Cerebrospinal fluid markers to distinguish bacterial meningitis from cerebral malaria in children

Wellcome Open Research

article

James M. Njunge¹  Ian N. Oyaro¹  Nelson K. Kibinge¹  Martin K. Rono¹  Symon M. Kariuki¹  Charles R. Newton¹  James A. Berkley¹  Evelyn N. Gitau¹ 

[1] KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research Coast;University of Nairobi;Pwani University Health and Research Institute, Pwani University;Department of Psychiatry, Medical Sciences Division, University of Oxford;Centre for Tropical Medicine and Global Health, University of Oxford;Alliance for Accelerating Excellence in Science in Africa

关键词: Biomarkers;    Acute Bacterial Meningitis;    Cerebral Malaria;    CSF;    proteomics;    Myeloperoxidase;    Lactotransferrin;   

DOI  :  10.12688/wellcomeopenres.11958.2

学科分类：内科医学

来源: Wellcome

【 摘 要 】

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 andStreptococcuspneumoniae) 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.

【 授权许可】

CC BY