ArticlemBio2016
Plasmodium falciparum Histidine-Rich Protein II Compromises Brain Endothelial Barriers and May Promote Cerebral Malaria Pathogenesis.
Article in mBio, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 3 of them syntheses that pooled it.
What it found
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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
55 citing papers in PubMed, 3 syntheses or guidelines pooled it, 76 citations in OpenAlex.
- Retinal imaging technologies in cerebral malaria: a systematic review.Malaria journal · 2023Pooled it
- Prevalence of Plasmodium falciparum field isolates with deletions in histidine-rich protein 2 and 3 genes in context with sub-Saharan Africa and India: a systematic review and meta-analysis.Malaria journal · 2020Pooled it
- Meta-analysis of Plasmodium falciparummBio · 2019Pooled it
- Article
- Potential biomarkers and their recent applications ofr point-of-care biosensors for the diagnosis of malaria.Mikrochimica acta · 2026Review
- Phenotypic and genotypic characterization of Plasmodium falciparum field isolates lacking pfhrp2 gene.Malaria journal · 2026Article
- Article
- Mechanisms of parasite-mediated disruption of brain vessels.FEBS letters · 2026Review
- 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
- Plasmodium falciparum egress disrupts endothelial junctions and activates JAK-STAT signaling in a microvascular 3D blood-brain barrier model.Nature communications · 2025Article
- Nilotinib attenuates vascular pathology in experimental cerebral malaria.Blood advances · 2025Article
- Severity of Vessel Color Changes and Macular and Peripheral Whitening in Malarial Retinopathy Are Associated with Higher Total Body and Sequestered Parasite Burdens.Tropical medicine and infectious disease · 2024Article
- Prediction of malaria positivity using patients' demographic and environmental features and clinical symptoms to complement parasitological confirmation before treatment.Tropical diseases, travel medicine and vaccines · 2023Article
- Review
- Probing cerebral malaria inflammation in 3D human brain microvessels.Cell reports · 2023Article
- Profile of Daniel E. Goldberg.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Histidine-rich protein II nanoparticle delivery of heme iron load drives endothelial inflammation in cerebral malaria.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- In vitro model of brain endothelial cell barrier reveals alterations induced by Plasmodium blood stage factors.Parasitology research · 2023Article
- Diagnosis of cerebral malaria: Tools to reduceFrontiers in cellular and infection microbiology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledCerebral malaria (CM) is a disease of the vascular endothelium caused by Plasmodium falciparum It is characterized by parasite sequestration, inflammatory cytokine production, and vascular leakage. A distinguishing feature of P. falciparum infection is parasite production and secretion of histidine-rich protein II (HRPII). Plasma HRPII is a diagnostic and prognostic marker for falciparum malaria. We demonstrate that disruption of a human cerebral microvascular endothelial barrier by P. falciparum-infected erythrocytes depends on expression of HRPII. Purified recombinant or native HRPII can recapitulate these effects. HRPII action occurs via activation of the inflammasome, resulting in decreased integrity of tight junctions and increased endothelial permeability. We propose that HRPII is a virulence factor that may contribute to cerebral malaria by compromising endothelial barrier integrity within the central nervous system. IMPORTANCE: Cerebral malaria is a devastating disease. Patients have high levels of the protein HRPII in their blood. We have found that endothelial cell barriers become leaky when treated with concentrations of HRPII similar to those found in patients. This result suggests that HRPII may be important in cerebral malaria. Our finding that HRPII functions by causing inflammation suggests points of intervention for therapy or vaccination against this disease.
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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.