Neopterin and procalcitonin are suitable biomarkers for exclusion of severe Plasmodium falciparum disease at the initial clinical assessment of travellers with imported malaria

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. Conclusion. 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

Hyponatraemia in imported malaria: the pathophysiological role of vasopressin

Background: In the pathophysiology of hyponatraemia in malaria, the relative contribution of appropriate and inappropriate arginine vasopressin (AVP) release is unknown; the trigger for inappropriate AVP release is also unknown. Methods: Serum copeptin, a stable and sensitive marker for AVP release, was analysed in a large cohort of patients with imported malaria (204 patients) and in a small prospective substudy (23 patients) in which urine sodium and osmolality were also available. Hyponatraemia was classified as mild (serum sodium 131-134 mmol/l) and moderate-to-severe (<131 mmol/l). Results: Serum copeptin on admission was higher in patients with moderate-to-severe hyponatraemia (median 18.5 pmol/L) compared with normonatraemic patients (12.7 pmol/L, p < 0.05). Despite prompt fluid resuscitation, the time to normalization of serum sodium was longer in patients with moderate-to-severe hyponatraemia (median 2.9 days) than in patients with mild hyponatraemia (median 1.7 days, p < 0.001). A poor correlation was found between serum sodium and copeptin levels on admission (r(s) = Conclusions: In hyponatraemic patients with imported malaria, AVP release was uniformly increased and was either appropriate or inappropriate. Although the exact trigger for inappropriate AVP release remains unknown, the higher body temperatures, correlations with C-reactive protein and long normalization times of serum sodium, suggest an important role of the host inflammatory response to the invading malaria parasite