Cerebrospinal fluid markers to distinguish bacterial meningitis

Few hospitals in high malaria endemic countries in Africa have Background. the diagnostic capacity for clinically distinguishing acute bacterial meningitis (ABM) from cerebral malaria (CM). As a result, empirical use of antibiotics is necessary. A biochemical marker of ABM would facilitate precise clinical diagnosis and management of these infections and enable rational use of antibiotics. We used label-free protein quantification by mass spectrometry to Methods. identify cerebrospinal fluid (CSF) markers that distinguish ABM (n=37) from CM (n=22) in Kenyan children. Fold change (FC) and false discovery rates (FDR) were used to identify differentially expressed proteins. Subsequently, potential biomarkers were assessed for their ability to discriminate between ABM and CM using receiver operating characteristic (ROC) curves. The host CSF proteome response to ABM ( Results. Haemophilus influenza and ) is significantly different to CM. Fifty two Streptococcus pneumoniae proteins were differentially expressed (FDR<0.01, Log FC≥2), of which 83% (43/52) were upregulated in ABM compared to CM. Myeloperoxidase and lactotransferrin were present in 37 (100%) and 36 (97%) of ABM cases, respectively, but absent in CM (n=22). Area under the ROC curve (AUC), sensitivity, and specificity were assessed for myeloperoxidase (1, 1, and 1; 95% CI, 1-1) and lactotransferrin (0.98, 0.97, and 1; 95% CI, 0.96-1). Myeloperoxidase and lactotransferrin have a high potential to Conclusion. distinguish ABM from CM and thereby improve clinical management. Their validation requires a larger cohort of samples that includes other bacterial aetiologies of ABM. 1 1,2 1 1,3 1 1,4 1,5