Observational studyThe Journal of infectious diseases2017
Effects of Aging on Parasite Biomass, Inflammation, Endothelial Activation, Microvascular Dysfunction and Disease Severity in Plasmodium knowlesi and Plasmodium falciparum Malaria.
Observational study in The Journal of infectious diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 4 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
35 citing papers in PubMed, 4 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Increased interleukin-6 levels associated with malaria infection and disease severity: a systematic review and meta-analysis.Scientific reports · 2022Pooled it
- Pooled it
- Prevalence of severe Plasmodium knowlesi infection and risk factors related to severe complications compared with non-severe P. knowlesi and severe P. falciparum malaria: a systematic review and meta-analysis.Infectious diseases of poverty · 2020Pooled it
- Deaths From Plasmodium knowlesi Malaria: Case Series and Systematic Review.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Pooled it
- Antiphosphatidylserine Immunoglobulin M and Immunoglobulin G Antibodies Are Higher in Vivax Than Falciparum Malaria, and Associated With Early Anemia in Both Species.The Journal of infectious diseases · 2019Trial
- Artemether-Lumefantrine Versus Chloroquine for the Treatment of Uncomplicated Plasmodium knowlesi Malaria: An Open-Label Randomized Controlled Trial CAN KNOW.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Trial
- Development of an Experimental Human Blood-Stage Model for Studying Plasmodium knowlesi.The Journal of infectious diseases · 2026Article
- Exploring the functions of NKG7 in CD4+ and CD8+ T cells during malaria.PLoS pathogens · 2026Article
- Latent cytomegalovirus disrupts innate NK cell responses to P. falciparum and impairs parasite control in first infection in adults.PLoS pathogens · 2026Article
- The problem with one-size-fits-all medicine: Biological sex and the aging immune system.PLoS biology · 2026Article
- Integrative genomics ofbioRxiv : the preprint server for biology · 2026Article
- Age is an intrinsic driver of inflammatory responses to malaria.Nature communications · 2025Article
- Comparative immunological study of Plasmodium knowlesi infections in humans and macaques: insights into cytokine dynamics.Malaria journal · 2025Article
- Osteoprotegerin and its ligands RANKL and TRAIL in falciparum, vivax, and knowlesi malaria.iScience · 2025Article
- Risk Factors for Imported Severe Malaria Cases - China, 2019-2023.China CDC weekly · 2025Article
- Neutrophil activation, acute lung injury and disease severity in Plasmodium knowlesi malaria.PLoS neglected tropical diseases · 2024Article
- Longitudinal changes in iron homeostasis in human experimental and clinical malaria.medRxiv : the preprint server for health sciences · 2023Article
- Clinical characteristics of platelet-mediated killing circulating parasite of major human malaria.Annals of medicine · 2023Article
- Review
- Quantification of parasite clearance in Plasmodium knowlesi infections.Malaria journal · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Background: In populations pauci-immune to malaria, risk of severe malaria increases with age. This is particularly apparent in Plasmodium knowlesi malaria. However, pathophysiological mechanisms underlying knowlesi malaria, and of the age-related increase in risk of severe malaria in general, are poorly understood. Methods: In Malaysian patients aged ≥12 years with severe (n = 47) and nonsevere (n = 99) knowlesi malaria, severe (n = 21) and nonsevere (n = 109) falciparum malaria, and healthy controls (n = 50), we measured parasite biomass, systemic inflammation (interleukin 6 [IL-6]), endothelial activation (angiopoietin-2), and microvascular function, and evaluated the effects of age. Results: Plasmodium knowlesi parasitemia correlated with age (Spearman's correlation coefficient [rs] = 0.36; P < .0001). In knowlesi malaria, IL-6, angiopoietin-2, and microvascular dysfunction were increased in severe compared to nonsevere disease, and all correlated with age, independent of parasitemia. In falciparum malaria, angiopoietin-2 increased with age, independent of parasite biomass (histidine-rich protein 2 [HRP2]). Independent risk factors for severe malaria included parasitemia and angiopoietin-2 in knowlesi malaria, and HRP2, angiopoietin-2, and microvascular dysfunction in falciparum malaria. Conclusions: Parasite biomass, endothelial activation, and microvascular dysfunction are associated with severe disease in knowlesi malaria and likely contribute to pathogenesis. The association of each of these processes with aging may account for the greater severity of malaria observed in older adults in low-endemic regions.
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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.