Brain-derived Neurotrophic Factor Is Associated With Disease Severity and Clinical Outcome in Ugandan Children Admitted to Hospital With Severe Malaria

Background: Malaria remains a leading cause of childhood death and neurologic disability in sub-Saharan Africa. Here, we test the hypothesis that malaria-induced alterations to circulating brain-derived neurotrophic factor (BDNF) are associated with poor clinical outcomes in children with severe malaria. Methods: We quantified BDNF (by enzyme-linked immunosorbent assay) in plasma samples collected [at presentation (day 1), day 3 and day 14], during a prospective study of Ugandan children admitted to hospital with severe malaria (n = 179). Results: BDNF concentration at presentation (day 1) was lower in children with cerebral malaria (P < 0.01), coma (P < 0.01), Lambarene Organ Dysfunction Score > 1 (P < 0.05) and respiratory distress (P < 0.01). Higher BDNF concentration at presentation was associated with shorter time to coma recovery [hazard ratio = 1.655 (1.194-2.293); P = 0.002] and a reduced odds ratio of disability [0.50 (0.27-0.94); P = 0.047] and death [0.45 (0.22-0.92); P = 0.035]. BDNF concentration was lower on day 1 and increased in children surviving severe malaria (day 14; P < 0.0001). Conclusions: Our findings provide the new evidence linking circulating BDNF with disease severity, coma recovery and clinical outcome in children with severe malaria.