ArticlePloS one2011
Inhaled nitric oxide reduces endothelial activation and parasite accumulation in the brain, and enhances survival in experimental cerebral malaria.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- Malaria and the Microbiome: A Systematic Review.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Pooled it
- Systematic review of the role of angiopoietin-1 and angiopoietin-2 in Plasmodium species infections: biomarkers or therapeutic targets?Malaria journal · 2016Pooled it
- Inhaled nitric oxide and cognition in pediatric severe malaria: A randomized double-blind placebo controlled trial.PloS one · 2018Trial
- Inhibition of merozoite invasion and transient de-sequestration by sevuparin in humans with Plasmodium falciparum malaria.PloS one · 2017Trial
- Methemoglobin and nitric oxide therapy in Ugandan children hospitalized for febrile illness: results from a prospective cohort study and randomized double-blind placebo-controlled trial.BMC pediatrics · 2016Trial
- Inhaled nitric oxide as adjunctive therapy for severe malaria: a randomized controlled trial.Malaria journal · 2015Trial
- Differential expression of mitochondria-associated genes in clinical samples of Plasmodium falciparum showing severe manifestations.BMC genomics · 2026Article
- Evaluation of clinically approved neuroprotective drugs as adjunct therapies in experimental cerebral malaria.Archives of microbiology · 2026Article
- Plasmodium falciparum impairs Ang-1 secretion by pericytes in a 3D brain microvessel model.EMBO molecular medicine · 2025Article
- Neurovascular Pathophysiology and Emerging Biomarkers in Cerebral Malaria: An Integrative Perspective.Neurology international · 2025Review
- Endothelial-specific telomerase inactivation causes telomere-independent cell senescence and multi-organ dysfunction characteristic of aging.Aging cell · 2024Article
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
- Cerebrospinal fluid biomarkers provide evidence for kidney-brain axis involvement in cerebral malaria pathogenesis.Frontiers in human neuroscience · 2023Article
- Potential Benefits of Lycopene Consumption: Rationale for Using It as an Adjuvant Treatment for Malaria Patients and in Several Diseases.Nutrients · 2022Review
- Nitric oxide in parasitic infections: a friend or foe?Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2022Review
- The association between acute fatty liver disease and nitric oxide during malaria in pregnancy.Malaria journal · 2021Article
- Pathophysiology and neurologic sequelae of cerebral malaria.Malaria journal · 2020Review
- Safety and Efficacy of Adjunctive Therapy With Artesunate in the Treatment of Severe Malaria: A Systematic Review and Meta-Analysis.Frontiers in pharmacology · 2020Review
- Terminalia albida treatment improves survival in experimental cerebral malaria through reactive oxygen species scavenging and anti-inflammatory properties.Malaria journal · 2019Article
- Genetics of Malaria Inflammatory Responses: A Pathogenesis Perspective.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
The host immune response contributes to the onset and progression of severe malaria syndromes, such as cerebral malaria. Adjunctive immunomodulatory strategies for severe malaria may improve clinical outcome beyond that achievable with artemisinin-based therapy alone. Here, we report that prophylaxis with inhaled nitric oxide significantly reduced systemic inflammation (lower TNF, IFNγ and MCP-1 in peripheral blood) and endothelial activation (decreased sICAM-1 and vWF, and increased angiopoeitin-1 levels in peripheral blood) in an experimental cerebral malaria model. Mice that received inhaled nitric oxide starting prior to infection had reduced parasitized erythrocyte accumulation in the brain, decreased brain expression of ICAM-1, and preserved vascular integrity compared to control mice.Inhaled nitric oxide administered in combination with artesunate, starting as late as 5.5 days post-infection, improved survival over treatment with artesunate alone (70% survival in the artesunate only vs. 100% survival in the artesunate plus iNO group, p = 0.03). These data support the clinical investigation of inhaled nitric oxide as a novel adjunctive therapy in patients with severe malaria.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.