title: Transcriptional profiling of Plasmodium falciparum parasites from patients with severe malaria identifies distinct low vs. high parasitemic clusters.
abstract: BACKGROUND
  In the past decade, estimates of malaria infections have dropped from 500 million to 225 million per year; likewise, mortality rates have dropped from 3 million to 791,000 per year. However, approximately 90% of these deaths continue to occur in sub-Saharan Africa, and 85% involve children less than 5 years of age. Malaria mortality in children generally results from one or more of the following clinical syndromes: severe anemia, acidosis, and cerebral malaria. Although much is known about the clinical and pathological manifestations of CM, insights into the biology of the malaria parasite, specifically transcription during this manifestation of severe infection, are lacking.
  
  
  RESULTS
  We collected peripheral blood from children meeting the clinical case definition of cerebral malaria from a cohort in Malawi, examined the patients for the presence or absence of malaria retinopathy, and performed whole genome transcriptional profiling for Plasmodium falciparum using a custom designed Affymetrix array. We identified two distinct physiological states that showed highly significant association with the level of parasitemia. We compared both groups of Malawi expression profiles with our previously acquired ex vivo expression profiles of parasites derived from infected patients with mild disease; a large collection of in vitro Plasmodium falciparum life cycle gene expression profiles; and an extensively annotated compendium of expression data from Saccharomyces cerevisiae. The high parasitemia patient group demonstrated a unique biology with elevated expression of Hrd1, a member of endoplasmic reticulum-associated protein degradation system.
  
  
  CONCLUSIONS
  The presence of a unique high parasitemia state may be indicative of the parasite biology of the clinically recognized hyperparasitemic severe disease syndrome.
authors: The Brigham and Women's Hospital, Department of Pathology, Boston, Massachusetts, United States of America. dmilner@partners.org
authors: Danny A
authors: DA
authors: Milner
authors: Nathalie
authors: N
authors: Pochet
authors: Malkie
authors: M
authors: Krupka
authors: Chris
authors: C
authors: Williams
authors: Karl
authors: K
authors: Seydel
authors: Terrie E
authors: TE
authors: Taylor
authors: Yves
authors: Y
authors: Van de Peer
authors: Aviv
authors: A
authors: Regev
authors: Dyann
authors: D
authors: Wirth
authors: Johanna P
authors: JP
authors: Daily
authors: Jill P
authors: JP
authors: Mesirov
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008018:Life Cycle Stages / Q000235:genetics; D016778:Malaria, Falciparum / Q000469:parasitology*; D008295:Malawi; D008297:Male; D008875:Middle Aged; D018512:Parasitemia / Q000235:genetics* / Q000469:parasitology*; D010271:Parasites / Q000235:genetics* / Q000254:growth & development; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development; D012164:Retinal Diseases / Q000235:genetics / Q000469:parasitology / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics