{"doi":"10.1172/jci.insight.136279","title":"Plasma cell-free DNA predicts pediatric cerebral malaria severity","abstract":"BACKGROUNDPrediction 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.METHODSIn this retrospective study, plasma from Malawian children with CM (n = 134), uncomplicated malaria (UM, n = 77), and healthy controls (HC, 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.RESULTSTotal cfDNA increased with malaria severity (HC versus UM, P < 0.001; HC versus CM, P < 0.0001; UM versus CM, P < 0.0001), was elevated in retinopathy-positive (Ret+) CM relative to Ret- CM (7.66 versus 5.47 ng/μL, P = 0.027), and differentiated Ret+ fatal cases from survivors (AUC 0.779; P < 0.001). cfDNA levels in patients with non-malarial febrile illness (NMF, P = 0.25) and non-malarial coma (NMC, P = 0.99) were comparable with UM. Host DNA, rather than parasite DNA, was the major cfDNA contributor (UM, 268 versus 67 pg/μL; CM, 2824 versus 463 pg/μL). Host and parasite cfDNA distinguished CM by retinopathy (host, AUC 0.715, P = 0.0001; parasite, AUC 0.745, P = 0.0001), but only host cfDNA distinguished fatal cases (AUC 0.715, P = 0.0001). Total cfDNA correlated with neutrophil markers IL-8 (rs = 0.433, P < 0.0001) and myeloperoxidase (rs = 0.683, P < 0.0001).CONCLUSIONQuantifying 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.FUNDINGNIH NCATS (AK), Burroughs-Wellcome (AK), and National Health and Medical Research Council of Australia (SJR).","journal":"JCI Insight","year":2020,"id":78028,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9497,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":407920,"name":"Anne Kessler","orcid":null,"position":1,"is_corresponding":false},{"id":407921,"name":"Li‐Min Ting","orcid":null,"position":2,"is_corresponding":false},{"id":406371,"name":"Visopo Harawa","orcid":"0000-0003-0682-1689","position":3,"is_corresponding":false},{"id":406372,"name":"Thomas H. Keller","orcid":"0000-0002-7553-6235","position":4,"is_corresponding":false},{"id":407922,"name":"Dylan Allen","orcid":null,"position":5,"is_corresponding":false},{"id":407923,"name":"Madi Njie","orcid":null,"position":6,"is_corresponding":false},{"id":407924,"name":"McKenze Moss","orcid":null,"position":7,"is_corresponding":false},{"id":407925,"name":"Monica Soko","orcid":null,"position":8,"is_corresponding":false},{"id":406373,"name":"Ajisa Ahmadu","orcid":"0000-0001-8248-7841","position":9,"is_corresponding":false},{"id":324970,"name":"Innocent Kadwala","orcid":null,"position":10,"is_corresponding":false},{"id":406374,"name":"Stephen Ray","orcid":"0000-0001-5818-1228","position":11,"is_corresponding":false},{"id":406375,"name":"Tonney S. Nyirenda","orcid":"0000-0002-4874-9518","position":12,"is_corresponding":false},{"id":406376,"name":"Wilson L. Mandala","orcid":"0000-0001-9386-9239","position":13,"is_corresponding":false},{"id":75970,"name":"Terrie E. Taylor","orcid":"0000-0001-7416-3986","position":14,"is_corresponding":false},{"id":406377,"name":"Stephen J. Rogerson","orcid":"0000-0003-4287-1982","position":15,"is_corresponding":false},{"id":75973,"name":"Karl B. Seydel","orcid":"0000-0001-9859-9549","position":16,"is_corresponding":false},{"id":406378,"name":"Kami Kim","orcid":"0000-0003-3384-152X","position":17,"is_corresponding":false},{"id":406370,"name":"Iset Vera","orcid":"0000-0003-4835-9437","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-18T21:49:40.769098Z","pmid":"32554925","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}