Plasma levels of angiopoietin-1 and -2 predict cerebral malaria outcome in Central India

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.Cerebral malaria (CM) is a severe form of central nervous system (CNS) pathology associated with Plasmodium falciparum infection. It is characterized by unarousable coma that often begins with seizures among children but coma in adults is less frequently associated with seizures [1]. Despite treatment, mortality due to CM can be as high as 30%, while neurological sequelae that are uncommon in adults occurred among 10% of children recovering from CM [1-3]. Further CM is also associated with cognitive deficit [4,5]. Early diagnosis and prompt treatment can minimize or avert mor