Transcriptional profiling of Plasmodium falciparum parasites from patients with severe malaria identifies distinct low vs. high parasitemic clusters

Danny A. Milner, Nathalie Pochet, Malkie Krupka, Chris Williams, Karl Seydel, Terrie E. Taylor, Yves van de Peer, Aviv Regev, Dyann Wirth, Johanna P. Daily, Jill P. Mesirov

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere40739
JournalPLoS One
Volume7
Issue number7
DOIs
StatePublished - Jul 18 2012

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Plasmodium falciparum
malaria
Malaria
Parasitemia
parasitemia
Parasites
Cerebral Malaria
parasites
Malawi
Biological Sciences
Endoplasmic Reticulum-Associated Degradation
Transcription
Gene expression
retinal diseases
Yeast
Child Mortality
Africa South of the Sahara
Life cycle
acidosis
Blood

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Transcriptional profiling of Plasmodium falciparum parasites from patients with severe malaria identifies distinct low vs. high parasitemic clusters. / Milner, Danny A.; Pochet, Nathalie; Krupka, Malkie; Williams, Chris; Seydel, Karl; Taylor, Terrie E.; van de Peer, Yves; Regev, Aviv; Wirth, Dyann; Daily, Johanna P.; Mesirov, Jill P.

In: PLoS One, Vol. 7, No. 7, e40739, 18.07.2012.

Research output: Contribution to journalArticle

Milner, DA, Pochet, N, Krupka, M, Williams, C, Seydel, K, Taylor, TE, van de Peer, Y, Regev, A, Wirth, D, Daily, JP & Mesirov, JP 2012, 'Transcriptional profiling of Plasmodium falciparum parasites from patients with severe malaria identifies distinct low vs. high parasitemic clusters', PLoS One, vol. 7, no. 7, e40739. https://doi.org/10.1371/journal.pone.0040739
Milner, Danny A. ; Pochet, Nathalie ; Krupka, Malkie ; Williams, Chris ; Seydel, Karl ; Taylor, Terrie E. ; van de Peer, Yves ; Regev, Aviv ; Wirth, Dyann ; Daily, Johanna P. ; Mesirov, Jill P. / Transcriptional profiling of Plasmodium falciparum parasites from patients with severe malaria identifies distinct low vs. high parasitemic clusters. In: PLoS One. 2012 ; Vol. 7, No. 7.
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