Tag Archives: Respiratory Syncytial Virus Infections

Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection. (Stulce)

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de Steenhuijsen Piters WA, et al. Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection. Am J Respir Crit Care Med. 2016 Nov 1;194(9):1104-1115.

RATIONALE: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity, especially among healthy children. We postulate that the severity of RSV infection is influenced by modulation of the host immune response by the local bacterial ecosystem.

OBJECTIVES: To assess whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and disease severity in children less than 2 years of age with RSV infection.

METHODS: We characterized the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy children by 16S-rRNA sequencing. In parallel, using multivariable models, we analyzed whole-blood transcriptome profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response, and clinical disease severity.

MEASUREMENTS AND MAIN RESULTS: We identified five nasopharyngeal microbiota clusters characterized by enrichment of either Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, or Staphylococcus aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus and negatively associated with S. aureus abundance, independent of age. Children with RSV showed overexpression of IFN-related genes, independent of the microbiota cluster. In addition, transcriptome profiles of children with RSV infection and H. influenzae- and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to Toll-like receptor and by neutrophil and macrophage activation and signaling.

CONCLUSIONS: Our data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.

Respiratory syncytial virus increases the virulence of streptococcus pneumoniae by binding to penicillin binding protein 1a. A new paradigm in respiratory infection. (Fortenberry)

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Smith CM, Sandrini S, Datta S, et al. Respiratory syncytial virus increases the virulence of streptococcus pneumoniae by binding to penicillin binding protein 1a. A new paradigm in respiratory infection. Am J Respir Crit Care Med. 2014 Jul 15;190(2):196-207.

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Rationale: Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are major respiratory pathogens. Coinfection with RSV and S. pneumoniae is associated with severe and often fatal pneumonia but the molecular basis for this remains unclear.

Objectives: To determine if interaction between RSV and pneumococci enhances pneumococcal virulence.

Methods: We used confocal microscopy and Western blot to identify the receptors involved in direct binding of RSV and pneumococci, the effects of which were studied in both in vivo and in vitro models of infection. Human ciliated respiratory epithelial cell cultures were infected with RSV for 72 hours and then challenged with pneumococci. Pneumococci were collected after 2 hours exposure and changes in gene expression determined using quantitative real-time polymerase chain reaction.

Measurements and Main Results: Following incubation with RSV or purified G protein, pneumococci demonstrated a significant increase in the inflammatory response and bacterial adherence to human ciliated epithelial cultures and markedly increased virulence in a pneumonia model in mice. This was associated with extensive changes in the pneumococcal transcriptome and significant up-regulation in the expression of key pneumococcal virulence genes, including the gene for the pneumococcal toxin, pneumolysin. We show that mechanistically this is caused by RSV G glycoprotein binding penicillin binding protein 1a.

Conclusions: The direct interaction between a respiratory virus protein and the pneumococcus resulting in increased bacterial virulence and worsening disease outcome is a new paradigm in respiratory infection.

Oral dexamethasone for bronchiolitis: a randomized trial. (Vats)

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Alansari K, Sakran M, Davidson BL, et al. Oral dexamethasone for bronchiolitis: a randomized trial. Pediatrics. 2013 Oct;132(4):e810-e816.

OBJECTIVE: Determine whether dexamethasone treatment added to salbutamol reduces time to readiness for discharge in patients with bronchiolitis and possible asthma.

METHODS: We compared efficacy and safety of dexamethasone, 1 mg/kg, then 0.6 mg/kg for 4 more days, with placebo for acute bronchiolitis in patients with asthma risk, as determined by eczema or a family history of asthma in a first-degree relative. All patients received inhaled salbutamol. Time to readiness for discharge was the primary efficacy outcome.

RESULTS: Two hundred previously healthy infants diagnosed with bronchiolitis, median age 3.5 months, were enrolled. Five placebo recipients needed admission to intensive care unit during infirmary treatment (P = .02). Among 100 dexamethasone recipients, geometric mean time to readiness for discharge was 18.6 hours (95% confidence interval [CI], 14.9 to 23.1 hours); among 90 control patients, 27.1 hours (95% CI, 21.8 to 33.8 hours). The ratio, 0.69 (95% CI, 0.51 to 0.93), revealed a mean 31% shortening of duration to readiness for discharge favoring dexamethasone (P = .015). Twenty-two dexamethasone and 19 control patients were readmitted to the short stay infirmary in the week after discharge (P = .9). No hospitalizations or side effects were reported during 7 days of surveillance.

CONCLUSIONS: Dexamethasone with salbutamol shortened time to readiness for infirmary discharge during bronchiolitis episodes in patients with eczema or a family history of asthma in a first-degree relative. Infirmary and clinic visits in the subsequent week occurred similarly for the 2 groups.

Full-text for Children’s and Emory users.