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. 2014 Oct 2;9(10):e109246.
doi: 10.1371/journal.pone.0109246. eCollection 2014.

Angiopoietin-2 and angiopoietin-2/angiopoietin-1 ratio as indicators of potential severity of Plasmodium vivax malaria in patients with thrombocytopenia

Luciano Teixeira Gomes  1 , Eduardo Rodrigues Alves-Junior  2 , Clebson Rodrigues-Jesus  3 , Andreia Ferreira Nery  4 , Thamires Oliveira Gasquez-Martin  3 , Cor Jesus Fontes  3
Affiliations

Angiopoietin-2 and angiopoietin-2/angiopoietin-1 ratio as indicators of potential severity of Plasmodium vivax malaria in patients with thrombocytopenia

Luciano Teixeira Gomes et al. PLoS One. .

Erratum in

Abstract

Introduction: Angiogenic factors such as angiopoietin 1 (Ang-1) and angiopoietin 2 (Ang-2) are biomarkers produced during activation and dysfunction of the vascular endothelium in several infectious diseases. The aim of this study was to determine the serum levels of Ang-1 and Ang-2 and to establish their relationship with the main indicators of worst-case prognosis in patients with P. vivax malaria.

Methods: This is a retrospective case-control study nested within a cohort of symptomatic malaria patients. A potentially severe case was defined as a patient that presented at least one of the main indicators of the worst-case prognosis for falciparum malaria, as established by the World Health Organization. Ang-2 and Ang-1 and the Ang-2/Ang-1 ratio were used to analyze the role of angiopoietins as biomarkers in signaling potentially severe vivax malaria. ROC curves were generated to identify a cut-off point discriminating between the angiopoietin concentrations that were most strongly associated with potential infection severity.

Results: The serum levels of Ang-2 and the Ang-2/Ang-1 ratio were higher in the case group. In contrast, the serum levels of Ang-1 were lower in the cases than in the control patients. The blood count for platelets showed a positive correlation with Ang-1 and a negative correlation with Ang-2 and with the Ang-2/Ang-1 ratio. The area under the ROC curve (AUC) for serum angiopoietins, as an indicator of worst-case prognosis in a potentially severe P. vivax malarial infection, was larger in the subgroup of patients with platelet counts <75,000/µL.

Conclusion: This study showed that patients with predictors of worst-case prognoses for P. vivax malaria have lower Ang-1 and higher Ang-2 serum levels (and higher values for the Ang-2/Ang-1 ratio) than controls. Elevated serum levels of Ang-2 and high values for the Ang-2/Ang-1 ratio may potentially be used as predictors of worst-case prognoses for P. vivax malaria, especially in patients with thrombocytopenia.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Boxplot and scatter graphs showing the association between the angiopoietin-2/angiopoietin-1 ratio (A), levels of angiopoietin-2 (B), and levels of angiopoietin-1 (C) with platelet counts in P. vivax malaria patients.
Figure 2
Figure 2. Assessment of the utility of Ang-2 levels and the Ang-2/Ang-1 ratio in discriminating between potentially severe malaria (cases) and controls using ROC analysis for all patients (A, B), patients with platelet counts <75,000/µL (C, D), and patients with platelet counts >75,000/µL (E, F).
The reference line represents the ROC curve for a test with no discriminatory ability. The area under the ROC curve (AUC) is displayed on each graph.
See this image and copyright information in PMC

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Publication types

Grants and funding

The authors are thankful for financial support provided by the Brazilian National Council for Scientific and Technological Development and State of Mato Grosso Research Foundation–PRONEX/CNPq/FAPEMAT (Malaria Network). The authors declare that the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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