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Copeptin does not accurately predict disease severity in imported malaria

Marlies E van Wolfswinkel1, Dennis A Hesselink2, Ewout J Hoorn2, Yolanda B de Rijke3, Rob Koelewijn4, Jaap J van Hellemond45 and Perry JJ van Genderen1*

Author Affiliations

1 Department of Internal Medicine, Harbour Hospital and Institute for Tropical Diseases, Haringvliet 2, 3011 TD Rotterdam, The Netherlands

2 Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

3 Department of Clinical Chemistry, Erasmus MC, Rotterdam, The Netherlands

4 Laboratory of Parasitology, Harbour Hospital and Institute for Tropical Diseases, Rotterdam, The Netherlands

5 Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands

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Malaria Journal 2012, 11:6  doi:10.1186/1475-2875-11-6

Published: 5 January 2012



Copeptin has recently been identified to be a stable surrogate marker for the unstable hormone arginine vasopressin (AVP). Copeptin has been shown to correlate with disease severity in leptospirosis and bacterial sepsis. Hyponatraemia is common in severe imported malaria and dysregulation of AVP release has been hypothesized as an underlying pathophysiological mechanism. The aim of the present study was to evaluate the performance of copeptin as a predictor of disease severity in imported malaria.


Copeptin was measured in stored serum samples of 204 patients with imported malaria that were admitted to our Institute for Tropical Diseases in Rotterdam in the period 1999-2010. The occurrence of WHO defined severe malaria was the primary end-point. The diagnostic performance of copeptin was compared to that of previously evaluated biomarkers C-reactive protein, procalcitonin, lactate and sodium.


Of the 204 patients (141 Plasmodium falciparum, 63 non-falciparum infection), 25 had severe malaria. The Area Under the ROC curve of copeptin for severe disease (0.66 [95% confidence interval 0.59-0.72]) was comparable to that of lactate, sodium and procalcitonin. C-reactive protein (0.84 [95% CI 0.79-0.89]) had a significantly better performance as a biomarker for severe malaria than the other biomarkers.


C-reactive protein but not copeptin was found to be an accurate predictor for disease severity in imported malaria. The applicability of copeptin as a marker for severe malaria in clinical practice is limited to exclusion of severe malaria.

Malaria; Imported; Severity; Biomarkers; Copeptin; Arginine vasopressin; C-reactive protein; CRP; Traveller