Transcriptional Profiling of Plasmodium falciparum Parasites from Patients with Severe Malaria Identifies Distinct Low vs. High Parasitemic Clusters

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Transcriptional Profiling of Plasmodium falciparum Parasites from Patients with Severe Malaria Identifies Distinct Low vs. High Parasitemic Clusters

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Title: Transcriptional Profiling of Plasmodium falciparum Parasites from Patients with Severe Malaria Identifies Distinct Low vs. High Parasitemic Clusters
Author: Milner, Danny Arnold; Pochet, Nathalie; Krupka, Malkie; Williams, Chris; Seydel, Karl; Taylor, Terrie E.; Van de Peer, Yves; Regev, Aviv; Wirth, Dyann Fergus; Daily, Johanna P.; Mesirov, Jill

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Citation: Milner, Danny A., Nathalie Pochet, Malkie Krupka, Chris Williams, Karl Seydel, Terrie E. Taylor, Yves Van de Peer, Aviv Regev, Dyann Wirth, Johanna P. Daily, and Jill P. Mesirov. 2012. Transcriptional profiling of Plasmodium falciparum parasites from patients with severe malaria identifies distinct low vs. high parasitemic clusters. PLoS ONE 7(7): e40739.
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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. Methods and Findings: 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.
Published Version: doi:10.1371/journal.pone.0040739
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399889/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10497295
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