Project Details

Probiotics in infants with cystic fibrosis: Effects of early intervention

K. C. (Keith) Ooi, MBBS, Dip Paeds, PhD, FRACP

Summary

BACKGROUND: Recently, the value of gene expression analyses for infectious diseases has been illustrated in several clinical and experimental settings. Several studies were able to show a difference in gene expression signatures between different types of influenza, between different types of bacterial infections, between tuberculosis and other inflammatory or infectious diseases in African children and between some viral infections and some bacterial infections. GAP: Until now, no one has addressed the value of gene expression data in differentiating between viral and bacterial meningitis. HYPOTHESIS: We hypothesize that viral and bacterial meningitis activate different gene pathways. METHODS: In a multicenter prospective study we obtained whole blood gene expression data from children with a clinical presentation suggestive for meningitis. We recruited 47 patients with proven enterovirus meningitis and 6 patients with proven bacterial meningitis (2 N meningitides, 3 Str Pneumoniae, 1 H Influenzae). We recruited 2 additional patients with another viral meningitis (varicella-zoster virus and herpes virus), 1 patient with pyelonephritis, 1 patient with lyme meningitis and 15 patients with rheumatologic conditions (in order to assess specificity of our classifier, see eg Herberg er al, JAMA, 2016). We used R (in particular DESeq2 for our data analyses) to identify differentially expressed genes (DEGs). RESULTS: We were able to build a classifier that is capable in differentiating enterovirus from bacterial meningitis. IMPACT: We believe that our research will majorly transform the assessment of patients presenting with signs of meningitis and will add to the development of new scoring systems in developed countries. Gene expression sequencing will add to the differentiation between viral and bacterial origins of meningitis in academic centers (i.e. where RNA micro-array analyses are possible) on the short term (< 3 years), and in other large hospitals on the longer term (<7 years). We believe that our proposed methodology will be of particular importance in situations were CSF sampling is not feasible or advisable. Furthermore, our study will allow us to develop a better understanding of the pathophysiology of and host immune response against meningitis.