ArticleCritical care medicine2012
Angiopoietin-2 levels are associated with retinopathy and predict mortality in Malawian children with cerebral malaria: a retrospective case-control study*.
Article in Critical care medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses that pooled it.
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Who cites it
82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 114 citations in OpenAlex.
- Prognostic models for the clinical management of malaria and its complications: a systematic review.BMJ open · 2019Pooled 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 as adjunctive therapy for severe malaria: a randomized controlled trial.Malaria journal · 2015Trial
- Impaired systemic tetrahydrobiopterin bioavailability and increased oxidized biopterins in pediatric falciparum malaria: association with disease severity.PLoS pathogens · 2015Trial
- Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria.PLoS pathogens · 2014Trial
- ETS-guided iPSC-endothelial models recapitulate malaria pathogenesis.EMBO molecular medicine · 2026Article
- Epidemiology of imported malaria in an area of North-Eastern Italy (2016-2025): clinical focus on cerebral malaria.Le infezioni in medicina · 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
- Febrile temperature enhancesbioRxiv : the preprint server for biology · 2025Article
- Elevated Levels of PDGF-BB and VEGF Are Associated With a Decreased Risk of Readmission or Death in Children With Severe Malarial Anemia.The Journal of infectious diseases · 2025Article
- A comprehensive review of cerebral malaria.Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2025Review
- Host biomarkers and parasite biomass are associated with severe malaria in Mozambican children: a case-control study.Scientific reports · 2025Article
- Elevated uric acid levels, mortality and cognitive impairment in children with severe malaria.Nature medicine · 2025Article
- The Angiopoietin-Tie-2 Axis in Children and Young Adults with Dengue Virus Infection in the Philippines.The American journal of tropical medicine and hygiene · 2024Article
- Angiopoietin-2 is associated with sickle cell complications, including stroke risk, and decreases with hydroxyurea therapy.Blood vessels, thrombosis & hemostasis · 2024Article
- Unravelling mysteries at the perivascular space: a new rationale for cerebral malaria pathogenesis.Trends in parasitology · 2024Review
- Circulating biomarkers associated with pediatric sickle cell disease.Frontiers in molecular biosciences · 2024Article
- Endothelial transcriptomic analysis identifies biomarkers of severe and cerebral malaria.JCI insight · 2023Article
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
22 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
objectiveTo investigate the relationship among the angiopoietin-Tie-2 system, retinopathy, and mortality in children with cerebral malaria.
designA case-control study of retinopathy-positive vs. retinopathy-negative children with clinically defined cerebral malaria.
settingQueen Elizabeth Central Hospital in Blantyre, Malawi. SUBJECTS: One hundred fifty-five children presenting with severe malaria and meeting a strict definition of clinical cerebral malaria (Blantyre Coma Score ≤ 2, Plasmodium falciparum parasitemia, no other identifiable cause for coma) were included in the study.
interventionsNone. MEASUREMENTS AND MAIN
resultsClinical and laboratory parameters were recorded at admission and funduscopic examinations were performed. Admission levels of angiopoietin-1, angiopoietin-2, and a soluble version of their cognate receptor were measured by enzyme-linked immunosorbent assay. We show that angiopoietin-1 levels are decreased and angiopoietin-2 and soluble Tie-2 levels are increased in children with cerebral malaria who had retinopathy compared with those who did not. Angiopoietin-2 and soluble Tie-2 were independent predictors of retinopathy (adjusted odds ratio [95% CI], angiopoietin-2, 4.3 [1.3-14.6], p = .019; soluble Tie-2, 9.7 [2.1-45.8], p = .004). Angiopoietin-2 and soluble Tie-2 were positively correlated with the number of hemorrhages, the severity or retinal whitening, and the extent of capillary whitening observed on funduscopic examination (p < .05 after adjustment for multiple comparisons). Angiopoietin-2 and soluble Tie-2 levels were elevated in children with cerebral malaria who subsequently died and angiopoetin-2 was an independent predictor of death (adjusted odds ratio: 3.9 [1.2-12.7], p = .024). When combined with clinical parameters, angiopoetin-2 improved prediction of mortality using logistic regression models and classification trees.
conclusionsThese results provide insights into mechanisms of endothelial activation in cerebral malaria and indicate that the angiopoietin-Tie-2 axis is associated with retinopathy and mortality in pediatric cerebral malaria.
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