Sequential dysregulated plasma levels of angiopoietins (ANG-2 and ratios of ANG-2/ANG-1) are associated with malaria severity and mortality among hospital admitted cases in South Bastar Region of Chhattisgarh, Central India.

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.