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

摘要: Background: In the past decade, estimates of malaria infections have dropped from 500 million to 225 per year; likewise, mortality rates 3 791,000 year. However, approximately 90% these deaths continue occur in sub-Saharan Africa, and 85% involve children less than 5 years age. Malaria generally results one or more following clinical syndromes: severe anemia, acidosis, cerebral malaria. Although much is known about pathological manifestations CM, insights into biology parasite, specifically transcription during this manifestation infection, are lacking. Methods Findings: We collected peripheral blood meeting case definition a cohort Malawi, examined patients for presence absence retinopathy, performed whole genome transcriptional profiling Plasmodium falciparum using custom designed Affymetrix array. identified two distinct physiological states that showed highly significant association with level parasitemia. compared both groups Malawi expression profiles our previously acquired ex vivo parasites derived infected mild disease; large collection vitro life cycle gene profiles; an extensively annotated compendium data Saccharomyces cerevisiae. The high parasitemia patient group demonstrated unique elevated Hrd1, member endoplasmic reticulum-associated protein degradation system. Conclusions: state may be indicative parasite clinically recognized hyperparasitemic disease syndrome.