{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:09:16Z","timestamp":1791929356903,"version":"4.3.4"},"reference-count":64,"publisher":"American Society for Clinical Investigation","issue":"12","funder":[{"DOI":"10.13039\/100006108","name":"NIH NCATS","doi-asserted-by":"crossref","award":["TL1TR001072"],"award-info":[{"award-number":["TL1TR001072"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Health and Medical Research Council of Australia Project Grant","award":["APP1061993"],"award-info":[{"award-number":["APP1061993"]}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"crossref","award":["Institutional Program Unifying Population"],"award-info":[{"award-number":["Institutional Program Unifying Population"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"crossref","award":["Laboratory Based Sciences"],"award-info":[{"award-number":["Laboratory Based Sciences"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,18]]},"abstract":"\n BACKGROUND<\/jats:title>\n Prediction of adverse outcomes in cerebral malaria (CM) is difficult. We hypothesized that cell-free DNA (cfDNA) levels would facilitate identification of severe and potentially fatal CM cases.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n In this retrospective study, plasma from Malawian children with CM (\n n<\/jats:italic>\n = 134), uncomplicated malaria (UM,\n n<\/jats:italic>\n = 77), and healthy controls (HC,\n n<\/jats:italic>\n = 60) was assayed for cfDNA using a fluorescence assay. Host and parasite cfDNA was measured by quantitative PCR. Immune markers were determined by ELISA, Luminex, or cytometric bead array.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Total cfDNA increased with malaria severity (HC versus UM,\n P<\/jats:italic>\n < 0.001; HC versus CM,\n P<\/jats:italic>\n < 0.0001; UM versus CM,\n P<\/jats:italic>\n < 0.0001), was elevated in retinopathy-positive (Ret\n +<\/jats:sup>\n ) CM relative to Ret\n \u2013<\/jats:sup>\n CM (7.66 versus 5.47 ng\/\u03bcL,\n P<\/jats:italic>\n = 0.027), and differentiated Ret\n +<\/jats:sup>\n fatal cases from survivors (AUC 0.779;\n P<\/jats:italic>\n < 0.001). cfDNA levels in patients with non\u2013malarial febrile illness (NMF,\n P<\/jats:italic>\n = 0.25) and non\u2013malarial coma (NMC,\n P<\/jats:italic>\n = 0.99) were comparable with UM. Host DNA, rather than parasite DNA, was the major cfDNA contributor (UM, 268 versus 67 pg\/\u03bcL; CM, 2824 versus 463 pg\/\u03bcL). Host and parasite cfDNA distinguished CM by retinopathy (host, AUC 0.715,\n P<\/jats:italic>\n = 0.0001; parasite, AUC 0.745,\n P<\/jats:italic>\n = 0.0001), but only host cfDNA distinguished fatal cases (AUC 0.715,\n P<\/jats:italic>\n = 0.0001). Total cfDNA correlated with neutrophil markers IL-8 (r\n s<\/jats:sub>\n = 0.433,\n P<\/jats:italic>\n < 0.0001) and myeloperoxidase (r\n s<\/jats:sub>\n = 0.683,\n P<\/jats:italic>\n < 0.0001).\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSION<\/jats:title>\n Quantifying plasma cfDNA is a simple assay useful in identifying children at risk for fatal outcome and has promise as a point-of-care assay. Elevated cfDNA suggests a link with host inflammatory pathways in fatal CM.<\/jats:p>\n <\/jats:sec>\n \n FUNDING<\/jats:title>\n NIH NCATS (AK), Burroughs-Wellcome (AK), and National Health and Medical Research Council of Australia (SJR).<\/jats:p>\n <\/jats:sec>","DOI":"10.1172\/jci.insight.136279","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T11:01:33Z","timestamp":1592391693000},"source":"Crossref","is-referenced-by-count":20,"title":["Plasma cell-free DNA predicts pediatric cerebral malaria severity"],"prefix":"10.1172","volume":"5","author":[{"given":"Iset Medina","family":"Vera","sequence":"first","affiliation":[{"name":"Morsani College of Medicine, University of South Florida, Tampa, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Kessler","sequence":"additional","affiliation":[{"name":"Albert Einstein College of Medicine, Bronx, New York, 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