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

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.

Managing Pediatric Asthma Exacerbations: The Role of Timely Systemic Corticosteroid Administration in Emergency Care Settings-A Multicentric Retrospective Study.

BACKGROUND: Asthma is the most prevalent chronic respiratory condition in children. An asthma exacerbation (AE) is a frequent reason for emergency department (ED) visits. An important step in the management of a moderate to severe AE is the administration of systemic corticosteroids (SCS) within 1 h after ED presentation. This study aimed to determine the timing of SCS administration and correlate this with the length of stay and oxygen therapy duration and to explore factors predicting timely administration. METHODS: This study used a retrospective multicenter observational design based on electronic medical records review. Children aged < 18 years, presenting to the ED with a moderate to severe AE were included. RESULTS: 205 patients were included. Only 28 patients received SCS within 60 min after ED arrival. The median time to SCS administration was 169 min (Q1 92-Q3 380). A correlation was found between timing and oxygen treatment duration (r = 0.363, p < 0.001) and length of stay (r = 0.368, p < 0.001). No patient characteristics predicted timely SCS administration. CONCLUSIONS: Three in four children who presented with a moderate to severe AE at the ED did not receive SCS within the first hour. A prolonged timing of SCS administration correlated with a prolonged length of stay and extended need for oxygen support.

Varied Age of First Presentation of Sickle Cell Disease: Case Presentations and Review.

Sickle cell disease is a multisystem condition characterized by hemolytic anemia and vasoocclusion. Not only are the symptoms of the first presentation but also the ages of presentation are very variable. Following three case reports, different causes of possible late presentation are discussed. Many factors are responsible for the age at which sickle cell disease is diagnosed: doctor's delay (unfamiliarity with the disease), patient's delay (education and financial position of the parents, cultural factors), high- versus low-resource country (availability of newborn screening), fetal hemoglobin, reticulocyte count, and genetic modulators, such as SCD genotype, alpha-thalassemia, fetal hemoglobin concentration, and G6PD deficiency. The individual course of sickle cell disease depends on (epi) genetic and environmental properties and the underlying interactions. In further studies, the role of each factor should be evaluated more deeply, and its use as a marker of disease severity or activity should be assessed.

Severe neutropenia in a breastfed infant: a case report and discussion of the differential diagnosis.

Neonatal neutropenia is regularly seen with variable etiology. We describe a breastfed infant with maternal medication use as a probable cause of neonatal neutropenia. An 8 days old exclusively breastfed female infant of Arab-Berber descent was referred to our hospital because of an infection of the umbilicus. Complete blood count showed a picture of severe isolated neutropenia. After initiating intravenous antibiotic treatment, the infection quickly resolved, but the isolated neutropenia persisted. Bone marrow aspiration indicated severe congenital neutropenia. The mother was known to have Crohn's disease, treated with methylprednisolone and adalimumab up to 3 months before delivery, and latent tuberculosis, for which she used isoniazid postnatally. Breast-feeding was terminated and filgrastim was started, with an increase of the neutrophilic count. After several weeks, filgrastim could be terminated. Bone marrow and complete blood count were repeated and were completely normal. This case report describes a very young breastfed female infant with severe neutropenia, causing an infection, in which maternal adalimumab use could not be excluded as a possible cause. Maternal isoniazid use is highly unlikely.