Specific Combinations of Inflammatory, Angiogenesis and Vascular Integrity Biomarkers Are Associated with Clinical Severity, Coma and Mortality in Beninese Children with Plasmodium Falciparum Malaria.

Bernard Tornyigah,Patrick Tettey,Christian Roussilhon,Azizath Moussiliou,Samuel Odarkwei Blankson,Rachida Tahar,Annick Amoussou,Nicaise Tuikue Ndam,Sylvie Pons,Benedicta Ayiedu Mensah,Lauriane Rietmeyer,Helena Lamptey,Maroufou J Alao,Rafiou Adamou,Bernard Addo,Liliane Dikroh,Caroline Padounou

doi:10.3390/diagnostics12020524

Abstract

Malaria-related deaths could be prevented if powerful diagnostic and reliable prognostic biomarkers were available to allow rapid prediction of the clinical severity allowing adequate treatment. 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 Beninese children with malaria to investigate their potential association with clinical manifestations of malaria. We found that all molecules showed higher levels in children with severe or cerebral malaria compared to those with uncomplicated malaria (p-value < 0.005). Plasma concentrations of Pentraxine-3, Procalcitonin, Ang-2 and the soluble receptors were significantly higher in children with coma as defined by a Blantyre Coma Score < 3 (p < 0.001 for Pentraxine-3, suPAR, and sTie-2, p = 0.004 for PCT, p = 0.005 for sICAM-1, p = 0.04 for Ang-2). Moreover, except for the PCT level, the concentrations of Pentraxine-3, suPAR, sEPCR, sICAM-1, sTie-2 and Ang-2 were higher among children who died from severe malaria compared to those who survived (p = 0.037, p = 0.035, p < 0.0001, p= 0.0008, p = 0.01 and p = 0.02, respectively). These findings indicate the ability of these molecules to accurately discriminate among clinical manifestations of malaria, thus, they might be potentially useful for the early prognostic of severe and fatal malaria, and to improve management of severe cases.

Highlights

Malaria continues to be a major public health challenge
Apart from the level of PCT which did not differ between children who died and those who survived, the levels of suPAR, sEPCR, sICAM-1, sTie-2, angiopoietin 2 (Ang-2) and PTX3 were higher in children who died from severe non-cerebral malaria group (SNCM) or cerebral malaria group (CM) than those who survived these pathologies (Figures 1–3) A–G
We found that the suPAR level was significantly higher in children with SNCM or CM compared to those with UM, in children with Blantyre Coma Score (BCS) < 3 compared to those with BCS > 2 and in children who died from SNCM or CM making this molecule a potential marker of severity, coma and fatality (Figures 1–3) A

Summary

Introduction

Malaria continues to be a major public health challenge. In 2020, the annual global mortality reached 627,000, leading to a 12% increase compared to 2019 with the majority of the mortality occurring in Africa [1,2,3]. The expression of the membranous form of urokinase plasminogen activator receptor (uPAR) has been associated with lesions during cerebral malaria suggesting a role of molecules implicated in the plasminogen activation pathway in cerebral malaria including suPAR [9]. This molecule as well as the pattern recognition glycoprotein pentraxine (PTX3) were found to differentiate between uncomplicated and severe malaria. These results, were obtained in a cohort of severe and cerebral malaria cases missing fatality [10]

Methods

Results

Conclusion