Increased adhesion of Plasmodium falciparum infected erythrocytes to ICAM-1 in children with acute intestinal injury

James A Church,Lydia Nyamako,Britta C Urban,Peter Olupot-Olupot,Kathryn Maitland

doi:10.1186/s12936-016-1110-3

Abstract

BackgroundChildren with severe malaria are at increased risk of invasive bacterial disease particularly infection with enteric gram-negative organisms. These organisms are likely to originate from the gut, however, how and why they breach the intestinal interface in the context of malaria infection remains unclear. One explanation is that accumulation of infected red blood cells (iRBCs) in the intestinal microvasculature contributes to tissue damage and subsequent microbial translocation which can be addressed through investigation of the impact of cytoadhesion in patients with malaria and intestinal damage.MethodsUsing a static adhesion assay, cytoadhesion of iRBCs was quantified in 48 children with malaria to recombinant proteins constitutively expressed on endothelial cell surfaces. Cytoadhesive phenotypes between children with and without biochemical evidence of intestinal damage [defined as endotoxemia or elevated plasma intestinal fatty acid binding protein (I-FABP)] was compared.ResultsThe majority of parasites demonstrated binding to the endothelial receptors CD36 and to a lesser extent to ICAM-1. Reduced adhesion to CD36 but not adhesion to ICAM-1 or rosetting was associated with malarial anaemia (p = 0.004). Increased adhesion of iRBCs to ICAM-1 in children who had evidence of elevated I-FABP (p = 0.022), a marker of intestinal ischaemia was observed. There was no correlation between the presence of endotoxemia and increased adhesion to any of the recombinant proteins.ConclusionIncreased parasite adhesion to ICAM-1 in children with evidence of intestinal ischaemia lends further evidence to a link between the cytoadherence of iRBCs in gut microvasculature and intestinal damage.

Highlights

Children with severe malaria are at increased risk of invasive bacterial disease infection with enteric gram-negative organisms
Children with severe Plasmodium falciparum malaria are at increased risk of concomitant invasive bacterial infection (IBI) with enteric gram-negative organisms (EGNOs) [1]
RBCs of 109 children hospitalized with P. falciparum malaria were cultured to allow infected red blood cells (iRBCs) to grow to maturity

Summary

Introduction

Children with severe malaria are at increased risk of invasive bacterial disease infection with enteric gram-negative organisms. These organisms are likely to originate from the gut, how and why they breach the intestinal interface in the context of malaria infection remains unclear. Children with severe Plasmodium falciparum malaria are at increased risk of concomitant invasive bacterial infection (IBI) with enteric gram-negative organisms (EGNOs) [1]. Adults with acute malaria have reduced absorptive capacity as well as increased intestinal permeability measured using a differential sugar absorption test, the highest ratios being noted in severe disease [3]. In 59 (29 %) children, raised plasma concentration of intestinal fatty acid binding protein (I-FABP), a marker of acute gut injury, were detected elevated I-FABP and endotoxemia were not associated

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Conclusion