title: Distinct clinical and immunologic profiles in severe malarial anemia and cerebral malaria in Zambia.
abstract: BACKGROUND
  The mechanisms of severe malarial anemia and cerebral malaria, which are extreme manifestations of Plasmodium falciparum malaria, are not fully understood.
  
  
  METHODS
  Children aged <6 years from southern Zambia presenting to the hospital with severe malarial anemia (n = 72), cerebral malaria (n = 28), or uncomplicated malaria (n = 66) were studied prospectively. Children with overlapping severe anemia and cerebral malaria were excluded.
  
  
  RESULTS
  Low interleukin 10 concentrations had the strongest association with severe anemia (standard β = .61; P < .001) followed by high tumor necrosis factor α and sFas concentrations, low weight-for-age z scores, presence of stool parasites, and splenomegaly (standard β = .15-.25; P ≤ .031); most of these factors were also associated with lower reticulocytes. Greater parasitemia was associated with higher interleukin 10 and tumor necrosis factor α concentrations, whereas sulfadoxizole/pyrimethamine therapy and lower weight-for-age z scores were associated with lower interleukin 10 levels. Thrombocytopenia and elevated tissue plasminogen activator inhibitor 1 levels had the strongest associations with cerebral malaria (standard β = .37 or .36; P < .0001), followed by exposure to traditional herbal medicine and hemoglobinuria (standard β = .21-.31; P ≤ .006).
  
  
  CONCLUSIONS
  Predictors of severe malarial anemia (altered immune responses, poor nutrition, intestinal parasites, and impaired erythropoiesis) differed from those of cerebral malaria (thrombocytopenia, herbal medicine, and intravascular hemolysis). Improved preventive and therapeutic measures may need to consider these differences.
authors.affiliation: Malaria Institute at Macha, Choma, Zambia.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Thuma
authors.forename: Janneke
authors.initials: J
authors.lastname: van Dijk
authors.forename: Rick
authors.initials: R
authors.lastname: Bucala
authors.forename: Zufan
authors.initials: Z
authors.lastname: Debebe
authors.forename: Sergei
authors.initials: S
authors.lastname: Nekhai
authors.forename: Thea
authors.initials: T
authors.lastname: Kuddo
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nouraie
authors.forename: Günter
authors.initials: G
authors.lastname: Weiss
authors.forename: Victor R
authors.initials: VR
authors.lastname: Gordeuk
mesh_terms: D001742:Blackwater Fever / Q000276:immunology* / Q000473:pathology*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D016779:Malaria, Cerebral / Q000276:immunology* / Q000473:pathology*; D016778:Malaria, Falciparum / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology / Q000472:pathogenicity; D012307:Risk Factors; D015024:Zambia