title: Angiopoietin-2 and angiopoietin-2/angiopoietin-1 ratio as indicators of potential severity of Plasmodium vivax malaria in patients with thrombocytopenia.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hospital Julio Müller, Federal University of Mato Grosso, Cuiabá, Brazil; Univag University Centre, Varzea Grande, Brazil; Facimed Cacoal Faculty of Medicine, Cacoal, Brazil.
authors.forename: Luciano Teixeira
authors.initials: LT
authors.lastname: Gomes
authors.affiliation: Univag University Centre, Varzea Grande, Brazil.
authors.forename: Eduardo Rodrigues
authors.initials: ER
authors.lastname: Alves-Junior
authors.affiliation: Hospital Julio Müller, Federal University of Mato Grosso, Cuiabá, Brazil.
authors.forename: Clebson
authors.initials: C
authors.lastname: Rodrigues-Jesus
authors.affiliation: Hospital Julio Müller, Federal University of Mato Grosso, Cuiabá, Brazil; Facimed Cacoal Faculty of Medicine, Cacoal, Brazil.
authors.forename: Andreia Ferreira
authors.initials: AF
authors.lastname: Nery
authors.affiliation: Hospital Julio Müller, Federal University of Mato Grosso, Cuiabá, Brazil.
authors.forename: Thamires Oliveira
authors.initials: TO
authors.lastname: Gasquez-Martin
authors.affiliation: Hospital Julio Müller, Federal University of Mato Grosso, Cuiabá, Brazil.
authors.forename: Cor Jesus
authors.initials: CJ
authors.lastname: Fontes
mesh_terms: D000328:Adult; D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D006801:Humans; D016780:Malaria, Vivax / Q000097:blood* / Q000150:complications* / Q000175:diagnosis; D008875:Middle Aged; D010966:Plasmodium vivax / Q000302:isolation & purification; D010976:Platelet Count; D011379:Prognosis; D012372:ROC Curve; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000097:blood / Q000150:complications*
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015415:Biomarkers