title: Analysis of Erythrocyte Invasion Mechanisms of Plasmodium falciparum Clinical Isolates Across 3 Malaria-Endemic Areas in Ghana.
abstract: BACKGROUND
  Plasmodium falciparum invades human erythrocytes by using an array of ligands that interact with several receptors, including sialic acid (SA), complement receptor 1 (CR1), and basigin. We hypothesized that in malaria-endemic areas, parasites vary invasion pathways under immune pressure. Therefore, invasion mechanisms of clinical isolates collected from 3 zones of Ghana with different levels of endemicity (from lowest to highest, Accra, Navrongo, and Kintampo) were compared using standardized methods.
  
  
  METHODS
  Blood samples were collected from children aged 2-14 years in whom malaria was diagnosed, and erythrocyte invasion phenotypes were determined using the enzymes neuraminidase, chymotrypsin, and trypsin, which differentially cleave receptors from the erythrocyte surface. In addition, antibodies against CR1 and basigin were used to determine the contributions of these receptors to invasion. Gene expression levels of P. falciparum invasion ligands were also examined.
  
  
  RESULTS
  The parasites generally expressed SA-independent invasion phenotypes across the malaria-endemic areas, with parasites from Kintampo showing the highest invasion rates in neuraminidase-treated erythrocytes. CR1 was a major mediator of SA-independent invasion, while basigin was essential for both SA-dependent and SA-independent invasion mechanisms. Furthermore, expression of the basigin ligand PfRh5 was the best predictor of donor parasitemia.
  
  
  CONCLUSIONS
  Erythrocyte invasion phenotypes expressed by P. falciparum are influenced by endemicity levels, and the PfRh5-basigin pathway is a potential vaccine target.
authors.affiliation: West African Center for Cell Biology of Infectious Pathogens Department of Biochemistry, Cell and Molecular Biology.
authors.forename: Henrietta E
authors.initials: HE
authors.lastname: Mensah-Brown
authors.affiliation: Kintampo Health Research Center.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Amoako
authors.affiliation: West African Center for Cell Biology of Infectious Pathogens Department of Biochemistry, Cell and Molecular Biology.
authors.forename: James
authors.initials: J
authors.lastname: Abugri
authors.affiliation: London School of Hygiene and Tropical Medicine, United Kingdom.
authors.forename: Lindsay B
authors.initials: LB
authors.lastname: Stewart
authors.affiliation: Navrongo Health Research Center, Ghana.
authors.forename: Godfred
authors.initials: G
authors.lastname: Agongo
authors.affiliation: Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon.
authors.forename: Emmanuel K
authors.initials: EK
authors.lastname: Dickson
authors.affiliation: Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Ofori
authors.affiliation: Department of Medicine, Pennsylvania State University College of Medicine, Hershey.
authors.forename: José A
authors.initials: JA
authors.lastname: Stoute
authors.affiliation: London School of Hygiene and Tropical Medicine, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Conway
authors.affiliation: West African Center for Cell Biology of Infectious Pathogens Department of Biochemistry, Cell and Molecular Biology Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon.
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Awandare
mesh_terms: D000293:Adolescent; D051926:Basigin / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D019353:Endemic Diseases; D004912:Erythrocytes / Q000469:parasitology*; D005260:Female; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology; D008297:Male; D019158:N-Acetylneuraminic Acid / Q000276:immunology*; D009439:Neuraminidase / Q000276:immunology / Q000378:metabolism; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D017463:Receptors, Complement 3b / Q000276:immunology
chemical_list: C497886:BSG protein, human; C509991:CR1 protein, human; D002352:Carrier Proteins; C531020:RH5 protein, Plasmodium falciparum; D017463:Receptors, Complement 3b; D051926:Basigin; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid
keywords: Plasmodium falciparum; basigin; complement receptor 1; endemicity; erythrocyte invasion; ligand gene expression; malaria
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