title: Plasma superoxide dismutase-1 as a surrogate marker of vivax malaria severity.
abstract: BACKGROUND
  Severe outcomes have been described for both Plasmodium falciparum and P. vivax infections. The identification of sensitive and reliable markers of disease severity is fundamental to improving patient care. An intense pro-inflammatory response with oxidative stress and production of reactive oxygen species is present in malaria. Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and antioxidant agents such as superoxide dismutase-1 (SOD-1) are likely candidate biomarkers for disease severity. Here we tested whether plasma levels of SOD-1 could serve as a biomarker of severe vivax malaria.
  
  
  RESULTS
  Plasma samples were obtained from residents of the Brazilian Amazon with a high risk for P. vivax transmission. Malaria diagnosis was made by both microscopy and nested PCR. A total of 219 individuals were enrolled: non-infected volunteers (n = 90) and individuals with vivax malaria: asymptomatic (n = 60), mild (n = 50) and severe infection (n = 19). SOD-1 was directly associated with parasitaemia, plasma creatinine and alanine amino-transaminase levels, while TNF-alpha correlated only with the later enzyme. The predictive power of SOD-1 and TNF-alpha levels was compared. SOD-1 protein levels were more effective at predicting vivax malaria severity than TNF-alpha. For discrimination of mild infection, elevated SOD-1 levels showed greater sensitivity than TNF-alpha (76% vs. 30% respectively; p<0.0001), with higher specificity (100% vs. 97%; p<0.0001). In predicting severe vivax malaria, SOD-1 levels exhibited higher sensitivity than TNF-alpha (80% vs. 56%, respectively; p<0.0001; likelihood ratio: 7.45 vs. 3.14; p<0.0001). Neither SOD-1 nor TNF-alpha could discriminate P. vivax infections from those caused by P. falciparum.
  
  
  CONCLUSIONS
  SOD-1 is a powerful predictor of disease severity in individuals with different clinical presentations of vivax malaria.
authors.affiliation: Centro de Pesquisas Gonçalo Moniz (Fundação Oswaldo Cruz [FIOCRUZ]), Salvador, Brazil.
authors.forename: Bruno B
authors.initials: BB
authors.lastname: Andrade
authors.forename: Antonio
authors.initials: A
authors.lastname: Reis-Filho
authors.forename: Sebastião Martins
authors.initials: SM
authors.lastname: Souza-Neto
authors.forename: Imbroinise
authors.initials: I
authors.lastname: Raffaele-Netto
authors.forename: Luis M A
authors.initials: LM
authors.lastname: Camargo
authors.forename: Aldina
authors.initials: A
authors.lastname: Barral
authors.forename: Manoel
authors.initials: M
authors.lastname: Barral-Netto
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers; D001938:Brazil; D005260:Female; D006801:Humans; D016780:Malaria, Vivax / Q000175:diagnosis* / Q000473:pathology*; D008297:Male; D008853:Microscopy; D008875:Middle Aged; D018512:Parasitemia; D010949:Plasma / Q000737:chemistry; D010966:Plasmodium vivax / Q000276:immunology / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D013482:Superoxide Dismutase / Q000097:blood*; D000072105:Superoxide Dismutase-1; D055815:Young Adult
chemical_list: D015415:Biomarkers; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
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