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：

---

糖萼分解与恶性疟原虫疟疾的严重疾病和致命结果相关。


背景技术内皮细胞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发挥着重要作用，微血管功能障碍和寄生虫隔离与恶化的结果相关。糖萼是内皮细胞内富含碳水化合物的一层，在血管稳态中发挥多种作用。糖萼在恶性疟疾中的作用以及与疾病严重程度的关系尚未得到研究。方法 我们前瞻性地招募了根据世界卫生组织标准定义的重度（SM）或中度重度（MSM）恶性疟疾印度尼西亚住院患者（年龄≥18岁）和健康对照（HC）。入组时，采集血液和尿液样本，同时测量血管一氧化氮（NO）生物利用度。使用二甲基亚甲蓝 (GAG-DMMB) 和液相色谱-串联质谱 (GAG-MS) 测定法对尿液中的糖萼分解产物（糖胺聚糖）进行测定。结果 总共招募了 129 名患者（SM = 43，MSM = 57，HC = 29）。与 MSM 患者（1.78、1.27-2.29 和 4.87， 4.27-5.46）和 HC（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，致命结果患者 (n = 3; 中位四分位数范围：6.72、3.80-27.87 和 12.15、7.88-17.20) 的 GAG-DMMB 和 GAG-MS 增加，0.46-4.5 和 4.64，2.02-15.20；P = 0.03）。 MSM（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生物利用度成反比。结论 内皮糖萼分解增加与成人恶性疟疾患者的严重疾病和致命结果相关。