ReviewFrontiers in microbiology2014
Malaria drives T cells to exhaustion.
Review in Frontiers in microbiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04661579 (A Phase 2b Randomized, Open-label, Controlled, Single Center Study in Plasmodium Falciparum-infected and Uninfected Adults Age 18-55 Years Old in Kenya to Evaluate the Efficacy of the Delayed, Fractional Dose RTS,S/AS01E Malaria Vaccine in Subjects Treated With Artemisinin Combination Therapy Plus Primaquine), which is not on this map. Cited by 56 papers.
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.
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.
A Phase 2b Randomized, Open-label, Controlled, Single Center Study in Plasmodium Falciparum-infected and Uninfected Adults Age 18-55 Years Old in Kenya to Evaluate the Efficacy of the Delayed, Fractional Dose RTS,S/AS01E Malaria Vaccine in Subjects Treated With Artemisinin Combination Therapy Plus Primaquine
Who cites it
56 citing papers in PubMed, 98 citations in OpenAlex.
- Efficacy of RTS,S/AS01E Only Seen in Baseline Parasitemic and Not Baseline Aparasitemic Plasmodium falciparum-Exposed, Drug-Treated Kenyan Adults.The Journal of infectious diseases · 2025Trial
- Impact of exposure to malaria and nutritional status on responses to the experimental malaria vaccine ChAd63 MVA ME-TRAP in 5-17 month-old children in Burkina Faso.Frontiers in immunology · 2022Trial
- Controlled Human Malaria Infection (CHMI) differentially affects cell-mediated and antibody responses to CSP and AMA1 induced by adenovirus vaccines with and without DNA-priming.Human vaccines & immunotherapeutics · 2015Trial
- Malaria and cancer: common features and interactions.Trends in parasitology · 2026Review
- CD103-Positive Tumor-Infiltrating Lymphocytes Predict a Favorable Prognosis in Colorectal Cancer with Liver Metastasis.Annals of surgical oncology · 2026Article
- cTfh Cell Activation and Changes in BTLA and LAG-3 Expression Differentially Associate With Poor Pregnancy Outcome in Plasmodium falciparum Placental Malaria.Journal of immunology research · 2026Article
- Management and monitoring strategies for severe cerebral malaria: a guide for the intensivist.Annals of intensive care · 2025Review
- Emerging Role of Splenic Macrophage in Malaria Pathogenesis and Immunity.Immunity, inflammation and disease · 2025Review
- Model Systems of Gammaherpesvirus Infection, Immunity, and Disease.Journal of medical virology · 2025Review
- Impact of co-infection with Plasmodium berghei ANKA in Leishmania major-parasitized mice on immune modulation and cutaneous leishmaniasis.PLoS neglected tropical diseases · 2025Article
- Malaria: Factors affecting disease severity, immune evasion mechanisms, and reversal of immune inhibition to enhance vaccine efficacy.PLoS pathogens · 2025Review
- Characteristics of splenic PD-1Immunologic research · 2024Article
- Chronic malaria exposure is associated with inhibitory markers on T cells that correlate with atypical memory and marginal zone-like B cells.Clinical and experimental immunology · 2024Article
- Cytolytic circumsporozoite-specific memory CD4Nature communications · 2023Article
- Background malaria incidence and parasitemia during the three-dose RTS,S/AS01 vaccination series do not reduce magnitude of antibody response nor efficacy against the first case of malaria.BMC infectious diseases · 2023Article
- A Lower Dose of Infection Generates a Better Long-Term Immune Response against Toxoplasma gondii.ImmunoHorizons · 2023Article
- Influenza virus-like particle vaccine containing both apical membrane antigen 1 and microneme-associated antigen proteins of Plasmodium berghei confers protection in mice.BMC immunology · 2022Article
- Deciphering the Plasmodium falciparum malaria-specific CD4+ T-cell response: ex vivo detection of high frequencies of PD-1+TIGIT+ EXP1-specific CD4+ T cells using a novel HLA-DR11-restricted MHC class II tetramer.Clinical and experimental immunology · 2022Article
- Role of the PD-1/PD-L1 Pathway in ExperimentalFrontiers in immunology · 2022Article
- Eryptosis as a New Insight in Malaria Pathogenesis.Frontiers in immunology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malaria is a significant global burden but after >30 years of effort there is no vaccine on the market. While the complex life cycle of the parasite presents several challenges, many years of research have also identified several mechanisms of immune evasion by Plasmodium spp. Recent research on malaria, has investigated the programmed cell death-1 (PD-1) pathway which mediates exhaustion of T cells, characterized by poor effector functions and recall responses and in some cases loss of the cells by apoptosis. Such studies have shown exhaustion of CD4(+) T cells and an unappreciated role for CD8(+) T cells in promoting sterile immunity against blood stage malaria. This is because PD-1 mediates up to a 95% reduction in numbers and functional capacity of parasite-specific CD8(+) T cells, thus masking their role in protection. The role of T cell exhaustion during malaria provides an explanation for the absence of sterile immunity following the clearance of acute disease which will be relevant to future malaria-vaccine design and suggests the need for novel therapeutic solutions. This review will thus examine the role of PD-1-mediated T cell exhaustion in preventing lasting immunity against malaria.
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What OpenQuestion holds
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.