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PubMed2005

Respiratory syncytial virus bronchiolitis.

Respiratory syncytial virus, the most common cause of bronchiolitis, is the leading cause of infant hospitalization in developed countries and accounts for substantial mortality and morbidity in developing countries. Children at increased risk of developing severe bronchiolitis are those <6 weeks of age, those born prematurely and those with an underlying cardiopulmonary disorder or immunodeficiency. Approximately 80% of cases occur in the first year of life. By two years of age, virtually all children have been infected by at least one strain of the virus. Classically, respiratory syncytial virus bronchiolitis manifests as cough, wheezing and respiratory distress. The mainstay of treatment is supportive care, consisting of adequate fluid intake, antipyretics to control fever and use of supplemental oxygen if necessary. Frequent and meticulous hand-washing is the best measure to prevent secondary spread. Treatment of respiratory syncytial virus bronchiolitis beyond supportive care should be individualized. Palivizumab has been shown to be effective in preventing severe respiratory syncytial virus bronchiolitis in high-risk children when given prophylactically. In the majority of cases, the disease is usually self-limited. The mortality rate is <1% and occurs predominantly in children at high risk for severe disease.

Adrenal Cortex Hormones↗

PubMed1993

Predictors of outcome of severe respiratory syncytial virus-associated respiratory failure treated with extracorporeal membrane oxygenation.

OBJECTIVE: To examine the Extracorporeal Life Support Organization registry data base for all infants and children with respiratory syncytial virus-associated respiratory failure managed with extracorporeal life support, to delineate predictors of outcome. DESIGN: Retrospective cohort study. SETTING: Extracorporeal Life Support Organization data registry. PATIENTS: All pediatric patients treated in the United States with extracorporeal life support for severe pediatric respiratory syncytial virus-associated respiratory failure reported to the registry, from 1982 through June 1992. INTERVENTIONS: Venoarterial or venovenous extracorporeal life support. MEASUREMENTS AND MAIN RESULTS: As of June 1992, fifty-three pediatric patients meeting study entry criteria were reported to the Pediatric Respiratory Failure Registry (n = 412) as having received extracorporeal membrane oxygenation (ECMO) for severe respiratory syncytial virus infection with pulmonary failure. Forty-nine percent (26/53) were successfully managed and survived to hospital discharge. The mean patient age was 5.0 +/- 8.6 months. Duration of mechanical ventilation before institution of extracorporeal life support was 8.1 +/- 6.2 days. Multivariate logistic regression analysis found four variables to be associated with patient nonsurvival at the p < 0.05 level: male gender, longer duration of mechanical ventilation before ECMO, higher peak inspiratory pressure, and lower ratio of arterial oxygen tension to fraction of inspired oxygen. Era of treatment was not associated with outcome. Receiver operator characteristic curve analysis of this multivariate model resulted in cutoff points of r = 0.5 and 0.1 that resulted in 92% sensitivity and 81% specificity (false-positive ratio 19%) and 96% sensitivity and 73% specificity (false-positive ratio 27%), respectively. CONCLUSIONS: Predictors of outcome of severe respiratory failure caused by respiratory syncytial virus infection managed with ECMO exist, and multivariate predictive models with high sensitivity and low false-positive risk are possible. Similar mathematical models may be helpful in establishing criteria for future trials of ECMO versus conventional respiratory support.

Acute Disease↗

PubMedDate not supplied

Detection of respiratory syncytial virus in nasopharyngeal secretions by 24-well plate precentrifugation assay using a monoclonal antibody against F protein.

BACKGROUND: Respiratory syncytial virus (RSV) is responsible for 50% of all bronchiolitis and 25% of pneumonia cases during the first month of life. Detection of the RSV antigen by immunofluorescence in exfoliated nasal epithelium or by other methods in nasopharyngeal swabs is useful in the potentially infected patient because results are available within a few hours. In contrast, RSV antigen detection in cell culture may require as much as 3 weeks. METHODS: Three methods for detection of respiratory syncytial virus in 131 clinical respiratory specimens from patients with acute respiratory disease and bronchiolitis were compared utilizing the following: a precentrifugation immunofluorescence assay using Hep-2 cells, indirect immunofluorescence assay, and conventional tube cell culture using Hep-2 cells. RESULTS: Respiratory syncytial virus was identified in 36 specimens by the three methods previously described. The virus was recovered in 41 (31.3%) samples by precentrifugation immunofluorescence assay, 40 (30.5%) were identified by the immunofluorescence technique, and 38 (29.0%) cases were positive by conventional cell culture. The sensitivity of the precentrifugation assay in relation to the immunofluorescence technique was 90%, the specificity 94.5%, and the agreement, 96.2%. A positive predictive value of 90.2% was obtained. Sensitivity, specificity, agreement, and positive predictive values obtained by the precentrifugation assay variant compared to the conventional cell were 90.8%, 94.5%, 93.1%, and 87.8%, respectively. CONCLUSIONS: The precentrifugation immunofluorescence assay method was as sensitive as the remainder of the methods used in our study and represents a valid alternative for rapid detection of respiratory syncytial virus in clinical samples.

Antibodies, Monoclonal↗

PubMed1970

The use of cough-nasal swabs in the rapid diagnosis of respiratory syncytial virus infection by the fluorescent antibody technique.

Thirty-five consecutive infants admitted into hospital in Newcastle upon Tyne with acute respiratory disease had cough/nasal swabs and nasopharyngeal secretions taken. Both types of specimens were examined by the fluorescent antibody technique for respiratory syncytial virus; isolation techniques were also used. Twenty-eight specimens of nasopharyngeal secretion were positive, as were 26 of the corresponding cough/nasal swab preparations. Respiratory syncytial virus was isolated from all but one.Sixteen consecutive children who were only suitable for examination by cough/nasal swab preparations were also investigated by isolation and fluorescent antibody techniques for respiratory syncytial virus. Respiratory syncytial virus was isolated from eight, seven of whom were positive by the fluorescent antibody technique. The use of cough/nasal swab preparations stained by the fluorescent antibody technique, although not as efficient as nasopharyngeal secretions, may have a place in the rapid diagnosis of respiratory virus infection in older children and children in general practice. The importance of rapid diagnosis for respiratory virus infection in relationship to antiviral therapy was also discussed.

Bronchiolitis, Viral↗

PubMed1991

A controlled trial of aerosolized ribavirin in infants receiving mechanical ventilation for severe respiratory syncytial virus infection.

BACKGROUND: Although the antiviral agent ribavirin improves the course of lower respiratory tract disease in spontaneously breathing infants with respiratory syncytial virus infection, it is not known whether ribavirin can benefit infants with severe respiratory syncytial virus disease who require mechanical ventilation. METHODS: We conducted a randomized, double-blind, placebo-controlled evaluation of ribavirin (20 mg per milliliter) administered continuously in aerosolized form to infants receiving mechanical ventilation for respiratory failure that was caused by documented respiratory syncytial virus infection. RESULTS: Of the 28 infants (mean [+/- SD] age, 1.4 +/- 1.7 months) enrolled, 7 had underlying diseases predisposing them to severe infection (mean age, 3.0 +/- 2.6 months), and 21 were previously normal (mean age, 0.8 +/- 0.9 month). Among the 14 infants who received ribavirin, the mean duration of mechanical ventilation was 4.9 days (as compared with 9.9 days among the 14 who received placebo; P = 0.01), and the mean length of supplemental oxygen use was 8.7 days (as compared with 13.5 days; P = 0.01). The mean length of the hospital stay was 13.3 days after treatment with ribavirin and 15.0 with placebo (P = 0.04). When only the 21 previously normal infants were considered, the mean length of the hospital stay was 9.0 days for the ribavirin recipients and 15.3 days for those who received placebo (P = 0.005). CONCLUSIONS: In infants who require mechanical ventilation because of severe respiratory syncytial virus infection, treatment with aerosolized ribavirin decreases the duration of mechanical ventilation, oxygen treatment, and the hospital stay.

Aerosols↗

PubMed2006

Randomized controlled multicenter trial of aerosolized ribavirin for respiratory syncytial virus upper respiratory tract infection in hematopoietic cell transplant recipients.

BACKGROUND: Respiratory syncytial virus infection of the upper airways may progress to fatal pneumonia in hematopoietic cell transplant recipients. The safety and efficacy of aerosolized ribavirin in preventing disease progression is unknown. METHODS: In a multicenter prospective trial, hematopoietic cell transplant recipients with respiratory syncytial virus infection of the upper airways were randomized to receive ribavirin (2 g 3 times daily) or supportive care for 10 days. The primary end point was progression to radiographically proven pneumonia. Secondary end points included virologically proven respiratory syncytial virus pneumonia, viral load changes, and safety. RESULTS: Fourteen patients were randomized to 1 of 2 treatment arms. The trial was discontinued after 5 years because of slow accrual. Pneumonia at 1 month after randomization occurred in 1 of 9 patients who received ribavirin and in 2 of 5 patients who received supportive care (P=.51); virologically proven respiratory syncytial virus pneumonia occurred in 0 of 9 and 2 of 5 patients, respectively (P=.11). At 10 days after randomization, the average viral load decreased by 0.75 log10 copies/mL in ribavirin recipients, compared with a viral load increase of 1.26 log10 copies/mL in untreated patients (P=.07). No discontinuations of ribavirin therapy because of adverse effects occurred during 84 drug administrations. Rates of adverse events were similar in both groups. CONCLUSIONS: Preemptive aerosolized ribavirin treatment appeared to be safe, and trends of decreasing viral load over time were observed. However, proof of efficacy remains elusive in hematopoietic cell transplant recipients.

Adolescent↗

PubMed1975

Quantitative shedding patterns of respiratory syncytial virus in infants.

Quantitative shedding patterns of respiratory syncytial virus in 40 infants hospitalized with acute disease of the lower respiratory tract were determined for elucidation of the pathophysiology of infection with the virus. Nasal wash specimens were collected on admission and daily thereafter and were tested for the presence and quantities of respiratory syncytial virus. The following pattern of shedding was observed. (1) The virus was shed for prolonged periods. For the first seven days of hospitalization, 92%-100% of the infants tested continued to shed virus. At discharge 87% were still shedding the virus. (2) Respiratory syncytial virus was present in high titer in the nasal secretions obtained at the time of admission. The mean titer in these samples was 5.0 log10 TCID50. (3) The titer of respiratory syncytial virus did not fall during the first few days of hospitalization, despite clinical improvement of the infants. Neither peak nor admission titers of virus could be correlated with age or with the severity of disease. However, the mean admission titer in patients with bronchiolitis appeared to be significantly higher than that in those with pneumonia.

Acute Disease↗

PubMed2006

The relationship between respiratory syncytial virus infections and the development of wheezing and asthma in children.

PURPOSE OF REVIEW: The relationship between respiratory syncytial virus lower-respiratory-tract infections in early childhood and asthma has been the subject of much debate. Most, but not all, previous cohort studies have failed to identify a link between early respiratory syncytial virus infection and atopic asthma. Recent studies have helped clarify some apparently contradictory findings. RECENT FINDINGS: Cohort studies focusing on wheezing in early childhood have indicated that this is associated with an increased incidence of atopic asthma but that this risk is not increased by respiratory syncytial virus infection. Indeed, wheeze associated with rhinovirus infection may be a better marker for possible asthma. In contrast, there is no increased risk of atopic disease in infants with respiratory syncytial virus 'acute bronchiolitis', a phenotype characterized by widespread crepitation. Post-bronchiolitic symptoms are associated with intercurrent viral infections in particular and the incidence of symptoms falls rapidly during infancy. SUMMARY: These studies confirm earlier suggestions that the phenotype of respiratory illness and hence the host response rather than the infecting organism is the best predictor of the future pattern of respiratory illness. Such considerations must be central to the design of any future intervention or cohort studies.

Asthma↗

PubMed2006

Predicting respiratory syncytial virus hospitalisation in Australian children.

BACKGROUND: There is limited information on respiratory syncytial virus infections among Australians, particularly those of Indigenous descent. AIM: This study identifies groups of infants at risk of hospitalisation with respiratory syncytial virus-positive lower respiratory tract infection who may be targeted for prevention with palivizumab. METHODS: Case control study: the case notes of 271 children with cases of respiratory syncytial virus-positive lower respiratory tract infection admitted to The Townsville Hospital were studied for risk factors. Controls were chosen randomly from babies born in The Townsville Hospital during that period. Multiple logistic regression analysis and classification and regression tree analysis were used to identify risk factors. RESULTS: Multiple logistic regression analysis identified birthweight <2500 g, maternal parity and marital status to be independent predictors of hospitalisation with respiratory syncytial virus-positive lower respiratory tract infection. Classification and regression tree analysis identified babies born weighing <2500 g who possessed older siblings to be at highest risk. Single mothers and smoking were additional risk factors. Indigenous babies were significantly more likely to be exposed to all of the identified risk factors. CONCLUSION: Babies born weighing <2500 g (especially with siblings) could be targeted for prevention. All Indigenous babies should be considered at high risk because of their exposure to multiple risk factors.

Adult↗

PubMed1981

Inhibition of respiratory syncytial virus-host cell interactions by mono- and diamidines.

Several aromatic mono- and diamidines were found to block cell fusion induced by respiratory syncytial virus. The best inhibitors were able to achieve complete suppression of syncytium formation at a concentration of 1.0 microM. Inhibition occurred in respiratory syncytial virus-infected HEp-2 and CV-1 cells, but the same inhibitors were ineffective in preventing fusion induced by parainfluenza virus type 3. The fusion inhibitors did not reduce single-cycle virus yields, but did reduce multiple-cycle yields. In addition, the active compounds caused a significant retardation of respiratory syncytial virus penetration. The mechanism by which amidines interfere with respiratory syncytial virus-host cell interactions is unknown, but parallels can be drawn between antiviral activity and the ability of the compounds to inhibit certain trypsin-like proteases.

Amidines↗

PubMed1984

Respiratory syncytial virus infection in mice.

The A2 strain of human respiratory syncytial virus replicated in the nose and lung of BALB/c mice, with virus growing to higher titers in older animals than in younger animals. Virus was recovered from the nose between days 2 and 7 with peak titers on days 3 and 4, and from the lungs between days 2 and 9, with peak titers on days 4 through 6. Serum antibody developed 2 weeks after infection. Viral antigen was demonstrated in the alveolar cells of the lung by immunofluorescence. Histopathological changes included infiltration by mononuclear cells of the peribronchiolar and perivascular tissue, some interstitial thickening, and formation of multinucleated giant cells. Virus could not be recovered from the respiratory tract of mice inoculated with bovine strains of respiratory syncytial virus. Growth of the A2 strain of human respiratory syncytial virus in different cell lines affected its infectivity for mice. Infection of BALB/c mice with respiratory syncytial virus provides a highly reproducible model for the study of the pathogenesis of and mechanisms of immunity to this virus.

Age Factors↗

PubMed1982

Comparison of direct and indirect immunofluorescence staining of clinical specimens for detection of respiratory syncytial virus antigen.

Immunofluorescence staining methods for respiratory syncytial virus antigen detection were compared. Of 50 specimens originally positive for respiratory syncytial virus by direct immunofluorescence and culture, 49 were positive by repeat direct immunofluorescence and 32 were positive by indirect immunofluorescence. Additional results obtained on specimens originally negative for respiratory syncytial virus by direct immunofluorescence, culture, or both indicate that direct immunofluorescence staining for respiratory syncytial virus antigen was more sensitive than was indirect immunofluorescence.

Antigens, Viral↗

PubMed1987

Subgroup characteristics of respiratory syncytial virus strains recovered from children with two consecutive infections.

Respiratory syncytial virus strains from 13 children who had repeat infections at least 1 year apart were identified as either subgroup A or subgroup B according to reaction patterns with several monoclonal antibodies directed against the large surface glycoprotein (G), fusion protein (F), nucleoprotein (NP), and matrix protein (M). The virus strains were characterized by enzyme immunoassay, polyacrylamide gel electrophoresis, and immunofluorescence procedures. During the first infection, 10 children had subgroup A strains and 3 had subgroup B strains. Of the 10 children with subgroup A strains during their first infection, 6 had subgroup B and 4 had subgroup A strains during the second infection. Of the three children with subgroup B strains during their first infection, one had subgroup A and two had subgroup B strains during their second infection. No child experienced unusually severe respiratory tract illnesses during second infections with respiratory syncytial virus. Fourfold or greater rises in serum antibody as determined by enzyme immunoassay were as common after the first infection as after the second infection among the seven children tested. Thus, second infections with strains of either subgroup of respiratory syncytial virus did not potentiate respiratory illness, and infection with subgroup A strains of respiratory syncytial virus provided some protection from a second infection with the homologous, but not the heterologous, subgroup of the virus.

Acute Disease↗

PubMed1985

The envelope-associated 22K protein of human respiratory syncytial virus: nucleotide sequence of the mRNA and a related polytranscript.

We recently determined that respiratory syncytial virus (strain A2) encodes a fourth unique envelope-associated virion protein that has molecular weight of approximately 24,000, as estimated by gel electrophoresis. The nucleotide sequence of the mRNA encoding this novel protein has now been determined from five cDNA clones, including three that contain the complete mRNA sequence. The complete mRNA sequence is 957 nucleotides, exclusive of polyadenylate, and contains two partially overlapping open reading frames. The 5'-proximal open reading frame is favored for utilization by the criteria of the location and sequence of its translational start site. Furthermore, the calculated molecular weight of the encoded protein, 22,153, is in agreement with the previous estimate of 24,000 for the authentic protein identified by hybrid selection and in vitro translation. The sequence of the predicted protein, now designated the 22K protein, contains 194 amino acids, is relatively hydrophilic, and appears to be the most basic of the respiratory syncytial virus proteins. The mRNA also contains a second, internal open reading frame which would encode a protein of 90 amino acids. However, no evidence for this translation product is known. The first nine nucleotides in the mRNA sequence, 5'-GGGGCAAAU, are identical to the conserved sequence identified previously at the 5' termini of seven other respiratory syncytial viral mRNAs; the sequence at the 3' end of the 22K mRNA, 5'. . . AGUUAUUU-polyadenylate, contains the elements of the previously identified 3'-terminal consensus sequence for respiratory syncytial virus mRNAs, AGUUAA(N)1-4-polyadenylate (P. L. Collins, Y. T. Huang, and G. W. Wertz, Proc. Natl. Acad. Sci. U.S.A. 81:7683-7687). In addition, we present and describe the intergenic sequence of a dicistronic RNA derived from readthrough of the F and 22K protein genes.

Amino Acid Sequence↗

PubMed1990

Excessive secretion of antidiuretic hormone in infections with respiratory syncytial virus.

The association between infections with respiratory syncytial virus and plasma concentrations of antidiuretic hormone was assessed in 48 patients who had been admitted to hospital. The mean (SEM) concentration of antidiuretic hormone was significantly raised in patients with bronchiolitis (9.3 (1.4) ng/l) compared with non-pulmonary respiratory syncytial virus infections that cause apnoea or upper respiratory tract symptoms (6.1 (1.7) ng/l). The highest concentrations of antidiuretic hormone were seen in patients receiving mechanical ventilation (18.0 (6.7) ng/l). There were no differences in mean serum sodium concentrations among the subgroups. Hypertranslucency on chest radiograph or an arterial carbon dioxide tension above 6.67 kPa were associated with a significantly higher concentration of antidiuretic hormone. Increased or normal maintenance fluid intake in children with pulmonary respiratory syncytial virus infections may cause the same symptoms of fluid overload as the syndrome of inappropriate secretion of antidiuretic hormone. Patients with pulmonary respiratory syncytial virus infection, hypertranslucency in chest radiograph, hypercapnia, or mechanical ventilation are at risk for raised concentrations of antidiuretic hormone. Restricted fluid intake and careful monitoring of fluid balance and plasma electrolyte concentrations are therefore necessary in these patients.

Bronchiolitis, Viral↗

PubMed1990

Latent sensitisation to respiratory syncytial virus during acute bronchiolitis and lung function after recovery.

To determine whether latent sensitivity to respiratory syncytial virus antigen(s) occurs after infection, 27 infants with acute bronchiolitis were studied and compared with 15 hospital controls. Blood was collected for whole blood challenge, and histamine release was measured by a high performance liquid chromatography technique with fluorometric detection. There was a significantly greater histamine release to respiratory syncytial virus antigen(s) in those with bronchiolitis than in controls, expressed either in amount (median 154 nmol/l compared with 104 nmol/l) or percentage release (median 20% compared with 3%). There was a significant difference between index and control groups in terms of individual histamine responses. These findings strongly suggest that infants develop latent sensitivity to respiratory syncytial virus antigen(s) during the course of acute bronchiolitis. Serial lung function tests were performed in 15 infants. All infants had abnormalities of lung function at some stage, but the small numbers of subjects precluded comparison between 'sensitised' and 'non-sensitised' infants. Further study is indicated to define the relation of latent sensitisation and subsequent bronchial hyper-responsiveness after respiratory syncytial virus infection in infants.

Acute Disease↗

PubMed1981

Respiratory syncytial virus infection: ten-year follow-up.

Studies within the last 20 years have shown that the incidence of asthma is increased in children who have been hospitalized with bronchiolitis due to respiratory syncytial virus. To evaluate such respiratory consequences in an ambulatory population, a follow-up study was done of 37 children who had respiratory syncytial virus infection documented at a community pediatric clinic in 1968 when they were younger than 4 years. This study, done ten years later by chart review and parental interview, showed that asthma had subsequently been diagnosed in three (8%). Thus, an increased risk for the development of asthma after respiratory syncytial virus infection was not found. Comparison of these data with those from previous reviews questions a causative role for respiratory syncytial virus in childhood asthma.

Asthma↗

PubMed1993

Characteristic differences in reverse transcription-polymerase chain reaction products of ovine, bovine, and human respiratory syncytial viruses.

In reverse transcription-polymerase chain reactions (RT-PCR) and DNA hybridizations using primers and an oligonucleotide probe to the fusion (F) protein mRNA of bovine respiratory syncytial virus (BRSV), all the BRSV isolates and a goat isolate could be distinguished from prototype isolates of human respiratory syncytial viruses (HRSV) and ovine (sheep and bighorn sheep) respiratory syncytial viruses (RSV). However, RT-PCR amplifications with primers to sequences of the HRSV F protein mRNA resulted in amplified products of approximately 243 bp if mRNA templates of subgroup A HRSV strains were present and slightly larger amplified products with subgroup B HRSV strains. No amplified products were observed in HRSV-primed RT-PCR with BRSV or goat or ovine RSV mRNA templates. Although the ovine RSV isolates were antigenically cross-reactive with the goat RSV, HRSV and BRSV isolates, they were no amplified with either HRSV- or BRSV-specific primers in RT-PCR. These results confirm previous immunological comparisons suggesting that some ovine RSV isolates should be considered as distinct respiratory syncytial viruses.

Animals↗