title: Increased adhesion of Plasmodium falciparum infected erythrocytes to ICAM-1 in children with acute intestinal injury.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre for Paediatrics, Blizard Institute, Queen Mary University of London, London, UK. j.church@qmul.ac.uk.|KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya. j.church@qmul.ac.uk.
authors.forename: James A
authors.initials: JA
authors.lastname: Church
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya. LNyamako@kemri-wellcome.org.
authors.forename: Lydia
authors.initials: L
authors.lastname: Nyamako
authors.affiliation: Mbale Regional Referral Hospital Clinical Research Unit (MCRU), Mbale, Uganda. polupotolupot@yahoo.com.|Busitema University Faculty of Health Sciences, Mbale Campus, Mbale, Uganda. polupotolupot@yahoo.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Olupot-Olupot
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya. k.maitland@imperial.ac.uk.|Wellcome Centre for Clinical Tropical Medicine, Imperial College, London, UK. k.maitland@imperial.ac.uk.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Maitland
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya. britta.urban@lstmed.ac.uk.|Parasitology Department, Liverpool School of Tropical Medicine, Liverpool, UK. britta.urban@lstmed.ac.uk.
authors.forename: Britta C
authors.initials: BC
authors.lastname: Urban
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D002675:Child, Preschool; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism* / Q000469:parasitology*; D005260:Female; D006801:Humans; D007223:Infant; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016778:Malaria, Falciparum / Q000378:metabolism* / Q000469:parasitology; D008297:Male; D010963:Plasmodium falciparum / Q000502:physiology*
chemical_list: D018799:Intercellular Adhesion Molecule-1
references.citation: BMC Med. 2014;12:31
references.pmid: 24548672
references.citation: Am J Respir Crit Care Med. 2011 Dec 1;184(11):1261-9
references.pmid: 21868501
references.citation: Innate Immun. 2014 Nov;20(8):881-7
references.pmid: 24398861
references.citation: Acta Trop. 2000 Jan 5;74(1):73-6
references.pmid: 10643910
references.citation: J Infect Dis. 2004 Aug 1;190(3):527-34
references.pmid: 15243928
references.citation: Am J Trop Med Hyg. 1991 Feb;44(2):168-75
references.pmid: 2012260
references.citation: Am J Pathol. 1994 Nov;145(5):1057-69
references.pmid: 7526692
references.citation: Semin Immunol. 1995 Oct;7(5):335-42
references.pmid: 8580465
references.citation: Clin Infect Dis. 1997 Mar;24(3):430-5
references.pmid: 9114195
references.citation: Am J Trop Med Hyg. 1997 Oct;57(4):389-98
references.pmid: 9347951
references.citation: Am J Trop Med Hyg. 1999 Sep;61(3):467-72
references.pmid: 10497992
references.citation: Am J Surg. 2005 Sep;190(3):393-400
references.pmid: 16105525
references.citation: Am J Gastroenterol. 2006 Jan;101(1):99-106
references.pmid: 16405540
references.citation: Am J Physiol Gastrointest Liver Physiol. 2006 Apr;290(4):G648-54
references.pmid: 16293653
references.citation: J Infect Dis. 2006 Jul 1;194(1):115-22
references.pmid: 16741890
references.citation: J Infect Dis. 2006 Jul 15;194(2):208-5
references.pmid: 16779727
references.citation: Crit Care. 2006;10(5):233
references.pmid: 17044947
references.citation: Am J Clin Nutr. 2007 Nov;86(5):1286-92
references.pmid: 17991637
references.citation: Crit Care Med. 2008 Sep;36(9):2562-8
references.pmid: 18679107
references.citation: Shock. 2009 Oct;32(4):374-8
references.pmid: 19295480
references.citation: Crit Care Med. 2010 Jan;38(1):133-7
references.pmid: 19730255
references.citation: PLoS One. 2011;6(3):e14741
references.pmid: 21390226
references.citation: N Engl J Med. 2011 Jun 30;364(26):2483-95
references.pmid: 21615299
references.citation: PLoS One. 2011;6(10):e24784
references.pmid: 22043276
references.citation: Clin Infect Dis. 2014 Mar;58(5):638-47
references.pmid: 24336909
references.citation: Sci Transl Med. 2012 Apr 11;4(129):129ra45
references.pmid: 22496547
references.citation: BMC Infect Dis. 2013;13:117
references.pmid: 23497104
references.citation: Infect Immun. 2013 Oct;81(10):3515-26
references.pmid: 23690397
references.citation: Neonatology. 2014;106(1):49-54
references.pmid: 24818641