Importance Of Respiratory Syncytial Virus Research Articles

Importance of respiratory syncytial virus as a predictor of hospital length of stay in bronchiolitis

Introduction : Bronchiolitis is the leading cause of hospitalization in children. Estimate potentially preventable variables that impact the length of hospital stay are a priority to reduce the costs associated with this disease. This study aims to identify clinical variables associated with length of hospital stay of bronchiolitis in children in a tropical middle-income country Methods: We conducted a retrospective cohort study in 417 infants with bronchiolitis in tertiary centers in Colombia. All medical records of all patients admitted through the emergency department were reviewed. To identify factors independently associated we use negative binomial regression model, to estimate incidence rate ratios (IRR) and adjust for potential confounding variables Results : The median of the length of hospital stay was 3.68 days, with a range of 0.74 days to 29 days, 138 (33.17%) of patients have a hospital stay of 5 or more days. After modeling and controlling for potential confounders age <6 months, comorbidities (CHD or neurological), BPD, chest indrawing, detection of RSV, and C-reactive protein were independent predictors of LOS Conclusions : Our results show that in infants with bronchiolitis, detection of RSV, age <6 months, comorbidities (CHD or neurological), BPD, chest indrawing, and C-reactive protein were independent predictors of LOS. As a potentially modifiable risk factor, efforts to reduce the probability of RSV infection can reduce the high medical cost associates with prolonged LOS in bronchiolitis.

Importance of respiratory syncytial virus as a predictor of hospital length of stay in bronchiolitis

IIntroduction : Bronchiolitis is the leading cause of hospitalization in children. Estimate potentially preventable variables that impact the length of hospital stay are a priority to reduce the costs associated with this disease. This study aims to identify clinical variables associated with length of hospital stay of bronchiolitis in children in a tropical middle-income country Methods: We conducted a retrospective cohort study in 417 infants with bronchiolitis in tertiary centers in Colombia. All medical records of all patients admitted to the emergency department were reviewed. To identify factors independently associated we use negative binomial regression model, to estimate incidence rate ratios (IRR) and adjust for potential confounding variables Results : The median of the length of hospital stay was 3.68 days, with a range of 0.74 days to 29 days, 138 (33.17%) of patients have a hospital stay of 5 or more days. After modeling and controlling for potential confounders age <6 months, comorbidities (CHD or neurological), BPD, chest indrawing, RSV isolation, and C-reactive protein were independent predictors of LOS Conclusions : Our results show that in infants with bronchiolitis, RSV isolation, age <6 months, comorbidities (CHD or neurological), BPD, chest indrawing, and C-reactive protein were independent predictors of LOS. As a potentially modifiable risk factor, efforts to reduce the probability of RSV infection can reduce the high medical cost associates with prolonged LOS in bronchiolitis.

Importance of respiratory syncytial virus as a predictor of hospital length of stay in bronchiolitis

Introduction: Bronchiolitis is the leading cause of hospitalization in children. Estimate potentially preventable variables that impact the length of hospital stay are a priority to reduce the costs associated with this disease. This study aims to identify clinical variables associated with length of hospital stay of bronchiolitis in children in a tropical middle-income country Methods: We conducted a retrospective cohort study in 417 infants with bronchiolitis in tertiary centers in Colombia. All medical records of all patients admitted to the emergency department were reviewed. To identify factors independently associated we use negative binomial regression model, to estimate incidence rate ratios (IRR) and adjust for potential confounding variables Results: The median of the length of hospital stay was 3.68 days, with a range of 0.74 days to 29 days, 138 (33.17%) of patients have a hospital stay of 5 or more days. After modeling and controlling for potential confounders age &lt;6 months, comorbidities (CHD or neurological), BPD, chest indrawing, RSV isolation, and C-reactive protein were independent predictors of LOS Conclusions: Our results show that in infants with bronchiolitis, RSV isolation, age &lt;6 months, comorbidities (CHD or neurological), BPD, chest indrawing, and C-reactive protein were independent predictors of LOS. As a potentially modifiable risk factor, efforts to reduce the probability of RSV infection can reduce the high medical cost associates with prolonged LOS in bronchiolitis.

Importance of respiratory syncytial virus as a predictor of hospital length of stay in bronchiolitis.

Introduction: Bronchiolitis is the leading cause of hospitalization in children. Estimate potentially preventable variables that impact the length of hospital stay are a priority to reduce the costs associated with this disease. This study aims to identify clinical variables associated with length of hospital stay of bronchiolitis in children in a tropical middle-income country Methods: We conducted a retrospective cohort study in 417 infants with bronchiolitis in tertiary centers in Colombia. All medical records of all patients admitted to the emergency department were reviewed. To identify factors independently associated we use negative binomial regression model, to estimate incidence rate ratios (IRR) and adjust for potential confounding variables Results: The median of the length of hospital stay was 3.68 days, with a range of 0.74 days to 29 days, 138 (33.17%) of patients have a hospital stay of 5 or more days. After modeling and controlling for potential confounders age <6 months, comorbidities (CHD or neurological), BPD, chest indrawing, RSV isolation, and C-reactive protein were independent predictors of LOS Conclusions: Our results show that in infants with bronchiolitis, RSV isolation, age <6 months, comorbidities (CHD or neurological), BPD, chest indrawing, and C-reactive protein were independent predictors of LOS. As a potentially modifiable risk factor, efforts to reduce the probability of RSV infection can reduce the high medical cost associates with prolonged LOS in bronchiolitis.

Characterization of the role of N-glycosylation sites in the respiratory syncytial virus fusion protein in virus replication, syncytium formation and antigenicity

Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization worldwide each year and there is presently no licensed vaccine to prevent severe RSV infections. Two major RSV glycoproteins, attachment (G) and fusion (F) protein, regulate viral replication and both proteins contain potential glycosylation sites which are highly variable for the G protein and conserved for the F protein among virus isolates. The RSV F sequence possesses five N-glycosylation sites located in the F2 subunit (N27 and N70), the p27 peptide (N116 and N126) and the F1 subunit (N500). The importance of RSV F N-glycosylation in virus replication and immunogenicity is not yet fully understood, and a better understanding may provide new insights for vaccine development. By using a BAC-based reverse genetics system, recombinant viruses expressing F proteins with loss of N-glycosylation sites were made. Mutant viruses with single N-glycosylation sites removed could be recovered, while this was not possible with the mutant with all N-glycosylation sites removed. Although the individual RSV F N-glycosylation sites were shown not to be essential for viral replication, they do contribute to the efficiency of in vitro and in vivo viral infection. To evaluate the role of N-glycosylation sites on RSV F antigenicity, serum antibody titers were determined after infection of BALB/c mice with RSV expressing the glycomutant F proteins. Infection with recombinant virus lacking the N-glycosylation site at position N116 (RSV F N116Q) resulted in significant higher neutralizing antibody titers compared to RSV F WT infection, which is surprising since this N-glycan is present in the p27 peptide which is assumed to be absent from the mature F protein in virions. Thus, single or combined RSV F glycomutations which affect virus replication and fusogenicity, and which may induce enhanced antibody responses upon immunization could have the potential to improve the efficacy of RSV LAV approaches.

Respiratory syncytial virus hospitalization in middle-aged and older adults

BackgroundThe importance of Respiratory Syncytial Virus (RSV) is increasingly recognized in hospitalized adults, but mainly in those ≥ 65 years. ObjectivesWe sought to describe the epidemiology and clinical severity of RSV compared to influenza in hospitalized adults ≥18 years. Study designAdults hospitalized with acute respiratory illnesses (ARI) of ≤10days duration were prospectively enrolled from two Michigan hospitals during two influenza seasons. Collected specimens were tested for RSV and influenza by real-time, reverse transcription polymerase chain reaction (RT-PCR). Viral load and subtype were determined for RSV-positive specimens. We evaluated factors associated with RSV and outcomes of infection using multivariable logistic regression. RSV-positive patients were separately compared to two reference groups: RSV-negative and influenza-negative, and influenza-positive patients. ResultsRSV was detected in 84 (7%) of 1259 hospitalized individuals (55 RSV-B, 29 RSV-A). The highest prevalence was found in 50–64year olds (40/460; 8.7%); 98% of RSV cases in this age group had at least one chronic comorbidity. RSV detection was associated with obesity (OR: 1.71 95% CI: 0.99-3.06, p=0.03). Individuals with RSV were admitted to the hospital later in their illness and had a higher median Charlson comborbidity index (3 vs 2 p<0.001) compared to those with influenza. Clinical severity of RSV-associated hospitalizations was similar to influenza-associated hospitalizations. DiscussionIn this study we observed the highest frequency of RSV-associated hospitalizations among adult 50–64 years old; many of whom had chronic comorbidities. Our results suggest the potential benefit of including these individuals in future RSV vaccination strategies.

Acute respiratory infections in hospitalized children in Vientiane, Lao PDR \u2013 the importance of Respiratory Syncytial Virus

The Human respiratory syncytial virus (RSV) is one of the most important viral pathogens, causing epidemics of acute respiratory infection (ARI), especially bronchiolitis and pneumonia, in children worldwide. To investigate the RSV burden in Laos, we conducted a one-year study in children <5 years old admitted to Mahosot Hospital, Vientiane Capital, to describe clinical and epidemiological characteristics and predictive factors for severity of RSV-associated ARI. Pooled nasal and throat swabs were tested using multiplex real-time PCR for 33 respiratory pathogens (FTD® kit). A total of 383 patients were included, 277 (72.3%) of whom presented with pneumonia. 377 (98.4%) patients were positive for at least one microorganism, of which RSV was the most common virus (41.0%), with a peak observed between June and September, corresponding to the rainy season. Most RSV inpatients had pneumonia (84.1%), of whom 35% had severe pneumonia. Children <3-months old were a high-risk group for severe pneumonia, independently of RSV infection. Our study suggests that RSV infection is frequent in Laos and commonly associated with pneumonia in hospitalized young children. Further investigations are required to provide a better overall view of the Lao nationwide epidemiology and public health burden of RSV infection over time.

Etiology of severe pneumonia in Ecuadorian children.

BackgroundIn Latin America, community-acquired pneumonia remains a major cause of morbidity and mortality among children. Few studies have examined the etiology of pneumonia in Ecuador.MethodsThis observational study was part of a randomized, double blind, placebo-controlled clinical trial conducted among children aged 2–59 months with severe pneumonia in Quito, Ecuador. Nasopharyngeal and blood samples were tested for bacterial and viral etiology by polymerase chain reaction. Risk factors for specific respiratory pathogens were also evaluated.ResultsAmong 406 children tested, 159 (39.2%) had respiratory syncytial virus (RSV), 71 (17.5%) had human metapneumovirus (hMPV), and 62 (15.3%) had adenovirus. Streptococcus pneumoniae was identified in 37 (9.2%) samples and Mycoplasma pneumoniae in three (0.74%) samples. The yearly circulation pattern of RSV (P = 0.0003) overlapped with S. pneumoniae, (P = 0.03) with most cases occurring in the rainy season. In multivariable analysis, risk factors for RSV included younger age (adjusted odds ratio [aOR] = 1.9, P = 0.01) and being underweight (aOR = 1.8, P = 0.04). Maternal education (aOR = 0.82, P = 0.003), pulse oximetry (aOR = 0.93, P = 0.005), and rales (aOR = 0.25, P = 0.007) were associated with influenza A. Younger age (aOR = 3.5, P = 0.007) and elevated baseline respiratory rate were associated with HPIV-3 infection (aOR = 0.94, P = 0.03).ConclusionThese results indicate the importance of RSV and influenza, and potentially modifiable risk factors including undernutrition and future use of a RSV vaccine, when an effective vaccine becomes available.Trial registrationClinicalTrials.gov NCT 00513929

Infant baboons infected with respiratory syncytial virus develop clinical and pathological changes that parallel those of human infants

Respiratory syncytial virus (RSV) infection of the lower respiratory tract is the leading cause of respiratory failure among infants in the United States of America and annually results in >300,000 deaths worldwide. Despite the importance of RSV, there is no licensed vaccine, and no specific form of therapy. This is largely due to the absence of an appropriate animal model for the evaluation of vaccines and therapeutic agents. We inoculated anesthetized infant (4 wk) baboons (Papio anubis) with a human strain of RSV intranasally or intratracheally. Baboons were monitored daily for clinical changes. Anesthetized baboons were intubated at various intervals, and bronchoalveolar lavage (BAL) was performed for viral culture and determination of leukocyte counts. Sham-infected baboons served as controls. Necropsies were performed on infected baboons on days 1, 3, 5, 8, or 13 after inoculation, with pathological analysis and immunohistochemical staining of lung tissues to detect RSV antigen. Infected baboons developed tachypnea and reduced oxygenation peaking from 4 to 8 days after infection and persisting for ≥14 days. Virus was recoverable in BAL fluid up to 8 days following infection. Necropsy revealed intense interstitial pneumonia, sloughing of the bronchiolar epithelium, and obstruction of the bronchiolar lumen with inflammatory cells and sloughed epithelial cells. RSV antigen was identified in bronchiolar and alveolar epithelium. We conclude that RSV-infected infant baboons develop clinical and pathological changes that parallel those observed in human infants with RSV infection. The infant baboon represents a much-needed model for studying the pathogenesis of RSV infection and evaluating antivirals and vaccines.

Nanobodies® Specific for Respiratory Syncytial Virus Fusion Protein Protect Against Infection by Inhibition of Fusion

Despite the medical importance of respiratory syncytial virus (RSV) infections, there is no vaccine or therapeutic agent available. Prophylactic administration of palivizumab, a humanized monoclonal RSV fusion (F) protein-specific antibody, can protect high-risk children. Previously, we have demonstrated that RSV can be neutralized by picomolar concentrations of a camelid immunoglobulin single-variable domain that binds the RSV protein F (F-VHHb nanobodies). Here, we investigated the mechanism by which these nanobodies neutralize RSV and tested their antiviral activity in vivo. We demonstrate that bivalent RSV F-specific nanobodies neutralize RSV infection by inhibiting fusion without affecting viral attachment. The ability of RSV F-specific nanobodies to protect against RSV infection was investigated in vivo. Intranasal administration of bivalent RSV F-specific nanobodies protected BALB/c mice from RSV infection, and associated pulmonary inflammation. Moreover, therapeutic treatment with these nanobodies after RSV infection could reduce viral replication and reduced pulmonary inflammation. Thus, nanobodies are promising therapeutic molecules for treatment of RSV.

The Association of Respiratory Syncytial Virus Infection and Influenza with Emergency Admissions for Respiratory Disease in London: An Analysis of Routine Surveillance Data

The importance of respiratory syncytial virus (RSV) infection in adults is not well known, because laboratory testing for RSV infection is not routine. Both RSV infection and influenza are seasonally related, and it is difficult to disentangle one from the other and to disentangle infection from the season and the cold. Emergency hospitalizations for respiratory disease from April 1994 to March 2001 were analyzed in relation to surveillance data on RSV infection and influenza, using Poisson regression models adapted for time series and adjusted for season, outdoor temperature, and other covariates. Age-specific admission rates attributable to the viruses were also estimated. Most of the crude relationships of emergency admissions of patients with RSV infection were confounded by season and, to a lesser extent, by cold temperatures. After adjustment for all covariates, including influenza, a 10th-90th percentile increase in RSV counts (defined as the daily number of laboratory reports of RSV) was associated with a rate ratio of 1.36 (95% CI, 1.27-1.45) for emergency admissions for respiratory disease in infants. The rate of hospitalization attributable to RSV infection in children aged <1 year was 5 per 1000 infants per year. The association in people > or =65 years old was much smaller (rate ratio, 1.09; 95% CI, 1.04-1.14; attributable rate of hospitalization , 0.7 per 1000 population); but unlike the association in infants, this association became smaller as the lag (interval) between infection and hospital admission became shorter. Admission rates attributable to influenza were highest in the > or =65-year age group (1.1 per 1000 population), but it was very small at younger ages. RSV infection appears to be an important determinant of hospitalization in infants in this data set but appears less certain for older persons and requires further investigation.

In Search of a Vaccine for Respiratory Syncytial Virus: The Saga Continues

More than 150 years ago, Eberle described bronchiolitis in infancy: the disease commences with cough and breathing [and] soon becomes laborious and wheezing.... The cough is at first dry, attended with a wheezing sound in the chest; but towards the termination of the complaint it frequently becomes humid and rattling (p. 222) [1]. This descriptive portrayal of respiratory syncytial virus (RSV) bronchiolitis remains accurate today. RSV epidemics continue to be characterized by lower respiratory tract disease in young infants, sleepless anxiety in parents, and increased workloads for medical personnel. It is now recognized that RSV is the major cause of respiratory tract disease in infants worldwide [2] and that infection with this virus consistently results in the increased use of health-care resources, including visits to physicians and the occupancy of hospital beds [3]. The importance of RSV in causing disease and morbidity in adults-part cularly in the debilitated and elderly-is also now appreciated [4]. It is known that, to prevent severe disease in infants, high levels of RSV-specific antibody can be administered as a monthly injection [5], but the costs of this antibody prophylaxis force health-care providers to make difficult choices when confronted by both expanding populations of high-risk infants and limited budgets. The seriousness and ubiquity of RSV disease was recognized and characterized by astute clinicians and researchers beginning in the late 1950s [6], although histologically confirmed disease from a 1937 outbreak was described as early as 1941 by Adams (figure 1) [7]. Propagation of the viral agent, obtained from infants with bronchiolitis, was reported from Chanock's laboratory at the National Institutes of Health (NIH) in 1957 [8], and RSV vaccine development began shortly after this time. This laboratory confirmed that this virus was the causal agent of chimpanzee coryza, described a year earlier by Morris et al. [9]. By 1969, it was stated with confidence that RS virus has been

Molecular and clinical characteristics of respiratory syncytial virus infections in hospitalized children.

The objective of this study was to determine the importance of respiratory syncytial virus (RSV) for hospitalization in the north east of Germany and to obtain molecular epidemiological data of the circulating strains. Using a rapid and sensitive reverse transcriptase-PCR, it was found that a quarter of pediatric respiratory disease admissions were due to RSV. Infections caused by RSV in hospitalized patients were determined over the whole year. Both RSV groups A and B were identified with a predominance of RSV A (86%) over the entire period. The analysis of the deduced amino acid sequences by direct sequencing showed that very similar RSV strains are circulating in the community.

Respiratory syncytial virus: the virus, the disease and the immune response.

RSV is the primary cause of hospitalisation in the first year of life for children in most parts of the world, and nearly 100% of children in the USA are infected with the virus by 2 to 3 years of age. The agent is an enveloped RNA virus with a non-segmented single-stranded negative-sense genome. The viral genome encodes 8 structural and 2 non-structural proteins. Important structural proteins include the fusion (F) protein and the attachment (G) protein which are essential for viral penetration and attachment to the host cells. Both proteins are important in development of immune responses. The virus is estimated to cause 3000 to 4000 deaths annually. Primary infections are as a rule symptomatic. The spectrum of clinical manifestations ranges from mild upper tract illness, infection in middle ear which progresses to acute otitis media, croup, to apnoea in premature infants, pneumonia and bronchiolitis. Premature babies born at 30–35 weeks of gestation, infants with cyanotic congenital heart disease, HIV-infected subjects, and patients on intensive immunosuppressive therapy especially after bone marrow transplant are considered to be at risk for increased mortality and morbidity during RSV infection. The virus does not normally replicate outside of the bronchopulmonary tree and the infection is exquisitely restricted to the respiratory mucosa. However, development of extrapulmonary disease has been observed in certain T and B cell immunodeficiency states. The association of RSV with asthma and reversible reactive airway disease in early childhood has attracted significant attention. Recurrent wheezing for up to 5 to 7 years of age and established airway disease has been observed in a significant number of children with a strong family history of allergy, after primary infection or reinfection with RSV. Immune response to primary infection is relatively small but on reinfection, a significant booster effect with sustained immunologic reactivity is observed in serum and respiratory mucosa. Both CD4- and CD8-specific as well as Th1- and Th2-cell specific immune responses have been observed during human infection. In addition, proinflammatory as well as immunoregulatory cytokines and chemokines are induced in the respiratory tract after natural and induced (in vitro) infection. Significant progress has been made in understanding the role of Th1 vs. Th2, IgE, viral induced cytokines and chemokines in the mechanisms of pathogenesis of the disease, development of wheezing and in the prevention and treatment of the infection and its sequelae. Respiratory syncytial virus (RSV) is one of the commonest human viral infections, and virtually every child is infected by the third birthday. Because of its restricted mucosal immunopathology, and frequent association with bronchial hyperreactivity and development of wheezing, RSV has served as an important model to investigate mechanisms of mucosal immune responses and development of mucosal disease following infection. The importance of RSV in bronchopulmonary disease and development of bronchial hyperreactivity has been the focus of several recent symposia [Kimpen JL, Simoes EAF. Am J Respir Crit Care Med 2001; 163:S1–S6]. This brief report will only summarise, based on selected references, the historical landmarks of its discovery and current understanding of the mechanisms of immunity, and their possible role in the pathogenesis of bronchopulmonary disease.

Respiratory Syncytial Virus Infection: An Emerging or Unappreciated Infection?

Respiratory syncytial virus (RSV) is a ubiquitous cause of respiratory infection with a worldwide distribution and seasonal occurrence. Natural immunity does not normally follow infection, and reinfection is the rule. Reinfection may even occur within a single season. Although its role in serious lower respiratory tract infection (LRTI) in infants is well recognized, the importance of RSV in disease of older children, adults and, especially in the elderly, is poorly appreciated. In large surveillance studies, RSV is at least as important in contributing to respiratory morbidity and mortality as influenza. These data would suggest that tens of millions of Americans suffer respiratory disease (LRTI and upper respiratory tract infection [URTI]) from RSV each winter. In addition, otitis media and episodic bronchospasm are complications following RSV infection. Unfortunately, there is no vaccine yet available for prevention. Prevention of disease with a hyperimmune globulin (RSVIG) and with a monoclonal antibody (MAb) (palivizuMab) is possible, but only for those neonates and infants at highest risk of morbidity and mortality from RSV infection. Therapy with the only approved antiviral for this indication, ribavirin, is difficult, is of questionable efficacy, and the compound itself is teratogenic. Infection by RSV constitutes an enormous but unappreciated medical need worldwide.