Abstract:
Background: Children 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.
Methods: Using 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.
Results: The 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.
Conclusion: Increased 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.
