% CI 6.6–125.0, p<0.001). RSV episodes were highly seasonal being responsible for 80.0% of all the pneumonia episodes occurring each October and November over the study period.ConclusionsThere was a high incidence of RSV associated pneumonia in this refugee population. Interventions to prevent RSV infection have the potential to reduce the incidence of clinically diagnosed pneumonia and hence unnecessary antibiotic usage in this population.

High Concentrations of Amniotic Fluid Proinflammatory Cytokines in Healthy Neonates Are Associated With Low Risk of Respiratory Syncytial Virus Bronchiolitis

The burden of respiratory syncytial virus (RSV) bronchiolitis in individual children and their families, the medical system and society is considerable. Mechanisms underlying RSV bronchiolitis in healthy term infants are largely unknown. Sterile intraamniotic inflammation and chorioamnionitis have been associated with increased lung volume and compliance. The aim of this study was to determine whether high amniotic fluid interleukin-8 (IL-8), and tumor necrosis factor-α protect against RSV bronchiolitis in healthy term infants. We conducted a prospective birth cohort study of healthy term newborns, born after uncomplicated pregnancy. Amniotic fluid was collected during labor. In case of medical attention for respiratory symptoms during the first year of life, a nose-throat swab was taken to establish the presence of respiratory viruses by polymerase chain reaction. Physician-attended RSV infection was observed in 27 (9.3%) of 292 children at median age 6 months. Amniotic fluid concentrations of IL-8 were higher in children without physician-attended RSV infection than in children with physician-attended RSV infection (11.1 versus 5.5 ng/mL; P = 0.002). Similarly, in children without physician-attended RSV, the proportion of detectable amniotic fluid tumor necrosis factor-α was higher (159/265 [60%] versus 8/27 [30%]; P = 0.002). Among children with physician-attended RSV infection, amniotic fluid IL-8 was inversely correlated to the number of wheezing days during the first year of life (ρ = -0.38; P = 0.048). High concentrations of amniotic fluid IL-8 and tumor necrosis factor-α are associated with low risk of RSV bronchiolitis in healthy term infants. We hypothesize that direct exposure of fetal lungs to proinflammatory signals induces local protection against viral infection during infancy.

Rates of Hospitalizations for Respiratory Syncytial Virus, Human Metapneumovirus, and Influenza Virus in Older Adults

We performed a prospective study to determine the disease burden of respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) in older adults in comparison with influenza virus. During 3 consecutive winters, we enrolled Davidson County (Nashville, TN) residents aged ≥ 50 years admitted to 1 of 4 hospitals with acute respiratory illness (ARI). Nasal/throat swabs were tested for influenza, RSV, and HMPV with reverse-transcriptase polymerase chain reaction. Hospitalization rates were calculated. Of 1042 eligible patients, 508 consented to testing. Respiratory syncytial virus was detected in 31 participants (6.1%); HMPV was detected in 23 (4.5%) patients; and influenza was detected in 33 (6.5%) patients. Of those subjects aged ≥ 65 years, 78% received influenza vaccination. Compared with patients with confirmed influenza, patients with RSV were older and more immunocompromised; patients with HMPV were older, had more cardiovascular disease, were more likely to have received the influenza vaccination, and were less likely to report fever than those with influenza. Over 3 years, average annual rates of hospitalization were 15.01, 9.82, and 11.81 per 10,000 county residents due to RSV, HMPV, and influenza, respectively. In adults aged ≥ 50 years, hospitalization rates for RSV and HMPV were similar to those associated with influenza.

The Burgeoning Burden of Respiratory Syncytial Virus Among Children

Respiratory syncytial virus (RSV) was first isolated from infants by Chanock and colleagues in 1957. However, control of this ubiquitous agent has yet to be achieved. RSV is recognized as the primary cause of hospitalization for acute lower respiratory tract illness (LRTI) among infants worldwide. Among children < 5 years old, annual hospitalization rates in the United States (US) is 3/1000 children, and rates in Canada and European countries are similar. In the US the hospitalization rate is 3 times higher than that from influenza or parainfluenza viral infections. Much less appreciated is the clinical and economic burden from RSV outpatients, as few have specific diagnostic testing. Nevertheless, RSV in the US is estimated to cause 1 of 334 hospitalizations, 1 of 38 emergency department visits, but 1 of 13 private practice visits. These outpatient children tend to have moderate to severe illness with approximately three-fourths manifesting labored respirations. RSV burden among outpatients, therefore, is considerable both in size and severity. The global burden of RSV infection is unknown as few studies are from developing countries. Estimates indicate about one-fourth of all acute LRTI occur among children < 5 years, and the greatest burden is among children in developing countries. Currently the only approved means of RSV prophylaxis is passive immunization with humanized F protein monoclonal antibody. Such prophylaxis, however, has limited availability, is expensive, and is recommended only for infants most at risk for severe RSV disease. Only widespread immunization of children is likely to diminish the current burden of RSV infection.

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.

PIN34 Cost-Effectiveness of Respiratory Syncytial Virus (RSV) Vaccination of Dutch Elderly

OBJECTIVES: Respiratory syncytial virus (RSV) is increasingly recognized as an important cause of morbidity, mortality and health-care resource use in the elderly. Therefore we determined whether there are specific levels of vaccine cost and effectiveness for which a hypothetical RSV-vaccine for Dutch elderly could be cost-effective. METHODS: The annual excess RSV-associated age- and risk-specific burden was estimated using a rate-difference method. Different vaccination strategies were evaluated, for various levels of vaccine effectiveness and different levels of willingness to pay per quality-adjusted life year gained (QALY). Outcome measures included costs, QALYs, life years gained (LYGs), and the amount of money that can be spent per vaccination, while remaining cost-effective. RESULTS: Significant excess RSV-associated deaths, hospitalisations, GP-visits and antibiotic prescriptions were found. The burden of RSV increased with age and was higher for high-risk (HR) elderly than for low-risk (LR) elderly. For several scenarios vaccination of the Dutch elderly appeared to be cost-effective. Using base-case assumptions, the amount of money that can be spent per vaccination, while remaining cost-effective, ranged from €26 when vaccinating all 60+ elderly to €68 when vaccinating only 85+elderly, for a willingness to pay of €50,000 per QALY and a vaccine effectiveness of 70%. For HR-elderly only these estimates ranged from €52 to €99. CONCLUSIONS: Vaccination of Dutch elderly with a hypothetical RSV vaccine was found cost-effective for several scenarios. Vaccination is more likely to be costeffective when vaccinating only HR elderly than when vaccinating all elderly, despite a decreased life expectancy and quality of life and a decreased effectiveness of the vaccine assumed in HR-elderly in the model. This study shows the major burden of RSV in the Dutch elderly, potential cost-effectiveness of vaccination, stressing the need to have an effective vaccine available shortly.

Virologically Confirmed Population-based Burden of Hospitalization Caused by Respiratory Syncytial Virus, Adenovirus, and Parainfluenza Viruses in Children in Hong Kong

To determine virologically confirmed hospitalization rates associated with respiratory syncytial virus (RSV), adenovirus, and parainfluenza viruses in Hong Kong children. All patients <18 years of age living on Hong Kong Island (within Hong Kong SAR) admitted for a febrile acute respiratory infection to 1 of the 2 public hospitals on 1 fixed day of the week between October 2003 and September 2006 were prospectively recruited. Hong Kong Island has a known population denominator and these 2 hospitals managed 72.5% of all general pediatric admissions for this population. Nasopharyngeal aspirates were tested for RSV, adenovirus, and parainfluenzae types 1, 2, and 3 by direct antigen detection and culture. The annual hospitalization rate for RSV in infants <6 months of age was 233.4 to 311.2 per 10,000. Parainfluenza type 3 had a hospitalization rate of 27.3 to 122.8 per 10,000 in the 1 to <2 years group. Adenovirus was associated with significant hospitalization in those 6 months to 1 year (25.9-77.8 per 10,000), and in those 2 to <5 years (38.1-59.2 per 10,000). The mean duration of hospitalization for RSV was 4.04 ± 2.61 days, significantly longer than the 3.12 ± 1.41 days for adenovirus and the 2.93 ± 2.54 days for parainfluenza infections (P = 0.013 and P = 0.038, respectively). We documented that the overall pediatric hospitalization burden of RSV was high and comparable to that of influenza. The burden for all the studied viruses was mainly in previously healthy children <5 years of age.

Burden of respiratory syncytial virus in hospitalized infants and young children in Amman, Jordan

Acute respiratory infections (ARI) play a major role in hospitalizations in the Middle East, but the specific viral causes are unknown. We conducted prospective viral surveillance in children <5 y of age admitted with ARI and/or fever at 2 dissimilar hospitals in Amman, Jordan during peak respiratory syncytial virus (RSV) season. We collected prospective clinical and demographic data and obtained nose/throat swabs for testing for RSV by real-time polymerase chain reaction (RT-PCR). We obtained clinical and laboratory data for 728/743 (98%) subjects enrolled. The children's median age was 4.3 months, 58.4% were males, 87% were breastfed, 4% attended day care, 67% were exposed to smokers, 7% were admitted to the intensive care unit, and 0.7% died (n = 5). Out of 728 subjects, 467 (64%) tested positive by RT-PCR for RSV. Comparing RSV-positive with RSV-negative subjects, the RSV-positive subjects had lower median age (3.6 vs 6.4 months, p < 0.001) and fewer males (55% vs 64%, p = 0.02). RSV-positive children had higher rates of oxygen use (72% vs 42%, p < 0.001), a longer hospital stay (5 vs 4 days, p = 0.001), and higher hospital charges (US$538 vs US$431, p < 0.001) than RSV-negative children. In young hospitalized Jordanian infants, the medical and financial burden of RSV was found to be high. Effective preventive measures, such as an RSV vaccine, would have a significant beneficial impact.

Strategies for Reducing the Burden of Respiratory Syncytial Virus in High-Risk Infants

Respiratory syncytial viral infections cause considerable childhood morbidity, and in some countries significant mortality, especially in infants with pre-existing conditions such as bronchopulmonary dysplasia and congenital heart disease. Currently, there is no active vaccine and attempts to prevent and ameliorate the effects of infection are focused on passive immunization by human monoclonal antibodies. This review focuses on the clinical sequelae of respiratory syncytial viral infections in high-risk patients and discusses the effects of public health measures and passive immunization on medical and socioeconomic outcomes.

Continuing Education

Journal Article Continuing Education: Addressing the burden of respiratory syncytial virus Get access American Journal of Health-System Pharmacy, Volume 65, Issue 23_Supplement_8, 1 December 2008, Pages S23–S25, https://doi.org/10.1093/ajhp/65.23_Supplement_8.S23 Published: 01 December 2008

Reducing the burden of respiratory syncytial virus: An audit of the use of palivizumab prophylaxis in the UK during the September 2001–March 2002 RSV season

Palivizumab has been licensed for the prevention of respiratory syncytial virus (RSV) infection in vulnerable infants in the UK since 1999. To obtain an understanding of the real world use of palivizumab in the UK, an audit was undertaken during the 2001–2002 RSV season. Of the 190 infants included, the main treatment groups were ex-premature infants with chronic lung disease (CLD; 118 babies; 62.8%), babies with congenital heart defects (29; 15.4%) and premature infants without CLD (17; 9%). Nine (4.7%) babies were hospitalised with RSV infections. Compliance to the dose regimen was impaired in these infants including initiation of prophylaxis late in the RSV season, discontinuation mid season or inappropriate intervals between doses. We strongly recommend adherence to the dose regimen and report strategies that may be implemented to improve compliance.

Influenza and respiratory syncytial virus in the elderly

Respiratory infections are one of the leading causes of morbidity and mortality worldwide: influenza and respiratory syncytial virus (RSV) are the predominant pathogens responsible. Annual vaccination and the use of antiviral drugs provides both protection and treatment against influenza, particularly protecting those patients most at risk, including the elderly and individuals with chronic comorbidities. Currently, there are extremely limited options in the protection against RSV infection, making those at-risk patients vulnerable to serious disease, complications and death. This review focuses on recent trends in respiratory illness in the elderly, particularly focusing on the burden of influenza and RSV on hospitalizations and mortality. We discuss the potential benefit of influenza vaccination on these outcomes, including the recent controversial debate over the effectiveness of influenza vaccination.

Respiratory syncytial virus infection: denominator-based studies in Indonesia, Mozambique, Nigeria and South Africa.

To assess the burden of respiratory syncytial virus (RSV)-associated lower respiratory infections (LRI) in children in four developing countries. A WHO protocol for prospective population-based surveillance of acute respiratory infections in children aged less than 5 years was used at sites in Indonesia, Mozambique, Nigeria and South Africa. RSV antigen was identified by enzyme-linked immunosorbent assay performed on nasopharyngeal specimens from children meeting clinical case definitions. Among children aged < 5 years, the incidence of RSV-associated LRI per 1000 child-years was 34 in Indonesia and 94 in Nigeria. The incidence of RSV-associated severe LRI per 1000 child-years was 5 in Mozambique, 10 in Indonesia, and 9 in South Africa. At all study sites, the majority of RSV cases occurred in infants. These studies demonstrate that RSV contributes to a substantial but quite variable burden of LRI in children aged < 5 years in four developing countries. The possible explanations for this variation include social factors, such as family size and patterns of seeking health care; the proportion of children infected by human immunodeficiency syndrome (HIV); and differences in clinical definitions used for obtaining samples. The age distribution of cases indicates the need for an RSV vaccine that can protect children early in life.

Respiratory syncytial virus hospitalizations among American Indian and Alaska Native infants and the general United States infant population.

To determine the burden of respiratory syncytial virus (RSV) disease among American Indian (AI) and Alaska Native (AN) infants, by examining RSV-associated hospitalizations. Infant hospitalizations from 1997 through 2001 with RSV listed as a diagnosis were selected by using Indian Health Service/tribal hospital discharge data for AIs/ANs and National Hospital Discharge Survey data for the general US population. In 2000-2001, RSV disease was listed as a diagnosis for 14.4% of all AI/AN infant hospitalizations, with bronchiolitis attributable to RSV infection (12.2%) being among the top 5 listed diagnoses. The rate of RSV-specific hospitalizations was 34.4 hospitalizations per 1000 infants for AI/AN infants and 27.4 hospitalizations per 1000 births for the general US infant population. The hospitalization rates for AI/AN infants living in the Alaska and Southwest regions (70.9 and 48.2 hospitalizations per 1000 infants, respectively) were much higher than the overall rate for US infants. RSV infection is one of the leading causes of hospitalization among all infants in the United States, and AI/AN infants living in the Southwest and Alaska regions are at especially high risk for hospitalizations associated with RSV infection. Development of vaccines, antiviral agents, and other strategies to prevent RSV disease could yield substantial public health benefits.

Age-dependent replication of respiratory syncytial virus in the cotton rat.

Despite the documented disease burden of respiratory syncytial virus (RSV) in the elderly, little is known about the underlying risk factors or pathogenesis of RSV in a geriatric population. This report describes an age-dependent change of RSV clearance in the lung and nose of the cotton rat. Six days postinfection with RSV, lung and nose viral titers were significantly higher in all older age groups as compared with 4- to 6-week old cotton rats (P < 0.05). When comparing the 4- to 6-week old animals to the 15- to 16-month old animals 6 days postinfection, there was over an 800- and 100-fold increase in lung and nose viral titers, respectively. The cotton rat may prove to be a useful model in eliciting mechanisms of severe RSV disease in the elderly.