Serum angiopoietin-1 and -2 levels discriminate cerebral malaria from uncomplicated malaria and predict clinical outcome in African children
Document Type
Article
Department
Paediatrics and Child Health (East Africa)
Abstract
Background
Limited tools exist to identify which individuals infected with Plasmodium falciparum are at risk of developing serious complications such as cerebral malaria (CM). The objective of this study was to assess serum biomarkers that differentiate between CM and non-CM, with the long-term goal of developing a clinically informative prognostic test for severe malaria.
Methodology/Principal Findings
Based on the hypothesis that endothelial activation and blood-brain-barrier dysfunction contribute to CM pathogenesis, we examined the endothelial regulators, angiopoietin-1 (ANG-1) and angiopoietin-2 (ANG-2), in serum samples from P. falciparum-infected patients with uncomplicated malaria (UM) or CM, from two diverse populations – Thai adults and Ugandan children. Angiopoietin levels were compared to tumour necrosis factor (TNF). In both populations, ANG-1 levels were significantly decreased and ANG-2 levels were significantly increased in CM versus UM and healthy controls (p<0.001). TNF was significantly elevated in CM in the Thai adult population (p<0.001), but did not discriminate well between CM and UM in African children. Receiver operating characteristic curve analysis showed that ANG-1 and the ratio of ANG-2∶ANG-1 accurately discriminated CM patients from UM in both populations. Applied as a diagnostic test, ANG-1 had a sensitivity and specificity of 100% for distinguishing CM from UM in Thai adults and 70% and 75%, respectively, for Ugandan children. Across both populations the likelihood ratio of CM given a positive test (ANG-1<15 ng/mL) was 4.1 (2.7–6.5) and the likelihood ratio of CM given a negative test was 0.29 (0.20–0.42). Moreover, low ANG-1 levels at presentation predicted subsequent mortality in children with CM (p = 0.027).
Conclusions/Significance
ANG-1 and the ANG-2/1 ratio are promising clinically informative biomarkers for CM. Additional studies should address their utility as prognostic biomarkers and potential therapeutic targets in severe malaria.
Publication (Name of Journal)
PloS one
DOI
https://doi.org/10.1371/journal.pone.0004912
Recommended Citation
Lovegrove, F. E.,
Tangpukdee, N.,
Opoka, R.,
Lafferty, E. I.,
Rajwans, N.,
Hawkes, M.,
Krudsood, S.,
Looareesuwan, S.,
John, C. C.,
Liles, W. C.,
Kain, K. C.
(2009). Serum angiopoietin-1 and -2 levels discriminate cerebral malaria from uncomplicated malaria and predict clinical outcome in African children. PloS one, 4(3), 912-912.
Available at:
https://ecommons.aku.edu/eastafrica_fhs_mc_paediatr_child_health/411
Comments
This work was published before the author joined Aga Khan University.