McDonald Chloe R, Conroy Andrea L, Hawkes Michael, Elphinstone Robyn E, Gamble Joel L, Hayford Kyla, Namasopo Sophie, Opoka Robert O, Liles W Conrad, Kain Kevin C
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.
Pediatr Infect Dis J. 2017 Feb;36(2):146-150. doi: 10.1097/INF.0000000000001382.
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.
疟疾仍然是撒哈拉以南非洲儿童死亡和神经残疾的主要原因。在此，我们检验以下假设：疟疾引起的循环脑源性神经营养因子（BDNF）改变与重症疟疾儿童的不良临床结局相关。
在一项对因重症疟疾住院的乌干达儿童（n = 179）的前瞻性研究中，我们（在就诊时（第1天）、第3天和第14天）收集血浆样本，通过酶联免疫吸附测定法对BDNF进行定量。
脑型疟疾（P < 0.01）、昏迷（P < 0.01）、兰巴雷内器官功能障碍评分>1（P < 0.05）和呼吸窘迫（P < 0.01）的儿童在就诊时（第1天）的BDNF浓度较低。就诊时较高的BDNF浓度与昏迷恢复时间较短[风险比 = 1.655（1.194 - 2.293）；P = 0.002]、残疾几率降低[0.50（0.27 - 0.94）；P = 0.047]和死亡几率降低[0.45（0.22 - 0.92）；P = 0.035]相关。第1天BDNF浓度较低，而重症疟疾存活儿童（第14天）的BDNF浓度升高（P < 0.0001）。
我们的研究结果提供了新的证据，将循环BDNF与重症疟疾儿童的疾病严重程度、昏迷恢复及临床结局联系起来。
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