Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection

Piters, Wouter A A de Steenhuijsen; Heinonen, Santtu; Hasrat, Raiza; Bunsow, Eleonora; Smith, B.; Suarez-Arrabal, M. Carmen; Chaussabel, Damien; Cohen, Daniel M.; Sanders, Elisabeth A. M.; Ramilo, Octavio; Bogaert, Debby; Mejías, Asunción

doi:10.1164/rccm.201602-0220oc

Cited by 342 publications

(429 citation statements)

References 45 publications

(53 reference statements)

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“…However, the difference of S. aureus abundance was significantly higher in RSV than in rhinovirus-infected infants [38]. Another prospective study investigated the nasopharyngeal microbiota in young infants with RSV infections by 16S-RNA sequencing; the authors found that RSV infection was positively associated with H. influenzae and S. pneumoniae , but negatively associated with S. aureus nasopharyngeal colonization [39]. In another study concerning nasopharyngeal aspirates from children with RSV infection aged between 6 months and 2 years, S. aureus was shown to colonize 77% of RSV-infected patients with a positive association between RSV and S. aureus nasopharyngeal carriage [40].…”

Section: Impact Of Viral Infections In the Respiratory Tract On Staphmentioning

confidence: 99%

Staphylococcus aureus colonization and non-influenza respiratory viruses: Interactions and synergism mechanisms

et al. 2018

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Viral infections of the respiratory tract can be complicated by bacterial superinfection, resulting in a significantly longer duration of illness and even a fatal outcome. In this review, we focused on interactions between S. aureus and non-influenza viruses. Clinical data evidenced that rhinovirus infection may increase the S. aureus carriage load in humans and its spread. In children, respiratory syncytial virus infection is associated with S. aureus carriage. The mechanisms by which some non-influenza respiratory viruses predispose host cells to S. aureus superinfection can be summarized in three categories: i) modifying expression levels of cellular patterns involved in S. aureus adhesion and/or internalization, ii) inducing S. aureus invasion of epithelial cells due to the disruption of tight junctions, and iii) decreasing S. aureus clearance by altering the immune response. The comprehension of pathways involved in S. aureus-respiratory virus interactions may help developing new strategies of preventive and curative therapy.

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Section: Impact Of Viral Infections In the Respiratory Tract On Staphmentioning

confidence: 99%

Staphylococcus aureus colonization and non-influenza respiratory viruses: Interactions and synergism mechanisms

et al. 2018

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“…Studies of the nasopharyngeal microbiota during RSV infection have also identified increased abundances of H. influenzae, S. pneumoniae and Moraxella species compared to non-RSV infections or healthy controls (1,14,15,25,56).…”

Section: Aetiology and Diagnosismentioning

confidence: 99%

“…Detection of potentially pathogenic bacteria in the nasopharynx has also been associated with increased severity during paediatric RSV infections (14,15 (real-time PCR), WBC (white blood cells), CRP (C-reactive protein).…”

Section: Disease Severitymentioning

confidence: 99%

“…influenzae, has been associated with increased concentrations of inflammatory mediators like interleukin (IL)-6, IL-8 and matrix metallopeptidase 9 (MMP-9) (14,15,98). Some of these RSV studies have found that this increased inflammation also correlated with increased measures of disease severity, such as hospitalisation or duration of supplemental oxygen (14,15 An overly robust inflammatory response could theoretically lead to excessive neutrophil influx and a cytokine storm, accentuating lung damage and significantly increasing morbidity.…”

Section: Synergistic Stimulation Of Inflammationmentioning

confidence: 99%

“…However, outside of epidemics, influenza is a relatively infrequent pathogen of young children (8). There is some evidence to suggest that bacterial co-infections with common paediatric viruses like RSV may be clinically relevant in young children (9)(10)(11)(12)(13)(14)(15). However, as healthy young children are often colonised by potentially pathogenic bacteria, distinguishing true bacterial co-infection, i.e.…”

Section: Introductionmentioning

confidence: 99%

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Viral/bacterial respiratory tract co-infections in children

Brealey¹

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Respiratory syncytial virus (RSV) is the most significant cause of paediatric acute respiratory infection (ARI). RSV and other respiratory viruses are commonly co-detected with potentially pathogenic bacteria, such as Streptococcus pneumoniae, in the upper airways of young children.While these bacteria are known to be carried asymptomatically, they are also capable of opportunistic infections. Interactions between RSV and S. pneumoniae have been demonstrated in both clinical and molecular studies. However, the clinical significance of these interactions remains debated, and the effect of clinically relevant strain variation in both virus and bacteria on these interactions is also unknown. This work aimed to better understand the role of S. pneumoniae colonisation during RSV infections.To determine the effect of RSV and S. pneumoniae co-detection on disease severity during ARI, molecular pathogen screening of nasopharyngeal samples was conducted in a cohort of young children under the age of two years presenting with ARI at the emergency department of the Royal Brisbane Children's Hospital, Australia. S. pneumoniae was co-detected in approximately 52% of RSV infections, and co-detection was associated with increased disease severity, suggesting that S. pneumoniae plays a pathogenic role in severe paediatric RSV infections.Having established a clinical role for S. pneumoniae during RSV infection, the dynamics of pneumococcal colonisation of the nasal cavity was investigated in the four weeks prior and subsequent to an RSV infection in a longitudinal birth cohort of Brisbane-based children.Approximately 33% of infants and young children with RSV infections were colonised by S. pneumoniae prior to the RSV detection, and strain characterisation of S. pneumoniae in the weeks immediately surrounding the viral infection suggested that any observed growth of S. pneumoniae during RSV infection arose from the pre-existing strain colonising the URT. In another 14% of RSV infections, S. pneumoniae was first detected during the virus infection, suggesting simultaneous acquisition of RSV and S. pneumoniae and possible co-transmission of the two pathogens.The results from the two paediatric cohorts suggested an interaction between RSV and S.pneumoniae that was advantageous to the bacteria. It was therefore hypothesised that the molecular mechanisms governing RSV and S. pneumoniae interactions might be pneumococcal strain-specific and stronger in strains frequently co-detected with RSV. Studies have shown that RSV can increase S. pneumoniae colonisation by enhancing pneumococcal adherence to airway epithelia, and virions iii can bind directly to the bacterium to form co-pathogen complexes. These interactions are in part mediated through the binding interactions between S. pneumoniae surface receptors and the RSV G surface glycoprotein. RSV G is highly variable, both antigenically and genetically, and is the main protein used to type RSV into subtypes A and B. The genetic variation of RSV G was characterised from nasophar...

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Impact of micro‐environmental changes on respiratory tract infections with intracellular bacteria

et al. 2016

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Edited by Wilhelm JustCommunity-acquired pneumonia is caused by intra-and extracellular bacteria, with some of these bacteria also being linked to the pathogenesis of chronic lung diseases, including asthma and chronic obstructive pulmonary disease. Chlamydia pneumoniae is an obligate intracellular pathogen that is highly sensitive to micro-environmental conditions controlling both pathogen growth and host immune responses. The availability of nutrients, as well as changes in oxygen, pH and interferon-c levels, have been shown to directly influence the chlamydial life cycle and clearance. Although the lung has been traditionally regarded as a sterile environment, sequencing approaches have enabled the identification of a large number of bacteria in healthy and diseased lungs. The influence of the lung microbiota on respiratory infections has not been extensively studied so far and data on chlamydial infections are currently unavailable. In the present study, we speculate on how lung microbiota might interfere with acute and chronic infections by focusing exemplarily on the obligate intracellular C. pneumoniae. Furthermore, we consider changes in the gut microbiota as an additional player in the control of lung infections, especially in view the increasing evidence suggesting the involvement of the gut microbiota in various immunological processes throughout the human body.

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Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection

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

Cited by 342 publications

References 45 publications

Staphylococcus aureus colonization and non-influenza respiratory viruses: Interactions and synergism mechanisms

Staphylococcus aureus colonization and non-influenza respiratory viruses: Interactions and synergism mechanisms

Viral/bacterial respiratory tract co-infections in children

Impact of micro‐environmental changes on respiratory tract infections with intracellular bacteria

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