BACKGROUND Interactions between the endothelium and infected erythrocytes play a major role in the pathogenesis of falciparum malaria, with microvascular dysfunction and parasite sequestration associated with worsening outcomes. The glycocalyx is a carbohydrate-rich layer that lines the endothelium, with multiple roles in vascular homeostasis. The role of the glycocalyx in falciparum malaria and the association with disease severity has not been investigated. METHODS We prospectively enrolled Indonesian inpatients (aged ≥18 years) with severe (SM) or moderately severe (MSM) falciparum malaria, as defined by World Health Organization criteria, and healthy controls (HCs). On enrollment, blood and urine samples were collected concurrently with measurements of vascular nitric oxide (NO) bioavailability. Urine was assayed for glycocalyx breakdown products (glycosaminoglycans) using a dimethylmethylene blue (GAG-DMMB) and liquid chromatography-tandem mass spectrometry (GAG-MS) assay. RESULTS A total of 129 patients (SM = 43, MSM = 57, HC=29) were recruited. GAG-DMMB and GAG-MS (g/mol creatinine) were increased in SM (mean, 95% confidence interval: 3.98, 2.44-5.53 and 6.82, 5.19-8.44) compared to MSM patients (1.78, 1.27-2.29 and 4.87, 4.27-5.46) and HCs (0.22, 0.06-0.37 and 1.24, 0.89-1.59; P < 0.001). In SM patients, GAG-DMMB and GAG-MS were increased in those with a fatal outcome (n = 3; median, interquartile range: 6.72, 3.80-27.87 and 12.15, 7.88-17.20) compared to survivors (n = 39; 3.10, 0.46-4.5 and 4.64, 2.02-15.20; P = 0.03). Glycocalyx degradation was significantly associated with parasite biomass in both MSM (r = 0.48, GAG-DMMB and r = 0.43, GAG-MS; P < 0.001) and SM patients (r = 0.47, P = 0.002 and r = 0.33, P = 0.04) and inversely associated with endothelial NO bioavailability. CONCLUSIONS Increased endothelial glycocalyx breakdown is associated with severe disease and a fatal outcome in adults with falciparum malaria.

中文翻译：

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糖萼分解与恶性疟原虫疟疾的严重疾病和致命结果有关。

背景 内皮和受感染的红细胞之间的相互作用在恶性疟疾的发病机制中起主要作用，微血管功能障碍和寄生虫隔离与恶化的结果相关。糖萼是排列在内皮细胞上的富含碳水化合物的层，在血管稳态中具有多种作用。糖萼在恶性疟疾中的作用以及与疾病严重程度的关联尚未得到研究。方法 我们前瞻性地招募了患有严重 (SM) 或中度严重 (MSM) 恶性疟疾的印度尼西亚住院患者（年龄≥18 岁）（根据世界卫生组织标准定义）和健康对照 (HCs)。入组时，在测量血管一氧化氮 (NO) 生物利用度的同时收集血液和尿液样本。使用二甲基亚甲基蓝 (GAG-DMMB) 和液相色谱-串联质谱 (GAG-MS) 测定法测定尿液中的糖萼分解产物（糖胺聚糖）。结果 共招募了 129 名患者（SM = 43，MSM = 57，HC = 29）。与 MSM 患者（1.78、1.27-2.29 和 4.87、1.78、1.27-2.29 和 4.87、 4.27-5.46) 和碳氢化合物 (0.22, 0.06-0.37 和 1.24, 0.89-1.59; P < 0.001)。在 SM 患者中，与幸存者 (n = 39；3.10) 相比，GAG-DMMB 和 GAG-MS 在具有致命结果的患者中增加（n = 3；中位数，四分位数范围：6.72、3.80-27.87 和 12.15、7.88-17.20） , 0.46-4.5 和 4.64, 2.02-15.20; P = 0.03)。糖萼降解与两种 MSM 中的寄生虫生物量显着相关（r = 0.48，GAG-DMMB 和 r = 0.43，GAG-MS；P < 0.001）和 SM 患者（r = 0.47，P = 0.002 和 r = 0.33，P = 0.04）并且与内皮 NO 生物利用度负相关。结论 内皮糖萼分解增加与恶性疟疾患者的严重疾病和致命结局相关。