ABSTRACT

Cerebral malaria (CM) is one of the most severe forms of P. falciparum infection, with an associated high case-fatality rate. Angiopoietins (ANG‐1 and ANG‐2) are important biomarkers of endothelial activation and dysfunction. This study was carried out in Maharani Hospital and associated Medical College, Jagdalpur, CG, Central India from 2010 to 2014. Based on the treatment recovery patterns, cases (n = 65) were classified as mild malaria with rapid recovery (MM-RR), n= 14; non-cerebral severe malaria with moderately fast recovery (NCSM‐MFR), n= 9; CM survivors with slow recovery (CMS-SR), n= 36 and deteriorated CM non-survivors (Det‐CMNS), n= 6. Plasma levels (pg/ml) of ANG-1 and ANG-2 were measured by ELISA in all the samples at the time of hospital admission and 48 hours of treatment. Levels were also measured in available samples at the third time point (time of discharge for survivors or 72 hours post-treatment in fatal cases). Data analysis was done by appropriate statistical tests using Stata 11.0 and SPSS 25.0 software. At the time of admission, ANG-2 and ratios of ANG-2/ANG-1 significantly distinguished Det‐CMNS cases from MM-RR and NCSM‐MFR cases with good AUC scores (0.8‐0.9). Further, Det-CMNS cases could also be distinguished from MM-RR, NCSM-MFR, and CMS-SR cases by ANG-2 (AUC scores 0.9) and ratios of ANG‐2/ANG-1 (AUC: 0.8‐0.9) at 48 hours of treatment. Paired analysis of sequential measurement of angiopoietins revealed that compared to admission levels, the ratios of ANG-2/ANG-1 significantly declined 48 hours after treatment in MM-RR (p= 0.041), NCSM-MFR (p= 0.050), and CMS-SR (p= 0.0002) cases but not in cases of Det-CMNS (p= 0.916). In conclusion, plasma levels of ANG-2 and ratios of ANG-2/ANG-1 may serve as good biomarkers to distinguish the malaria severity at the time of hospital admission and recovery patterns upon treatment in Central India

摘要

脑型疟疾（CM）是恶性疟原虫感染最严重的形式之一，具有较高的病死率。血管生成素（ANG-1 和 ANG-2）是内皮激活和功能障碍的重要生物标志物。这项研究于 2010 年至 2014 年在印度中部贾格达尔布尔的 Maharani 医院和相关医学院进行。根据治疗恢复模式，病例 (n = 65) 被分类为快速恢复的轻度疟疾 (MM-RR) ，n=14；中等快速恢复的非脑型严重疟疾 (NCSM-MFR)，n= 9；恢复缓慢的 CM 幸存者 (CMS-SR)，n = 36 和恶化的 CM 非幸存者 (Det-CMNS)，n = 6。通过 ELISA 测量 ANG-1 和 ANG-2 的血浆水平 (pg/ml)所有样本均在入院时和治疗48小时内采集。还在第三个时间点（幸存者出院时或死亡病例治疗后 72 小时）的可用样本中测量了该水平。使用Stata 11.0和SPSS 25.0软件通过适当的统计检验进行数据分析。入院时，ANG-2 和 ANG-2/ANG-1 比率可显着区分 Det-CMNS 病例与具有良好 AUC 评分的 MM-RR 和 NCSM-MFR 病例 (0.8-0.9)。此外，Det-CMNS 病例还可以通过 ANG-2（AUC 评分 0.9）和 ANG-2/ANG-1 比率（AUC：0.8-0.9）与 MM-RR、NCSM-MFR 和 CMS-SR 病例区分开来。治疗48小时时。血管生成素序贯测量的配对分析显示，与入院水平相比，MM-RR (p = 0.041)、NCSM-MFR (p = 0.050) 和 NCSM-MFR (p = 0.050) 治疗后 48 小时，ANG-2/ANG-1 比率显着下降。 CMS-SR (p= 0.0002) 病例，但 Det-CMNS 病例则不然 (p= 0.916)。总之，血浆 ANG-2 水平和 ANG-2/ANG-1 比值可以作为良好的生物标志物，用于区分印度中部入院时疟疾的严重程度和治疗后的恢复模式