Plasmodium falciparum erythrocyte membrane protein 1 domain cassettes 8 and 13 are associated with severe malaria in children

Publication: Research - peer-reviewJournal article – Annual report year: 2012

  • Author: Lavstsen, Thomas

    University of Copenhagen2, Denmark

  • Author: Turner, Louise

    University of Copenhagen2, Denmark

  • Author: Saguti, Fredy

    bNational Institute for Medical Research, Tanga Medical Research Centre, Tanzania, United Republic of

  • Author: Magistrado, Pamela Almeida

    University of Copenhagen2, Denmark

  • Author: Rask, Thomas Salhøj

    Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet, 2800, Lyngby, Denmark

  • Author: Jespersen, Jakob S.

    University of Copenhagen2, Denmark

  • Author: Wang, Christian W.

    University of Copenhagen2, Denmark

  • Author: Berger, Sanne Schou

    University of Copenhagen2, Denmark

  • Author: Baraka, Vito

    bNational Institute for Medical Research, Tanga Medical Research Centre, Tanzania, United Republic of

  • Author: Marquard, Andrea M.

    University of Copenhagen2, Denmark

  • Author: Seguin-Orlando, Andaine

    University of Copenhagen2, Denmark

  • Author: Willerslev, Eske

    University of Copenhagen2, Denmark

  • Author: Gilbert, Marcus Thomas Pius

    University of Copenhagen2, Denmark

  • Author: Lusingu, John Peter Andrea

    University of Copenhagen2, Denmark

  • Author: Theander, Thor Grundtvig

    University of Copenhagen2, Denmark

View graph of relations

The clinical outcome of Plasmodium falciparum infections ranges from asymptomatic parasitemia to severe malaria syndromes associated with high mortality. The virulence of P. falciparum infections is associated with the type of P. falciparum erythrocyte membrane protein 1 (PfEMP1) expressed on the surface of infected erythrocytes to anchor these to the vascular lining. Although var2csa, the var gene encoding the PfEMP1 associated with placental malaria, was discovered in 2003, the identification of the var/PfEMP1 variants associated with severe malaria in children has remained elusive. To identify var/PfEMP1 variants associated with severe disease outcome, we compared var transcript levels in parasites from 88 children with severe malaria and 40 children admitted to the hospital with uncomplicated malaria. Transcript analysis was performed by RT-quantitative PCR using a set of 42 primer pairs amplifying var subtype-specific loci covering most var/PfEMP1 subtypes. In addition, we characterized the near-full-length sequence of the most prominently expressed var genes in three patients diagnosed with severe anemia and/or cerebral malaria. The combined analysis showed that severe malaria syndromes, including severe anemia and cerebral malaria, are associated with high transcript levels of PfEMP1 domain cassette 8-encoding var genes. Transcript levels of group A var genes, including genes encoding domain cassette 13, were also significantly higher in patients with severe syndromes compared with those with uncomplicated malaria. This study specifies the var/PfEMP1 types expressed in severe malaria in children, and thereby provides unique targets for future efforts to prevent and treat severe malaria infections.
Original languageEnglish
JournalNational Academy of Sciences. Proceedings
Publication date2012
Volume109
Issue26
PagesE1791-E1800
ISSN0027-8424
DOIs
StatePublished
CitationsWeb of Science® Times Cited: 29
Download as:
Download as PDF
Select render style:
APAAuthorCBEHarvardMLAStandardVancouverShortLong
PDF
Download as HTML
Select render style:
APAAuthorCBEHarvardMLAStandardVancouverShortLong
HTML
Download as Word
Select render style:
APAAuthorCBEHarvardMLAStandardVancouverShortLong
Word

ID: 9855578