title: Quantitative Assessment of Multiorgan Sequestration of Parasites in Fatal Pediatric Cerebral Malaria.
abstract: Children in sub-Saharan Africa continue to acquire and die from cerebral malaria, despite efforts to control or eliminate the causative agent, Plasmodium falciparum. We present a quantitative histopathological assessment of the sequestration of parasitized erythrocytes in multiple organs obtained during a prospective series of 103 autopsies performed between 1996 and 2010 in Blantyre, Malawi, on pediatric patients who died from cerebral malaria and controls. After the brain, sequestration of parasites was most intense in the gastrointestinal tract, both in patients with cerebral malaria and those with parasitemia in other organs. Within cases of histologically defined cerebral malaria, which includes phenotypes termed "sequestration only" (CM1) and "sequestration with extravascular pathology" (CM2), CM1 was associated with large parasite numbers in the spleen and CM2 with intense parasite sequestration in the skin. A striking histological finding overall was the marked sequestration of parasitized erythrocytes across most organs in patients with fatal cerebral malaria, supporting the hypothesis that the disease is, in part, a result of a high level of total-body parasite sequestration.
authors: Department of Pathology, Brigham and Women's Hospital Department of Immunology and Infectious Disease, Harvard School of Public Health, Boston, Massachusetts Blantyre Malaria Project, University of Malawi College of Medicine.
authors: Danny A
authors: DA
authors: Milner
authors: Department of Pathology, Brigham and Women's Hospital.
authors: Jonathan J
authors: JJ
authors: Lee
authors: Department of Pathology, Brigham and Women's Hospital.
authors: Charles
authors: C
authors: Frantzreb
authors: CellNetix, Olympia, Washington.
authors: Richard O
authors: RO
authors: Whitten
authors: University of Malawi, College of Medicine.
authors: Steve
authors: S
authors: Kamiza
authors: Department of Histopathology, South Warwickshire General Hospitals, Warwick.
authors: Richard A
authors: RA
authors: Carr
authors: Department of Pathology, Brigham and Women's Hospital.
authors: Alana
authors: A
authors: Pradham
authors: Department of Pathology, Brigham and Women's Hospital.
authors: Rachel E
authors: RE
authors: Factor
authors: Department of Pathology, Brigham and Women's Hospital.
authors: Krupa
authors: K
authors: Playforth
authors: University of Malawi, College of Medicine.
authors: George
authors: G
authors: Liomba
authors: University of Malawi, College of Medicine.
authors: Charles
authors: C
authors: Dzamalala
authors: College of Osteopathic Medicine, Michigan State University, East Lansing Blantyre Malaria Project, University of Malawi College of Medicine.
authors: Karl B
authors: KB
authors: Seydel
authors: University of Malawi, College of Medicine Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi Liverpool School of Tropical Medicine, University of Liverpool, United Kingdom.
authors: Malcolm E
authors: ME
authors: Molyneux
authors: College of Osteopathic Medicine, Michigan State University, East Lansing Blantyre Malaria Project, University of Malawi College of Medicine.
authors: Terrie E
authors: TE
authors: Taylor
mesh_terms: D001344:Autopsy; D001921:Brain / Q000469:parasitology / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D004912:Erythrocytes / Q000469:parasitology; D041981:Gastrointestinal Tract / Q000469:parasitology / Q000473:pathology; D006801:Humans; D016779:Malaria, Cerebral / Q000401:mortality / Q000469:parasitology* / Q000473:pathology; D016778:Malaria, Falciparum / Q000401:mortality / Q000469:parasitology* / Q000473:pathology; D008295:Malawi / Q000453:epidemiology; D059208:Parasite Load / Q000379:methods; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000302:isolation & purification*; D011446:Prospective Studies; D012867:Skin / Q000469:parasitology / Q000473:pathology; D013154:Spleen / Q000469:parasitology / Q000473:pathology
keywords: Africa; Malawi; autopsy; cerebral malaria; pathology; pediatrics