title: Association of severe malaria outcomes with platelet-mediated clumping and adhesion to a novel host receptor.
abstract: BACKGROUND
  Severe malaria has been attributed partly to the sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the microvasculature of vital host organs. Identification of P. falciparum cytoadherence phenotypes that are associated with severe malaria may lead to the development of novel strategies against life-threatening malaria.
  
  
  RESULTS
  Forty-six P. falciparum isolates from Mozambican children under 5 years of age with severe malaria (cases) were examined and compared to 46 isolates from sex and age matched Mozambican children with uncomplicated malaria (controls). Cytoadherence properties such as platelet-mediated clumping, rosetting and adhesion to purified receptors (CD36, ICAM1 and gC1qR), were compared between these matched pairs by non-parametric tests. The most common clinical presentation associated with severe malaria was prostration. Compared to matched controls, prevalence of platelet-mediated clumping was higher in cases (P = .019), in children presenting with prostration (P = .049) and in children with severe anaemia (P = .025). Prevalence of rosetting and gC1qR adhesion were also higher in isolates from cases with severe anemia and multiple seizures, respectively (P = .045 in both cases), than in controls.
  
  
  CONCLUSIONS
  These data indicate a role for platelet-mediated clumping, rosetting and adhesion to gC1qR in the pathogenesis of severe malaria. Inhibition of these cytoadherence phenotypes may reduce the occurrence or improve the prognosis of severe malaria outcomes.
authors.affiliation: Barcelona Centre for International Health Research (CRESIB), Hospital Clínic/Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mayor
authors.forename: Abdul
authors.initials: A
authors.lastname: Hafiz
authors.forename: Quique
authors.initials: Q
authors.lastname: Bassat
authors.forename: Eduard
authors.initials: E
authors.lastname: Rovira-Vallbona
authors.forename: Sergi
authors.initials: S
authors.lastname: Sanz
authors.forename: Sónia
authors.initials: S
authors.lastname: Machevo
authors.forename: Ruth
authors.initials: R
authors.lastname: Aguilar
authors.forename: Pau
authors.initials: P
authors.lastname: Cisteró
authors.forename: Betuel
authors.initials: B
authors.lastname: Sigaúque
authors.forename: Clara
authors.initials: C
authors.lastname: Menéndez
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Alonso
authors.forename: Chetan E
authors.initials: CE
authors.lastname: Chitnis
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology* / Q000469:parasitology; D002352:Carrier Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D002448:Cell Adhesion; D002675:Child, Preschool; D004912:Erythrocytes / Q000469:parasitology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000628:therapy*; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009073:Mozambique; D010641:Phenotype; D010973:Platelet Adhesiveness; D010976:Platelet Count; D016896:Treatment Outcome
chemical_list: C087299:C1QBP protein, human; D002352:Carrier Proteins; D024101:Mitochondrial Proteins