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Fig 1.

Unadjusted association of CSF white blood cells with CSF and blood clinical features.

A (i)–levels of stratified CSF white blood cells. A (ii)–levels of CSF proteins. B (i)–levels of peripheral blood CD4+ T cells. B (ii)–levels of peripheral blood–CD8+ T cells. C–CSF fungal burden. D–peripheral white blood cells. The interlinking bars–shows two variable unpaired comparison. The flat bar shows three variables analysis of variance (ANOVA) comparisons. The error bars show median and 95% confidence intervals (CI). A-(i) both the medians and interquartile range was 4 cells/μL, (reported as <5 cells/μL). Asterisk *—show statistically significant variables reported at p-value <0.050, at 95% CI. §The flat bar shows three variables analysis using ANOVA test.

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Table 1.

Participants Baseline Demographics and Clinical Features by CSF Leukocytes.

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Fig 2.

Unadjusted Correlation of CSF cytokines and chemokine levels with CSF leukocyte counts.

A- Th1 cytokines; A (i)—Interleukin 2, A (ii)—Interferon gamma, A (iii)—Tumor necrosis factor alpha. B—Th17 cytokine, IL-17A. C–Immune regulatory elements; (i)–Interleukin 10 (IL-10), and programmed death 1 ligand (PD-L1). D Chemokines; D (i) CXCL10/IP-10 and D (ii)–CCL11/Eotaxin. The CSF white cells; (≤50 cells/μL; n = 318), (51–200 cells/μL; n = 57) and (201–500 cells/μL; n = 26) participants. The interlinking bars–shows two variable unpaired comparison. Error bars–show median and 95% CI. The flat bar shows three variables ANOVA comparisons. Asterisks *—show statistically significant variables reported at p-value <0.050, at 95% confidence intervals.

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Fig 3.

Correlation of CSF white cells with 18-week survival.

A–survival by CSF white cell intervals (<5 cells/μL; n = 245), (5–20 cells/μL; n = 31), (21–50 cells/μL; n = 42), (51–100 cells/μL; n = 26), (101–200 cells/μL; n = 31), and (201–500 cells/μL; n = 26). B—18 weeks survival by CSF white cells; (≤50 cells/μL; n = 318), (51–200 cells/μL; n = 57) and (201–500 cells/μL; n = 26) participants. C– 18-week survival with CSF ≤50 cells/μL. D (i-iii)–illustrates trends in immune responses between survivors and those who died during 18-weeks of follow-up. Statistics—Mann-Whitney unpaired t-test. *—show statically significant variables. NS- not significant. Error bars–show 95% confidence intervals. p-values, p<0.050 were statistically significant.

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Fig 4.

Principal Component Analyses showing data clusters and variations on principal component, PC1 and PC2.

(A)—(I & ii) orthogonal Eigenvectors showing clustering and variation of the principal components between CSF fungal burden and survival with the expressed cytokine/chemokine profile. (i & iii) diagonal Eigenvectors showing clustering and variation of the principal components between CSF fungal burden and survival with CSF fungal burden and host survival and CSF white cells, CSF protein, peripheral white cells, CD4+ and CD8+ T cells. Eigenvectors projection at >5 from the center of the plane shows greater power of the principal components to predict the outcome. Also, the furthest the component to the cluster variation among all principal components. C—contribution of each principal component to the cluster variation among a subset (cytokines and chemokines) principal components.

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Table 2.

Independent Immune Predictors of the Frequency of Cerebrospinal Fluid Leukocyte influx with Cryptococcal Meningitis.

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Table 3.

Independent Immune Predictors of Survival with Cryptococcal Meningitis.

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Table 4.

Programmed death ligand 1 independent predictors of CSF cytokine and chemokine responses.

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