Inhaled Nitric Oxide as an Adjunctive Treatment for Cerebral Malaria in Children: A Phase II Randomized Open-Label Clinical Trial.

Mwanga-Amumpaire J Carroll RW Baudin E Kemigisha E Nampijja D Mworozi K Santorino D Nyehangane D Nathan DI De Beaudrap P Etard JF Feelisch M Fernandez BO Berssenbrugge A Bangsberg D Bloch KD Boum Y Zapol WM
Open forum infectious diseases 2015 Sep ; 2(3); ofv111. doi: 10.1093/ofid/ofv111. Epub 2015 07 24
Plasmodium falciparum cerebral malaria methemoglobin nitric oxide


Background.  Children with cerebral malaria (CM) have high rates of mortality and neurologic sequelae. Nitric oxide (NO) metabolite levels in plasma and urine are reduced in CM. Methods.  This randomized trial assessed the efficacy of inhaled NO versus nitrogen (N2) as an adjunctive treatment for CM patients receiving intravenous artesunate. We hypothesized that patients treated with NO would have a greater increase of the malaria biomarker, plasma angiopoietin-1 (Ang-1) after 48 hours of treatment. Results.  Ninety-two children with CM were randomized to receive either inhaled 80 part per million NO or N2 for 48 or more hours. Plasma Ang-1 levels increased in both treatment groups, but there was no difference between the groups at 48 hours (P = not significant [NS]). Plasma Ang-2 and cytokine levels (tumor necrosis factor-α, interferon-γ, interleukin [IL]-1β, IL-6, IL-10, and monocyte chemoattractant protein-1) decreased between inclusion and 48 hours in both treatment groups, but there was no difference between the groups (P = NS). Nitric oxide metabolite levels-blood methemoglobin and plasma nitrate-increased in patients treated with NO (both P