Plasma levels of eight different mediators and their potential as biomarkers of various clinical malaria conditions in African children

Background: Plasmodium falciparum infection can lead to several clinical manifestations ranging from asymptomatic infections (AM) and uncomplicated malaria (UM) to potentially fatal severe malaria (SM), including cerebral malaria (CM). Factors implicated in the progression towards severe disease are not fully understood. Methods: In the present study, an enzyme-linked immunosorbent assay (ELISA) method was used to investigate the plasma content of several biomarkers of the immune response, namely Neopterin, sCD163, suPAR, Pentraxin 3 (PTX3), sCD14, Fractalkine (CX3CL1), sTREM-1 and MIG (CXCL9), in patients with distinct clinical manifestations of malaria. The goal of this study was to determine the relative involvement of these inflammatory mediators in the pathogenesis of malaria and test their relevance as biomarkers of disease severity. Results: ROC curve analysis show that children with AM were characterized by high levels of Fractalkine and sCD163 whereas children with UM were distinguishable by the presence of PTX3 in their plasma. Furthermore, principal component analysis indicated that the combination of Fractalkine, MIG, and Neopterin was the best predictor of AM condition, while suPAR, PTX3 and sTREM-1 combination was the best indicator of UM when compared to AM. The association of Neopterin, suPAR and Fractalkine was strongly predictive of SM or CM compared to UM. Conclusions: The results indicate that the simultaneous evaluation of these bioactive molecules as quantifiable blood parameters may be helpful to get a better insight into the clinical syndromes in children with malaria.