title: Elevated plasma von Willebrand factor and propeptide levels in Malawian children with malaria.
abstract: BACKGROUND
  In spite of the significant mortality associated with Plasmodium falciparum infection, the mechanisms underlying severe disease remain poorly understood. We have previously shown evidence of endothelial activation in Ghanaian children with malaria, indicated by elevated plasma levels of both von Willebrand factor (VWF) and its propeptide. In the current prospective study of children in Malawi with retinopathy confirmed cerebral malaria, we compared these markers with uncomplicated malaria, non malarial febrile illness and controls.
  
  
  RESULTS
  Children with cerebral malaria, mild malaria and controls without malaria were recruited into the study. All comatose patients were examined by direct and indirect ophthalmoscopy. Plasma VWF and propeptide levels were measured by ELISA. Median VWF and propeptide levels were significantly higher in patients with uncomplicated malaria than in children with non-malarial febrile illness of comparable severity, in whom levels were higher than in non-febrile controls. Median concentrations of both markers were higher in cerebral malaria than in uncomplicated malaria, and were similar in patients with and without retinopathy. Levels of both VWF and propeptide fell significantly 48 hours after commencing therapy and were normal one month later.
  
  
  CONCLUSIONS
  In children with malaria plasma VWF and propeptide levels are markedly elevated in both cerebral and mild paediatric malaria, with levels matching disease severity, and these normalize upon recovery. High levels of both markers also occur in retinopathy-negative 'cerebral malaria' cases, many of whom are thought to be suffering from diseases other than malaria, indicating that further studies of these markers will be required to determine their sensitivity and specificity.
authors: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi.
authors: Happy T
authors: HT
authors: Phiri
authors: Daniel J
authors: DJ
authors: Bridges
authors: Simon J
authors: SJ
authors: Glover
authors: Jan A
authors: JA
authors: van Mourik
authors: Bas
authors: B
authors: de Laat
authors: Bridon
authors: B
authors: M'baya
authors: Terrie E
authors: TE
authors: Taylor
authors: Karl B
authors: KB
authors: Seydel
authors: Malcolm E
authors: ME
authors: Molyneux
authors: E Brian
authors: EB
authors: Faragher
authors: Alister G
authors: AG
authors: Craig
authors: James E G
authors: JE
authors: Bunn
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005334:Fever / Q000097:blood / Q000150:complications / Q000175:diagnosis; D006801:Humans; D007223:Infant; D016779:Malaria, Cerebral / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D016778:Malaria, Falciparum / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D008295:Malawi; D008297:Male; D009887:Ophthalmoscopy; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D012164:Retinal Diseases / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D012680:Sensitivity and Specificity; D055815:Young Adult; D014841:von Willebrand Factor / Q000032:analysis*
chemical_list: D015415:Biomarkers; D011498:Protein Precursors; D014841:von Willebrand Factor