Low plasma arginine concentrations in children with cerebral malaria and decreased nitric oxide production

Lancet. 2003 Feb 22;361(9358):676-8. doi: 10.1016/S0140-6736(03)12564-0.


Nitric oxide (NO) production and mononuclear cell NO synthase 2 (NOS2) expression are high in healthy Tanzanian children but low in those with cerebral malaria. Factors that downregulate NOS2 also diminish factors involved in cellular uptake and biosynthesis of L-arginine, the substrate for NO synthesis. We therefore postulated that L-arginine concentrations would be low in individuals with cerebral malaria. We measured concentrations of L-arginine in cryopreserved plasma samples from Tanzanian children with and without malaria. L-arginine concentrations were low in individuals with cerebral malaria (mean 46 micromol/L, SD 14), intermediate in those with uncomplicated malaria (70 micromol/L, 20), and within the normal range in healthy controls (122 micromol/L, 22; p<0.0001). Analysis by logistic regression showed that hypoargininaemia was significantly associated with cerebral malaria case-fatality. Hypoargininaemia may contribute to limited NO production in children with cerebral malaria and to severe disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arginine / blood*
  • Case-Control Studies
  • Child, Preschool
  • Female
  • Humans
  • Logistic Models
  • Malaria, Cerebral / blood*
  • Male
  • Nitric Oxide / biosynthesis*
  • Tanzania


  • Nitric Oxide
  • Arginine