ArticleJCI insight2020
Plasma cell-free DNA predicts pediatric cerebral malaria severity.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Bradykinin contributes to vasogenic edema in murine experimental cerebral malaria.The Journal of clinical investigation · 2026Article
- Prolonged dysregulation of gene expression and biomarkers of coagulation, fibrinolysis, and endothelium in pediatric central nervous system malaria.BMC infectious diseases · 2025Article
- Cell-free DNA as a complementary diagnostic tool for neglected tropical diseases towards achieving the WHO NTDs elimination by 2030.The journal of liquid biopsy · 2025Article
- Age-specific malaria vulnerability and transmission reservoir among children.Global pediatrics · 2023Review
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
- Liquid Biopsy in Neurological Diseases.Cells · 2023Review
- Cell-free DNA-based liquid biopsies in neurology.Brain : a journal of neurology · 2023Review
- Elevated plasma interleukin-8 as a risk factor for mortality in children presenting with cerebral malaria.Infectious diseases of poverty · 2023Article
- The spectrum of clinical biomarkers in severe malaria and new avenues for exploration.Virulence · 2022Review
- Determinants of brain swelling in pediatric and adult cerebral malaria.JCI insight · 2021Article
- Bioengineered 3D Microvessels for Investigating Plasmodium falciparum Pathogenesis.Trends in parasitology · 2021Review
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
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).
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