title: Comparison of parasite sequestration in uncomplicated and severe childhood Plasmodium falciparum malaria.
abstract: OBJECTIVE
  To determine whether sequestration of parasitized red blood cells differs between children with uncomplicated and severe Plasmodium falciparum malaria.
  
  
  METHODS
  We quantified circulating-, total- and sequestered-parasite biomass, using a mathematical model based on plasma concentration of P. falciparum histidine rich protein 2, in Gambian children with severe (n = 127) and uncomplicated (n = 169) malaria.
  
  
  RESULTS
  Circulating- and total-, but not sequestered-, parasite biomass estimates were significantly greater in children with severe malaria than in those with uncomplicated malaria. Sequestered biomass estimates in children with hyperlactataemia or prostration were similar to those in uncomplicated malaria, whereas sequestered biomass was higher in patients with severe anaemia, and showed a trend to higher values in cerebral malaria and fatal cases. Blood lactate concentration correlated with circulating- and total-, but not sequestered parasite biomass. These findings were robust after controlling for age, prior antimalarial treatment and clonality of infection, and over a realistic range of variation in model parameters.
  
  
  CONCLUSIONS
  Extensive sequestration is not a uniform requirement for severe paediatric malaria. The pathophysiology of hyperlactataemia and prostration appears to be unrelated to sequestered parasite biomass. Different mechanisms may underlie different severe malaria syndromes, and different therapeutic strategies may be required to improve survival.
authors.affiliation: Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
authors.forename: Aubrey J
authors.initials: AJ
authors.lastname: Cunnington
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bretscher
authors.forename: Sarah I
authors.initials: SI
authors.lastname: Nogaro
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Riley
authors.forename: Michael
authors.initials: M
authors.lastname: Walther
mesh_terms: D000953:Antigens, Protozoan / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000469:parasitology* / Q000473:pathology; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D016779:Malaria, Cerebral / Q000097:blood / Q000469:parasitology*; D016778:Malaria, Falciparum / Q000097:blood / Q000469:parasitology*; D008297:Male; D008954:Models, Biological; D018512:Parasitemia / Q000097:blood / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000302:isolation & purification*; D015800:Protozoan Proteins / Q000097:blood; D012044:Regression Analysis; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: D000953:Antigens, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; D015800:Protozoan Proteins; D019344:Lactic Acid
keywords: Anaemia; Cerebral malaria; HRP2; Lactic acid; Microcirculation; Parasite Biomass; Sequestration