title: Differential PfEMP1 expression is associated with cerebral malaria pathology.
abstract: Plasmodium falciparum is unique among human malarias in its ability to sequester in post-capillary venules of host organs. The main variant antigens implicated are the P. falciparum erythrocyte membrane protein 1 (PfEMP1), which can be divided into three major groups (A-C). Our study was a unique examination of sequestered populations of parasites for genetic background and expression of PfEMP1 groups. We collected post-mortem tissue from twenty paediatric hosts with pathologically different forms of cerebral malaria (CM1 and CM2) and parasitaemic controls (PC) to directly examine sequestered populations of parasites in the brain, heart and gut. Use of two different techniques to investigate this question produced divergent results. By quantitative PCR, group A var genes were upregulated in all three organs of CM2 and PC cases. In contrast, in CM1 infections displaying high levels of sequestration but negligible vascular pathology, there was high expression of group B var. Cloning and sequencing of var transcript tags from the same samples indicated a uniformly low expression of group A-like var. Generally, within an organ sample, 1-2 sequences were expressed at dominant levels. 23% of var tags were detected in multiple patients despite the P. falciparum infections being genetically distinct, and two tags were observed in up to seven hosts each with high expression in the brains of 3-4 patients. This study is a novel examination of the sequestered parasites responsible for fatal cerebral malaria and describes expression patterns of the major cytoadherence ligand in three organ-derived populations and three pathological states.
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi; Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Dumizulu L
authors.initials: DL
authors.lastname: Tembo
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Nyoni
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi.
authors.forename: Rekah V
authors.initials: RV
authors.lastname: Murikoli
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi; Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Mavuto
authors.initials: M
authors.lastname: Mukaka
authors.affiliation: Blantyre Malaria Project, College of Medicine, Blantyre, Malawi; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Department of Immunology and Infectious Disease, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Danny A
authors.initials: DA
authors.lastname: Milner
authors.affiliation: Pathogen Sequencing Unit, Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Berriman
authors.affiliation: Department of Medicine, The University of Melbourne, Melbourne, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rogerson
authors.affiliation: Blantyre Malaria Project, College of Medicine, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Taylor
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi; Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Molyneux
authors.affiliation: Department of Basic Medical Sciences, College of Medicine, Blantyre, Malawi.
authors.forename: Wilson L
authors.initials: WL
authors.lastname: Mandala
authors.affiliation: Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Alister G
authors.initials: AG
authors.lastname: Craig
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi; Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Jacqui
authors.initials: J
authors.lastname: Montgomery
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D016779:Malaria, Cerebral / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D016778:Malaria, Falciparum / Q000378:metabolism / Q000473:pathology; D008297:Male; D010963:Plasmodium falciparum / Q000378:metabolism*; D015800:Protozoan Proteins / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum