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Title: | Diagnosing enterovirus meningitis via blood transcriptomics: an alternative for lumbar puncture? | Authors: | Bartholomeus, Esther De Neuter, Nicolas Lemay, Annelies Pattyn, Luc Tuerlinckx, David Weynants, David Van Lede, Koen van Berlaer, Gerlant Bulckaert, Dominique Boiy, Tine Vander Auwera, Ann RAES, Marc Van der Linden, Dimitri Verhelst, Helene Van Steijn, Susanne Jonckheer, Tijl Dehoorne, Joke Joos, Rik Jansens, Hilde Suls, Arvid Van Damme, Pierre Laukens, Kris Mortier, Geert Meysman, Pieter OGUNJIMI, Benson |
Issue Date: | 2019 | Publisher: | BMC | Source: | Journal of translational medicine (Online), 17 (1) (Art N° 282) | Abstract: | Background Meningitis can be caused by several viruses and bacteria. Identifying the causative pathogen as quickly as possible is crucial to initiate the most optimal therapy, as acute bacterial meningitis is associated with a significant morbidity and mortality. Bacterial meningitis requires antibiotics, as opposed to enteroviral meningitis, which only requires supportive therapy. Clinical presentation is usually not sufficient to differentiate between viral and bacterial meningitis, thereby necessitating cerebrospinal fluid (CSF) analysis by PCR and/or time-consuming bacterial cultures. However, collecting CSF in children is not always feasible and a rather invasive procedure. Methods In 12 Belgian hospitals, we obtained acute blood samples from children with signs of meningitis (49 viral and 7 bacterial cases) (aged between 3 months and 16 years). After pathogen confirmation on CSF, the patient was asked to give a convalescent sample after recovery. 3 ' mRNA sequencing was performed to determine differentially expressed genes (DEGs) to create a host transcriptomic profile. Results Enteroviral meningitis cases displayed the largest upregulated fold change enrichment in type I interferon production, response and signaling pathways. Patients with bacterial meningitis showed a significant upregulation of genes related to macrophage and neutrophil activation. We found several significantly DEGs between enteroviral and bacterial meningitis. Random forest classification showed that we were able to differentiate enteroviral from bacterial meningitis with an AUC of 0.982 on held-out samples. Conclusions Enteroviral meningitis has an innate immunity signature with type 1 interferons as key players. Our classifier, based on blood host transcriptomic profiles of different meningitis cases, is a possible strong alternative for diagnosing enteroviral meningitis. | Notes: | Ogunjimi, B (reprint author), Univ Antwerp, AUDACIS, Antwerp, Belgium.; Ogunjimi, B (reprint author), Antwerp Univ Hosp, Dept Paediat, Edegem, Belgium.; Ogunjimi, B (reprint author), Antwerp Ctr Paediat Rheumatol & Autolnflammatory, Antwerp, Belgium.; Ogunjimi, B (reprint author), Univ Antwerp, CHERMID, Vaccine & Infect Dis Inst VAXINFECTIO, Antwerp, Belgium.; Ogunjimi, B (reprint author), Univ Antwerp, ACTIV, Vaccine & Infect Dis Inst VAXINFECTIO, Univ Pl 1, B-2610 Antwerp, Belgium.; Ogunjimi, B (reprint author), Univ Hosp Brussels, Dept Pediat, Jette, Belgium. benson.ogunjimi@uantwerpen.be |
Keywords: | Meningitis; Enterovirus; Bacterial meningitis; Differential gene;expression | Document URI: | http://hdl.handle.net/1942/31422 | e-ISSN: | 1479-5876 | DOI: | 10.1186/s12967-019-2037-6 | ISI #: | WOS:000483364200001 | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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s12967-019-2037-6.pdf | Published version | 1.05 MB | Adobe PDF | View/Open |
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