Evidence map›Paper›PMID 27354391›Full record

ArticleEMBO molecular medicine2016

Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains.

Jakob S Jespersen, Christian W Wang, Sixbert I Mkumbaye, Daniel Tr Minja, Bent Petersen, Louise Turner, Jens Ev Petersen, John Pa Lusingu, Thor G Theander, Thomas Lavstsen

Open access · goldAbstract read
In one paragraph

Article in EMBO molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 1 pooled it
13.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

69 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.

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  15. Broadly inhibitory antibodies against severe malaria virulence proteins.bioRxiv : the preprint server for biology · 2024
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  18. Diagnosis of cerebral malaria: Tools to reduceFrontiers in cellular and infection microbiology · 2023
    Review
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  20. Article

9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Jakob S JespersenCentre for Medical Parasitology, Department of Immunology & Microbiology, University of Copenhagen, Copenhagen, Denmark Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0002-4930-5900
Christian W WangCentre for Medical Parasitology, Department of Immunology & Microbiology, University of Copenhagen, Copenhagen, Denmark Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
Sixbert I MkumbayeKilimanjaro Christian Medical University College, Kilimanjaro Clinical Research Institute, Moshi, Tanzania.
Daniel Tr MinjaNational Institute for Medical Research, Tanga Research Centre, Tanga, Tanzania.
Bent PetersenCentre for Biological Sequence Analysis, Technical University of Denmark, Kgs. Lyngby, Denmark.
Louise TurnerCentre for Medical Parasitology, Department of Immunology & Microbiology, University of Copenhagen, Copenhagen, Denmark Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
Jens Ev PetersenCentre for Medical Parasitology, Department of Immunology & Microbiology, University of Copenhagen, Copenhagen, Denmark Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
John Pa LusinguCentre for Medical Parasitology, Department of Immunology & Microbiology, University of Copenhagen, Copenhagen, Denmark Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark National Institute for Medical Research, Tanga Research Centre, Tanga, Tanzania.
Thor G TheanderCentre for Medical Parasitology, Department of Immunology & Microbiology, University of Copenhagen, Copenhagen, Denmark Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
Thomas LavstsenCentre for Medical Parasitology, Department of Immunology & Microbiology, University of Copenhagen, Copenhagen, Denmark Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark thomasl@sund.ku.dk.ORCID 0000-0002-3044-4249
University of Copenhagen · DKKilimanjaro Christian Medical Centre · TZNational Institute for Medical Research · TZTechnical University of Denmark · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding human endothelial protein C receptor (EPCR) through the CIDRα1 domain of certain PfEMP1 were recently associated with severe malaria in children. However, it has remained unclear to which extend the EPCR-binding CIDRα1 domains epitomize PfEMP1 expressed in severe malaria. Here, we characterized the near full-length transcripts dominating the var transcriptome in children with severe malaria and found that the only common feature of the encoded PfEMP1 was CIDRα1 domains. Such genes were highly and dominantly expressed in both children with severe malarial anaemia and cerebral malaria. These observations support the hypothesis that the CIDRα1-EPCR interaction is key to the pathogenesis of severe malaria and strengthen the rationale for pursuing a vaccine or adjunctive treatment aiming at inhibiting or reducing the damaging effects of this interaction.

Indexed as

Protein DomainsAntigens, CDChild, PreschoolEndothelial Protein C ReceptorFemaleGene Expression ProfilingHost-Pathogen InteractionsHumansInfantMalaria, FalciparumMalePlasmodium falciparumProtein BindingProtozoan ProteinsReceptors, Cell SurfaceAntigens, CDEndothelial Protein C Receptorerythrocyte membrane protein 1, Plasmodium falciparumPROCR protein, humanProtozoan ProteinsReceptors, Cell SurfaceCIDREPCRPfEMP1severe childhood malariavar

Identifiers

PMID27354391
PMCPMC4967939
OpenAlexW2473661440

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Registered trials

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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.