Regional Medical Research Center for Tribals (ICMR), Nagpur Road, Garha, 482003 Jabalpur, Madhya Pradesh, India.
Malar J. 2011 Dec 23;10:383. doi: 10.1186/1475-2875-10-383.
The mechanisms underlying the pathogenesis of cerebral malaria (CM) syndrome are not well understood. Previous studies have shown a strong association of inflammatory chemokines, apoptotic markers and angiogenic molecules with CM associated mortality. Recognizing the importance of angiopoietins (ANG) in the pathogenesis of CM, a retrospective investigation was carried out in a hospital cohort of malaria patients with Plasmodium infection in central India to determine if these factors could be suitable markers of CM associated severity.
Patients enrolled in the study were clinically characterized as healthy controls (HC), mild malaria (MM), CM survivors (CMS) and CM non-survivors (CMNS) based on their malaria status and hospital treatment outcome. Plasma ANG-1 and ANG-2 levels were assessed using sandwich ELISA. Receiver operating characteristic (ROC) curve analysis was used to calculate area under the curve (AUC) for each biomarker in order to assess predictive accuracy of individual biomarkers.
The plasma levels of ANG-1 were lower in CMS and CMNS compared to control groups (mild malaria and healthy controls) at the time of hospital admission. On the contrary, ANG-2 levels positively correlated with malaria severity and were significantly higher in CMNS. The ratio of ANG-2/ANG-1 was highest in CMNS compared to other groups. Receiver operating characteristic curves revealed that compared to ANG-1 (AUC = 0.35), ANG-2 (AUC = 0.95) and ratio of ANG-2/ANG-1 (AUC = 0.90) were better markers to discriminate CMNS from MM cases. However, they were less specific in predicting fatal outcome amongst CM cases at the time of hospital admission.
These results suggest that at the time of admission plasma levels of ANG-2 and ratio of ANG-2/ANG-1 are clinically informative biomarkers to predict fatal CM from MM cases while they have limited usefulness in discriminating fatal CM outcomes in a pool of CM cases in endemic settings of Central India.
脑型疟疾（CM）综合征发病机制尚不清楚。先前的研究表明，炎症趋化因子、凋亡标志物和血管生成分子与 CM 相关死亡率密切相关。鉴于血管生成素（ANG）在 CM 发病机制中的重要性，我们对印度中部疟疾感染患者的医院队列进行了回顾性研究，以确定这些因素是否可以作为 CM 相关严重程度的合适标志物。
根据疟疾状态和医院治疗结果，将入组研究的患者临床特征分为健康对照组（HC）、轻度疟疾（MM）、CM 幸存者（CMS）和 CM 非幸存者（CMNS）。使用夹心 ELISA 法检测血浆 ANG-1 和 ANG-2 水平。为了评估单个标志物的预测准确性，使用受试者工作特征（ROC）曲线分析计算每个标志物的曲线下面积（AUC）。
入院时 CMS 和 CMNS 的血浆 ANG-1 水平低于对照组（轻度疟疾和健康对照组）。相反，ANG-2 水平与疟疾严重程度呈正相关，且在 CMNS 中显著升高。与其他组相比，CMNS 中 ANG-2/ANG-1 比值最高。ROC 曲线显示，与 ANG-1（AUC=0.35）相比，ANG-2（AUC=0.95）和 ANG-2/ANG-1 比值（AUC=0.90）是更好的标志物，可区分 MM 病例和 CMNS。然而，它们在预测入院时 CM 病例的致命结局方面特异性较低。
这些结果表明，入院时血浆 ANG-2 水平和 ANG-2/ANG-1 比值是预测 MM 病例从 CM 病例中发生致命性 CM 的有临床意义的生物标志物，而在印度中部流行地区的 CM 病例中，它们在区分致命性 CM 结局方面的用途有限。
