Publications by authors named "O Ramilo"

245 Publications

Nasopharyngeal Codetection of H. influenzae and S. pneumoniae and Respiratory Syncytial Virus Disease Outcomes in Children.

J Infect Dis 2021 Sep 20. Epub 2021 Sep 20.

Division of Infectious Diseases, Department of Pediatrics, Nationwide Children's Hospital-The Ohio State University College of Medicine, Columbus, OH, USA.

Background: The role of nasopharyngeal bacteria on RSV disease has been underestimated. We measured the frequency and quantitative detection of potentially pathogenic bacteria in the upper respiratory tract of infants with RSV infection over seven respiratory seasons, and their impact on clinical outcomes.

Methods: Children <2 years old with mild (outpatients; n=115) or severe (inpatients; n=566) RSV infection, and matched healthy controls (n=161) were prospectively enrolled. Nasopharyngeal samples were obtained for RSV, S. pneumoniae, S. aureus, M. catarrhalis, and H. influenzae detection and quantitation by PCR. Multivariable models were constructed to identify variables predictive of severe disease.

Results: S. pneumoniae, H. influenzae, and M. catarrhalis, but not S. aureus, were detected more frequently in RSV-infected children (84%) than healthy controls (46%; p<0.001). Detection of S. pneumoniae and/or H. influenzae was associated with fever, more frequent antibiotic treatment, worse radiologic findings, and higher neutrophil counts (p<0.01). In adjusted analyses S. pneumoniae/H. influenzae co-detection was associated with greater odds (OR; 95% CI) of hospitalization (2.25 [1.07-4.74), higher disease severity scores (1.93 [1.14-3.26]), prolonged oxygen administration (2.23 [1.01-4.91]), and longer hospitalization (2.53 [1.33-4.79]).

Conclusions: Nasopharyngeal co-detection of S. pneumoniae and H. influenzae in infants with RSV infection is associated with increased disease severity.
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http://dx.doi.org/10.1093/infdis/jiab481DOI Listing
September 2021

Development of a fixed module repertoire for the analysis and interpretation of blood transcriptome data.

Nat Commun 2021 07 19;12(1):4385. Epub 2021 Jul 19.

Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, USA.

As the capacity for generating large-scale molecular profiling data continues to grow, the ability to extract meaningful biological knowledge from it remains a limitation. Here, we describe the development of a new fixed repertoire of transcriptional modules, BloodGen3, that is designed to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome data. The construction of this repertoire is based on co-clustering patterns observed across sixteen immunological and physiological states encompassing 985 blood transcriptome profiles. Interpretation is supported by customized resources, including module-level analysis workflows, fingerprint grid plot visualizations, interactive web applications and an extensive annotation framework comprising functional profiling reports and reference transcriptional profiles. Taken together, this well-characterized and well-supported transcriptional module repertoire can be employed for the interpretation and benchmarking of blood transcriptome profiles within and across patient cohorts. Blood transcriptome fingerprints for the 16 reference cohorts can be accessed interactively via:  https://drinchai.shinyapps.io/BloodGen3Module/ .
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http://dx.doi.org/10.1038/s41467-021-24584-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289976PMC
July 2021

Sex Differences in Blood Transcriptional Profiles and Clinical Phenotypes in Pediatric Patients with Eosinophilic Esophagitis.

J Allergy Clin Immunol Pract 2021 Sep 12;9(9):3350-3358.e8. Epub 2021 Jul 12.

Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio; Division of Infectious Diseases, Department of Pediatrics, Nationwide Children's Hospital and the Ohio State University College of Medicine, Columbus, Ohio.

Background: Eosinophilic esophagitis (EoE) is an increasingly recognized, chronic inflammatory disease. Recent reports suggest clinical differences between males and females.

Objective: To define the relevant molecular pathways that could be related to clinical phenotypes in children with EoE.

Methods: We performed blood RNA expression analysis in children with newly diagnosed EoE and matched, healthy controls, and applied bioinformatics tools to define EoE host immune biosignatures. Questionnaires and medical records were used to characterize symptoms, esophagogastroduodenoscopy results, and treatment response.

Results: Forty-one subjects (aged 2-17 years) were enrolled; the cohort consisted of 27 males and 14 females. Patients were randomly divided into a discovery cohort (21 EoE patients and 12 controls) that identified 544 significant differentially expressed transcripts (P ≤ .01; 1.25-fold change). Those 544 transcripts correctly classified most EoE patients in the validation cohort (n = 20) from healthy controls. Global transcriptional perturbation relative to healthy controls, Molecular Distance to Health scores were greater in EoE patients than controls (P = .003). When we analyzed subjects based on age and sex, males 13 years of age and older were more likely to have food impactions (P = .033) and to have higher endoscopic severity scores (P = .036). Separate group comparisons according to sex identified 294 differentially expressed transcripts in males and 643 transcripts in female EoE patients. Of those, 37 genes were shared and similarly expressed irrespective of sex.

Conclusions: Whole blood transcriptional analysis represents a promising noninvasive tool to assess activity of the immune/inflammatory response in children with EoE. Male and female EoE patients showed robust differences in gene expression suggesting distinct pathogenic endotypes.
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http://dx.doi.org/10.1016/j.jaip.2021.06.043DOI Listing
September 2021

Host transcriptional signatures as predictive markers of infection in children.

Curr Opin Infect Dis 2021 Oct;34(5):552-558

Division of Pediatric Infectious Diseases and Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital and The Ohio State University, Columbus, Ohio, USA.

Purpose Of Review: Analyses of the host transcriptional response to infection has proved to be an alternative diagnostic strategy to standard direct pathogen detection. This review summarizes the value of applying blood and mucosal transcriptome analyses for the diagnosis and management of children with viral and bacterial infections.

Recent Findings: Over the years, studies have validated the concept that RNA transcriptional profiles derived from children with infectious diseases carry a pathogen-specific biosignature that can be qualitatively and quantitively measured. These biosignatures can be translated into a biologically meaningful context to improve patient diagnosis, as seen in children with tuberculosis, rhinovirus infections, febrile infants and children with pneumonia; understand disease pathogenesis (i.e. congenital CMV) and objectively classify patients according to clinical severity (i.e. respiratory syncytial virus).

Summary: The global assessment of host RNA transcriptional immune responses has improved our understanding of the host-pathogen interactions in the clinical setting. It has shown the potential to be used in clinical situations wherein our current diagnostic tools are inadequate, guiding the diagnosis and classification of children with infectious diseases.
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http://dx.doi.org/10.1097/QCO.0000000000000750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446306PMC
October 2021

Early changes in interferon gene expression and antibody responses following influenza vaccination in pregnant women.

J Infect Dis 2021 Jul 1. Epub 2021 Jul 1.

Center for Vaccines and Immunity, Columbus, Ohio 43205, USA.

Background: Influenza immunization during pregnancy provides protection to the mother and the infant. Studies in adults and children with inactivated influenza vaccine (IIV) have identified changes in immune gene expression that correlated with antibody responses.

Objective: To define baseline blood transcriptional profiles and changes induced by IIV in pregnant women and to identify correlates with antibody responses.

Methods: Pregnant women were immunized with IIV during the 2013-14 and 2014-15 seasons. Blood samples were collected on day (d) 0 (pre-vaccination), d1 and d7 post-vaccination for transcriptional profile analyses; and d0, d30, delivery and cord blood to measure antibody titers.

Results: Transcriptional analysis demonstrated overexpression of interferon-stimulated genes (ISGs) on d1 and of plasma cell genes on d7. Pre-vaccination ISGs expression and ISGs over-expressed on d1 significantly correlated with increased H3N2, B Yamagata and B Victoria antibody titers. Plasma-cell gene expression on d7 correlated with increased B Yamagata and B Victoria antibody titers. Compared with women vaccinated during the previous influenza season, women who were not vaccinated the prior year showed more frequent significant correlations between ISGs and antibody titers.

Conclusions: Influenza vaccination in pregnant women resulted in enhanced expression of ISGs and plasma cell genes that correlated with antibody responses.
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http://dx.doi.org/10.1093/infdis/jiab345DOI Listing
July 2021
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