ArticleOpen forum infectious diseases2015
Inhaled Nitric Oxide as an Adjunctive Treatment for Cerebral Malaria in Children: A Phase II Randomized Open-Label Clinical Trial.
Article in Open forum infectious diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- Increased interleukin-6 levels associated with malaria infection and disease severity: a systematic review and meta-analysis.Scientific reports · 2022Pooled it
- Systematic review of the role of angiopoietin-1 and angiopoietin-2 in Plasmodium species infections: biomarkers or therapeutic targets?Malaria journal · 2016Pooled it
- Sickle Trait and Alpha Thalassemia Increase NOS-Dependent Vasodilation of Human Arteries Through Disruption of Endothelial Hemoglobin-eNOS Interactions.Circulation · 2025Article
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
- Nitric oxide: Clinical applications in critically ill patients.Nitric oxide : biology and chemistry · 2022Review
- Malaria Related Neurocognitive Deficits and Behavioral Alterations.Frontiers in cellular and infection microbiology · 2022Review
- Pediatric Cerebral Malaria.Current tropical medicine reports · 2021Article
- High-Dose Inhaled Nitric Oxide as Adjunct Therapy in Cystic Fibrosis TargetingCase reports in pediatrics · 2020Article
- Cerebral Plasmodium falciparum malaria: The role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it.Immunological reviews · 2020Review
- New insights into microvascular injury to inform enhanced diagnostics and therapeutics for severe malaria.Virulence · 2019Review
- Electrically generated nitric oxide from air: a safe and economical treatment for pulmonary hypertension.Intensive care medicine · 2019Article
- Inhaled nitric oxide.British journal of pharmacology · 2019Review
- Citrulline protects mice from experimental cerebral malaria by ameliorating hypoargininemia, urea cycle changes and vascular leak.PloS one · 2019Article
- Interplay between Plasmodium falciparum haemozoin and L-arginine: implication for nitric oxide production.Malaria journal · 2018Article
- Opportunities for Host-targeted Therapies for Malaria.Trends in parasitology · 2018Review
- Chitinase-3-like 1 is a biomarker of acute kidney injury and mortality in paediatric severe malaria.Malaria journal · 2018Article
- Adjunctive therapy for severe malaria: a review and critical appraisal.Malaria journal · 2018Review
- Sex-Associated Differential mRNA Expression of Cytokines and Its Regulation by Sex Steroids in Different Brain Regions in aMediators of inflammation · 2018Article
- Article
- Pathophysiological Mechanisms in Gaseous Therapies for Severe Malaria.Infection and immunity · 2016Review
Corrections and comments
- Erratum issuedERRATUM.2015
Authors and funding
18 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 < .05). Seven patients in the N2 group and 4 patients in the NO group died. Five patients in the N2 group and 6 in the NO group had neurological sequelae at hospital discharge. Conclusions. Breathing NO as an adjunctive treatment for CM for a minimum of 48 hours was safe, increased blood methemoglobin and plasma nitrate levels, but did not result in a greater increase of plasma Ang-1 levels at 48 hours.
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