Dataset Information

Early nasopharyngeal microbial signature associated with severe influenza in children: a retrospective pilot study.

ABSTRACT: A few studies have highlighted the importance of the respiratory microbiome in modulating the frequency and outcome of viral respiratory infections. However, there are insufficient data on the use of microbial signatures as prognostic biomarkers to predict respiratory disease outcomes. In this study, we aimed to evaluate whether specific bacterial community compositions in the nasopharynx of children at the time of hospitalization are associated with different influenza clinical outcomes. We utilized retrospective nasopharyngeal (NP) samples (n=36) collected at the time of hospital arrival from children who were infected with influenza virus and had been symptomatic for less than 2 days. Based on their clinical course, children were classified into two groups: patients with mild influenza, and patients with severe respiratory or neurological complications. We implemented custom 16S rRNA gene sequencing, metagenomic sequencing and computational analysis workflows to classify the bacteria present in NP specimens at the species level. We found that increased bacterial diversity in the nasopharynx of children was strongly associated with influenza severity. In addition, patients with severe influenza had decreased relative abundance of Staphylococcus aureus and increased abundance of Prevotella (including P. melaninogenica), Streptobacillus, Porphyromonas, Granulicatella (including G. elegans), Veillonella (including V. dispar), Fusobacterium and Haemophilus in their nasopharynx. This pilot study provides proof-of-concept data for the use of microbial signatures as prognostic biomarkers of influenza outcomes. Further large prospective cohort studies are needed to refine and validate the performance of such microbial signatures in clinical settings.

SUBMITTER: Langevin S

PROVIDER: S-EPMC7011740 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Early nasopharyngeal microbial signature associated with severe influenza in children: a retrospective pilot study.

Langevin Stanley S Pichon Maxime M Smith Elise E Morrison Juliet J Bent Zachary Z Green Richard R Barker Kristi K Solberg Owen O Gillet Yves Y Javouhey Etienne E Lina Bruno B Katze Michael G MG Josset Laurence L

The Journal of general virology 20170908 10

A few studies have highlighted the importance of the respiratory microbiome in modulating the frequency and outcome of viral respiratory infections. However, there are insufficient data on the use of microbial signatures as prognostic biomarkers to predict respiratory disease outcomes. In this study, we aimed to evaluate whether specific bacterial community compositions in the nasopharynx of children at the time of hospitalization are associated with different influenza clinical outcomes. We uti ...[more]

PMID: 28884664

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Project description:Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1.We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene.Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1beta), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-gamma) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-alpha, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients.While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness.

Project description:BackgroundInfluenza virus-associated encephalopathy (IAE) can lead to neurological sequela and mortality among children. Therefore, instant recognition and therapeutic intervention for IAE are crucial. In some clinical subtypes of IAE, steroid pulse therapy might be beneficial, especially when it is administered in the early phase. However, early identification of patients who may benefit from steroid pulse therapy is sometimes difficult. We aimed to assess the effectiveness of early steroid pulse therapy among children with IAE.MethodsIn this retrospective observational study, we used a national database that covers half of the acute care inpatients across Japan to identify inpatients aged ≤ 18 years with a diagnosis of IAE between July 2010 and March 2017. Unfavorable outcome was defined as a composite outcome of sequela including Japan Coma Scale ≥ 10 at discharge, requiring tracheostomy, mechanical ventilation, enteral tube feeding, rehabilitation at discharge, or in-hospital death. Propensity score matching was performed to compare unfavorable outcome and in-hospital mortality between patients with and without steroid pulse therapy within 2 days of admission.ResultsAmong 692 patients included in the study, the mean age was 5.8 years, and 55.8% were male. The overall in-hospital mortality was 1.3%, and the proportion of the unfavorable outcome was 15.0%. We observed no significant difference in the unfavorable outcome between matched patients (168 patients in each group) with and without early steroid pulse therapy (13.7% vs 8.3%; P = 0.16) or in-hospital mortality (0.6% vs 1.2%; P = 1.0).ConclusionsWe did not observe the effectiveness of early steroid pulse therapy on patient outcomes among children with IAE in our study population including all clinical subtypes of IAE. Further studies considering severity of illness are warranted to determine whether steroid pulse therapy is beneficial, especially for specific clinical subtypes of IAE.

Dataset Information

Early nasopharyngeal microbial signature associated with severe influenza in children: a retrospective pilot study.

Publications

Early nasopharyngeal microbial signature associated with severe influenza in children: a retrospective pilot study.

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