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PubMed1996

Detection of respiratory syncytial virus (RSV) antigen in the lungs of guinea pigs 6 weeks after experimental infection and despite of the production of neutralizing antibodies.

Infections with respiratory syncytial virus (RSV) are characterized by frequently occurring reinfections and are regarded to be responsible for bronchial hyperreactivity. In this report we describe a small-animal model suited to study RSV-induced pathogenesis and immune response. Guinea pigs are infected by inhalation of an RSV-aerosol. Lungs of infected animals show signs of a bronchiolitis at 7 days after the initial infection. Although neutralizing serum antibodies are synthesized viral proteins are still detectable at 6 weeks post infection. Therefore, the presence of neutralizing antibodies is obviously not sufficient for rapid clearance of persistent RSV-proteins from the lungs of infected guinea pigs.

Animals↗
PubMed1996

Immunological response of mice to the bovine respiratory syncytial virus fusion glycoprotein expressed in recombinant baculovirus infected insect cells.

Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in calves. The BRSV genome encodes two major glycoproteins, G and F, which are the major targets for the host antibody response. We have expressed the F glycoprotein in insect cells (Sf9) using a recombinant baculovirus vector. A comparison of the F protein expressed in mammalian and insect cells by SDS-PAGE showed that only part of the baculovirus-produced protein was soluble and processed like the native protein. The antigenicity of the soluble form of the F protein expressed in insect cells was identical to that of the F protein expressed in mammalian cells. Immunization with the F protein expressed in insect cells induced neutralizing antibodies in mice. This antigenic preparation adjuvanted with Quil-A produced an increased neutralizing antibody titer and induced protection.

Animals↗
PubMed1995

Respiratory syncytial virus, a rare cause of severe pneumonia following bone marrow transplantation.

Mixed alveolar interstitial pneumonia is a much-feared complication in bone marrow transplant recipients because it carries a high mortality. Many cases in which an etiological agent is identified are due to fungi or cytomegalovirus; rarely, other infectious agents such as Pneumocystis carinii or (para)influenzavirus are involved. In this report we describe a patient who received intense chemotherapy followed by autologous bone marrow transplantation for relapse of testis seminoma and who developed a severe alveolar interstitial pneumonia caused by respiratory syncytial virus in the early posttransplant period. The patient fully recovered after treatment with ribavirin.

Adult↗
PubMed1995

The clinical picture presented by premature neonates infected with the respiratory syncytial virus.

During the course of a 3-year epidemic of respiratory syncytial virus (RSV) in an Neonatal Intensive Care Unit, we examined premature neonates for the clinical features of RSV infections and the risk factors predisposing towards transmission of the disease. Seventy-nine infants with a median gestational age of 31 weeks were tested in 113 episodes of clinical deterioration for the presence of RSV antigen in nasopharyngeal secretions. Forty-seven results were positive and 66 negative. Bradycardia, which is gestational-age dependent, was the main presenting clinical symptom of an RSV infection in 75% of cases. The probability of an RSV-positive result in an episode with bradycardia, hypercapnia and fever was calculated to be 0.75. The only identifiable epidemiological risk factor was the total number of symptomatic RSV-infected infants in the ward. CONCLUSION. Bradycardia may indicate the presence of an RSV infection: the appropriate tests should be carried out and infection control reinforced immediately.

Antigens, Viral↗
PubMedDate not supplied

Respiratory syncytial virus infection in children with congenital heart disease: a review.

This paper reviews recent changes in morbidity and mortality of respiratory syncytial virus (RSV) infection in infants with congenital heart disease. Mortality since the late 1970s has declined substantially, from approximately 37% to 3%. Although the frequency of admission to intensive care units has declined from approximately 60% to 30%, the frequency for mechanical ventilatory support has not changed significantly. Because mortality dropped prior to the widespread use of ribavirin, it is difficult to ascribe the improvement to this therapy. In infants with congenital heart disease (CHD), nosocomial infection remains a significant problem, accounting for approximately 33% of the RSV cases. Some authors report significant reductions in hospital-acquired RSV by use of gloves and gowns for contacts with infectious cases. Efforts at primary prevention have encountered problems with development of an RSV vaccine. Preliminary data from studies of passive immunization using immune globulins with high RSV antibody titers suggest that this therapy may reduce the severity of RSV infection in infants with serious heart disease.

Antiviral Agents↗
PubMed2002

Immunological mechanisms of severe respiratory syncytial virus bronchiolitis.

Respiratory syncytial virus (RSV) bronchiolitis resulting in respiratory insufficiency is frequently encountered during the winter season in paediatric intensive care units. This review evaluates potential determinants described in severe RSV bronchiolitis with special attention to the role of immaturity of immune responses during infancy. Pre-existent cardiac or pulmonary compromises have been documented as clinical risk factors for severe RSV bronchiolitis. In addition to this group of infants with pre-morbidity, a large proportion of mechanically ventilated RSV bronchiolitis patients are previously healthy full-term infants or premature neonates without predisposing risk factors. In general, infants at this early age have maturation-related deficient cellular immunity. Several studies show an association between decreased cellular immunity and severe RSV bronchiolitis, indeed suggesting that a maturation-related defect of the cellular immune system facilitates severe RSV. In addition, low virus-specific antibody titres prior to RSV bronchiolitis have been shown to be a risk factor for severe RSV bronchiolitis. A low level of cellular and humoral immunity would explain that higher viral titres are found in infants with most severe illness. In conclusion, immaturity of the physiological functions in healthy pre-term infants and neonates, in particular the immune system, appears to be an important factor in the pathogenesis of RSV bronchiolitis resulting in mechanical ventilation.

Bronchiolitis, Viral↗
PubMed1998

Severe respiratory syncytial virus pulmonary infection in a patient treated with fludarabine for chronic lymphocytic leukemia.

Fludarabine phosphate is currently proposed for the treatment of refractory chronic lymphocytic leukemia (CLL). CD4 T-lymphocyte depletion, myelosuppression, and subsequent severe infections are the major side effects of fludarabine phosphate therapy. We report here on a heretofore undescribed respiratory syncytial virus (RSV) infection in a patient with a long-standing history of refractory CLL that was treated with fludarabine phosphate. The patient developed a severe infection of the upper and lower respiratory tract with bilateral pulmonary infiltrates and severe hypoxemia. RSV was the only infectious agent that could be isolated, and treatment with aerosolized ribavirin lead to prompt improvement of all symptoms.

Administration, Inhalation↗
PubMed2000

Respiratory syncytial virus-induced chronic bronchiolitis in experimentally infected calves.

Human (RSV) and bovine (BRSV) respiratory syncytial virus cause similar infections of the lower respiratory tract. Therefore, experimentally infected calves are suited to the study of RSV-induced chronic bronchiolitis. Colostrum-fed calves aged 17-24 days were successfully infected with BRSV. BRSV strain 375 was applied as an aerosol on 4 consecutive days. Clinical symptoms were already evident on the 1st day after infection. The calves were necropsied 12 weeks after the first infection. Focal severe chronic bronchiolitis with atelectasis and focal bronchiolitis obliterans were demonstrated. The bronchiolar lumina were filled with secretion. Transmission electron microscopy revealed an alteration of the ciliogenesis and partial loss of cilia. Immunhistochemically virus P protein could still be detected, mainly in the epithelial cells of the inflamed bronchioli.

Animals↗
PubMed2005

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

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

Child↗
PubMed2000

Treatment and prevention of respiratory syncytial virus infection.

UNLABELLED: This review discusses the current knowledge on treatment and prevention of respiratory syncytial virus (RSV) infections in children. Unfortunately, an effective therapy is not yet available. The efficacy of corticosteroids and bronchodilators has not yet been adequately documented and the use of ribavirin is only indicated in a highly selected group of high risk patients with T-cell immunodeficiency. The results of studies on the efficacy of vitamin A, interferon and antibiotics showed disappointing results. Vaccination research has produced candidate vaccines such as the recombinant vaccine BBG2Na, a subunit vaccine PFP-2 and cold-passaged-temperature sensitive vaccines. However, phase III efficacy trials in infants, young children and the elderly are still lacking. Passive protection against infections by RSV can be conferred by the use of RSV hyperimmune globulin or by the administration of palivizumab, a monoclonal antibody. However, large costs are involved. In addition, major differences have been reported in the prevalence of RSV lower respiratory tract infections in different countries, regions and even within well-known high-risk populations. CONCLUSION: We suggest the development of local and regional guidelines based on hospitalisation rates in high-risk infants and cost-benefit analysis studies.

Adrenal Cortex Hormones↗
PubMed2004

Genotypes of respiratory syncytial virus group B identified in Uruguay.

Genotypes of Human respiratory syncytial virus (HRSV) of group B from Uruguay were assigned to strains isolated during 1999 and 2001 outbreaks and others formerly reported isolated in the period 1989-1996. The nucleotide sequences of the C-terminal portion of the G protein were compared to sequences representative of previously defined HRSV genotypes. Most Uruguayan strains clustered into five of the previously identified genotypes. Nine isolates clustered in two genotypes named URU1 and URU2 which were not described up to present. Two of the analyzed sequences isolated in 2001 have a six nucleotide duplication that is discussed in terms of HRSV variability.

Disease Outbreaks↗
PubMed1997

Heparin-dependent attachment of respiratory syncytial virus (RSV) to host cells.

In this study we could demonstrate that heparin (ED50 = 0.32 +/- 0.12 microgram/ml), but not heparan sulphate or chondroitin sulphate C is able to inhibit in vitro infection of cells by respiratory syncytial virus (RSV). In addition, this protective effect of heparin could only be observed, when heparin was present at the time of inoculation. Enzymatic digestion of cell surface glycosaminoglycans with heparinase and heparitinase, but not chondroitin sulphate ABC lyase reduced the effectiveness of RSV-infection. Affinity chromatography experiments, using immobilised heparin further demonstrated that RSV attachment protein G was able to bind specifically to heparin. Therefore heparin-like proteoglycans showed properties required for attachment of RSV to host cells.

Animals↗
PubMed1997

Antibody responses against epitopes on the F protein of bovine respiratory syncytial virus differ in infected or vaccinated cattle.

The fusion protein F of bovine respiratory syncytial virus (BRSV) is an important target for humoral and cellular immune responses, and antibodies against the F protein have been associated with protection. However, the F protein can induce antibodies with different biological activity, possibly related to distinct antigenic regions on the protein. Therefore, epitopes were mapped on the F protein using monoclonal antibodies. Two epitopes (A and B) were identified that induced neutralizing antibodies, and one epitope (C) that did not elicit neutralizing antibodies. Subsequently, antibody responses were analysed against these epitopes in cattle sera after natural infection, experimental infection or vaccination. After natural infection or reinfection, the antibody titres against epitope A were significantly higher than those against epitope B or C. After experimental infection and after vaccination with an inactivated vaccine, antibody titres against epitope B and C were significantly higher than after natural infection. Conversely, virus neutralizing antibody titres were significantly lower in these animals with higher antibody titres against epitopes B and C than in naturally infected cattle. Because after natural infection the epitope-specific-antibody titres against epitope A, B or C differed markedly between the cattle, the magnitude of the antibody titres against epitope A, B or C in relation to the major histocompatibility complex (MHC) genes of cattle (BoLA) was studied. The magnitude of the antibody responses against epitope A of the F protein, but not against the G protein, appeared to be associated with the bovine lymphocyte antigen (BoLA) haplotype.

Animals↗
PubMed1998

Immune response of calves experimentally infected with non-cell-culture-passaged bovine respiratory syncytial virus.

The immune response of calves was studied following infection with non-cell-passaged Bovine respiratory syncytial virus (BRSV). Two groups of 6 specific pathogen free (SPF) calves were housed in separate isolation rooms. One group was inoculated intranasally with a non-cell-passaged BRSV strain and the control group was mock-infected. A BRSV specific antibody response was observed for all the BRSV infected calves. These antibodies were shown to have neutralizing activity. No lymphocyte proliferation response was detected in the mock-infected group whereas three animals in the infected group were positive three weeks after the infection. All BRSV-infected calves, except one, produced interferon-gamma (IFN-gamma) one week post-infection and IFN-gamma was observed in all six infected calves after three weeks. The control group showed no IFN-gamma synthesis. In spite of the limits of the BRSV infection model, humoral and cellular immune responses were actively developed by all the calves against this pathogen.

Animals↗
PubMedDate not supplied

Enzyme-linked immunoassay for respiratory syncytial virus is not predictive of bronchiolitis in sudden infant death syndrome.

Although respiratory syncytial virus (RSV)-infected infants may present with apnea, the role that RSV plays in sudden infant death syndrome (SIDS) is speculative. To determine whether RSV is associated with bronchiolitis in these patients, we examined histologic sections of lungs from 41 apparent SIDS cases and compared the results with those of enzyme-linked immunofluorescent assay (EIA) from nasal washings. Bronchiolitis was defined by a bronchiolar inflammatory cell infiltrate plus epithelial necrosis. A positive EIA was associated with bronchiolitis in 8 instances, compared with 6 having a positive EIA and negative histology, 14 having a negative EIA and positive histology, and 13 having EIA and histology both negative. These results yield a predictive value of a positive test of 57% and a predictive value of a negative test of 48% (P > .9 by chi square analysis). Although RSV of the upper respiratory tract may be related to SIDS, our results indicate that EIA of nasal washings is not predictive of bronchiolitis, and we recommend other means of verification of histologic results.

Antibodies, Viral↗
PubMedDate not supplied

Respiratory syncytial virus infects the Bonnet monkey, Macaca radiata.

The Bonnet monkey model of respiratory syncytial virus (RSV) infection may be a useful nonhuman primate model for studying RSV disease in humans because Bonnet monkeys can predictably be infected to obtain an orderly sequence of morphologic, cytologic, virologic, serologic, and inflammatory changes related to time of infection. Young feral Bonnet monkeys, Macaca radiata, were infected endotracheally with 10(6) plaque-forming units (pfu) of the Long strain of RSV. RSV was recovered from the animals' lungs at necropsy on days 3, 5, and 7 with the highest viral titer obtained on day 3 (1.1 and 5.2 x 10(3) pfu/g of tissue in the upper and lower lobes, respectively). RSV antigen and F protein mRNA were detected 3-5 days after infection in alveolar macrophages and in the epithelium of bronchi, terminal bronchioles, and alveoli. Histologic analysis of RSV-infected lungs at necropsy revealed progressive bronchiolar mucosal and submucosal inflammation, periarterial mononuclear interstitial inflammation, and focal alveolitis, with a maximal response at 7 days after infection. Cell counts in bronchoalveolar lavage (BAL) increased with time with neutrophils and macrophages predominating on day 3 (6.47 and 5.85 x 10(5)/mm3, respectively) and lymphocytes predominating on day 9 (4.18 x 10(5)/mm3). Serum-neutralizing antibody appeared on day 5 and IgG antibody to RSV was detected on day 9. This sequence of morphologic, cytologic, virologic, serologic, and inflammatory change following RSV infection creates a useful model in the study of experimentally induced RSV disease with a potential for testing future vaccine-induced alterations in RSV disease response.

Animals↗
PubMed2003

Bronchiolitis caused by respiratory syncytial virus in an area of portugal: epidemiology, clinical features, and risk factors.

The aim of the present study was to analyse the clinical and epidemiological characteristics of bronchiolitis caused by respiratory syncytial virus (RSV) in 225 children observed in a paediatric hospital in Lisbon, Portugal, and to determine the clinical, epidemiological, or laboratory parameters that correlate with greater severity of the disease. This prospective study included hospitalised and ambulatory children younger than 36 months of age with a diagnosis of bronchiolitis and was conducted during two consecutive RSV epidemiological seasons (November-March 2000/01 and 2001/02). The median age of the patients was 5 months, and the male-to-female ratio was 1.6:1. RSV was isolated in 60.9% of patients, predominantly in the hospitalised group. The subtype A:B ratio was 7.4:1 and was similar in both seasons. RSV-positive patients were younger, had more severe clinical forms of bronchiolitis, and fewer changes in leucocyte total and differential counts. Among infected patients, higher clinical severity scores occurred in association with first wheezing episodes, overcrowded households, attendance at day-care centres, or prematurity (<36 weeks). This first prospective study of RSV epidemiology in Portugal provides a foundation for appropriate surveillance programmes of RSV infection in this country. A multicentre study is desirable in order to delineate optimal prophylactic and therapeutic guidelines for RSV infection in Portugal.

Age Distribution↗
PubMed2001

Incidence of respiratory syncytial virus-positive hospitalizations in Germany.

Epidemiological data, especially population-based data, on respiratory syncytial virus (RSV)-related hospitalizations in Germany have been lacking to date. Since Palivizumab (Synagis, Abbott, USA) is already available and new vaccines for active immunization are under development, these data are urgently needed. From July 1996 to June 1999, nasopharyngeal aspirates of children hospitalized in Kiel with an acute respiratory tract infection were tested by multiplex reverse transcriptase polymerase chain reaction. Of 1,241 patients, 150 (12.1%) were RSV positive. RSV was the predominant pathogen detected through the end of the second year. In 37 (25%) children an underlying condition was present. For the city of Kiel and close surroundings, the cumulative incidence of RSV-positive hospitalizations in infants was 1,214/10(5) (725/10(5) in children less than 2 years). For those children less than 2 years old born with a gestational age of less than 32 weeks or 32-37 weeks, the cumulative incidence was 2,025/10(5) and 1,202/10(5), respectively (dose-effect response). For the group less than 32 weeks of age, bronchopulmonary dysplasia (BPD) as an underlying condition carried a relative risk of 17.8. The RSV season began between the end of September and January and ended between March and July. The population-based incidence of RSV-positive hospitalizations in Kiel is close to that reported from the UK and Scandinavia. Throughout Germany, approximately 10.000 RSV-related hospitalizations in infants can be expected annually. Prematurity is an effect modifier and BPD a strong risk factor for RSV-positive hospitalization in population-based studies. There is considerable variation in the start and end of the yearly epidemic.

Acute Disease↗