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

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

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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.


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 ( Identifier: NCT01255215).

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