Nitric oxide for the adjunctive treatment of severe malaria: hypothesis and rationale

Med Hypotheses. 2011 Sep;77(3):437-44. doi: 10.1016/j.mehy.2011.06.003. Epub 2011 Jul 13.

Abstract

We hypothesize that supplemental inhaled nitric oxide (iNO) will improve outcomes in children with severe malaria receiving standard antimalarial therapy. The rationale for the hypothesized efficacy of iNO rests on: (1) biological plausibility, based on known actions of NO in modulating endothelial activation; (2) pre-clinical efficacy data from animal models of experimental cerebral malaria; and (3) a human trial of the NO precursor l-arginine, which improved endothelial function in adults with severe malaria. iNO is an attractive new candidate for the adjunctive treatment of severe malaria, given its proven therapeutic efficacy in animal studies, track record of safety in clinical practice and numerous clinical trials, inexpensive manufacturing costs, and ease of administration in settings with limited healthcare infrastructure. We plan to test this hypothesis in a randomized controlled trial (ClinicalTrials.gov Identifier: NCT01255215).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Biological Availability
  • Child
  • Clinical Trials as Topic
  • Endothelial Cells / drug effects*
  • Humans
  • Lung / blood supply
  • Malaria / drug therapy*
  • Nitric Oxide / administration & dosage
  • Nitric Oxide / pharmacology*
  • Nitric Oxide / therapeutic use
  • Nitric Oxide Synthase / genetics*

Substances

  • Nitric Oxide
  • Nitric Oxide Synthase

Associated data

  • ClinicalTrials.gov/NCT01255215