title: Genetic analysis of circulating and sequestered populations of Plasmodium falciparum in fatal pediatric malaria.
abstract: Falciparum malaria is characterized by cytoadherence of host erythrocytes containing mature asexual-stage parasites and the consequent sequestration of these forms in tissue microvasculature. A postmortem study of pediatric malaria provided us with the opportunity to compare the genetic complexity of circulating and sequestered Plasmodium falciparum populations, in patients with fatal cerebral malaria (CM) versus control subjects with incidental P. falciparum parasitemia who died of causes other than malaria. Parasite genotypes identified in peripheral blood collected at the time of admission to the hospital constituted a subset of those detected in the tissues at death. Despite a higher tissue burden of parasitized erythrocytes in patients with CM than in parasitemic control subjects, parasite populations in tissues from patients with CM were less genetically complex, and the genotypes were more homogeneously distributed throughout the body, than in patients with incidental infection. Our findings support the notion that CM is associated with the emergence of a small number of dominant genotypes in an infected individual.
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi. jmontgomery@mlw.medcol.mw
authors.forename: Jacqui
authors.initials: J
authors.lastname: Montgomery
authors.forename: Danny A
authors.initials: DA
authors.lastname: Milner
authors.forename: Man Tsuey
authors.initials: MT
authors.lastname: Tse
authors.forename: Alfred
authors.initials: A
authors.lastname: Njobvu
authors.forename: Kondwani
authors.initials: K
authors.lastname: Kayira
authors.forename: Charles P
authors.initials: CP
authors.lastname: Dzamalala
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Taylor
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rogerson
authors.forename: Alister G
authors.initials: AG
authors.lastname: Craig
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Molyneux
mesh_terms: D000740:Anemia / Q000453:epidemiology / Q000209:etiology; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D001921:Brain / Q000469:parasitology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000469:parasitology; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D016779:Malaria, Cerebral / Q000401:mortality / Q000469:parasitology / Q000473:pathology; D016778:Malaria, Falciparum / Q000401:mortality / Q000469:parasitology* / Q000473:pathology*; D020066:Merozoite Surface Protein 1 / Q000235:genetics; D018512:Parasitemia / Q000469:parasitology; D010963:Plasmodium falciparum / Q000145:classification / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics
chemical_list: D000953:Antigens, Protozoan; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium