title: High pneumococcal density correlates with more mucosal inflammation and reduced respiratory syncytial virus disease severity in infants.
abstract: BACKGROUND
  Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract infections in infants. A small percentage of the infected infants develops a severe infection, while most of these severely ill patients were previously healthy. It remains unclear why these children develop severe RSV infections. In this study, we investigate whether pneumococcal nasopharyngeal carriage patterns correlate with mucosal inflammation and severity of disease.
  
  
  METHODS
  In total, 105 infants hospitalized with RSV infection were included and recovery samples were taken from 42 patients. The presence and density of Streptococcus pneumoniae was determined by RT qPCR to study its relation to viral load, inflammation (MMP-9 and IL-6) and severity of RSV disease.
  
  
  RESULTS
  We show that pneumococcal presence or absence in the nasopharynx does not correlate with viral load, inflammation or severity of disease. However, when pneumococcus is present in patients, a higher nasopharyngeal pneumococcal density was correlated with a higher RSV load, higher MMP-9 levels and a less severe course of disease.
  
  
  CONCLUSIONS
  Our results show correlations between S. pneumoniae density and viral load, inflammation and disease severity, suggesting that pneumococcal density may be an indicator for severity in paediatric RSV disease.
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P. O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Marloes
authors.initials: M
authors.lastname: Vissers
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P. O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Inge M
authors.initials: IM
authors.lastname: Ahout
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P. O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Corné H
authors.initials: CH
authors.lastname: van den Kieboom
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P. O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Christa E
authors.initials: CE
authors.lastname: van der Gaast-de Jongh
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P. O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Groh
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P. O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Amelieke J
authors.initials: AJ
authors.lastname: Cremers
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P. O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: de Groot
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P. O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Marien I
authors.initials: MI
authors.lastname: de Jonge
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P. O. Box 9101, 6500 HB, Nijmegen, The Netherlands. gerben.ferwerda@radboudumc.nl.
authors.forename: Gerben
authors.initials: G
authors.lastname: Ferwerda
mesh_terms: D002662:Child Health Services; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009305:Nasopharynx / Q000382:microbiology / Q000821:virology; D009426:Netherlands / Q000453:epidemiology; D018357:Respiratory Syncytial Virus Infections / Q000453:epidemiology* / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000302:isolation & purification* / Q000472:pathogenicity; D012141:Respiratory Tract Infections / Q000453:epidemiology* / Q000821:virology; D012720:Severity of Illness Index; D013296:Streptococcus pneumoniae / Q000302:isolation & purification* / Q000472:pathogenicity; D019562:Viral Load
keywords: Disease severity; MMP-9; Nasopharyngeal colonization; Respiratory syncytial virus; Streptococcus pneumoniae