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Respiratory syncytial virus immune globulin for prophylaxis against respiratory syncytial virus disease in infants and children with congenital heart disease. The Cardiac Study Group.

OBJECTIVE: To examine the effectiveness of respiratory syncytial virus immune globulin administered intravenously (RSV-IGIV) in reducing hospitalization for treatment of RSV in children with congenital heart disease (CHD). METHODS: Children younger than 4 years of age were randomly assigned to a treatment group receiving RSV-IGIV, 750 mg/kg, monthly or to a control group not receiving infusions. Surveillance for respiratory tract infections was carried out and management decisions were made by physicians blinded to treatment group. RESULTS: Hospitalization for treatment of an RSV infection occurred in 32 of 214 (15%) of control children and 21 of 202 (10%) of the children receiving RSV-IGIV, a 31% reduction (P = .16). However, in infants younger than 6 months of age at study entry, 20 of 82 (24%) in the control group and 10 of 96 (10%) in the RSV-IGIV group had RSV hospitalizations (58% reduction, P = .01). The incidence of hospitalization for any respiratory tract symptomatology was lower in the RSV-IGIV group (34 of 202, 17%) than in the control group (57 of 214, 27%; P = .02). There was a significantly higher frequency of unanticipated cyanotic episodes and of poor outcomes after surgery among children with cyanotic CHD in the RSV-IGIV group (22 of 78, 28%) than in the control group (4 of 47, 8.5%; P = .009). CONCLUSION: RSV-IGIV should not be used for prophylaxis of RSV disease in children with cyanotic CHD. RSV-IGIV did not reduce RSV hospitalization in all children with CHD, but it was effective in preventing RSV hospitalization in infants younger than 6 months of age. Further studies in these children are indicated.

Age Factors↗

Respiratory syncytial virus immunoglobulin and monoclonal antibodies in the prevention and treatment of respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) infection is particularly severe in infants with bronchopulmonary dysplasia (BPD) and in premature infants without BPD. Attempts to develop a vaccine against RSV have been unsuccessful. Passive immunoprophylaxis of premature infants with or without BPD using a hyperimmune human globulin against RSV (RSVIg) decreases the severity of RSV infection such that the rate of hospitalization following infection is reduced by 40%. The severity of illness among hospitalized infants is also reduced. To avoid the difficulties associated with intravenous infusion of immunoglobulins, monoclonal IgG antibodies against the fusion protein of RSV have been developed. In one trial, the antibodies were ineffective, although subsequent trials using higher doses of the antibody show more promising results. Studies of IgA monoclonal antibodies directed against RSV, which are administered in the form of nose drops, are also in progress. None of these preparations appear to be effective in the treatment of established RSV infection. Each of the preparations appeared to be safe, with one exception. Infants with cyanotic heart disease who received RSVIg had an increased risk of surgical complications, perhaps related to increases in serum viscosity as a result of receiving the hyperimmunoglobulin monthly in doses of 750 mg/kg. While definitive cost/benefit analyses are pending, RSVIg may be useful in infants and children with BPD who have current or recent oxygen requirements, as well as in certain premature infants without BPD. Recommendations on the use of RSVIg are provided.

Antibodies, Monoclonal↗

Role of antibody and the use of respiratory syncytial virus immunoglobulin in the prevention of respiratory syncytial virus disease in preterm infants with and without bronchopulmonary dysplasia.

Respiratory syncytial virus (RSV) is the only viral respiratory pathogen that produces an annual epidemic of respiratory illness. Infants with cardiac disease or infants born prematurely with or without bronchopulmonary dysplasia are at increased risk of severe RSV disease. A recently developed RSV immunoglobulin (RSVIG) was studied to determine safety and efficacy in prevention of severe RSV disease in such children who are high risk for severe RSV illness. Results from this prospective, blinded trial involving 249 children (102 with broncho-pulmonary dysplasia, 87 with congenital heart disease and 60 who were born prematurely) indicate that high dose RSVIG reduced the incidence and severity of RSV lower respiratory tract infection. It is a safe and effective means of RSV prophylaxis in selected high risk children.

Antibodies, Viral↗

Prophylaxis for respiratory syncytial virus with respiratory syncytial virus-immunoglobulin intravenous among preterm infants of thirty-two weeks gestation and less: reduction in incidence, severity of illness and cost.

OBJECTIVE: To determine the impact of respiratory syncytial virus (RSV) prophylaxis among preterm infants of < or =32 weeks gestation by comparing the severity of illness and cost of RSV-related care during the two winter seasons before (1994 to 1995, 1995 to 1996) with the two seasons after initiation of prophylaxis (1996 to 1997, 1997 to 1998). METHODS: Preterm infants of < or =32 weeks gestation at risk for hospitalization with RSV infection were identified retrospectively from the infants hospitalized in our neonatal units. Infants were included if they (1) were born 6 months before or during four winter seasons (1994 to 1998), (2) were discharged from the neonatal unit and (3) had remained in the university outpatient clinic system during at least the first winter of life. Preterm infants of < or =32 weeks gestation hospitalized with RSV were identified from our RSV database (which includes cost of hospitalization, duration of hospital stay, pediatric intensive care unit stay and intubation). Infants receiving prophylaxis were identified prospectively. RESULTS: The incidence of hospitalization with RSV was significantly lower among the cohort of infants born after initiation of prophylaxis: 8.7% (17 of 195) vs. 22% (35 of 159), P = 0.00049 by two tailed Fisher's exact test. Among the cohort of infants born after initiation of prophylaxis (n = 195), 100 infants received prophylaxis. The gestational and chronologic ages of the prophylaxis-treated infants were significantly lower than those of the non-prophylaxis-treated infants (n = 95). The prophylaxis-treated infants also were more likely to have bronchopulmonary dysplasia. Only 1 (1%) of the prophylaxis-treated infants required hospitalization for RSV. Comparison of the cohort of infants born before initiation of prophylaxis to the cohort born after initiation of prophylaxis (includes prophylaxis-treated and non-prophylaxis-treated infants) revealed a significant reduction in severity of illness and cost. The length of stay in the cohort born before initiation of prophylaxis was reduced 83.8%: 373.6 days per 100 infants at risk vs. 60.5 (P = 0.00055). The length of stay in the pediatric intensive care unit was reduced 92.7%: 218.2 days per 100 infants at risk vs. 15.9 (P = 0.00029). The duration of intubation was reduced 95.6%: 187.4 days per 100 infants at risk vs. 8.2 (P = 0.00024). The dollars spent for RSV-related care (hospitalizations and prophylaxis) per 100 infants at risk for RSV was reduced 65% in the cohort of infants born after prophylaxis: $670,590 per 100 infants at risk vs. $234,596 (P = 0.00056). This reduction remained significant (64.9%) if the cost of ribavirin (drug and administration fees) was excluded from the cost of hospitalization. CONCLUSIONS: These data reveal that RSV prophylaxis significantly reduced the incidence of RSV hospitalizations and severity of illness as well as the cost of RSV-related care among these infants.

Female↗

Contribution of respiratory syncytial virus G antigenicity to vaccine-enhanced illness and the implications for severe disease during primary respiratory syncytial virus infection.

BACKGROUND: Immunization of BALB/c mice with vaccinia virus expressing the G glycoprotein (vvG) of respiratory syncytial virus (RSV) or with formalin-inactivated alum-precipitated RSV (FI-RSV) predisposes for severe illness, type 2 cytokine production and pulmonary eosinophilia after challenge with live RSV. This similar disease profile has led to the proposal that the presence of the G glycoprotein in the FI-RSV preparation was the immunologic basis for the vaccine-associated enhancement of disease observed in the failed clinical trials of the 1960s. However, processes of disease pathogenesis observed in FI-RSV- and vvG-immunized mice suggest that FI-RSV and vvG immunizations induce immune responses of different compositions and requirements that converge to produce similar disease outcomes upon live virus challenge. METHODS: The potential role of RSV G present in FI-RSV preparations in increasing postimmunization disease severity was explored in mice. RESULTS: The absence of RSV G or its immunodominant epitope during FI-RSV immunization does not reduce disease severity after RSV challenge. Furthermore although depletion of V beta 14+ T cells during RSV challenge modulates disease in G-primed mice, minimal impact on disease in FI-RSV-immunized mice is observed. CONCLUSION: FI-RSV vaccine-enhanced illness is not attributable to RSV G. Furthermore formulation of a safe and effective RSV vaccine must ensure RSV antigen production, processing and presentation via the endogenous pathways. Thus gene delivery by vector, by DNA or by live attenuated virus are attractive vaccine approaches.

Animals↗

Immunoprophylaxis and immunotherapy of respiratory syncytial virus-infected mice with respiratory syncytial virus-specific immune serum.

The effects of passive respiratory syncytial virus (RSV) immune serum given as preinoculation prophylaxis, postinoculation prophylaxis, and as therapy on d 5 after inoculation were evaluated in an illness model of RSV infection in BALB/c mice. Pre- and postinoculation prophylaxis reduced RSV replication in lung after primary RSV infection and prevented illness. Day 5 treatment did not affect peak titer of RSV in lung but resulted in more rapid recovery from illness than seen in untreated mice. Prophylaxis prevented antibody responses and lymphocytic infiltrates in lung after primary RSV infection. Treatment caused diminished antibody and pathologic responses. Prophylaxis increased susceptibility to reinfection, although illness after rechallenge was mild. Mice treated therapeutically were less susceptible to reinfection than mice treated prophylactically, but they also experienced mild illness after rechallenge. Passive antibody prophylaxis and treatment of RSV infection are promising approaches to attenuating lower respiratory tract illness from primary RSV infection. The ability to measure illness endpoints and pathology make the BALB/c mouse model of RSV infection a useful system for the preclinical evaluation of immunoprophylactic and immunotherapeutic modalities.

Animals↗

Respiratory syncytial virus (RSV) immune globulin intravenous therapy for RSV lower respiratory tract infection in infants and young children at high risk for severe RSV infections: Respiratory Syncytial Virus Immune Globulin Study Group.

OBJECTIVES: To evaluate the efficacy of high-titer intravenous respiratory syncytial virus immune globulin (RSVIG) in the treatment of children at high risk for severe RSV infection who were hospitalized with proven RSV. METHODS: Infants and young children younger than 2 years with bronchopulmonary dysplasia, chronic lung disease, congenital heart disease, or prematurity (<32 weeks' gestational age), hospitalized with a history of lower respiratory tract infection (LRI) of less than 4 days, were enrolled in this study. Patients were randomized in a blinded fashion to receive either 1500 mg/kg RSVIG or placebo in equal volumes. They were evaluated daily for safety and respiratory scores and for RSV nasal shedding. RESULTS: One hundred seven high-risk children were randomized--54 in the RSVIG group and 53 in the placebo group. Of these children, 51 in each group were considered evaluable. Children with pulmonary disease, congenital heart disease, or prematurity were equally distributed between the two treatment groups. However, two important differences were found in baseline variables between the two groups: there were more patients in the placebo group who had histories of previous LRI and there was a trend toward more severe disease at study entry in the RSVIG group. This was manifested by a higher entry respiratory score in the RSVIG group than in the placebo group (3.4 +/- 0.2 vs 3.1 +/- .01). A higher proportion of children in the RSVIG group (47%) than in the placebo group (28%) required intensive care at entry and mechanical ventilation at study entry (31% RSVIG-treated vs 18% placebo-treated patients). No significant difference was found between groups in the mean unadjusted duration of hospitalization (RSVIG group, 9.10 +/- 1.18 days; control group, 8.17 +/- 1.08 days). When the mean was adjusted for entry respiratory score, likewise, no difference was observed between each group (8.41 +/- 0.97 vs 8.89 +/- .99 days). The lack of efficacy observed in the study primary endpoint was observed in all diagnostic groups. No differences between the RSVIG and placebo groups were observed in the following secondary endpoints: duration of intensive care unit stay, duration of intensive care unit stay for RSV, mechanical ventilation, or supplemental oxygen. No significant differences in adverse events were reported in the RSVIG group (16 children) when compared with the control group (10 children). CONCLUSION: RSVIG treatment was safe but not efficacious in the treatment of children with bronchopulmonary dysplasia, congenital heart disease, or premature gestation who were hospitalized with RSV LRI.

Bronchiolitis↗

PICNIC (Pediatric Investigators Collaborative Network on Infections in Canada) study of the role of age and respiratory syncytial virus neutralizing antibody on respiratory syncytial virus illness in patients with underlying heart or lung disease.

OBJECTIVE: To determine the effects of age and respiratory syncytial virus (RSV) antibody status on frequency and severity of RSV infections in children with underlying heart or lung disease. DESIGN: Cohort study conducted during two consecutive RSV seasons. SETTING: Ambulatory patients at eight Canadian pediatric tertiary care centers. METHODS: Subjects under 3 years old with underlying heart disease who were digoxin-dependent or had not received corrective cardiac surgery or with underlying lung disease were enrolled. Demographic information and an acute sera for RSV neutralizing antibody was obtained on enrollment. Weekly telephone follow-up consisting of a respiratory illness questionnaire was followed with a home visit to obtain a nasopharyngeal aspirate when there was new onset of respiratory symptoms. The specimen was used to detect RSV antigen. RSV illnesses were grouped as upper or lower respiratory tract infection (LRI) based on clinical and radiographic findings. RSV hospitalizations were considered to be those RSV infections that resulted in hospitalization. RESULTS: Of 427 enrolled subjects, 160 had underlying lung disease only, 253 had underlying heart disease only, and 14 had both. Eleven percent and 12% of lung and heart disease groups, respectively, had an RSV LRI. Three percent and 6% of lung and heart disease groups, respectively, were hospitalized with RSV infection. A significant decrease in frequency of RSV LRI and RSV hospitalization occurred with increasing age, with a major drop in those older than 1 year vs those younger than 1 year. Acute sera were available from 422 subjects. Geometric mean RSV antibody titers demonstrated a U-shaped distribution with increasing age. The trend to lower antibody concentrations in premature infants did not reach statistical significance. The frequency of RSV infection and RSV LRI was lower in patients with antibody at a titer more than 100, although the difference for RSV hospitalization was not statistically significant. These differences remained significant after age adjustment. CONCLUSION: Both age and RSV antibody status impact on RSV illness and LRI. Reduction in illness frequency with increasing age may lead to more informed targeting of those children most likely to benefit from RSV immune globulin prophylaxis.

Age Distribution↗

Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. The IMpact-RSV Study Group.

OBJECTIVE: To determine the safety and efficacy of prophylaxis with palivizumab in reducing the incidence of hospitalization because of respiratory syncytial virus (RSV) infection in high-risk infants. METHODS: A randomized, double-blind, placebo-controlled trial was conducted at 139 centers in the United States, the United Kingdom, and Canada. During the 1996 to 1997 RSV season, 1502 children with prematurity (less than or equal to 35 weeks) or bronchopulmonary dysplasia (BPD) were randomized to receive 5 injections of either palivizumab (15 mg/kg) or an equivalent volume of placebo by intramuscular injection every 30 days. The primary endpoint was hospitalization with confirmed RSV infection. Children were followed for 150 days (30 days from the last injection). Those with hospitalization as a result of RSV infection were evaluated for total number of days in the hospital, total days with increased supplemental oxygen, total days with moderate or severe lower respiratory tract illness, and incidence and total days of intensive care and mechanical ventilation. The incidence of hospitalization for respiratory illness not caused by RSV and the incidence of otitis media were also evaluated. The placebo and palivizumab groups were balanced at entry for demographics and RSV risk factors. Ninety-nine percent of children in both groups completed the protocol and approximately 93% received all five scheduled injections. RESULTS: Palivizumab prophylaxis resulted in a 55% reduction in hospitalization as a result of RSV (10.6% placebo vs 4.8% palivizumab). Children with prematurity but without BPD had a 78% reduction in RSV hospitalization (8.1% vs 1.8%); children with BPD had a 39% reduction (12.8% vs 7.9%). When gender, entry age, entry weight, BPD, and gestational age were included in a logistic regression model, the effect of prophylaxis with palivizumab remained statistically significant. The palivizumab group had proportionally fewer total RSV hospital days, fewer RSV hospital days with increased oxygen, fewer RSV hospital days with a moderate/severe lower respiratory tract illness, and a lower incidence of intensive care unit admission. Palivizumab was safe and well tolerated. No significant differences were observed in reported adverse events between the two groups. Few children discontinued injections for related adverse events (0.3%). Reactions at the site of injection were uncommon (1.8% placebo vs 2.7% palivizumab); the most frequent reaction was mild and transient erythema. Mild or moderate elevations of aspartate aminotransferase occurred in 1.6% of placebo recipients and 3.6% of palivizumab recipients; for alanine aminotransferase these percentages were 2.0% and 2.3%, respectively. Hepatic and renal adverse events related to the study drug were similar in the two groups. CONCLUSIONS: Monthly intramuscular administration of palivizumab is safe and effective for prevention of serious RSV illness in premature children and those with BPD.

Antibodies, Monoclonal↗

Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections, and association between respiratory syncytial virus infection risk factors and disease severity.

This study was designed to collect data on the prevalence of respiratory syncytial virus (RSV) infection in Italy in infants hospitalized for lower respiratory tract infections, and to evaluate which of the recognized risk factors might be associated with disease severity. Thirty-two centers throughout Italy participated in the study. Over a 6-month period (November 1,1999 to April 30, 2000), we evaluated all children < 2 years of age hospitalized for lower respiratory tract infections. All subjects were tested for RSV within 24 hr of hospitalization by using an immuno-enzymatic diagnostic test (Abbott Testpack, RSV). Logistic regression was used to identify the factors that might be associated with more severe disease or could increase the likelihood of RSV positivity in hospitalized infants. Out of a total of 1,232 children enrolled, 40.6% were found to be RSV-positive (RSV+). The peak of the RSV epidemic occurred in February, while the lowest prevalence of RSV positivity was seen in November (P < 0.05). A high proportion of study subjects had low birth weight and low gestational age. The clinical diagnosis at hospitalization was bronchiolitis in 66.7%, pneumonia in 15.3%, and wheezy bronchitis in 18.1%. In the bronchiolitis group, a higher prevalence of RSV+ was found in patients with gestational age or= 36 weeks (P < 0.04). No differences were found in the proportion of RSV+ patients in the three gestational age subgroups with pneumonia and wheezy bronchitis (P > 0.05, each comparison). Independent of the clinical diagnosis at admission, RSV infection was associated with more severe respiratory impairment. Environmental smoke exposure was higher in subjects with bronchiolitis than in those with wheezy bronchitis (P < 0.04), and RSV+ was positively related with the birth order (P < 0.05). The presence of older siblings and birth order plays an important role in RSV infection. The collected data show that, in Italy, RSV is an important cause of lower respiratory tract infection in infants. Gestational age, birth order, birth weight, and exposure to tobacco smoke affected the prevalence and severity of RSV-related lower respiratory tract disease.

Acute Disease↗

Polylactosaminoglycan modification of the respiratory syncytial virus small hydrophobic (SH) protein: a conserved feature among human and bovine respiratory syncytial viruses.

We investigated the nature of the oligosaccharide modification of the glycosylated forms of the small hydrophobic integral membrane protein, SH (previously designated 1A), of respiratory syncytial (RS) virus. Analysis of SH protein expressed in cells infected with RS virus or with a recombinant vaccinia virus revealed two glycosylated SH protein species, SHg and SHp, which contained N-linked carbohydrate residues. SHp migrated diffusely on polyacrylamide gels, which suggested modification by polylactosaminoglycan oligosaccharides. Polylactosaminoglycan modification of SHp was established from three lines of investigation: (1) the synthesis of SHp in a cell line (IdID) conditionally defective in the ability to add specific carbohydrate residues to N- or O-linked oligosaccharide chains required the addition of galactose, which is a component of the N-acetyllactosamine repeating unit; (2) SHp was sensitive to digestion with endo-beta-galactosidase, which cleaves the beta 1-4 linkage between galactose and N-acetylglucosamine of the repeated N-acetyllactosamine subunit; and (3) SHp was selected by Datura stramonium lectin (Dsl), which has specificity for polylactosaminoglycans. The presence of SHp as a component of purified human subgroups A and B and bovine RS virus particles was demonstrated by Dsl affinity selection. In addition to SHp, nonglycosylated SHo was selected by Dsl affinity, indicating that SHp and SHo may associate to form complexes within infected cells and virus particles. To identify conserved amino acid residues among the human and bovine SH glycoproteins that may function as signals for polylactosaminoglycan modification, the nucleotide sequences of the SH protein genes of a human subgroup B virus (8/60) and a bovine virus (391-2) were determined and compared to those of a human subgroup A virus (A2), a subgroup B virus (18537), and a bovine virus (A51908). A comparison of the deduced amino acid sequences of the human and bovine RS virus SH proteins indicated that a central hydrophobic region and the presence of potential N-linked glycosylation sites on either side of the central hydrophobic region were conserved features that may be required for the polylactosaminoglycan modification of SH.

Amino Acid Sequence↗

Interleukin 1 and interleukin 1 inhibitor production by human macrophages exposed to influenza virus or respiratory syncytial virus. Respiratory syncytial virus is a potent inducer of inhibitor activity.

Respiratory viral infections are commonly associated with altered immune responses, such as proliferative responses to mitogens and antigens. To examine potential mechanisms, we examined production of IL-1 and IL-1 inhibitors by purified human peripheral blood-derived macrophages exposed to influenza virus or respiratory syncytial virus (RSV). IL-1 and IL-1 inhibitor activities in supernatant fluids from macrophages exposed to the viruses 24 h previously were measured using the standard mouse thymocyte comitogen assay. Crude fluids from macrophages exposed to influenza virus contained substantial IL-1 activity, whereas crude fluids from macrophages exposed to RSV contained marked IL-1 inhibitor activity. Assays with gel filtration-separated fractions revealed that both influenza virus and RSV induced production of both IL-1 and IL-1 inhibitors. Neither IL-2 nor IL-2 inhibitor activities were detected. Thus, effects of human macrophage-derived factors on thymocyte proliferation, or potentially on human lymphocyte proliferation, may reflect the total or net activity of multiple composite factors, the balance of which varies according to the challenge. The data raise the possibility that marked production of IL-1 inhibitor activity in response to RSV plays a role in the clinical recurrence of RSV infection despite the absence of clear evidence for antigenic shift or drift of the virus.

Humans↗

Populations at risk for developing respiratory syncytial virus and risk factors for respiratory syncytial virus severity: infants with predisposing conditions.

According to National Vital Statistics Reports, premature infants (< 36 weeks gestation) account for approximately 7.4% of all births. During the 8 years from 1989 to 1997, multiple births steadily increased across all categories from twin to quintuplet and higher orders. During that same period low birth weight (< 2500 g) births increased almost 12%, and very low birth weight (< 1500 g) births increased approximately 20%.Attendant to these national trends in multiple and preterm births, overall gestation-specific survival rates have improved substantially. This improved outcome can be attributed in large measure to advances in neonatal care and technology. Despite the encouraging statistics on survival, infants born prematurely, at low or very low birth weights and/or with chronic conditions that predispose to lower respiratory tract illness, continue to incur serious risk of long term morbidity and the consumption of inpatient hospital services. In a recent 2-year study of US children, low and very low birth weights were found to be independent risk factors for bronchiolitis-associated mortality. In the past 14 years what defines bronchopulmonary dysplasia (BPD)/chronic lung disease (CLD) has shifted away from clinical, radiographic and pathologic findings in the preterm infant toward the pathophysiology of arrested lung development and the need for supportive care beyond 36 weeks corrected gestational age. The incidence of BPD/CLD ranges from 14 to 43%, with higher rates observed among infants of lower gestational age and birth weight. The health care team approach to the management of BPD directs its efforts toward minimizing pulmonary vascular resistance, alleviating airway obstruction and improving short term lung mechanics. Measures to prevent BPD/CLD attempt to forestall both acute and chronic lung function abnormalities. To that end researchers have investigated the early use of continuous positive airway pressure, vitamin supplementation and recombinant human copper/zinc superoxide dismutase. Despite significant gains in the survival of infants born at lower gestational ages, prematurity, low birth weight and/or underlying chronic pulmonary disease put the pediatric patient at risk for increased frequency and severity of respiratory syncytial virus lower respiratory tract illness and the potential for its long term sequelae.

Airway Obstruction↗

Antibody response to respiratory syncytial virus structural proteins in children with acute respiratory syncytial virus infection.

The purified respiratory syncytial virus (RSV), Randall strain contained 10 polypeptides (72,000 molecular weight [72K], 66K, 48K, 42K, 40K, 36K, 30K, 23K, 18K, and 15K), 8 of which proved to be virus specific, and polypeptides 48K and 23K were glycosylated. In addition, a high-molecular-weight (150K), virus-specific glycopolypeptide was immunoprecipitated from RSV-infected cell lysate. The antibody response in human sera serially collected from children with primary RSV infection was mainly directed against the polypeptides 30K, 48K, and 72K. The immune response against the other viral proteins was also already detectable in the acute-phase sera. These results indicate that the immune response in RSV infection differs significantly from those for other diseases caused by paramyxoviruses.

Acute Disease↗

Respiratory syncytial virus infection: admissions to hospital in industrial, urban, and rural areas. Report to the Medical Research Council Subcommittee on Respiratory Syncytial Virus Vaccines.

A collaborative study of 10 centres during the winters of 1973-4 and 1974-5 showed that respiratory syncytial virus (RSV) was the major cause of admission to hospital for respiratory disease in children under 5 years of age in industrial, urban, and rural communities. In all areas the distribution of clinical symptoms and their severity was similar, but the rate of admission in relation to population was over twice as high in industrial as in other areas. The maximum yearly admission rate occurred among infants aged 1 to 3 months: 24.5 per 1000 of that age group were admitted to hospital. Two methods of diagnosing RSV infection--virus isolation and immunofluorescence from postnasal aspirates--were compared, and the two methods were found to agree in 91% of cases. The results of this study confirmed the importance of RSV as a respiratory pathogen in young children. Further studies are needed to determine how the virus produces its effects and to develop preventive measures.

Age Factors↗

Reduction of respiratory syncytial virus hospitalization among premature infants and infants with bronchopulmonary dysplasia using respiratory syncytial virus immune globulin prophylaxis. The PREVENT Study Group.

OBJECTIVE: To determine the safety and efficacy of monthly prophylaxis with respiratory syncytial virus immune globulin, intravenous (RSV-IGIV) for reduction of the incidence of RSV-associated hospitalization. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted at 54 centers in the United States during the 1994 to 1995 RSV season. A total of 510 children with bronchopulmonary dysplasia and/or a history of prematurity were randomized to receive either 750 mg/kg RSV-IGIV (n = 250) or placebo (1% albumin; n = 260) intravenously every 30 days. Randomized groups were well balanced at entry for demographics, RSV risk factors, and birth characteristics. Children were monitored for adverse events and for RSV-associated hospitalization from randomization through 30 days after the last infusion visit; serious adverse events were monitored for an additional 30 days. For children hospitalized with RSV, data were collected regarding the total days of RSV stay, total days of increased oxygen requirement, total days with a moderate or severe lower respiratory tract illness, and frequency and duration of intensive care unit stay and mechanical ventilation. Ninety-five percent of participants completed the protocol and 85% received a complete course of infusions. RESULTS: The incidence of RSV hospitalization was reduced by 41% in children receiving RSV-IGIV prophylaxis; 35 (13.5%) of the children in the placebo group were hospitalized for RSV, compared with 20 (8.0%) RSV-IGIV recipients. RSV-IGIV recipients had a 53% reduction in the total number of RSV hospital days per 100 children, a 60% reduction in the number of RSV days with increased oxygen requirement, and a 54% reduction in the number of RSV hospital days with a moderate or severe lower respiratory tract illness. In addition, children receiving RSV-IGIV had a 38% reduction in hospitalization for respiratory illness of any cause and a 46% reduction in total hospital days for respiratory illness per 100 children. RSV-IGIV was safe and well tolerated, with a safety profile similar to other IGIV preparations. Between 1% to 3% of children had medically significant adverse events related to RSV-IGIV administration. CONCLUSIONS: Monthly administration of 750 mg/kg of RSV-IGIV was safe and well tolerated and was effective in reducing the incidence and total days of both RSV hospitalization and overall respiratory hospitalization in infants with a history of prematurity or bronchopulmonary dysplasia or both.

Bronchopulmonary Dysplasia↗