Serious Respiratory Tract Disease Caused by Respiratory Syncytial Virus: Prospects for Improved Therapy and Effective Immunization

PEDIATRICS ◽  
1992 ◽  
Vol 90 (1) ◽  
pp. 137-143
Author(s):  
Robert M. Chanock ◽  
Robert H. Parrott ◽  
Mark Connors ◽  
Peter L. Collins ◽  
Brian R. Murphy
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Durable Resistance ◽  
Secretory Iga ◽  
Upper Respiratory Tract ◽  
Viral Pathogen ◽  
Rsv Infection ◽  
Upper Respiratory ◽  
Syncytial Virus

On this felicitous occasion we honor Dr Saul Krugman for his many contributions to the study and control of a wide variety of important pediatric viral diseases. In preparing our remarks we found it difficult to identify a major pediatric viral pathogen upon which Saul had not left his mark. One of the few that escaped, for reasons unknown, is respiratory syncytial virus (RSV). Since RSV is the major pediatric respiratory tract viral pathogen, we thought this agent might pique his interest. Those of us studying RSV need all the help we can receive from biomedical scientists of Saul's caliber. What follows is a summary of current efforts to develop improved therapy and effective immunoprophylaxis for this elusive respiratory tract viral pathogen. IMMUNITY TO RSV DISEASE The mechanisms by which the immune system protects the respiratory tract against RSV infection and disease are not completely understood. However, it is clear that infection (or reinfection) induces resistance in the upper respiratory tract that is neither complete nor long lasting.1,2 The situation is some-what more favorable in the lower respiratory tract, where infection (or reinfection) induces more substantial and more durable resistance to disease. As a consequence, cumulative immunity from multiple reinfections protects older children and adults against the more serious forms of disease involving the lower respiratory tract such as bronchiolitis and pneumonia. Resistance to RSV infection in the upper respiratory tract appears to be mediated primarily by local secretory IgA antibodies, which explains the transitory nature of immunity in this region.3

scholarly journals Chinchilla and Murine Models of Upper Respiratory Tract Infections with Respiratory Syncytial Virus

2005 ◽  
Vol 79 (10) ◽  
pp. 6035-6042 ◽  
Author(s):  
Negin Gitiban ◽  
Joseph A. Jurcisek ◽  
Randall H. Harris ◽  
Sara E. Mertz ◽  
Russell K. Durbin ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Upper Airway ◽  
Upper Respiratory Tract ◽  
Viral Pathogen ◽  
Rsv Infection ◽  
Upper Respiratory ◽  
Syncytial Virus ◽  
Tract Infections

ABSTRACT Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants and the elderly. While the primary infection is the most serious, reinfection of the upper airway throughout life is the rule. Although relatively little is known about either RSV infection of the upper respiratory tract or host mucosal immunity to RSV, recent literature suggests that RSV is the predominant viral pathogen predisposing to bacterial otitis media (OM). Herein, we describe mouse and chinchilla models of RSV infection of the nasopharynx and Eustachian tube. Both rodent hosts were susceptible to RSV infection of the upper airway following intranasal challenge; however, the chinchilla proved to be more permissive than the mouse. The chinchilla model will likely be extremely useful to test the role of RSV in bacterial OM and the efficacy of RSV vaccine candidates designed to provide mucosal and cytotoxic T-lymphocyte immunity. Ultimately, we hope to investigate the relative ability of these candidates to potentially protect against viral predisposal to bacterial OM.

scholarly journals Presumed Risk Factors and Biomarkers for Severe Respiratory Syncytial Virus Disease and Related Sequelae: Protocol for an Observational Multicenter, Case-Control Study From the Respiratory Syncytial Virus Consortium in Europe (RESCEU)

2020 ◽  
Vol 222 (Supplement_7) ◽  
pp. S658-S665 ◽  
Author(s):  
Kimberley Jefferies ◽  
Simon B Drysdale ◽  
Hannah Robinson ◽  
Elizabeth Ann Clutterbuck ◽  
Luke Blackwell ◽  
...  
Keyword(s):  
Risk Factors ◽  
Respiratory Syncytial Virus ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Disease Severity ◽  
Lower Respiratory Tract ◽  
Viral Pathogen ◽  
Rsv Infection ◽  
Syncytial Virus

Abstract Respiratory syncytial virus (RSV) is the leading viral pathogen associated with acute lower respiratory tract infection and hospitalization in children < 5 years of age worldwide. While there are known clinical risk factors for severe RSV infection, the majority of those hospitalized are previously healthy infants. There is consequently an unmet need to identify biomarkers that predict host response, disease severity, and sequelae. The primary objective is to identify biomarkers of severe RSV acute respiratory tract infection (ARTI) in infants. Secondary objectives include establishing biomarkers associated with respiratory sequelae following RSV infection and characterizing the viral load, RSV whole-genome sequencing, host immune response, and transcriptomic, proteomic, metabolomic and epigenetic signatures associated with RSV disease severity. Six hundred thirty infants will be recruited across 3 European countries: the Netherlands, Spain, and the United Kingdom. Participants will be recruited into 2 groups: (1) infants with confirmed RSV ARTI (includes upper and lower respiratory tract infections), 500 without and 50 with comorbidities; and (2) 80 healthy controls. At baseline, participants will have nasopharyngeal, blood, buccal, stool, and urine samples collected, plus complete a questionnaire and 14-day symptom diary. At convalescence (7 weeks ± 1 week post-ARTI), specimen collection will be repeated. Laboratory measures will be correlated with symptom severity scores to identify corresponding biomarkers of disease severity. Clinical Trials Registration NCT03756766.

scholarly journals Recombinant Respiratory Syncytial Virus Bearing a Deletion of either the NS2 or SH Gene Is Attenuated in Chimpanzees

1999 ◽  
Vol 73 (4) ◽  
pp. 3438-3442 ◽  
Author(s):  
Stephen S. Whitehead ◽  
Alexander Bukreyev ◽  
Michael N. Teng ◽  
Cai-Yen Firestone ◽  
Marisa St. Claire ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Recombinant Virus ◽  
Lower Respiratory Tract ◽  
Vaccine Candidate ◽  
Upper Respiratory Tract ◽  
Wild Type ◽  
Vaccine Candidates ◽  
Upper Respiratory ◽  
Syncytial Virus

ABSTRACT The NS2 and SH genes of respiratory syncytial virus (RSV) have been separately deleted from a recombinant wild-type RSV strain, A2 (M. N. Teng and P. L. Collins, J. Virol. 73:466–473, 1998; A. Bukreyev et al., J. Virol. 71:8973–8982, 1997; and this study). The resulting viruses, designated rA2ΔNS2 and rA2ΔSH, were administered to chimpanzees to evaluate their levels of attenuation and immunogenicity. Recombinant virus rA2ΔNS2 replicated to moderate levels in the upper respiratory tract, was highly attenuated in the lower respiratory tract, and induced significant resistance to challenge with wild-type RSV. The replication of rA2ΔSH virus was only moderately reduced in the lower, but not the upper, respiratory tract. However, chimpanzees infected with either virus developed significantly less rhinorrhea than those infected with wild-type RSV. These findings demonstrate that a recombinant RSV mutant lacking either the NS2 or SH gene is attenuated and indicate that these deletions may be useful as attenuating mutations in new, live recombinant RSV vaccine candidates for both pediatric and elderly populations. The ΔSH mutation was incorporated into a recombinant form of thecpts248/404 vaccine candidate, was evaluated for safety in seronegative chimpanzees, and can now be evaluated as a vaccine for humans.

scholarly journals Viral etiology and epidemiology of pediatric patients hospitalized for acute respiratory tract infections in Macao: a retrospective study from 2014 to 2017

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Cheng Lei ◽  
Lisong Yang ◽  
Cheong Tat Lou ◽  
Fan Yang ◽  
Kin Ian SiTou ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Pediatric Patients ◽  
Respiratory Infections ◽  
Upper Respiratory Tract ◽  
Viral Etiology ◽  
Upper Respiratory ◽  
Syncytial Virus ◽  
Tract Infections

Abstract Background Acute respiratory infections (ARIs) are among the leading causes of hospitalization in children. Understanding the local dominant viral etiologies is important to inform infection control practices and clinical management. This study aimed to investigate the viral etiology and epidemiology of respiratory infections among pediatric inpatients in Macao. Methods A retrospective study using electronic health records between 2014 and 2017 at Kiang Wu Hospital was performed. Nasopharyngeal swab specimens were obtained from hospitalized children aged 13 years or younger with respiratory tract diseases. xMAP multiplex assays were employed to detect respiratory agents including 10 respiratory viruses. Data were analyzed to describe the frequency and seasonality. Results Of the 4880 children enrolled in the study, 3767 (77.1%) were positive for at least one of the 13 viral pathogens tested, of which 2707 (55.5%) being male and 2635 (70.0%) under 2 years old. Among the positive results, there were 3091 (82.0%) single infections and 676 (18.0%) multiple infections. The predominant viruses included human rhinovirus/enterovirus (HRV/EV 27.4%), adenovirus (ADV, 15.8%), respiratory syncytial virus B (RSVB, 7.8%) and respiratory syncytial virus A (RSVA, 7.8%). The detection of viral infection was the most prevalent in autumn (960/1176, 81.6%), followed by spring (1095/1406, 77.9%), winter (768/992, 77.4%), and summer (944/1306, 72.3%), with HRV/EV and ADV being most commonly detected throughout the 4 years of study period. The detection rate of viral infection was highest among ARI patients presented with croup (123/141, 87.2%), followed by lower respiratory tract infection (1924/2356, 81.7%) and upper respiratory tract infection (1720/2383, 72.2%). FluA, FluB and ADV were positive factors for upper respiratory tract infections. On the other hand, infection with RSVA, RSVB, PIV3, PIV4, HMPV, and EV/RHV were positively associated with lower respiratory tract infections; and PIV1, PIV2, and PIV3 were positively associated with croup. Conclusions This is the first study in Macao to determine the viral etiology and epidemiology of pediatric patients hospitalized for ARIs. The study findings can contribute to the awareness of pathogen, appropriate preventative measure, accurate diagnosis, and proper clinical management of respiratory viral infections among children in Macao.

Reappraisal of respiratory syncytial virus as an aetiology of severe acute lower respiratory tract infections in children younger than 5 years in Nigeria

2019 ◽  
Vol 113 (8) ◽  
pp. 446-452
Author(s):  
Damilola M Oladele ◽  
Dimeji P Oladele ◽  
Rasheedat M Ibraheem ◽  
Mohammed B Abdulkadir ◽  
Rasaki Adewole Raheem ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Preventive Strategy ◽  
Lower Respiratory Tract Infections ◽  
Cross Sectional ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections

Abstract Background Acute lower respiratory tract infections (ALRIs) especially severe ALRIs, constitute a global high burden of morbidity and mortality in children <5 y of age and respiratory syncytial virus (RSV) has been documented to a play a major aetiological role. However, Nigerian reports on severe childhood RSV ALRIs are rare and most reports are old. With recent advances in RSV preventive strategy, arises the need for a recent appraisal of RSV infection in children with severe ALRI. The current study thus set out to determine the prevalence of RSV infection among hospitalized children <5 y of age and describe the related social determinants. Methods We performed a descriptive cross-sectional study conducted over 1 y of 120 children, ages 2–59 months, diagnosed with ALRI. Relevant data were obtained and an antigen detection assay was used for viral studies. Results The prevalence of RSV infection was 34.2% and its peak was in the rainy months. The proportion of infants in the RSV-positive group was significantly higher than that in the RSV-negative group (82.9% vs 54.4%; p=0.002). These findings were largely consistent with those of earlier reports. Conclusions RSV has remained a common cause of severe ALRI in infants, especially during the rainy months in Nigeria. It is thus suggested that more effort be focused towards implementing the current global recommendations for the prevention of RSV-associated LRI, particularly in infants.

Respiratory viruses

2011 ◽  
pp. 208-211
Author(s):  
Dr Mark Harrison
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Common Cold ◽  
Respiratory Viruses ◽  
Upper Respiratory Tract Infections ◽  
Upper Respiratory Tract ◽  
The Common ◽  
Upper Respiratory ◽  
Syncytial Virus ◽  
Tract Infections

15.1 Rhinovirus, 209 15.2 Influenza, 210 15.3 Parainfluenza, 211 15.4 Respiratory syncytial virus (RSV), 211 • There are more than 100 different serotypes of rhinovirus. • Rhinovirus is chiefly limited to upper respiratory tract infections and is the major cause of the common cold....

Outbreak of Nosocomial Respiratory Syncytial Virus Infections in a Hematology and Transplant Unit.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3032-3032
Author(s):  
Nicola Lehners ◽  
Paul Schnitzler ◽  
Gerlinde Egerer ◽  
Peter Dreger ◽  
Christoph Eisenbach ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Sequence Analysis ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Outbreak Strain ◽  
Major Mode ◽  
Rsv Infection ◽  
Tract Involvement ◽  
Syncytial Virus ◽  
Respiratory Specimens

Abstract Abstract 3032 Respiratory syncytial virus (RSV) is a pathogen associated with bronchiolitis in infants and small children. However, immunocompromised adults might also be at risk for severe lower respiratory tract involvement induced by RSV. We report the rapid control of an outbreak of nosocomial RSV infections in an institution with special focus on allogeneic and autologous stem cell transplantations. Between November 2011 and March 2012 56 patients were diagnosed with RSV infection by RT-PCR at our institution. In order to identify possible risk factors for lower respiratory tract involvement in RSV infected patients, clinical course of infection as well as radiological and laboratory findings were evaluated. Characterization of RSV strains in respiratory specimens was achieved by sequence analysis of part of the RSV glycoprotein G gene and phylogenetic comparison of outbreak and community strains was performed. Out of 56 patients with RSV infection, 39 patients showed signs of lower respiratory tract involvement. 14 fatal outcomes were observed. In most of the lethal cases coinfections with other pathogens such as Aspergillus spp. or Pseudomonas aeruginosa were present. Therefore the exact impact of RSV on the fatal outcome remains difficult, if not impossible, to assess. Age, sex, underlying disease, disease control or transplant status did not differ significantly between severe and non-severe cases. However, hypogammaglobulinemia was associated with a higher risk for fatal infection (p = 0.03) in univariate analysis, whereas therapy with oral ribavirin might show a protective effect (p = 0.02). Prolonged viral shedding was frequently observed (median 22.5 [1 – 143] days), most pronounced in patients folllowing allogeneic transplantation (p = 0.04). The major mode of RSV transmission seemed to be direct patient-to-patient contact as suggested by evaluation of patient movements on the wards. Sequence analysis on respiratory specimens obtained from 46 patients revealed the presence of a particular outbreak strain in 40 patients, characterized by an identical nucleotide sequence of RSV GA2 subtype. Phylogenetic analysis showed low prevalence of the outbreak strain in the community. By implementation of rigorous isolation measures containment of outbreak was achieved. Highly contagious viral pathogens such as RSV are able to cause rapidly spreading outbreaks among immunocompromised patients. Hypogammaglobulinemia might be a risk factor for severe lower respiratory tract infection. Treatment with oral ribavirin might have a positive effect on outcome. Rigorous isolation measures are essential to the containment of outbreak. Disclosures: Off Label Use: ribavirin aerosol is FDA approved for severe cases of RSV in infants and young children.

scholarly journals Prevalence of upper respiratory tract infections at a tertiary care hospital in the city of São Paulo

2010 ◽  
Vol 8 (2) ◽  
pp. 197-199 ◽  
Author(s):  
Amilton Mouro ◽  
Luci Black Tabacow Hidal ◽  
Marines Dalla Valle Martino ◽  
Jacyr Pasternark
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Sao Paulo ◽  
Care Hospital ◽  
Upper Respiratory Tract ◽  
Upper Respiratory ◽  
Syncytial Virus ◽  
The City

ABSTRACT Objective: To evaluate the prevalence of pathogens in the upper respiratory tract according to age at a tertiary care hospital in the city of São Paulo. Methods: A total of 6,144 biological material tests from upper respiratory airways were analyzed: 740 bacterial cultures, 726 virus screenings and 4,678 rapid tests for S. pyogenes. Results: The most frequently found etiological agent was respiratory syncytial virus (29.6%; 215/726). The main agents detected per age groups were: respiratory syncytial virus (25.34%; 184/726) in patients aged 28 days-3 years; S. pyogenes (9.5%; 70/740) in 3-12 year-old children; influenza virus (8.8%; 64/726) in adults (18-59 years). Conclusions: The etiologic agents of upper respiratory infections vary according to age and imply diverse clinical and therapeutic management.

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