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

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          Abstract

          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.

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          Most cited references30

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          Integration of biological networks and gene expression data using Cytoscape.

          Cytoscape is a free software package for visualizing, modeling and analyzing molecular and genetic interaction networks. This protocol explains how to use Cytoscape to analyze the results of mRNA expression profiling, and other functional genomics and proteomics experiments, in the context of an interaction network obtained for genes of interest. Five major steps are described: (i) obtaining a gene or protein network, (ii) displaying the network using layout algorithms, (iii) integrating with gene expression and other functional attributes, (iv) identifying putative complexes and functional modules and (v) identifying enriched Gene Ontology annotations in the network. These steps provide a broad sample of the types of analyses performed by Cytoscape.
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            Humans and our ancestors have evolved since the most ancient times with a commensal microbiota. The conservation of indicator species in a niche-specific manner across all of the studied human population groups suggests that the microbiota confer conserved benefits on humans. Nevertheless, certain of these organisms have pathogenic properties and, through medical practices and lifestyle changes, their prevalence in human populations is changing, often to an extreme degree. In this Essay, we propose that the disappearance of these ancestral indigenous organisms, which are intimately involved in human physiology, is not entirely beneficial and has consequences that might include post-modern conditions such as obesity and asthma.
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              Antibiotics have been used effectively as a means to treat bacterial infections in humans and animals for over half a century. However, through their use, lasting alterations are being made to a mutualistic relationship that has taken millennia to evolve: the relationship between the host and its microbiota. Host-microbiota interactions are dynamic; therefore, changes in the microbiota as a consequence of antibiotic treatment can result in the dysregulation of host immune homeostasis and an increased susceptibility to disease. A better understanding of both the changes in the microbiota as a result of antibiotic treatment and the consequential changes in host immune homeostasis is imperative, so that these effects can be mitigated.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                17 October 2012
                : 7
                : 10
                : e47711
                Affiliations
                [1 ]Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
                [2 ]Research Center Linnaeus Institute, Spaarne Hospital, Hoofddorp, The Netherlands
                [3 ]Laboratory of Medical Microbiology and Immunology, St Elisabeth Hospital, Tilburg, The Netherlands
                [4 ]Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
                [5 ]Regional Laboratory of Public Health, Haarlem, The Netherlands
                The Ohio State Unversity, United States of America
                Author notes

                Competing Interests: DB declares to have received consulting fees from Pfizer. EAMS declares to have received unrestricted research support from Pfizer and Baxter, consulting fees from Pfizer and GlaxoSmithKline, lecturing fees from Pfizer, and grant support for vaccine studies from Pfizer and GlaxoSmithKline. RHV declares to have received research support from GlaxoSmithKline and Pfizer for vaccine studies and consulting fees from GlaxoSmithKline. None of the fees or grants listed here were received for the research described in this paper. For all other authors no conflicts of interest were declared. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

                Critical revision of the manuscript for important intellectual content: MRvdB EJMvG GB RHV JWAR JPB WAAdSP AATMB XW CB DB EAMS. Study supervision: DB EAMS. Conceived and designed the experiments: DB EAMS. Performed the experiments: RHV EJMvG MRvdB WAAdSP AATMB JPB JWAR. Analyzed the data: MRvdB XW CWBB DB. Contributed reagents/materials/analysis tools: RHV GB JWAR JPB. Wrote the paper: MRvdB EJMvG DB EAMS.

                Article
                PONE-D-12-17706
                10.1371/journal.pone.0047711
                3474735
                23082199
                6401e793-6911-421c-a90d-ff716ab6aea4

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 19 June 2012
                : 13 September 2012
                Page count
                Pages: 9
                Funding
                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.
                Categories
                Research Article
                Biology
                Ecology
                Biota
                Microbial Ecology
                Medicine
                Otorhinolaryngology
                Pediatric Otorhinolaryngology
                Pediatrics
                Pediatric Pulmonology
                Pulmonology
                Respiratory Infections
                Lower Respiratory Tract Infections
                Upper Respiratory Tract Infections

                Uncategorized
                Uncategorized

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