ArticleProceedings of the National Academy of Sciences of the United States of America2016
Severe adult malaria is associated with specific PfEMP1 adhesion types and high parasite biomass.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 2 of them syntheses that pooled it.
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Who cites it
79 citing papers in PubMed, 2 syntheses or guidelines pooled it, 117 citations in OpenAlex.
- Prognostic factors in malaria patients with acute kidney injury: a systematic review and meta analysis.Renal failure · 2026Pooled it
- Meta-analysis of Plasmodium falciparummBio · 2019Pooled it
- Longitudinal analysis of naturally acquired PfEMP1 CIDR domain variant antibodies identifies associations with malaria protection.JCI insight · 2020Trial
- Plasmodium falciparum malaria parasite var gene expression is modified by host antibodies: longitudinal evidence from controlled infections of Kenyan adults with varying natural exposure.BMC infectious diseases · 2017Trial
- ETS-guided iPSC-endothelial models recapitulate malaria pathogenesis.EMBO molecular medicine · 2026Article
- Systems Biological Analysis of Immune-Metabolic Host Responses to Distinct Malaria Parasites.ACS omega · 2025Article
- A monoclonal antibody selectively recognizing PfEMP1 proteins associated with cerebral malaria.Scientific reports · 2025Article
- Febrile temperature enhancesbioRxiv : the preprint server for biology · 2025Article
- Identification of broadly inhibitory anti-PfEMP1 antibodies by mass spectrometry sequencing of plasma IgG from a malaria-exposed child.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A whole blood assay for antibody dependent phagocytosis of Plasmodium falciparum infected erythrocytes.Communications medicine · 2025Article
- Var genes, strain hyperdiversity, and malaria transmission dynamics.Trends in parasitology · 2025Review
- A paradoxical population structure of var DBLα types in Africa.PLoS pathogens · 2025Article
- Breaking the bind: PfEMP1-specific antibodies in cerebral malaria.Frontiers in immunology · 2025Review
- Identification of novel PfEMP1 variants containing domain cassettes 11, 15 and 8 that mediate the Plasmodium falciparum virulence-associated rosetting phenotype.PLoS pathogens · 2025Article
- A machine learning approach for early identification of patients with severe imported malaria.Malaria journal · 2024Article
- Broadly inhibitory antibodies against severe malaria virulence proteins.bioRxiv : the preprint server for biology · 2024Article
- A novel computational pipeline foreLife · 2024Article
- PfEMP1 and var genes - Still of key importance in Plasmodium falciparum malaria pathogenesis and immunity.Advances in parasitology · 2024Review
- Variable Surface Antigens ofProtein and peptide letters · 2024Review
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
The interplay between cellular and molecular determinants that lead to severe malaria in adults is unexplored. Here, we analyzed parasite virulence factors in an infected adult population in India and investigated whether severe malaria isolates impair endothelial protein C receptor (EPCR), a protein involved in coagulation and endothelial barrier permeability. Severe malaria isolates overexpressed specific members of the Plasmodium falciparum var gene/PfEMP1 (P. falciparum erythrocyte membrane protein 1) family that bind EPCR, including DC8 var genes that have previously been linked to severe pediatric malaria. Machine learning analysis revealed that DC6- and DC8-encoding var transcripts in combination with high parasite biomass were the strongest indicators of patient hospitalization and disease severity. We found that DC8 CIDRα1 domains from severe malaria isolates had substantial differences in EPCR binding affinity and blockade activity for its ligand activated protein C. Additionally, even a low level of inhibition exhibited by domains from two cerebral malaria isolates was sufficient to interfere with activated protein C-barrier protective activities in human brain endothelial cells. Our findings demonstrate an interplay between parasite biomass and specific PfEMP1 adhesion types in the development of adult severe malaria, and indicate that low impairment of EPCR function may contribute to parasite virulence.
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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.