Plasma levels of angiopoietin-1 and -2 predict cerebral malaria outcome in Central India
- PMID: 22192385
- PMCID: PMC3286486
- DOI: 10.1186/1475-2875-10-383
Plasma levels of angiopoietin-1 and -2 predict cerebral malaria outcome in Central India
Abstract
Background: The 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.
Methods: Patients 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.
Results: The 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.
Conclusion: These 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.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3286486/bin/1475-2875-10-383-1.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3286486/bin/1475-2875-10-383-2.gif)
Similar articles
-
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.Pathog Glob Health. 2022 Feb;116(1):47-58. doi: 10.1080/20477724.2021.1953685. Epub 2021 Jul 26. Pathog Glob Health. 2022. PMID: 34308785 Free PMC article.
-
Systematic review of the role of angiopoietin-1 and angiopoietin-2 in Plasmodium species infections: biomarkers or therapeutic targets?Malar J. 2016 Dec 1;15(1):581. doi: 10.1186/s12936-016-1624-8. Malar J. 2016. PMID: 27905921 Free PMC article. Review.
-
Potential serological biomarkers of cerebral malaria.Dis Markers. 2011;31(6):327-35. doi: 10.3233/DMA-2011-0854. Dis Markers. 2011. PMID: 22182805 Free PMC article. Review.
-
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. Malar J. 2009. PMID: 20003529 Free PMC article.
-
Serum angiopoietin-1 and -2 levels discriminate cerebral malaria from uncomplicated malaria and predict clinical outcome in African children.PLoS One. 2009;4(3):e4912. doi: 10.1371/journal.pone.0004912. Epub 2009 Mar 20. PLoS One. 2009. PMID: 19300530 Free PMC article.
Cited by
-
Elevated brain derived neurotrophic factor in plasma and interleukin-6 levels in cerebrospinal fluid in meningitis compared to cerebral malaria.J Neurol Sci. 2023 Jul 15;450:120663. doi: 10.1016/j.jns.2023.120663. Epub 2023 May 2. J Neurol Sci. 2023. PMID: 37182424
-
The spectrum of clinical biomarkers in severe malaria and new avenues for exploration.Virulence. 2022 Dec;13(1):634-653. doi: 10.1080/21505594.2022.2056966. Virulence. 2022. PMID: 36036460 Free PMC article. Review.
-
Angiogenic and angiostatic factors present in the saliva of malaria patients.Malar J. 2022 Jul 14;21(1):220. doi: 10.1186/s12936-022-04221-7. Malar J. 2022. PMID: 35836234 Free PMC article.
-
Genetics of cerebral malaria: pathogenesis, biomarkers and emerging therapeutic interventions.Cell Biosci. 2022 Jun 17;12(1):91. doi: 10.1186/s13578-022-00830-6. Cell Biosci. 2022. PMID: 35715862 Free PMC article. Review.
-
Neuregulin-1/ErbB4 signaling modulates Plasmodium falciparum HRP2-induced damage to brain cortical organoids.iScience. 2022 May 14;25(6):104407. doi: 10.1016/j.isci.2022.104407. eCollection 2022 Jun 17. iScience. 2022. PMID: 35663028 Free PMC article.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous