Plasma concentrations of soluble urokinase-type plasminogen activator receptor are increased in patients with malaria and are associated with a poor clinical or a fatal outcome

Background. Blood concentrations of soluble urokinase-type plasminogen activator receptor (suPAR) are increased in conditions with immune activation, and high concentrations of suPAR often predict a poor clinical outcome. This study explored the hypothesis that high plasma concentrations of suPAR are associated with disease severity in malaria. Methods. At admission to the hospital, plasma concentrations of suPAR were measured by ELISA in samples from 645 African children with clinical symptoms of malaria: 478 had malaria, and 167 had a blood film negative for Plasmodium parasites. Fourteen healthy children were included for comparison. Results. Plasma concentrations of suPAR were higher in patients with malaria (median, 7.90 ng/mL [interquartile range {IQR}, 6.56-9.15 ng/mL]), compared with those in plasmodium-negative patients (median, 5.59 ng/mL [IQR, 4.54-8.16 ng/mL];) and those in healthy children (3.94 ng/mL [IQR, 3.46-4.82 ng/mL]; P < .001). The highest concentrations were found in patients with malaria who died (P = .008) or had complicated malaria (P < .001). In univariate logistic regression analysis, a 1 ng/mL increase in plasma concentration of suPAR was associated with increased risk of mortality (odds ratio, 1.42 [95% confidence interval, 1.09-1.86]; P = .009). In multivariate linear regression analysis, lower platelet count, lower hemoglobin level, and higher neutrophil count were independently associated with a higher plasma concentration of suPAR. Conclusions. If the plasma concentration of suPAR reflects the extent of parasite-induced immune activation, this may explain why a high concentration of suPAR is associated with a poor clinical outcome in patients with malaria.