Associations Between Pathogens in the Upper Respiratory Tract of Young Children: Interplay Between Viruses and Bacteria

PLoS One. 2012;7(10):e47711. doi: 10.1371/journal.pone.0047711. Epub 2012 Oct 17.


Background: High rates of potentially pathogenic bacteria and respiratory viruses can be detected in the upper respiratory tract of healthy children. Investigating presence of and associations between these pathogens in healthy individuals is still a rather unexplored field of research, but may have implications for interpreting findings during disease.

Methodology/principal findings: We selected 986 nasopharyngeal samples from 433 6- to 24-month-old healthy children that had participated in a randomized controlled trial. We determined the presence of 20 common respiratory viruses using real-time PCR. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus were identified by conventional culture methods. Information on risk factors was obtained by questionnaires. We performed multivariate logistic regression analyses followed by partial correlation analysis to identify the overall pattern of associations. S. pneumoniae colonization was positively associated with the presence of H. influenzae (adjusted odds ratio 1.60, 95% confidence interval 1.18-2.16), M. catarrhalis (1.78, 1.29-2.47), human rhinoviruses (1.63, 1.19-2.22) and enteroviruses (1.97, 1.26-3.10), and negatively associated with S. aureus presence (0.59, 0.35-0.98). H. influenzae was positively associated with human rhinoviruses (1.63, 1.22-2.18) and respiratory syncytial viruses (2.78, 1.06-7.28). M. catarrhalis colonization was positively associated with coronaviruses (1.99, 1.01-3.93) and adenoviruses (3.69, 1.29-10.56), and negatively with S. aureus carriage (0.42, 0.25-0.69). We observed a strong positive association between S. aureus and influenza viruses (4.87, 1.59-14.89). In addition, human rhinoviruses and enteroviruses were positively correlated (2.40, 1.66-3.47), as were enteroviruses and human bocavirus, WU polyomavirus, parainfluenza viruses, and human parechovirus. A negative association was observed between human rhinoviruses and coronaviruses.

Conclusions/significance: Our data revealed high viral and bacterial prevalence rates and distinct bacterial-bacterial, viral-bacterial and viral-viral associations in healthy children, hinting towards the complexity and potential dynamics of microbial communities in the upper respiratory tract. This warrants careful consideration when associating microbial presence with specific respiratory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria / growth & development
  • Bacteria / metabolism*
  • Child, Preschool
  • Colony Count, Microbial
  • Female
  • Humans
  • Infant
  • Male
  • Microbial Interactions*
  • Nasopharynx / microbiology
  • Nasopharynx / virology
  • Odds Ratio
  • Respiratory System / microbiology*
  • Respiratory System / pathology
  • Respiratory System / virology*
  • Respiratory Tract Infections / microbiology*
  • Respiratory Tract Infections / virology*
  • Risk Factors
  • Viruses / metabolism*

Grant support

This work was supported by The Netherlands Organisation for Scientific Research through NWO-VENI Grant 91610121, ZonMW Grant 91209010 and the Dutch Ministry of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.