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
Departments of 1Infectious Diseases, 2Clinical Immunology, and 3Clinical Microbiology, 4Finsen Laboratory, 5Copenhagen Muscle Research Centre, and 6Centre for Medical Parasitology, Rigshospitalet, Copenhagen, Denmark; 7Department of Child Health, Korle‐Bu Teaching Hospital, Accra, and 8Immunology Unit, Noguchi Memorial Institute for Medical Research, Legon, Ghana
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]; 
). The highest concentrations were found in patients with malaria who died (
) or had complicated malaria (
). 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]; 
). 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.
Received 17 August 2004; accepted 8 November 2004; electronically published 14 March 2005.
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Online publication date: 1-Aug-2009.
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Financial support: Enhancement of Research Capacity program of the Danish International Development Assistance; Danish Council for Development Research; Danish Medical Research Council; World Health Organization/Special Programme for Research and Training in Tropical Diseases/Multilateral Initiative on Malaria (project 980037); European Union International Cooperation–Developing Countries (project ERB 3514 PL973009).