title: Brain-derived Neurotrophic Factor Is Associated With Disease Severity and Clinical Outcome in Ugandan Children Admitted to Hospital With Severe Malaria.
abstract: 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.
  
  
  
  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).
  
  
  
  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).
  
  
  
  Our findings provide the new evidence linking circulating BDNF with disease severity, coma recovery and clinical outcome in children with severe malaria.
authors: 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.
authors: Chloe R
authors: CR
authors: McDonald
authors: Andrea L
authors: AL
authors: Conroy
authors: Michael
authors: M
authors: Hawkes
authors: Robyn E
authors: RE
authors: Elphinstone
authors: Joel L
authors: JL
authors: Gamble
authors: Kyla
authors: K
authors: Hayford
authors: Sophie
authors: S
authors: Namasopo
authors: Robert O
authors: RO
authors: Opoka
authors: W Conrad
authors: WC
authors: Liles
authors: Kevin C
authors: KC
authors: Kain
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D002675:Child, Preschool; D003128:Coma; D005260:Female; D006760:Hospitalization; D006801:Humans; D007223:Infant; D016779:Malaria, Cerebral / Q000097:blood* / Q000453:epidemiology*; D016778:Malaria, Falciparum / Q000097:blood* / Q000453:epidemiology*; D008297:Male; D010963:Plasmodium falciparum; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014454:Uganda / Q000453:epidemiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human