title: Clinical features and outcome in children with severe Plasmodium falciparum malaria: a meta-analysis.
abstract: BACKGROUND
  Although global malaria mortality is declining, estimates may not reflect better inpatient management of severe malaria (SM) where reported case fatality rates (CFRs) vary from 1-25%.
  
  
  METHODS
  A meta-analysis of prospective studies of SM was conducted to examine i) whether hypothesized differences between clinical features and outcome in Melanesian compared with African or Asian children really exist, and ii) to explore temporal changes in overall and complication-specific CFRs. The proportions of different SM complications and, overall and complication-specific CFRs were incorporated into the meta-analysis. Adjustments were made for study-level covariates including geographic region, SM definition, artemisinin treatment, median age of participants and time period.
  
  
  RESULTS
  Sixty-five studies were included. Substantial heterogeneity (I(2)>80%) was demonstrated for most outcomes. SM definition contributed to between-study heterogeneity in proportions of cerebral malaria (CM), metabolic acidosis (MA), severe anemia and overall CFR, whilst geographic region was a significant moderator in for CM and hypoglycemia (HG) rates. Compared with their African counterparts, Melanesian children had lower rates of HG (10% [CI95 7-13%] versus 1% [0-3%], P<0.05), lower overall CFR (2% [0-4%] versus 7% [6-9%], P<0.05) and lower CM-specific CFR (8% [0-17%] versus 19% [16-21%], P<0.05). There was no temporal trend for overall CFR and CM-specific CFR but declining HG- and MA- specific CFRs were observed.
  
  
  CONCLUSIONS
  These data highlight that recent estimates of declining global malaria mortality are not replicated by improved outcomes for children hospitalized with SM. Significant geographic differences in the complication rates and subsequent CFRs exist and provide the first robust confirmation of lower CFRs in Melanesian children, perhaps due to less frequent HG.
authors: School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia.
authors: Laurens
authors: L
authors: Manning
authors: School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia.
authors: Moses
authors: M
authors: Laman
authors: School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia.
authors: Wendy A
authors: WA
authors: Davis
authors: School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia.
authors: Timothy M E
authors: TM
authors: Davis
mesh_terms: D002648:Child; D005843:Geography; D006801:Humans; D016778:Malaria, Falciparum / Q000150:complications / Q000401:mortality* / Q000473:pathology*; D008954:Models, Biological; D013997:Time Factors; D016896:Treatment Outcome