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Nitric Oxide-Dependent Endothelial Dysfunction and Reduced Arginine Bioavailability in Plasmodium vivax Malaria but No Greater Increase in Intravascular Hemolysis in Severe Disease.

Publication ,  Journal Article
Barber, BE; William, T; Grigg, MJ; Piera, KA; Chen, Y; Wang, H; Weinberg, JB; Yeo, TW; Anstey, NM
Published in: J Infect Dis
November 15, 2016

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.

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Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

November 15, 2016

Volume

214

Issue

10

Start / End Page

1557 / 1564

Location

United States

Related Subject Headings

  • Young Adult
  • Prospective Studies
  • Nitric Oxide
  • Middle Aged
  • Microbiology
  • Male
  • Malaria, Vivax
  • Humans
  • Hemolysis
  • Female
 

Citation

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Barber, B. E., William, T., Grigg, M. J., Piera, K. A., Chen, Y., Wang, H., … Anstey, N. M. (2016). Nitric Oxide-Dependent Endothelial Dysfunction and Reduced Arginine Bioavailability in Plasmodium vivax Malaria but No Greater Increase in Intravascular Hemolysis in Severe Disease. J Infect Dis, 214(10), 1557–1564. https://doi.org/10.1093/infdis/jiw427
Barber, Bridget E., Timothy William, Matthew J. Grigg, Kim A. Piera, Youwei Chen, Hao Wang, J Brice Weinberg, Tsin W. Yeo, and Nicholas M. Anstey. “Nitric Oxide-Dependent Endothelial Dysfunction and Reduced Arginine Bioavailability in Plasmodium vivax Malaria but No Greater Increase in Intravascular Hemolysis in Severe Disease.J Infect Dis 214, no. 10 (November 15, 2016): 1557–64. https://doi.org/10.1093/infdis/jiw427.
Barber, Bridget E., et al. “Nitric Oxide-Dependent Endothelial Dysfunction and Reduced Arginine Bioavailability in Plasmodium vivax Malaria but No Greater Increase in Intravascular Hemolysis in Severe Disease.J Infect Dis, vol. 214, no. 10, Nov. 2016, pp. 1557–64. Pubmed, doi:10.1093/infdis/jiw427.
Barber BE, William T, Grigg MJ, Piera KA, Chen Y, Wang H, Weinberg JB, Yeo TW, Anstey NM. Nitric Oxide-Dependent Endothelial Dysfunction and Reduced Arginine Bioavailability in Plasmodium vivax Malaria but No Greater Increase in Intravascular Hemolysis in Severe Disease. J Infect Dis. 2016 Nov 15;214(10):1557–1564.
Journal cover image

Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

November 15, 2016

Volume

214

Issue

10

Start / End Page

1557 / 1564

Location

United States

Related Subject Headings

  • Young Adult
  • Prospective Studies
  • Nitric Oxide
  • Middle Aged
  • Microbiology
  • Male
  • Malaria, Vivax
  • Humans
  • Hemolysis
  • Female