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

• Published in: PloS one Vol. 9; no. 10; p. e109246
• Main Authors: Gomes, Luciano Teixeira, Alves-Junior, Eduardo Rodrigues, Rodrigues-Jesus, Clebson, Nery, Andreia Ferreira, Gasquez-Martin, Thamires Oliveira, Fontes, Cor Jesus
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02-10-2014; Public Library of Science (PLoS)
• Subjects: Adult; Analysis; Angiogenesis; Angiopoietin; Angiopoietin-1 - blood; Angiopoietin-2 - blood; Bioindicators; Biomarkers; Biomarkers - blood; Blood platelets; Care and treatment; Case-Control Studies; Correlation; Disease; Endothelium; Erythrocytes; Health aspects; Hospitals; Humans; Indicators; Infections; Infectious diseases; Laboratories; Malaria; Malaria, Vivax - blood; Malaria, Vivax - complications; Malaria, Vivax - diagnosis; Medical prognosis; Medicine and Health Sciences; Middle Aged; Mortality; Patients; Plasmodium vivax; Plasmodium vivax - isolation & purification; Platelet Count; Platelets; Prognosis; Retrospective Studies; ROC Curve; Serum levels; Signaling; Studies; Subgroups; Thrombocytopenia; Thrombocytopenia - blood; Thrombocytopenia - complications; Vector-borne diseases; Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0109246

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.
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.
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.
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.