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Title: Nitric Oxide-Dependent Endothelial Dysfunction and Reduced Arginine Bioavailability in Plasmodium vivax Malaria but No Greater Increase in Intravascular Hemolysis in Severe Disease.
Authors: Barber, Bridget E
William, Timothy
Grigg, Matthew J
Piera, Kim A
Chen, Youwei
Wang, Hao
Weinberg, J Brice
Yeo, Tsin W
Anstey, Nicholas M
Citation: The Journal of infectious diseases 2016-11-15; 214(10): 1557-1564
Abstract:  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.  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.  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.  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.
Click to open PubMed article: https://www.ezpdhcs.nt.gov.au/login?url=https://www.ncbi.nlm.nih.gov/pubmed/27630198
Click to open Pubmed Article: https://www.ezpdhcs.nt.gov.au/login?url=https://www.ncbi.nlm.nih.gov/pubmed/27630198
Journal title: The Journal of infectious diseases
Publication Date: 2016-11-15
Type: Journal Article
URI: https://hdl.handle.net/10137/5317
DOI: 10.1093/infdis/jiw427
Appears in Collections:(a) NT Health Research Collection

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