ArticleInfection and immunity2012
Mild Plasmodium falciparum malaria following an episode of severe malaria is associated with induction of the interferon pathway in Malawian children.
Article in Infection and immunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Host Transcriptional Meta-signatures Reveal Diagnostic Biomarkers for Plasmodium falciparum Malaria.The Journal of infectious diseases · 2024Pooled it
- Reviewing and assessing existing meta-analysis models and tools.Briefings in bioinformatics · 2021Pooled it
- Evaluation of immunophenotypic alterations of peripheral blood lymphocytes and their sub-sets in uncomplicated P. Falciparum infection.BMC immunology · 2024Article
- Hepatocytes and the art of killing Plasmodium softly.Trends in parasitology · 2024Review
- Immunogenomic profile at baseline predicts host susceptibility to clinical malaria.Frontiers in immunology · 2023Article
- Diagnosis of cerebral malaria: Tools to reduceFrontiers in cellular and infection microbiology · 2023Review
- Endothelial type I interferon response and brain diseases: identifying STING as a therapeutic target.Frontiers in cell and developmental biology · 2023Review
- Understanding the Intransigence of Malaria in Malawi.The American journal of tropical medicine and hygiene · 2022Article
- Review
- Brain endothelial STING1 activation byProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria.eLife · 2022Article
- Decoding the complexities of human malaria through systems immunology.Immunological reviews · 2020Review
- Type I Interferons and Malaria: A Double-Edge Sword Against a Complex Parasitic Disease.Frontiers in cellular and infection microbiology · 2020Review
- Use of gene expression studies to investigate the human immunological response to malaria infection.Malaria journal · 2019Review
- Gene expression profiling in blood from cerebral malaria patients and mild malaria patients living in Senegal.BMC medical genomics · 2019Article
- TRPV1 Contributes to Cerebral Malaria Severity and Mortality by Regulating Brain Inflammation.Oxidative medicine and cellular longevity · 2019Article
- Integrated pathogen load and dual transcriptome analysis of systemic host-pathogen interactions in severe malaria.Science translational medicine · 2018Article
- Transcriptomic Studies of Malaria: a Paradigm for Investigation of Systemic Host-Pathogen Interactions.Microbiology and molecular biology reviews : MMBR · 2018Review
- Type I Interferon Receptor Variants in Gene Regulatory Regions are Associated with Susceptibility to Cerebral Malaria in Malawi.The American journal of tropical medicine and hygiene · 2018Article
- A systematic and prospectively validated approach for identifying synergistic drug combinations against malaria.Malaria journal · 2018Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Infection with Plasmodium falciparum can lead to a range of severe to minimal symptoms, occasionally resulting in death in young children or nonimmune adults. In areas of high transmission, older children and adults generally suffer only mild or asymptomatic malaria infections and rarely develop severe disease. The immune features underlying this apparent immunity to severe disease remain elusive. To gain insight into host responses associated with severe and mild malaria, we conducted a longitudinal study of five children who first presented with severe malaria and, 1 month later, with mild malaria. Employing peripheral blood whole-genome profiling, we identified 68 genes that were associated with mild malaria compared to their expression in the severe malaria episode (paired Students t test, P < 0.05). These genes reflect the interferon (IFN) pathway and T cell biology and include IFN-induced protein transcripts 1 to 3, oligoadenylate synthetases 1 and 3, and the T cell markers cathepsin W and perforin. Gene set enrichment analysis identified Gene Ontology (GO) pathways associated with mild malaria to include the type I interferon-mediated signaling pathway (GO 0060337), T cell activation (GO 0042110), and other GO pathways representing many aspects of immune activation. In contrast, only six genes were associated with severe malaria, including thymidine kinase 1, which was recently found to be a biomarker of cerebral malaria susceptibility in the murine model, and carbonic anhydrase, reflecting the blood's abnormal acid base environment during severe disease. These data may provide potential insights to inform pathogenesis models and the development of therapeutics to reduce severe disease outcomes due to P. falciparum infection.
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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.