Plasma Biomarkers Predict Severity of Malaria Infection

Two biomarkers have been found suitable to assess the severity of malaria in travelers returning with the disease.

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. Neopterin belongs to the chemical group known as pteridines and procalcitonin is a peptide precursor of the hormone calcitonin. Both substances are involved in the systemic proinflammatory response of the host to invading pathogens.

In a study carried at the Erasmus Medical Center (Rotterdam, the Netherlands), levels of the biomarkers for severe P. falciparum disease was evaluated in 104 travelers with imported malaria. Twenty-six patients had non-P. falciparum malaria, 64 patients were with uncomplicated P. falciparum malaria and 14 patients had severe P. falciparum malaria). The diagnostic performance of TREM-1, procalcitonin and neopterin for malaria disease severity was compared with that of plasma lactate, which is routinely measured in returning travelers who are ill.

Malaria was diagnosed by Quantitative Buffy Coat analysis, by a rapid diagnostic antigen test for malaria and by conventional microscopy of stained thick and thin blood smears. TREM-1 and neopterin levels were determined in serum samples using commercially available enzyme-linked immunoassay (ELISA) tests. Procalcitonin levels in serum samples were determined using a commercially available enzyme immunoassay test. Normal serum values are <100 pg/mL for TREM-1, <3 ng/mL for neopterin and < 0.1 ng/mL for procalcitonin.

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. No significant differences in TREM-1 levels were detected between the different patient groups. 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. The study was published online in September 14, 2010, in the Malaria Journal.

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 returned travelers from malaria-endemic regions and who need to decide on subsequent oral antimalarial treatment or timely referral to a specialized center for high-level monitoring and intensified parenteral treatment.

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