Observational studyBMC medicine2015
Microvascular obstruction and endothelial activation are independently associated with the clinical manifestations of severe falciparum malaria in adults: an observational study.
Observational study in BMC medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.
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Who cites it
56 citing papers in PubMed, 2 syntheses or guidelines pooled it, 81 citations in OpenAlex.
- Meta-analysis of Plasmodium falciparummBio · 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
- The Safety of a Conservative Fluid Replacement Strategy in Adults Hospitalised with Malaria.PloS one · 2015Trial
- Bilateral ascending dry gangrene following documented smear-positive malaria in a patient with multivalvular rheumatic heart disease and normal CT angiography findings: a case report.International journal of surgery case reports · 2026Article
- ETS-guided iPSC-endothelial models recapitulate malaria pathogenesis.EMBO molecular medicine · 2026Article
- Assessing the Health and Functionality of the Microcirculation Using Thermal Imaging.Journal of biophotonics · 2026Review
- Assessment of Long-Term Sequelae After Severe Malaria: A Retrospective Study.Pathogens (Basel, Switzerland) · 2026Article
- Alert for Imported Malaria in Non-Endemic Areas: A Case Report of Atypical Falciparum Malaria in a Young Child and Diagnostic Experience.Tropical medicine and infectious disease · 2026Article
- Feline panleukopenia-associated clinicopathological abnormalities: first evaluation of diagnostic and prognostic roles of endothelial glycocalyx degradation biomarkers.The veterinary quarterly · 2025Article
- Plasmodium falciparum impairs Ang-1 secretion by pericytes in a 3D brain microvessel model.EMBO molecular medicine · 2025Article
- Osteoprotegerin and its ligands RANKL and TRAIL in falciparum, vivax, and knowlesi malaria.iScience · 2025Article
- Clinical, immune and genetic risk factors of malaria-associated acute kidney injury in Zambian children: A study protocol.PloS one · 2025Observational
- Evaluation of endothelial glycocalyx injury biomarkers in feline hemotropic mycoplasmosis.Scientific reports · 2024Article
- Involvement of Inflammatory Cytokines, Renal NaPi-IIa Cotransporter, and TRAIL Induced-Apoptosis in Experimental Malaria-Associated Acute Kidney Injury.Pathogens (Basel, Switzerland) · 2024Article
- Immunofluorescence study of cytoskeleton in endothelial cells induced with malaria sera.Malaria journal · 2024Article
- Intestinal injury and the gut microbiota in patients with Plasmodium falciparum malaria.PLoS pathogens · 2023Review
- Cellular iron governs the host response to malaria.PLoS pathogens · 2023Article
- Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture.PloS one · 2023Article
- Elevated endothelial dysfunction-related biomarker levels indicate the severity and predict sepsis incidence.Scientific reports · 2022Article
- Diverse Malaria Presentations across National Institutes of Health South Asia International Center for Excellence in Malaria Research Sites in India.The American journal of tropical medicine and hygiene · 2022Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 7 countries.
Funding
Abstract
backgroundMicrovascular obstruction and endothelial dysfunction have both been linked to tissue hypoperfusion in falciparum malaria, but their relative contributions to the disease's pathogenesis and outcome are unknown.
methodsMicrovascular blood flow was quantified in adults with severe falciparum malaria on their admission to hospital; plasma biomarkers of endothelial function were measured simultaneously. The relationship between these indices and the patients' clinical findings and in-hospital course was examined.
resultsMicrovascular obstruction was observed in 119/142 (84 %) patients; a median (interquartile range (IQR)) of 14.9 % (6.6-34.9 %) of capillaries were obstructed in patients that died versus 8.3 % (1.7-26.6 %) in survivors (P = 0.039). The proportion of obstructed capillaries correlated with the estimated parasite biomass (rs = 0.25, P = 0.004) and with plasma lactate (rs = 0.38, P <0.0001), the strongest predictor of death in the series. Plasma angiopoietin-2 (Ang-2) concentrations were markedly elevated suggesting widespread endothelial activation; the median (IQR) Ang-2 concentration was 21.9 ng/mL (13.4-29.4 ng/mL) in patients that died versus 14.9 ng/mL (9.8-29.3 ng/mL) in survivors (P = 0.035). Ang-2 concentrations correlated with estimated parasite biomass (rs = 0.35, P <0.001) and plasma lactate (rs = 0.37, P <0.0001). Microvascular obstruction and Ang-2 concentrations were not significantly correlated with each other (rs = 0.17, P = 0.06), but were independently associated with plasma lactate (P <0.001 and P = 0.002, respectively).
conclusionsMicrovascular obstruction and systemic endothelial activation are independently associated with plasma lactate, the strongest predictor of death in adults with falciparum malaria. This supports the hypothesis that the two processes make an independent contribution to the pathogenesis and clinical manifestations of the disease.
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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.