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PubMed1996

Invasive monitoring in infants with respiratory syncytial virus infection.

OBJECTIVE: Coincident with a change in the physician staff in our pediatric intensive care unit (PICU), the frequency and duration of invasive monitoring were decreased. We examined the impact of this change on outcomes, complications, and hospital charges in infants admitted to the PICU with respiratory syncytial virus (RSV) infection. STUDY DESIGN: We reviewed medical records of all children less than 1 year of age who were admitted to the PICU from January 1989 to July 1993 with confirmed RSV infection. Patient characteristics, therapeutic interventions, outcomes, and hospital charges were extracted and compared. RESULTS: Seventy-eight patients were identified, 38 admitted from January 1989 through July 1991 (group 1) and 40 from July 1991 through July 1993 (group 2). The groups were well matched in age, preexisting disease, and cardiorespiratory status on admission. Group 1 had significantly greater use of invasive monitoring, pharmacologic paralysis, inotropes, blood products, antibiotics, and parenteral nutrition. Outcomes were not different, but group 1 patients had significantly longer stays, more complications, and higher hospital charges. CONCLUSIONS: Routine use of invasive monitoring of PICU patients with RSV disease was associated with increased laboratory testing, overtreatment, and significant increases in costs and morbidity without improvement in outcome.

Case-Control Studies↗
PubMed1996

Effectiveness of ribavirin in otherwise well infants with respiratory syncytial virus-associated respiratory failure. Pediatric Critical Study Group.

OBJECTIVE: To examine ribavirin's effectiveness in otherwise well infants with respiratory syncytial virus (RSV)-associated respiratory failure. DESIGN: Prospective multicenter cohort study. SETTING: Pediatric critical care units affiliated with the Pediatric Critical Care Study Group; 38 centers from the United States and Canada participated. PATIENTS: Infants with RSV-associated respiratory failure undergoing mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data collected included demographic information; dates of hospitalization, intensive care, and mechanical ventilation; all patient diagnoses; reason for tracheal intubation; dates of ribavirin use before and during mechanical ventilation; time in hours after intubation until ribavirin administration; Pediatric Risk of Mortality (PRISM) score; and outcome. A total of 439 patients received mechanical ventilation for RSV-associated respiratory failure; 223 were classified as previously well and met entry criteria. Ninety-one infants (41%) received ribavirin during mechanical ventilation. The PRISM scores during the initial 24 hours of intensive care and blood gas measurements before intubation were similar for patients who received ribavirin versus those who did not. Use of ribavirin during mechanical ventilation was associated with prolonged duration of mechanical ventilation (p < 0.01) in a multivariate model that controlled for patient age, gender, prematurity status, and use of ribavirin before intubation. Subgroup analysis of mechanical ventilation days for previously well patients was 5.0 +/- 4.2 in the no-ribavirin group versus 6.4 +/- 5.0 in the ribavirin group (p < 0.05) and for well premature infants was 6.3 +/- 4.9 in the no-ribavirin group versus 9.0 +/- 6.3 in the ribavirin group (p < 0.01). The mortality rates for the term and the premature groups were similar for treated and untreated patients. CONCLUSIONS: Ribavirin administration during mechanical ventilation to previously well infants with RSV infection was not associated with reductions in either mortality rates or duration of mechanical ventilation. Additional clinical effectiveness studies are required to define specific groups in which the use of aerosolized ribavirin is indicated.

Administration, Inhalation↗
PubMed1997

Respiratory syncytial virus bronchiolitis: a double-blind dexamethasone efficacy study.

The efficacy of dexamethasone therapy for primary respiratory syncytial virus bronchiolitis was studied in a double-blind placebo design in 29 previously healthy infants (median age, 194 days). No significant differences were found between the groups in evolution of respiratory rate, oxygen saturation, clinical score, or pulmonary function tests on day 3.

Analysis of Variance↗
PubMed1998

Polymerase chain reaction-based detection of rhinovirus, respiratory syncytial virus, and coronavirus in otitis media with effusion.

OBJECTIVES: To study the association of human rhinovirus (HRV), respiratory syncytial virus (RSV), and human coronavirus infections in children aged 6 months to 12 years with otitis media with effusion (OME). To determine how long HRV RNA can be detected after HRV infection. METHODS: Middle ear effusion (MEE) samples collected at the time of tympanostomy tube placement from 100 children with OME were examined. Viral RNA was detected by reverse-transcriptase polymerase chain reaction. For HRV the results were compared with virus isolation in cell culture. In vitro studies of the persistence of HRV infectivity and RNA were conducted by combining approximately 10(5) median cell culture infectious doses of HRV with pooled MEE at 37 degrees C and assaying serial samples for 12 weeks. RESULTS: Virus RNA was detected in 30 children. HRV was detected by reverse-transcriptase polymerase chain reaction in 19 children with OME and by virus isolation in 5 children. RSV RNA was found in 8 and HCV in 3 children with OME. No dual viral infection was found. Bacterial pathogens were isolated from 35 MEE samples and were associated with viral RNA in 11 cases, most often with HRV (9 cases). Under in vitro conditions, HRV culture positivity declined rapidly (<2 days), but RNA was detectable for up to 8 weeks. CONCLUSIONS: These results suggest that virus infection, particularly HRV infection, either alone or concurrent with bacteria, is present in a larger percentage of children with OME than previously suspected. It remains to be determined how often the presence of viral RNA in MEE represents persistent RNA, ongoing viral replication, or recurrent infection.

Bacterial Infections↗
PubMed2001

Modeling epidemics caused by respiratory syncytial virus (RSV).

Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infection in children. In this paper we use models of RSV transmission to interpret the pattern of seasonal epidemics of RSV disease observed in different countries, and to estimate epidemic and eradication thresholds for RSV infection. We compare the standard SIRS model with a more realistic model of RSV transmission in which individuals acquire immunity gradually after repeated exposure to infection. The models are fitted to series of monthly hospital case reports of RSV disease from developed and developing countries. The models can explain many of the observed patterns: regular yearly outbreaks in some countries, and in other countries cycles of alternating larger and smaller annual epidemics, with shifted maxima in alternate years. Previously these patterns have been attributed to the transmission of different strains of RSV. In some countries the timing of epidemics is not consistent with increased social contact among school children during term time being the major driving mechanism. Climatic factors appear to be more important. Qualitatively different models gave equally good fits to the data series, but estimates of the transmission parameter were different by a factor of 4. Estimates of the basic reproduction number (R(0)) ranged from 1.2 to 2.1 with the SIRS model, and from 5.4 to 7.1 with the model with gradual acquisition of partial immunity.

Child↗
PubMed2000

Influenza and respiratory syncytial virus. Update on infection, management, and prevention.

This article is an overview of the epidemiology and spectrum of clinical disease attributed to influenza and respiratory syncytial virus in children. It separately discusses the pathogenesis of the two diseases and the host responses to the viruses to emphasize each infection's significance and need for a vaccine. Updates on current preventive measures and a preview of potential future vaccine developments are presented.

Adjuvants, Immunologic↗
PubMed1996

Influence of selective T-lymphocyte depletion on the lung pathology of gnotobiotic calves and the distribution of different T-lymphocyte subsets following challenge with bovine respiratory syncytial virus.

The depletion of CD8+ T-lymphocytes with a murine monoclonal antibody (mAb) specific for the CD8 molecule delayed the ability of three gnotobiotic calves to clear bovine respiratory syncytial virus (BRSV) from their lungs within 10 days after an experimental challenge with the virus. This protracted infection was associated with an enhanced pneumonic consolidation score (21.6 per cent) compared with seven control calves (7.4 per cent) and a histological lesion of active respiratory epithelial hypertrophy. Three gnotobiotic calves depleted of the CD4+ subpopulation with the appropriate mAb also had enhanced macroscopic lesions (16.6 per cent) but the histological lesion was less active. The depletion of the gamma/delta TCR+ WC1+ subpopulation had no apparent effect on the macroscopic or microscopic pulmonary lesions. Although the depletion of the CD8+ or the CD4+ subpopulations enhanced the pulmonary lesions, no clinical signs of respiratory disease were detected. Immunoperoxidase labelling and image analysis of the lymphocyte subpopulations in lung tissue revealed an increase in the number of CD8+ T cells after the infection of non-depleted, control calves, especially in the lamina propria of the large bronchioles. Calves depleted of individual lymphocyte subsets and infected with BRSV showed no compensatory increase in the remaining subpopulations and no lymphoreticular hyperplasia.

Animals↗
PubMedDate not supplied

Cytokine expression in pulmonary and peripheral blood mononuclear cells from calves infected with bovine respiratory syncytial virus.

The possible involvement of cytokines in the acute viral pneumonia induced by respiratory syncytial virus (RSV) infection was studied in calves. The patterns of cytokine mRNA expression in mononuclear cells (MNC) isolated from the lung and peripheral blood of six gnotobiotic calves infected seven days previously with bovine RSV were analysed by reverse-transcription polymerase chain reaction using primers specific for bovine cytokines. The pattern of cytokines detected indicated a mixed type of response to RSV infection as mRNAs for IFN-gamma, IL-2, IL-4 and IL-10 were detected in pulmonary and peripheral blood MNC from calves with extensive pneumonic consolidation. In contrast, only mRNA for IFN-gamma was detected in MNC from the lungs and peripheral blood of uninfected animals. These data provide preliminary information on the potential range of cytokines produced in calves following infection with bovine RS virus.

Animals↗
PubMed1996

Induction of allergen-specific IL-2 responsiveness of lymphocytes after respiratory syncytial virus infection and prediction of onset of recurrent wheezing and bronchial asthma.

BACKGROUND: In pediatric patients with bronchial asthma and/or atopic dermatitis, peripheral lymphocytes are activated if they are stimulated with the responsible antigen, resulting in induction of responsiveness to IL-2. Because some nursing infants experience recurrent wheezing after respiratory syncytial virus (RSV) infection, attention is being directed to progression of the disease to bronchial asthma. OBJECTIVE: The study was designed to elucidate the mechanism of the onset of allergic diseases after RSV infection. METHODS: We examined allergen-specific IL-2 responsiveness induced in lymphocytes in the peripheral blood of infants after infection by RSV. The relationship between the onset of recurrent wheezing and antigen-specific IL-2 responsiveness was analyzed in 25 pediatric patients who could be followed up for 3 years after RSV infection. RESULTS: Stimulation of lymphocytes with ovalbumin, alpha-casein, and mite (Dermatophagoides farinae) antigens induced significantly higher responsiveness to IL-2 in the RSV-infected infant group than in the healthy infant and disease control groups of the same age. There was no clear correlation between the IgE RAST scores for D. farinae, ovalbumin, and alpha-casein and IL-2 responsiveness. The families of RSV-infected infants had a high incidence of history of allergy (67%), but there was no significant difference in the incidence of patients with positive test results for IL-2 responsiveness between the groups with and without a familial history of allergy. The D. farinae-specific IL-2 responsiveness was significantly increased in the group with the symptom (16 patients) for a value of 1.64 +/- 0.13 (mean +/- SEM) compared with the value of 1.31 +/- 0.21 in the asymptomatic group (9 patients). The incidence of patients with positive test results for IL-2 responsiveness was 68.8% in the symptomatic group and 44.4% in the asymptomatic group. Similarly, the ovalbumin-specific IL-2 responsiveness was significantly increased in the symptomatic group (1.63 +/- 0.17) compared with the asymptomatic group (1.12 +/- 0.26). The incidence of patients with positive test results was 62.5% and 22.2%, respectively. alpha-Casein-specific IL-2 responsiveness was also higher in the symptomatic group than in the asymptomatic group, but the difference was not statistically significant. In the patient groups without RSV infection, on the other hand, the D. farinae-, ovalbumin-, and alpha-casein-specific IL-2 responsiveness in the symptomatic group were all similar to that in the asymptomatic group; no significant increases were detected. CONCLUSION: The results indicated that after RSV infection, lymphocytes acquire specific susceptibility to D. farinae, a mite antigen, and food antigens, particularly ovalbumin. Hence, it is thought that positive IL-2 responsiveness specific for D. farinae and/or ovalbumin, detected several months after RSV infection, can be a prediction factor for the onset of allergic diseases, such as recurrent wheezing and bronchial asthma.

Allergens↗
PubMed2004

Interleukin 9 production in the lungs of infants with severe respiratory syncytial virus bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis is the most prevalent acute wheezing disorder in infants and is associated with recurrent wheeze and asthma in childhood. Interleukin 9, a type 2 cytokine has been proposed as a key cytokine in susceptibility to asthma. We aimed to investigate whether interleukin 9 was produced in the lungs of infants with severe RSV disease and if found, from which cells it originated. METHODS: We did 150 non-bronchoscopic bronchoalveolar lavages during the course of ventilation in 24 term infants and 21 preterm infants ventilated for RSV bronchiolitis. We also did 10 bronchoalveolar lavages on the day of intubation in 10 control infants ventilated for non-respiratory causes. We measured pulmonary interleukin 9 mRNA and protein in samples from all groups. We used immunostaining to identify the cells that produce interleukin 9. FINDINGS: Interleukin 9 mRNA expression, which persisted over the course of ventilation, was noted in all infants with bronchiolitis. Three of the control group also showed interleukin 9 mRNA expression. Median interleukin 9 protein concentration on day 1 (1.9 microg/L [range 0.1-36.2]) was significantly greater in term infants with bronchiolitis than either preterm infants (0.4 microg/L [0.1-2.9]; p<0.05) or the control group (0.7 microg/L [0.4-2.5]; p<0.05). There was a trend for interleukin 9 protein concentrations in term, but not preterm infants to decrease over time. Immunostained cell smears showed that most interleukin 9 expression in bronchoalveolar lavage was by neutrophils. INTERPRETATION: In term infants with RSV bronchiolitis, we noted large amounts of interleukin 9 mRNA and interleukin 9 protein. Neutrophils seem to be the main source of this type 2 cytokine. Interleukin 9 production by neutrophils may contribute to the pathogenesis of RSV disease. These findings may be relevant to other disease processes in the lung where neutrophils are the predominant inflammatory cell type.

Acute Disease↗
PubMedDate not supplied

Respiratory syncytial virus or influenza?

We compared data from clinical surveillance of acute respiratory infections in elderly people reported by a network of sentinel general practitioners, virus isolate data for respiratory syncytial virus (RSV) and influenza A and B viruses, and registered deaths, during the past four winters. Cases of acute respiratory disease (ARD) and deaths (3-week moving averages) showed strong similarity in timing. Periods of high incidence of ARD and numbers of deaths were followed within 2-3 weeks by reports of high numbers of RSV or influenza virus isolates. The epidemic period in December, 1989, was followed by high numbers of both virus isolates, but in all other epidemic periods one virus predominated. The lethality of epidemics due to RSV or influenza A or B varied both within and between years. These analyses suggest that RSV is as important as influenza viruses in causing morbidity and excess deaths among elderly people. RSV was prevalent at the end of each of the past four years in the UK; its importance as a cause of excess deaths would therefore be concealed in any analysis based on several years' experience. By contrast, the inconsistency of epidemics due to influenza viruses makes excess deaths due to these viruses easily recognisable. Integrated clinical and viriological surveillance is essential if epidemics due to RSV, influenza virus, or any other virus are to be correctly interpreted.

Adolescent↗
PubMed1999

Respiratory syncytial virus infection.

Respiratory syncytial virus (RSV), long recognised as the major viral pathogen of the lower respiratory tract of infants, has also been implicated in severe lung disease in adults, especially the elderly. This fact, and the demonstration that passive prophylaxis with either polyclonal or monoclonal antibody to RSV prevents severe lung disease in high-risk infants and children, has led to renewed interest in the immune mechanisms surrounding protection, and the development of vaccines

Adult↗
PubMed2002

Comparative evaluation of indirect and sandwich ELISA for the detection of antibodies to bovine respiratory syncytial virus (BRSV) in dairy cattle.

Seroprevalence of bovine respiratory syncytial virus (BRSV) infection in both exotic and crossbred cattle were described. A baculovirus expressed recombinant purified nucleocapsid (N) protein was used in indirect and sandwich ELISA for screening of 499 bovine sera samples from all over the state for the presence of BRSV antibodies. The seroprevalence rate of BRSV was found to be 46.09% through indirect ELISA while it would found to be 65.33% by sandwich ELISA. The result also indicated that exotic breeds were more susceptible to BRSV infection compared to crossbred cattle. A comprehensive analysis on susceptibility to BRSV as regards to various factors like age and sex was also summarized.

Animals↗
PubMed1999

The effects of bovine respiratory syncytial on normal ovine lymphocyte responses to mitogens or antigens in vitro.

In the present study peripheral blod mononuclear cells (MNC) obtained from normal uninfected lambs were used to study the possible effects of bovine respiratory syncytial virus (BRSV) on lymphocyte responses to the mitogens, phytohaemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM) in vitro. Live BRSV had a depressive effect on the proliferative responses of normal MNC to PHA, Con A and PWM. Inactivated BRSV and a commercial preparation of prostaglandin E2 were also found to depress the proliferative responses of normal ovine MNC to PHA but recombinant tumour necrosis factor-alpha (TNF-alpha) had no such effect. Serum samples obtained from BRSV-infected lambs contained substances inhibitory to PHA-driven lymphocyte blastogenesis. Memory blastogenic responses to border disease virus (BDV) of lymyphocytes obtained from lambs previously primed with BDV were significantly reduced when lymphocytes were exposed to infectious BRSV.

Animals↗
PubMed2000

Palivizumab for respiratory syncytial virus prophylaxis in high-risk infants: a cost-effectiveness analysis.

BACKGROUND: Prophylactic therapy with palivizumab, a humanized monoclonal antibody, has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in preterm infants. The cost-effectiveness of this therapy has not been evaluated from the provider's perspective using cost data. OBJECTIVES: The objectives of this study were to determine the cost per RSV infection episode avoided by using prophylactic palivizumab therapy in a high-risk infant population and to determine whether certain subgroups of infants derived greater benefit from prophylactic therapy. METHODS: A decision-analytic model simulating an RSV infection episode was developed to evaluate the cost-effectiveness of palivizumab prophylaxis from the perspective of the health care system (provider). Data to populate the model were gathered from the medical literature (identified through a MEDLINE search of studies on the incidence of RSV infection) and the IMpact-RSV clinical trial. Data included incidence of RSV infection and the associated health care resource use and costs. Costs to the provider were determined using a university-affiliated hospital cost-accounting system. Cost-effectiveness ratios were calculated over a range of RSV infection incidence rates in a control population. Sensitivity analyses were performed for the cost of palivizumab therapy, the cost of RSV-related hospitalization, and the number of emergency department, physician office, and home health care visits. For the subgroup analysis, infants were classified by gestational age (<32 and > or = 32 weeks) and stratified by severity of chronic lung disease. RESULTS: The cost per additional RSV infection episode avoided ranged from dollars 0 (cost savings) to dollars 39,591 for palivizumab prophylaxis costs of dollars 2500 and from dollars 2702 to dollars 79,706 for palivizumab prophylaxis costs of dollars 4500. The model was insensitive to changes in the number of emergency department, physician office, and home health care visits. The difference in RSV incidence between the treatment and control groups was greater among infants > or = 32 weeks' gestational age than among infants <32 weeks' gestational age. onclusions: The incremental cost-effectiveness of palivizumab compared with no prophylactic therapy was sensitive to changes in the incidence of RSV infection in control infants, the average cost of RSV hospitalization, and the cost of palivizumab. Clinicians may use this information along with additional factors to determine whether palivizumab is cost-effective in their clinical setting and geographic area.

Antibodies, Monoclonal↗
PubMed1999

Impact of palivizumab on expected costs of respiratory syncytial virus infection in preterm infants: potential for savings.

In its clinical assessment of the respiratory syncytial virus (RSV)-specific monoclonal antibody palivizumab, the IMpact-RSV Study Group demonstrated a reduction in hospitalizations for RSV-related lower respiratory tract infection in infants who received prophylaxis compared with infants who did not receive prophylaxis. An assessment of the RSV-related expenses for managing both groups of infants is needed to provide insight into the value of prophylaxis. The present study was conducted to identify and compare RSV-related health care expenditures incurred by infants who did not receive prophylaxis throughout one RSV season and after. Using a decision-analytic model populated with data from the contemporary medical literature, a pharmacoeconomic study was conducted from the perspective of the payer. Probabilities for RSV-related hospitalizations of infants who did and did not receive prophylaxis were abstracted from several published studies. Components of inpatient and outpatient care were identified through examination of hospital records, reviews of the published literature, and consultation with expert clinicians. Charges related to prophylaxis and medical management of infection were abstracted from hospital billing records and published data. Appropriate charges were applied to decision-tree branches and multiplied by in-line probabilities for outcomes. Products at terminal nodes were summed to establish total expected charges for both groups of infants. Widespread clinical use of prophylactic palivizumab would result in incremental expenses < or =$3459 per infant or cost savings < or =$39,107 per infant. The variability in value of prophylaxis derives from the rate of RSV-related hospitalizations in the community and the total health care expense of managing infected infants.

Antibodies, Monoclonal↗
PubMed1998

The effect of fluticasone propionate on respiratory syncytial virus-induced chemokine release by a human bronchial epithelial cell line.

Respiratory syncytial virus (RSV) is an important cause of bronchiolitis in infants, is an important trigger of asthma exacerbation, and stimulates chemokine production by human respiratory epithelial cells in vitro. We tested the effect of the corticosteroid fluticasone propionate (FP) on RSV-stimulated production of the chemokines interleukin 8 (IL-8) and RANTES (regulated upon activation, normal T cell expressed and secreted) by a human bronchial epithelial cell line, BEAS-2B. Confluent BEAS-2B cultures were inoculated with RSV at approximately 1 plaque-forming unit/cell, and media were collected at 24 h intervals. Concentrations of IL-8 and RANTES were measured in supernatants using ELISA. The effect of FP at varying concentrations on RSV-induced chemokine release was determined. RSV stimulated increased release of both IL-8 and RANTES, particularly at 24-48 h after virus inoculation. Significant but incomplete inhibition of RSV-stimulated increases for both chemokines was found when cultures were treated with FP at > or = 10(-8) M (for IL-8) or > or = 10(-7) M (for RANTES). There was no significant effect of FP on release of RSV itself from infected BEAS-2B cells. We conclude that a possible mechanism for the efficacy of inhaled corticosteroids in reducing the frequency or severity of asthma exacerbations is inhibition of virus-induced chemokine production by airway cells.

Androstadienes↗
PubMed1997

Systemic and local immune responses of four cases with lower respiratory tract illness due to reinfection with respiratory syncytial virus.

Four infants and children who had tracheobronchitis or bronchiolitis by respiratory syncytial virus (RSV) reinfection were presented. Their clinical features, systemic and local immune reactions to RSV were compared with those of eleven age-matched patients who had lower respiratory tract illness with primary RSV infection. Moderate antibody activities in their nasopharyngeal secretions and sera which were comparable to those of convalescent phase of primary infection were observed within several days after onset of illness; however, their clinical symptoms, such as fever or wheezing, lasted almost as long as in primary RSV infection. These observations suggest that the higher serum and secretory antibody activity to RSV during acute phase does not always bring about clinical amelioration in RSV reinfection. The contribution of immunopathological reaction between RSV and RSV-specific antibodies might also be considered as a cause of inflammation during the acute phase of RSV reinfection.

Antibody Formation↗