title: Neopterin and procalcitonin are suitable biomarkers for exclusion of severe Plasmodium falciparum disease at the initial clinical assessment of travellers with imported malaria.
abstract: BACKGROUND
  Most clinicians in developed, non-malaria endemic countries have limited or no experience in making clinical assessments of malaria disease severity and subsequent decisions regarding the need for parenteral therapy or high-level monitoring in febrile patients with imported malaria. In the present study, the diagnostic accuracy of plasma soluble Triggering Receptor Expressed on Myeloid cells 1 (TREM-1), neopterin and procalcitonin levels as biomarkers for severe Plasmodium falciparum disease was evaluated in 104 travellers with imported malaria (26 patients with non-P. falciparum malaria, 64 patients with uncomplicated P. falciparum malaria and 14 patients with severe P. falciparum malaria).
  
  
  METHODS
  TREM-1, neopterin and procalcitonin were determined in serum using commercially available ELISA or EIA tests. The diagnostic performance of these biomarkers for severe disease was compared with plasma lactate, a well-validated parameter for disease severity in patients with malaria, as reference. Severe malaria was defined according to the modified WHO criteria.
  
  
  RESULTS
  No significant differences in TREM-1 levels were detected between the different patient groups. Patients with severe P. falciparum malaria had significantly higher neopterin and procalcitonin levels on admission when compared to patients with uncomplicated P. falciparum malaria or non-P. falciparum malaria. Receiver Operating Characteristic (ROC) curve analysis showed that neopterin had the highest Area-Under-the-ROC curve (AUROC 0.85) compared with plasma lactate (AUROC 0.80) and procalcitonin (AUROC 0.78). At a cut-off point of 10.0 ng/ml, neopterin had a positive and negative predictive value of 0.38 and 0.98 whereas procalcitonin, at a cut-off point of 0.9 ng/ml, had a positive and negative predictive value of 0.30 and 1.00.
  
  
  CONCLUSIONS
  Although the diagnostic value of neopterin and procalcitonin is limited, the high negative predictive value of both neopterin and procalcitonin may be helpful for a rapid exclusion of severe malaria disease on admission. This may be a valuable tool for physicians only occasionally dealing with ill-returned travellers from malaria-endemic regions and who need to decide on subsequent oral anti-malarial treatment or timely referral to a specialized centre for high-level monitoring and intensified parenteral treatment.
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Centre, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. r.tewitt@erasmusmc.nl
authors.forename: René
authors.initials: R
authors.lastname: te Witt
authors.forename: Marlies E
authors.initials: ME
authors.lastname: van Wolfswinkel
authors.forename: Pieter L
authors.initials: PL
authors.lastname: Petit
authors.forename: Jaap J
authors.initials: JJ
authors.lastname: van Hellemond
authors.forename: Rob
authors.initials: R
authors.lastname: Koelewijn
authors.forename: Alex
authors.initials: A
authors.lastname: van Belkum
authors.forename: Perry J J
authors.initials: PJ
authors.lastname: van Genderen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D002648:Child; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019344:Lactic Acid / Q000097:blood; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D019798:Neopterin / Q000097:blood*; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000097:blood*; D011971:Receptors, Immunologic / Q000097:blood; D014195:Travel; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D055815:Young Adult
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D008562:Membrane Glycoproteins; D011498:Protein Precursors; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D019344:Lactic Acid; D019798:Neopterin; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide