Fig 1.
Flow chart of the study design and classification of participants.
CRF: case report form; TBM: tuberculous meningitis; ‘not TBM’: children included on suspicion of meningitis and had an alternative diagnosis after investigations (other meningitis and no-meningitis). The ‘not TBM’ group included 2 children with bacterial meningitis, 2 with viral meningitis, and children with no-meningitis (Table 1). Children diagnosed with TBM were further classified as TBM with stroke and no stroke based on brain imaging findings at baseline.
Table 1.
Clinical and demographic characteristics of the study participants.
Fig 2.
The concentrations of sVCAM-1 (A), MMP-1 (B), sRAGE (C), CXCL10/IP-10 (D), PDGF-AA (E), and lipocalin-2/NGAL (F) detected in cerebrospinal fluid samples from children who had TBM-related stroke and TBM without stroke (no-stroke). Horizontal bars depict median values and error bars are interquartile ranges. The p-values represent a comparison between TBM with stroke and TBM without stroke. The p-values shown were not corrected for multiple testing.
Table 2.
Expression of CSF host protein biomarkers amongst study participants with TBM and stroke/no stroke at admission, and utility of individual CSF host protein biomarkers to indicate stroke in TBM patients.
The mean values shown (95% confidence intervals in brackets) are the least square (LS) means. Markers showing significant differences (p-value<0.05) or trends (0.05<p-value≤0.09) between the TBM patients with stroke and no stroke are shown. The differences in the concentrations of all other host markers are shown in S2 Table. #reported in ng/ml, all other markers are reported in pg/ml.
Fig 3.
Receiver operator characteristic (ROC) curves showing the accuracies of baseline CSF lipocalin-2/NGAL (A), sVCAM-1 (B), sRAGE (C), MMP-1 (D), CXCL10/IP-10 (E), and PDGF-AA (F) in indicating stroke among children diagnosed with TBM. ROC curves for analytes with AUC≥0.70 are shown.
Fig 4.
Accuracy of the 4-marker CSF host protein biosignature (VEGF-A, complement component 5a, complement factor 1 and BDNF) in indicating stroke amongst children with TBM.
(A) Scatter plot depicting the separation of children as TBM with stroke/no-stroke using the 4-marker biosignature. (B) ROC curve depicting the performance of the 4-marker biosignature. Red squares: TBM-related stroke. Blue circles: TBM, no stroke.
Fig 5.
The concentrations of D-dimer (A), IL-13 (B), ADAMTS13 (C), CCL2/MCP-1 (D), SAA (E), Ferritin (F) and GDF-15 (G) detected in serum samples from children who had TBM-related stroke and TBM without stroke (no-stroke). Horizontal bars depict median values and error bars are interquartile ranges. The p-values represent a comparison between TBM with stroke and TBM without stroke. The p-values shown were not corrected for multiple testing.
Table 3.
Expression of serum host protein markers amongst study participants with TBM and stroke/no stroke at admission, and their accuracies in indicating stroke in TBM patients.
The mean values shown (95% confidence intervals in brackets) are the least square (LS) means. Markers showing significant difference (p-value<0.05) or showing trends (0.05<p-value≤0.09) between the TBM patients with stroke and no stroke are shown. The expressions of all other host markers are shown in S3 Table. #reported in ng/ml, all other markers are reported in pg/ml.
Fig 6.
Receiver operator characteristic (ROC) curves showing the accuracies of baseline serum GDF-15 (A), D-dimer (B), ADAMTS13 (C), CCL2/MCP-1 (D), Ferritin (E), and SAA (F) in indicating stroke among children diagnosed with TBM. ROC curves for analytes with AUC≥0.75 are shown.
Fig 7.
Accuracy of the 3-marker serum host protein biosignature (IL-1β, IL-4, and Alpha-2-antitrypsin) in indicating stroke in children with TBM.
(A) Scatterplot depicting the separation of children as TBM with stroke or no stroke using the 3-marker biosignature. (B) ROC curve depicting the performance of the 3-marker biosignature. Red squares: TBM-related stroke. Blue circles: TBM, no stroke.