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PubMed2002

Enhanced IL-4 responses in children with a history of respiratory syncytial virus bronchiolitis in infancy.

Infants who recover from respiratory syncytial virus (RSV)-induced bronchiolitis are at high risk of developing asthma and recurrent wheezing. It is not known whether severe RSV infection itself causes persistent effects or is a marker of a "wheezy" predisposition. To determine the long-term immunological correlates of infantile bronchiolitis, interleukin (IL)-4 and interferon (IFN)-gamma responses to a panel of antigens were studied in a well-characterised cohort of 7-8-yr-old children with a history of severe RSV bronchiolitis in infancy. Peripheral blood lymphocytes from 37 children who were hospitalised with RSV bronchiolitis in infancy and from 69 age-, sex- and location-matched controls were stimulated in vitro with RSV, house-dust mite, birch and cat antigens. Cellular proliferation, and enzyme-linked immunoSPOT IFN-gamma and IL-4 production were measured. IL-4 producing T-cells responding to RSV and cat antigens were significantly more frequent in exbronchiolitics. Other responses (including the IFN-gamma response to RSV) were equally strong in exbronchiolitics and controls. Respiratory syncytial virus infection primes memory T-cells that make interferon-gamma, but virus and aeroallergen-specific and interleukin-4 producing T-cells are also frequently primed in bronchiolitics. Respiratory syncytial virus bronchiolitis in infancy may increase the risk of allergic sensitisation by providing a local interleukin-4-rich environment, in which airborne allergens are first encountered.

Asthma↗
PubMed1998

Neutrophils induce damage to respiratory epithelial cells infected with respiratory syncytial virus.

The mechanisms by which respiratory syncytial virus (RSV) infection induces bronchiolitis and airway disease are unclear. The presence of large numbers of polymorphonuclear leukocytes (PMN) in the airways of infants with RSV infection suggests a potential role of PMN in airway injury associated with RSV infection. To investigate the potential role of neutrophils in RSV bronchiolitis, human alveolar type II cells (A549 cells) were infected with different doses of RSV for 6-48 h. A 51Cr-releasing assay was used to measure PMN-induced damage and image analysis was used to determine PMN adhesion and detachment of epithelial cells. The results showed that RSV infection of epithelial cells enhanced PMN adherence in a dose- and time-dependent pattern, RSV infection alone could damage and detach epithelial cells to a limited extent and PMN significantly augmented RSV infection-induced damage and detachment of epithelial cells. These data suggest that respiratory syncytial virus infection of respiratory epithelial cells enhances neutrophil adhesion to the epithelium and that activated neutrophils augment the damage and detachment of epithelium infected with the virus. Polymorphonuclear leukocytes may contribute to the pathogenesis of respiratory syncytial virus airway disease by inducing epithelial damage and cell loss.

Cell Adhesion↗
PubMed2003

Bronchiolitis, respiratory syncytial virus, and recurrent wheezing: what is the relationship?

Various follow-up studies of children hospitalized with bronchiolitis caused by respiratory syncytial virus have demonstrated that a significant proportion of infants (50%) have recurrent wheezing during childhood. Nevertheless, the relationship between these two entities, if any, has not been established. In order to explain this observation, several hypotheses have been proposed. The first suggests that some children could have an individual predisposition to bronchiolitis caused by respiratory syncytial virus and recurrent wheezing. The virus could be a marker of this condition, and the individual predisposition could in turn be related to an individual hypersensitivity to common allergens (atopy), airway hyperreactivity, or to some disorder related to pulmonary anatomy or physiology that was present before the acute episode of bronchiolitis. Another hypothesis proposes that respiratory syncytial virus could be directly responsible for recurrent wheezing. During an episode of bronchiolitis, the damage in the airway mucosa caused by the vital inflammatory response to infection contributes to sensitivity to other allergens or exposes irritant receptors, resulting in recurrent wheezing. For this review, we analyzed the studies that discuss these hypotheses with the purpose of clarifying the mechanisms for the important issue of recurrent wheezing in childhood.

Bronchiolitis, Viral↗
PubMed2001

[Primary respiratory syncytial virus infection in mice].

OBJECTIVE: To establish a mice-model of primary respiratory syncytial virus infection. METHODS: Twelve Balb/c mice (8-12 w) were divided into two groups with three different titers of RSV infection in the experimental group. Mice were anaesthetized with pentobabitone(30 mg/kg) and infected by nasal drip of 0.1 ml of RSV which was harvested from HEP-2 cell culture. Three mice in the control group received sham infection with HEP-2 cell media. Five days later, lungs were removed in aseptic condition. Right lung was weighted and homoginized with MEM(1:10 ratio), then centrifuged at 4 degrees C, 2,000 r/min for 20 minutes. Supernatants were collected for virus isolation and plaque forming assay. Left lung was collected for histopathological and electromicroscopic examination. RESULTS: (1) RSV grew with a characteristic syncytial formation in HEP-2 cells, leading to the fusion of cells with round, elliptic, map or tree like shape. (2) Virus was isolated and detected in the lung tissue in experiment group. (3) There was a positive correlation between RSV titer added and that replicated in the lung. (4) After the eclipse phase, viral replication in the lung reached maximum within 4 and 6 days. The most apparent pathological change was found between day 5 and 8. Mononuclear cell infiltration was presented in the perivascular, peribronchial and in the alveoli spacers. (5) Huge viral replication with its fuzzy coat was detected inside the cytoplasm of the type II alveolar lining cell at high magnification. CONCLUSION: An animal model of RSV infection Balb/c mice was successfully established by nasal inoculation with respiratory syncytial virus.

Animals↗
PubMed1992

[Detection of respiratory syncytial and adenovirus in nasopharyngeal aspirates: comparison of cellular cultures and immunofluorescence].

Respiratory syncytial and adenovirus are 2 of the most important pathogens for respiratory infection in infancy. We compared the results of cellular cultures and immunofluorescence in the detection of these agents in nasopharyngeal exudates from hospitalized infants. Evidence for respiratory syncytial virus was searched in 776 samples. Immunofluorescence was much more sensitive, detecting 303 positive results, compared to only 142 for cell culture. Compared to immunofluorescence, the sensitivity and specificity of cell culture was 44% and 98%, respectively. Adenoviruses were investigated in 498 samples by both techniques. 88 positive results were identified by cell culture and only 30 by immunofluorescence. The sensitivity of immunofluorescence, compared to cell culture, was 31%, with a specificity of 99%. Thus, immunofluorescence is the technique of choice for detection of respiratory syncytial virus, while cell culture is preferable for adenovirus.

Adenoviridae Infections↗
PubMedDate not supplied

[Concentrations of interleukin-2 in the nasopharyngeal secretion of children with acute respiratory syncytial virus bronchiolitis].

OBJECTIVE: To assess interleukin-2 concentrations in nasopharyngeal secretion of children (0-24 months) with acute respiratory syncytial virus bronchiolitis, within the first 12 hours of hospital admission, and compare the levels of IL-2 with the severity of the illness. METHODS: Prospective study performed between June and August 1999. The study included 62 patients, previously healthy, hospitalized with acute viral bronchiolitis characterized by recent prodromes of coryza and/or nasal obstruction, which evolved to at least two of the following signs: respiratory dysfunction, tachypnea, wheezing or rales, and detection of respiratory syncytial virus in nasopharyngeal aspirate. The nasopharyngeal specimens were collected within 12 hours of hospital admission. The interleukin-2 levels were obtained by enzyme immunoassay. Severity of illness was assessed through oxygen saturation by pulse oximetry, Modified Clinical Score System, time of supplemental oxygen required, length of hospital stay, and mechanical ventilation. Spearman's correlation and Kruskal-Wallis test were used to compared these variables in relation to the median of interleukin-2. The chi-square test was used for categorical analysis of interleukin-2. RESULTS: The mean age of patients was 2.2 (1.3-4) months. Males comprised 54% of cases. Hemoglobin oxygen saturation by pulse oximetry at hospital admission was below 95% in 66.1% of patients. The mean time of supplemental oxygen use was 4.7 days (+/-3.54). The mean length of hospital stay was 4.25 days (+/-1.76). Mechanical ventilation was used in 4.8% of patients. The values of interleukin-2 in nasopharyngeal aspirates varied from 0 to 40,256 ng/ml with median of 86 ng/ml (4.4 - 457.3). The study showed no statistical difference between levels of IL-2 and severity of illness. CONCLUSIONS: The interleukin-2 levels showed a heterogeneous behavior. We found no association between interleukin-2 levels in nasopharyngeal secretion and respiratory syncytial virus bronchiolitis.

Acute Disease↗
PubMed1990

Serological studies of bovine respiratory syncytial virus in feedlot cattle in South Africa.

Serum antibody titres to bovine respiratory syncytial virus were determined in cattle (n = 282). Samples were obtained at various feedlots and were collected in the 1989 and 1990 winter seasons, during the course of investigations into outbreaks of respiratory tract infections in feedlot cattle. Results of the survey revealed an antibody prevalence of 43% to bovine respiratory syncytial virus. Titres ranged from 1:10 to 1:1280 as determined by the indirect fluorescent antibody test. The results also indicate that bovine respiratory syncytial virus is probably widespread in feedlot cattle in South Africa, and that this virus may be a contributing factor in the bovine respiratory complex.

Animals↗
PubMed1997

Milk production and reproductive performance in dairy cows given bovine respiratory syncytial virus vaccine prior to parturition.

OBJECTIVE: To assess the effect of vaccination against bovine respiratory syncytial virus on milk production, reproductive performance, and health in lactating dairy cows. DESIGN: Prospective randomized block design. ANIMALS: 385 Holstein dairy cows and heifers. PROCEDURE: Cows were grouped by lactation number, season of calving, and previous mature equivalent 305-day milk production (where appropriate). Prior to parturition, cows and heifers were randomly assigned to be vaccinated i.m. against infectious bovine rhinotracheitis, bovine viral diarrhea, and parainfluenza 3 viruses by use of a three-way vaccine, or to be vaccinated against those viruses as well as bovine respiratory syncytial virus, using a four-way vaccine. Milk production was measured daily through 305 days of lactation. Reproductive and medical records were reviewed to obtain insemination dates and record medical problems of cows in each vaccine treatment group. RESULTS: Compared with the three-way vaccine, administration of the four-way vaccine was associated with higher milk production (1.39 kg [3.06 lb] more milk/d) in first-parity cows during the first 21 weeks of lactation. Vaccination did not have any effect on milk production after the first 21 weeks of lactation in cows of any parity. Conception rates at first insemination were higher for four-way vaccinated first-parity cows than for three-way vaccinated first-parity cows (54.6 vs 32.7%). Compared with second-parity cows that received the three-way vaccine, first insemination conception rate was improved for second-parity cows vaccinated with the four-way vaccine (28.9 vs 47.8%, respectively). In cows of third or greater parity, first insemination conception rate was not different between the 2 vaccine treatment groups. CLINICAL IMPLICATIONS: Vaccination of heifers against bovine respiratory syncytial virus prior to partrition may increase milk production and first insemination conception rates.

Animals↗
PubMed1997

[Respiratory syncytial viruses: viral characteristics and epizootiology of the disease].

Human respiratory syncytial virus (HRSV) is the major respiratory tract pathogen of infants and young children. Bovine respiratory syncytial virus (BRSV) is recognized as an important cause of respiratory tract disease in calves. Both these viruses and their respective diseases share many similarities. After a description of the general properties of the virus, this review covers the epizootology of bovine respiratory syncytial virus infection.

Animals↗
PubMed1996

[Subgroups classification of strains of the respiratory syncytial virus isolated in an outbreak in Ciudad de La Havana].

A high number of acute respiratory diseases was detected among children under one year admitted in a hospital of Havana City. 25 respiratory syncytial virus strains were obtained from 93 patients studied. Viral isolations were multiplied in HEP-2 cells and after observing a cytopathic effect of 80%, they were classified into subgroups by the indirect immunofluorescence technique, using anti-protein G antibodies from the respiratory syncytial virus. All the samples studied were classified within subgroup A. It is the first time a study like this is conducted in our country, which allowed us to deepen into the viral cause of these diseases and to know that the subgroup A of the respiratory syncytial virus circulated during the outbreak.

Cuba↗
PubMed1993

Preterm twins and triplets. A high-risk group for severe respiratory syncytial virus infection.

OBJECTIVE: To assess the impact of multiple births and crowded homes on the severity of respiratory syncytial virus illness in preterm infants with bronchopulmonary dysplasia. RESEARCH DESIGN: Retrospective case-control chart review from a prospective longitudinal respiratory illness study. SETTING: Neonatal High-Risk Follow-Up Clinic (outpatient setting) and tertiary care hospitals (inpatient setting). PARTICIPANTS: Fourteen sets of twins and two sets of triplets followed up between 1983 and 1989 and matched with 34 singleton infants for date of birth (within 3 months) and gestational age (within 1 month). MEASUREMENTS/MAIN RESULTS: The risk of developing respiratory syncytial virus illness was significantly higher in multiple-birth infants than in singletons (53% vs 24%; P = .01). Multiple-birth infants were also at greater risk for developing pneumonia (24% vs 6%; P = .05) and requiring hospitalization (32% vs 18%; P = .05) than were singletons. Additional risk factors for developing pneumonia and bronchiolitis were examined in all 68 children. Multiple birth (P = .05), gestational age of less than 30 weeks (P = .02), and crowded homes (defined as more than one person living in 19 m2 of living space [P = .002] or more than one child living in 22 m2 of living space [P = .004]) were additional risk factors for developing pneumonia. CONCLUSION: Multiple-birth preterm infants are at a higher risk of developing pneumonia than are singletons. Additional risk factors for developing pneumonia in preterm infants with bronchopulmonary dysplasia include gestational age of less than 30 weeks and crowded homes. At-risk infants with any of these risk factors should be targeted for prophylactic and therapeutic interventions against respiratory syncytial virus.

Birth Weight↗
PubMed1996

Ribavirin for respiratory syncytial virus lower respiratory tract infection. A systematic overview.

OBJECTIVE: To systematically review the evidence evaluating the efficacy of aerosolized ribavirin for the treatment of infants with respiratory syncytial virus lower respiratory tract infection. DESIGN: A computerized search of MEDLINE from 1975 to the present, a review of the reference lists of each retrieved article, and contact with experts. PATIENTS: infants with documented respiratory syncytial virus lower respiratory tract infection who were the subjects of 8 double-blind randomized placebo-controlled trials. METHODS: Two independent reviewers assessed study quality and extracted data on the study populations, the drug regimens, and clinically relevant outcome measurements. RESULTS: Ribavirin does not significantly reduce mortality rate (relative risk [RR] = 0.42, 95% confidence interval [CI] = 0.13, 1.44) or lower the probability of respiratory deterioration (RR = 0.42, 95% CI = 0.16, 1.34) when meta-analysis is used to pool the outcomes of 3 trials, although strong trends in the direction of benefit are present. No study found ribavirin to shorten length of hospitalization. Results on length of ventilation and oxygen supplementation are conflicting. CONCLUSIONS: Use of ribavirin in infants with respiratory syncytial virus lower respiratory tract infection is not supported by evidence of significant benefit. However, previous studies lack sufficient power to rule out a potential reduction in mortality rate or respiratory deterioration. A large randomized controlled trial of ribavirin for ventilated and other high-risk patients is needed.

Antiviral Agents↗
PubMed2000

Immunoglobulin for preventing respiratory syncytial virus infection.

BACKGROUND: Respiratory Syncytial virus, the most important cause of lower respiratory tract infections in infants and young children in industrialized countries, is associated with increased morbidity in premature infants with or without bronchopulmonary dysplasia as well as those with congenital heart disease. Because of observations that lower rates of disease occur immediately after birth, presumably due to vertical transmission of maternal antibody, and animal studies where protection from pneumonia was observed through administration of immune globulin, the efficacy of passive prophylaxis in premature infants has been studied. OBJECTIVES: This meta-analysis was performed to assess the effects of polyclonal respiratory syncytial virus hyperimmune globulin or monoclonal antibody in preventing RSV hospitalization, receipt of intensive care, mechanical ventilation, and mortality in those with underlying prematurity, bronchopulmonary dysplasia, or congenital heart disease. SEARCH STRATEGY: We searched the Cochrane Acute Respiratory Infections trials register and MEDLINE in March, 1999. In addition, abstracts on these topics were sought from the Pediatric Academies Meetings and the Intersciences Conference on Antimicrobial Agents and Chemotherapy for the years 1994 to 1997, inclusive. SELECTION CRITERIA: Randomized, controlled trials of prevention of RSV using immune globulin, respiratory syncytial virus immune globulin, or monoclonal RSV antibody in children with prematurity, bronchopulmonary dysplasia or congenital heart disease. DATA COLLECTION AND ANALYSIS: Two authors independently abstracted data and assessed study quality. Only incidences could be pooled because data for durations was summarized in a manner that did not allow combining results across the studies. MAIN RESULTS: Four studies with a total of 2598 subjects were included in the main analysis. All were randomized controlled trials. Two trials were not blinded. Three studies examined RSV hyperimmune globulin and one examined monoclonal RSV antibody. A study of a different monoclonal RSV antibody could not be included because it has not been presented or published. The pooled Peto Odds Ratios favoring prophylaxis were 0.48 (95% CI 0.37, 0.64), 0.47 (0.29, 0. 77), and 0.99 (0.48, 2.07) for incidence of hospitalization, incidence of ICU admission, and incidence of mechanical ventilation, respectively. The numbers needed to prevent one hospitalization and one ICU admission are 17 and 50 respectively. REVIEWER'S CONCLUSIONS: RSVIG is effective in preventing RSV hospitalizations and admission to the intensive care unit, but not in preventing mechanical ventilation. There was a non-significant trend towards a higher mortality in children given RSVIG.

Antibodies, Monoclonal↗
PubMed1985

A survey of respiratory syncytial virus and parainfluenza virus type 3 neutralising and immunoprecipitating antibodies in relation to Paget disease.

The aetiology of Paget disease of bone has not been established but certain features have suggested involvement of a parainfluenzalike virus. To seek further evidence of the possible role of paramyxoviruses in Paget disease we have surveyed the presence of neutralising and immunoprecipitating antibodies to both respiratory syncytial virus and parainfluenza virus type 3 in the sera of patients attending a bone disease clinic. These two viruses were implicated by the sporadic observation of viral antigen in individual nuclei of osteoclasts in Paget disease bone lesions. A total of 315 samples were obtained from 177 patients attending the clinic during 1 year. Thirty-six of the patients had confirmed Paget disease and the remainder other conditions. All sera possessed neutralising activity to both viruses. The mean titres for each virus were similar in patients with Paget disease and those with other conditions whether matched or not. In the case of respiratory syncytial virus the neutralising titres were distributed closer to the mean in the Paget group and showed little variation in repeat samples taken over periods of up to 1 year in contrast to the greater variability of the control group. The antigenic specificity of 20 age- and sex-matched sera from each group was examined by immunoprecipitation. No significant differences were observed between Paget and non-Paget patients. These results do not provide confirmation of involvement of either virus in Paget disease, but the serological data suggest that persistent infection with respiratory syncytial virus can occur.

Adolescent↗
PubMed2002

Respiratory syncytial virus bronchiolitis: disease severity, interleukin-8, and virus genotype.

In infants with respiratory syncytial virus (RSV) bronchiolitis, we investigated whether disease severity is associated with the genotype of the infecting virus, or with the infant's immunological response to the infection, as determined by measurement of interleukin-8 mRNA in the nasopharyngeal aspirate. This was a cross-sectional observational study, performed in the Accident and Emergency Department, wards, and Intensive Care Unit of a large pediatric hospital. Participants included 276 infants with respiratory syncytial virus infection. Outcome variables included: disease severity (infants requiring oxygen or ventilation were classified as having severe disease); RSV virus genotype (determined according to typing scheme based on the nucleoprotein and G glycoprotein genes); and amount of interleukin-8 mRNA in the nasopharyngeal aspirate, as measured by a semiquantitative polymerase chain reaction assay. This was corrected for the amount of cellular material in the sample by expressing it relative to mRNA for a constitutively expressed gene, HGPRT. We found a highly significant association between the ratio of interleukin-8 mRNA/HGPRT mRNA in the nasopharyngeal aspirate and the occurrence of severe disease. Odds ratio per unit increase of interleukin-8 mRNA/HGPRT mRNA was 1.15 (95% CI, 1.06, 1.24), P = 0.0004. There was no association between virus genotype and either disease severity or amount of interleukin-8 mRNA/HGPRT mRNA. In conclusion, there is a strong, dose-related association between interleukin-8 mRNA produced locally in the airways and disease severity, and a lack of association with virus genotype. This suggests that clinical manifestations of respiratory syncytial virus bronchiolitis are determined by local immunological responses to infection, rather than by characteristics of the infecting virus.

Bronchiolitis↗
PubMed2000

Therapy for respiratory tract infections caused by respiratory syncytial virus.

UNLABELLED: Respiratory syncytial virus (RSV) is the most common viral cause of lower respiratory tract infection (LRTI) in infancy and young children. No effective treatment for RSV lower respiratory tract infection (RSV-LRTI) exists. Ribavirin initially proved to be an effective anti-viral drug for RSV-LTRI. However, subsequently performed trials could not reproduce these positive results and, based on the current available evidence, there is no place for ribavirin in the routine treatment of RSV-LTRI. The use of nebulised bronchodilator therapy in RSV-LTRI has been subject of many trials, with conflicting results. Although the individual patient may have some short-term benefit from nebulised bronchodilators, there does not seem to be a sufficient scientific basis for the standard use of bronchodilator therapy in infants and children with RSV-LTRI. There is increasing evidence that RSV-LTRI is an immune-mediated disease and therefore corticosteroids may be an effective treatment. The results from efficacy trials have demonstrated that corticosteroids are not effective for patients with mild RSV infection. In contrast there are indications that it may be beneficial in patients with more severe RSV-LTRI. It has been demonstrated that in children with RSV infection the vitamin A concentration is inversely related to disease severity. The use of vitamin A in the treatment of patients with RSV-LTRI, however, proved not to be effective. Immunoprophylaxis with hyperimmune immunoglobulins and monoclonal antibody against the viral F-protein have been shown to be effective in the prevention of RSV-LRTI. From the results of the therapeutic efficacy trials, however, it can be discerned that immunoglobulins have no place in the treatment of RSV-LRTI. CONCLUSION: Although respiratory syncytial virus infections each year have a considerable socioeconomic impact, attempts to find an effective therapy have so far been quite unsuccessful. Anti-viral therapy with ribavirin has not been proven to be effective. Symptomatic therapy with bronchodilators may give only short-term relief of symptoms in some individual patients, but has no effect on hospitalisation rates, or duration of hospitalisation. The beneficial effect of corticosteroids in patients with mild respiratory syncytial virus infection is very disappointing, however, there are indications that there might be an effect in patients with more severe infection. So far no beneficial therapeutic effect has been demonstrated with immune globulins.

Adrenal Cortex Hormones↗
PubMed1991

Molecular cloning and sequence analysis of bovine respiratory syncytial virus mRNA encoding the major nucleocapsid protein.

The nucleotide sequence of the gene encoding the major nucleocapsid (N) protein of bovine respiratory syncytial virus (BRSV) has been determined. The N mRNA is 1196 nucleotides long with a single, large open reading frame. The derived polypeptide has 391 amino acids corresponding to a calculated molecular weight of 42,600 Da. This is in agreement with the molecular weight of 43,000 Da determined for the BRSV N protein by SDS-polyacrylamide gel electrophoresis (PAGE). Comparison of the nucleotide sequence of BRSV N gene with the sequence of the N gene of human respiratory syncytial virus (HRSV) revealed a homology of 80.7%. There is a 93.3% homology at the amino acid level between the N proteins of BRSV and HRSV. The 5'- and 3'-terminal untranslated sequences that are conserved among HRSV mRNAs were also identified in the N mRNA of BRSV. The results indicate that the N genes are highly conserved in the bovine and human strains of respiratory syncytial virus.

Amino Acid Sequence↗
PubMed1987

Differences in fluorescent antibody staining of bovine respiratory syncytial virus-infected cells by ovine and bovine sera.

In indirect fluorescent antibody tests in which sera from cattle and sheep with respiratory disease problems were used to stain foetal bovine lung cells infected with a bovine respiratory syncytial virus strain, differences were noted in the pattern of fluorescence produced by some sheep sera and that produced by positive bovine sera. In serum neutralisation tests, also using a bovine respiratory syncytial virus strain, 4 of 7 sera giving this atypical pattern of fluorescence had very low neutralising antibody titres (highest 1/4), and 3 were negative. It is suggested that two related but antigenically distinguishable respiratory syncytial virus types are present in sheep, one of which is similar to bovine strains.

Animals↗