title: Supraorbital postmortem brain sampling for definitive quantitative confirmation of cerebral sequestration of Plasmodium falciparum parasites.
abstract: BACKGROUND
  The conventional clinical case definition of cerebral malaria (CM) is imprecise but specificity is improved by a definitive clinical feature such as retinopathy or confirming sequestration of parasites in a post-mortem examination of the brain. A full autopsy is often not possible, since it is costly and may encounter resistance of the deceased's family.
  
  
  METHODS
  We have assessed the use of a cytological smear of brain tissue, obtained post-mortem by supraorbital sampling, for the purpose of quantifying cerebral sequestration in children with fatal malaria in Blantyre, Malawi. We have compared this method to histological quantification of parasites at autopsy.
  
  
  RESULTS
  The number of parasites present on cytological smears correlated with the proportion of vessels parasitized as assessed by histology of fixed and stained brain tissue. Use of cytological results in addition to the standard clinical case definition increases the specificity of the clinical case definition alone from 48.3% to 100% with a minimal change in sensitivity.
  
  
  CONCLUSIONS
  Post-mortem supraorbital sampling of brain tissue improves the specificity of the diagnosis of fatal cerebral malaria and provides accurate quantitative estimates of cerebral sequestration. This tool can be of great value in clinical, pathogenetic, and epidemiological research studies on cerebral malaria.
authors.affiliation: Brigham & Women's Hospital, Boston, Massachusetts 02115, USA. dmilner@partners.org
authors.forename: Danny A
authors.initials: DA
authors.lastname: Milner
authors.forename: Clarissa
authors.initials: C
authors.lastname: Valim
authors.forename: Robert
authors.initials: R
authors.lastname: Luo
authors.forename: Krupa B
authors.initials: KB
authors.lastname: Playforth
authors.forename: Steve
authors.initials: S
authors.lastname: Kamiza
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Molyneux
authors.forename: Karl B
authors.initials: KB
authors.lastname: Seydel
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Taylor
mesh_terms: D001707:Biopsy, Needle; D001927:Brain Diseases / Q000175:diagnosis* / Q000401:mortality / Q000469:parasitology; D002648:Child; D003584:Cytological Techniques; D005625:Frontal Lobe / Q000166:cytology / Q000469:parasitology*; D006652:Histological Techniques; D006801:Humans; D016779:Malaria, Cerebral / Q000175:diagnosis* / Q000401:mortality / Q000469:parasitology; D008295:Malawi; D010963:Plasmodium falciparum / Q000166:cytology / Q000302:isolation & purification*; D052939:Schizonts; D012680:Sensitivity and Specificity; D053058:Trophozoites