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]; P < .001) 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.
Ostrowski
Sisse R
SR
Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark. sro@dadlnet.dk
Ullum
Henrik
H
Goka
Bamenla Q
BQ
Høyer-Hansen
Gunilla
G
Obeng-Adjei
George
G
Pedersen
Bente K
BK
Akanmori
Bartholomew D
BD
Kurtzhals
Jørgen A L
JA
D000818:Animals; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D016015:Logistic Models; D008288:Malaria / Q000097:blood* / Q000401:mortality* / Q000469:parasitology / Q000503:physiopathology; D008297:Male; D016017:Odds Ratio; D010961:Plasmodium / Q000502:physiology; D011956:Receptors, Cell Surface / Q000097:blood*; D055293:Receptors, Urokinase Plasminogen Activator; D012306:Risk; D012995:Solubility
C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator