Procalcitonin, Pentraxine 3, and Molecules of the Vascular Endothelium are Hallmark of Pathogenicity and Predict Coma and Mortality Among Children with Severe and Cerebral Malaria

Abstract

Background: Malaria-related deaths could be prevented if prompt diagnosis and prognostic biomarkers are available to allow rapid adequate treatment. Understanding of the mechanisms implicated in the progression from P. falciparum asymptomatic and uncomplicated malaria infections to severe life-threatening disease is necessary to identify such indicators. Methods: Using quantitative ELISA, we assessed the plasma concentrations of Procalcitonin, Pentraxine 3, Ang-2, sTie-2, suPAR, sEPCR, and sICAM-1 in a cohort of 337 Beninese children who presented with pediatric malaria to investigate the potential association with clinical manifestations and outcomes. Results: The molecules showed higher levels in children with severe or cerebral malaria compared to those with uncomplicated malaria. Plasmas concentrations of PTX3, PCT and the soluble receptors suPAR, sTie-2, sICAM-1 were significantly higher in children with deep coma as defined by a Blantyre Coma Score < 3 (P <0.001 for PTX3, suPAR, sTie-2, p=0.004 for PCT and p=0.005 for sICAM-1). Moreover, the concentrations of PTX3, suPAR and sEPCR were higher among children who died from severe malaria compared to those who survived with (p=0.037, p=0.035, and p=0.002 respectively).Conclusion: Our findings indicate the ability of these seven bioactive molecules to discriminate among the clinical manifestations of malaria and therefore, given their potential utility as prognostic biomarkers for severe and fatal malaria, they might be useful to improve severe cases management.