Abstract
BackgroundHigh 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 FindingsWe 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/SignificanceOur 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.
Highlights
Koch’s original postulates, designed to link one causative microbe to one specific disease, have been subject to reconsideration since they were formulated in 1884 [1,2,3]
We aimed to evaluate the prevalence of a wide range of common respiratory viruses as well as co-occurrence patterns with four of the most commonly detected bacterial pathogens in clinical practice (S. pneumoniae, H. influenzae, M. catarrhalis and S. aureus), while taking well described epidemiologic and environmental determinants into account
When simultaneously adjusting for driving risk factors (Figure 1B) all correlations remain, except for those between H. influenzae and M. catarrhalis (P = 0.17), and between M. catarrhalis and coronaviruses (P = 0.064). This is the first study in which co-occurrence patterns of four potentially pathogenic bacteria and 20 common respiratory viruses in nasopharyngeal samples from otherwise healthy young children are investigated by multivariate and partial correlation network analysis
Summary
Koch’s original postulates, designed to link one causative microbe to one specific disease, have been subject to reconsideration since they were formulated in 1884 [1,2,3]. Several residents of the nasopharyngeal microbiome, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus, are major contributors to disease in childhood. They are common, transient colonizers of the nasopharynx of healthy children, especially in the youngest, whose immune systems are still maturing. Colonization of this niche in the upper respiratory tract appears to be a dynamic process of acquisition and elimination of various microbes, during which they interact with the host, its maturing immune system and each other [6]. 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
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