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This sequestration is central to pathogenesis. Severe malaria is associated with parasites expressing an antigenically distinct\n            <jats:named-content content-type=\"genus-species\">P. falciparum<\/jats:named-content>\n            erythrocyte membrane protein 1 (PfEMP1) subset mediating binding to endothelial receptors. Previous studies indicate that PfEMP1 adhesins with so-called CIDR\u03b11 domains capable of binding endothelial protein C receptor (EPCR) constitute the PfEMP1 subset associated with severe pediatric malaria. To analyze the relative importance of different subtypes of CIDR\u03b11 domains, we compared Pf\n            <jats:italic>emp1<\/jats:italic>\n            transcript levels in children with severe malaria (including 9 fatal and 114 surviving cases), children hospitalized with uncomplicated malaria (\n            <jats:italic>n<\/jats:italic>\n            = 42), children with mild malaria not requiring hospitalization (\n            <jats:italic>n<\/jats:italic>\n            = 10), and children with parasitemia and no ongoing fever (\n            <jats:italic>n<\/jats:italic>\n            = 12). High levels of transcripts encoding EPCR-binding PfEMP1 were found in patients with symptomatic infections, and the abundance of these transcripts increased with disease severity. The compositions of CIDR\u03b11 subtype transcripts varied markedly between patients, and none of the subtypes were dominant. Transcript-level analyses targeting other domain types indicated that subtypes of DBL\u03b2 or DBL\u03b6 domains might mediate binding phenomena that, in conjunction with EPCR binding, could contribute to pathogenesis. These observations strengthen the rationale for targeting the PfEMP1-EPCR interaction by vaccines and adjunctive therapies. Interventions should target EPCR binding of all CIDR\u03b11 subtypes.\n          <\/jats:p>","DOI":"10.1128\/iai.00841-16","type":"journal-article","created":{"date-parts":[[2017,1,31]],"date-time":"2017-01-31T02:20:26Z","timestamp":1485829226000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":75,"title":["The Severity of Plasmodium falciparum Infection Is Associated with Transcript Levels of\n            <i>var<\/i>\n            Genes Encoding Endothelial Protein C Receptor-Binding P. falciparum Erythrocyte Membrane Protein 1"],"prefix":"10.1128","volume":"85","author":[{"given":"Sixbert I.","family":"Mkumbaye","sequence":"first","affiliation":[{"name":"Kilimanjaro Christian Medical University College and Kilimanjaro Clinical Research Institute, Moshi, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian W.","family":"Wang","sequence":"additional","affiliation":[{"name":"Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Lyimo","sequence":"additional","affiliation":[{"name":"National Institute for Medical Research, Mwanza Research Centre, Mwanza, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob S.","family":"Jespersen","sequence":"additional","affiliation":[{"name":"Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alphaxard","family":"Manjurano","sequence":"additional","affiliation":[{"name":"National Institute for Medical Research, Mwanza Research Centre, Mwanza, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacklin","family":"Mosha","sequence":"additional","affiliation":[{"name":"National Institute for Medical Research, Mwanza Research Centre, Mwanza, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reginald A.","family":"Kavishe","sequence":"additional","affiliation":[{"name":"Kilimanjaro Christian Medical University College and Kilimanjaro Clinical Research Institute, Moshi, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven B.","family":"Mwakalinga","sequence":"additional","affiliation":[{"name":"Kilimanjaro Christian Medical University College and Kilimanjaro Clinical Research Institute, Moshi, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel T. 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