Persistent endothelial activation and inflammation after Plasmodium falciparum Infection in Malawian children

Christopher A Moxon, Ngawina V Chisala, Samuel C Wassmer, Terrie E Taylor, Karl B Seydel, Malcolm E Molyneux, Brian Faragher, Neil Kennedy, Cheng-Hock Toh, Alister G Craig, Robert S Heyderman, Christopher A Moxon, Ngawina V Chisala, Samuel C Wassmer, Terrie E Taylor, Karl B Seydel, Malcolm E Molyneux, Brian Faragher, Neil Kennedy, Cheng-Hock Toh, Alister G Craig, Robert S Heyderman

Abstract

Endothelial dysregulation is central to the pathogenesis of acute Plasmodium falciparum infection. It has been assumed that this dysregulation resolves rapidly after treatment, but this return to normality has been neither demonstrated nor quantified. We therefore measured a panel of plasma endothelial markers acutely and in convalescence in Malawian children with uncomplicated or cerebral malaria. Evidence of persistent endothelial activation and inflammation, indicated by increased plasma levels of soluble intracellular adhesion molecule 1, angiopoetin 2, and C-reactive protein, were observed at 1 month follow-up visits. These vascular changes may represent a previously unrecognized contributor to ongoing malaria-associated morbidity and mortality.

Keywords: Plasmodium falciparum; cardiovascular disease; endothelial activation; endothelial dysfunction; inflammation; pathogen burden; pediatric; stroke.

Figures

Figure 1.
Figure 1.
Plasma markers at admission and at follow-up in Malawian children with malaria, nonmalarial febrile illness, and cerebral malaria compared with healthy controls. Levels of soluble intercellular adhesion molecule 1, C-reactive protein, and angiopoetin 2 were measured by enzyme-linked immunosorbent assay at admission and at 7 day and 28 day follow-up visits in 84 children with uncomplicated malaria, 88 children with nonmalarial febrile illness, and 18 children with cerebral malaria. Results are compared with 36 Malawian healthy controls who were well children at the hospital for elective surgical procedures. Horizontal lines indicate geometric means, and bars indicate 95% confidence intervals. Numbers below data labels of the x-axis are the number of children in each group at each time point. Comparison was performed with a 1-way analysis of variance with the Tukey honestly significant difference test to adjust for multiple comparisons. Asterisks (*) indicate a statistically significant difference in comparison with the healthy controls: *P ≤ .05; **P ≤ .01 ***P ≤ .001. Abbreviations: Ang2, angiopoetin 2; CM, cerebral malaria; CRP, C-reactive protein; HC, healthy control; MF, nonmalarial febrile illness; sICAM-1, soluble intercellular adhesion moleculre 1; UM, uncomplicated malaria.

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