ArticleEmerging microbes & infections2018
Intravascular haemolysis in severe Plasmodium knowlesi malaria: association with endothelial activation, microvascular dysfunction, and acute kidney injury.
Article in Emerging microbes & infections, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 3 of them syntheses that pooled 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.
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
45 citing papers in PubMed, 3 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Kidney and endothelial injury biomarkers as predictors of complications and mortality in patients with malaria: a systematic review.Malaria journal · 2026Pooled it
- Clinical characteristics and outcome of malaria-associated acute kidney injury in adult patients: a systematic review and meta analysis.Malaria journal · 2026Pooled it
- Alterations in von Willebrand Factor Levels in Patients with Malaria: A Systematic Review and Meta-Analysis of Disease Severity.Medicina (Kaunas, Lithuania) · 2025Pooled it
- The Effect of Regularly Dosed Acetaminophen vs No Acetaminophen on Renal Function in Plasmodium knowlesi Malaria (PACKNOW): A Randomized, Controlled Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Trial
- Population Pharmacokinetics and Pharmacodynamics of Paracetamol in Malaysian Patients With Plasmodium knowlesi Malaria.CPT: pharmacometrics & systems pharmacology · 2026Article
- Comparative immunological study of Plasmodium knowlesi infections in humans and macaques: insights into cytokine dynamics.Malaria journal · 2025Article
- Malaria associated pathogenesis of chronic kidney disease (MAP-CKD): a prospective study of children hospitalized with severe malaria.BMC nephrology · 2025Article
- Osteoprotegerin and its ligands RANKL and TRAIL in falciparum, vivax, and knowlesi malaria.iScience · 2025Article
- Animal Models of Malaria-Associated Acute Kidney Injury.Seminars in nephrology · 2025Review
- The differential effect of Interferon-gamma on acute kidney injury and parasitemia in experimental malaria.Scientific reports · 2025Article
- Neutrophil activation, acute lung injury and disease severity in Plasmodium knowlesi malaria.PLoS neglected tropical diseases · 2024Article
- Ascorbate protects human kidney organoids from damage induced by cell-free hemoglobin.Disease models & mechanisms · 2023Article
- Renin as a Biomarker of Acute Kidney Injury and Mortality in Children With Severe Malaria or Sickle Cell Disease.Cureus · 2023Article
- Mechanism of Immune Evasion in Mosquito-Borne Diseases.Pathogens (Basel, Switzerland) · 2023Review
- Hemoglobin increases leukocyte adhesion and initiates lung microvascular endothelial activation via Toll-like receptor 4 signaling.American journal of physiology. Cell physiology · 2023Article
- The kidney-brain pathogenic axis in severe falciparum malaria.Trends in parasitology · 2023Review
- Primaquine-induced Severe Hemolysis in the Absence of Concomitant Malaria: Effects on G6PD Activity and Renal Function.The American journal of tropical medicine and hygiene · 2023Article
- The spectrum of clinical biomarkers in severe malaria and new avenues for exploration.Virulence · 2022Review
- Narrative Review of the Control and Prevention of Knowlesi Malaria.Tropical medicine and infectious disease · 2022Review
- Blackwater fever and acute kidney injury in children hospitalized with an acute febrile illness: pathophysiology and prognostic significance.BMC medicine · 2022Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 6 countries.
Funding
Abstract
Plasmodium knowlesi occurs throughout Southeast Asia, and is the most common cause of human malaria in Malaysia. Severe disease in humans is characterised by high parasite biomass, reduced red blood cell deformability, endothelial activation and microvascular dysfunction. However, the roles of intravascular haemolysis and nitric oxide (NO)-dependent endothelial dysfunction, important features of severe falciparum malaria, have not been evaluated, nor their role in acute kidney injury (AKI). In hospitalised Malaysian adults with severe (n = 48) and non-severe (n = 154) knowlesi malaria, and in healthy controls (n = 50), we measured cell-free haemoglobin (CFHb) and assessed associations with the endothelial Weibel-Palade body (WPB) constituents, angiopoietin-2 and osteoprotegerin, endothelial and microvascular function, and other markers of disease severity. CFHb was increased in knowlesi malaria in proportion to disease severity, and to a greater extent than previously reported in severe falciparum malaria patients from the same study cohort. In knowlesi malaria, CFHb was associated with parasitaemia, and independently associated with angiopoietin-2 and osteoprotegerin. As with angiopoietin-2, osteoprotegerin was increased in proportion to disease severity, and independently associated with severity markers including creatinine, lactate, interleukin-6, endothelial cell adhesion molecules ICAM-1 and E-selectin, and impaired microvascular reactivity. Osteoprotegerin was also independently associated with NO-dependent endothelial dysfunction. AKI was found in 88% of those with severe knowlesi malaria. Angiopoietin-2 and osteoprotegerin were both independent risk factors for acute kidney injury. Our findings suggest that haemolysis-mediated endothelial activation and release of WPB constituents is likely a key contributor to end-organ dysfunction, including AKI, in severe knowlesi malaria.
Indexed as
Identifiers
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.