Baseline clinical characteristics of participants.

<p>*For difference between all 3 groups by one way analysis of variance.</p><p>†Mean (95% confidence interval).</p><p>‡Median (interquartile range).</p

Plasma assessment of tryptophan catabolism.

<p>The concentration of plasma tryptophan (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021185#pone-0021185-g001" target="_blank">Fig. 1A</a>), kynurenine (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021185#pone-0021185-g001" target="_blank">Fig. 1B</a>) and the KT ratio (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021185#pone-0021185-g001" target="_blank">Fig. 1C</a>) in 50 severe sepsis patients, 30 non-severe sepsis patients and 40 hospital controls. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021185#pone-0021185-g001" target="_blank">Fig. 1D</a> shows the KT ratio in severe sepsis patients on admission (n = 50), day 2 (n = 34) and day 7 (n = 16). The KT ratio is determined by dividing the plasma kynurenine concentration (µmol/L) by the plasma tryptophan concentration (µmol/L) and multiplying the quotient by 1000. Horizontal lines represent median values for the group. P value analysis in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021185#pone-0021185-g001" target="_blank">Figs. 1A–C</a> used a Mann Whitney test, and in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021185#pone-0021185-g001" target="_blank">Fig. 1D</a>, a paired Wilcoxon test.</p

Immunological characteristics of participants (median and interquartile range).

<p>*p values, all sepsis vs controls, Mann Whitney test.</p><p>†Performed in a subset of patients representative of the entire cohort, as described in methods and results. Severe sepsis n = 11, non-severe sepsis n = 12, control n = 4.</p

Proposed model of tryptophan catabolism in sepsis.

<p>IDO = Indoleamine 2,3-dioxygenase, IL6 = interleukin-6, IL10 = interleukin-10, IFN-γ = interferon gamma and NO = nitric oxide.</p

Baseline characteristics.

<p>a – by Chi² test for difference between all 3 groups.</p><p>b – Mean (sd).</p><p>c – n (%).</p><p>d – Median (Interquartile range).</p

Longitudinal results in subjects with sepsis.

<p>Note: ADMA = Asymmetric dimethylarginine. RH-PAT index = Reactive hyperaemia peripheral arterial tonometry index. SDMA = Symmetric dimethylarginine. IL-6 = Interleukin 6. SOFA score = Sequential Organ Failure Assessment Score.</p

Ratio of L-arginine to asymmetric dimethylarginine in baseline plasma samples, according to disease category, compared with baseline microvascular reactivity according to disease category.

<p>Panel A shows plasma arginine: ADMA ratio and panel B shows reactive hyperaemia peripheral arterial tonometry index. P values represent comparisons between groups. Solid circles represent individual sepsis subjects and solid triangles represent individual control subjects. Horizontal lines represent median group values, and error bars represent interquartile range. In panel B, solid circles represent mean group values for sepsis subjects, and the solid triangle for control subjects. Error bars represent standard error of the mean.</p

Plasma asymmetric dimethylarginine and related variables at time of initial measurement.

<p>a. median (Interquartile range);</p><p>b. n = septic shock 19, sepsis without shock 37, controls 27;</p><p>c. n (%).</p><p>d. mean (sd).</p

Plasma dimethylarginine concentrations in each group on enrollment (ANOVA: p<0.001).

<p><b>A.</b> Plasma asymmetric dimethylarginine (ADMA) concentrations in each group on enrollment (ANOVA: p<0.001). In the severe malaria group, open circles represent fatal cases and closed circles survivors. Horizontal lines indicate mean for each group. <b>B.</b> Plasma symmetric dimethylarginine (SDMA) concentrations in each group on enrollment (ANOVA: p<0.001). In the severe malaria group, open circles represent fatal cases and closed circles survivors. Horizontal lines indicate mean for each group.</p

Top panel is the nonparametric receiver operating curve (ROC) assessing asymmetrical dimethylarginine (AUROC, 0.85; 95%CI 0.71–0.99) and the bottom panel venous lactate (AUROC 0.63; 95%CI 0.41–0.83) as prognostic markers for mortality in severe malaria (p = 0.003).

<p>Top panel is the nonparametric receiver operating curve (ROC) assessing asymmetrical dimethylarginine (AUROC, 0.85; 95%CI 0.71–0.99) and the bottom panel venous lactate (AUROC 0.63; 95%CI 0.41–0.83) as prognostic markers for mortality in severe malaria (p = 0.003).</p