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PubMed1999

A colorimetric microtiter plate PCR system detects respiratory syncytial virus in nasal aspirates and discriminates subtypes A and B.

We developed a colorimetric microtiter plate (MTP) PCR system for specific detection of the respiratory syncytial virus (RSV) nucleocapsid gene and differentiation of viral subtypes A and B. Of 47 pediatric nasal aspirate specimens, the sensitivity and specificity were 94.4% (17 of 18) and 100% (15 of 15), respectively, when compared with RSV cell culture isolation in HEp-2 cells. An additional 14 specimens positive for adenoviruses, rhinoviruses, influenza, or parainfluenza viruses did not give positive reactions. PCR testing detected a mean of 0.15 (0.01 to 7.00) plaque-forming units of RSV virions. Inhibition of PCR amplification was detected in 33.3% (6/18) of undiluted specimens and could be avoided by a dilution (1:10) of extracted RNA without decreasing test sensitivity. RSV subtype, as determined by allele-specific probes, was identical to that determined by an immunofluorescence assay. These results indicate that the MTP PCR system provides a sensitive and specific test for clinical laboratory diagnosis and simultaneous subgroup classification of RSV infection.

Cell Culture Techniques↗
PubMed1998

Acute lower respiratory infections due to respiratory syncytial virus and adenovirus among hospitalized children from Argentina.

BACKGROUND: Acute lower respiratory infection (ALRI) is one of the main causes of morbidity and mortality in small children. OBJECTIVE: The aim of this study was to determine the frequency, seasonality and association with clinical entities of respiratory syncytial virus (RSV) and adenoviruses in children with ALRI. STUDY DESIGN: During 2 consecutive years (1991-1992), 168 children under 2 years of age hospitalized due to ALRI in a public pediatric hospital of Buenos Aires, Argentina, were studied. RSV and adenoviruses were investigated on nasopharyngeal aspirates (NPA) by indirect immunofluorescence (IIF). HEp-2 cells were used for adenovirus isolation. RESULTS: RSV was detected in 36.3% and adenoviruses in 14.3% of the cases (P < 0.0001). All adenoviruses detected by IIF were also isolated in culture. Out of 61 RSV cases, 57% corresponded to bronchiolitis and 43% to pneumonia. Ninety-two per cent of children with RSV were less than 1 year old and 70% were less than 5 months. The highest number of RSV cases were observed during winter, with a clear peak in July. Seventy-one per cent of adenovirus cases were associated with pneumonia and only 24% with bronchiolitis (P < 0.02), and predominated in children older than 5 months of age (P < 0.0001). Adenoviruses were detected in almost all months of the year with a small peak at the end of winter and beginning of spring. No significant differences in clinical features at admission, breast feeding or malnutrition were observed among children with RSV or adenovirus diagnosis versus those with no viral etiology. The overall fatality rate was 2.4%. In all fatal cases adenovirus was detected in NPA. Thus, fatality rate among patients with adenoviruses reached 16.7%. CONCLUSIONS: Our findings show the importance of RSV and adenoviruses associated with ALRI in hospitalized children under 2 years of age and the different epidemiological patterns of the two viruses in Buenos Aires, Argentina.

Acute Disease↗
PubMed1998

-Prevention of respiratory syncytial virus infection-.

Respiratory syncytial virus (RSV) is responsible for annual outbreaks of severe respiratory disease among infants. Its prevention has been considered for many years but the first vaccination trials resulted in diseases of increased severity. New vaccines are in progress with promising results, although their efficacy in the presence of maternal antibodies, and their tolerance in very young babies, remain to be demonstrated. Concerning passive immunization, intravenous anti-RSV immunoglobulins have been successfully tested in children at risk of severe bronchiolitis; however this prophylaxis is not applicable to healthy children. The use of local immunization with intranasal monoclonal antibodies is under study. While waiting for a safe and efficient immunization against RSV, prevention of nosocomial infections by cohorting and handwashing is recommended.

Administration, Intranasal↗
PubMed1999

[Coincidental outbreaks of rotavirus and respiratory syncytial virus in Paris: a survey from 1993 to 1998].

PATIENTS AND METHODS: In a pediatric hospital of Paris, from 1993 to 1998, respiratory secretions were positive for respiratory syncytial virus (RSV) in 26.3% of 4,738 children (0-5 years) examined or hospitalized for lower respiratory tract infections. Rotavirus detection was positive in stools of 23.7% of the 8,537 children of the same age with acute diarrhea. RESULTS: The RSV epidemic peak occurred annually in Paris in December and the rotavirus outbreak peaks were observed in December/January. The winter seasonal peaks remained constant for both pathogens and the temporal appearance of these peaks was constant from 1993 to 1998. Fifty to sixty-one percent of rotavirus and 77 to 92% of RSV infections were observed in November, December or January. These simultaneous outbreaks provoked important problems in hospital organization and prevention of nosocomial infections. CONCLUSION: The coincidence of RSV and rotavirus peaks is not found in all countries. The epidemic patterns have to be checked in other parts of France and Europe because this could be important when active immunization programs will be available for these two pathogens.

Child, Preschool↗
PubMed2002

Respiratory syncytial virus prophylaxis--the story so far.

Respiratory syncytial virus (RSV) is a common and highly contagious pathogen that infects nearly all children by the age of 2 years. It is responsible for significant morbidity and mortality worldwide among certain high-risk paediatric populations. Therapy is sub-optimal for RSV, thus treatment focuses on ameliorating symptoms. Since discovery of the virus in the 1950s, efforts have been ongoing to develop a safe and effective vaccine. These efforts have met with serious obstacles. Passive immunoprophylaxis presents a viable alternative to active immunization. In 1998, the genetically engineered humanized monoclonal antibody (palivizumab) was granted FDA (Food and Drug Administration) approval for prophylaxis of high-risk children in the United States; EMEA (European Agency for the Evaluation of Medicinal Products) approval followed in 1999 for Europe. It is now approved in over 45 countries worldwide. Palivizumab was shown to significantly reduce RSV-related hospitalizations in North America and Europe with few adverse effects. Clinical trial and outcomes data documenting experience with palivizumab to date continue to extend the initial safety and efficacy observations.

Antibodies, Monoclonal↗
PubMed2001

The discovery of RFI-641 as a potent and selective inhibitor of the respiratory syncytial virus.

The design and synthesis of a new potent and selective inhibitor of the respiratory syncytial virus are described. This compound, RFI-641, emerged from analysis of the structure-activity relationship in a series of biphenyl triazine anionic compounds possessing specific anti-RSV activity. The key synthetic step involves coupling of diaminobiphenyl 11 with two equivalents of chlorotriazine 10 under microwave conditions. RFI-641 inhibited RSV in vitro and in vivo models.

Animals↗
PubMed2005

Relationship between atopic status and nasal interleukin 10 and 11 levels in infants with respiratory syncytial virus bronchiolitis.

BACKGROUND: Interleukin 10 (IL-10) and IL-11 are known to have anti-inflammatory activities, and they have been implicated in the pathogenesis of respiratory syncytial virus (RSV) infection. OBJECTIVES: To determine IL-10, IL-11, and myeloperoxidase levels in nasal secretions of infants with acute RSV bronchiolitis and to investigate whether there are any differences in these levels in patients with vs without atopy. METHODS: We measured IL-10, IL-11, and myeloperoxidase levels in nasal secretions of 44 infants (20 were atopic) with acute RSV bronchiolitis. The nasal secretion samples were obtained from patients at hospital admission and were stored immediately at -70 degrees C until analysis. Atopy was defined as having at least 1 positive skin prick test reaction to common allergens, a history of atopic dermatitis, or a high serum IgE level compared with age-matched controls. RESULTS: Levels of IL-10, IL-11, and myeloperoxidase increased significantly in samples from infants with acute RSV bronchiolitis. Levels of IL-10 and IL-11 were significantly lower in patients with vs without atopy (P < .05). Myeloperoxidase levels showed no significant difference in patients with vs without atopy (P = .18). Patients with severe symptoms tended to have lower IL-10 levels (P = .09), but no relationship was shown between symptom severity and IL-11 levels. Nasal myeloperoxidase levels were significantly higher in patients with severe symptoms (P < .05). CONCLUSIONS: Production of IL-10 and IL-11 was significantly lower in patients with vs without atopy during acute RSV bronchiolitis. The airway inflammation induced by RSV infection may be different in patients with vs without atopy, and this is associated with lower induction of these immunoregulatory cytokines in children with atopy.

Bodily Secretions↗
PubMed2004

Soluble CD14 as a predictor of subsequent development of recurrent wheezing in hospitalized young children with respiratory syncytial virus-induced bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) infection in infancy that causes severe bronchiolitis had been implicated as potentially responsible for the subsequent development of asthma. The CD14 receptor responds to the microbial burden in the environment and modulates the development of the allergic phenotype. OBJECTIVE: To investigate the relationship between the serum level of soluble CD14 (sCD14) in children hospitalized because of RSV-induced bronchiolitis and the subsequent development of recurrent wheezing. METHODS: Serum levels of sCD14 were measured in 21 children younger than 14 months who were hospitalized because of RSV-induced bronchiolitis. The diagnosis of significant wheezing was evaluated by recurrent episodes of coughing, wheezing, and respiratory distress, which were relieved by inhalation of beta-agonists and corticosteroids. RESULTS: Of the 21 children, 19 were followed up for 12 months. The mean sCD14 serum level of 14,521 +/- 1,773 pg/mL in the group of 6 children who did not exhibit recurrent wheezing was significantly higher than the level of 11,243 +/- 3,264 pg/mL in the group of 13 children who exhibited significant recurrent wheezing (P < .05). The subsequent development of recurrent wheezing was not influenced by positive family history of asthma, number of siblings, sex, or breast-feeding. CONCLUSION: A follow-up period of 12 months in this small pilot group showed that high serum levels of sCD14 modulate the influence of RSV on subsequent recurrent episodes of wheezing.

Bronchiolitis, Viral↗
PubMed2003

Isolation and characterisation of potential respiratory syncytial virus receptor(s) on epithelial cells.

Respiratory syncytial virus (RSV) infection causes severe lower respiratory diseases in infancy, early childhood and the elderly. RSV infections respond poorly to current therapies. Therefore, we initiated a search for novel drug targets by investigating the characteristics and identity of RSV adhesion receptors on mammalian cells. Soluble human lectins, complex polysaccharides and a low molecular selectin antagonist, TBC1269, were used to characterise and isolate the RSV receptor on a human epithelial cell line (Hep2 cells). The binding characteristics of the RSV receptor on Hep2 cells were similar to those reported for L-selectin. The carbohydrate-based selectin antagonists, fucoidan and TBC 1269, inhibit RSV infection both in vitro and in a mouse model of infection. Furthermore, we have isolated annexin II as a potential RSV receptor on Hep2 cells. The expression of annexin II was increased after RSV infection. Recombinant annexin II binds to RSV G-protein, heparin and plasminogen and the binding is inhibited by a selectin antagonist, TBC1269. These findings indicate that inhibitors of annexin II could have potential in treating RSV infection.

Animals↗
PubMed1999

Recent developments in the biology of respiratory syncytial virus: are vaccines and new treatments just round the corner?

Respiratory syncytial virus (RSV) is the major cause of infantile bronchiolitis, and is an important pathogen in the elderly and in the developing world. The production of full length cDNA clones now allows precise genetic engineering of RSV, while knowledge of the immunopathogenesis of augmented disease gives hope that effective vaccines will soon be developed.

Animals↗
PubMed2003

Respiratory syncytial virus associated illness in high-risk children and national characterisation of the circulating virus genotype in South Africa.

BACKGROUND: There is limited information about respiratory syncytial virus (RSV) in high-risk children from developing countries or on the genotype characterisation of the circulating virus. OBJECTIVE: To define the proportion of children with RSV associated lower respiratory tract infections (LRTI) that had risk factors for severe disease and to genotype the circulating RSV strains across the country. STUDY DESIGN: A prospective study was performed in four distinct regions. During April 2000-December 2000 (period 1), all children, with LRTI or without underlying high risk factors for severe RSV disease were enrolled. During January to September 2001 (period 2), only children with LRTI with underlying high risk factors were enrolled. Nasopharyngeal aspirates were evaluated for RSV infection using an ELISA test. RSV isolates were also subtyped and genotyped. RESULTS: Fifty three (24%) of 220 children enrolled during period 1 had risk factors for severe RSV disease; in addition to which a further 38 high-risk children were enrolled during 2001. RSV was isolated from 16 (30%) of 53 and 37 (22%) of 167 high-risk and non-high risk children, respectively, P=0.31. High-risk children were more likely to require intensive unit care (25 vs. 2.7%, P=0.02) and were also more likely to be hospitalised for a longer duration (median 7 vs. 5 days, P=0.06) than non high-risk infants. Overall (periods 1 and 2), RSV was isolated from 34 (37.4%) of the 91 high-risk infants enrolled. Among high-risk children, those from whom RSV was isolated were more likely to require hospitalisation (73.5 vs. 54.4%, P=0.07) and admission to an intensive care unit (14.7 vs. 1.8%, P=0.03) than those from whom RSV was not isolated. Of 40 isolates subtyped during period one, 92.5% were subtype A. Further, 27 (83.3%) of 30 subtype A isolates genotyped during period 1 clustered with GA2. CONCLUSION: RSV is an important cause of LRTI among high-risk infants in a developing country such as South Africa. For the season in question, the genotype that was dominant in Johannesburg was isolated throughout the country, suggesting that successful genotypes may have the ability to spread nationwide.

Disease Outbreaks↗
PubMed2003

Lack of sensitivity of rapid antigen tests for the diagnosis of respiratory syncytial virus infection in adults.

The diagnosis of respiratory syncytial virus (RSV) infection in older individuals and adults with cardiopulmonary diseases using available rapid antigen detection tests may be difficult due to the low virus shedding in this population. These tests have been extensively evaluated in hospitalized infants, but there is only limited data on their usefulness in adult populations. We evaluated the performance of three different rapid antigen detection tests: Becton Dickinson Directigen RSV (BD), Bartels RSV Direct Fluorescent Antibody Test (DFA) and the VIDAS RSV assay (VIDAS) in nasopharyngeal specimens from 60 older persons with RSV infection documented by cell culture, serology or reverse transcription polymerase chain reaction (RT-PCR). The three rapid antigen assays tested on all 60 samples performed poorly. DFA detected 14 (23%), VIDAS detected 12 (20%) and BD detected only 6 (10%) of the RSV infected persons. Rapid antigen detection tests for the diagnosis of RSV respiratory illness in adults are of limited value.

Adult↗
PubMed2003

Respiratory syncytial virus in healthy adults: the cost of a cold.

Respiratory syncytial virus (RSV) is well recognized as a major pathogen of lower respiratory tract infection and hospitalization in young infants. More recently the pathogenicity of RSV has been demonstrated in elderly adults, institutionalized individuals, and those with compromised immune function. In these populations RSV spreads with ease and frequently results in severe or fatal cardiopulmonary complications. In younger, healthy adults, however, the manifestations and importance of RSV infection have been studied little, and RSV is generally not considered as a cause of respiratory illness in this healthy, working population. RSV occurs in yearly outbreaks and is highly contagious. Immunity after infection is neither complete nor durable. Repeated infections, therefore, occur throughout life. In most cases these recurrent infections involve the upper respiratory tract and thus do not receive a specific diagnosis. However, recent studies indicate that in the younger, healthy adult these respiratory illnesses tend to be more severe than the average 'cold' and may have manifestations similar to influenza. An appreciable proportion results in work absence. Thus, the emerging information suggests that RSV infection clearly occurs frequently in healthy adults in contact with children, but is generally not diagnosed. The potential burden on the healthcare system is unestimated, possibly unappreciated, and should be considered in strategies being developed for preventing RSV infection.

Adolescent↗
PubMed1998

Development of human antibodies against linear antigenic and immunogenic regions of respiratory syncytial virus (RSV) nucleocapsid and phospho-proteins shows the site-directed characteristics.

BACKGROUND: The successful development of an RSV vaccine requires a better understanding of the pathogenesis of primary infection, susceptibility to reinfection, and the immunopathology of enhanced illness in children immunized with a non-replicating RSV candidate vaccine. The exact role of different immune parameters in RSV pathogenesis remains controversial. OBJECTIVES: To study the contribution of antibodies directed to the linear antigenic and immunogenic regions of the N and P proteins in the titer rise and avidity maturation of total anti-RSV antibodies. STUDY DESIGN: The occurrence of antibodies directed against three linear antigenic and immunogenic regions in each of the nucleocapsid (N): N3 (Thr11 to Gly30), N25 (Ser231 to Ala250) and N39 (Thr371 to Leu391), and the phospho-(P) proteins of respiratory syncytial virus (RSV), subgroup A: P49 (Pro91 to Asp110), P56 (Ser161 to Lys180) and P62 (Glu221 to Phe241), were analyzed in ELISA with (a) 32 paired sera from humans with recent or previous RSV subgroup A and/or B infection diagnosed by conventional ELISA, detection of antigen in nasopharyngeal aspirates and measurement of antibody avidity change; and (b) 40 RSV antibody-positive sera (HCS) obtained from patients during their convalescence from RSV infection and possessing clearly demonstrable titers of RSV IgG in conventional enzyme immunoassays (EIA) based on whole RSV antigen. RESULTS: The titer rise of antibodies directed to the combined three peptides representing the RSV N protein was well correlated with the rise in anti-RSV antibodies measured in whole antigen ELISA. Surprisingly, the rise in antibodies against a truncated main C-terminal epitope (Gln381 to Leu391) of the N protein (represented by subgroup A specific sequence of the N39/1 peptide) was inversely correlated with the titer rise of total anti-RSV antibodies. The titer rise of antibodies to the C-terminal linear site of the RSV N (N39/1) protein was subgroup-specific during the course of primary RSV infection. A titer rise in antibodies to the C-terminal linear sites of RSV N (i.e. N39/1) and P (P62) proteins had a dominating appearance in sera from newborn infants (6-7 months) and from patients with RSV reinfections. Anti-RSV antibody titers of late convalescent sera correlated with the titers of antibodies directed to the C-terminal linear site of RSV P (P62) protein. The avidity maturation of the anti-RSV immune response followed the titer rise of anti-P62 antibodies during the course of primary or secondary RSV infection.

Antibodies, Monoclonal↗
PubMed1999

Comparison of VIDAS with direct immunofluorescence for the detection of respiratory syncytial virus in clinical specimens.

BACKGROUND: requirements for infection control measures and the decision for treatment with antiviral agents make the rapid detection of respiratory syncytial virus (RSV) essential for hospitalized, pediatric and immunocompromised patients. Immunofluorescence is considered to be the most rapid and sensitive method for direct detection of RSV in clinical specimens, but several enzyme-linked immunoassays have also been commercially available. OBJECTIVES: to compare the performance of VIDAS RSV assay (Vitek ImmunoDiagnostic Assay System, BioMerieux Vitek), which is an automated enzyme-linked fluorescent immunoassay (ELFA) to direct immunofluorescence (DFA), in rapid detection of RSV in respiratory specimens. STUDY DESIGN: respiratory specimens collected during the 'RSV season', between the months of November 1997 and February 1998, were tested by both methods. DFA was performed upon receipt of the sample and an aliquot of the original specimen was stored in -70 degrees C for batch testing with VIDAS. RESULTS: from 238 samples that were tested, 231 could be evaluated by both methods. The two assays were in agreement for 213 specimens (92%), or 32 positive and 181 negative results. Eighteen discrepant results were generated; seven specimens were VIDAS-/DFA+ and 11 specimens were VIDAS+/DFA-. In addition, seven specimens had an inadequate number of cells for evaluation with DFA. One of these samples tested positive with VIDAS. VIDAS relative sensitivity and specificity were 82% and 94%, respectively, when compared to DFA. CONCLUSIONS: VIDAS is simple to perform, does not require expertise in interpretation and appears to be an acceptable method for the rapid detection of RSV.

Enzyme-Linked Immunosorbent Assay↗
PubMed2024

Genotypic and phenotypic characterisation of respiratory syncytial virus after nirsevimab breakthrough infections: a large, multicentre, observational, real-world study.

BACKGROUND: Nirsevimab, a long-acting monoclonal antibody, has been approved for the prevention of respiratory syncytial virus (RSV) infection in infants. In France, more than 210&#x2009;000 single doses were administered in infants younger than 1 year during the 2023-24 season. In this context, the selection and spread of escape variants might be a concern. Here, we aimed to characterise RSV associated with breakthrough infection. METHODS: We did a multicentre, national, observational study in France during the 2023-24 RSV season in RSV-infected infants (aged <1 year) who either received or did not receive a dose of nirsevimab before their first RSV season. We excluded infants with insufficient information about nirsevimab treatment or without parental consent. We used respiratory samples collected in each laboratory for full-length RSV RNA sequencing to analyse changes in the nirsevimab binding site &#xd8;. We tested clinical RSV isolates for neutralisation by nirsevimab. We analysed F candidate substitutions by fusion-inhibition assay. FINDINGS: Of the 695 RSV infected infants, we analysed 545 (78%) full-length RSV genome sequences: 260 (48%) from nirsevimab-treated breakthrough infections (236 [91%] RSV-A and 24 [9%] RSV-B) and 285 (52%) from untreated RSV-infected infants (236 [83%] RSV-A and 49 [17%] RSV-B). Analysis of RSV-A did not reveal any substitution in site &#xd8; known to be associated with resistance to nirsevimab. Two (8%) of 24 RSV-B breakthrough infections had resistance-associated substitutions: F:N208D (dominant resistance-associated substitution) and a newly described F:I64M plus F:K65R combination (minority resistance-associated substitution), both of which induced high levels of resistance in the fusion-inhibition assay. INTERPRETATION: This study is, to the best of our knowledge, the largest genotypic and phenotypic surveillance study of nirsevimab breakthrough infections to date. Nirsevimab breakthrough variants remain very rare despite the drug's widespread use. The detection of resistance-associated substitutions in the RSV-B F protein highlights the importance of active molecular surveillance. FUNDING: ANRS Maladies Infectieuses Emergentes and the French Ministry of Health and Prevention.

Humans↗
PubMed2003

Current strategies in the prevention of respiratory syncytial virus disease.

Infants infected with respiratory syncytial virus (RSV) develop both upper and lower respiratory tract infections resulting in laryngotracheobronchitis, bronchiolitis and pneumonia. Premature infants of less than 32 weeks' gestation and those with underlying chronic lung disease are particularly susceptible and incur significant morbidity and mortality following hospitalisation. Conservative RSV prevention strategies focus on the interruption of transmission by proper hand-washing techniques and reducing exposure to potential environmental risk factors. Major challenges have impeded the development of an RSV vaccine but a licensed product may be expected in the near future. Prophylaxis with a humanised mouse monoclonal antibody (palivizumab) has been effective in reducing the rate of RSV hospitalisation in high-risk premature infants in phase II-IV trials and is available for use within internationally approved guidelines. Experimental studies evaluating the use of palivizumab in patients with congenital heart disease, those with cystic fibrosis and immunosuppressed bone marrow transplant recipients are well underway, the results of which are eagerly awaited.

Antibodies, Monoclonal↗
PubMed2004

Respiratory syncytial virus: the virus, the disease and the immune response.

RSV is the primary cause of hospitalisation in the first year of life for children in most parts of the world, and nearly 100% of children in the USA are infected with the virus by 2 to 3 years of age. The agent is an enveloped RNA virus with a non-segmented single-stranded negative-sense genome. The viral genome encodes 8 structural and 2 non-structural proteins. Important structural proteins include the fusion (F) protein and the attachment (G) protein which are essential for viral penetration and attachment to the host cells. Both proteins are important in development of immune responses. The virus is estimated to cause 3000 to 4000 deaths annually. Primary infections are as a rule symptomatic. The spectrum of clinical manifestations ranges from mild upper tract illness, infection in middle ear which progresses to acute otitis media, croup, to apnoea in premature infants, pneumonia and bronchiolitis. Premature babies born at 30-35 weeks of gestation, infants with cyanotic congenital heart disease, HIV-infected subjects, and patients on intensive immunosuppressive therapy especially after bone marrow transplant are considered to be at risk for increased mortality and morbidity during RSV infection. The virus does not normally replicate outside of the bronchopulmonary tree and the infection is exquisitely restricted to the respiratory mucosa. However, development of extrapulmonary disease has been observed in certain T and B cell immunodeficiency states. The association of RSV with asthma and reversible reactive airway disease in early childhood has attracted significant attention. Recurrent wheezing for up to 5 to 7 years of age and established airway disease has been observed in a significant number of children with a strong family history of allergy, after primary infection or reinfection with RSV. Immune response to primary infection is relatively small but on reinfection, a significant booster effect with sustained immunologic reactivity is observed in serum and respiratory mucosa. Both CD(4)- and CD(8)-specific as well as Th(1)- and Th(2)-cell specific immune responses have been observed during human infection. In addition, proinflammatory as well as immunoregulatory cytokines and chemokines are induced in the respiratory tract after natural and induced (in vitro) infection. Significant progress has been made in understanding the role of Th(1) vs. Th(2), IgE, viral induced cytokines and chemokines in the mechanisms of pathogenesis of the disease, development of wheezing and in the prevention and treatment of the infection and its sequelae. Respiratory syncytial virus (RSV) is one of the commonest human viral infections, and virtually every child is infected by the third birthday. Because of its restricted mucosal immunopathology, and frequent association with bronchial hyperreactivity and development of wheezing, RSV has served as an important model to investigate mechanisms of mucosal immune responses and development of mucosal disease following infection. The importance of RSV in bronchopulmonary disease and development of bronchial hyperreactivity has been the focus of several recent symposia [Kimpen JL, Simoes EAF. Am J Respir Crit Care Med 2001; 163:S1-S6]. This brief report will only summarise, based on selected references, the historical landmarks of its discovery and current understanding of the mechanisms of immunity, and their possible role in the pathogenesis of bronchopulmonary disease.

Adult↗