title: Spleen volume and clinical disease manifestations of severe Plasmodium falciparum malaria in African children.
abstract: BACKGROUND
  Plasmodium falciparum malaria is common in African children. Severe disease manifestations include severe malarial anemia (SMA) and cerebral malaria (CM). In vitro studies suggest that splenic sequestration is associated with SMA and protective against CM. We sought to characterize the relationship between ultrasonographically derived spleen volume (SV), clinical manifestations and outcome.
  
  
  METHODS
  We conducted a prospective observational study of severe malaria and SV in children aged 3 months to 12 years in Eastern Uganda. An SV normogram was generated from 186 healthy controls and adjusted for total body surface area (TBSA). Children with severe P. falciparum malaria were classified according to disease phenotype, and SV z-scores were compared for cases and controls to assess the degree of spleen enlargement.
  
  
  RESULTS
  One hundred and four children with severe malaria, median age 19.2 months, were enrolled; 54 were classified as having SMA and 15 with CM. Mortality was 27% in the CM group vs 1.9% in the SMA group. TBSA-adjusted SV z-scores were lower in children with CM compared to SMA (1.98 [95% CI 1.38-2.57] vs 2.73 [95% CI 2.41-3.04]; p=0.028). Mean SV z-scores were lower in children who died (1.20 [95% CI 0.14-2.25]) compared to survivors (2.58 [95% CI 2.35-2.81]); p=0.004.
  
  
  CONCLUSIONS
  SV is lower in CM compared to SMA. Severe malaria with no increase in SV z-score may be associated with mortality.
authors.affiliation: Division of Global Health, Department of Emergency Medicine, Yale University School of Medicine, 464 Congress Ave, Suite 260 New Haven, CT 06519, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Kotlyar
authors.forename: Julius
authors.initials: J
authors.lastname: Nteziyaremye
authors.forename: Peter
authors.initials: P
authors.lastname: Olupot-Olupot
authors.forename: Samuel O
authors.initials: SO
authors.lastname: Akech
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Moore
authors.forename: Kathryn
authors.initials: K
authors.lastname: Maitland
mesh_terms: D000740:Anemia / Q000276:immunology*; D000818:Animals; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007223:Infant; D016779:Malaria, Cerebral / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D016778:Malaria, Falciparum / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008403:Mass Screening; D010963:Plasmodium falciparum / Q000276:immunology* / Q000472:pathogenicity; D017410:Practice Guidelines as Topic; D011446:Prospective Studies; D012720:Severity of Illness Index; D013154:Spleen / Q000276:immunology / Q000473:pathology*; D014454:Uganda / Q000453:epidemiology
keywords: Africa; Anemia; Falciparum; Malaria; Spleen; Ultrasonography