title: Nitric oxide for the adjunctive treatment of severe malaria: hypothesis and rationale.
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).
authors: Sandra A. Rotman Laboratories, McLaughlin-Rotman Centre for Global Health, Tropical Disease Unit, Division of Infectious Diseases, Department of Medicine, University Health Network-Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
authors: Michael
authors: M
authors: Hawkes
authors: Robert Opika
authors: RO
authors: Opoka
authors: Sophie
authors: S
authors: Namasopo
authors: Christopher
authors: C
authors: Miller
authors: Andrea L
authors: AL
authors: Conroy
authors: Lena
authors: L
authors: Serghides
authors: Hani
authors: H
authors: Kim
authors: Nisha
authors: N
authors: Thampi
authors: W Conrad
authors: WC
authors: Liles
authors: Chandy C
authors: CC
authors: John
authors: Kevin C
authors: KC
authors: Kain
mesh_terms: D000280:Administration, Inhalation; D001682:Biological Availability; D002648:Child; D002986:Clinical Trials as Topic; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000098:blood supply; D008288:Malaria / Q000188:drug therapy*; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000235:genetics*
chemical_list: D009569:Nitric Oxide; D019001:Nitric Oxide Synthase