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

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

KEYWORDS:

• Severe malaria
• angiopoietins
• sequential measurement
• central india

Acknowledgments

This study was funded by ICMR-Tribal Sub Plan from 2010-2014. We are grateful to the patients and their guardians for kindly taking part in the study. Thanks are also due to the hospital staff and Doctors for their kind help in multiple ways during the study. We are grateful to Dr. Aparup Das, Director, ICMR-NIRTH for his constant encouragement and guidance for publishing work carried out under biomarker study. We also thank Mr. MP Singh for useful suggestions in data analysis. “The manuscript has been approved by the Publication Screening Committee of ICMR-NIRTH, Jabalpur and assigned with the number ICMR-NIRTH/PSC/03/2021.”

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Disclosure statement

No potential conflict of interest was reported by the author(s).

Financial support

This work was carried out with the financial support of the ICMR-Tribal Sub Plan (TSP), New Delhi.

Additional information

Funding

This work was supported by the Indian Council of Medical Research.