| dc.description.abstract |
Background. Few hospitals in high malaria endemic countries in Africa have 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. Methods. We used label-free
protein quantification by mass spectrometry to 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. Results. The host CSF proteome response to ABM
( Haemophilusinfluenza and Streptococcuspneumoniae) is significantly different to CM.
Fifty two 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). Conclusion. Myeloperoxidase and lactotransferrin have a high
potential to distinguish ABM from CM and thereby improve clinical management. Their
validation requires a larger cohort of samples that includes other bacterial aetiologies of
ABM. |
en_US |