Chloe R McDonald1, Andrea L Conroy, Michael Hawkes, Robyn E Elphinstone, Joel L Gamble, Kyla Hayford, Sophie Namasopo, Robert O Opoka, W Conrad Liles, Kevin C Kain. 1. From the *Department of Medicine, and †Sandra A. Rotman Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada; ‡Division of Pediatric Infectious Diseases, University of Alberta, Edmonton, Alberta, Canada; §Department of Pediatrics, Jinja Regional Referral Hospital, Jinja, Uganda; ¶Department of Pediatrics and Child Health, Mulago Hospital and Makerere University, Kampala, Uganda; ‖Department of Medicine, University of Washington, Seattle, Washington; and **Tropical Disease Unit, Division of Infectious Diseases, Department of Medicine, UHN-Toronto General Hospital, Toronto, Ontario, Canada.
Abstract
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), Lambaréné 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.
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), Lambaréné 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.
Authors: Adriana Harbuzariu; Sidney Pitts; Juan Carlos Cespedes; Keri Oxendine Harp; Annette Nti; Andrew P Shaw; Mingli Liu; Jonathan K Stiles Journal: Sci Rep Date: 2019-12-16 Impact factor: 4.379
Authors: Andrea L Conroy; Robert O Opoka; Paul Bangirana; Ruth Namazzi; Allen E Okullo; Michael K Georgieff; Sarah Cusick; Richard Idro; John M Ssenkusu; Chandy C John Journal: BMC Med Date: 2021-07-28 Impact factor: 8.775