Publication: Whole blood angiopoietin-1 and -2 levels discriminate cerebral and severe (non-cerebral) malaria from uncomplicated malaria
2
Accepted Date
2009-12-15
Issued Date
2009-12-15
Copyright Date
2009
Resource Type
Language
eng
ISSN
1475-2875 (electronic)
Rights
Mahidol University
Rights Holder(s)
BioMed Central
Bibliographic Citation
Conroy AL, Lafferty EI, Lovegrove FE, Krudsood S, Tangpukdee N, Liles WC, et al. Whole blood angiopoietin-1 and -2 levels discriminate cerebral and severe (non-cerebral) malaria from uncomplicated malaria. Malar J. 2009 Dec 15;8:295.
Suggested Citation
Conroy, Andrea L., Lafferty, Erin I., Lovegrove, Fiona E., Srivicha Krudsood, ศรีวิชา ครุฑสูตร, Noppadon Tangpukdee, นพดล ตั้งภักดี, Liles, W. Conrad, Kain, Kevin C. Whole blood angiopoietin-1 and -2 levels discriminate cerebral and severe (non-cerebral) malaria from uncomplicated malaria. Conroy AL, Lafferty EI, Lovegrove FE, Krudsood S, Tangpukdee N, Liles WC, et al. Whole blood angiopoietin-1 and -2 levels discriminate cerebral and severe (non-cerebral) malaria from uncomplicated malaria. Malar J. 2009 Dec 15;8:295.. doi:10.1186/1475-2875-8-295 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/735
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Title
Whole blood angiopoietin-1 and -2 levels discriminate cerebral and severe (non-cerebral) malaria from uncomplicated malaria
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Abstract
BACKGROUND: Severe and cerebral malaria are associated with endothelial
activation. Angiopoietin-1 (ANG-1) and angiopoietin-2 (ANG-2) are major
regulators of endothelial activation and integrity. The aim of this study was to
investigate the clinical utility of whole blood angiopoietin (ANG) levels as
biomarkers of disease severity in Plasmodium falciparum malaria.
METHODS: The utility of whole blood ANG levels was examined in Thai patients to
distinguish cerebral (CM; n = 87) and severe (non-cerebral) malaria (SM; n = 36)
from uncomplicated malaria (UM; n = 70). Comparative statistics are reported
using a non-parametric univariate analysis (Kruskal-Wallis test or Chi-squared
test, as appropriate). Multivariate binary logistic regression was used to
examine differences in whole blood protein levels between groups (UM, SM, CM),
adjusting for differences due to ethnicity, age, parasitaemia and sex. Receiver
operating characteristic curve analysis was used to assess the diagnostic
accuracy of the ANGs in their ability to distinguish between UM, SM and CM.
Cumulative organ injury scores were obtained for patients with severe disease
based on the presence of acute renal failure, jaundice, severe anaemia,
circulatory collapse or coma.
RESULTS: ANG-1 and ANG-2 were readily detectable in whole blood. Compared to UM
there were significant decreases in ANG-1 (p < 0.001) and significant increases
in ANG-2 (p < 0.001) levels and the ratio of ANG-2: ANG-1 (p < 0.001) observed in
patients with SM and CM. This effect was independent of covariates (ethnicity,
age, parasitaemia, sex). Further, there was a significant decrease in ANG-1
levels in patients with SM (non-cerebral) versus CM (p < 0.001). In participants
with severe disease, ANG-2, but not ANG-1, levels correlated with cumulative
organ injury scores; however, ANG-1 correlated with the presence of renal
dysfunction and coma. Receiver operating characteristic curve analysis
demonstrated that the level of ANG-1, the level of ANG-2 or the ratio of ANG-2:
ANG-1 discriminated between individuals with UM and SM (area under the curve,
p-value: ANG-2, 0.763, p < 0.001; ANG-1, 0.884, p < 0.001; Ratio, 0.857, p <
0.001) or UM and CM (area under the curve, p-value: ANG-2, 0.772, p < 0.001;
ANG-1, 0.778, p < 0.001; Ratio, 0.820, p < 0.001).
CONCLUSIONS: These results suggest that whole blood ANG-1/2 levels are promising
clinically informative biomarkers of disease severity in malarial syndromes.