Endothelial Activation, Acute Kidney Injury, and Cognitive Impairment in Pediatric Severe Malaria.
Endothelial Activation, Acute Kidney Injury, and Cognitive Impairment in Pediatric Severe Malaria.
复制标题
DOI：
10.1097/ccm.0000000000004469
复制
发表时间：
2020-09
影响因子：
8.8
通讯作者：
Conroy AL
中科院分区：
文献类型：
--
作者：
Ouma BJ;Ssenkusu JM;Shabani E;Datta D;Opoka RO;Idro R;Bangirana P;Park G;Joloba ML;Kain KC;John CC;Conroy AL
评估内皮激活、疟疾并发症和严重疟疾幸存者长期认知结果之间的关系。脑型疟疾、严重疟疾性贫血或社区儿童的前瞻性队列研究。乌干达坎帕拉的穆拉戈国家转诊医院。对18个月至12岁的重度疟疾（脑型疟疾，n = 253或重度疟疾性贫血，n = 211）或社区儿童（n = 206）进行了24个月的随访。没有。儿童在入组时（社区儿童）或出院后一周（严重疟疾）以及6个月、12个月和24个月随访时接受神经认知评估。在入院时对血浆样本（血管性血友病因子、血管生成素-1和血管生成素-2、可溶性细胞间粘附分子-1、可溶性血管细胞粘附分子-1、可溶性E-选择素和P-选择素）进行内皮活化评估。错误发现率用于调整多重比较。与社区儿童相比，严重疟疾与广泛的内皮激活相关（所有标志物p < 0.0001）。急性肾损伤与血管性血友病因子、可溶性细胞间粘附分子-1、可溶性E-选择素、P-选择素和血管生成素-2的变化独立相关（均p < 0.0001）。在各年龄组中，血管生成素-2的log 10增加与较低的认知z评分相关（儿童< 5岁，β −0.42，95% CI，−0.69至−0.15，p = 0.002; ≥ 5岁儿童，β −0.39，95%CI，−0.67至−0.11，p = 0.007），与疾病严重程度（昏迷、癫痫发作次数、急性肾损伤）和社会人口学因素无关。血管生成素-2与溶血（乳酸脱氢酶、总胆红素）和炎症（肿瘤坏死因子-α、白细胞介素-10）相关。在接受腰椎穿刺的脑型疟疾患儿中，血管生成素-2与血脑屏障功能障碍以及脑脊液中神经炎症和损伤的标志物（肿瘤坏死因子-α、犬尿烯酸、tau蛋白）相关。这些数据支持血管生成素-2作为衡量疾病严重程度的指标，也是严重疟疾儿童长期认知损伤的危险因素。
Evaluate the relationship between endothelial activation, malaria complications, and long-term cognitive outcomes in severe malaria survivors. Prospectively cohort study of children with cerebral malaria, severe malarial anemia, or community children. Mulago National Referral Hospital in Kampala, Uganda. Children 18 months to 12 years old with severe malaria (cerebral malaria, n = 253 or severe malarial anemia, n = 211) or community children (n = 206) were followed for 24 months. None. Children underwent neurocognitive evaluation at enrollment (community children) or a week following hospital discharge (severe malaria) and 6, 12, and 24 months follow-up. Endothelial activation was assessed at admission on plasma samples (von Willebrand factor, angiopoietin-1 and angiopoietin-2, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-Selectin, and P-Selectin). False discovery rate was used to adjust for multiple comparisons. Severe malaria was associated with widespread endothelial activation compared with community children (p < 0.0001 for all markers). Acute kidney injury was independently associated with changes in von Willebrand factor, soluble intercellular adhesion molecule-1, soluble E-Selectin, P-Selectin, and angiopoietin-2 (p < 0.0001 for all). A log10 increase in angiopoietin-2 was associated with lower cognitive z scores across age groups (children < 5, β −0.42, 95% CI, −0.69 to −0.15, p = 0.002; children ≥ 5, β −0.39, 95% CI, −0.67 to −0.11, p = 0.007) independent of disease severity (coma, number of seizures, acute kidney injury) and sociodemographic factors. Angiopoietin-2 was associated with hemolysis (lactate dehydrogenase, total bilirubin) and inflammation (tumor necrosis factor-α, interleukin-10). In children with cerebral malaria who had a lumbar puncture performed, angiopoietin-2 was associated with blood-brain barrier dysfunction, and markers of neuroinflammation and injury in the cerebrospinal fluid (tumor necrosis factor-α, kynurenic acid, tau). These data support angiopoietin-2 as a measure of disease severity and a risk factor for long-term cognitive injury in children with severe malaria.