Nitric oxide-dependent endothelial dysfunction and reduced arginine bioavailability in plasmodium vivax malaria but no greater increase in intravascular hemolysis in severe disease

Bridget E. Barber, Timothy William, Matthew J. Grigg, Kim A. Piera, Youwei Chen, Hao Wang, J. Brice Weinberg, Tsin W. Yeo, Nicholas M. Anstey

    Research output: Contribution to journalArticle

    Abstract

    Background: Pathogenesis of severe Plasmodium vivax malaria is poorly understood. Endothelial dysfunction and reduced nitric oxide (NO) bioavailability characterize severe falciparum malaria, but have not been assessed in severe vivax malaria.

    Methods: In patients with severe vivax malaria (n = 9), patients with nonsevere vivax malaria (n = 58), and healthy controls (n = 79), we measured NO-dependent endothelial function by using reactive hyperemia-peripheral arterial tonometry (RH-PAT) and assessed associations with arginine, asymmetric dimethylarginine (ADMA), and hemolysis.

    Results: The L-arginine level and the L-arginine to ADMA ratio (a measure of L-arginine bioavailability) were reduced in patients with severe vivax malaria and those with nonsevere vivax malaria, compared with healthy controls (median L-arginine level, 65, 66, and 98 μmol/mL, respectively [P =. 0001]; median L-arginine to ADMA ratio, 115, 125, and 187, respectively [P =. 0001]). Endothelial function was impaired in proportion to disease severity (median RH-PAT index, 1.49, 1.73, and 1.97 in patients with severe vivax malaria, those with nonsevere vivax malaria, and healthy controls, respectively; P =. 018) and was associated with the L-arginine to ADMA ratio. While the posttreatment fall in hemoglobin level was greater in severe vivax malaria as compared to nonsevere vivax malaria (2.5 vs 1 g/dL; P =. 0001), markers of intravascular hemolysis were not higher in severe disease.

    Conclusions: Endothelial function is impaired in nonsevere and severe vivax malaria, is associated with reduced L-arginine bioavailability, and may contribute to microvascular pathogenesis. Severe disease appears to be more associated with extravascular hemolysis than with intravascular hemolysis.

    Original languageEnglish
    Pages (from-to)1557-1564
    Number of pages8
    JournalJournal of Infectious Diseases
    Volume214
    Issue number10
    DOIs
    Publication statusPublished - 15 Nov 2016

    Fingerprint Dive into the research topics of 'Nitric oxide-dependent endothelial dysfunction and reduced arginine bioavailability in plasmodium vivax malaria but no greater increase in intravascular hemolysis in severe disease'. Together they form a unique fingerprint.

  • Cite this