Plasma cell-free DNA predicts pediatric cerebral malaria severity
| Autor: | Ajisa Ahmadu, Dylan Allen, Kami Kim, McKenze Moss, Thomas Keller, Tonney S. Nyirenda, Innocent Kadwala, Stephen J. Rogerson, Stephen Ray, Visopo Harawa, Karl B. Seydel, Terrie E. Taylor, Iset Medina Vera, Monica Soko, Anne Kessler, Wilson L. Mandala, Madi Njie, Li-Min Ting |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Adolescent Neutrophils Fluorescence assay Malaria Cerebral Inflammation Plasma cell Free dna Gastroenterology Uncomplicated malaria 03 medical and health sciences Plasma 0302 clinical medicine Internal medicine Medicine Humans Malaria Falciparum Child biology business.industry General Medicine 030104 developmental biology Real-time polymerase chain reaction medicine.anatomical_structure Cerebral Malaria 030220 oncology & carcinogenesis Myeloperoxidase Child Preschool biology.protein Female medicine.symptom Clinical Medicine business Cell-Free Nucleic Acids Biomarkers |
| Zdroj: | JCI Insight |
| ISSN: | 2379-3708 |
| Popis: | BACKGROUND: 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. METHODS: In 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. RESULTS: Total 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 (r(s) = 0.433, P < 0.0001) and myeloperoxidase (r(s) = 0.683, P < 0.0001). CONCLUSION: 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. FUNDING: NIH NCATS (AK), Burroughs-Wellcome (AK), and National Health and Medical Research Council of Australia (SJR). |
| Databáze: | OpenAIRE |
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