Dataset Information

Diagnosing enterovirus meningitis via blood transcriptomics: an alternative for lumbar puncture?

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.

SUBMITTER: Bartholomeus E

PROVIDER: S-EPMC6708255 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Diagnosing enterovirus meningitis via blood transcriptomics: an alternative for lumbar puncture?

Bartholomeus Esther E De Neuter Nicolas N Lemay Annelies A Pattyn Luc L Tuerlinckx David D Weynants David D Van Lede Koen K van Berlaer Gerlant G Bulckaert Dominique D Boiy Tine T Vander Auwera Ann A Raes Marc M Van der Linden Dimitri D Verhelst Helene H Van Steijn Susanne S Jonckheer Tijl T Dehoorne Joke J Joos Rik R Jansens Hilde H Suls Arvid A Van Damme Pierre P Laukens Kris K Mortier Geert G Meysman Pieter P Ogunjimi Benson B

Journal of translational medicine 20190823 1

<h4>Background</h4>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, th ...[more]

PMID: 31443725

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Project description:BackgroundThe ratio of cerebrospinal fluid (CSF) to peripheral blood glucose at the same period is an important index for diagnosing and monitoring the efficacy of central nervous system infection, especially bacterial meningitis. Some guidelines refer that blood glucose measurement should be carried out before lumbar puncture. The main reason is to avoid possible effect of stress response induced by lumbar puncture on the level of blood glucose. However, there is no consensus on whether it should be followed in actual clinical work, since up to now no research work having been published on whether lumbar puncture will induce the changes on blood glucose. Our study aimed to investigate the changes of peripheral blood glucose before and after lumbar puncture.MethodsIn order to clarify the influence of timing of peripheral blood glucose measurement at the same period of lumbar puncture, a prospective study was conducted including children with an age range from 2 months to 12 years old in the neurology department of a medical center. For those children who need lumbar puncture due to their illness, their blood glucose was measured within 5 min before and after lumbar puncture, respectively. The blood glucose level and the ratio of CSF to blood glucose before and after lumbar puncture were compared. Meanwhile, the patients were divided into different groups according to the factors of sex, age and sedation or not for further comparison. All statistical analyses of the data were performed using SPSS version 26.0 for Windows.ResultsIn total, 101 children who needed lumbar puncture during hospitalization from January 1, 2021, to October 1, 2021, were recruited with 65 male and 36 female respectively. There was no significant difference on the level of blood glucose, CSF to blood glucose ratio before and after lumbar puncture among the children (p > 0.05). No differences were observed within different groups (sex, age, sedation or not) either.ConclusionIt is unnecessary to emphasize blood glucose measurement should be carried out before lumbar puncture, especially for pediatric patients. From the perspective of facilitating smoother cerebrospinal fluid puncture in children, blood glucose measurement after lumbar puncture might be a better choice.

Project description:Neuroinflammation is evident and one of the primary induced responses after central nervous system (CNS) injury, lumbar puncture and CNS surgery. In rare cases, complications could arise after the lumbar puncture or CNS surgery leading to inflammation, bleeding or other problems such as cerebrospinal fluid (CSF) leakage. The present dataset describes the occurrence of such a condition after the dura breakage or postoperative complication leading to the development of neuroinflammation in the adult Wistar rats. Therefore, objective of the study is to report such a rare condition and detect the most reliable glial proteins upregulated 2-3 weeks after the lumbar puncture which may help the neuroscience community to a better understanding their cause of action. In response to neuroinflammation, glial cells leak into the extracellular space, where they can be identified in the CSF or serum and may act as diagnostic biomarkers. Laminectomy was performed at the thoraco-lumbar (T12-L1) region and the dura was punctured. After that, the exposed part was covered with silica gel and adhesive followed by dental cement. The skin was closed using sterile sutures. After, the rats were given buprenorphine (0.05 mg/kg, every 8 h for 3 days) and carprofen (5 mg/kg, once a day for 5 days) as analgesic and anti-inflammatory and baytril (5 mg/kg, once a day for 10 days) as antibiotic drugs. Note, the buprenorphine and lidocaine were also given before starting the procedure. After the laminectomy, the functional outcomes of the rats were tested (starting from the day of surgery to the last day) and the rats which were locomoting normally using all the limbs were included in the study. In case of any decompression, the functional outcomes showing any kind of laming or partial paralysis of hindlimbs were excluded from the study. Unexpected neuroinflammation has occurred 2-3 weeks after performing the given procedure. Data presented in the article implicate active microglia measured by using protein biomarker such as Iba-1 [1, 3] and astrocytes measured by using Glial fibrillary acidic protein (GFAP) [2, 3] and S100 (strongly targets S100B and weakly A1) [7, 8] in the CSF collected two-three weeks after the laminectomy and dura breakage from the adult rats. Later paraformaldehyde (PFA) fixed spinal cord slices were also collected from the animals and immunolabelled with the same biomarkers. Western blots were performed with the collected CSF which showed high expression of glial markers such as GFAP, Iba-1 and S100 which has shown to target S100B with no expression of A1 (or A2, play an important role in neuroprotection) astrocytes which have recently been shown to be produced by microglia at the site of injury [9]. However, S100B [10] and GFAP [2] are known to be adequately discharged by the distinct cells in stress conditions which seems to occur in the present report. In addition, the spinal slices immunolabelled with the same biomarkers also showed increased expression of glia. Cross-talk between microglia-astrocyte in CNS stress is crucial for the neurons to survive and function after the injury. Reactive microglia (shown by high Iba-1 expression) leading to microgliosis comprise the first line of defense to phagocytose the dead cells [11]. Astrocytes act as the second line of defense leading to a process known as astrogliosis and upregulate GFAP and S100B to limit the damage [12]. Further studies are needed to explain the molecular mechanism/s of different astrocytes release such as A2 and their interaction with microglia after the lumbar puncture.

Dataset Information

Diagnosing enterovirus meningitis via blood transcriptomics: an alternative for lumbar puncture?

Background

Methods

Results

Conclusions

Publications

Diagnosing enterovirus meningitis via blood transcriptomics: an alternative for lumbar puncture?

Similar Datasets

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