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

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.

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

Transactions of the Royal Society of Tropical Medicine and Hygiene ◽

10.1093/trstmh/trz026 ◽

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.

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

PEDIATRICS ◽

10.1542/peds.90.1.137 ◽

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

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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)

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa239 ◽

2020 ◽

Vol 222 (Supplement_7) ◽

pp. S658-S665 ◽

Cited By ~ 1

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.

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Respiratory Syncytial Virus Infection: Immune Response, Immunopathogenesis, and Treatment

Clinical Microbiology Reviews ◽

10.1128/cmr.12.2.298 ◽

1999 ◽

Vol 12 (2) ◽

pp. 298-309 ◽

Cited By ~ 143

Author(s):

Joseph B. Domachowske ◽

Helene F. Rosenberg

Keyword(s):

Immune Response ◽

Respiratory Syncytial Virus ◽

Respiratory Tract ◽

Neutralizing Antibodies ◽

Lower Respiratory Tract ◽

Immunoglobulin E ◽

Neutralizing Antibody ◽

Rsv Infection ◽

Syncytial Virus

SUMMARY Respiratory syncytial virus (RSV) is the single most important cause of lower respiratory tract infection during infancy and early childhood. Once RSV infection is established, the host immune response includes the production of virus-neutralizing antibodies and T-cell-specific immunity. The humoral immune response normally results in the development of anti-RSV neutralizing-antibody titers, but these are often suboptimal during an infant’s initial infection. Even when the production of RSV neutralizing antibody following RSV infection is robust, humoral immunity wanes over time. Reinfection during subsequent seasons is common. The cellular immune response to RSV infection is also important for the clearance of virus. This immune response, vital for host defense against RSV, is also implicated in the immunopathogenesis of severe lower respiratory tract RSV bronchiolitis. Many details of the immunology and immunopathologic mechanisms of RSV disease known at present have been learned from rodent models of RSV disease and are discussed in some detail. In addition, the roles of immunoglobulin E, histamine, and eosinophils in the immunopathogenesis of RSV disease are considered. Although the treatment of RSV bronchiolitis is primarily supportive, the role of ribavirin is briefly discussed. Novel approaches to the development of new antiviral drugs with promising anti-RSV activity in vitro are also described.

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Factors associated with severe respiratory syncytial virus disease in hospitalised children: a retrospective analysis

Archives of Disease in Childhood ◽

10.1136/archdischild-2021-322435 ◽

2021 ◽

pp. archdischild-2021-322435

Author(s):

Jeremy Anderson ◽

Michelle Oeum ◽

Eva Verkolf ◽

Paul V Licciardi ◽

Kim Mulholland ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Tract Infection ◽

Respiratory Tract ◽

Respiratory Tract Infection ◽

Lower Respiratory Tract ◽

Severe Disease ◽

Severe Respiratory Syncytial Virus ◽

Factors Associated ◽

Rsv Infection ◽

Syncytial Virus

BackgroundEarly recognition of children at risk of severe respiratory syncytial virus (RSV) lower respiratory tract infection is important as it informs management decisions. We aimed to evaluate factors associated with severe disease among young children hospitalised with RSV infection.MethodsWe conducted a retrospective cohort study of all children <2 years of age hospitalised for RSV lower respiratory tract infection at a single tertiary paediatric hospital over three RSV seasons (January 2017–December 2019). We classified children as having ‘moderate’ or ‘severe’ disease based on the level of respiratory intervention and used univariable and multivariable regression models to determine factors associated with severe disease.ResultsOf 970 hospitalised children, 386 (40%) were classified as having ‘severe’ and 584 (60%) as having ‘moderate’ RSV disease. On multivariable analyses, age <2 months (OR: 2.3, 95% CI 1.6 to 3.3, p<0.0001), prematurity (OR: 1.6, 95% CI 1.1 to 2.4, p=0.02) and RSV–parainfluenza virus type 3 (PIV3) codetection (OR: 2.6, 95% CI 1.05 to 6.5, p=0.04) were independently associated with severe disease.ConclusionYounger age, prematurity and PIV3 codetection were associated with severe RSV disease in children <2 years of age hospitalised with RSV infection. The association between PIV3 and severe RSV disease is a novel finding and warrants further investigation.

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In SilicoApproach towards Designing Virtual Oligopeptides for HRSV

The Scientific World JOURNAL ◽

10.1155/2014/613293 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Ruchi Jain ◽

Shanmughavel Piramanayagam

Keyword(s):

Respiratory Syncytial Virus ◽

Respiratory Tract ◽

Virus Replication ◽

Lower Respiratory Tract ◽

Specific Interaction ◽

Infection Process ◽

Rational Choices ◽

Respiratory Tract Illness ◽

Syncytial Virus ◽

Infants And Young Children

HRSV (human respiratory syncytial virus) is a serious cause of lower respiratory tract illness in infants and young children. Designing inhibitors from the proteins involved in virus replication and infection process provides target for new therapeutic treatments. In the present study,in silicodocking was performed using motavizumab as a template to design motavizumab derived oligopeptides for developing novel anti-HRSV agents. Additional simulations were conducted to study the conformational propensities of the oligopeptides and confirmed the hypothesis that the designed oligopeptide is highly flexible and capable of assuming stable confirmation. Our study demonstrated the best specific interaction of GEKKLVEAPKS oligopeptide for glycoprotein strain A among various screened oligopeptides. Encouraged by the results, we expect that the proposed scheme will provide rational choices for antibody reengineering which is useful for systematically identifying the possible ways to improve efficacy of existing antibody drugs.

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Effect of Zinc Salts on Respiratory Syncytial Virus Replication

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.3.783-790.2004 ◽

2004 ◽

Vol 48 (3) ◽

pp. 783-790 ◽

Cited By ~ 45

Author(s):

Rahaman O. Suara ◽

James E. Crowe

Keyword(s):

Respiratory Syncytial Virus ◽

Respiratory Tract ◽

Zinc Acetate ◽

Lower Respiratory Tract ◽

Divalent Cations ◽

Cell Monolayer ◽

Inhibitory Effect ◽

Plaque Formation ◽

Zinc Salts ◽

Syncytial Virus

ABSTRACT Zinc supplementation decreases the morbidity of lower respiratory tract infection in pediatric patients in the developing world. We sought to determine if zinc mediates a specific inhibitory effect against the major cause of pediatric lower respiratory tract disease, respiratory syncytial virus (RSV). We determined the in vitro inhibitory effect of three zinc salts (zinc acetate, lactate, and sulfate) on the replication of RSV at various concentrations of 10 and 1 mM and 100 and 10 μM. The degree of inhibition of RSV replication was examined in the presence of zinc during preincubation, adsorption, or penetration and was compared with that caused by salts of other divalent cations. Complete inhibition of RSV plaque formation was observed at 1 and 10 mM, representing reductions that were ≥106-fold. At the lowest concentration tested, 10 μM, we observed ≥1,000-fold reductions in RSV yield when zinc was present during preincubation, adsorption, penetration, or egress of virus. The therapeutic indices, determined as ratios of 50% toxicity concentration to 50% inhibitory concentration, were 100, 150, and 120 for zinc acetate, zinc lactate, and zinc sulfate, respectively. The inhibitory effect of zinc salts on RSV was concentration dependent and was not observed with other salts containing divalent cations such as calcium, magnesium, and manganese. RSV plaque formation was prevented by pretreatment of HEp-2 cell monolayer cultures with zinc or by addition of zinc to methylcellulose overlay media after infection. The results of this study suggest that zinc mediates antiviral activity on RSV by altering the ability of the cell to support RSV replication.

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