High levels of erythropoietin are associated with protection against neurological sequelae in African children with cerebral malaria
High levels of erythropoietin are associated with protection against neurological sequelae in African children with cerebral malaria
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DOI：
10.1073/pnas.0709715105
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发表时间：
2008-02-19
影响因子：
11.1
通讯作者：
Newton, Charles R. J. C.
中科院分区：
文献类型：
--
作者：
Casals-Pascual, Climent;Idro, Richard;Newton, Charles R. J. C.
儿童脑型疟疾（CM）与高死亡率和长期神经认知后遗症相关。促红细胞生成素（Epo）和血管内皮生长因子（VEGF）均具有神经保护作用。我们假设这些细胞因子的高血浆和脑脊液（CSF）水平可以预防CM儿童的神经系统后遗症。我们测量了肯尼亚CM患儿血浆和CSF配对样本中的Epo、VEGF和肿瘤坏死因子。Logistic回归模型用于识别与神经系统后遗症发展相关的风险和保护因素。CM儿童（n = 124）分为三组：76无后遗症，32有后遗症，16人死亡。将32名有CM和神经系统后遗症的患者与64名无后遗症的CM患者按血红蛋白水平分层，进行条件logistic回归分析，估计血浆Epo（>200单位/升）与发生神经系统后遗症的风险降低>80%相关[校正比值比（OR）0.18; 95% C.I. 0.05-0.93; P = 0.041]。深度昏迷入院（调整OR 5.47; 95% C.I. 1.45-20.67; P = 0.012）和入院后惊厥（校正OR 16.35; 95% CI. 2.94-90.79; P = 0.001）也与神经系统后遗症独立相关。高水平的Epo与CM儿童神经系统后遗症的风险降低相关。年龄依赖性的Epo对贫血的反应和年龄依赖性的保护作用可能影响CM的临床流行病学。这些数据支持进一步研究Epo作为CM的辅助治疗。
Cerebral malaria (CM) in children is associated with a high mortality and long-term neurocognitive sequelae. Both erythropoietin (Epo) and vascular endothelial growth factor (VEGF) have been shown to be neuroprotective. We hypothesized that high plasma and cerebrospinal fluid (CSF) levels of these cytokines would prevent neurological sequelae in children with CM. We measured Epo, VEGF, and tumor necrosis factor in paired samples of plasma and CSF of Kenyan children admitted with CM. Logistic regression models were used to identify risk and protective factors associated with the development of neurological sequelae. Children with CM (n = 124) were categorized into three groups: 76 without sequelae, 32 with sequelae, and 16 who died. Conditional logistic regression analysis matching the 32 patients with CM and neurological sequelae to 64 patients with CM without sequelae stratified for hemoglobin level estimated that plasma Epo (>200 units/liter) was associated with >80% reduction in the risk of developing neurological sequelae [adjusted odds ratio (OR) 0.18; 95% C.I. 0.05-0.93; P = 0.041]. Admission with profound coma (adjusted OR 5.47; 95% C.I. 1.45-20.67; P = 0.012) and convulsions after admission (adjusted OR 16.35; 95% C.I. 2.94-90.79; P = 0.001) were also independently associated with neurological sequelae. High levels of Epo were associated with reduced risk of neurological sequelae in children with CM. The age-dependent Epo response to anemia and the age-dependent protective effect may influence the clinical epidemiology of CM. These data support further study of Epo as an adjuvant therapy in CM.