Cerebrospinal fluid markers to distinguish bacterial meningitis from cerebral malaria in children [version 2; referees: 2 approved]
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 c...
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| Format: | Article |
| Language: | English |
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Wellcome
2017-09-01
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| Series: | Wellcome Open Research |
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| Online Access: | https://wellcomeopenresearch.org/articles/2-47/v2 |
| _version_ | 1828303598514077696 |
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| author | James M. Njunge Ian N. Oyaro Nelson K. Kibinge Martin K. Rono Symon M. Kariuki Charles R. Newton James A. Berkley Evelyn N. Gitau |
| author_facet | James M. Njunge Ian N. Oyaro Nelson K. Kibinge Martin K. Rono Symon M. Kariuki Charles R. Newton James A. Berkley Evelyn N. Gitau |
| author_sort | James M. Njunge |
| collection | DOAJ |
| description | 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 (Haemophilus influenza and Streptococcus pneumoniae) 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. |
| first_indexed | 2024-04-13T13:56:31Z |
| format | Article |
| id | doaj.art-45e7cc390d4741a9be50ed0c7920e4e5 |
| institution | Directory Open Access Journal |
| issn | 2398-502X |
| language | English |
| last_indexed | 2024-04-13T13:56:31Z |
| publishDate | 2017-09-01 |
| publisher | Wellcome |
| record_format | Article |
| series | Wellcome Open Research |
| spelling | doaj.art-45e7cc390d4741a9be50ed0c7920e4e52022-12-22T02:44:10ZengWellcomeWellcome Open Research2398-502X2017-09-01210.12688/wellcomeopenres.11958.213799Cerebrospinal fluid markers to distinguish bacterial meningitis from cerebral malaria in children [version 2; referees: 2 approved]James M. Njunge0Ian N. Oyaro1Nelson K. Kibinge2Martin K. Rono3Symon M. Kariuki4Charles R. Newton5James A. Berkley6Evelyn N. Gitau7KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research Coast, Kilifi, KenyaUniversity of Nairobi, Nairobi, KenyaKEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research Coast, Kilifi, KenyaPwani University Health and Research Institute, Pwani University, Kilifi, KenyaKEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research Coast, Kilifi, KenyaDepartment of Psychiatry, Medical Sciences Division, University of Oxford, Oxford, OX3 7JX, UKCentre for Tropical Medicine and Global Health, University of Oxford, Oxford, OX3 7FZ, UKAlliance for Accelerating Excellence in Science in Africa (AESA), Nairobi, KenyaBackground. 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 (Haemophilus influenza and Streptococcus pneumoniae) 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.https://wellcomeopenresearch.org/articles/2-47/v2Bacterial InfectionsImmunological BiomarkersParasitology |
| spellingShingle | James M. Njunge Ian N. Oyaro Nelson K. Kibinge Martin K. Rono Symon M. Kariuki Charles R. Newton James A. Berkley Evelyn N. Gitau Cerebrospinal fluid markers to distinguish bacterial meningitis from cerebral malaria in children [version 2; referees: 2 approved] Wellcome Open Research Bacterial Infections Immunological Biomarkers Parasitology |
| title | Cerebrospinal fluid markers to distinguish bacterial meningitis from cerebral malaria in children [version 2; referees: 2 approved] |
| title_full | Cerebrospinal fluid markers to distinguish bacterial meningitis from cerebral malaria in children [version 2; referees: 2 approved] |
| title_fullStr | Cerebrospinal fluid markers to distinguish bacterial meningitis from cerebral malaria in children [version 2; referees: 2 approved] |
| title_full_unstemmed | Cerebrospinal fluid markers to distinguish bacterial meningitis from cerebral malaria in children [version 2; referees: 2 approved] |
| title_short | Cerebrospinal fluid markers to distinguish bacterial meningitis from cerebral malaria in children [version 2; referees: 2 approved] |
| title_sort | cerebrospinal fluid markers to distinguish bacterial meningitis from cerebral malaria in children version 2 referees 2 approved |
| topic | Bacterial Infections Immunological Biomarkers Parasitology |
| url | https://wellcomeopenresearch.org/articles/2-47/v2 |
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