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

Malaria Journal

Research

Anna J Blackstock¹  Naomi W Lucchi¹  Venkatachalam Udhayakumar¹  Nana O Wilson²  Jonathan K Stiles²  Mrigendra P Singh³  Avinash C Nagpal⁴  Pradeep K Joel⁴  Vidhan Jain⁵  Neeru Singh⁶ 

[1]Atlanta Research and Education foundation Decatur, GA, USA

[2]Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA

[3]Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA

[4]National Institute of Malaria Research Field Unit (ICMR), Jabalpur, Madhya Pradesh, India

[5]Nethaji Subhash Chandra Bose Medical College Hospital, Jabalpur, Madhya Pradesh, India

[6]Regional Medical Research Center for Tribals (ICMR), Nagpur Road, Garha, 482003, Jabalpur, Madhya Pradesh, India

[7]Regional Medical Research Center for Tribals (ICMR), Nagpur Road, Garha, 482003, Jabalpur, Madhya Pradesh, India

[8]National Institute of Malaria Research Field Unit (ICMR), Jabalpur, Madhya Pradesh, India

关键词: Angiopoietins;    Cerebral malaria;    Pathogenesis;    Biomarkers;    Receiver operating characteristic analysis;   

DOI  :  10.1186/1475-2875-10-383

 received in 2011-08-30, accepted in 2011-12-23,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsPatients 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.ResultsThe 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.ConclusionThese 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.

【 授权许可】

Unknown   
© Jain et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.